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Sample records for octreotide long-acting repeatable

  1. Efficacy of the long-acting repeatable formulation of the somatostatin analogue octreotide in postoperative dumping.

    PubMed

    Arts, Joris; Caenepeel, Philip; Bisschops, Raf; Dewulf, Dominiek; Holvoet, Lieselot; Piessevaux, Hubert; Bourgeois, Stefan; Sifrim, Daniel; Janssens, Jozef; Tack, Jan

    2009-04-01

    Several studies have established symptomatic and mechanistic benefits of the somatostatin analogue octreotide in patients with dumping syndrome, but clinical use is hampered by the requirement for subcutaneous administration 3 times daily. We compared the efficacy of subcutaneous octreotide with that of the long-acting repeatable (LAR) octreotide formulation, which is administered monthly, in patients with dumping syndrome. The study included 30 consecutive patients with postoperative dumping, evidenced by oral glucose tolerance test (OGTT) results and insufficient response to dietary measures. OGTT, dumping severity score (summary of scores 0-3 for 8 early and 6 late dumping symptoms), and quality-of-life data were evaluated at baseline, after 3 days of subcutaneous administration of octreotide (0.5 mg), and then after 3 monthly intramuscular injections of octreotide LAR (20 mg). Both formulations of octreotide significantly reduced total dumping severity scores (21.7 +/- 1.6 at baseline, 11.2 +/- 1.2 for subcutaneous and 14.0 +/- 1.8 for LAR formulations; P < .05). This reduction was associated with significant improvements in the increase in pulse rate (13.8 +/- 5.8 at baseline vs -0.3 +/- 2.2 and 1.9 +/- 1.7; P < .05) as well as the increase in hematocrit level (4.0 +/- 1.4 at baseline vs 0.3 +/- 0.9. and 0.4 +/- 1.0; P < .05), and the lowest glycemia level in the OGTT (54.1 +/- 6.7 at baseline vs 98.9 +/- 7.1 and 67.8 +/- 5.9; P < .05). LAR octreotide administration significantly improved patients' quality of life. Patients' evaluations of their overall treatment efficacy was higher on LAR compared with the subcutaneous formulation (83% vs 52%; P = .01). Gallbladder stones occurred in 4 patients. Monthly administration of LAR octreotide improves OGTT results, symptoms, and quality of life in patients with postoperative dumping.

  2. A prospective, multicentre study to investigate the efficacy, safety and tolerability of octreotide LAR® (long-acting repeatable octreotide) in the primary therapy of patients with acromegaly

    PubMed Central

    Mercado, Moises; Borges, Fatima; Bouterfa, Hakim; Chang, Tien-Chun; Chervin, Alberto; Farrall, Andrew J; Patocs, Attila; Petersenn, Stephan; Podoba, Jan; Safari, Mitra; Wardlaw, Joanna

    2007-01-01

    Objective To evaluate the efficacy, safety and tolerability of octreotide LAR® (long-acting repeatable octreotide) in the primary therapy of acromegaly. Design and patients Ninety-eight previously untreated acromegalics were recruited into this prospective multicentre study. A total of 68 patients successfully completed 48 weeks of the study period, received 12 doses of octreotide LAR 10–30 mg every 4 weeks, and constituted the population used for this analysis. Measurements and results A clinically relevant reduction (i.e. to ≤ 5 µg/l) in mean GH (mGH) was recorded in 72% of patients after 24 weeks of treatment, and 42% reached a ‘safe’ GH value (≤ 2·5 µg/l). At week 48, 16 more patients were considered partial GH responders (GH > 2·5 µg/l and ≤ 5 µg/l) and 44% had reached a GH level ≤ 2·5 µg/l. IGF-1 levels normalized in 38% and 34% of patients after 24 and 48 weeks of treatment, respectively. At study completion, 10 patients (14·7%) who had not normalized their IGF-1 levels had achieved at least a 50% decrement in this marker. In eight microadenoma patients, tumour volume decreased from a mean baseline level of 298 ± 145 mm3 to 139 ± 94 mm3 after 24 weeks and to 99 ± 70 mm3 after 48 weeks of therapy. In 60 patients with macroadenoma, the corresponding values were 3885 ± 5077 mm3 at baseline and 2723 ± 3435 and 2406 ± 3207 mm3 after 24 and 48 weeks, respectively. At weeks 24 and 48, a significant (> 20%) tumour volume reduction was reported in 63% and 75% of patients, respectively. A reduction in the severity of symptoms of acromegaly was observed early in treatment and was maintained throughout the study period. Conclusion Octreotide LAR represents a viable alternative to surgery for primary treatment of acromegaly leading to a progressive regression of tumour volume, a sustained control of biochemical abnormalities and an adequate relief of symptoms of the disease. PMID:17465997

  3. Hormonal secretion and quality of life in Nelson syndrome and Cushing disease after long acting repeatable octreotide: a short series and update.

    PubMed

    Arregger, Alejandro L; Cardoso, Estela M L; Sandoval, Olga B; Monardes Tumilasci, Elida G; Sanchez, Rocío; Contreras, Liliana N

    2014-01-01

    Clinical management of persistent adrenocorticotropin hormone (ACTH) excess in Nelson syndrome (NS) and Cushing disease (CD) remains a challenge. Somatostatin and its analogs as octreotide decrease ACTH secretion through somatostatin receptors of pituitary cells. To our knowledge, there are no reports on the effect of long-acting repeatable octreotide (oct-lar) on hormonal secretion and quality of life in patients with NS and CD who failed conventional therapy. Herein, we describe the effects of treatment with oct-lar (20 mg/month intramurally) in 1 woman with NS and 2 women with persistent CD. Oct-lar therapy reduced ACTH secretion and improved the quality of life in NS patient. By contrast, in CD patients, it failed to control ACTH and cortisol secretion, and the quality of life remained unchanged.

  4. Subcutaneously Administered Self-Cleaving Hydrogel-Octreotide Conjugates Provide Very Long-Acting Octreotide.

    PubMed

    Schneider, Eric L; Henise, Jeff; Reid, Ralph; Ashley, Gary W; Santi, Daniel V

    2016-07-20

    We developed a long-acting drug-delivery system that supports subcutaneous administration of the peptidic somatostatin agonist octreotide-a blockbuster drug used to treat acromegaly and neuroendocrine tumors. The current once-a-month polymer-encapsulated octreotide, Sandostatin LAR, requires a painful intragluteal injection through a large needle by a health-care professional. To overcome such shortcomings, Tetra-PEG hydrogel microspheres were covalently attached to the α-amine of d-Phe(1) or the ε-amine of Lys(5) of octreotide by a self-cleaving β-eliminative linker; upon subcutaneous injection in the rat using a small-bore needle, octreotide was slowly released. The released drug from the ε-octreotide conjugate showed a remarkably long serum half-life that exceeded two months. The α-octreotide conjugate had a half-life of ∼2 weeks, and showed an excellent correlation of in vitro and in vivo drug release. Pharmacokinetic models indicate these microspheres should support once-weekly to once-monthly self-administered subcutaneous dosing in humans. The hydrogel-octreotide conjugate shows the favorable pharmacokinetics of Sandostatin LAR without its drawbacks.

  5. Long acting release-octreotide as "rescue" therapy to control angiodysplasia bleeding: A retrospective study of 98 cases.

    PubMed

    Nardone, Gerardo; Compare, Debora; Scarpignato, Carmelo; Rocco, Alba

    2014-08-01

    Gastrointestinal angiodysplasias are an important cause of difficult to manage bleeding, especially in older patients. To retrospectively evaluate the long-term efficacy of long acting release-octreotide in controlling angiodysplasia bleeding. 98 patients with a history of bleeding due to gastrointestinal angiodysplasias lasting over 2 years were retrospectively selected among those treated from January 2000 to December 2008. All patients had received octreotide 0.1mg tid for 28 days and, then from day 14, long acting release-octreotide 20mg monthly, for 6 months. The mean follow-up was 78 months. In all patients mean haemoglobin levels significantly increased and the number of bleeding episodes, hospitalizations, patients requiring blood transfusions and units of transfused red cells significantly decreased, compared to the two-year observation period before starting therapy. According to outcome patients were classified as: 40 full responders (40.8%), 32 relapsers (32.6%) and 26 poor responders (26.5%). At multivariate analysis age >65 years, male sex, chronic antiplatelet therapy, chronic obstructive pulmonary disease and chronic renal failure were the only covariates independently associated with poor response to therapy. Our study suggests that long acting release-octreotide could be used as rescue therapy to control bleeding due to gastrointestinal angiodysplasias in patients not suitable for endoscopic or surgical treatments. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  6. Time course of GH and IGF-1 levels following withdrawal of long-acting octreotide in acromegaly.

    PubMed

    Lorcy, Y; Dejager, S; Chanson, P

    2000-11-01

    for 12 months with octreotide LAR. The duration of GH suppression after treatment withdrawal is variable. Mean GH levels remained below 2.5 micrograms/L in 15% of our patients for up to 21 weeks following withdrawal of octreotide LAR. In practice, it may be preferable to wait several months after long-acting somatostatin analog withdrawal before reassessing hormone status. Owing this long-lasting effect, a dose reduction to 10 mg and/or a longer interval between injections could be considered for very good responders, as this would lead to considerable cost savings without affecting GH or IGF-1 control.

  7. [Cost-effectiveness analysis of octreotide long acting release and lanreotide slow release for the treatment of postoperative patients with active acromegaly in China].

    PubMed

    Xuan, J W; Zhang, Z Y; Wang, Y F; Mao, Z G; Lu, Y J; Wang, R Z

    2017-03-14

    Objective: To evaluate the cost-effectiveness of octreotide long acting release (LAR) vs lanreotide slow release (SR) for the treatment of postoperative acromegalic patients with elevated levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) in China. Methods: A decision tree model was constructed and the treatment impact was projected for one year in Chinese setting. The clinical efficacy measure used was the percentage of patients achieving normalization (control) of either IGF-1 or GH levels. Efficacy of octreotide LAR and lanreotide SR, incidence of comorbidities, impact of acromegaly on health-related quality of life, and drug-related side effects data were obtained from literature. The cost of medication was collected through a chart review from five hospitals in five cities of China. Clinical experts from these hospitals were requested to complete a questionnaire to document the utilization of medical resources, costs of comorbidities, side effects as well as cost of administration. One-way sensitivity analysis was performed to evaluate the robustness of the results. Results: Compared to lanreotied SR group, the percentage of patients achieving normalization of IGF-1 and GH levels of octreotide LAR group were 10% and 9% higher, respectively. When either IGF-1 or GH control were used as the efficacy measure, patients in the octreotide LAR group exhibit less comorbidities and need less continued treatment with a second operation and radiotherapy than those in lanreotide SR group. When IGF-1 was used as efficacy measure, octreotide LAR not only achieved better efficacy but resulted in overall cost-saving, with a total cost savings of ¥ 3 792 per patient for one year, which demonstrated that octreotide LAR was a dominant cost-saving strategy. When GH control was used as the efficacy measure, octreotide LAR achieved a better overall clinical efficacy with a slightly higher total costs (¥ 4 121 higher per patient per year). Sensitivity

  8. Pituitary apoplexy causing spontaneous remission of acromegaly following long-acting octreotide therapy: a rare drug side effect or just a coincidence

    PubMed Central

    Kumar, Sunil; Sharma, Shruti

    2016-01-01

    Pituitary apoplexy is characterized by abrupt onset of haemorrhage or non-haemorrhagic infarction of a pituitary adenoma. The clinical features include acute onset severe headache, visual field defects, meningeal irritation, ophthalmoplegia and hypopituitarism. The pituitary apoplexy may be clinically silent in ∼25% of patients. We report a case of acromegaly due to pituitary macroadenoma. The patient was started on long-acting octreotide therapy. On 3-month follow-up, the patient showed clinical and biochemical remission and the magnetic resonance imaging (MRI) of the brain showed subclinical haemorrhage and resolution of tumour. The octreotide therapy was stopped. On 6-month follow-up, the patient was still in remission and the MRI of brain revealed non-enhancing mixed intensities haemorrhagic and cystic areas of the pituitary gland. In our patient, whether spontaneous remission of acromegaly due to subclinical pituitary haemorrhage was coincidental or due to long-acting octreotide therapy is still a dilemma. We report this case because of rarity and clinical importance of this unusual occurrence. PMID:27123308

  9. Pituitary apoplexy causing spontaneous remission of acromegaly following long-acting octreotide therapy: a rare drug side effect or just a coincidence.

    PubMed

    Kumar, Sunil; Sharma, Shruti

    2016-04-01

    Pituitary apoplexy is characterized by abrupt onset of haemorrhage or non-haemorrhagic infarction of a pituitary adenoma. The clinical features include acute onset severe headache, visual field defects, meningeal irritation, ophthalmoplegia and hypopituitarism. The pituitary apoplexy may be clinically silent in ∼25% of patients. We report a case of acromegaly due to pituitary macroadenoma. The patient was started on long-acting octreotide therapy. On 3-month follow-up, the patient showed clinical and biochemical remission and the magnetic resonance imaging (MRI) of the brain showed subclinical haemorrhage and resolution of tumour. The octreotide therapy was stopped. On 6-month follow-up, the patient was still in remission and the MRI of brain revealed non-enhancing mixed intensities haemorrhagic and cystic areas of the pituitary gland. In our patient, whether spontaneous remission of acromegaly due to subclinical pituitary haemorrhage was coincidental or due to long-acting octreotide therapy is still a dilemma. We report this case because of rarity and clinical importance of this unusual occurrence.

  10. Somatostatin receptor expression indicates improved prognosis in gastroenteropancreatic neuroendocrine neoplasm, and octreotide long-acting release is effective and safe in Chinese patients with advanced gastroenteropancreatic neuroendocrine tumors

    PubMed Central

    Wang, Yuhong; Wang, Wei; Jin, Kaizhou; Fang, Cheng; Lin, Yuan; Xue, Ling; Feng, Shiting; Zhou, Zhiwei; Shao, Chenghao; Chen, Minhu; Yu, Xianjun; Chen, Jie

    2017-01-01

    Gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is known to overexpress somatostatin receptors (SSTRs), most commonly SSTR2 and SSTR5. The expression of SSTRs on tumor cells forms the basis for somatostatin analog treatment of patients with NEN. The present study detected the expression of SSTR2 and SSTR5 in GEP-NEN and investigated the efficacy and safety of octreotide long-acting release (LAR) in the treatment of advanced gastroenteropancreatic neuroendocrine tumors (GEP-NET) in China. The present study reported that functionality of the pancreas, G1 and G2 grading, NET classification and Tumor-Node-Metastasis stages I and II were associated with higher SSTR2 positive expression. Similarly, SSTR5 was increased in pancreatic and well-differentiated tumors. SSTR2 and SSTR5 positive expression predicted improved survival in GEP-NEN patients. The median overall survival of patients treated with octreotide LAR was not reached. The median time to progression was 20.2 months, with the objective response rate being 5.6% and the stable disease rate being 79.6%. A total of 25.9% of the patients experienced adverse drug reactions. In conclusion, the present study demonstrated that SSTR2 and SSTR5 are heterogeneously expressed in GEP-NEN. Both markers may serve as potential prognostic factors. Octreotide LAR is effective and safe in the treatment of Chinese patients with advanced GEP-NET. PMID:28454229

  11. Somatostatin receptor expression indicates improved prognosis in gastroenteropancreatic neuroendocrine neoplasm, and octreotide long-acting release is effective and safe in Chinese patients with advanced gastroenteropancreatic neuroendocrine tumors.

    PubMed

    Wang, Yuhong; Wang, Wei; Jin, Kaizhou; Fang, Cheng; Lin, Yuan; Xue, Ling; Feng, Shiting; Zhou, Zhiwei; Shao, Chenghao; Chen, Minhu; Yu, Xianjun; Chen, Jie

    2017-03-01

    Gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is known to overexpress somatostatin receptors (SSTRs), most commonly SSTR2 and SSTR5. The expression of SSTRs on tumor cells forms the basis for somatostatin analog treatment of patients with NEN. The present study detected the expression of SSTR2 and SSTR5 in GEP-NEN and investigated the efficacy and safety of octreotide long-acting release (LAR) in the treatment of advanced gastroenteropancreatic neuroendocrine tumors (GEP-NET) in China. The present study reported that functionality of the pancreas, G1 and G2 grading, NET classification and Tumor-Node-Metastasis stages I and II were associated with higher SSTR2 positive expression. Similarly, SSTR5 was increased in pancreatic and well-differentiated tumors. SSTR2 and SSTR5 positive expression predicted improved survival in GEP-NEN patients. The median overall survival of patients treated with octreotide LAR was not reached. The median time to progression was 20.2 months, with the objective response rate being 5.6% and the stable disease rate being 79.6%. A total of 25.9% of the patients experienced adverse drug reactions. In conclusion, the present study demonstrated that SSTR2 and SSTR5 are heterogeneously expressed in GEP-NEN. Both markers may serve as potential prognostic factors. Octreotide LAR is effective and safe in the treatment of Chinese patients with advanced GEP-NET.

  12. Preoperative long-acting octreotide treatment for invasive thyrotropin-secreting pituitary macroadenoma after previous radioiodine thyroid ablation.

    PubMed

    Gruszka, Anna; Zielinski, Grzegorz M; Kunert-Radek, Jolanta

    2014-02-01

    We report a 33-year-old woman with invasive thyrotropin-secreting pituitary adenoma after previous thyroid ablation with radioiodine who was successfully treated with transsphenoidal surgery after pre-treatment with octreotide-LAR for 10 months. Since invasive and aggressive thyrotropin-secreting macroadenomas are more frequently observed in patients who have undergone thyroid ablation, we suggest preoperative treatment with somatostatin analogs should be considered in these patients to reduce serum thyrotropin and stabilize or reduce tumor size.

  13. Octreotide Injection

    MedlinePlus

    ... hormone (a natural substance) produced by people with acromegaly (condition in which the body produces too much ... Octreotide long-acting injection is used to control acromegaly, carcinoid tumors, and VIP-omas in people who ...

  14. The effect of long-acting reversible contraception on rapid repeat pregnancy in adolescents: a review.

    PubMed

    Baldwin, Maureen K; Edelman, Alison B

    2013-04-01

    Repeat pregnancy within 2 years of a previous birth or abortion occurs in approximately 35% of recently pregnant female adolescents. The majority of these pregnancies are classified as unintended with about half ending in births and the remainder in abortions. Rapid repeat pregnancy (RRP) is associated with increased maternal and neonatal morbidity and continues a cycle of economic deprivation for young women and their families. Immediately following a pregnancy, most young women report an intention to avoid pregnancy in the near future, but many change their minds or become ambivalent within months. Lack of contraceptive use is more common among those teens that resume sexual intercourse earlier, live with a male partner, had a preterm delivery, or had an intended teen pregnancy. Adolescents who do not initiate a long-acting reversible contraceptive (LARC) method (intrauterine device or contraceptive implant) have up to a 35 times increased risk of RRP compared with their peers using LARC. Risk of RRP is decreased when LARC methods are initiated earlier after an abortion or within the postpartum period. This review will focus on the prevalence of RRP, the risk factors for RRP, and the effectiveness of strategies to reduce unintended RRP including counseling and early initiation of long-acting contraceptive methods.

  15. Improvement of sleep apnoea due to acromegaly during short-term treatment with octreotide.

    PubMed

    Leibowitz, G; Shapiro, M S; Salameh, M; Glaser, B

    1994-08-01

    Two acromegalic patients suffering from severe obstructive sleep apnoea syndrome were treated with the long-acting somatostatin analogue octreotide. Daytime sleepiness and fatigue improved within a few days. Repeat sleep studies performed after octreotide treatment revealed more confluent sleep with a shorter duration of sleep apnoea. Nocturnal hypoxaemia improved in one patient. Octreotide might be an effective noninvasive treatment for sleep apnoea of acromegaly.

  16. A multicenter, randomized, double-blind, placebo-controlled, dose-finding trial of a long-acting formulation of octreotide in promoting weight loss in obese adults with insulin hypersecretion

    PubMed Central

    Lustig, RH; Greenway, F; Velasquez-Mieyer, P; Heimburger, D; Schumacher, D; Smith, D; Smith, W; Soler, N; Warsi, G; Berg, W; Maloney, J; Benedetto, J; Zhu, W; Hohneker, J

    2006-01-01

    Objective To compare changes in weight in obese patients who received long-acting octreotide (octreotide LAR) at one of three dose levels (20, 40, or 60 mg) or placebo over 6 months and to identify the lowest dose of octreotide LAR that safely achieved optimal weight loss. Design Randomized, double-blind, placebo-controlled trial of octreotide LAR at three dose levels. Patients A total of 172 adults (28 men and 144 women) with at least moderate obesity (body mass index (BMI) range 30–65 kg/m2) and evidence of insulin hypersecretion were enrolled. Patients were predominantly either Caucasian (50.0%) or African American (45.3%). The mean age (38±11 year), weight (110.7±23 kg), and BMI (39.8±6.5 kg/m2) were similar across the four treatment groups. Measurements Efficacy measures included weight, BMI, fasting serum glucose; triglycerides; percentage of total body fat and abdominal fat as measured by dual-energy X-ray absorptiometry; skin fold thickness; waist-to-hip circumference; leptin; percentage of carbohydrates, fat, and protein ingested; nutritional evaluation (including dietary analysis – 3-day food record); quality of life (QoL; using the Impact of Weight on Quality of Life-Lite™); Beck Depression Inventory; and Carbohydrate Craving Questionnaire. Safety measures included medical history, vital signs, physical examinations, hematology, blood chemistries, thyroid function tests, hemoglobin A1c, gallbladder ultrasound, electrocardiograms, and adverse events. Results After 6 months of treatment, patients receiving 40 or 60 mg of octreotide LAR experienced statistically significant weight loss compared to baseline, with mean differences from placebo in percent weight change of −1.98 and −1.87%, respectively. This finding was accompanied by statistically significant mean decreases in BMI compared to baseline, that is, a mean decrease of 0.73 and 0.79 kg/m2 for the 40 and 60 mg treatment arms, respectively. The observed weight loss was progressive during

  17. The long-acting integrase inhibitor GSK744 protects macaques from repeated intravaginal SHIV challenge.

    PubMed

    Radzio, Jessica; Spreen, William; Yueh, Yun Lan; Mitchell, James; Jenkins, Leecresia; García-Lerma, J Gerardo; Heneine, Walid

    2015-01-14

    Daily preexposure prophylaxis (PrEP) with Truvada is a proven HIV prevention strategy; however, its effectiveness is limited by low adherence. Antiretroviral drug formulations that require infrequent dosing may increase adherence and thus PrEP effectiveness. We investigated whether monthly injections of a long-acting formulation of the HIV integrase inhibitor GSK1265744 (GSK744 LA) prevented simian/human immunodeficiency virus (SHIV) infection by vaginal challenge in macaques. Female pigtail macaques (n = 12) were exposed to intravaginal inoculations of SHIV twice a week for up to 11 weeks. Half of the animals received a GSK744 LA injection every 4 weeks, and half received placebo. GSK744 LA, at plasma concentrations achievable with quarterly injections in humans, protected all six macaques from infection. Placebo controls were all infected after a median of 4 (range, 2 to 20) vaginal challenges with SHIV. Efficacy was related to high and sustained vaginal and plasma drug concentrations that remained above the protein-adjusted 90% inhibitory concentration during the dosing cycles. These data support advancement of GSK744 LA as a potential PrEP candidate for women.

  18. A Long-Acting Integrase Inhibitor Protects Female Macaques from Repeated High-Dose Intravaginal SHIV Challenge

    PubMed Central

    Andrews, Chasity D.; Yueh, Yun Lan; Spreen, William R.; St. Bernard, Leslie; Boente-Carrera, Mar; Rodriguez, Kristina; Gettie, Agegnehu; Russell-Lodrigue, Kasi; Blanchard, James; Ford, Susan; Mohri, Hiroshi; Cheng-Mayer, Cecilia; Hong, Zhi; Ho, David D.; Markowitz, Martin

    2015-01-01

    GSK1265744 long-acting (GSK744 LA) is a strand-transfer inhibitor of HIV/SIV integrase and was shown to be an effective pre-exposure prophylaxis agent in a low-dose intrarectal SHIV rhesus macaque challenge model. Here, we examined the pharmacokinetics and efficacy of GSK744 LA as PrEP against repeat high-dose intravaginal SHIV challenge in female rhesus macaques treated with Depo-Provera which promotes viral transmission vaginally. When Depo-Provera-treated female rhesus macaques were dosed with 50 mg/kg of GSK744 LA monthly, systemic and tissue drug concentrations were lower than previously observed in male rhesus macaques. GSK744 concentrations were 5-fold lower on average in cervical tissues than rectal tissues. Eight female rhesus macaques were treated with GSK744 LA at week 0, and four female rhesus macaques served as controls. All animals received a high dose challenge of SHIV162P3 at week 1. No infection was detected in GSK744 LA-treated rhesus macaques, whereas viremia was detected 1 to 2 weeks after SHIV challenge in all control animals. The GSK744 LA-treated rhesus macaques were given a second administration of drug at week 4 and further challenged at weeks 5 and 7. GSK744 LA treatment protected 6 of 8 female rhesus macaques against three high-dose SHIV challenges, whereas all control animals became infected after the first challenge (P = 0.0003, log-rank test). These results support further clinical development of GSK744 LA for pre-exposure prophylaxis. PMID:25589630

  19. A long-acting integrase inhibitor protects female macaques from repeated high-dose intravaginal SHIV challenge.

    PubMed

    Andrews, Chasity D; Yueh, Yun Lan; Spreen, William R; St Bernard, Leslie; Boente-Carrera, Mar; Rodriguez, Kristina; Gettie, Agegnehu; Russell-Lodrigue, Kasi; Blanchard, James; Ford, Susan; Mohri, Hiroshi; Cheng-Mayer, Cecilia; Hong, Zhi; Ho, David D; Markowitz, Martin

    2015-01-14

    Long-acting GSK1265744 (GSK744 LA) is a strand transfer inhibitor of the HIV/SIV (simian immunodeficiency virus) integrase and was shown to be an effective preexposure prophylaxis (PrEP) agent in a low-dose intrarectal SHIV (simian-human immunodeficiency virus) rhesus macaque challenge model. We examined the pharmacokinetics and efficacy of GSK744 LA as PrEP against repeat high-dose intravaginal SHIV challenge in female rhesus macaques treated with Depo-Provera (depot medroxyprogesterone acetate), which promotes viral transmission vaginally. When Depo-Provera-treated female rhesus macaques were dosed with GSK744 LA (50 mg/kg) monthly, systemic and tissue drug concentrations were lower than previously observed in male rhesus macaques. GSK744 concentrations were fivefold lower on average in cervical tissues than in rectal tissues. Eight female rhesus macaques were treated with GSK744 LA at week 0, and four female rhesus macaques served as controls. All animals received a high-dose challenge of SHIV162P3 at week 1. No infection was detected in GSK744 LA-treated rhesus macaques, whereas viremia was detected 1 to 2 weeks after SHIV challenge in all control animals. The GSK744 LA-treated rhesus macaques were given a second administration of drug at week 4 and further challenged at weeks 5 and 7. GSK744 LA treatment protected six of eight female rhesus macaques against three high-dose SHIV challenges, whereas all control animals became infected after the first challenge (P = 0.0003, log-rank test). These results support further clinical development of GSK744 LA for PrEP.

  20. Case study of a 15-year-old boy with McCune-Albright syndrome combined with pituitary gigantism: effect of octreotide-long acting release (LAR) and cabergoline therapy.

    PubMed

    Tajima, Toshihiro; Tsubaki, Junko; Ishizu, Katsura; Jo, Wakako; Ishi, Nobuaki; Fujieda, Kenji

    2008-07-01

    The use of octreotide-LAR and cabergoline therapy has shown great promise in adults with acromegaly; however, the experience in pediatric patients has rarely been reported. We described a clinical course of a 15-year-old boy of McCune-Albright syndrome (MAS) with pituitary gigantism. At the age of 8 years, a growth hormone (GH) and prolactin (PRL) producing pituitary adenoma was diagnosed at our hospital. He also had multiple fibrous dysplasia, so that he was diagnosed as having MAS. The tumor was partially resected, and GNAS1 gene mutation (R201C) was identified in affected tissues. We introduced octreotide to suppress GH secretion (100 mug 2/day s.c). During therapy with octreotide, IGF-1 and GH levels could not be suppressed and the patient frequently complained of nausea from octreotide treatment. Therefore, the therapy was changed to monthly injections of octreotide-LAR at the age of 12.3 years and was partially effective. However, as defect of left visual field worsened due to progressive left optic canal stenosis, he underwent second neurological decompression of the left optic nerve at 13.4 years of age. After surgery, in addition to octreotide-LAR, cabergoline (0.25 mg twice a month) was started. This regimen normalized serum levels of GH and IGF-1; however, he showed impaired glucose tolerance and gallstones at 15.7 years of age. Therefore, the dose of octreotide-LAR was reduced to 10 mg and the dose of cabergoline increased. This case demonstrated the difficulty of treating pituitary gigantism due to MAS. The use of octreotide-LAR and cabergoline should be considered even in pediatric patients; however, adverse events due to octreotide-LAR must be carefully examined.

  1. Phase III study of pasireotide long-acting release in patients with metastatic neuroendocrine tumors and carcinoid symptoms refractory to available somatostatin analogues

    PubMed Central

    Wolin, Edward M; Jarzab, Barbara; Eriksson, Barbro; Walter, Thomas; Toumpanakis, Christos; Morse, Michael A; Tomassetti, Paola; Weber, Matthias M; Fogelman, David R; Ramage, John; Poon, Donald; Gadbaw, Brian; Li, Jiang; Pasieka, Janice L; Mahamat, Abakar; Swahn, Fredrik; Newell-Price, John; Mansoor, Wasat; Öberg, Kjell

    2015-01-01

    In a randomized, double-blind, Phase III study, we compared pasireotide long-acting release (pasireotide LAR) with octreotide long-acting repeatable (octreotide LAR) in managing carcinoid symptoms refractory to first-generation somatostatin analogues. Adults with carcinoid tumors of the digestive tract were randomly assigned (1:1) to receive pasireotide LAR (60 mg) or octreotide LAR (40 mg) every 28 days. Primary outcome was symptom control based on frequency of bowel movements and flushing episodes. Objective tumor response was a secondary outcome. Progression-free survival (PFS) was calculated in a post hoc analysis. Adverse events were recorded. At the time of a planned interim analysis, the data monitoring committee recommended halting the study because of a low predictive probability of showing superiority of pasireotide over octreotide for symptom control (n=43 pasireotide LAR, 20.9%; n=45 octreotide LAR, 26.7%; odds ratio, 0.73; 95% confidence interval [CI], 0.27–1.97; P=0.53). Tumor control rate at month 6 was 62.7% with pasireotide and 46.2% with octreotide (odds ratio, 1.96; 95% CI, 0.89–4.32; P=0.09). Median (95% CI) PFS was 11.8 months (11.0 – not reached) with pasireotide versus 6.8 months (5.6 – not reached) with octreotide (hazard ratio, 0.46; 95% CI, 0.20–0.98; P=0.045). The most frequent drug-related adverse events (pasireotide vs octreotide) included hyperglycemia (28.3% vs 5.3%), fatigue (11.3% vs 3.5%), and nausea (9.4% vs 0%). We conclude that, among patients with carcinoid symptoms refractory to available somatostatin analogues, similar proportions of patients receiving pasireotide LAR or octreotide LAR achieved symptom control at month 6. Pasireotide LAR showed a trend toward higher tumor control rate at month 6, although it was statistically not significant, and was associated with a longer PFS than octreotide LAR. PMID:26366058

  2. Six-month preoperative octreotide treatment in unselected, de novo patients with acromegaly: effect on biochemistry, tumour volume, and postoperative cure.

    PubMed

    Carlsen, Sven M; Svartberg, Johan; Schreiner, Thomas; Aanderud, Sylvi; Johannesen, Oivind; Skeie, Svein; Lund-Johansen, Morten; Fougner, Stine L; Bollerslev, Jens

    2011-06-01

    Treatment with somatostatin analogues is the primary medical treatment of acromegaly. Controversies still exist whether acute octreotide effect predicts long-term biochemical effects, tumour regression or surgical cure. This prospective study investigates effect of 6-month treatment with octreotide long-acting repeatable (LAR) on insulin-like growth factor-1 (IGF-1) and growth hormone (GH) levels, pituitary function, tumour regression and postoperative cure in de novo acromegalic patients. After a baseline evaluation including fasting hormone levels, MRI scan and an acute 50 μg octreotide test, 32 patients were treated with octreotide LAR 20 mg every 28th day for 6 months before surgery. Treatment effects on IGF-1 and GH levels, serum hormone levels and tumour volume were monitored. Surgical cure was evaluated 3 months postoperatively. Mean tumour volume reduction was 35%, in one-third of the patients more than 50%, while approximately one-third achieved biochemical remission evaluated by normalized IGF-1 levels. The GH reduction following an acute octreotide test was 81 ± 19% and associated with long-term GH reduction (r = 0·78, P < 0·0005). However, neither acute (r = 0·29, P = 0·12) nor the long-term octreotide effect (r = 0·11, P = 0·58) on GH levels was associated with tumour volume reduction and did not predict subsequent surgical cure. Six months of long-acting octreotide using a fixed dose, 1/3 of the patients came in biochemical remission, while 2/3 had significant tumour reduction. Moreover, an acute effect of octreotide seemed to be a prerequisite for long-term effect. © 2011 Blackwell Publishing Ltd.

  3. Gastrointestinal neuroendocrine tumors treated with high dose octreotide-LAR: A systematic literature review

    PubMed Central

    Broder, Michael S; Beenhouwer, David; Strosberg, Jonathan R; Neary, Maureen P; Cherepanov, Dasha

    2015-01-01

    AIM: To review literature on efficacy and safety of octreotide-long-acting repeatable (LAR) used at doses higher than the Food and Drug Administration (FDA)-approved 30 mg/mo for treatment of neuroendocrine tumors (NETs). METHODS: We searched PubMed and Cochrane Library from 1998-2012, 5 conferences (American Society of Clinical Oncology, Endocrine Society, European Neuroendocrine Tumor Society, European Society for Medical Oncology, North American Neuroendocrine Tumor Society) from 2000-2013 using MeSH and keyterms including neuroendocrine tumors, carcinoid tumor, carcinoma, neuroendocrine, and octreotide. Bibliographies of accepted articles were also searched. Two reviewers reviewed titles, abstracts, and full-length articles. Studies that reported data on efficacy and safety of ≥ 30 mg/mo octreotide-LAR for NETs in human subjects, published in any language were included in the review. RESULTS: The search identified 1086 publications, of which 238 underwent full-text review (20 were translated into English); 17 were included in the review. Studies varied in designs, subjects, octreotide-LAR regimens, and definition of outcomes. Eleven studies reported use of higher doses to control symptoms and tumor progression, although symptom severity and formal quality-of-life analysis were not quantitatively measured. Ten studies reported efficacy, describing 260 subjects with doses ranging from 40 mg/mo or 30 mg/3 wk up to 120 mg/mo. Eight studies reported expert clinical opinion that supported dose escalation of octreotide-LAR up to 60 mg/mo for symptom control and suggested increased doses may be effective at preventing tumor progression. Eight studies reported safety; there was no evidence of increased toxicity associated with doses of octreotide-LAR > 30 mg/mo. CONCLUSION: As reported in this review, octreotide-LAR at doses > 30 mg/mo is being prescribed for symptom and tumor control in NET patients. Furthermore, expert clinical opinion provided support for

  4. Efficacy of a slow-release formulation of lanreotide (Autogel) 120 mg) in patients with acromegaly previously treated with octreotide long acting release (LAR): an open, multicentre longitudinal study.

    PubMed

    Ronchi, C L; Boschetti, M; Degli Uberti, E C; Mariotti, S; Grottoli, S; Loli, P; Lombardi, G; Tamburrano, G; Arvigo, M; Angeletti, G; Boscani, P F; Beck-Peccoz, P; Arosio, M

    2007-10-01

    Lanreotide Autogel 120 mg (ATG120; Ipsen S.p.A, Milan, Italy) is a high-dose, sustained-release aqueous gel formulation, supplied in a prefilled syringe and given by deep subcutaneous injection. The aim of this study was to compare efficacy and tolerability of ATG120 given every 4-8 weeks with those of octreotide LAR (o-LAR) given every 4 weeks. DESIGN PATIENTS AND INTERVENTION: A phase III multicentre Italian open clinical study of 23 acromegalic patients (15 female, 8 male). All patients had received o-LAR for 6-18 months and, after 3 months wash out, ATG120 was given every 6 weeks for a total of four injections (Period 1). Then the interval between ATG120 injections was adjusted according to three different schemes: every 4, 6 or 8 weeks depending on GH levels (GH > 2.5 microg/l; 1 < GH

  5. Octreotide and Lanreotide in Gastroenteropancreatic Neuroendocrine Tumors.

    PubMed

    Pokuri, Venkata K; Fong, Mei Ka; Iyer, Renuka

    2016-01-01

    Neuroendocrine tumors are heterogeneous, rare malignancies that arise most commonly in the gastrointestinal tract and pancreas. They often secrete vasoactive substances resulting in carcinoid syndrome and the tumor cells exclusively express somatostatin receptors. Octreotide and lanreotide are the two synthetic somatostatin analogs used for the control of carcinoid symptoms and tumor progression in advanced inoperable disease. Recent pivotal trials (PROMID and CLARINET studies) established their antitumor activity. We discuss the available data to support their use as symptom controlling and antiproliferative agents. This article also reviews the guidelines (National Comprehensive Cancer Network and North American Neuro Endocrine Tumor Society), cost-analysis (suggesting the cost-effectiveness of lanreotide autogel compared to higher doses of octreotide long acting release formulation in refractory patients), and future directions of somatostatin analogs in the management of patients refractory to conventional doses of octreotide and lanreotide.

  6. Octreotide for conservative management of intractable high output post operative chylous fistula: a case report.

    PubMed

    Prabhu, Sundararaman; Thomas, Shaji

    2015-03-01

    A case of high output post neck dissection chylous fistula is presented, which was successfully managed conservatively with octreotide; a long acting somatostatin analogue. Routine measures had failed, and secondary complications precluded thoracoscopic ligation. We discuss the spectrum of problems associated with chylous fistula and review the rationale behind the use of octreotide.

  7. Long-acting progestogens.

    PubMed

    Affandi, Biran

    2002-04-01

    Steroids can be administered in at least five different ways: injectables; hormone-releasing intra-uterine devices (IUDs); implants; vaginal rings; and pills. Progestogens which are synthetic steroids, are used as the main bioactive substances. Different progestogens are effective for different periods of time. Progestins in daily oral pills are effective for 24 hours. The effectiveness of a progestogen can be prolonged by incorporating it in a sustained-release system that gradually releases the hormone; therefore they can be effective up to 5 years or more. Two progestogen-only injectables are widely available in the family planning programmes, (DMPA and NET-EN) and two combined injectables, Cyclofem (DMPA + EC), and Mesigyna (NET-EN + EV). The ring is placed by the woman in her vagina, where it gradually releases hormone. Implantable contraceptives are placed just under the skin on the inside of the woman's arm. Implant capsules release the progestogen at a slow, steady rate. There are three implantables available in the market: Implanon; Norplant; and Jadelle. They are effective for 1-5 years, but then must be replaced. Natural and synthetic progestogens were first added to IUDs in the early 1970s. The main problem of long-acting progestogens is the disruption of the menstrual cycle.

  8. Mifepristone Improves Octreotide Efficacy in Resistant Ectopic Cushing's Syndrome

    PubMed Central

    Moraitis, Andreas G.; Auchus, Richard J.

    2016-01-01

    A 30-year-old Caucasian man presented with severe Cushing's syndrome (CS) resulting from ectopic adrenocorticotropin syndrome (EAS) from a metastatic pancreatic neuroendocrine tumor. The patient remained hypercortisolemic despite treatment with steroidogenesis inhibitors, chemotherapy, and octreotide long-acting release (LAR) and was enrolled in a 24-week, phase 3 clinical trial of mifepristone for inoperable hypercortisolemia. After mifepristone was added to ongoing octreotide LAR treatment, EAS symptoms essentially resolved. Cortisol decreased dramatically, despite mifepristone's competitive glucocorticoid receptor antagonist effects. The clinical and biochemical effects reversed upon mifepristone discontinuation despite the continued use of octreotide LAR therapy. Substantial improvement in octreotide LAR efficacy with mifepristone use was noted in this patient with ectopic CS, consistent with upregulation of somatostatin receptors previously downregulated by hypercortisolemia. PMID:26989527

  9. Randomized Clinical Trial of Long-Acting Somatostatin for Autosomal Dominant Polycystic Kidney and Liver Disease

    PubMed Central

    Masyuk, Tetyana V.; Page, Linda J.; Kubly, Vickie J.; Bergstralh, Eric J.; Li, Xujian; Kim, Bohyun; King, Bernard F.; Glockner, James; Holmes, David R.; Rossetti, Sandro; Harris, Peter C.; LaRusso, Nicholas F.; Torres, Vicente E.

    2010-01-01

    There are no proven, effective therapies for polycystic kidney disease (PKD) or polycystic liver disease (PLD). We enrolled 42 patients with severe PLD resulting from autosomal dominant PKD (ADPKD) or autosomal dominant PLD (ADPLD) in a randomized, double-blind, placebo-controlled trial of octreotide, a long-acting somatostatin analogue. We randomly assigned 42 patients in a 2:1 ratio to octreotide LAR depot (up to 40 mg every 28 ± 5 days) or placebo for 1 year. The primary end point was percent change in liver volume from baseline to 1 year, measured by MRI. Secondary end points were changes in total kidney volume, GFR, quality of life, safety, vital signs, and clinical laboratory tests. Thirty-four patients had ADPKD, and eight had ADPLD. Liver volume decreased by 4.95% ± 6.77% in the octreotide group but remained practically unchanged (+0.92% ± 8.33%) in the placebo group (P = 0.048). Among patients with ADPKD, total kidney volume remained practically unchanged (+0.25% ± 7.53%) in the octreotide group but increased by 8.61% ± 10.07% in the placebo group (P = 0.045). Changes in GFR were similar in both groups. Octreotide was well tolerated; treated individuals reported an improved perception of bodily pain and physical activity. In summary, octreotide slowed the progressive increase in liver volume and total kidney volume, improved health perception among patients with PLD, and had an acceptable side effect profile. PMID:20431041

  10. Short-term preoperative octreotide treatment for TSH-secreting pituitary adenoma.

    PubMed

    Fukuhara, Noriaki; Horiguchi, Kentaro; Nishioka, Hiroshi; Suzuki, Hisanori; Takeshita, Akira; Takeuchi, Yasuhiro; Inoshita, Naoko; Yamada, Shozo

    2015-01-01

    Preoperative control of hyperthyroidism in patients with TSH-secreting pituitary adenomas (TSHoma) may avoid perioperative thyroid storm. Perioperative administration of octreotide may control hyperthyroidism, as well as shrink tumor size. The effects of preoperative octreotide treatment were assessed in a large number of patients with TSHomas. Of 81 patients who underwent surgery for TSHoma at Toranomon Hospital between January 2001 and May 2013, 44 received preoperative short-term octreotide. After excluding one patient because of side effects, 19 received octreotide as a subcutaneous injection, and 24 as a long-acting release (LAR) injection. Median duration between initiation of octreotide treatment and surgery was 33.5 days. Octreotide normalized free T4 in 36 of 43 patients (84%) and shrank tumors in 23 of 38 (61%). Length of octreotide treatment did not differ significantly in patients with and without hormonal normalization (p=0.09) and with and without tumor shrinkage (p=0.84). Serum TSH and free T4 concentrations, duration of treatment, incidence of growth hormone (GH) co-secretion, results of octreotide loading tests, form of administration (subcutaneous injection or LAR), tumor volume, and tumor consistency did not differ significantly in patients with and without hormonal normalization and with and without tumor shrinkage. Short-term preoperative octreotide administration was highly effective for TSHoma shrinkage and normalization of excess hormone concentrations, with tolerable side effects.

  11. Long-acting muscarinic antagonists.

    PubMed

    Melani, Andrea S

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is a major cause of death and disability worldwide. Inhaled bronchodilators are the mainstay of COPD pharmacological treatment. Long-acting muscarinic antagonists (LAMAs) are a major class of inhaled bronchodilators. Some LAMA/device systems with different characteristics and dosing schedules are currently approved for maintenance therapy of COPD and a range of other products are being developed. They improve lung function and patient-reported outcomes and reduce acute bronchial exacerbations with good safety. LAMAs are used either alone or associated with long-acting β₂-agonists, eventually in fixed dose combinations. Long-acting β₂-agonist/LAMA combinations assure additional benefits over the individual components alone. The reader will obtain a view of the safety and efficacy of the different LAMA/device systems in COPD patients.

  12. Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial.

    PubMed

    Gadelha, Mônica R; Bronstein, Marcello D; Brue, Thierry; Coculescu, Mihail; Fleseriu, Maria; Guitelman, Mirtha; Pronin, Vyacheslav; Raverot, Gérald; Shimon, Ilan; Lievre, Kayo Kodama; Fleck, Juergen; Aout, Mounir; Pedroncelli, Alberto M; Colao, Annamaria

    2014-11-01

    Many patients with acromegaly do not achieve biochemical control despite receiving high doses of the first-generation somatostatin analogues octreotide or lanreotide. In the PAOLA trial, we aimed to assess the efficacy and safety of two different doses of the somatostatin analogue pasireotide long-acting release compared with active control (octreotide or lanreotide) in patients with inadequately controlled acromegaly. In a multicentre, randomised, phase 3 trial, we enrolled eligible patients aged 18 years or older with acromegaly who were inadequately controlled (5-point, 2 h mean growth hormone concentration >2·5 μg/L and insulin-like growth factor 1 [IGF-1] concentration >1·3 times the upper normal limit) and had received 30 mg octreotide long-acting repeatable or 120 mg lanreotide (Somatuline Autogel; Ipsen, UK) as monotherapy for 6 months or longer. We randomly assigned patients in a 1:1:1 ratio with an interactive voice-web response system to receive 40 mg pasireotide long-acting release once every 28 days for 24 weeks, 60 mg pasireotide long-acting release once every 28 days for 24 weeks, or continued treatment with octreotide or lanreotide (active control). Patients were stratified according to previous treatment (octreotide or lanreotide) and growth hormone concentrations at screening (2·5-10 μg/L and >10 μg/L). Patients and study investigators were not masked to study drug assignment but were masked to pasireotide dose allocation. The primary endpoint was number of patients achieving biochemical control, defined as mean growth hormone concentration less than 2·5 μg/L and normalised IGF-1 concentration. Efficacy analyses were based on intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01137682. Between Dec 17, 2010, and Aug 6, 2012, 198 patients were enrolled and randomly assigned to pasireotide 40 mg (n=65), pasireotide 60 mg (n=65), or active control (n=68) groups. At 24 weeks, ten (15%) patients in the pasireotide 40

  13. Octreotide in variceal bleeding.

    PubMed Central

    Burroughs, A K

    1994-01-01

    Bleeding from oesophageal varices has a high death rate. Injection sclerotherapy is the most appropriate treatment but facilities for this are not always available. Balloon tamponade and vasoactive therapy may be used as stop gap measures. Somatostatin and octreotide are therapeutic candidates for the treatment of variceal bleeding and there are several trials that have compared somatostatin and octreotide with other treatments for this condition. The results of these trials are summarised and discussed. A meta analysis of the group of trials of placebo or H2 antagonists v somatostatin or octreotide showed a significant advantage of somatostatin or octreotide in terms of efficacy, but no difference in mortality. The trials discussed seem to show that somatostatin and octreotide are at least as effective as other treatments, with the benefit of fewer adverse effects, and thus represent the best vasoactive agents. Additionally, they may have a role as adjuvant treatment to emergency sclerotherapy for active bleeders and this must be further investigated. PMID:8206396

  14. Long-acting reversible contraception.

    PubMed

    Peck, Susan A

    2013-10-01

    Although short-acting reversible hormonal contraceptives, such as oral contraceptives and the contraceptive patch and vaginal ring, remain the most commonly used contraceptive methods in the United States, they are also associated with the highest failure rates. Long-acting reversible contraception (LARC) methods, such as intrauterine devices and contraceptive implants, offer high continuation rates and very low failure rates, and are safe for use in most women. The provision of LARC methods to adolescent, young adult and nulliparous women is a relatively new concept that offers an innovative option for these populations.

  15. Treatment adherence and persistence with long-acting somatostatin analog therapy for the treatment of acromegaly: a retrospective analysis.

    PubMed

    Gurel, Michelle H; Han, Yi; Stevens, Andrea L; Furtado, Aaron; Cox, David

    2017-04-04

    Many patients with acromegaly require medical treatment that includes somatostatin analogs (SSAs). Long-acting SSA formulations are widely used, due in part to increased patient convenience and increased treatment adherence vs daily medications. Although medication compliance can be poor in patients with chronic conditions, adherence and persistence with these SSAs in patients with acromegaly has not been evaluated. This analysis utilized claims data to estimate treatment adherence and persistence for lanreotide depot and long-acting octreotide in this population. This retrospective analysis used the MarketScan® database (~100 payors, 500 million claims in the US), which was searched between January 2007 and June 2012 to identify patients with acromegaly taking either lanreotide depot or long-acting octreotide. Patients switching treatments were excluded. Treatment adherence was assessed using medication possession ratio (MPR; number of doses dispensed in relation to dispensing period; ≥80% is considered adherent), injection count, and treatment time. Persistence was estimated by Kaplan-Meier analyses and Cox proportional hazards modeling. A washout period, defined as no acromegaly-related prescription activity 180 days prior to the index date, was employed to minimize effects of prior therapy and focus on patients more likely to be treatment-naïve. Altogether 1308 patients with acromegaly receiving a single SSA for treatment (1127 octreotide, 181 lanreotide) who had not switched treatments were identified. Mean MPR in patients with a 180-day washout (n = 663) was 89% for those receiving octreotide (n = 545) and 87% for those receiving lanreotide (n = 118). Median number of days on therapy was 169 (95% CI 135-232) for octreotide patients and 400 (95% CI 232-532) for lanreotide patients. The point estimate of the Cox proportional hazard ratio for stopping treatment was 1.385 for octreotide vs lanreotide (95% CI 1.079-1.777), suggesting a 38

  16. Population pharmacodynamic analysis of octreotide in acromegalic patients.

    PubMed

    Comets, Emmanuelle; Mentré, France; Grass, Peter; Kawai, Ryosei; Marbach, Peter; Vonderscher, Jacky

    2003-01-01

    Octreotide is an octapeptide analog of somatostatin used to normalize growth hormone levels in acromegaly. This article presents a population analysis of the relationship between octreotide and growth hormone concentrations in 94 patients with acromegaly, including 10 patients responding incompletely to subcutaneous treatment (poor responders). Growth hormone and octreotide concentrations were recorded hourly over 12-hour time periods during long-term subcutaneous treatment. Twelve-hour profiles were also collected on different days up to 2 months after intramuscular injection of the long-acting formulation. We modeled the inhibition of growth hormone secretion by octreotide with a direct maximum inhibition model. A joint analysis of both formulations was performed with NONMEM (GloboMax, LLC, Hanover, Md). During model building, we examined the relationships between parameters and demographic covariates or formulations with the use of likelihood ratio tests. The baseline growth hormone level was higher in poor responders and was best described by a bimodal distribution. The maximum inhibition was common to both formulations and had a mean of 90%, with low interindividual variability. Sensitivity to octreotide (50% inhibitory concentration) was found to be slightly lower on average with intramuscular administration than with subcutaneous administration. Given adequate doses of octreotide, in 72% of 94 patients, growth hormone would decrease to levels below 2.5 ng. mL(-1), considered to be a desirable target concentration in acromegaly. This study provides a way to identify poor responders during subcutaneous treatment, allowing an early clinical decision to be made to switch nonresponders to alternative therapies.

  17. A Case of Dermatomyositis and Anti-EJ Autoantibody with Chronic Intestinal Pseudoobstruction Successfully Treated with Octreotide

    PubMed Central

    Yamada, Chiho; Sasaki, Noriko; Kurabayashi, Takayoshi; Sasaki, Sho; Koyama, Yasushi; Wakabayashi, Takayuki; Suzuki, Yasuo

    2016-01-01

    Chronic intestinal pseudoobstruction (CIPO) is a serious complication in patients with connective tissue disease (CTD) and is sometimes life-threatening or fatal despite intensive medical treatment. Here, we report a patient with dermatomyositis (DM) and anti-EJ autoantibody who developed CIPO that was improved by octreotide. Because her abdominal pain and bloatedness were so severe and persistent, we introduced octreotide to relieve symptoms. In this case, continuous intravenous administration as well as long-acting subcutaneous injection of octreotide was effective for treating CIPO. PMID:27885350

  18. Octreotide Uptake in Parathyroid Adenoma

    PubMed Central

    Karaçavuş, Seyhan; Kula, Mustafa; Cihan Karaca, Züleyha; Ünlühızarcı, Kürşad; Tutuş, Ahmet; Bayram, Fahri; Çoban, Ganime

    2012-01-01

    The patient with a history of bone pain and muscle weakness, was thought to have oncogenic osteomalacia as a result of biochemical investigations and directed to Nuclear Medicine Department for a whole-body bone scintigraphy and 111In-octreotide scintigraphy. There was no focal pathologic tracer uptake, but generalized marked increase in skeletal uptake on bone scintigraphy. Octreotide scintigraphy showed accumulation of octreotide in the region of the left lobe of the thyroid gland in the neck. Thereafter, parathyroid scintigraphy was performed with technetium-99m labeled metroxy-isobutyl-isonitryl (99mTc-MIB) and MIBI scan demonstrated radiotracer uptake at the same location with octreotide scintigraphy. The patient underwent left inferior parathyroidectomy and histopathology confirmed a parathyroid adenoma. Somatostatin receptor positive parathyroid adenoma may show octreotide uptake. Octreotide scintigraphy may be promising and indicate a possibility of using somatostatin analogues for the medical treatment of somatostatin receptor positive Conflict of interest:None declared. PMID:23487397

  19. Long-acting contraceptive options.

    PubMed

    Kaunitz, A M

    1996-01-01

    Long-acting contraceptive methods are appropriate choices for women who prefer the convenience and high contraceptive efficacy of methods not requiring frequent compliance, and women for whom contraceptive doses of estrogen are either medically contraindicated or associated with persistent intolerable side effects. Annual pregnancy rates for the three methods described below are less than 1 per 100 woman-years. As currently formulated, levonorgestrel implants (Norplant) consist of six 34 x 2.4 mm soft plastic implants, each filled with 36 mg of crystalline levonorgestrel. Irregular and often persistent menstrual bleeding and spotting constitute the most important side effects experienced by and leading to method discontinuation in implant users. Implant removal is technically more difficult and time-consuming than insertion. Depot-medroxyprogesterone acetate (DMPA or Depo-Provera) is injected as an aqueous suspension of microcrystals. Intramuscular injection of 150 mg of DMPA results in more than 3 months of contraception. Irregular bleeding and spotting followed by amenorrhea, constitute the most importance side effects experienced by DMPA users. Because DMPA use can result in prolonged (but not permanent) infertility, DMPA is not an optimum contraceptive choice for women who may want to conceive in the next one or two years. The Copper T380A intrauterine device (IUD) provides reversible contraception for up to 10 years. IUDs act as contraceptives, not early abortafacients. Recent epidemiologic data indicate that long-term IUD use does not increase the occurrence of pelvic inflammatory disease. Heavier menstrual flow and cramps constitute the main side effects experienced by women using the copper IUD. Intrauterine device insertion and removal are accomplished during brief office-based procedures.

  20. Experimental and clinical studies with somatostatin analogue octreotide in small cell lung cancer.

    PubMed Central

    Macaulay, V. M.; Smith, I. E.; Everard, M. J.; Teale, J. D.; Reubi, J. C.; Millar, J. L.

    1991-01-01

    We have detected somatostatin receptors (SSR) by autoradiography in 3/4 established small cell lung cancer (SCLC) cell lines but not in two non-SCLC cell lines. The growth of 1/3 SSR positive SCLC cell lines was significantly inhibited by the long-acting somatostatin analogue octreotide (SMS 201-995, Sandostatin) 10(-9) M. We treated 20 SCLC patients with octreotide 250 micrograms three times daily for 1 week prechemotherapy (six patients) or at relapse after chemotherapy (14). Octreotide was well tolerated, and serum insulin-like growth factor-I levels were suppressed to 62 +/- 7% of pre-treatment levels. However there was no evidence of anti-tumour activity measured by tumour bulk or serum levels of neuron-specific enolase. In one patient metastatic skin nodules were shown to be SSR positive before and at the end of 2 weeks octreotide. Despite this the patient had progressive disease, and tumour cells obtained by fine needle aspirate before and after treatment showed no growth inhibition when cultured with octreotide immediately or following establishment as a cell line. In summary we saw little correlation between SSR expression and growth inhibition by octreotide, either in vitro or clinically. Images Figure 4 PMID:1654981

  1. Long-acting local anesthetics in dentistry.

    PubMed Central

    Sisk, A. L.

    1992-01-01

    Long-acting local anesthetics have proved to be effective for the suppression of both intraoperative and postoperative pain. They are useful for lengthy dental treatments and for prevention of severe pain following many types of surgical procedures. Although the currently available long-acting local anesthetics for dentistry have minimal side effects in the doses usually employed, there are potential problems. Bupivacaine, for example, can cause significant cardiac depressant and dysrhythmogenic responses. Etidocaine has less pronounced effects on the cardiovascular system, but its use may be associated with inadequate control of intraoperative bleeding. A new long-acting local anesthetic, ropivacaine, appears to offer advantages over either of the currently used long-acting agents. PMID:1308373

  2. Long-acting local anesthetics in dentistry.

    PubMed

    Sisk, A L

    1992-01-01

    Long-acting local anesthetics have proved to be effective for the suppression of both intraoperative and postoperative pain. They are useful for lengthy dental treatments and for prevention of severe pain following many types of surgical procedures. Although the currently available long-acting local anesthetics for dentistry have minimal side effects in the doses usually employed, there are potential problems. Bupivacaine, for example, can cause significant cardiac depressant and dysrhythmogenic responses. Etidocaine has less pronounced effects on the cardiovascular system, but its use may be associated with inadequate control of intraoperative bleeding. A new long-acting local anesthetic, ropivacaine, appears to offer advantages over either of the currently used long-acting agents.

  3. Population Pharmacokinetic Modeling After Repeated Administrations of RBP-6000, a New, Subcutaneously Injectable, Long-Acting, Sustained-Release Formulation of Buprenorphine, for the Treatment of Opioid Use Disorder.

    PubMed

    Laffont, Celine M; Gomeni, Roberto; Heidbreder, Christian; Jones, J P; Nasser, Azmi F

    2016-07-01

    RBP-6000 is a novel sustained-release formulation of buprenorphine for the treatment of opioid use disorder, which has been designed for once-monthly (28 days) subcutaneous (SC) injections. A population pharmacokinetic (PK) model was developed to describe the time course of buprenorphine plasma concentrations after repeated SC injections of RBP-6000 at 50 mg, 100 mg, 200 mg, or 300 mg in treatment-seeking opioid-dependent subjects previously on sublingual buprenorphine (Subutex(®) ) treatment. The μ-opioid receptor occupancy was predicted using a previously developed PK/PD Emax model. The results of the population PK analysis jointly with the predicted level of μ-opioid receptor occupancy provided quantitative criteria for clinical dose selection for RBP-6000: the dose of 300 mg every 28 days seems appropriate for immediately achieving an effective exposure after the first SC injection and to maintain effective levels of exposure during chronic treatment. Furthermore, simulations conducted to evaluate the potential impact of a holiday in drug intake indicated that in the unexpected event of a 2-week holiday, levels of μ-opioid receptor occupancy remained consistently above 70% with no significant loss of drug efficacy. This analysis indicated that RBP-6000 has the potential for becoming an effective treatment for opioid-dependent subjects by addressing compliance issues associated with the current once-a-day treatments.

  4. Treatment of autonomic neuropathy, postural tachycardia and orthostatic syncope with octreotide LAR.

    PubMed

    Hoeldtke, Robert D; Bryner, Kimberly D; Hoeldtke, Martin E; Hobbs, Gerald

    2007-12-01

    The purpose of this study was to determine whether autonomic neuropathy and the postural tachycardia syndrome can be treated with octreotide LAR (Long Acting Release). This was an open-label pilot project. Protocol 1 Patients with autonomic neuropathy (n = 4) were given increasing doses of octreotide LAR once a month for three months. Blood pressure was measured in the sitting posture every two weeks. Pretreatment mean blood pressure averaged 83.8 +/- 7.1 mm Hg. After four, six and eight weeks of therapy the blood pressures averaged 96.3 +/- 6.4, 98.2 +/- 6.1 (p < .025), and 104.1 +/- 3.1 (p < .025) respectively. Therapy led to a dramatic improvement in symptoms in one patient but another had an unacceptable elevation in supine blood pressure. Protocol 2 Patients with POTS or orthostatic intolerance were given 10, 20, or 30 mg of octreotide LAR over three months. Seven patients entered and five completed the study. After two months treatment, standing time increased from 36.0 +/- 9.2 to 59.2 +/- .8 minutes (p < .01). Heart rate in the standing position was suppressed from 106 +/- .83 to 93.2 +/- .8 beats per minute (p < .05). Orthostatic dizziness and chronic fatigue improved. We conclude that octreotide LAR can be used to treat autonomic neuropathy but there is a risk of an excessive pressor response. Octreotide LAR improved standing time and suppressed tachycardia in patients with orthostatic intolerance.

  5. Double benefit of long-acting somatostatin analogs in a patient with coexistence of acromegaly and ulcerative colitis.

    PubMed

    Yarman, S; Yalın, G Y; Dogansen, S C; Canbaz, B; Tanrıkulu, S; Akyuz, F

    2016-10-01

    Somatostatin analogs control GH/IGF-1 excess in acromegaly. Somatostatin receptors also mediate the complex effects of somatostatin on the gastrointestinal tract and may be defensive in inflammatory bowel diseases, such as ulcerative colitis. We present a patient who showed good response to long-acting octreotide (OCT-LAR) treatment in terms of both acromegaly and ulcerative colitis (UC). A 58-year-old female patient with diagnosis of acromegaly and ulcerative colitis was started on long-acting somatostatin treatment as a first-line treatment for acromegaly as she refused to undergo transsphenoidal surgery. During the follow-up period, a significant amelioration was also observed in the course of ulcerative colitis, and clinical remission of both diseases was achieved uneventfully. Somatostatin appears to be a promising candidate in the treatment of inflammatory bowel diseases. © 2016 John Wiley & Sons Ltd.

  6. Efficacy of octreotide acetate in treatment of severe postgastrectomy dumping syndrome.

    PubMed Central

    Geer, R J; Richards, W O; O'Dorisio, T M; Woltering, E O; Williams, S; Rice, D; Abumrad, N N

    1990-01-01

    The present study evaluates the acute and chronic use of a long-acting somatostatin analog, octreotide acetate, in the treatment of patients with severe postgastrectomy dumping syndrome. In the acute phase, 10 patients with severe dumping were studied over 2 consecutive days before and for 3 hours after the ingestion of a 'dumping breakfast' in a randomized double-blind fashion. On one day octreotide (100 micrograms) was given subcutaneously 30 minutes before the test meal and on the other day an equal volume of vehicle was injected. An additional group of six postgastrectomy patients without dumping were studied in a similar fashion and these acted as controls. During placebo treatment the test meal resulted in an immediate increase (p less than 0.01) in the pulse rate and in plasma levels of glucose, glucagon, pancreatic polypeptide, neurotensin, and insulin. Similar changes were seen in the control group with respect to placebo; however glucagon and neurotensin (p less than 0.05) did not show the same magnitude of increase as seen with placebo. Treatment with octreotide acetate prevented the development of both vasomotor and gastrointestinal symptoms and completely ablated all of the above responses in plasma peptides. These changes were associated with complete ablation of diarrhea (p less than 0.001). Pretreatment with octreotide acetate completely suppressed the rise in plasma insulin response to the meal and this ablated the late hypoglycemia of dumping. Treatment with octreotide acetate resulted in delayed gastric emptying and transit time (578 +/- 244 minutes) versus 76 +/- 23 minutes with placebo and 125 +/- 36 minutes in controls (p less than 0.05). Chronic daily treatment with octreotide acetate resulted in minimal side effects. These patients demonstrated a stable fasting plasma glucose, normal liver function tests, and an average weight gain of 11% during a 12-month period. In addition most patients were able to resume employment. The long-acting

  7. Short term reduction of left ventricular mass in primary hypertrophic cardiomyopathy by octreotide injections.

    PubMed Central

    Günal, A. I.; Işik, A.; Celiker, H.; Eren, O.; Celebi, H.; Günal, S. Y.; Lüleci, C.

    1996-01-01

    Growth factors have been shown to be associated with primary hypertrophic cardiomyopathy. Octreotide, a long acting somatostatin analogue, can prevent the stimulating effect of growth factors and decrease the left ventricular mass in patients with acromegaly. In the light of these results, three patients with primary hypertrophic cardiomyopathy were treated with subcutaneous octreotide (50 micrograms three times a day during the first week and 100 micrograms twice a day for the following three weeks). Initially, two patients were in New York Heart Association class II in and one was in class III. At the end of a four week treatment session all were in class I. There were significant decreases in left ventricular posterior wall thickness, interventricular septum thickness, and left ventricular mass in all three patients. Both left ventricular end diastolic and end systolic diameters had increased in all of the patients at the end of the fourth week. Two of three patients showed improved diastolic filling: their hyperdynamic systolic performance returned to normal. No side effects were observed during octreotide treatment. The considerable improvement obtained with the short term octreotide treatment in patients with primary hypertrophic cardiomyopathy seems promising. PMID:8944587

  8. Treatment with long-acting lanreotide autogel in early infancy in patients with severe neonatal hyperinsulinism.

    PubMed

    Corda, Heike; Kummer, Sebastian; Welters, Alena; Teig, Norbert; Klee, Dirk; Mayatepek, Ertan; Meissner, Thomas

    2017-06-02

    Treatment of severe diffuse congenital hyperinsulinism (CHI) without sufficient response to diazoxide is complicated by the lack of approved drugs. Therefore, patients are often hospitalized long-term or have to undergo pancreatic surgery if episodes of severe hypoglycaemia cannot be prevented. A long-acting somatostatin analogue, octreotide, has been reported to be an effective treatment option that prevents severe hypoglycaemia in children with CHI, and its off-label use is common in CHI. However, octreotide requires continuous i.v. or s.c. infusion or multiple daily injections. Here, we report our experiences with the use of a monthly application of a long-acting somatostatin analogue, lanreotide autogel® (LAN-ATG), in early infancy. The mean blood glucose concentration within 7 days before the first LAN-ATG administration were compared to 7 days after the first LAN-ATG administration and increased by 0.75 mmol/L (range 0.39-1.19 mmol/L). In the following weeks intravenous glucose infusions, octreotide, and glucagon treatment could be successfully stopped in all patients 3-20 days after the first LAN-ATG injection without substantial worsening of the hypoglycaemia rate. Increased carbohydrate requirements could be normalized with an average reduction in the carbohydrate-intake of 7 g/kg body weight/d (range 1.75-12.8 g/kg body weight/d). Over a total of 52 treatment months, no serious adverse effects occurred. Long-term LAN-ATG treatment improved blood glucose concentrations, lowered the frequency of hypoglycaemia or allowed for normalization of oral carbohydrate intake in infants with CHI younger than 6 months of age. No severe side effects were observed. LAN-ATG might be an alternative treatment option in infants with severe CHI who lack risk factors for necrotizing enterocolitis and are not responding to current treatment regimens as an alternative to surgery after careful individual evaluation.

  9. Long-Acting Reversible Contraception for Adolescents.

    PubMed

    Fontenot, Holly B; Fantasia, Heidi Collins

    2015-01-01

    In 2013 and 2014, the Centers for Disease Control and Prevention (CDC) publicized its recommendations for the use of long-acting reversible contraception (LARC) (including intrauterine devices and implants) as first-line, highly effective options for pregnancy prevention. The use of LARC by adolescents has had growing support by national health and women's health organizations. Ongoing research is beginning to uncover facilitators and barriers to LARC use in adolescents. The purpose of this column is to highlight two recent U.S.-based studies in which researchers examined perspectives related to and factors associated with LARC use in adolescent and young adult women.

  10. Rendu-Osler disease: treatment with oestrogen/progestagen versus octreotide

    PubMed Central

    Jeanneret, Séverin; Regazzoni, Loic; Favrat, Bernard

    2011-01-01

    In Rendu-Osler disease, haemorrhages due to gastrointestinal vascular malformations are common. Surgical and endoscopic treatments for haemorrhage due to gastrointestinal vascular malformations are compromised when lesions are diffuse, escape identification or are inaccessible to treatment. Hormonal treatment with oestrogen and progestagens is still controversial based on contradictory results from two randomised clinical trials. Although somatostatin and its long-acting analogue, octreotide, have been reported to be beneficial in preventing rebleeding, there is no consensus on this type of treatment. This case report shows how the combination of ethinyloestradiol and norethisterone markedly reduced the need for blood transfusions with few side effects in one patient; in comparison, octreotide seems less effective but this could be related to a worsening of the disease. PMID:22707551

  11. Effect of Octreotide Injection on Postoperative Drainage After Neck Dissection: A Preliminary Report of a Prospective, Matched Case-Control Study

    PubMed Central

    Ahn, Dongbin; Jeon, Jae Han; Kim, Heejin; Sohn, Jin Ho

    2016-01-01

    Objectives Somatostatin inhibits lymph production and reduces lymph flow into the lymphatic duct. We hypothesized that octreotide, a long-acting somatostatin analog, would reduce drainage after neck dissection (ND) by reducing the overall lymphatic flow in the neck as well as thoracic duct flow. Methods From 2012 to 2014, total 123 patients who had undergone left-sided comprehensive ND, were divided into an octreotide group (49 patients) and a control group (74 patients). Seventeen patients from the octreotide group and 17 from the control group were individually matched by age (±10 years), sex, body mass index (±1 kg/m2), type of cancer, surgeon, and the extent of surgery. These 34 patients were finally included in the study. Results The total fluid drainage volume (540.9 mL vs. 707.9 mL) and drainage volume during the period of octreotide use (the first 5 postoperative days) (461.1 mL vs. 676.4 mL) were significantly lower in the octreotide group. The duration of drain placement (6.3 days vs. 9.4 days) was also shorter in the octreotide group. In the octreotide group, the mean triglyceride concentration in the drainage fluid was significantly lower than that in the control group (43.1 mg/dL vs. 88.8 mg/dL). There was no complication associated with the use of octreotide. Conclusion Our study has shown that postoperative octreotide injections reduce postoperative drainage and the duration of drain placement. Further studies with larger patient populations are warranted to confirm these results and to evaluate the clinical benefits for patients. PMID:27090270

  12. Octreotide blunts postprandial splanchnic hyperemia in cirrhotic patients: a double-blind randomized echo-Doppler study.

    PubMed

    Buonamico, P; Sabbá, C; Garcia-Tsao, G; Berardi, E; Antonica, G; Ferraioli, G; Jensen, J E; Lerner, E; Taylor, K J; Albano, O

    1995-01-01

    The effect of octreotide, a long-acting synthetic analog of somatostatin, on fasting and postprandial splanchnic hemodynamics was investigated in cirrhotic patients. Splanchnic hemodynamics were assessed using an echo-Doppler duplex system in a prospective, double-blind, placebo-controlled, crossover study performed on 2 separate days, 1 week apart, in 30 cirrhotic patients. Measurements of portal vein (PV) cross-sectional area (PV-A) and mean velocity (PV-V), and of superior mesenteric artery (SMA) mean velocity (SMA-V) and pulsatility index (SMA-PI) (an index of vascular resistance) were performed at baseline, 30 minutes after octreotide (200 micrograms subcutaneously) or placebo administration, and 30 and 60 minutes after the ingestion of a liquid meal. In the fasted state, octreotide induced a significant decrease in PV-V (-7%) and in SMA-V (-10%) and an increase in PI (+16%). On the day of placebo administration, meal ingestion induced a significant increase in PV-V (+21%) and in SMA-V (+43%) and a decrease in PI (-21%). In contrast, meal ingestion on octreotide day induced significantly smaller increases in PV-V (+10%) and in SMA-V (+18%) and a significantly smaller decrease in PI (-10%). Octreotide, although producing a mild reduction in PV-V and SMA-V in the fasted state, markedly blunts postprandial splanchnic hyperemia in cirrhotic patients.

  13. Long-acting steroid contraceptive technology.

    PubMed

    Grubb, G

    1991-01-01

    Long-acting steroid contraceptive technologies that have either been recently approved or are currently under study are reviewed and the status of contraceptive research in the US is noted. The benefits and drawbacks, as well as the duration and possible cost, of each method are discussed. Approved by the Food and Drug Administration on December 10, 1990, Norplant is reportedly the first new contraceptive technology available to women in the US since the 1960s. This implant delivery system, which lasts up to 5 years, is cheaper than the pill and nearly as effective as sterilization. Study is currently under way on other multiyear, nonbiodegradable and biodegradable implants. Although already used by 4 million women worldwide, the long-acting injectable Depo-Provera has yet to be approved for use in the US. 5 new types of injectables are being developed. Steroid-containing IUDs have been in the market for some time, and current research is attempting to increase their contraceptive life beyond 1 year. Contraceptive developers are also exploring transdermal delivery systems, vaginal rings, and buccal and sublingual delivery. It is considered misleading to call Norplant the first new contraceptive introduced since the pill. Over the past 20 years, virtually every contraceptive has been significantly improved, developments that have enhanced the contraceptive options of couples. Because new contraceptive technologies are increasingly complex, their development is much slower. Consequently, it is concluded that in the foreseeable future, the demand for more acceptable contraceptives will be met through improvements of currently available technologies.

  14. Long-Acting Reversible Contraception (LARC): IUD and Implant

    MedlinePlus

    f AQ FREQUENTLY ASKED QUESTIONS FAQ184 CONTRACEPTION Long-Acting Reversible Contraception (LARC): IUD and Implant • What are long-acting reversible contraception (LARC) methods? • How effective are LARC methods? • How ...

  15. MS-24SYSTEMIC TREATMENT OF MENINGIOMAS: IS THERE A ROLE FOR LONG-ACTING SOMATOSTATIN?

    PubMed Central

    Soffietti, Riccardo; Magistrello, Michela; Trevisan, Elisa; Bertero, Luca; Pellerino, Alessia; Rudà, Roberta

    2014-01-01

    BACKGROUND: Meningiomas are the most common primary brain tumors. Resection and/or radiation therapy are the treatments of choice. Medical therapies have been investigated for inoperable, recurrent and aggressive meningiomas, but the optimal medical treatment is still to be defined. Among biologic agents, somatostatin has been found to inhibit meningioma growth due to the presence of somatostatin receptors on the surface of the tumors. AIM: We retrospectively reviewed our experience with sandostatin to assess the efficacy and toxicity in the treatment of recurrent meningiomas failing standard treatments. PATIENTS AND METHODS: A total of 17 patients (7 women and 10 men, median age 65 years) with recurrent grade I or II or III meningiomas have been studied. All patients had already been treated with multiple surgeries or radiation treatments, and all had an overexpression of somatostatin receptors by octreotide scintigraphy. Before treatment KPS ranged from 60 to 90. The patients received long-acting somatostatin on a monthly administration schedule. Radiographic response on MRI has been assessed by MacDonald Criteria. RESULTS: Patients received 3 to 18 cycles (median 9) of somatostatin. Progression-free survival (PFS) at 6 months was 56%, while PFS ranged from 3 to 25 months with a median of 6 months. Two radiological responses on MRI were achieved (1 PR and 1). Toxicity was uncommon and manageable (2 patients with diarrhea). CONCLUSION: Long acting somatostatin displays minor activity as salvage treatment for recurrent meningiomas after surgery and radiation therapy.

  16. Somatostatin analog octreotide LAR in gastro-entero-pancreatic tumors.

    PubMed

    Oberg, Kjell

    2009-05-01

    Neuroendocrine tumors (NETs) are considered to be rare but, during the last two decades, their incidence and prevalence has considerably increased in gastro-entero-pancreatic (GEP) NETs. Most GEP-NETs express somatostatin receptors, which could be targets for treatment. The development of somatostatin analogs for treatment of functioning NETs was a revolution in the treatment of these patients and is still a cornerstone for managing hormone-related clinical symptoms. Furthermore, somatostatin analogs have also demonstrated an anti-tumor effect, with stabilization of tumor growth over long periods of time. The development of a long-acting formulation of octreotide long-acting release (LAR) significantly improved the quality of life for patients with functioning NETs in terms of necessitating only monthly injections. The side effects are few and easily manageable. In the future, somatostatin analogs will continue to be a major treatment option for functioning NETs, but will be combined with other biologicals, such as a-interferons, mTOR inhibitors and VEGF inhibitors. A new multireceptor somatostatin analog, SOM230 (pasireotide), as well as chimeric molecules, such as dopastatin (a combination of a somatostatin analogue plus a dopamine agonist), will come into the clinical management of GEP-NETs.

  17. Investigation into the efficacy and safety of octreotide LAR in Japanese patients with acromegaly: Shizuoka study.

    PubMed

    Oki, Yutaka; Inoue, Tatsuhide; Imura, Mitsuo; Tanaka, Tokutaro; Genma, Rieko; Iwabuchi, Masayasu; Hataya, Yuji; Matsuzawa, Yuji; Iino, Kazumi; Nishizawa, Shigeru; Nakamura, Hirotoshi

    2009-01-01

    The efficacy and safety of the long-acting repeatable formulation of octreotide (OCT-LAR) treatment in patients suffering from acromegaly was investigated retrospectively in Shizuoka prefecture, Japan. Thirty patients (11 male, 19 female; average age, 48.9 years old), 29 of whom had undergone transsphenoidal surgery previously, were treated with OCT-LAR. OCT-LAR was injected i.m. every 4 weeks with an intended protocol of 20 mg over 24 months, however, 46.7% of patients required the dose of OCT-LAR to be increased. The final average dose of OCT-LAR was 25.0 +/- 6.8 mg. Administering OCT-LAR significantly decreased serum GH and insulin-like growth factor 1 (IGF-1) levels (from 13.7 +/- 11.9 to 5.8 +/- 7.3 microg/L and from 585 +/- 263 to 339 +/- 193.7 microg/L after 3 months, respectively). Among patients treated with OCT-LAR, 56.7% expressed

  18. Long-acting steroidal contraception: an update.

    PubMed

    Bardin, C W

    1989-01-01

    Long-acting, injectable contraceptives first became available in the 1960s. It is currently estimated that almost 3.5 million women are now using depo-medroxyprogesterone acetate (DMPA); 800,000 are using norethindrone enanthate (NET-EN), and another few hundred thousand are using a variety of once-a-month injectables comprised of progestin plus estrogen. The advantages of injectable contraceptives are that they are highly effective, independent of coitus, easily administered, and they ensure regular contact with health services personnel. The last factor may be considered a disadvantage by some, since contact is more frequent than would be required for routine health services. The major disadvantage of the progestin-only formulations is disruption of normal menses, giving rise to unpredicted episodes of bleeding and spotting. With the once-a-month formulation, on the other hand, there are few discontinuations due to disruption of menses. For a long-acting method to be used longer than 6 months, it is desirable to choose an implant, since the method can be discontinued at will. The first implant system to be developed was Norplant, a set of six rubber capsules filled with levonorgestrel and implanted under the skin. The implant releases sufficient levels of medication to protect against pregnancy. For the first 5 years, the average failure rate was four or five per thousand users per year. The failure rate for women using standard oral contraceptives is approximately 20 to 50 per thousand. The most common side effect of the implant method is the disruption of the menstrual cycle, an effect that is particularly marked in the first month of use.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Serum levels of bone Gla protein (osteocalcin, BGP) and carboxyterminal propeptide of type I procollagen (PICP) in acromegaly: effects of long-term octreotide treatment.

    PubMed

    Terzolo, M; Piovesan, A; Osella, G; Pia, A; Reimondo, G; Pozzi, C; Raucci, C; Torta, M; Paccotti, P; Angeli, A

    1993-03-01

    We measured serum concentrations of bone Gla-protein (osteocalcin, BGP) and carboxyterminal propeptide of type I procollagen (PICP) in 14 patients with active acromegaly. Blood was collected at 0800 for measurement of bone Gla-protein (BGP), carboxyterminal propeptide of type I procollagen (PICP), and insulin-like growth factor I (IGF-I); growth hormone (GH) was then determined at 15-minute intervals for 3 hours and the integrated mean was calculated. The same protocol was repeated at regular intervals during treatment with the long-acting somatostatin analog, octreotide, 150-450 micrograms/day for 6-33 months (median 15). In a case-control analysis, serum BGP concentrations recorded in the acromegalic patients were significantly elevated (14.2 +/- 4.2 micrograms/liter versus 8.0 +/- 3.3 micrograms/liter, P < 0.001). Octreotide treatment induced a roughly parallel reduction in serum GH, IGF-I, and BGP. We found a significant positive correlation between BGP levels recorded before and during therapy and the logarithm of corresponding mean GH levels (r = 0.67, P < 0.001). Also IGF-I concentrations were positively correlated with BGP (r = 0.66, P < 0.001). On the other hand, PICP levels recorded in the acromegalics did not differ from control subjects (146 +/- 46 micrograms/liter versus 127 +/- 44 micrograms/liter, NS) and no correlation was found between either GH and PICP or IGF-I and PICP. To conclude, the present data are compatible with the view that GH and IGF-I play an important role in the control of BGP but not PICP production. It could be that BGP and PICP are submitted to different hormonal modulation.

  20. Five-year follow-up of a 13-year-old boy with a pituitary adenoma causing gigantism--effect of octreotide therapy.

    PubMed

    Schoof, Ellen; Dörr, Helmuth G; Kiess, Wieland; Lüdecke, Dieter K; Freitag, Eduard; Zindel, Volker; Rascher, Wolfgang; Dötsch, Jörg

    2004-01-01

    In children, there is little experience with octreotide therapy for pituitary tumors, especially growth hormone (GH) producing adenomas. We report on a 13-year-old boy with gigantism due to a GH-producing pituitary adenoma caused by a Gsalpha mutation on the basis of McCune-Albright syndrome. At the age of 6.5 years a GH- and prolactin-producing pituitary adenoma was diagnosed. The adenoma was surgically removed. Immediately thereafter, the small adenoma residuum was treated with octreotide (2 x 100 microg/day s.c.). During therapy with octreotide, the growth rate dropped to normal values; however, rose again after 2 years of treatment. The insulin-like growth factor I (IGF-I) levels remained above the 95th percentile, the GH level mostly >2 microg/l. After 5 years of octreotide therapy, GH (6.9 microg/l), IGF-I (620 microg/l), IGF-binding protein 3 (5.4 mg/l), and prolactin (17.0 ng/ml) levels were still elevated. The growth velocity was +2.4 SDS (standard deviation score), the pubertal status was mature, and the bone age was 14.3 years (prospective final height 208 cm). A magnetic resonance imaging scan showed an unchanged residual 4-mm rim of adenoma at the pituitary site. Side effects from octreotide therapy were not reported by the patient or his family. The therapy was changed to the long-acting release octreotide analog octreotide-LAR. After 1 year of treatment with octreotide-LAR, the GH level was 1.0 microg/l, and the prospective final height dropped by 10 cm. This case demonstrates that combined surgical and medical treatment can influence the prognosis of childhood gigantism; however, the prognosis of this rare condition remains uncertain. Copyright 2004 S. Karger AG, Basel

  1. Incidence of gall stone formation in acromegalic patients on octreotide therapy

    PubMed Central

    Chakravarty, Aditi A.; Ajmani, Ajay; Manchanda, Smita; Kulshreshtha, Bindu; Chopra, Shweta

    2012-01-01

    Objective: Octreotide, a long-acting synthetic somatostatin analog, has been widely used for ac-romegalic patients. Gastrointestinal (GI) side effects and gall stones are predominant side effects. We report incidence of gall stones in our cohort of acromegalic patients treated with octreotide therapy. Design: Retrospective case observational study. Setting: Endocrinology Unit, Dr. Ram Manohar Lohia, Hospital, New Delhi. Materials and Methods: Patients of acromegaly on primary or secondary octreotide therapy. Intervention: Patients were enquired regarding complaints related to the GI system and their medical records were reviewed. Ultrasound films at various intervals while on octerotide therapy were evaluated by the radiologist for presence of sludge and development of gall stones. Results: Of seven patients, five developed gallstones and sludge was seen in three patients at intervals ranging from 11 to 36 months postoctreotide initiation. Conclusion: A high incidence of gall stone formation in the present study as compared to the West was noted, the reasons for which are not clear. PMID:22629508

  2. [Octreotide in the treatment of angiodysplasia in patients with advanced chronic renal failure].

    PubMed

    Rivera, M; Lucero, J; Guerrero, A; Márquez, J L; Montes, R; Suñer, M; Ruiz, A; Valdivia, M A; Mateos, J

    2005-01-01

    Angiodysplasia is an important cause of gastrointestinal bleeding in patients with chronic renal failure. Octreotide, a long-acting synthetic somatostatin analogue that reduces splachnic blood flow have been used to treat esophageal varicose hemorrhage, but its efficacy for bleeding vascular ecstasies is awaiting support. We present three patients with chronic renal failure (two with diabetic nephropaty and the third with mesangiocapilar glomerulonephritis and hepatic cirrosis), seric creatinine 3-4,5 mg/dl, and recurrent gastrointestinal bleeding due to diffuse angiodysplasia and vascular ecstasies, diagnosed by oral endoscopy, colonoscopy and video capsule. They all were treated with octreotide, administered subcutanesly 0.1 mg twice a day for six months, with significantly decreased blood requirements in all of them, as well as the occurrence of bleeding episodes. It was well tolerated and none side-effects occurred in any subject. In our experience, octreotide is an effective and safe drug in bleeding angiodysplasia and ecstasies vascular of the gastrointestinal tract in patients with chronic renal failure, and it may be a good option especially in patients who are not candidates for surgery or endoscopic treatment due to inaccessible sites, spread of the lesion, old age and/or concomitant disorders.

  3. [Long-term treatment of acromegaly and gigantism with octreotide (SMS 201-995)].

    PubMed

    Shimatsu, A; Imura, H; Irie, M; Nakagawa, S; Goto, Y; Shimizu, N; Takeda, R; Kato, Y; Saito, S; Ibayashi, H

    1992-02-20

    Twenty-one patients with active acromegaly and two patients with pituitary gigantism were treated with the long-acting somatostatin analogue octreotide (100-600 micrograms/day, sc, two or three times daily or 300-1500 micrograms daily by intermittent sc infusion) for 9-63 months. There was rapid clinical improvement. The fasting plasma GH levels were significantly suppressed (less than 50% of the values before treatment) in 17 patients and were normalized (less than 5 ng/ml) in 6 patients (27.3%). Plasma IGF-I levels were lowered by 50% and were normalized in 7 out of 18 cases. The effect of octreotide on pituitary tumor size was evaluated in 13 patients. In 4 cases, the shrinkage of the pituitary tumor was detected by computed tomographic scans and/or magnetic resonance imaging studies. The drug was generally well tolerated. However, there were probably newly formed gallstones in two patients during the therapy. Our study suggests that octreotide is an effective and relatively safe new approach for treating active acromegaly and gigantism.

  4. Octreotide LAR and Prednisone as Neoadjuvant Treatment in Patients with Primary or Locally Recurrent Unresectable Thymic Tumors: A Phase II Study

    PubMed Central

    Kirzinger, Lukas; Boy, Sandra; Marienhagen, Jörg; Schuierer, Gerhard; Neu, Reiner; Ried, Michael; Hofmann, Hans-Stefan; Wiebe, Karsten; Ströbel, Philipp; May, Christoph; Kleylein-Sohn, Julia; Baierlein, Claudia; Bogdahn, Ulrich; Marx, Alexander; Schalke, Berthold

    2016-01-01

    Therapeutic options to cure advanced, recurrent, and unresectable thymomas are limited. The most important factor for long-term survival of thymoma patients is complete resection (R0) of the tumor. We therefore evaluated the response to and the induction of resectability of primarily or locally recurrent unresectable thymomas and thymic carcinomas by octreotide Long-Acting Release (LAR) plus prednisone therapy in patients with positive octreotide scans. In this open label, single-arm phase II study, 17 patients with thymomas considered unresectable or locally recurrent thymoma (n = 15) and thymic carcinoma (n = 2) at Masaoka stage III were enrolled. Octreotide LAR (30 mg once every 2 weeks) was administered in combination with prednisone (0.6 mg/kg per day) for a maximum of 24 weeks (study design according to Fleming´s one sample multiple testing procedure for phase II clinical trials). Tumor size was evaluated by volumetric CT measurements, and a decrease in tumor volume of at least 20% at week 12 compared to baseline was considered as a response. We found that octreotide LAR plus prednisone elicited response in 15 of 17 patients (88%). Median reduction of tumor volume after 12 weeks of treatment was 51% (range 20%–86%). Subsequently, complete surgical resection was achieved in five (29%) and four patients (23%) after 12 and 24 weeks, respectively. Octreotide LAR plus prednisone treatment was discontinued in two patients before week 12 due to unsatisfactory therapeutic effects or adverse events. The most frequent adverse events were gastrointestinal (71%), infectious (65%), and hematological (41%) complications. In conclusion, octreotide LAR plus prednisone is efficacious in patients with primary or recurrent unresectable thymoma with respect to tumor regression. Octreotide LAR plus prednisone was well tolerated and adverse events were in line with the known safety profile of both agents. PMID:27992479

  5. Octreotide LAR and Prednisone as Neoadjuvant Treatment in Patients with Primary or Locally Recurrent Unresectable Thymic Tumors: A Phase II Study.

    PubMed

    Kirzinger, Lukas; Boy, Sandra; Marienhagen, Jörg; Schuierer, Gerhard; Neu, Reiner; Ried, Michael; Hofmann, Hans-Stefan; Wiebe, Karsten; Ströbel, Philipp; May, Christoph; Kleylein-Sohn, Julia; Baierlein, Claudia; Bogdahn, Ulrich; Marx, Alexander; Schalke, Berthold

    2016-01-01

    Therapeutic options to cure advanced, recurrent, and unresectable thymomas are limited. The most important factor for long-term survival of thymoma patients is complete resection (R0) of the tumor. We therefore evaluated the response to and the induction of resectability of primarily or locally recurrent unresectable thymomas and thymic carcinomas by octreotide Long-Acting Release (LAR) plus prednisone therapy in patients with positive octreotide scans. In this open label, single-arm phase II study, 17 patients with thymomas considered unresectable or locally recurrent thymoma (n = 15) and thymic carcinoma (n = 2) at Masaoka stage III were enrolled. Octreotide LAR (30 mg once every 2 weeks) was administered in combination with prednisone (0.6 mg/kg per day) for a maximum of 24 weeks (study design according to Fleming´s one sample multiple testing procedure for phase II clinical trials). Tumor size was evaluated by volumetric CT measurements, and a decrease in tumor volume of at least 20% at week 12 compared to baseline was considered as a response. We found that octreotide LAR plus prednisone elicited response in 15 of 17 patients (88%). Median reduction of tumor volume after 12 weeks of treatment was 51% (range 20%-86%). Subsequently, complete surgical resection was achieved in five (29%) and four patients (23%) after 12 and 24 weeks, respectively. Octreotide LAR plus prednisone treatment was discontinued in two patients before week 12 due to unsatisfactory therapeutic effects or adverse events. The most frequent adverse events were gastrointestinal (71%), infectious (65%), and hematological (41%) complications. In conclusion, octreotide LAR plus prednisone is efficacious in patients with primary or recurrent unresectable thymoma with respect to tumor regression. Octreotide LAR plus prednisone was well tolerated and adverse events were in line with the known safety profile of both agents.

  6. Long-acting contraceptive agents: levonorgestrel esters of unsaturated acids.

    PubMed

    Wan, A S; Ngiam, T L; Leung, S L; Go, M L; Francisco, C G; Freire, R; Hernandez, R; Salazar, J A; Suarez, E; García, G A

    1983-03-01

    Esters of levonorgestrel (13 beta-ethyl-17 beta-ethynyl-17 beta-hydroxygon-4-en-3-one) with a variety of unsaturated carboxylic acids have been synthesized for evaluation as potential long-acting, injectable contraceptive agents.

  7. Long-acting contraceptive agents: testosterone esters of unsaturated acids.

    PubMed

    Francisco, C G; Freire, R; Gawronski, J; Hernández, R; Kielczewski, M; Salazar, J A; Savabi, F; Shafiee, A; Strekowski, L; Suárez, E

    1990-01-01

    The synthesis of 13 new esters of testosterone is described, with the esterifying acids bearing acetylenic, olefinic, or polyunsaturated functions in the chain, for evaluation as long-acting androgens.

  8. Pharmacokinetic and pharmacodynamic studies with long-acting propranolol

    PubMed Central

    McAinsh, J.; Baber, N. S.; Smith, R.; Young, J.

    1978-01-01

    1 The whole blood concentrations of propranolol have been compared, over a 48 h period, in twelve healthy male volunteers dosed with a 160 mg long-acting capsule formulation (LA, United Kingdom patent application No. 23114/77) and three standard tablet regimens; 160 mg once a day (CP160), 80 mg twice a day (CP80) and 40 mg four times a day (CP40). 2 The mean peak blood level for the long-acting formulation was significantly lower than that obtained with the 160 mg standard tablet. However, from 12 h on the mean levels for the long-acting formulation were higher. 3 The mean peak blood level for the long-acting formulation was significantly lower than that obtained with the 80 mg twice a day regimen and this difference was maintained up to 24 h. Thereafter, however, the situation was reversed. 4 The mean blood levels between 12 and 15 h were lower for the long-acting formulation when compared with the 40 mg four times a day regimen. At all other times, however, the observed levels were very similar. 5 The profiles achieved with the long-acting formulation in two separate studies were almost identical over a 48 h period. 6 The percentage reductions in exercise heart rate over the 3-24 h post dosing period were similar for the long-acting formulation and the two standard regimens studied (i.e. CP40 and CP80) when compared with placebo. 7 In the 2 h post dosing period the 80 mg twice a day regimen produced a significant reduction in the post-exercise systolic blood pressure when compared with the long-acting formulation. PMID:678387

  9. Testing the effects of long-acting steroids in edema and ecchymosis after closed rhinoplasty.

    PubMed

    Gutierrez, Santiago; Wuesthoff, Carolina

    2014-01-01

    Steroids have proven to be of some benefit in rhinoplasty edema and ecchymosis when administered at a high and repeated dose. To evaluate the effects of single-dose, long-acting intramuscular steroids on postoperative edema and ecchymosis after closed rhinoplasty with osteotomies compared with placebo. A randomized, double-blinded, placebo-controlled trial was performed. Fifty-four patients were randomly assigned to two groups: 28 received a single dose of long-acting dexamethasone (mean [± SD] dose 16±4 mg) immediately before anesthetic induction; the remaining 26 received an intramuscular injection of saline solution. The same surgeon performed all surgeries, with patients under general anesthesia. Acetaminophen was the only analgesic used to control postoperative pain. High-resolution digital photographs were taken on postoperative days 1, 3, 7 and 14. Scoring was performed separately for eyelid swelling and ecchymosis by an independent observer using a graded scale (0 to 5) for edema and a scoring system (0 to 13) for ecchymosis. No statistically significant differences in terms of age, sex or amount of bleeding during surgery were found between the two groups. No statistically significant difference was observed in the decrease of both ecchymosis and edema between placebo and high-dose, long-acting dexamethasone. A statistically significant difference in operation time was found, favouring the steroid group. No severe complications were observed due to steroid use. Osteotomies are basically a form of (controlled) trauma, with considerable disruption of the abundant blood vessels in this facial region and, therefore, are associated with with undesirable effects. A recent meta-analysis failed to show benefits of the use of steroids after postoperative day 3. Only a trend toward reduction in edema and ecchymosis with the use of long-acting steroids compared with placebo was demonstrated in the present study. There was no benefit in administering single

  10. Testing the effects of long-acting steroids in edema and ecchymosis after closed rhinoplasty

    PubMed Central

    Gutierrez, Santiago; Wuesthoff, Carolina

    2014-01-01

    BACKGROUND: Steroids have proven to be of some benefit in rhinoplasty edema and ecchymosis when administered at a high and repeated dose. OBJECTIVE: To evaluate the effects of single-dose, long-acting intramuscular steroids on postoperative edema and ecchymosis after closed rhinoplasty with osteotomies compared with placebo. METHODS: A randomized, double-blinded, placebo-controlled trial was performed. Fifty-four patients were randomly assigned to two groups: 28 received a single dose of long-acting dexamethasone (mean [± SD] dose 16±4 mg) immediately before anesthetic induction; the remaining 26 received an intramuscular injection of saline solution. The same surgeon performed all surgeries, with patients under general anesthesia. Acetaminophen was the only analgesic used to control postoperative pain. High-resolution digital photographs were taken on postoperative days 1, 3, 7 and 14. Scoring was performed separately for eyelid swelling and ecchymosis by an independent observer using a graded scale (0 to 5) for edema and a scoring system (0 to 13) for ecchymosis. RESULTS: No statistically significant differences in terms of age, sex or amount of bleeding during surgery were found between the two groups. No statistically significant difference was observed in the decrease of both ecchymosis and edema between placebo and high-dose, long-acting dexamethasone. A statistically significant difference in operation time was found, favouring the steroid group. No severe complications were observed due to steroid use. DISCUSSION: Osteotomies are basically a form of (controlled) trauma, with considerable disruption of the abundant blood vessels in this facial region and, therefore, are associated with with undesirable effects. A recent meta-analysis failed to show benefits of the use of steroids after postoperative day 3. Only a trend toward reduction in edema and ecchymosis with the use of long-acting steroids compared with placebo was demonstrated in the present study

  11. Long-acting injectable antiretrovirals for HIV treatment and prevention

    PubMed Central

    Spreen, William R.; Margolis, David A.; Pottage, John C.

    2013-01-01

    Purpose of review Long-acting antiretroviral (ARV) drugs may improve adherence to therapy and extend opportunities for therapeutic or prophylactic intervention to underserved patient populations. This review focuses on recent advances in the development of small molecule long-acting injectable ARV agents. Recent findings The need for combination ART and physicochemical and dosing limitations of current ARV drugs impede attempts to redevelop them as long-acting injectable formulations. However, the intrinsic properties of rilpivirine, a nonnucleoside reverse transcriptase inhibitor, and GSK1265744, an HIV-1 integrase strand transfer inhibitor, have enabled crystalline nanoparticle formulations to progress to clinical trials. Summary Investigational long-acting injectable nanoformulations of rilpivirine and GSK1265744 are clinical-stage development candidates. Complementary pharmacologic properties of both agents – different mechanisms of action, resistance profiles, metabolic pathways, lack of drug interactions and low daily oral doses – offer the potential for combination use. Phase I studies of the pharmacokinetics and safety of each long-acting formulation alone and in combination indicate that a monthly dosing regimen is possible for HIV treatment. An ongoing phase IIb trial of oral GSK1265744 and oral rilpivirine is evaluating this two-drug regimen for maintenance of virologic suppression; results will inform future studies using the injectable formulations. Additional preclinical and clinical studies indicate a potential use of each agent for HIV pre-exposure prophylaxis. PMID:24100877

  12. Long-acting injectable hormonal dosage forms for contraception.

    PubMed

    Wu, Linfeng; Janagam, Dileep R; Mandrell, Timothy D; Johnson, James R; Lowe, Tao L

    2015-07-01

    Although great efforts have been made to develop long-acting injectable hormonal contraceptives for more than four decades, few long-acting injectable contraceptives have reached the pharmaceutical market or even entered clinical trials. On the other hand, in clinical practice there is an urgent need for injectable long-acting reversible contraceptives which can provide contraceptive protection for more than 3 months after one single injection. Availability of such products will offer great flexibility to women and resolve certain continuation issues currently occurring in clinics. Herein, we reviewed the strategies exploited in the past to develop injectable hormonal contraceptive dosages including drug microcrystal suspensions, drug-loaded microsphere suspensions and in situ forming depot systems for long-term contraception and discussed the potential solutions for remaining issues met in the previous development.

  13. Reassessing the importance of long-acting contraception.

    PubMed

    Karpilow, Quentin C; Thomas, Adam T

    2017-02-01

    Several recent studies have highlighted the need for greater use of long-acting contraception. The most influential of these studies is the Contraceptive CHOICE Project, which was credited with substantially reducing participants' pregnancy risk by increasing their use of long-acting methods such as intrauterine devices and subdermal implants. However, because participants' rates of nonuse and condom use fell to zero at the outset of the intervention, it is possible that sizable pregnancy reductions could still have been achieved if enrollees had chosen shorter-acting, female-controlled methods such as oral contraception. The objective of the study was to estimate the proportion of the CHOICE Project's fertility impacts that could have been achieved without any increase in long-acting method use. The FamilyScape 3.0 microsimulation model was used to estimate CHOICE's impact on pregnancy risk and to simulate the counterfactual effect of moving all nonusers and condom users onto shorter-acting, female-controlled methods. FamilyScape models the sexual and contraceptive behaviors of women in the United States between 2006 and 2010, which is the period when CHOICE was implemented. Nearly three quarters of the CHOICE intervention's effects on pregnancy risk could have been achieved if participants had chosen shorter-acting, female-controlled methods over long-acting methods. Prioritizing the adoption of long-acting contraception may not be the most advisable strategy for reducing unintended pregnancy. The most impactful interventions will likely be those that increase the use of female-controlled methods, long-acting or otherwise. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Comparative effectiveness of long-acting injectable risperidone vs. long-acting injectable first-generation antipsychotics in bipolar disorder.

    PubMed

    Wu, Chi-Shin; Hsieh, Ming H; Tang, Chao-Hsiun; Chang, Ching-Jui

    2016-06-01

    The aim of this study was to compare the treatment effectiveness between long-acting injectable risperidone and long-acting injectable first-generation antipsychotics among patients with bipolar disorder. We conducted a retrospective cohort study using Taiwan's National Health Insurance Research Database. Patients with bipolar disorder aged 15 years or higher, who were newly administered long-acting injectable antipsychotics between June 1, 2004 and December 31, 2011 were included. The clinical outcome indexes were hospitalization for any mood, manic/mixed, or depressive episodes. In addition, the all-cause discontinuation of long-acting injectable antipsychotic treatment was also assessed. A total of 3916 patients with bipolar disorder were extracted. Compared with risperidone, the use of first-generation antipsychotics was associated with a higher rate of hospitalization for any mood episode and major depressive episode. However, there was no statistically significant difference in treatment discontinuation rate between risperidone and first-generation antipsychotics. Information for the severity of mood symptoms, social support, life style, neurological and metabolic adverse effect was not available in this database. In addition, we only measured severe mood episodes with hospitalization as our outcome index. It may not be possible to generalize our findings to mild mood episodes. Our findings suggested that patients treated with long-acting injectable risperidone might be superior to first-generation antipsychotics in the rate of psychiatric hospitalization. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Clinical blood chemistry values and long acting phenothiazines.

    PubMed

    Schneider, S J; Kirby, E J; Itil, T M

    1981-05-01

    Fifty-nine chronic schizophrenic patients received one year of treatment with either fluphenazine enanthate or pipothiazine palmitate IM. Both long acting neuroleptics significantly decreased serum albumin, total protein and creatinine values. Triglycerides were decreased only early in treatment. Pretreatment findings from therapy responders, as compared with those who failed to respond to treatment, included higher albumin values and to a lesser extent, lower lactic dehydrogenase values and greater height. These results were discussed with an eye toward the hepatocellular effects of long acting phenothiazines and the effect of liver function on the pharmacokinetics of these medications.

  16. [Aripiprazole long-acting for the maintenance treatment of schizophrenia.

    PubMed

    Samalin, L; Charpeaud, T; Llorca, P-M

    2014-11-13

    Antipsychotics are the cornerstone for the maintenance treatment of schizophrenia patients. Their long-acting formulations are helpful for preventing relapses through improvement of adherence to medication and a better pharmacokinetic coverage. However, their use is often reserved for refractory or non-observant clinical forms because of limitations among both clinicians and patients. The development of a new formulation of long-acting injectable aripiprazole administered every 4 weeks is a new option. Two randomized controlled trials vs. placebo and vs. oral aripiprazole respectively show a superiority and non-inferiority in terms of relapse prevention. Meanwhile, a mirror-image study demonstrates fewer hospitalizations. The safety profile is comparable to the oral formulation, particularly in terms of metabolic and neurological side-effects. As mentioned in various professional recommendations, long-acting injectable antipsychotics, so long-acting injectable aripiprazole, are one of the major strategies of the maintenance treatment for patients with schizophrenia. Copyright © 2014. Published by Elsevier Masson SAS.

  17. Long-acting contraceptive agents: norethisterone esters of polyunsaturated acids.

    PubMed

    Francisco, C G; Freire, R; Hernandez, R; Salazar, J A; Suarez, E; Vlahov, R; Tarpanov, V; Boshkova-Ljapova, M; Milenkov, B; Stoilova, V

    1983-03-01

    Some new derivatives of norethisterone (17 alpha-ethynyl-17 beta-hydroxyestr-4-en-3-one) are described in which the 17 beta-hydroxyl group of the steroid is esterified with polyunsaturated aliphatic acids. The potential of these compounds as long-acting contraceptive agents has been evaluated.

  18. Narcotic tapering in pregnancy using long-acting morphine

    PubMed Central

    Dooley, Roisin; Dooley, Joe; Antone, Irwin; Guilfoyle, John; Gerber-Finn, Lianne; Kakekagumick, Kara; Cromarty, Helen; Hopman, Wilma; Muileboom, Jill; Brunton, Nicole; Kelly, Len

    2015-01-01

    Abstract Objective To document the management of and outcomes for patients receiving narcotic replacement and tapering with long-acting morphine preparations during pregnancy. Design A prospective cohort study over 18 months. Setting Northwestern Ontario. Participants All 600 births at Meno Ya Win Health Centre in Sioux Lookout, Ont, from January 1, 2012, to June 30, 2013, including 166 narcotic-exposed pregnancies. Intervention Narcotic replacement and tapering of narcotic use with long-acting morphine preparations. Main outcome measures Prenatal management of maternal narcotic use, incidence of neonatal abstinence syndrome, and other neonatal outcomes. Results The incidence of neonatal abstinence syndrome fell significantly to 18.1% of pregnancies exposed to narcotics (from 29.5% in a previous 2010 study, P = .003) among patients using narcotic replacement and tapering with long-acting morphine preparations. Neonatal outcomes were otherwise equivalent to those of the nonexposed pregnancies. Conclusion In many patients, long-acting morphine preparations can be safely used and tapered in pregnancy, with a subsequent decrease in observed neonatal withdrawal symptoms. PMID:25821873

  19. Long-acting reversible contraceptives for teenagers: primary care recommendations.

    PubMed

    Atkin, Kathryn; Beal, Margaret W; Long-Middleton, Ellen; Roncari, Danielle

    2015-03-12

    Long-acting reversible contraceptive (LARC) methods are underutilized in the adolescent population despite their superior efficacy over non-LARC methods. The purpose of this article is to discuss the barriers that lead to underutilization of these methods and present an evidence-based approach for the use of LARC methods among adolescents in the primary care setting.

  20. Use of long-acting reversible contraceptives to reduce the rate of teen pregnancy.

    PubMed

    Rome, Ellen

    2015-11-01

    Long-acting reversible contraceptives (LARCs) are safe for use in adolescents and do not rely on compliance or adherence for effectiveness. Continuation rates are higher and pregnancy rates are lower for adolescent users of LARCs compared with short-acting methods such as oral contraceptives. Similarly, repeat pregnancy rates are lower when LARCs are used compared with other forms of contraception. Myths and misconceptions about LARCs and other contraceptives remain a barrier to their use. Health care providers are in a unique position to provide confidential care to adolescents, and should provide education to them about the various contraceptive options, especially LARCs. Copyright © 2015 Cleveland Clinic.

  1. Combined treatment by octreotide and everolimus: Octreotide enhances inhibitory effect of everolimus in aggressive meningiomas.

    PubMed

    Graillon, Thomas; Defilles, Céline; Mohamed, Amira; Lisbonis, Christophe; Germanetti, Anne-Laure; Chinot, Olivier; Figarella-Branger, Dominique; Roche, Pierre-Hugues; Adetchessi, Tarek; Fuentes, Stéphane; Metellus, Philippe; Dufour, Henry; Enjalbert, Alain; Barlier, Anne

    2015-08-01

    Treatment for recurrent and aggressive meningiomas remains an unmet medical need in neuro-oncology, and chemotherapy exhibits limited clinical activity, if any. Merlin expression, encoded by the NF2 gene, is lost in a majority of meningiomas, and merlin is a negative regulator of mTORC1. The sst2 somatostatin receptor, targeted by octreotide, is highly expressed in meningiomas. To investigate new therapeutic strategies, we evaluated the activity of everolimus (mTOR inhibitor), BKM-120 and BEZ-235 (new Pi3K/Akt/mTOR inhibitors), octreotide and a combined treatment (octreotide plus everolimus), on cell proliferation, signaling pathways, and cell cycle proteins, respectively. The in vitro study was conducted on human meningioma primary cells extracted from fresh tumors, allowing the assessment of somatostatin analogs at the concentration levels used in patients. The results were correlated to WHO grades. Further, everolimus decreased cell viability of human meningiomas, but concomitantly, induced Akt activation, reducing the antiproliferative effect of the drug. The new Pi3K inhibitors were not more active than everolimus alone, limiting their clinical relevance. In contrast, a clear cooperative inhibitory effect of octreotide and everolimus was observed on cell proliferation in all tested meningiomas, including WHO grades II-III. Octreotide not only reversed everolimus-induced Akt phosphorylation but also displayed additive and complementary effects with everolimus on downstream proteins involved in translation (4EB-P1), and controlling cell cycle (p27Kip1 and cyclin D1). We have demonstrated a co-operative action between everolimus and octreotide on cell proliferation in human meningiomas, including aggressive ones, establishing the basis for a clinical trial.

  2. Octreotide use and safety in infants with hyperinsulinism

    PubMed Central

    McMahon, Ann W.; Wharton, Gerold T.; Thornton, Paul; De Leon, Diva D.

    2017-01-01

    Background Octreotide is a synthetic peptide analog of naturally occurring somatostatin. Octreotide is used off-label in children <6 years of age for hyperinsulinism, chylothorax, and gastrointestinal bleeding. There is a lack of controlled data on efficacy or potential adverse events from this off-label use. Methods Three pediatric hospitals participated in this study. Patients were hospitalized January 2007–December 2010 and administered octreotide for congenital hyperinsulinism (CHI) at least 1 day. Variables assessed included octreotide dosage, patient demographics, medical interventions, concomitant medicines, serious adverse events (SAEs) including necrotizing enterocolitis (NEC), and mortality. Results The 103 patient sample had a median gestational age of 38 weeks. During the study period, two patients died: one from NEC and the other from cardiomyopathy/sepsis. There were 11 other SAEs in the 101 surviving patients. Conclusion This study highlights potential risks in administering octreotide off-label. This study, like several other published studies, has highlighted NEC in a full-term infant treated with octreotide. It is important to study the efficacy and the safety of octreotide for hyperinsulinism. In the interim, it might be prudent to prescribe octreotide in CHI neonates only in the absence of other risk factors for NEC. PMID:27910218

  3. Status of long-acting-growth hormone preparations--2015.

    PubMed

    Høybye, Charlotte; Cohen, Pinchas; Hoffman, Andrew R; Ross, Richard; Biller, Beverly M K; Christiansen, Jens Sandahl

    2015-10-01

    Growth hormone (GH) treatment has been an established therapy for GH deficiency (GHD) in children and adults for more than three decades. Numerous studies have shown that GH treatment improves height, body composition, bone density, cardiovascular risk factors, physical fitness and quality of life and that the treatment has few side effects. Initially GH was given as intramuscular injections three times per week, but daily subcutaneous injections were shown to be more effective and less inconvenient and the daily administration has been used since its introduction in the 1980s. However, despite ongoing improvements in injection device design, daily subcutaneous injections remain inconvenient, painful and distressing for many patients, leading to noncompliance, reduced efficacy and increased health care costs. To address these issues a variety of long-acting formulations of GH have been developed. In this review we present the current status of long-acting GH preparations and discuss the specific issues related to their development.

  4. Two cases of long-acting paliperidone in adolescence

    PubMed Central

    Fàbrega, Marina; Sugranyes, Gisela; Baeza, Inmaculada

    2015-01-01

    Paliperidone palmitate long-acting injection (PPLAI) is an atypical antipsychotic agent currently approved by the European Medicine Agency for the acute and maintenance treatment of schizophrenia in adults. However, there is no information so far on safety and effectiveness in patients under 18 years of age. We report on two clinical cases of adolescents with a psychotic spectrum disorder treated with PPLAI in an inpatient setting. The cases illustrate that PPLAI may hold potential as an effective and acceptably tolerated antipsychotic drug in adolescents with psychotic spectrum disorders. Given the lack of approved long acting injectable antipsychotics in patients under 18 years of age, reports on the effectiveness and safety of such medications in children and adolescent patients are of importance. PMID:26557986

  5. Long-acting estrogenic responses of estradiol fatty acid esters.

    PubMed

    Vazquez-Alcantara, M A; Menjivar, M; Garcia, G A; Díaz-Zagoya, J C; Garza-Flores, J

    1989-12-01

    Estradiol esters at C-17 and C-3 with palmitic, stearic and oleic acids were chemically synthesized and then evaluated for their long-acting estrogenic responses in ovariectomized rats. The duration of the biological effects was measured after a single subcutaneous dose of 0.1 mumol of each ester and compared with those observed with 17 beta-estradiol, estradiol 3-benzoate and estradiol 17-enanthate. Vaginal citology, uterophyc action, serum gonadotropins inhibition and 17 beta-estradiol levels were measured 0, 5, 10, 20, 30 and 60 days after injection. The results disclosed that most of the estradiol derivatives evaluated exhibited a long-acting estrogenic action. However, the monoesters at C-17 showed longer effects that monoesters at C-3, while the estradiol diesters exhibited the shortest effects. In addition as shown by its low serum levels, all estradiol esters with unsaturated fatty acids show a decreased E2 absorption. The overall results indicated that esterification of E2 with long chain fatty acids provided long-acting properties to it, being higher with C-17 esters. Whether some of these compounds could be employed in substitutive endocrine therapy remains to be established.

  6. Pharmacokinetics and tolerability of long-acting risperidone in schizophrenia.

    PubMed

    Eerdekens, Mariëlle; Van Hove, Ilse; Remmerie, Bart; Mannaert, Erik

    2004-09-01

    The pharmacokinetics and tolerability of long-acting risperidone (Risperdal Consta) were evaluated in a multicenter, prospective, open-label, 15-week study of 86 patients with schizophrenia. Subjects stabilized on 2, 4 or 6 mg of oral risperidone once daily for at least 4 weeks were assigned to receive i.m. injections of 25, 50 or 75 mg of risperidone, respectively, every 2 weeks for 10 weeks. The 90% confidence intervals for the i.m./oral ratios of the mean steady-state plasma-AUC, corrected for dosing interval, and of the average plasma concentration of the active moiety (risperidone plus 9-hydroxyrisperidone) were within the range of 80-125%, indicating bioequivalence of the i.m. and oral formulations. However, mean steady-state peak concentrations of the active moiety were 25-32% lower with i.m. than oral dosing (P < 0.05) and fluctuations in plasma active-moiety levels were 32-42% lower with the i.m. than oral regimen. Symptoms of schizophrenia continued to improve after switching from oral to i.m. dosing. Long-acting risperidone was well tolerated locally and systematically. Although overall bioequivalence of the two formulations was established, the differences in pharmacokinetic profiles between the two formulations indicate potential benefits for long-acting risperidone.

  7. Long Acting Contraception Provision by Rural Primary Care Physicians

    PubMed Central

    Smith, Paul; Grewal, Manpreet; Kumaraswami, Tara; Cowett, Allison; Harwood, Bryna

    2014-01-01

    Abstract Objectives: Unplanned pregnancy is a public health problem in the United States, including in rural areas. Primary care physicians are the main providers of health care to women in rural areas and are uniquely positioned to help reduce unplanned pregnancy in rural women. This study documents provision of contraception by rural primary care physicians, focusing on the most effective, long acting methods, intrauterine devices (IUDs) and contraceptive implants. Methods: We surveyed all primary care physicians practicing in rural areas of Illinois and Wisconsin. Bivariate analysis was performed using chi squared and Fisher's exact test, and multivariable analysis was performed with logistic regression to determine factors associated with provision. Results: The response rate was 862 out of 2312 physicians (37%). Nine percent of respondents place implants and 35% place IUDs. Eighty-seven percent of physicians had not had training in implant placement, and 41% had not had training in IUD placement. In multivariable analysis, factors associated with placement of long acting contraception include provision of maternity care, and female gender of the physician. The most common reasons for not providing the methods were lack of training and perceived low demand from patients. Conclusions: Many rural primary care providers do not place long acting contraceptive devices due to lack of training. Female physicians and those providing maternity care are the most likely to place these devices. Increased training for primary care physicians both during and after residency would help increase access to these options for women in rural areas. PMID:24443930

  8. Novel long-acting bronchodilators for COPD and asthma

    PubMed Central

    Cazzola, M; Matera, M G

    2008-01-01

    An important step in simplifying asthma and chronic obstructive pulmonary disease (COPD) management and improving adherence with prescribed therapy is to reduce the dose frequency to the minimum necessary to maintain disease control. Therefore, the incorporation of once-daily dose administration is an important strategy to improve adherence and is a regimen preferred by most patients, which may also lead to enhancement of compliance, and may have advantages leading to improved overall clinical outcomes. Once-daily β2-agonists or ultra long-acting β2-agonists (LABAs) such as carmoterol, indacaterol, GSK-159797, GSK-597901, GSK-159802, GSK-642444 and GSK-678007 are under development for the treatment of asthma and COPD. Also some new long-acting antimuscarinic agents (LAMAs) such as aclidinium, LAS-35201, GSK656398, GSK233705, NVA-237 (glycopyrrolate) and OrM3 are under development. In any case, the current opinion is that it will be advantageous to develop inhalers containing combination of several classes of long-acting bronchodilator drugs in an attempt to simplify treatment regimens as much as possible. Consequently, several options for once-daily dual-action ultra LABA+LAMA combination products are currently being evaluated. A different approach is to have a dimer molecule in which both pharmacologies are present (these molecules are known as M3 antagonist-β2 agonist (MABA) bronchodilators). The advent of a successful MABA product will revolutionize the field and open the door for a new range of combination products. PMID:18604231

  9. Pharmacogenomics of long-acting β2-agonists.

    PubMed

    Blake, Kathryn; Lima, John

    2015-01-01

    Long-acting β2-agonists are an effective class of drugs, when combined with inhaled corticosteroids, for reducing symptoms and exacerbations in patients with asthma that is not adequately controlled by inhaled corticosteroids alone. However, because this class of drugs has been associated with severe adverse events, including hospitalization and death in small numbers of patients, efforts to identify a pharmacogenetic profile for patients at risk has been diligently investigated. The PubMed search engine of the National Library of Medicine was used to identify English-language and non-English language articles published from 1947 to March 2015 pertinent to asthma, pharmacogenomics, and long-acting β2-agonists. Keywords and topics included: asthma, asthma control, long-acting β2-agonists, salmeterol, formoterol, pharmacogenetics, and pharmacogenomics. This strategy was also used for the Cochrane Library Database and CINAHL. Reference types were randomized controlled trials, reviews, and editorials. Additional publications were culled from reference lists. The publications were reviewed by the authors and those most relevant were used to support the topics covered in this review. Children, who carry the ADRB2 Arg16Arg genotype, may be at greater risk than adults for severe adverse events. Rare ADRB2 variants appear to provide better clues for identifying the at-risk population of asthmatics.

  10. A case of bronchial carcinoid: diagnosis and follow-up with 111In-DTPA-octreotide.

    PubMed

    Orsolon, P; Bagni, B; Basadonna, P; Geatti, O; Talmassons, G; Guerra, U P

    1995-12-01

    Scintigraphy with radiolabelled analogue of somatostatin is highly sensitive in detecting carcinoid tumors especially if performed with Single Photon Computed Tomography (SPECT). In this report we describe our experience with 111In-DTPA-Octreotide in a female patient affected by a small asymptomatic intrabronchial carcinoid demonstrated by CT scan and bronchial endoscopy performed after recurrent left pneumonias. Planar views and SPECT images, using 111In-DTPA-Octreotide, were collected before and four hours after the first endoscopic laser resection. All groups of SPECT images were positive in the left parahilar region but at a different degree. Scans performed after resection showed a low degree of uptake which was considered to be probably secondary to local swelling; CT scan was negative. Follow up endoscopic biopsy repeated at six months, showed a relapse always in the same site; CT scan of the thorax was again negative. 111In-DTPA-Octreotide images obtained at twelve months were positive always in the left parahilar region, CT scan was negative but another biopsy was not possible. Therefore it was suspected a relapse of the carcinoid which was probably growing only through the bronchial wall without spreading towards the bronchial lumen and/or the lung parenchima. In this occasion, it was also thought that images collected four hours after resection could be positive not only for swelling but for a relapse as well. In every scintigraphic session, SPECT images presented higher quality than planar. This case suggests that 111In-DTPA-Octreotide SPECT is a non-invasive diagnostic technique which could be applied as a follow-up tool especially to patients with no-secreting carcinoid neoplasm and/or with negative or doubtful endoscopic and radiological investigations.

  11. Patient and Health Care Provider Perspectives on Long Acting Injectable Antipsychotics in Schizophrenia and the Introduction of Olanzapine Long-Acting Injection

    PubMed Central

    Wehring, Heidi J.; Thedford, Sheryl; Koola, Maju; Kelly, Deanna L.

    2011-01-01

    Olanzapine long acting injection has joined risperidone and paliperidone as the second generation long acting antipsychotic injection options for treatment of patients with schizophrenia. Long acting injections are important alternatives to oral medications for patients who have difficulty adhering to daily or multiple daily medication administrations, yet may be underutilized or not well understood. Patient perceptions, adherence, and preferences are important issues for health care providers to address when discussing treatment options with their patients. Reviewed here are overall patient and health care provider attitudes and perceptions regarding long acting injections and the details of olanzapine long acting injectable, the newest agent, and how it will fit in the marketplace. In addition, efficacy, safety, dosing and use data regarding this newest long acting agent are reviewed and compared to other available long acting agents. PMID:23293546

  12. The combination of octreotide and midodrine is not superior to albumin in preventing recurrence of ascites after large-volume paracentesis.

    PubMed

    Bari, Khurram; Miñano, Cecilia; Shea, Martha; Inayat, Irteza B; Hashem, Hashem J; Gilles, Hochong; Heuman, Douglas; Garcia-Tsao, Guadalupe

    2012-10-01

    Large-volume paracentesis (LVP) is the treatment of choice for patients with cirrhosis and refractory ascites. However, LVP can lead to postparacentesis circulatory dysfunction (PCD), which is associated with faster ascites recurrence and renal failure. PCD results from vasodilatation, which reduces effective blood volume, and is prevented by intravenous administration of albumin. Vasoconstrictors could be used instead of albumin and, with longer use, prevent PCD and delay ascites recurrence. We performed a multicenter, randomized, double-blind, placebo-controlled trial to compare albumin with the vasoconstrictor combination of octreotide and midodrine in patients with refractory ascites who underwent LVP. Patients in the albumin group received a single intravenous dose of albumin at the time of LVP plus placebos for midodrine and octreotide (n = 13). Patients in the vasoconstrictor group received saline solution (as a placebo for albumin), 10 mg of oral midodrine (3 times/day), and a monthly 20-mg intramuscular injection of long-acting octreotide (n = 12). Patients were followed up until recurrence of ascites. The median times to recurrence of ascites were 10 days in the albumin group and 8 days in the vasoconstrictor group (P = .318). There were no significant differences in PCD between the albumin group (18%) and the vasoconstrictor group (25%, P = .574). When ascites recurred, serum levels of creatinine were higher in the vasoconstrictor group (1.2 vs 0.9 mg/dL in the albumin group; P = .051). The combination of midodrine and octreotide after LVP is not superior to albumin in delaying recurrence of ascites or preventing PCD in patients with cirrhosis. Outcomes appear to be worse in patients given octreotide and midodrine. ClinicalTrials.gov number, NCT00108355. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

  13. The Combination of Octreotide and Midodrine is not Superior to Albumin in Preventing Recurrence of Ascites after Large-Volume Paracentesis

    PubMed Central

    Bari, Khurram; Minano, Cecilia; Shea, Martha; Inayat, Irteza B.; Hashem, Hashem J.; Gilles, HoChong; Heuman, Douglas; Garcia-Tsao, Guadalupe

    2012-01-01

    Background & Aims Large-volume paracentesis (LVP) is the treatment of choice for patients with cirrhosis and refractory ascites. However, LVP can lead to post-paracentesis circulatory dysfunction (PCD), which is associated with faster ascites recurrence and renal failure. PCD results from vasodilatation, which reduces effective blood volume, and is prevented by intravenous administration of albumin. Vasoconstrictors could be used instead of albumin and, with longer use, prevent PCD and delay ascites recurrence. Methods We performed a multicenter, randomized, double-blind, placebo controlled trial to compare albumin with the vasoconstrictor combination of octreotide and midodrine in patients with refractory ascites who underwent LVP. Patients in the albumin group received a single intravenous dose of albumin at the time of LVP plus placebos for midodrine and octreotide (n=13). Patients in the vasoconstrictor group received saline solution (as a placebo for albumin), 10 mg of oral midodrine (3 times daily), and a monthly, 20 mcg intra-muscular injection of long-acting octreotide (n=12). Patients were followed until recurrence of ascites. Results The median times to recurrence of ascites were 10 days in the albumin group and 8 days in the vasoconstrictor group (P=.318). There were no significant differences in PCD between the albumin group (18%) and the vasoconstrictor group (25%, P=.574). When ascites recurred, serum levels of creatinine were higher in the vasoconstrictor group (1.2 vs 0.9 mg/dL in the albumin group, P=.051). Conclusions The combination of midodrine and octreotide after LVP is not superior to albumin in delaying recurrence of ascites or preventing PCD in patients with cirrhosis. Outcomes appear to be worse in patients given octreotide and midodrine. PMID:22801062

  14. Somatostatin receptor subtypes, octreotide scintigraphy, and clinical response to octreotide treatment in patients with neuroendocrine tumors.

    PubMed

    Kölby, L; Wängberg, B; Ahlman, H; Tisell, L E; Fjälling, M; Forssell-Aronsson, E; Nilsson, O

    1998-07-01

    Several types of neuroendocrine tumor express high numbers of somatostatin receptors (sstr). We have compared the expression of sstr subtypes with the outcome of octreotide scintigraphy in patients with carcinoids and medullary thyroid carcinoma (MTC) in comparison with Hürthle cell tumors. The effect of sstr activation (octreotide treatment) on tumor markers was also studied in patients with disseminated carcinoid tumors. Six patients with carcinoid tumors (four midgut and two foregut), and three patients with thyroid tumors (one MTC, one Hürthle cell carcinoma, and one Hürthle cell adenoma) were studied. Octreotide scintigraphy visualized tumor sites in all nine patients. Macroscopic tumor was verified at these sites at subsequent surgical exploration. Using Northern blotting and subtype-specific riboprobes, sstr could be detected in all tumors examined. All five sstr subtypes were detected in most of the carcinoid tumors. All six carcinoids expressed sstr2. This was in contrast to the findings for the thyroid tumors analyzed, which also expressed several sstr subtypes but in some cases lacked expression of sstr2. This was also the case for normal thyroid tissue. Clinically, octreotide treatment of the patients with midgut carcinoid tumors resulted in palliation of hormonal symptoms accompanied by a significant reduction of urinary 5-HIAA levels (28-71%). These results indicate that carcinoid tumors frequently express all five sstr subtypes. The thyroid tumors also expressed multiple sstr but could lack expression of sstr2. Nevertheless, these tumors were visualized by octreotide scintigraphy, indicating that sstr2 expression is not a prerequisite for tumor imaging.

  15. The pharmacokinetics of a long-acting OROS hydromorphone formulation.

    PubMed

    Turgeon, J; Gröning, R; Sathyan, G; Thipphawong, J; Richarz, U

    2010-01-01

    New formulations of opiods can provide round-the-clock pain relief to improve pain management and quality of life for patients with chronic pain. Information and comments on the pharmacokinetic processes associated with a new once-daily formulation of the potent opiod hydromorphone. This review presents an overview of data from several small pharmacokinetic studies to gain a better perspective on the pharmacokinetic properties of a new long-acting formulation of hydromorphone. The development of advanced oral formulation that deliver analgesic drugs over an extended period provides new solutions to improve pain management and quality of life for patients with chronic pain.

  16. The hope and reality of long-acting hemophilia products.

    PubMed

    Pipe, Steven W

    2012-05-01

    Recombinant DNA technology and protein engineering are creating hope that we can address ongoing challenges in hemophilia care such as reducing the costs of therapy, increasing the availability to the developing world, and improving the functional properties of these proteins. Technological advances to improve the half-life of recombinant clotting factors have brought long-acting clotting factors for hemophilia replacement therapy closer to reality. Preclinical and clinical trial results are reviewed as well as the potential benefits and risks of these novel therapies. Copyright © 2012 Wiley Periodicals, Inc.

  17. [Treatment of acromegaly with octreotide LAR].

    PubMed

    Sosa, Ernesto; Espinosa-de-los-Monteros, Ana Laura; González, Baldomero; Vargas, Guadalupe; Mier, Fernando; Mercado, Moisés

    2008-01-01

    Treatment of acromegaly with somastostatin analogues, albeit highly effective, is not curative and its elevated cost represents a major disadvantage. Hereby we describe our Center's experience using a fixed, 20 mg q.4 weeks- dose of octreotide LAR. 97 patients, 69 females, 71 with macroadenomas, treated with 20-mg im injections of octreotide LAR every 4 weeks, in 23 as primary therapy. No dose escalation was allowed. Patients were evaluated with GH and IGF-1 levels at 4 weeks after the third injection; thereafter, assessments occurred at 3 to 6 months intervals. In 27 unselected patients, evaluations were also performed 6 weeks after the SA injection. A GH concentration < 2.5 ng/mL was reached by 71%, 75% and 83% of patients at the 3rd , 6th and 12th months of follow up respectively, whereas over 30% achieved an IGF-1 index < or = 1.0 at each of these time points, and both biochemical goals were achieved by 30%, 33% and 32% of patients at the same time points. Biochemical success was the same for those patients treated primarily and those treated secondarily and prior radiation made no difference. A baseline GH level > 10 ng/mL was associated with a poor response. A biochemical control rate comparable with other published series it is feasible to reach with the treatment with a fixed dose of 20 mg.

  18. A review of aripiprazole long-acting injection.

    PubMed

    Chue, Pierre; Chue, James

    2016-01-01

    To review the published literature on aripiprazole once monthly, a second generation antipsychotic (SGA) recently developed as a long-acting injection (LAI), in the form of a suspension of lyophilized aripiprazole reconstituted with an aqueous diluent, for intramuscular administration. An electronic database search was conducted using the key words; relevant articles were then hand searched and websites (FDA, EMA, Otsuka, Lundbeck, NIH) reviewed. Efficacy has been demonstrated in preventing relapse in a 52 week study versus placebo, and non-inferiority to oral aripiprazole in a 38 week study, as well as in the treatment of hospitalized adult patients with acutely relapsed schizophrenia. Aripiprazole LAI appears cost-effective versus other SGA-LAIs, with improved health-related quality of life and functioning in a head-to-head study with paliperidone LAI. A 6 month (pre and post), mirror-image switch study demonstrated a reduction in hospitalization and associated costs compared with previous antipsychotic treatment. Safety and tolerability are comparable to oral aripiprazole with no new safety signals. Experience with oral aripiprazole and the current availability of the long-acting formulation suggest a potential benefit in a variety of clinical scenarios and therefore consideration as a treatment option in the treatment of schizophrenia.

  19. Long-acting Injectable Antipsychotics in First-episode Schizophrenia

    PubMed Central

    Jeong, Hyun-Ghang

    2013-01-01

    Antipsychotic medications are important for the successful management of schizophrenia. Continuous treatment with medication is superior in relapse prevention and non-adherence to antipsychotic medication is associated with a poor clinical outcome. Long-acting injectable antipsychotics (LAIs) that can guarantee adherence to a treatment regimen could be a useful treatment option. With the introduction of second-generation atypical antipsychotics-long acting injection (SGA-LAI), the risks for extrapyramidal adverse events are decreased. The indications for SGA-LAI have been extended from chronic, stabilized patients to acute psychotic patients. Some studies investigated the use of LAI in first-episode schizophrenia patients and raised the possibility of prescribing LAI as a treatment option. However, there is still limited research using LAI in first-episode schizophrenia. More well-designed, randomized, controlled clinical trials using SGA-LAIs in first episode schizophrenia are needed. Additionally, studies on side effects of SGA-LAI in long-term use are required prior to recommending LAI for patients with first episode schizophrenia. PMID:23678347

  20. A qualitative analysis of long-acting reversible contraception.

    PubMed

    Sundstrom, Beth; Baker-Whitcomb, Annalise; DeMaria, Andrea L

    2015-07-01

    Increasing access to long-acting reversible contraception (LARC), including the intrauterine device and the implant is a public health and clinical imperative to reduce rates of unintended pregnancy. In 2012, the American College of Obstetricians and Gynecologists recommended these methods for all women, including adolescents. Little research explores why young women reject these safe, effective contraceptive methods. A total of 53 women aged 18-24 years completed in-depth interviews. Analytical techniques from the grounded theory approach were used to identify patterns and themes across the data. Participants initiated hormonal contraception for "the pill's" beneficial side effects and believed a myth of perfect use, which constructed a false choice of LARC methods. Barriers to LARC options included access, medical resistance, and cost. Participants described a sense of unease about methods perceived as "alien." These women underestimated the risks of oral contraceptive pills and overestimated the risks of long-acting reversible contraception, including infertility. The myth of perfect use emerged as participants wanted to be in control by taking "the pill" every day; however, many described imperfect adherence. Findings include strategies for public health professionals and health care providers to distribute satisfactory and effective contraception for young women. Effective health communication campaigns will emphasize the desirable side effects, safety and increased effectiveness of LARC methods.

  1. Prophylactic use of octreotide for asparaginase-induced acute pancreatitis.

    PubMed

    Sakaguchi, Sachi; Higa, Takeshi; Suzuki, Mitsuyoshi; Fujimura, Junya; Shimizu, Toshiaki

    2017-08-01

    In the present study, we sought to evaluate the prophylactic use of octreotide for asparaginase-induced acute pancreatitis. We reviewed the medical records of seven patients in two institutions who received prophylactic octreotide for re-administration of asparaginase after asparaginase-induced acute pancreatitis. Three patients completed asparaginase treatment without developing pancreatitis, and four experienced recurrence of pancreatitis. A literature search using PubMed identified four additional patients in whom asparaginase was successfully re-administered with octreotide. Prophylactic use of octreotide may, thus, be warranted for patients who would benefit from re-administration of asparaginase for cancer treatment; however, careful observation is needed to monitor for breakthrough recurrence of pancreatitis.

  2. Carcinoid tumor and intravenous octreotide infusion during labor and delivery.

    PubMed

    Le, B T; Bharadwaj, S; Malinow, A M

    2009-04-01

    There are limited numbers of reports concerning the management of pregnancy complicated by carcinoid tumors. Octreotide, the synthetic analogue of somatostatin, has been found to be beneficial in preventing the perioperative exacerbation of carcinoid syndrome. We present a case of the successful use of neuraxial analgesia/anesthesia for labor and vaginal delivery in a symptomatic parturient afflicted with carcinoid syndrome, who received an intravenous infusion of octreotide throughout labor and vaginal delivery.

  3. The effect of 1 month of therapy with midodrine, octreotide-LAR and albumin in refractory ascites: a pilot study.

    PubMed

    Tandon, Puneeta; Tsuyuki, Ross T; Mitchell, Lesley; Hoskinson, Michael; Ma, Mang M; Wong, Winnie W; Mason, Andrew L; Gutfreund, Klaus; Bain, Vincent G

    2009-02-01

    The pathogenesis of refractory ascites (RA) is linked to splanchnic vasodilation. We hypothesized that a combination of midodrine, octreotide long-acting release (LAR) and albumin would result in increased natriuresis, better control of ascites and an improvement in renal function in patients with RA+/-Type 2 hepatorenal syndrome. A prospective pilot study in patients with RA as defined by the International Ascites Club. Consecutive patients received an intramuscular injection of octreotide-LAR, 50 g of albumin three times per week and midodrine titrated to increase the systolic blood pressure for 1 month. Ten patients with RA were enrolled and eight with complete data to 1 month post-treatment were included in the analysis. There was no change in renal function but there was a trend towards a reduction in the volume of ascites removed by paracentesis (P=0.08) and a significant reduction in the plasma renin (P=0.01) and aldosterone concentrations (P=0.01). Interestingly, there was a transient worsening in the model for end-stage liver disease (MELD) score (P=0.01). The deterioration in MELD was completely reversible after discontinuation of therapy. To our knowledge, this is the first study of prolonged midodrine, octreotide and albumin therapy in RA. We observed a significant reduction in the plasma renin and aldosterone concentrations and a trend towards a reduction in the volume of ascites removed by paracentesis without an effect on renal function. The beneficial effects are at the expense of a reversible deterioration in the MELD score. Large controlled trials are needed before this therapy can be routinely recommended.

  4. Immediate postpartum provision of long-acting reversible contraception.

    PubMed

    Goldthwaite, Lisa M; Shaw, Kate A

    2015-12-01

    The objective of this review is to describe current literature regarding the role and characteristics of long-acting reversible contraception (LARC) used immediately postpartum. Copper and levonorgestrel intrauterine devices (IUDs) inserted immediately postpartum at the time of both vaginal and cesarean deliveries are associated with higher rates of continuation at 6-12 months when compared with IUDs placed at the postpartum visit (4-8 weeks after delivery), despite higher rates of expulsion. IUDs and contraceptive implants are cost-effective when used immediately postpartum, and they are associated with longer interpregnancy intervals. There is limited evidence regarding the effects of immediate postpartum LARC on breastfeeding. Use of LARC methods in the immediate postpartum period is both effective and safe, and could reduce unmet need for contraception during this time. More research is needed to explore various immediate postpartum IUD insertion methods and the effects of immediate postpartum progestin-containing LARC on breastfeeding.

  5. Long acting porous microparticle for pulmonary protein delivery.

    PubMed

    Kwon, Min Jung; Bae, Jun Ho; Kim, Jung Ju; Na, Kun; Lee, Eun Seong

    2007-03-21

    This study investigated the porous-microparticle (PM) with low mass density and large size for pulmonary drug delivery. PM was prepared by the water-in-oil-in-water (W(1)/O/W(2)) multi-emulsion method with cyclodextrin derivative as a porogen and a stabilizer of peptide drugs. Herein, sucrose ethyl acetate (SAIB) was incorporated in PM for long acting protein release. In vitro release studies, the rapid release rate of proteins from PM was reduced due to the high viscosity of the added SAIB. As a result, BSA release from PM continued up to 7 days. This result suggests that PM having sustained release characteristics may be successfully applied for long-term pulmonary administration of protein or peptide drug. In addition, it is expected that these particles arrive at a deep lung epithelium due to low density (high porosity) and limit macrophage recognition because of big particle size (more than 5 microm).

  6. Long-acting injectable antipsychotics: focus on olanzapine pamoate

    PubMed Central

    Lindenmayer, JP

    2010-01-01

    Medication non-adherence in patients with schizophrenia continues to be a significant problem and threatens successful treatment outcomes. Medication non-adherence is often associated with negative consequences, including symptom exacerbation, more frequent emergency room visits, re-hospitalizations and relapse. Long-acting injectable (LAI) forms of antipsychotics allow for rapid identification of non-adherence, obviate the need for the patient to take the medication on a daily basis and increase adherence to some significant degree. Eli Lilly has developed a long-acting depot formulation of olanzapine, olanzapine pamoate, which has recently been approved by the FDA for the US market, and which will be reviewed here. Olanzapine LAI appears to be an effective antipsychotic at dosages of 210 mg every 2 weeks, 300 mg every 2 weeks and 405 mg every 4 weeks in patients with acute schizophrenia, and at 150 mg every 2 weeks, 300 mg every 2 weeks and at 405 mg every 4 weeks for the maintenance treatment of stable patients. Oral supplementation appears not to be needed, particularly not at the onset of treatment with the LAI as is necessary with risperidone LAI. Its efficacy is in general comparable to the efficacy seen with oral olanzapine at a corresponding dose. The side effect profile is also comparable to the side effects observed with oral olanzapine, including lower rates of extrapyramidal symptoms, prolactin elevation and cardiovascular side effects, but significant metabolic effects. The latter include significant weight gain, lipid abnormalities and glucose dysregulation. While the injection site adverse events are overall mild, the most significant serious adverse event is the post-injection delirium sedation syndrome (PDSS). While rare, this syndrome results from inadvertent intravascular injection of olanzapine LAI and can cause a range of olanzapine overdose-type of symptoms. Olanzapine LAI needs therefore to be administered by trained personnel in settings

  7. The value of an acute octreotide suppression test in predicting short-term efficacy of somatostatin analogues in acromegaly.

    PubMed

    Wang, Meng; Shen, Ming; He, Wenqiang; Yang, Yeping; Liu, Wenjuan; Lu, Yun; Ma, Zengyi; Ye, Zhao; Zhang, Yichao; Zhao, Xiaolong; Lu, Bin; Hu, Ji; Huang, Yun; Shou, Xuefei; Wang, Yongfei; Ye, Hongying; Li, Yiming; Li, Shiqi; Zhao, Yao; Zhang, Zhaoyun

    2016-09-30

    Predicting the efficacy of long-acting somatostatin analogues (SSA) remains a challenge. We aim to quantitatively evaluate the predictive value of the octreotide suppression test (OST) in short-term efficacy of SSA in active acromegaly. Sixty-seven newly diagnosed acromegaly patients were assessed with OST. Subsequently, all patients were treated with long-acting SSA for 3 months, followed by reassessment. Nine parameters were tested, including GHn (the nadir GH during OST), ΔGH1 (= [GH0h-GHn]/GH0h, GH0h was the baseline GH during OST), ΔGH2 (= [GHm-GHn]/GHm, GHm was the mean GH on day curve), AUC(0-6h) (the GH area under the curve during OST) , ΔAUC1 (= [GH0h-AUC(0-6h)]/GH0h), ΔAUC2 (=[GHm-AUC(0-6h)]/GHm), AUC(m-6h) (the GH AUC during OST where GHm was used instead of GH0h), ΔAUC1' (=[GH0h-AUC(m-6h)]/GH0h) and ΔAUC2' (=[GHm-AUC(m-6h)]/GHm). The Youden indices were calculated to determine the optimal cutoffs to predict the short-term efficacy of SSA. ΔGH2 more than 86.83%, ΔAUC2 more than -57.48% and ΔAUC2' more than -57.98% provided the best predictors of a good GH response (sensitivity 93.8%, specificity 85.7%). ΔGH2 more than 90.51% provided the best predictor of a good tumor size response (sensitivity 84.8%, specificity 87.5%). The percentage fall of GHn (ΔGH) was a better predictive parameter than GHn. OST showed higher efficiency in predicting the efficacy of octreotide LAR than lanreotide SR. In conclusion, OST is a valid tool to predict both GH and tumor size response to short-term efficacy of SSA in acromegaly, especially for octreotide LAR. GHm is better to be used as basal GH than GH0 during OST.

  8. Comparison of octreotide LAR and lanreotide autogel as post-operative medical treatment in acromegaly.

    PubMed

    Tutuncu, Yasemin; Berker, Dilek; Isik, Serhat; Ozuguz, Ufuk; Akbaba, Gulhan; Kucukler, Ferit Kerim; Aydin, Yusuf; Guler, Serdar

    2012-09-01

    Long-acting somatostatin analogs are frequently used as adjuvant treatment of acromegaly patients after noncurative surgery. This sudy aims to compare the efficacy of octreotide long-acting release (OCT) and lanreotide Autogel (LAN) in acromegaly patients. Sixty-eight patients not cured by transsphenoidal endoscopic or microscopic pituitary surgery between 2003 and 2009 were retrospectively analyzed (25 men; 43 women; mean age 41.1 ± 10.9 years [range 18-65 years]). The patients were assigned randomly to OCT (n = 36) and LAN (n = 32) groups. Evaluations included insulin-like growth factor I (IGF-I) and growth hormone (GH) after oral glucose tolerance test (OGTT) 3, 6, 12 and 18 months after starting medical treatment; pituitary magnetic resonance imaging was performed before treatment and after 3 and 12 months. Patients achieving IGF-I levels within the age and gender normal range and GH level <1 μg/l following OGTT were considered a 'biochemical cure'. Mean IGF-I and GH values and tumor volumes (cm(3)) in the LAN and OCT groups were similar in the post-operative period before initiation of medical treatment. A statistically significant decrease in GH and IGF-I levels was obtained for both treatment groups at each follow-up visit compared to the previous value. Tumor shrinkage after 12 months of treatment was statistically significant in both groups but the percentage tumor shrinkage (28.5% vs. 34.9%, P = 0.166) and rate of patients achieving biochemical cure (63.9 and 78.1%, P = 0.454) were similar between OCT and LAN groups, respectively. OCT and LAN treatment options have similar efficacy for ensuring biochemical cure and tumor shrinkage in acromegaly patients who had noncurative surgery.

  9. Long-Acting Beta Agonists Enhance Allergic Airway Disease.

    PubMed

    Knight, John M; Mak, Garbo; Shaw, Joanne; Porter, Paul; McDermott, Catherine; Roberts, Luz; You, Ran; Yuan, Xiaoyi; Millien, Valentine O; Qian, Yuping; Song, Li-Zhen; Frazier, Vincent; Kim, Choel; Kim, Jeong Joo; Bond, Richard A; Milner, Joshua D; Zhang, Yuan; Mandal, Pijus K; Luong, Amber; Kheradmand, Farrah; McMurray, John S; Corry, David B

    2015-01-01

    Asthma is one of the most common of medical illnesses and is treated in part by drugs that activate the beta-2-adrenoceptor (β2-AR) to dilate obstructed airways. Such drugs include long acting beta agonists (LABAs) that are paradoxically linked to excess asthma-related mortality. Here we show that LABAs such as salmeterol and structurally related β2-AR drugs such as formoterol and carvedilol, but not short-acting agonists (SABAs) such as albuterol, promote exaggerated asthma-like allergic airway disease and enhanced airway constriction in mice. We demonstrate that salmeterol aberrantly promotes activation of the allergic disease-related transcription factor signal transducer and activator of transcription 6 (STAT6) in multiple mouse and human cells. A novel inhibitor of STAT6, PM-242H, inhibited initiation of allergic disease induced by airway fungal challenge, reversed established allergic airway disease in mice, and blocked salmeterol-dependent enhanced allergic airway disease. Thus, structurally related β2-AR ligands aberrantly activate STAT6 and promote allergic airway disease. This untoward pharmacological property likely explains adverse outcomes observed with LABAs, which may be overcome by agents that antagonize STAT6.

  10. Long-Acting Beta Agonists Enhance Allergic Airway Disease

    PubMed Central

    Knight, John M.; Mak, Garbo; Shaw, Joanne; Porter, Paul; McDermott, Catherine; Roberts, Luz; You, Ran; Yuan, Xiaoyi; Millien, Valentine O.; Qian, Yuping; Song, Li-Zhen; Frazier, Vincent; Kim, Choel; Kim, Jeong Joo; Bond, Richard A.; Milner, Joshua D.; Zhang, Yuan; Mandal, Pijus K.; Luong, Amber; Kheradmand, Farrah

    2015-01-01

    Asthma is one of the most common of medical illnesses and is treated in part by drugs that activate the beta-2-adrenoceptor (β2-AR) to dilate obstructed airways. Such drugs include long acting beta agonists (LABAs) that are paradoxically linked to excess asthma-related mortality. Here we show that LABAs such as salmeterol and structurally related β2-AR drugs such as formoterol and carvedilol, but not short-acting agonists (SABAs) such as albuterol, promote exaggerated asthma-like allergic airway disease and enhanced airway constriction in mice. We demonstrate that salmeterol aberrantly promotes activation of the allergic disease-related transcription factor signal transducer and activator of transcription 6 (STAT6) in multiple mouse and human cells. A novel inhibitor of STAT6, PM-242H, inhibited initiation of allergic disease induced by airway fungal challenge, reversed established allergic airway disease in mice, and blocked salmeterol-dependent enhanced allergic airway disease. Thus, structurally related β2-AR ligands aberrantly activate STAT6 and promote allergic airway disease. This untoward pharmacological property likely explains adverse outcomes observed with LABAs, which may be overcome by agents that antagonize STAT6. PMID:26605551

  11. Long-Acting Reversible Contraception (LARC) for Adolescent

    PubMed Central

    McNicholas, Colleen; Peipert, Jeffrey F

    2014-01-01

    Purpose of review Teen pregnancy continues to plague the United States. This review will discuss long-acting reversible contraceptive (LARC) method use in teens. It will specifically address the myths about appropriate candidates as well as continuation and satisfaction among teen users. Recent findings The American College of Obstetrics and Gynecology along with the American Academy of Pediatrics, the Centers for Disease Control, and the World health Organization have recognized the potential impact of LARC (comprising intrauterine contraception and subdermal implants) to reduce unintended pregnancies. They have affirmed the safety of such devices, and no effects on long-term fertility have been identified. Teen users of these methods have been shown to have high continuation and satisfaction rates. On the other hand, oral contraceptive pills, the patch, and the contraceptive vaginal ring have significantly higher contraceptive failure rates, and these rates are magnified in young women. Summary LARC methods should be considered first-line options for teens seeking contraception. PMID:22781078

  12. Possible interaction between letrozole and long-acting injectable zuclopenthixol.

    PubMed

    Lertxundi, Unax; Hernandez, Rafael; Albeniz, Juan Medrano; Echaburu, Saioa Domingo; Ruiz, Borja; García, Montserrat García; Aguirre, Carmelo

    2015-01-01

    Mrs A, a 68-year-old woman with paranoid schizophrenia, was on long-term psychiatric treatment with long-acting intramuscular zuclopenthixol, quetiapine and alprazolam when, in April 2012, she was diagnosed with right breast infiltrating ductal carcinoma. After starting treatment with letrozole on 4 July, Mrs A progressively developed extrapyramidal symptoms and these were particularly evident after each zuclopenthixol administration. On 9 January, both quetiapine and alprazolam were stopped due to excessive lethargy. After the administration of the last dose of zuclopenthixol on 26 January, she presented with sedation, sialorrhea, festinant gait, axial dystonia and dysphagia, all of which were severe. The introduction of letrozole was the only change that had been made to her pharmacotherapeutic regimen in that period. The rest of the findings on neurological examination were normal. Renal function was adequate. Slow symptom onset and progressive worsening until full-blown clinical presentation after 6 months, and the dramatic improvement in the clinical picture achieved 2 days after treatment with biperiden, suggests a long-term insidious interaction leading to zuclopenthixol accumulation. To the best of our knowledge, this is the first report of a possible interaction between letrozole and zuclopenthixol. We consider that it warrants further investigation. In the meanwhile, physicians should be aware of the occurrence of this potentially serious drug-drug interaction.

  13. Efficacy and Safety of Long-Acting Reversible Contraception

    PubMed Central

    Stoddard, Amy; McNicholas, Colleen; Peipert, Jeffrey F.

    2013-01-01

    Long-acting reversible contraception (LARC) includes intrauterine devices (IUDs) and the subdermal implant. These methods are the most effective reversible methods of contraception, and have the additional advantages of being long-lasting, convenient, well liked by users and cost effective. Compared with other user-dependent methods that increase the risk of noncompliance-related method failure, LARC methods can bring ‘typical use’ failure rates more in line with ‘perfect use’ failure rates. LARC methods are ‘forgettable’; they are not dependent on compliance with a pill-taking regimen, remembering to change a patch or ring, or coming back to the clinician for an injection. LARC method failure rates rival that of tubal sterilization at <1% for IUDs and the subdermal implant. For these reasons, we believe that IUDs and implants should be offered as first-line contraception for most women. This article provides a review of the LARC methods that are currently available in the US, including their effectiveness, advantages, disadvantages and contraindications. Additionally, we dispel myths and misconceptions regarding IUDs, and address the barriers to LARC use. PMID:21668037

  14. Long-acting injectable antipsychotics: recommendations for clinicians.

    PubMed

    Malla, Ashok; Tibbo, Phil; Chue, Pierre; Levy, Emmanuelle; Manchanda, Rahul; Teehan, Michael; Williams, Richard; Iyer, Srividya; Roy, Marc-André

    2013-05-01

    A major source of limitation to the real effectiveness of antipsychotics is the high rate of patient nonadherence or, more frequently, partial adherence. Using long-acting injectable (LAI) formulations is likely to reduce the impact of such adherence problems. Conversely, the use of LAIs in Canada remains low relative to many other jurisdictions. Based on effectiveness data from randomized control trials and other, less rigorous, studies, as well as our 2 qualitative studies exploring numerous issues around the use of LAIs, including their low use, we put forward 10 different recommendations for consideration by clinicians. These are also based on the experience of many clinicians and clinician scientists. These recommendations address mostly clinical challenges associated with the use of LAIs. Their application in clinical settings is illustrated in our report through several case examples highlighting the large variation across patients and different phases of illness. It is recommended that LAIs should be considered as a treatment option for psychotic disorders across all phases, including the first 2 to 5 critical years.

  15. Octreotide Attenuates Acute Kidney Injury after Hepatic Ischemia and Reperfusion by Enhancing Autophagy

    PubMed Central

    Sun, Huiping; Zou, Shuangfa; Candiotti, Keith A.; Peng, Yanhua; Zhang, Qinya; Xiao, Weiqiang; Wen, Yiyun; wu, Jiao; Yang, Jinfeng

    2017-01-01

    Octreotide exerts a protective effect in hepatic ischemia-reperfusion (HIR) injury. However, whether octreotide preconditioning could also reduce acute kidney injury (AKI) after HIR is unknown. This study was designed to investigate the role of octreotide in AKI after HIR. Male Sprague-Dawley rats were pretreated with octreotide or octreotide combined with 3-methyladenine (autophagy inhibitor, 3MA). Plasma creatinine, inflammation markers (e.g., TNF-α and IL-6 etc.), apoptosis, autophagy and phosphorylation of protein kinase B/mammalian target of rapamycin/p70 ribosomal S6 kinase (Akt/mTOR/p70S6K) in the kidney were measured after 60 minutes of liver ischemia and 24 hours of reperfusion for each rat. Octreotide pretreatment significantly preserved renal function and reduced the severity of renal injury. Moreover, octreotide alleviated inflammation and apoptosis in the kidney after HIR. Additionally, octreotide induced autophagy and autophagy inhibition with 3MA markedly reversed the renoprotective, anti-inflammatory and anti-apoptotic effects of octreotide after HIR. Finally, octreotide abrogated the activation of phosphorylation of Akt, mTOR and p70S6K in the kidney after HIR. Our results indicate that octreotide reduced renal injury after HIR due to its induction of autophagy. The enhancement of autophagy may be potentially linked to the octreotide mediated Akt/mTOR/p70S6K pathway deactivation and reduction of kidney inflammation and apoptosis after HIR. PMID:28205545

  16. Octreotide prevents postprandial splanchnic hyperemia in patients with portal hypertension.

    PubMed

    Albillos, A; Rossi, I; Iborra, J; Lledó, J L; Calleja, J L; Barrios, C; García, P; Escartín, P

    1994-07-01

    An increase in splanchnic blood flow is a physiological response to food intake. In patients with cirrhosis whose hepatic vascular resistance is already high, this increase in flow leads to marked increases in portal pressure. This study investigates whether octreotide prevents the increases in hepatic flow and portal pressure that follow the ingestion of a meal in patients with cirrhosis. Twenty-two patients with cirrhosis and portal hypertension were randomized to receive a mixed liquid meal (520 kcal) plus a single subcutaneous injection of either placebo or octreotide (200 micrograms). In the placebo group the ingestion of a meal was followed by an increase in the hepatic venous pressure gradient (+ 19.4 +/- 4.3%, p < 0.01) and hepatic blood flow (+ 38.2 +/- 14.6%, p < 0.05) at 30 min. In contrast, in the octreotide group eating caused no significant change in the hepatic venous pressure gradient (-2.8 +/- 3.6%, NS), while hepatic flow was decreased (-6.08 +/- 5.4%, p < 0.05). Octreotide blunted the postprandial increase in serum insulin and glucagon levels observed in the placebo group. In conclusion, in patients with cirrhosis and portal hypertension, octreotide prevents the postprandial increase in hepatic blood flow, and consequently also in portal pressure. These findings suggest that this drug could play a role in the long-term management of portal hypertension.

  17. Octreotide in the treatment of refractory diarrhoea and intestinal fistulae.

    PubMed Central

    Farthing, M J

    1994-01-01

    Persistent, refractory diarrhoea continues to be an important clinical problem. The mechanisms involved are associated with reduced intestinal absorption and increased intestinal secretion. Reduced intestinal absorption can result from small intestinal resection or from disorders in which there is damage to the small intestine. Motility disorders may also impair absorptive function. The rationale for using octreotide in refractory diarrhoea, intestinal motility disorders, and fistulae relates to its ability to promote intestinal absorption and inhibit gastric, pancreatic, and intestinal secretion. Several clinical studies in patients with short bowel syndrome have reported a reduction of intestinal output in patients taking octreotide compared with controls. Additionally, a number of studies have shown that octreotide improves secretory diarrhoea resulting from neuroendocrine tumours, intestinal infections in AIDS patients, and intestinal graft v host disease. Octreotide may be of use in patients suffering from intestinal motility disorders such as those associated with systemic sclerosis. Octreotide may also be of value in promoting closure of gastrointestinal and pancreatic fistulae. PMID:8206397

  18. Octreotide for cancer of the liver and biliary tree.

    PubMed

    Kouroumalis, E A

    2001-01-01

    Inoperable liver tumors have an unfavorable natural course despite various therapeutic modalities. Octreotide, a somatostatin analog, has shown considerable antitumor activity on animal models of various hepatic tumors and on isolated cell culture lines. In this paper, a review of the experimental evidence is presented. Moreover clinical papers of case reports of uncontrolled studies of patients are also reviewed. The majority of clinical studies provide evidence of a clinical and biochemical response of liver endocrine tumors while regression of tumor size is a rare event. A randomized controlled trial of octreotide in the treatment of advanced hepatocellular carcinoma has shown a significant survival benefit in the treated patients. Literature reports indicate a stimulatory effect of octreotide on Kupffer cells as a possible antitumor mechanism, but other antiproliferative actions of octreotide have been suggested but not proved. Finally the question of the presence and affinity of somatostatin receptors on liver tumor tissue is discussed. In conclusion, according to our experience, octreotide administration is the best available treatment for advanced inoperable hepatocellular carcinoma and future better patient selection, based on receptor subtypes, might further improve the results. Copyright 2001 S. Karger AG, Basel

  19. Octreotide for treatment of postoperative alimentary tract fistulas.

    PubMed

    Paran, H; Neufeld, D; Kaplan, O; Klausner, J; Freund, U

    1995-01-01

    Eighteen patients with postoperative fistulas of the gastrointestinal tract were treated with the somatostatin analog octreotide between November 1989 and November 1992. Fourteen patients had enterocutaneous fistulas: seven from the duodenum and seven from the ileum. Another three patients had pancreatic fistulas, and one patient had a biliary fistula. Within 24 hours of octreotide treatment, a mean reduction of 52% in the intestinal fistulas' output, 40% in the pancreatic fistulas, and 30% in the biliary fistula was noted. In the intestinal fistulas group the closure rate was 72% after a mean of 11 days. Early closure (mean 6 days) was achieved in all three pancreatic fistulas. In the patient with the biliary fistula a 30% reduction was observed twice following the administration of octreotide, and an increase occurred when it was withheld. The reduction rate of the secretions in high-output intestinal fistulas (> 500 ml/day) was higher than in the low-output fistulas (63 +/- 8% versus 39 +/- 4%, p < 0.05). Fistula output and the initial response to octreotide treatment had no value in predicting spontaneous healing. In conclusion, octreotide is a valuable tool for the conservative treatment of fistulas of the digestive tract. It is especially valuable for management of high-output enteric fistulas and pancreatic fistulas.

  20. Therapeutic potential of octreotide in the treatment of liver metastases.

    PubMed

    Davies, N; Cooke, T G; Jenkins, S A

    1996-01-01

    Octreotide is a synthetic analogue of somatostatin that has clear inhibitory effects on the growth of many animal and human cell lines, including colorectal cell lines both in vitro and in vivo. Colorectal cancer metastatic to the liver is clinically important, both in terms of the number of patients affected and the lack of any effective treatment for the majority of patients. Octreotide inhibits the growth of colorectal liver tumour in a number of experimental models and, in at least three tumour types, inhibits the growth of established micro-metastases. The precise mechanism of action is not known. However, the drug is likely to be most beneficial in the treatment of liver metastases when the tumour burden is relatively small. The available evidence, although experimental, suggests that octreotide may also have a beneficial effect on the development of liver metastases when used as an adjuvant to surgery in colorectal cancer and this area warrants urgent clinical investigation. The cytotoxics which are currently used as an adjuvant to surgery for colorectal cancer have unpleasant side effects which can be life-threatening. There will also be a proportion of patients who have undergone a truly curative resection of their tumour and will thus be treated unnecessarily. The potential benefits of octreotide in the adjuvant setting, although promising, remain speculative, but octreotide has an acceptably low incidence of side effects and can be administered safely for a prolonged period of time.

  1. Effects of Discontinuation of Paliperidone Long-Acting Injectable After Switching from Risperidone Long-Acting Injectable Switching

    PubMed Central

    Watanabe, Takafumi; Yamada, Atsurou

    2016-01-01

    Background Risperidone long-acting injection (RLAI) is increasingly being switched to paliperidone palmitate (PP) because of several benefits. However, this switching is not always successful. Methods We examined patient profiles following discontinuation of PP after switching from RLAI. We collected the electronic records of 24 patients with schizophrenia who had switched from RLAI to PP treatment at our hospital between November 2013 and March 2014. Twelve patients continued PP injection for over 1 year (PP-continuers), the other 12 patients discontinued within 1 year (PP-discontinuers), and both groups were followed up until December 31, 2014. Results PP-discontinuers had significantly shorter RLAI-administration period (mean 73.1 ± 59.0 weeks versus 148.5 ± 75.0 weeks), and lower chlorpromazine (CP) equivalent mean doses (mean 553.5 ± 251.0 mg versus 1002.5 ± 529.3 mg) compared with PP-continuers. The CP equivalent mean dose of PP-discontinuers had increased at the time of discontinuation and their social status became significantly worse. Six PP-discontinuers (50%) re-switched to RLAI, and their social status was not significantly worse at the end of the observation period. Conclusions On switching from RLAI to PP, we need to consider that some patients have had a shorter RLAI-administration period and may require lower amounts of antipsychotics. PMID:27738379

  2. Aripiprazole Lauroxil Long-Acting Injectable: The Latest Addition to Second-Generation Long-Acting Agents.

    PubMed

    Aggarwal, Arpit; Gopalakrishna, Ganesh; Lauriello, John

    2016-01-01

    Antipsychotics have long been the mainstay for the treatment of schizophrenia and other psychotic disorders. Long-acting injectables (LAI) of antipsychotics-provided once every two weeks to once every three months-promise to reduce the incidence of nonadherence. ARISTADA(™) (aripiprazole lauroxil; ALLAI) extended-release injectable suspension was approved by the U.S. Food and Drug Administration in October 2015 for the treatment of schizophrenia, and is the newest entrant in the LAI market. ALLAI is available as a single-use, pre-filled syringe, can be started in three different dosages, and also has the option of every six-week dosing. Treatment with oral aripiprazole is recommended for the first twenty-one days after the first ALLAI injection, which is a potential disadvantage. Adverse effects include sensitivity to extrapyramidal symptoms, especially akathisia, which is well documented in other aripiprazole preparations. There is no available data comparing ALLAI to other antipsychotics, and more head-to-head trials comparing different LAI formulations are needed. Based on the available data, ALLAI is an effective and safe option for treatment of schizophrenia. Further studies and post-marketing data will provide better understanding of this formulation.

  3. Pharmacokinetics of olanzapine long-acting injection: the clinical perspective

    PubMed Central

    Kraemer, Susanne; Bergstrom, Richard F.; Detke, Holland C.

    2014-01-01

    Olanzapine long-acting injection (OLAI) is a sustained-release depot antipsychotic for the treatment of schizophrenia in adults. Our objective was to explain the pharmacokinetics of OLAI to provide clinical insight. Simulation models and data from clinical trials are presented. Olanzapine concentrations were observed immediately upon injection. Half-life was ∼30 days, controlled by the slow rate of intramuscular absorption rather than the 30-h elimination rate-based half-life of oral olanzapine. As each injection builds on the drug still being released from previous injections, concentrations increase gradually until a steady state is reached after ∼3 months. Concentrations were similar to oral olanzapine and proportional to the dose; the average steady-state concentrations (10th–90th percentile) for the 150, 210, and 300 mg/2-week doses were 16–32, 15–55, and 20–67 ng/ml, respectively, and those for the 300 and 405 mg/4-week doses were 19–48 and 19–62 ng/ml, respectively. Peak concentrations most often occurred at 2–4 days after injection. Peak-to-trough fluctuation was greater for the 4-week dosing interval than the 2-week one, with no apparent clinical ramifications for these differences. Trough concentrations were above the lower end of the therapeutic range, even at the first injection. Long-term use up to 6 years indicated no additional accumulation. The impact of smoking and sex was similar, but less pronounced than for oral olanzapine. PMID:24815672

  4. Implementing Immediate Postpartum Long-Acting Reversible Contraception Programs.

    PubMed

    Hofler, Lisa G; Cordes, Sarah; Cwiak, Carrie A; Goedken, Peggy; Jamieson, Denise J; Kottke, Melissa

    2017-01-01

    To understand the most important steps required to implement immediate postpartum long-acting reversible contraception (LARC) programs in different Georgia hospitals and the barriers to implementing such a program. This was a qualitative study. We interviewed 32 key personnel from 10 Georgia hospitals working to establish immediate postpartum LARC programs. Data were analyzed using directed qualitative content analysis principles. We used the Stages of Implementation to organize participant-identified key steps for immediate postpartum LARC into an implementation guide. We compared this guide to hospitals' implementation experiences. At the completion of the study, LARC was available for immediate postpartum placement at 7 of 10 study hospitals. Participants identified common themes for the implementation experience: team member identification and ongoing communication, payer preparedness challenges, interdependent department-specific tasks, and piloting with continuing improvements. Participants expressed a need for anticipatory guidance throughout the process. Key first steps to immediate postpartum LARC program implementation were identifying project champions, creating an implementation team that included all relevant departments, obtaining financial reassurance, and ensuring hospital administration awareness of the project. Potential barriers included lack of knowledge about immediate postpartum LARC, financial concerns, and competing clinical and administrative priorities. Hospitals that were successful at implementing immediate postpartum LARC programs did so by prioritizing clear communication and multidisciplinary teamwork. Although the implementation guide reflects a comprehensive assessment of the steps to implementing immediate postpartum LARC programs, not all hospitals required every step to succeed. Hospital teams report that implementing immediate postpartum LARC programs involves multiple departments and a number of important steps to consider. A

  5. Long-acting reversible contraception: a review in special populations.

    PubMed

    Prescott, Gina M; Matthews, Christina M

    2014-01-01

    Almost half of the pregnancies in the United States are unintended. Currently available contraceptive methods are highly efficacious, but the most commonly used methods rely on patients for appropriate use. There has been a push to advocate for long-acting reversible contraceptives (LARCs) as first-line methods because they are placed by medical professionals and are the most effective form of reversible contraception available. There are four LARCs currently available in the United States: the Copper T intrauterine device, two forms of the levonorgestrel intrauterine system, and the etonogestrel subdermal implant. Once inserted, they can be left in place for 3-10 years, depending on the device. Some of these devices have been available for a number of years, but their use is limited in the United States due to controversies and misconceptions. A MEDLINE search from 1990-2012 was conducted to identify articles describing the use of LARCs in populations with limited data, including postpartum women, adolescents and nulliparous women, and women with sexually transmitted infections, including human immunodeficiency virus (HIV). Health care provider safety concerns surrounding intrauterine device (IUD) expulsions and infection are issues for use in adolescents and nulliparous women. Concern regarding IUD expulsion in the postpartum population questions the benefit of immediate versus delayed insertion, and the progestin effect in the levonorgestrel IUD and etonogestrel implant is of theoretic concern for breastfeeding women. In women with HIV, concerns have been raised about increased viral shedding with the IUD and drug interactions with the progestin methods. Many misconceptions surrounding LARCs are unfounded, but individual risk factors may leave LARC users at risk of unintended pregnancy if not addressed properly.

  6. Octreotide treatment in patients with severe acute pancreatitis.

    PubMed

    Paran, H; Mayo, A; Paran, D; Neufeld, D; Shwartz, I; Zissin, R; Singer, P; Kaplan, O; Skornik, Y; Freund, U

    2000-11-01

    We investigated the effect of octreotide in the treatment of severe acute pancreatitis in a case-control study. Experimental and clinical studies on the effect of octreotide in the treatment of acute pancreatitis have shown controversial results. Since January 1992, we have been conducting a prospective randomized study on the effect of octreotide in severe acute pancreatitis, in three hospitals in Israel. The entering criteria included three or more of the Ranson prognostic signs and CT findings of severe pancreatitis. Patients were randomly assigned to conservative treatment either with or without octreotide (0.1 mg subcutaneously three times a day). The end points of the study included: complication rate (ARDS, sepsis, renal failure, pseudocyst, fistula, and abscess), length of hospital stay, and mortality. From January 1992 to December 1996, 60 patients entered the study. After evaluating the files, 10 patients were excluded due to failure to meet the entering criteria, incomplete data, or incorrect diagnosis. Of the remaining 50 patients, 25 were assigned to octreotide (treatment group) and 25 to conservative treatment only (control group). The two groups matched with regard to age, sex, etiology, and severity of the disease. The complication rate was lower in the treatment group with regard to sepsis (24% vs 76%, P = 0.0002) and ARDS (28% vs 56%, P = 0.04). The hospital stay was shorter in the treatment group (20.6 vs 33.1 days, P = 0.04). Two patients died in the treatment group and eight in the control group (P < 0.019). These results suggest that octreotide may have a beneficial effect in the treatment of severe acute pancreatitis.

  7. Design, synthesis and biological evaluation of negatively charged ¹¹¹In-DTPA-octreotide derivatives.

    PubMed

    Oshima, Nobuhiro; Akizawa, Hiromichi; Zhao, Songji; Zhao, Yan; Nishijima, Ken-ichi; Kitamura, Yoji; Arano, Yasushi; Kuge, Yuji; Ohkura, Kazue

    2014-02-15

    Our previous studies indicated that (111)In-diethylenetriaminepentaacetic acid ((111)In-DTPA)-octreotide derivatives with an additional negative charge by replacing N-terminal d-phenylalanine (d-Phe) with an acidic amino acid such as l-aspartic acid (Asp) or its derivative exhibited low renal radioactivity levels when compared with (111)In-DTPA-D-Phe(1)-octreotide. On the basis of the findings, we designed, synthesized and evaluated two Asp-modified (111)In-DTPA-conjugated octreotide derivatives, (111)In-DTPA-Asp(1)-octreotide and (111)In-DTPA-Asp(0)-D-Phe(1)-octreotide. While (111)In-DTPA-Asp(1)-octreotide showed negligible AR42J cell uptake, (111)In-DTPA-Asp(0)-D-Phe(1)-octreotide exhibited AR42J cell uptake similar to that of (111)In-DTPA-D-Phe(1)-octreotide. When administered to AR42J tumor-bearing mice, (111)In-DTPA-Asp(0)-D-Phe(1)-octreotide exhibited renal radioactivity levels significantly lower than did (111)In-DTPA-D-Phe(1)-octreotide at 1 and 3 h post-injection. No significant differences were observed in tumor accumulation between (111)In-DTPA-Asp(0)-D-Phe(1)-octreotide and (111)In-DTPA-D-Phe(1)-octreotide after 1 and 3h injection. The findings in this study suggested that an interposition of an Asp at an appropriate position in (111)In-DTPA-D-Phe(1)-octreotide would constitute a useful strategy to develop (111)In-DTPA-D-Phe(1)-octreotide derivatives of low renal radioactivity levels while preserving tumor accumulation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Octreotide for chylous effusions in congenital diaphragmatic hernia

    PubMed Central

    Landis, Melissa W.; Butler, Dawn; Lim, Foong Yen; Keswani, Sundeep; Frischer, Jason; Haberman, Beth; Kingma, Paul S.

    2013-01-01

    Background/Purpose Chylothorax is a frequent complication in congenital diaphragmatic hernia (CDH) infants and is associated with significant morbidity. The optimal treatment strategy remains unclear. We hypothesize that octreotide decreases chylous effusions in infants with CDH. Methods This is a retrospective study of all infants with CDH admitted to our institution from October 2006 to October 2011. Results Eleven (12%) infants developed a chylothorax. Five infants were managed conservatively with thoracostomy and total parenteral nutrition. Six infants were started on octreotide therapy. None of the infants required surgical intervention to stop the effusion. There was no significant difference in survival to discharge, length of stay, or average daily chest tube output between groups. There appeared to be a temporally associated drop in chest tube output upon initiation of octreotide in two infants; however, the overall rate of decline in chest tube drainage was unchanged. In addition, there were infants in the conservative group who demonstrated a similar drop in daily chest tube output despite the absence of octreotide. Conclusions Our data suggest that the majority of chylous effusions in CDH infants resolve with conservative therapy alone. PMID:24210190

  9. Contraception for Adolescents: Focusing on Long-Acting Reversible Contraceptives (LARC) to Improve Reproductive Health Outcomes

    PubMed Central

    Salcedo, Jennifer

    2015-01-01

    Adolescent pregnancy rates in the U.S. have reached an all-time low from their peak in the 1980s and 1990s. However, the U.S. maintains the highest rate of teenage pregnancy among developed nations. Adolescents experience higher typical use failure rates for user-dependent contraceptives compared to their adult counterparts. Long-acting reversible contraception (LARC), IUDs and implants, have failure rates that are both very low and independent of user age. In settings where the most effective methods are prioritized and access barriers are removed, the majority of adolescents initiate LARC. Use of LARC by adolescents significantly reduces rates of overall and repeat teen pregnancy. All methods of contraception are safe for use in teens, including IUDs and DMPA. Dual use of LARC and barrier methods to reduce risk of sexually transmitted infection, is the optimal contraceptive strategy for most adolescents. Adolescent access to evidence-based and confidential contraceptive services, provided in a manner that respects autonomy, is a vital public health goal. PMID:27635305

  10. Contraception for Adolescents: Focusing on Long-Acting Reversible Contraceptives (LARC) to Improve Reproductive Health Outcomes.

    PubMed

    Kaneshiro, Bliss; Salcedo, Jennifer

    2015-03-01

    Adolescent pregnancy rates in the U.S. have reached an all-time low from their peak in the 1980s and 1990s. However, the U.S. maintains the highest rate of teenage pregnancy among developed nations. Adolescents experience higher typical use failure rates for user-dependent contraceptives compared to their adult counterparts. Long-acting reversible contraception (LARC), IUDs and implants, have failure rates that are both very low and independent of user age. In settings where the most effective methods are prioritized and access barriers are removed, the majority of adolescents initiate LARC. Use of LARC by adolescents significantly reduces rates of overall and repeat teen pregnancy. All methods of contraception are safe for use in teens, including IUDs and DMPA. Dual use of LARC and barrier methods to reduce risk of sexually transmitted infection, is the optimal contraceptive strategy for most adolescents. Adolescent access to evidence-based and confidential contraceptive services, provided in a manner that respects autonomy, is a vital public health goal.

  11. Long-Acting Reversible Contraception Initiation With a 2- to 3-Week Compared With a 6-Week Postpartum Visit.

    PubMed

    Chen, Melissa J; Hou, Melody Y; Hsia, Jennifer K; Cansino, Catherine D; Melo, Juliana; Creinin, Mitchell D

    2017-10-01

    To evaluate whether a department policy changing the scheduling of the postpartum visit from 6 weeks to 2-3 weeks after delivery is associated with higher long-acting reversible contraception initiation at the postpartum visit. We conducted a quasiexperimental before-after study to evaluate long-acting reversible contraception initiation, specifically an intrauterine device or contraceptive implant, at the postpartum visit between women scheduled for follow-up at 6 weeks (before policy change) and 2-3 weeks after delivery (after policy change). Secondary outcomes included postpartum visit completion, overall contraception initiation at the postpartum visit, overall contraceptive use at 6 months after delivery, and repeat pregnancies by 6 months postpartum. We obtained delivery and postpartum information using the electronic medical record and contacted participants 3 and 6 months after delivery to assess contraception use and repeat pregnancies. We enrolled 586 participants between December 2014 and November 2015, of whom 512 women (256 in each cohort) continued to meet eligibility criteria after delivery. Long-acting reversible contraception initiation rates at the postpartum visit were lower in the 2- to 3-week (16.5%, 95% CI 12.2-21.8) compared with the 6-week group (31.1%, 95% CI 25.2-37.7, P<.01), primarily as a result of patient and health care provider preferences for delaying intrauterine device insertion to a later visit. More women completed a scheduled 2- to 3-week postpartum visit (90.2%, 95% CI 86.0-93.3) compared with a 6-week visit (81.6%, 95% CI 76.4-85.9, P<.01). Deferral of any contraception initiation was higher in the 2- to 3-week group (27.3%, 95% CI 21.9-33.4) compared with the 6-week group (15.8%, 95% CI 11.5-21.4, P<.01), but there were no differences in overall contraceptive use patterns at 6 months postpartum. No intrauterine device perforations or expulsions were observed in women who underwent insertion at 2-3 weeks postpartum. Five

  12. Octreotide-Treated Diabetes Accompanied by Endogenous Hyperinsulinemic Hypoglycemia and Protein-Losing Gastroenteropathy

    PubMed Central

    Takahashi, Nobuhiko; Nagamine, Miho; Fukuda, Mitsuko; Motomura, Wataru; Abiko, Atsuko; Haneda, Masakazu; Fujiya, Mikihiro; Ieko, Masahiro; Kohgo, Yutaka

    2011-01-01

    Occurrence of hypoglycemia in diabetes patients is very rare. We report here a case of frequent hypoglycemic attacks caused by inappropriate endogenous hyperinsulinemia in a female patient with poorly controlled diabetes and protein-losing gastroenteropathy. The blood glucose profiles of the patient were unstable. Results of the fasting test performed to investigate the cause of hypoglycemia suggested endogenous hyperinsulinism. Repeated selective arterial calcium injection tests suggested that hyperinsulinemia might be extrapancreatic in origin. However, efforts to detect a responsible lesion such as insulinoma were unsuccessful. Octreotide was used for the treatment of hypoglycemia and protein-losing gastroenteropathy. After treatment, although her leg edema caused by hypoalbuminemia persisted, hypoglycemia almost disappeared. PMID:21826148

  13. Use of Long-Acting Somatostatin Analogue (Lanreotide) in an Adolescent with Diazoxide-Responsive Congenital Hyperinsulinism and Its Psychological Impact.

    PubMed

    Shah, Pratik; Rahman, Sofia A; McElroy, Sharon; Gilbert, Clare; Morgan, Kate; Hinchey, Louise; Senniappan, Senthil; Levy, Hannah; Amin, Rakesh; Hussain, Khalid

    2015-01-01

    Congenital hyperinsulinism (CHI) is a common cause of hypoglycaemia due to unregulated insulin secretion from pancreatic β cells. Medical management includes use of oral diazoxide (a KATP channel agonist) and daily injectable octreotide (somatostatin analogue) therapy. However, diazoxide is associated with severe sideeffects such as coarse facies, hypertrichosis and psychosocial/compliance issues in adolescents. Lanreotide (a long-acting somatostatin analogue) is used in adults with neuroendocrine tumours; however, its role in patients with CHI has not been well described. A 15-year-old girl with diazoxide-responsive CHI had severe hypertrichosis secondary to diazoxide and subsequent compliance/psychosocial issues. She was commenced on 30 mg of lanreotide every 4 weeks as a deep subcutaneous injection, in an attempt to address these issues. She was able to come off diazoxide treatment 2 months after starting lanreotide. Presently, after 2.5 years of lanreotide treatment, her blood glucose control is stable with complete resolution of hypertrichosis. Clinically significant improvements in the self-reported Paediatric Quality of Life (PedsQL) questionnaire and Strengths and Difficulties Questionnaire (SDQ) were reported after 1 year on lanreotide. No side effects were found, and her liver/thyroid function and abdominal ultrasound have been normal. We report the first case on the use of lanreotide in an adolescent girl with diazoxide-responsive CHI with significant improvement of quality of life. © 2015 S. Karger AG, Basel.

  14. Sustained release octreotide may have a role in the treatment of malignant bowel obstruction.

    PubMed

    Massacesi, Cristian; Galeazzi, Giordano

    2006-10-01

    Daily or continuous infusion octreotide is effective in relieving the gastrointestinal symptoms associated with inoperable malignant bowel obstruction (MBO). The sustained release (LAR) formulation of octreotide provides sustained exposure of the drug. This preliminary study aimed to investigate the efficacy of octreotide LAR (20 mg) for reducing gastrointestinal symptoms or nasogastric tube (NGT) secretions in patients with MBO. In patients with NGT (n = 8), octreotide LAR reduced NGT secretions from day one onwards, and NGT was removed in one patient. In patients without NGT (n = 4), octreotide LAR reduced episodes of vomiting and the severity of nausea, and this reduction was maintained throughout the study. Tolerability was good. In conclusion, the more convenient dosing schedule and potential activity of octreotide LAR may have a role in controlling MBO symptoms, and, therefore, it deserves further studies.

  15. [Effects of octreotide on experimental orthostatic neurogenic hypotension].

    PubMed

    Verwaerde, P; Bordet, R; Portolan, G; Tran, M A; Marques, M A; Montastruc, J L; Sénard, J M

    1996-08-01

    The synthetic somatostatin analogue, octreotide, has recently been proposed for the treatment of both postprandial and orthostatic hypotension (OH) in humans with autonomic failure related to multiple system atrophy (MSA) or diabetes mellitus. However, pharmacodynamic data are not still available in experimental models of orthostatic hypotension. We investigated in a model of neurogenic orthostatic hypotension, obtained by chronic sinoaortic denervation (SAD) in chloralose-anaesthetized dogs, the effects of octreotide (0.1 mg/kg, subcutaneous route) during a double-blind cross-over study vs placebo. Blood pressure (BP) and heart rate (HR) average values, SBP and HR short-term variabilities (using fast Fourier transformation) in both low (LF: 50-150 mHz) and high frequency range (respiratory rate +/- 50 mHz) and plasma noradrenaline (NA) levels (HPLC) were measured in supine position and during head-up tilt test (HUT: 80 degrees, 10 min) before and 45 min after drug administration. In controls, as expected, head-up tilt test induced a significant increase in DBP (+14 +/- 8 mmHg), HR (+36 +/- 21 beat/min), NA (296 +/- 118 vs 141 +/- 63 pg/ml), SBP-LF (25 +/- 5 vs 14 +/- 3%) whereas HR-HF significantly decreased. The changes during head-up tilt test were not modified after placebo or octreotide administration. In SAD dogs, head-up tilt test elicited a dramatic fall in SBP (-74 +/- 39 mmHg), DBP (-20 +/- 15 mmHg) without any significant change in HR (-5 +/- 12 beat/min), NA (708 +/- 213 vs 606 +/- 331 pg/ml), SBP-LF (16 +/- 3 vs 16 +/- 3%), HR-HF (8 +/- 2 vs 7 +/- 1%). Octreotide or placebo failed to significantly modify any of the measured parameters during head-up tilt test performed 45 min after drug administration. At the dose used, octreotide elicited a 80% decrease in insulin plasma levels after 45 min in both normal and SAD dogs. These results suggest that 1) this experimental model of orthostatic hypotension in SAD dogs is reproductible and can be used to

  16. New second-generation long-acting injectable antipsychotics for the treatment of schizophrenia.

    PubMed

    Citrome, Leslie

    2013-07-01

    Long-acting injectable (depot) antipsychotics are one approach in the management of individuals with schizophrenia. Since the introduction of risperidone long-acting injection in 2003, three additional second-generation antipsychotics have become available in a long-acting injectable formulation: paliperidone, olanzapine and aripiprazole. Although these different depot options can help with adherence and thus encourage better treatment outcomes, they differ in terms of specific indications, approved injection sites, needle gauge, injection volume, injection interval, requirements for oral supplementation, availability of prefilled syringes, storage needs and postinjection observation period, as well as potential drug-drug interactions and commonly encountered adverse reactions. After a review of the evidence base, guidance is offered on the appropriate selection among the long-acting injectable formulations of both first and second-generation antipsychotics.

  17. Octreotide-induced hepatitis in a child with persistent hyperinsulinemia hypoglycemia of infancy.

    PubMed

    Ben-Ari, Josef; Greenberg, Meidad; Nemet, Dan; Edelstein, Evgeny; Eliakim, Alon

    2013-01-01

    Persistent hyperinsulinemic hypoglycemia of infancy (PHHI), the most common cause of persistent hypoglycemia in the neonatal period and infancy, is a genetic disorder characterized by abnormal regulation of insulin secretion. Octreotide, a somatostatin analog, is often used as a second-line treatment when diazoxide therapy fails to control hypoglycemia. We report herein a rare development of octreotide-induced hepatitis following prolonged treatment for PHHI in an infant. Octreotide-induced hepatitis may occur mostly when high doses are given, or when dosing is increased. This warrants routine examination of liver function. When hepatitis develops, prompt cessation of octreotide therapy will probably result in subsequent resolution.

  18. [A long-acting second generation anti-psychotic--experience in Israel].

    PubMed

    Stein-Reisner, Orit; Preisman, Olga; Alfici, Susana; Melamed, Yuval; Bleich, Avi

    2004-06-01

    Schizophrenia is a chronic disease characterized by psychotic symptoms as well as negative symptoms such as affective flattening, social withdrawal and occupational dysfunction. Anti-psychotic medications reduce the risk of psychotic exacerbations and hospitalization. Poor compliance is common among patients with schizophrenia. Long-acting medications have such advantages as stabilizing drug levels and improving compliance. Second generation anti-psychotic medications were found to be more effective and tolerable compared to first generation drugs. These medications cause less extra-pyramidal symptoms, and compliance with them was shown to be better. Until recently there were only first generation long-acting anti-psychotics in use. Recently a new second generation long-acting anti-psychotic drug was introduced in Israel. We present our experience with a first schizophrenic patient treated with long-acting Risperidone (Risperdal Consta). The patient was treated in the past with several first generation anti-psychotics and suffered severe extra-pyramidal symptoms. His compliance with treatment was poor. Under treatment with oral Risperidone a considerable improvement was recorded, however compliance remained poor. Under treatment with long-acting Risperidone, Intramuscularly 25 Mg every two week, both positive and negative symptoms improved substantially, as well as compliance with treatment. The results of this case study encourage us to believe that many more patients will benefit from the advantages of both a second-generation anti-psychotic and a long-acting preparation.

  19. Patient outcomes within schizophrenia treatment: a look at the role of long-acting injectable antipsychotics.

    PubMed

    Bera, Rimal B

    2014-01-01

    Compliance is a critical issue across all chronic conditions, including schizophrenia. Compliance is not an all-or-nothing phenomenon, with a continuum from taking all medications as prescribed to partial compliance to complete noncompliance. Partial compliance is a serious problem that may result in abrupt dose changes leading to unanticipated adverse effects and can demoralize the patient. Further, there is a nearly 5-fold increase in the risk of relapse in first-episode patients when antipsychotic drug treatment is discontinued. Taken together, these data indicate that it is critical to ensure continuous delivery of antipsychotic treatment. Atypical antipsychotic medications were expected to result in better adherence, primarily because of the anticipated improved efficacy and safety profile. However, atypical agents have poor adherence, irrespective of the type of atypical medication, making it difficult to predict which patients are taking their oral medications. Long-acting injectable (LAI) agents may minimize the fluctuations in peak and overall plasma levels compared with oral agents, indicating they may allow more consistent and predictable administration. Based on clinical experience in my practice, several important observations regarding LAI use in patients with schizophrenia have been identified. First, there are potential advantages to using LAIs, including assistance in understanding reasons for poor response, the possibility of eliminating daily pill ingestion, and the elimination of the abrupt loss of medication coverage. There are also several potential obstacles to the use of LAIs, including a lack of infrastructure for the delivery and disposal of syringes and the ease of use with the oral agents. Several strategies can be used to increase patient willingness to initiate and continue LAI therapy. Strategies to improve acceptance involve presenting the option with enthusiasm, ensuring proper goal setting, educating the patient that this treatment

  20. Chylous Fistula following Axillary Lymphadenectomy: Benefit of Octreotide Treatment.

    PubMed

    González-Sánchez-Migallón, Elena; Aguilar-Jiménez, José; García-Marín, José Andrés; Aguayo-Albasini, José Luis

    2016-01-01

    Chyle leak following axillary lymph node clearance is a rare yet important complication. The treatment of postoperative chyle fistula still remains unclear. Conservative management is the first line of treatment. It includes axillary drains on continuous suction, pressure dressings, bed rest, and nutritional modifications. The use of somatostatin analogue is well documented as a treatment for chylous fistulas after neck surgery. We present a case of chylous fistula after axillary surgery resolved with the use of octreotide.

  1. Long-standing malignant pancreatic carcinoid treated with octreotide.

    PubMed

    Varas-Lorenzo, M J

    2010-11-01

    A male presented with a metastatic, plasma serotonin-secreting (high 5-HIAA in urine), malignant pancreatic carcinoid with a carcinoid-like syndrome, and was assessed using ultrasounds (US), computerized tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasonography (EUS) and Octreoscan; he sequentially received chemotherapy, interferon and octreotide, with long-term, 12-year survival after diagnosis. Given this unusual case, the second reported in our country, the overall literature is reviewed.

  2. Imaging of small-cell lung cancer xenografts with I-125, In-111, and Re-188 octreotides

    SciTech Connect

    Hosono, M.; Hosono, M.N.; Haberberger, T. ||

    1995-05-01

    Somatostatin receptor imaging has been reported to be valuable for the localization of small-cell lung cancer (SCLC). We estimated the efficiency of I-125-Tyr-3-octreotide(I-125-octreotide), In-111-DTPA-D-Phe-1-octreotide (in-111-octreotide), and Re-188-octreotide in a mouse model of SCLC. Tyr-3-octreotide was labeled with I-125 by the chloramine T method, and In-111-octreotide was supplied by Mallinckrodt Medical (The Netherlands), while Re-188 was obtained from a W-188/Re-188 generator, and octreotide was labeled with Re-188 efficiently by a direct labeling using stannous chloride as a reduction agent. The expression of somatostatin receptor on NCI-H69 cells (a SCLC cell line) had been previously reported and we confirmed it by a cell binding assay. I-125-, In-111-, and Re-188-octreotides were injected i.v. into nude mice bearing NCI-H69 xenografts. Biodistributions were determined at 15 min, 2, 4, 8, and 24 h after injection. Specific binding of radiolabeled octreotides was observed by pretreatment of mice with unlabeled octreotide. Tumor uptake of I-125-, In-111-, and Re-188-octreotides at 2 h was 0.9{plus_minus}0.3, 0.3{plus_minus}0.1, 0.5{plus_minus}0.1% ID/g, respectively. Tumor-to-blood ratios were 0.91, 7.45, 0.41 at 2 h, 1.66, 11.16, 1.23 at 8 h for I-125-, In-111-, and Rej-188-octreotides, respectively. I-125-and Re-188 octreotides showed significant accumulations in the liver and GI tract. By contrast, In-111-octreotide cleared more rapidly from the blood and accumulated in normal tissues less than I-125- and Re-188- octreotides, resulting in high tumor-to-normal tissue ratios. In conclusion, as absolute level of tumor uptake of Re-188-octreotide is higher than that of In-111-octreotide, and Re-188-octreotide can be prepared easily as a kit, Re-188-octreotide is useful for the targeting of SCLC as well as I-125-octreotide, while In-111-octreotide is potent to achieve clear tumor-to-normal tissue contrast.

  3. SALTO: a randomized, multicenter study assessing octreotide LAR in inoperable bowel obstruction.

    PubMed

    Laval, Guillemette; Rousselot, Hubert; Toussaint-Martel, Sophie; Mayer, Françoise; Terrebonne, Eric; François, Eric; Brixi, Hédia; Nguyen, Thierry; Bourdeix, Isabelle; Bisot-Locard, Ségolène; Zelek, Laurent

    2012-02-01

    This phase II, multicenter, randomized, double-blind, non-comparative study assessed the efficacy and safety of immediate-release octreotide and octreotide LAR, in combination with corticosteroids and standard medical care, on the symptoms of inoperable malignant bowel obstruction (MBO) due to peritoneal carcinomatosis. The primary efficacy endpoint was "success" at day 14 defined as a composite endpoint including the absence of a nasogastric tube, and vomiting less than twice per day and no use of anticholinergic agents. Patients in the octreotide arm received octreotide LAR 30 mg intramuscular (im) on days 1, 29 and 57, as well as daily immediate-release octreotide 600 μg per day plus methylprednisolone on days 1 to 6. Placebo-treated patients received methylprednisolone and matched placebo instead of octreotide. Difficulties associated with enrolling patients at palliative-care stage meant only 64 patients (instead of the planned 102 patients) were randomized, 32 to octreotide and 32 to placebo. Despite randomization, more patients in the octreotide arm (46.4%) than in the placebo arm (21.9%) had a baseline Karnofsky score less than 50. An intention-to-treat analysis showed that in the octreotide and placebo arms, 12 (38%) and nine (28%), respectively, patients were successfully treated at day 14, which increased to 9/15 (60%) and 7/25 (28%), respectively, among patients with a baseline Karnofsky score greater or equal to 50. Octreotide-treated patients reported three drug-related adverse events (AEs), and no drug-related serious AEs or deaths. Octreotide LAR may have a key role in treating patients with a MBO due to peritoneal carcinomatosis, particularly in those with moderately severe disease.

  4. Comparison of Subjective Experiences and Effectiveness of First-Generation Long-Acting Injectable Antipsychotics and Risperidone Long-Acting Injectables in Patients With Schizophrenia.

    PubMed

    Chen, Wen-Yin; Lin, Shih-Ku

    2016-10-01

    We conducted a cross-sectional study to compare the subjective experiences and clinical effects of first-generation long-acting injectable (FGA-LAI) antipsychotics with those of risperidone long-acting injectables (RIS-LAIs) in 434 schizophrenia patients. Compared with the RIS-LAI group, the patients treated with FGA-LAIs had a significantly longer duration of illness and LAI treatment and were older. Our results suggest that patients treated with FGA-LAI have more satisfactory subjective experiences compared with patients treated with RIS-LAI and that both FGA-LAI and RIS-LAI treatments can prevent relapses and hospitalization. Additional longitudinal studies determining the long-term benefits of RIS-LAI are warranted.

  5. P-glycoprotein- and mrp2-mediated octreotide transport in renal proximal tubule

    PubMed Central

    Gutmann, Heike; Miller, David S; Droulle, Agathe; Drewe, Jürgen; Fahr, Alfred; Fricker, Gert

    2000-01-01

    Transepithelial transport of a fluorescent derivative of octreotide (NBD-octreotide) was studied in freshly isolated, functionally intact renal proximal tubules from killifish (Fundulus heteroclitus). Drug accumulation in the tubular lumen was visualized by means of confocal microscopy and was measured by image analysis. Secretion of NBD-octreotide into the tubular lumen was demonstrated and exhibited the all characteristics of specific and energy-dependent transport. Steady state luminal fluorescence averaged about five times cellular fluorescence and was reduced to cellular levels when metabolism was inhibited by NaCN. NBD-octreotide secretion was inhibited in a concentration-dependent manner by unlabelled octreotide, verapamil and leukotriene C4 (LTC4). Conversely, unlabelled octreotide reduced in a concentration dependent manner the p-glycoprotein (Pgp)-mediated secretion of a fluorescent cyclosporin A derivative (NBDL-CS) and the mrp2-mediated secretion of fluorescein methotrexate (FL-MTX). This inhibition was not due to impaired metabolism or toxicity since octreotide had no influence on the active transport of fluorescein (FL), a substrate for the classical renal organic anion transport system. The data are consistent with octreotide being transported across the brush border membrane of proximal kidney tubules by both Pgp and mrp2. PMID:10694230

  6. Long-acting injectable risperidone: safety and efficacy in stable patients switched from conventional depot antipsychotics.

    PubMed

    Turner, Martin; Eerdekens, Els; Jacko, Mary; Eerdekens, Mariëlle

    2004-07-01

    Long-acting injectable risperidone was assessed in schizophrenia patients who were symptomatically stable on conventional depot antipsychotics and who were then switched to long-acting risperidone. Participants in this open-label, multicentre, 12-week trial had received flupenthixol decanoate, fluphenazine decanoate, haloperidol decanoate, or zuclopenthixol decanoate for 4 months or longer. Each was considered symptomatically stable by investigators. After receiving two cycles of their conventional depot antipsychotic during the run-in period, patients were switched to receive long-acting risperidone every 2 weeks for 12 weeks at an initial dose of 25 mg. This dose could be increased in 12.5-mg increments at 4-week intervals. Ninety-two percent of the patients received all six injections; 62% received the 25-mg dose throughout the treatment period. Adverse events related to movement disorders were reported in 3%. Severity of movement disorders decreased during long-acting risperidone treatment. Positive and Negative Syndrome Scale (PANSS) total and factor scores and scores on the Clinical Global Impressions severity scale were significantly reduced during treatment; 48% of these stable patients showed further symptom improvement (> or =20% decrease in PANSS score at endpoint). The results indicate that patients with schizophrenia who are symptomatically stable during treatment with a conventional depot antipsychotic can be safely and effectively switched to long-acting injectable risperidone without a prior transition to oral risperidone.

  7. Evaluation of a treatment manual for risperidone long-acting injectable.

    PubMed

    Docherty, John P; Jones, Robert; Turkoz, Ibrahim; Lasser, Robert A; Kujawa, Mary

    2007-06-01

    We evaluated the usefulness of a treatment manual to facilitate the use of long-acting injectable risperidone in community mental health centers (CMHCs) during an open-label observational study. Perceived clinical utility and clinician adherence to the manual were evaluated. Patient adherence to treatment satisfaction, Clinical Global Impression of Severity (CGI-S) and the Schizophrenia Quality-of-Life Scale (SQLS) were assessed. Mean score for overall utility of the guidebook was 4.2 +/- .6 (scale ratings ranged from 1 = not at all to 5 = extremely). Most clinicians (89-100%) found the guidebook useful, and were adherent to key aspects of appropriate treatment use including concomitant oral risperidone use and injection and dosing parameters for long-acting risperidone. Most patients were adherent to treatment (86.7%), preferred long-acting risperidone over oral risperidone (72.6%) or other oral antipsychotics (78.4%) and were satisfied with long-acting risperidone (90.1%). The open-label observational design limits interpretation of these data. However, in this study manual-supported use of long-acting risperidone was associated with successful implementation of this pharmacologic treatment in the CMHC setting.

  8. Long-acting injectable risperidone in partially adherent and nonadherent patients with schizophrenia

    PubMed Central

    Louzã, Mário Rodrigues; Elkis, Helio; Ruschel, Sandra; de Oliveira, Irismar Reis; Bressan, Rodrigo Affonseca; Belmonte-de-Abreu, Paulo; Grabowski, Hamilton; Appolinário, José Carlos

    2011-01-01

    Background: Long-acting injectable antipsychotics may improve medication adherence, thereby improving overall treatment effectiveness. This study aimed to evaluate the effectiveness, safety, and tolerability of risperidone long-acting injection in schizophrenic patients switched from oral antipsychotic medication. Methods: In a 12-month, multicenter, open-label, noncomparative study, symptomatically stable patients on oral antipsychotic medication with poor treatment adherence during the previous 12 months received intramuscular injections of risperidone long-acting injection (25 mg starting dose) every 2 weeks. The primary endpoint was the change in Positive and Negative Syndrome Scale (PANSS) total score. Results: Of the 60 patients who were screened, 53 received at least one injection (safety population), and 51 provided at least one postbaseline assessment. Mean PANSS total scores improved significantly throughout the study and at endpoint. Significant improvements were also observed in Clinical Global Impression of Severity, Personal and Social Performance, and Drug Attitude Inventory scales. Risperidone long-acting injection was safe and well-tolerated. Severity of movement disorders on the Extrapyramidal Symptom Rating Scale was reduced significantly. The most frequently reported adverse events were insomnia (22.6%), increased prolactin (17.0%), and weight gain (13.2%). Conclusion: Risperidone long-acting injection was associated with significant symptomatic improvements in stable patients with schizophrenia following a switch from previous antipsychotic medications. PMID:21822391

  9. Long acting β2-adrenocepter agonists are not associated with atrial arrhythmias after pulmonary resection.

    PubMed

    Yamanashi, Keiji; Marumo, Satoshi; Sumitomo, Ryota; Shoji, Tsuyoshi; Fukui, Motonari; Katayama, Toshiro; Huang, Cheng-Long

    2017-05-19

    Long-acting β2-adrenoceptor agonists have been shown to increase the risk of atrial arrhythmias in patients with stable chronic obstructive pulmonary disease. The aim of this study was to investigate whether perioperative long-acting β2-adrenoceptor agonists treatment would increase the risk of postoperative atrial arrhythmias after lung cancer surgery in chronic obstructive pulmonary disease patients. We retrospectively analyzed 174 consecutive chronic obstructive pulmonary disease patients with non-small-cell lung cancer who underwent lobectomy or segmentectomy. The subjects were divided into those with or without perioperative long-acting β2-adrenoceptor agonists treatment. Postoperative cardiopulmonary complications were compared between the two groups. There were no statistically significant differences between the perioperative long-acting β2-adrenoceptor agonists treatment group and the control group in the incidence of postoperative atrial arrhythmias (P = 0.629). In 134 propensity-score-matched pairs, including variables such as age, gender, comorbidities, smoking history, operation procedure, lung-cancer staging, and respiratory function, there were no significant differences between the two groups in the incidence of postoperative cardiopulmonary complications, including atrial arrhythmias. Perioperative administration of long-acting β2-adrenoceptor agonists might not increase the incidence of postoperative atrial arrhythmias after surgical resection for non-small-cell lung cancer in chronic obstructive pulmonary disease patients.

  10. Long-acting injectable formulations of antipsychotic drugs for the treatment of schizophrenia.

    PubMed

    Park, Eun Ji; Amatya, Sarmila; Kim, Myung Sun; Park, Jong Hoon; Seol, Eunyoung; Lee, Heeyong; Shin, Young-Hee; Na, Dong Hee

    2013-06-01

    Antipsychotic drugs have been used to treat patients with schizophrenia and other psychotic disorders. Long-acting injectable antipsychotic drugs are useful for improving medication compliance with a better therapeutic option to treat patients who lack insight or adhere poorly to oral medication. Several long-acting injectable antipsychotic drugs are clinically available. Haloperidol decanoate and fluphenazine decanoate are first-generation depot drugs, but the use of these medicines has declined since the advent of second-generation depot agents, such as long-acting risperidone, paliperidone palmitate, and olanzapine pamoate. The second-generation depot drugs are better tolerated and have fewer adverse neurological side effects. Long-acting injectable risperidone, the first depot formulation of an atypical antipsychotic drug, was prepared by encapsulating risperidone into biodegradable microspheres. Paliperidone palmitate is an aqueous suspension of nanocrystal molecules, and olanzapine pamoate is a microcrystalline salt of olanzapine and pamoic acid suspended in aqueous solution. This review summarizes the characteristics and recent research of formulations of each long-acting injectable antipsychotic drug.

  11. Somatostatin analogue (octreotide) inhibits bile duct epithelial cell proliferation and fibrosis after extrahepatic biliary obstruction.

    PubMed Central

    Tracy, T. F.; Tector, A. J.; Goerke, M. E.; Kitchen, S.; Lagunoff, D.

    1993-01-01

    Extrahepatic biliary obstruction leads to bile duct epithelial cell proliferation. Somatostatin and its analogue, octreotide, have been shown to inhibit DNA synthesis and proliferation in hepatocytes. We investigated the effect of octreotide on the biliary epithelial cell proliferative responses to biliary obstruction. Male Sprague-Dawley rats underwent common bile duct ligation and subcutaneous injection of either saline or octreotide (6 micrograms/kg) twice daily for 7 days. Morphometric analysis of hepatocytes, bile duct epithelial cells, and periportal connective tissue was performed by computerized point counting. Hepatocyte volume was preserved with octreotide treatment, which also significantly decreased bile duct proliferation and periportal extracellular matrix deposition in response to biliary obstruction compared with saline treated, duct-ligated animals. These results indicate that octreotide prevents the morphological changes that accompany extrahepatic biliary obstruction. Images Figure 1 PMID:8256850

  12. "Set it and forget it": women's perceptions and opinions of long-acting topical vaginal gels.

    PubMed

    van den Berg, Jacob J; Rosen, Rochelle K; Bregman, Dana E; Thompson, Lara A; Jensen, Kathleen M; Kiser, Patrick F; Katz, David F; Buckheit, Karen; Buckheit, Robert W; Morrow, Kathleen M

    2014-05-01

    Women's initial understandings and anticipated acceptability of long-acting vaginal gels as potential anti-HIV microbicides was investigated by exploring the perceptibility variables associated with prototype formulations. Four focus groups with 29 women, aged 18-45, were conducted to consider gel prototypes with varied physicochemical and rheological properties. Participants responded favorably to the concept of long-acting vaginal gels as microbicides. Distinctions in understandings and stated needs regarding product dosing, characteristics, and effectiveness offer valuable insights into product design. Long-acting vaginal gels capable of protecting against HIV/STIs will be a viable option among potential users, with dosing frequency being an important factor in willingness to use.

  13. Amlodipine as an antiischemic drug is superior to long acting nitrates

    PubMed Central

    Koraćević, Goran P.; Veličković-Radovanović, Radmila M.; Apostolović, Svetlana R.; Krstić, Nebojša H.; Tasić, Ivan S.; Zdravković, Marija D.; Antonijević, Nebojša M.; Damnjanović, Goran N.; Kostić, Tomislav L.

    2015-01-01

    European Society of Cardiology Guidelines cite results of meta-analysis that the use of calcium channel blockers results in fewer angina episodes per week vs. long-acting nitrates. Moreover, we listed 12 reasons more to prefer amlodipine over long-acting nitrates, especially in stable angina pectoris patients with arterial hypertension. It may be the way to decrease polypharmacy without loosing efficacy. Some important advantages of amlodipine versus long-acting nitrate(s) are: amlodipine also treats hypertension, it helps reducing hypertensive target organ damages (e.g. left ventricular hypertrophy) and prevents morning blood pressure surge. Moreover, amlodipine can be given once daily (which improves adherence), it produces neither tolerance nor rebound, it has less side effects. PMID:28352677

  14. Effectiveness of long-acting injectable antipsychotics in delusional disorders with nonprominent hallucinations and without hallucinations.

    PubMed

    González-Rodríguez, Alexandre; Molina-Andreu, Oriol; Penadés, Rafael; Bernardo, Miquel; Catalán, Rosa

    2014-05-01

    The presence of nonprominent hallucinations in delusional disorder (DD) has been accepted by the current Diagnostic and Statistical Manual of Mental Disorders, 5th ed. A recent meta-analysis revealed that patients with schizophrenia treated with long-acting atypical antipsychotics showed a significant improvement in psychotic symptoms. However, little research has been conducted on DD. Our goal was to investigate demographic and clinical differences between two subgroups of DD patients, those with nonprominent hallucinations and those without hallucinations, and to determine treatment effectiveness of long-acting antipsychotics in these patients. We conducted a longitudinal observational study with a 6-month follow-up period in a clinical group of 45 DD outpatients. Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance Scale, and Hamilton Rating Scale for Depression-17 (HRSD-17) were used for assessment. Age at onset of DD, scores in baseline assessment scales, and drug compliance were included in the analysis as potential confounders. When uncorrected for influencing factors, patients treated with long-acting antipsychotics showed lower scores in PANSS positive and negative subscales. There were no statistically significant clinical subgroup×treatment group interactions for any of the scores in assessment scales at 6 months. After adjustment, patients treated with long-acting antipsychotics showed lower scores in the PANSS negative subscale and a tendency toward improvement in scores in the PANSS positive subscale. Our study suggests that risperidone long-acting injection and paliperidone palmitate long-acting injection may be useful in the treatment of DD patients, specifically those with nonprominent hallucinations.

  15. What Is New in Long-Acting Reversible Contraception?: Best Articles From the Past Year.

    PubMed

    Stuart, Gretchen S

    2016-06-01

    This month we focus on current research in contraception and women choosing long-acting reversible contraception (LARC). Long-acting reversible contraception improves the health of women and their families. Dr. Stuart discusses four recent publications, which are concluded with a "bottom line" that is the take-home message. The articles highlighted can be used to support actions practitioners can take to increase provision of LARC to their patients. The complete reference for each can be found in on this page, along with direct links to the abstracts.

  16. Use of Aripiprazole Long Acting Injection in Negative Symptoms of Schizophrenia

    PubMed Central

    James, Suneeta; Kapugama, Chaya; Al-Uzri, Mohammed

    2016-01-01

    Background. Evidence for the efficacious use of second-generation antipsychotics for the treatment of negative symptoms in schizophrenia is scant. Case Presentation. We report the case of a 34-year-old female of Afro-Caribbean origin, who presented with prominent negative symptoms of schizophrenia and was successfully treated with aripiprazole long acting injection. Within a period of six to nine months, the patient returned to her premorbid level of functioning. Conclusion. Aripiprazole long acting injection promises benefits in the treatment of negative symptoms of schizophrenia. Further research needs to be conducted on the use of this drug. PMID:26981301

  17. Optimized labeling of NOTA-conjugated octreotide with F-18.

    PubMed

    Laverman, Peter; D'Souza, Christopher A; Eek, Annemarie; McBride, William J; Sharkey, Robert M; Oyen, Wim J G; Goldenberg, David M; Boerman, Otto C

    2012-04-01

    We recently reported a facile method based on the chelation of [(18)F]aluminum fluoride (Al(18)F) by NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid). Here, we present a further optimization of the (18)F labeling of NOTA-octreotide (IMP466). Octreotide was conjugated with the NOTA chelate and was labeled with (18)F in a two-step, one-pot method. The labeling procedure was optimized with regard to the labeling buffer, ionic strength, peptide concentration, and temperature. Radiochemical yield, specific activity, in vitro stability, and receptor affinity were determined. Biodistribution of (18)F-IMP466 was studied in AR42J tumor-bearing mice. In addition, microPET/CT images were acquired. IMP466 was labeled with Al(18)F in a single step with 97% yield in the presence of 80% (v/v) acetonitrile or ethanol. The labeled product was purified by HPLC to remove unlabeled peptide and unbound Al(18)F. The radiolabeling, including purification, was performed for 45 min. Specific activities of 48,000 GBq/mmol could be obtained. (18)F-IMP466 showed a high tumor uptake and excellent tumor-to-blood ratios at 2 h post-injection. In addition, the low bone uptake indicated that the Al(18)F-NOTA complex was stable in vivo. PET/CT scans revealed excellent tumor delineation and specific accumulation in the tumor. Uptake in receptor-negative organs was low. NOTA-octreotide could be labeled with (18)F in quantitative yields using a rapid two-step, one-pot, method. The compound was stable in vivo and showed rapid accretion in SSTR(2)-receptor-expressing AR42J tumors in nude mice. This method can be used to label other NOTA-conjugated compounds such as RGD peptides, GRPR-binding peptides, and Affibody molecules with (18)F.

  18. 90Y-Edotreotide for Metastatic Carcinoid Refractory to Octreotide

    PubMed Central

    Bushnell, David L.; O'Dorisio, Thomas M.; O'Dorisio, M. Sue; Menda, Yusuf; Hicks, Rodney J.; Van Cutsem, Eric; Baulieu, Jean-Louis; Borson-Chazot, Francoise; Anthony, Lowell; Benson, Al B.; Oberg, Kjell; Grossman, Ashley B.; Connolly, Mary; Bouterfa, Hakim; Li, Yong; Kacena, Katherine A.; LaFrance, Norman; Pauwels, Stanislas A.

    2010-01-01

    Purpose Metastatic carcinoid is an incurable malignancy whose symptoms, such as diarrhea and flushing, can be debilitating and occasionally life-threatening. Although symptom relief is available with octreotide, the disease eventually becomes refractory to octreotide, leaving no proven treatment options. The goal of this study was to evaluate the clinical effect of using 90Y-edotreotide to treat symptomatic patients with carcinoid tumors. Patients and Methods Patients enrolled had metastatic carcinoid, at least one sign/symptom refractory to octreotide, and at least one measurable lesion. Study treatment consisted of three cycles of 4.4 GBq (120 mCi) 90Y-edotreotide each, once every 6 weeks. Results Ninety patients were enrolled in the study. Using Southwest Oncology Group tumor response criteria, 67 (74.%) of 90 patients (95% CI, 65.4% to 83.4%) were objectively stable or responded. A statistically significant linear trend toward improvement was demonstrated across all 12 symptoms assessed. Median progression-free survival was significantly greater (P = .03) for the 38 patients who had durable diarrhea improvement than the 18 patients who did not (18.2 v 7.9 months, respectively). Adverse events (AEs) were reported in 96.7% (87 of 90) of patients. These AEs consisted primarily of reversible GI events (76 of 90), which could be caused in part by concomitant administration of amino acid solution given to reduce radiation exposure to the kidneys. There was one case each of grade 3 oliguria and grade 4 renal failure, each lasting 6 days. Conclusion 90Y-edotreotide treatment improved symptoms associated with malignant carcinoid among subjects with no treatment alternatives. Treatment was well-tolerated and had an acceptable expected AE profile. PMID:20194865

  19. Long-acting neuroleptics used in wildlife management do not impair thermoregulation or physical activity in goats (Capra hircus).

    PubMed

    Fick, Linda; Mitchell, Duncan; Fuller, Andrea

    2007-06-01

    Long-acting neuroleptics commonly are used in wildlife management to decrease stress-related mortality in wild animals, but with possible effects on thermoregulation, which may contribute to residual morbidity and mortality. We investigated the effects of haloperidol (0.01, 0.1, 1 mg kg(-1), n=4), zuclopenthixol (0.1, 1, 10 mg kg(-1), n=4) and perphenazine (0.1, 1, 10 mg kg(-1), n=8), as well as control injections of sunflower oil, on body temperature and physical activity of laboratory goats under hot, cold and thermoneutral ambient temperatures. Implanted data loggers continuously recorded abdominal temperature, and data loggers attached externally on the foreleg recorded movement of unrestrained goats, in a climatic chamber at 35 degrees C, 10 degrees C and 22 degrees C. Cycling ambient temperature between 35 degrees C in daytime and 10 degrees C at night time caused a significant increase in amplitude of the circadian rhythm of body temperature in goats given sunflower oil (P=0.0012, unpaired t-test, n=8), but the administration of zuclopenthixol or perphenazine did not affect this change in amplitude (P>0.05, two-way ANOVA, n=4). Mean daily body temperature after administration of zuclopenthixol or perphenazine, and mean daily activity after zuclopenthixol administration, were not significantly different to those after control injections, at any ambient temperature, for the expected duration of drug activity (all P>0.05, two-way ANOVA, n=4). Thermal response indices, and mean activity, during heat, cold or thermoneutral exposure, of goats for 7 h after haloperidol injection, were not significantly different, at any dose or any ambient temperature, to those following control injections (all P>0.05, repeated measures ANOVA, n=4). Long-acting neuroleptics did not impair activity or thermoregulation of goats subjected to inescapable thermal challenges.

  20. Pharmacokinetics of Short- and Long-acting Formulations of Oxytetracycline After Intramuscular Administration in Chickens.

    PubMed

    Gberindyer, Aondover F; Okpeh, Ene R; Semaka, Asaaga A

    2015-12-01

    Both short- and long-acting formulations of oxytetracycline are commonly used in veterinary medicine to treat animals infected with gram-negative and gram-positive bacteria, rickettsiae, mycoplasma, and chlamydiae. To compare pharmacokinetics of short- and long-acting oxytetracycline in chickens, injectable formulations from the same pharmaceutical company were administered to healthy 6-week-old broiler chickens in accordance to the labeled instructions. Fourteen chickens were separated into 2 groups: chickens in group A (n = 7) were administered the short-acting formulation (10 mg/kg IM q24h) for 4 consecutive days, whereas those in group B (n = 7) were treated with a single dose (20 mg/kg IM) of the long-acting formulation. Blood samples were collected into heparinized tubes before and at 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, and 24 hours after initial treatment. Thereafter, blood samples were taken every 24 hours up to 120 hours. Plasma concentrations of oxytetracycline were determined by competitive enzyme-linked immunoabsorbent assay, and pharmacokinetic parameters were obtained. Both formulations delivered therapeutic plasma concentrations of oxytetracycline for approximately 100% of their respective dosing intervals as recommended. However, considering the additional labor, patient stress, and mortalities associated with handling, in addition to rejection of the carcass due to tissue necrosis resulting from multiple injections, we recommend use of the long-acting instead of the short-acting injectable formulation in broiler chickens.

  1. Long-acting β-adrenoceptor agonists in the management of COPD: focus on indacaterol

    PubMed Central

    Beier, Jutta; Beeh, Kai M

    2011-01-01

    Bronchodilators are the cornerstone of severe chronic obstructive pulmonary disease (COPD) treatment to improve airflow, symptoms, exercise tolerance, and exacerbations. There is convincing evidence that regular treatment with long-acting bronchodilators is more effective and convenient than treatment with short-acting bronchodilators. Long-acting β-2-agonists include the twice-daily drugs formoterol and salmeterol and, more recently, once-daily indacaterol. Studies with head-to-head comparisons of long-acting bronchodilators are scant, but novel data from controlled trials with the once-daily β(2)-agonist indacaterol indicate superior bronchodilation and clinical efficacy of indacaterol at recommended doses over twice-daily long-acting β(2)-agonists, and at least equipotent bronchodilation compared with once-daily tiotropium. The recent therapeutic developments in COPD underscore a shift from short-acting bronchodilators with multiple dosings per day to reduced dosing frequency and prolonged duration of action, including once-daily treatment, with more consistent effects on various clinical outcomes. This review summarizes relevant clinical data for twice-daily β-2-agonists in COPD, and further focuses on novel data for once-daily indacaterol, including head-to-head comparison trials. PMID:21814459

  2. Long-acting contraceptive agents: norethisterone esters of monoalkenyl and monoalkynyl acids.

    PubMed

    Francisco, C G; Freire, R; Hernandez, R; Salazar, J A; Suarez, E; García de la Mora, G A; Noguez, J A; Acosta, A; Jimeno, O

    1983-03-01

    The synthesis of nine new esters of norethisterone (17 alpha-ethynyl-17 beta-hydroxyestr-4-en-3-one) is described, with the esterifying acids bearing an acetylenic or olefinic function in a chain of eight or nine carbon atoms, for evaluation as long-acting contraceptive agents.

  3. Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations

    USDA-ARS?s Scientific Manuscript database

    The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrino...

  4. Does Prolonged Therapy with a Long-Acting Stimulant Suppress Growth in Children with ADHD?

    ERIC Educational Resources Information Center

    Spencer, Thomas J.; Faraone, Stephen V.; Biederman, Joseph; Lerner, Marc; Cooper, Kimberly M.; Zimmerman, Brenda

    2006-01-01

    Objective: To investigate whether prolonged therapy with a long-acting stimulant affects growth in children with attention-deficit/hyperactivity disorder (ADHD). Method: One hundred seventy-eight children ages 6 to 13 years received OROS methylphenidate (OROS MPH, CONCERTA) for at least 21 months. Height and weight were measured monthly during the…

  5. Reversible inhibition of central precocious puberty with a long acting GnRH analogue.

    PubMed Central

    Ward, P S; Ward, I; McNinch, A W; Savage, D C

    1985-01-01

    A 7 year old girl with precocious puberty was treated with buserelin, a long acting analogue of gonadotrophin releasing hormone. Spontaneous and stimulated gonadotrophin secretion became prepubertal but returned to pubertal values when buserelin was withdrawn, suggesting that normal sexual maturation should follow cessation of treatment. PMID:3931565

  6. Differences in acute anorectic effects of long-acting GLP-1 receptor agonists in rats

    USDA-ARS?s Scientific Manuscript database

    Long-acting glucagon-like peptide-1 receptor (GLP-1R) agonists have both glucose- and weight-lowering effects. The brain is poised to mediate both of these actions since GLP-1Rs are present in key areas known to control weight and glucose. Although some research has been performed on the effects of ...

  7. Long-acting reversible contraceptives: intrauterine devices and the contraceptive implant.

    PubMed

    Espey, Eve; Ogburn, Tony

    2011-03-01

    The provision of effective contraception is fundamental to the practice of women's health care. The most effective methods of reversible contraception are the so-called long-acting reversible contraceptives, intrauterine devices and implants. These methods have multiple advantages over other reversible methods. Most importantly, once in place, they do not require maintenance and their duration of action is long, ranging from 3 to 10 years. Despite the advantages of long-acting reversible contraceptive methods, they are infrequently used in the United States. Short-acting methods, specifically oral contraceptives and condoms, are by far the most commonly used reversible methods. A shift from the use of short-acting methods to long-acting reversible contraceptive methods could help reduce the high rate of unintended pregnancy in the United States. In this review of long-acting reversible contraceptive methods, we discuss the intrauterine devices and the contraceptive implant available in the United States, and we describe candidates for each method, noncontraceptive benefits, and management of complications.

  8. Treatment-completion rates with olanzapine long-acting injection versus risperidone long-acting injection in a 12-month, open-label treatment of schizophrenia: indirect, exploratory comparisons

    PubMed Central

    Ascher-Svanum, Haya; Montgomery, William S; McDonnell, David P; Coleman, Kristina A; Feldman, Peter D

    2012-01-01

    Background Little is known about the comparative effectiveness of atypical antipsychotics in long-acting injection formulation. Due to the absence of head-to-head studies comparing olanzapine long-acting injection and risperidone long-acting injection, this study was intended to make exploratory, indirect, cross-study comparisons between the long-acting formulations of these two atypical antipsychotics in their effectiveness in treating patients with schizophrenia. Methods Indirect, cross-study comparisons between olanzapine long-acting injection and risperidone long-acting injection used 12-month treatment-completion rates, because discontinuation of an antipsychotic for any cause is a recognized proxy measure of the medication’s effectiveness in treating schizophrenia. Following a systematic review of the literature, two indirect comparisons were conducted using open-label, single-cohort studies in which subjects were stabilized on an antipsychotic medication before depot initiation. The first analysis compared olanzapine long-acting injection (one study) with pooled data from nine identified risperidone long-acting injection studies. The second analysis was a “sensitivity analysis,” using only the most similar studies, one for olanzapine long-acting injection and one for risperidone long-acting injection, which shared near-identical study designs and involved study cohorts with near-identical patient characteristics. Pearson Chi-square tests assessed group differences on treatment-completion rates. Results Comparison of olanzapine long-acting injection data (931 patients) with the pooled data from the nine risperidone long-acting injection studies (3950 patients) provided almost identical 12-month treatment-completion rates (72.7% versus 72.4%; P = 0.87). When the two most similar studies were compared, the 12-month completion rate for olanzapine long-acting injection was significantly higher than for risperidone long-acting injection (81.3% versus 47

  9. Long-term effects of octreotide on pituitary gigantism: its analgesic action on cluster headache.

    PubMed

    Otsuka, Fumio; Mizobuchi, Satoshi; Ogura, Toshio; Sato, Kenji; Yokoyama, Masataka; Makino, Hirofumi

    2004-10-01

    We report the case of 19-year-old man with pituitary gigantism due to growth hormone-producing pituitary macroadenoma. The patient complained of recurrent headache and excessive growth spurt since age 15. Octreotide administration was initiated following transsphenoidal pituitary adenomectomy. Octreotide injection for 4 years efficaciously reduced the size of remnant adenoma as well as serum growth hormone levels. Notably, octreotide exhibited a potent analgesic effect on his intractable cluster headache that has continued even after reduction of the adenoma volume. The analgesic effect lasted 2 to 6 hours after each injection and no tachyphylaxis to octreotide appeared during 4-year treatment. To characterize the headache and the pain intensity, analgesic drugs including octreotide, lidocaine, morphine and thiopental were tested using a visual analogue scale (VAS) evaluation, with the result that octreotide exhibited a prompt and complete disappearance of the headache. Headache relief was in part reproduced by morphine injection (56% reduction) but not by lidocaine or thiopental. The present case suggests that the intractable headache associated with pituitary gigantism is possibly related to the endogenous opioid system. Thus, the headache control by octreotide is clinically helpful for continuation of the self-injection regimen.

  10. Production of peptides as generic drugs: a patent landscape of octreotide.

    PubMed

    Sabatino, Giuseppina; Guryanov, Ivan; Rombecchi, Andrea; Zanon, Jacopo; Ricci, Antonio; Cabri, Walter; Papini, Anna Maria; Rovero, Paolo

    2016-01-01

    New low-cost strategies and enhancement of the already described methods to manufacture peptide molecules on an industrial scale are highly requested, particularly for peptides such as octreotide, which, along with goserelin and leuprolide, dominate the global peptide market. A number of patents related to the production of octreotide can be found, concerning both solution and solid-phase synthesis. Thus, there is a need to revise the existing synthetic approaches in order to organize them in a more comprehensible way. The octreotide patent landscape could help improvement of the methods for manufacturing of octreotide in industrial scale, leading to the appearance of innovative approaches. The pharmaceutical value of octreotide can be seen from its high market percentage among other peptide drugs. The complex chemical structure of octreotide represents the main challenge for its industrial production. Two synthetic steps are crucial in the preparation of octreotide: (i) threoninol attachment or on resin formation working in solid-phase and (ii) disulphide bond formation to achieve cyclic structure. Analysis of various patents filed to date allows us to see the trend in simplification of the synthetic approaches from the labor intensive syntheses in solution to the more versatile and rapid solid-phase methods.

  11. Deltoid Injections of Risperidone Long-acting Injectable in Patients with Schizophrenia

    PubMed Central

    Quiroz, Jorge A.; Rusch, Sarah; Thyssen, An; Kushner, Stuart

    2011-01-01

    Background Risperidone long-acting injectable was previously approved for treatment of schizophrenia as biweekly injections in the gluteal muscle only. We present data on local injection-site tolerability and safety of risperidone long-acting injectable and comparability of systemic exposure of deltoid versus gluteal injections. Methods Risperidone long-acting injectable was administered in an open-label, single-dose, two-way crossover study, with patients randomized to receive either 25mg gluteal/37.5mg deltoid crossover in two treatment periods or 50mg gluteal/50mg deltoid injections crossover; each treatment period was separated by an 85-day observation period (Study 1) and an open-label, multiple-dose study (4 sequential 37.5mg or 50mg deltoid injections every 2 weeks) (Study 2). The pharmacokinetic results from both the studies have already been published. Results In Study 1 (n=170), the majority of patients had no local injection-site findings, based on investigator and patient-rated evaluations. In Study 2 (n=53), seven of the 51 patients who received at least two deltoid injections discontinued (primary endpoint). However, none of the discontinuations were due to injection-site related reasons. The 90-percent upper confidence limit of the true proportion of injection-site issue withdrawals was 5.7 percent. No moderate or severe injection-site reactions were reported. Conclusion Intramuscular injections via the deltoid and gluteal sites are equivalent routes of administration of risperidone long-acting injectable with respect to local injection-site tolerability. The overall safety and tolerability profile of risperidone long-acting injectable was comparable when administered as an intramuscular injection in the deltoid (37.5mg and 50mg) and gluteal (25mg and 50mg) sites. PMID:21779538

  12. Deltoid injections of risperidone long-acting injectable in patients with schizophrenia.

    PubMed

    Quiroz, Jorge A; Rusch, Sarah; Thyssen, An; Palumbo, Joseph M; Kushner, Stuart

    2011-06-01

    Risperidone long-acting injectable was previously approved for treatment of schizophrenia as biweekly injections in the gluteal muscle only. We present data on local injection-site tolerability and safety of risperidone long-acting injectable and comparability of systemic exposure of deltoid versus gluteal injections. Risperidone long-acting injectable was administered in an open-label, single-dose, two-way crossover study, with patients randomized to receive either 25mg gluteal/37.5mg deltoid crossover in two treatment periods or 50mg gluteal/50mg deltoid injections crossover; each treatment period was separated by an 85-day observation period (Study 1) and an open-label, multiple-dose study (4 sequential 37.5mg or 50mg deltoid injections every 2 weeks) (Study 2). The pharmacokinetic results from both the studies have already been published. In Study 1 (n=170), the majority of patients had no local injection-site findings, based on investigator and patient-rated evaluations. In Study 2 (n=53), seven of the 51 patients who received at least two deltoid injections discontinued (primary endpoint). However, none of the discontinuations were due to injection-site related reasons. The 90-percent upper confidence limit of the true proportion of injection-site issue withdrawals was 5.7 percent. No moderate or severe injection-site reactions were reported. Intramuscular injections via the deltoid and gluteal sites are equivalent routes of administration of risperidone long-acting injectable with respect to local injection-site tolerability. The overall safety and tolerability profile of risperidone long-acting injectable was comparable when administered as an intramuscular injection in the deltoid (37.5mg and 50mg) and gluteal (25mg and 50mg) sites.

  13. The role of tiotropium bromide, a long-acting anticholinergic bronchodilator, in the management of COPD.

    PubMed

    Saberi, Farzad; O'Donnell, Denis E

    2005-01-01

    Bronchodilator therapy forms the mainstay of treatment for symptomatic patients with COPD. Long-acting bronchodilators, which maintain sustained airway patency over a 24-hour period, represent an advance in therapy. Tiotropium bromide is a new long-acting inhaled anticholinergic agent with superior pharmacodynamic properties compared with the short-acting anticholinergic, ipratropium bromide. Tiotropium bromide has been consistently shown to have a greater impact than ipratropium bromide on clinically important outcome measures such as health status. The mechanisms of clinical benefit with tiotropium bromide are multifactorial, but improved airway function, which enhances lung emptying and allows sustained deflation of over-inflated lungs, appears to explain improvements in dyspnea and exercise endurance in COPD. Inhaled tiotropium bromide therapy has also been associated with reduction in acute exacerbations of COPD as well as reduced hospitalizations. The safety profile of tiotropium bromide is impressive: dry mouth is the most common adverse event and rarely necessitates termination of the drug. No tachyphylaxis to tiotropium bromide has been demonstrated in clinical trials lasting up to 1 year. There is preliminary information that the combination of long-acting anticholinergics and long-acting beta2-adrenoceptor agonists provides additive physiological and clinical benefits. According to recent international guidelines, long-acting bronchodilators should be considered early in the management of symptomatic patients with COPD in order to achieve effective symptom alleviation and reduction in activity limitation. Tiotropium bromide, because of its once-daily administration and its established efficacy and tolerability profile, has emerged as an attractive therapeutic option for this condition.

  14. Switching from risperidone long-acting injectable to paliperidone long-acting injectable or oral antipsychotics: analysis of a Medicaid claims database.

    PubMed

    Voss, Erica A; Ryan, Patrick B; Stang, Paul E; Hough, David; Alphs, Larry

    2015-05-01

    This report examines relapse risk following a switch from risperidone long-acting injectable (RLAI) to another long-acting injectable antipsychotic [paliperidone palmitate (PP)] versus a switch to oral antipsychotics (APs). Truven Health's MarketScan Multistate Medicaid Database compared relapses following switches from RLAI. New user cohorts for these two groups were created on the basis of first incidence of exposure to the 'switched to' drug. Groups were balanced using 1:1 propensity score matching. Time-to-event analysis assessed schizophrenia-related hospital/emergency department visits. A total of 188 patients switched from RLAI to PP, and 131 patients switched from RLAI to oral AP. Propensity score-matched cohort included 109 patients who switched to PP and 109 patients who switched to an oral AP. Patients who switched from RLAI to PP had fewer events (26 vs. 32), longer time to an event (mean 70 vs. 47 days), and lower risk of relapse (hazard ratio, 0.54; 95% confidence interval, 0.32-0.92; P=0.024) compared with those who switched from RLAI to oral AP. Switching from RLAI to PP may be associated with a lower risk for relapse and longer duration of therapy compared with switching to oral AP. Given the limitations of observational studies, these results should be confirmed by other prospective evaluations.

  15. Octreotide reduces hepatic, renal and breast cystic volume in autosomal-dominant polycystic kidney disease.

    PubMed

    Peces, Ramón; Cuesta-López, Emilio; Peces, Carlos; Pérez-Dueñas, Virginia; Vega-Cabrera, Cristina; Selgas, Rafael

    2011-06-01

    A 43-year-old woman with autosomal-dominant polycystic kidney disease (ADPKD) received octreotide for 12 months, and this was associated with a 6.3% reduction in liver volume, an 8% reduction in total kidney volume and stabilization of renal function. There was also a reduction of cyst size in fibrocystic disease of breast. These data suggest that the cyst fluid accumulation in different organs from patients with ADPKD is a dynamic process which can be reversed by octreotide. This is the first report of a case of simultaneous reduction in hepatic, renal and breast cystic volume with preservation of renal function in a patient with ADPKD receiving octreotide.

  16. Stability of octreotide acetate decreases in a sodium bisulfate concentration-dependent manner: compatibility study with morphine and metoclopramide injections.

    PubMed

    Tanabe, Kouichi; Wada, Junko; Ohkubo, Jun; Nitta, Atsumi; Ikezaki, Tomoaki; Takeuchi, Miyako; Handa, Aya; Tanaka, Mai; Murakami, Nozomu; Kashii, Tatsuhiko; Kitazawa, Hidenori

    2015-05-01

    Sodium bisulfate is known to affect the stability of octreotide. However, the critical concentration of sodium bisulfate is not known. Therefore, we assessed the critical concentration of sodium bisulfate needed to preserve the stability of octreotide using actual drugs containing sodium bisulfate. Although morphine and metoclopramide preparations are considered to be compatible with octreotide, some of their products are known to contain sodium bisulfate. Thus, octreotide was mixed with preparations of sodium bisulfate solutions at serial concentrations and morphine and metoclopramide preparations containing sodium bisulfate, and octreotide stability was then evaluated using high performance liquid chromatography. Octreotide concentrations decreased significantly at a sodium bisulfate concentration of 0.1 mg/mL or higher after 10 days when octreotide was mixed with sodium bisulfate solutions at various concentrations. A significant decrease in octreotide concentrations also occurred when it was mixed with morphine and metoclopramide preparations containing sodium bisulfate and stored for 10 days; however, slight decreases were observed in the mixture with both preparations and were within the clinically acceptable range for morphine preparations. These results indicate that the residual rate of octreotide decreases with time in a sodium bisulfate concentration-dependent manner when octreotide was mixed with morphine or metoclopramide. However, this incompatibility may be clinically acceptable when the final sodium bisulfate concentration is lower than 0.1 mg/mL and the mixed solution is used within 7 days.

  17. Reversible Hydrophobic Ion-Paring Complex Strategy to Minimize Acylation of Octreotide during Long-Term Delivery from PLGA Microparticles

    PubMed Central

    Vaishya, Ravi D.; Mandal, Abhirup; Gokulgandhi, Mitan; Patel, Sulabh; Mitra, Ashim K.

    2015-01-01

    Acylation of peptide has been reported for a number of peptides and proteins during release from polymers comprising of lactide and glycolide. We hypothesize that reversible hydrophobic ion-pairing (HIP) complex may minimize octreotide acylation during release. Sodium dodecyl sulfate (SDS), dextran sulfate A (DSA, Mw 9–20kDa) and dextran sulfate B (DSB, Mw 36–50kDa) were selected as ion-pairing agents to prepare reversible HIP complex with octreotide. Complexation efficiency was optimized with respect to the mole ratio of ion-pairing agent to octreotide to achieve 100% complexation of octreotide. Dissociation studies suggested that DSA-octreotide and DSB-octreotide complexes dissociate completely at physiological pH in presence of counter ions unlike SDS-octreotide complex. DSA-octreotide and DSB-octreotide complex encapsulated PLGA microparticles (DSAMPs and DSBMPs) were prepared using the S/O/W emulsion method. Entrapment efficiencies for DSAMPs and DSBMPs were 74.7±8.4% and 81.7±6.3%, respectively. In vitro release of octreotide was performed by suspending MPs in gel. A large fraction of peptide was released in chemically intact form and <7% was acylated from DSAMPs and DSBMPs in gel over 55 days. Therefore, HIP complexation could be a viable strategy to minimize acylation of peptides and proteins during extended release from lactide and glycolide based polymers. PMID:25940041

  18. Minimal injection site pain and high patient satisfaction during treatment with long-acting risperidone.

    PubMed

    Lindenmayer, Jean-Pierre; Jarboe, Kathleen; Bossie, Cynthia A; Zhu, Young; Mehnert, Angelika; Lasser, Robert

    2005-07-01

    Long-acting injectable antipsychotic formulations of conventional antipsychotics were developed to address the problem of partial adherence among patients with schizophrenia. Injection site pain, other skin reactions and patient satisfaction with treatment were assessed in two large, multicentre studies of long-acting injectable risperidone (Risperdal CONSTA, Janssen Pharmaceutica Products, Titusville, New Jersey, USA), the first available long-acting atypical antipsychotic agent. Patients rated injection site pain using a 100-mm Visual Analogue Scale (VAS), and investigators rated injection site pain, redness, swelling and induration. Patient satisfaction with treatment was assessed with the Drug Attitude Inventory (DAI). VAS pain ratings were low at all visits across all doses in both studies, and decreased from first to final injection. In the 12-week, double-blind study, mean +/- SD VAS scores at the first and final injections were 15.6 +/- 20.7 and 12.5 +/- 18.3 for placebo-treated patients, and 11.8 +/- 14.4 (first) and 10.0 +/- 12.4 (final) for 25 mg; 16.3+/-21.9 (first) and 13.6 +/- 21.7 (final) for 50 mg; and 16.0 +/- 17.9 (first) and 9.6 +/- 16.0 (final, P<0.01) for 75 mg of long-acting risperidone. Mean VAS scores in the 50-week, open-label study at the first and final injection were: 17.9 +/- 22.2 (first) and 9.5 +/- 16.7 (final, P<0.0001) for 25 mg; 18.1 +/- 19.7 (first) and 10.4 +/- 14.8 (final, P<0.0001) for 50 mg; and 18.5 +/- 21.6 (first) and 13.6 +/- 19.9 (final, P = 0.0001) for 75 mg of long-acting risperidone. Overall, there was no or minimal injection site pain and skin reactions were rare. Mean DAI ratings were available for the 50-week study and indicated high patient satisfaction throughout the trial (baseline = 7.30; endpoint = 7.70; P<0.0001 versus baseline). These findings may positively affect patient and clinician attitudes towards long-term therapy with long-acting injectable risperidone.

  19. Emerging treatments in the management of bipolar disorder – focus on risperidone long acting injection

    PubMed Central

    El-Hage, Wissam; Surguladze, Simon A

    2010-01-01

    Bipolar disorder is a life-long psychiatric illness characterized by a high frequency of relapses and substantial societal costs. Almost half of the patients are prescribed second generation antipsychotics for treatment of manic states, or as the maintenance therapy. Risperidone long acting injection (RLAI) as a monotherapy or as adjunctive therapy to lithium or valproate for the maintenance treatment of bipolar I disorder was approved by Food and Drug Administration (FDA) in United States in May 2009. In this review we will consider the aspects of pharmacology, pharmacokinetics, metabolism, safety and tolerability, and clinical trials focusing on the efficacy of RLAI in bipolar disorder. The patients’ perspective and attitudes to long-acting injections will also be discussed. PMID:20856609

  20. Initiation and continuation of long-acting reversible contraception in the United States military healthcare system.

    PubMed

    Chiles, Daniel P; Roberts, Timothy A; Klein, David A

    2016-09-01

    Long-acting reversible contraception is more effective for pregnancy prevention than shorter-acting contraceptive methods and has the potential to reduce healthcare disparities and costs. However, long-acting reversible contraception is underused in the United States. One population of interest is beneficiaries of the United States military healthcare system who have access to universal healthcare, including no-cost, no-copay contraception with unlimited method switching, and comprise a large, actual use cohort. Efforts to increase long-acting reversible contraception initiation and continuation in this population may improve health outcomes and mitigate the profound consequences of unintended or mistimed pregnancy on readiness and cost to the military. We aimed to determine long-acting reversible contraception initiation and continuation rates among the diverse population with universal healthcare who are enrolled in the US military healthcare system. This study is a retrospective cohort of >1.7 million women, aged 14-40 years, who were enrolled in the US military healthcare system, TRICARE Prime, between October 2009 and September 2014. Individuals were assessed for long-acting reversible contraception initiation and continuation with the use of medical billing records. Method continuation and factors that were associated with early method discontinuation were evaluated with the Kaplan-Meier estimator and Cox proportional hazard models. During the study dates, 188,533 women initiated long-acting reversible contraception. Of these, 74.6% women selected intrauterine contraceptives. Method initiation rates remained relatively stable (41.7-50.1/1000 women/year) for intrauterine methods, although the rate for subdermal implants increased from 6.1-23.0/1000 women/year. In analysis of women who selected intrauterine contraceptives, 61.2% continued their method at 36 months, and 48.8% continued at 60 months. Among women who selected the implant, 32.0% continued their

  1. PHARMACOKINETICS OF CEFTIOFUR CRYSTALLINE FREE ACID, A LONG-ACTING CEPHALOSPORIN, IN AMERICAN FLAMINGOS (PHOENICOPTERUS RUBER).

    PubMed

    Kilburn, Jennifer J; Cox, Sherry K; Backues, Kay A

    2016-06-01

    Antibiotic usage is a vital component of veterinary medicine but the unique anatomy of some species can make administration difficult. The objective of this study was to determine the pharmacokinetic parameters of ceftiofur crystalline free acid (CCFA), a long-acting cephalosporin antibiotic, after parenteral administration in American flamingos ( Phoenicopterus ruber ). A dose of 10 mg/kg of CCFA was administered intramuscularly to 11 birds and blood was collected at various time points from 0 to 192 hr. Pharmacokinetic parameters for ceftiofur equivalents were determined and reached levels above minimum inhibitory concentrations of various bacterial organisms in other avian species through 96 hr in 9/11 birds. Based on these findings and comparison to other avian studies, ceftiofur crystalline free acid appears to be a long-acting antibiotic option for American flamingos. Administration of this antibiotic should be utilized in conjunction with culture and sensitivity of suspected pathogens.

  2. Effectiveness of long-acting antipsychotics in clinical practice: 2. Effects of antipsychotic polypharmacy on risperidone long-acting injection and zuclopenthixol decanoate

    PubMed Central

    Cordiner, Matthew; Shajahan, Polash; McAvoy, Sarah; Bashir, Muhammad; Taylor, Mark

    2016-01-01

    Objectives: Antipsychotic polypharmacy (APP) is common clinical practice. Theoretically, APP runs the risk of additional side effects, drug interactions, adherence and cost. A limited evidence base is emerging to support the effectiveness of APP in clinical practice. Our companion paper highlighted the extent of APP alongside commonly prescribed long-acting antipsychotic injections (LAIs). We aimed to examine the effects of APP on discontinuation rates and Clinical Global Impression (CGI) outcomes in patients commenced on risperidone long-acting injection (RLAI) and zuclopenthixol decanoate. Method: LAI-naïve patients commenced on RLAI (n = 102) and zuclopenthixol decanoate(n = 105) were identified using our electronic patient record (running from 2002) within NHS Lanarkshire, Scotland, UK. This was a retrospective, electronic case note review with an 18-month follow up. Patient groups were divided into those receiving the LAI as the sole antipsychotic and those who were receiving additional oral antipsychotic polypharmacy (APP) for at least 50% of the duration of the treatment with their LAI. Kaplan–Meier statistics were calculated for discontinuation rates. CGI severity and improvement scores were retrospectively assigned by the investigating team. Results: Antipsychotic polypharmacy occurred with RLAI (37%) and zuclopenthixol decanoate (46%) and was associated with lower discontinuation rates (statistical significant with zuclopenthixol for any cause and adverse effects discontinuation). APP had no adverse outcomes on hospital admissions or CGI ratings. Patients on APP did not have more severe, chronic or treatment resistant illnesses. Conclusions: For RLAI and zuclopenthixol decanoate, APP had some favourable outcomes when examining discontinuation rates for any cause, and adverse effects. This was unexpected as we had considered APP would signal illness chronicity and severity and be associated with increased adverse effects resulting in early

  3. Long Acting Risperidone in an Adolescent with Conduct Disorder: A Case Report.

    PubMed

    Tutkunkardaş, Mustafa Deniz; Abali, Osman

    2011-09-15

    Adolescent conduct disorder (CD) is generally hard to manage clinically, as this population often refuses to take oral medications. Families and acquaintances of these adolescents usually suffer from extreme psychological, financial and social difficulties. Oral antipsychotics are the primary drugs of choice clinically, after behavioral treatments. Here we report a case with attention deficit hyperactivity disorder and conduct disorder who refuses to take any medications, was not eligible for behavioral treatments and was treated successfully with long acting risperidone.

  4. Long-acting contraceptive agents: analysis and purification of steroid esters.

    PubMed

    Matlin, S A; Chan, L; Hadjigeogiou, P; Prazeres, M A; Mehani, S; Roshdi, S

    1983-03-01

    More than 200 samples of esters of norethisterone (17 alpha-ethynyl-17 beta-hydroxyestr-4-en-3-one) and levonorgestrel (13 beta-ethyl-17 alpha-ethynyl-17 beta-hydroxygon-4-en-3 -one) have been analysed by a combination of techniques, including high performance liquid chromatography (HPLC). Compounds having a purity below the required limit (99.5%) were purified, mainly by preparative HPLC, prior to formulation and biological evaluation as long-acting progestogens.

  5. Hospitalizations and economic analysis in psychotic patients with paliperidone palmitate long-acting injection.

    PubMed

    Mesones-Peral, Jesús E; Gurillo-Muñoz, Pedro; Sánchez-Sicilia, Mari Paz; Miller, Adam; Griñant-Fernández, Alejandra

    Prevent hospitalizations in psychotic disorders is an important aim, so long-acting antipsychotic is a good option that can control better the correct adherence. Moreover, in the current economic context pharmacoeconomic studies are necessary. We estimate the effect in prevention of paliperidone palmitate long-acting injection (PP-LAI) and calculate the economic cost in the 12 months preceding the start of treatment with PP-LAI and 12 months later. Mirror image study of 71 outpatients diagnosed with psychotic disorders and treated with PP-LAI. In a first analysis, we measured along one year: number of hospitalizations/year, number of hospitalization in days, number of emergency assists/year and if there is antipsychotics associated to long-acting treatment. After this phase, we applied Fees Act of Valencia for economic analysis and estimate of the cost per hospitalization (€ 5,640.41) and hospital emergency (€ 187.61). After one year of treatment with PP-LAI (mean dose=130.65mg/month), we obtained greater numbers in assistance variables: total hospitalizations decrease, 78.8% (P=.009); shortening in hospitalization days, 89.4% (P=.009); abridgement of number of emergency assists, 79.1% (P=.002); decrease of rate of antipsychotics associated to long-acting treatment, 21% (P<.0001); increase in monotherapy, 53.8% (P<.0001). Therefore, after 12 months of treatment with PP-LAI we obtained a reduction in inpatient spending (savings of € 175,766.54) and increased spending on antipsychotics 32% (equivalent to € 151,126.92). PP-LAI can be an effective therapy for the treatment of patients with severe psychotic disorders: improves symptomatic stability and can prevent hospitalizations with cost-effective symptom control. Copyright © 2016 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Committee opinion no. 539: adolescents and long-acting reversible contraception: implants and intrauterine devices.

    PubMed

    2012-10-01

    Long-acting reversible contraception (LARC)—intrauterine devices and the contraceptive implant—are safe and appropriate contraceptive methods for most women and adolescents. The LARC methods are top-tier contraceptives based on effectiveness, with pregnancy rates of less than 1% per year for perfect use and typical use. These contraceptives have the highest rates of satisfaction and continuation of all reversible contraceptives. Adolescents are at high risk of unintended pregnancy and may benefit from increased access to LARC methods.

  7. The Somatostatin Analogue Octreotide Inhibits Growth of Small Intestine Neuroendocrine Tumour Cells

    PubMed Central

    Li, Su-Chen; Martijn, Cécile; Cui, Tao; Essaghir, Ahmed; Luque, Raúl M.; Demoulin, Jean-Baptiste; Castaño, Justo P.; Öberg, Kjell; Giandomenico, Valeria

    2012-01-01

    Octreotide is a widely used synthetic somatostatin analogue that significantly improves the management of neuroendocrine tumours (NETs). Octreotide acts through somatostatin receptors (SSTRs). However, the molecular mechanisms leading to successful disease control or symptom management, especially when SSTRs levels are low, are largely unknown. We provide novel insights into how octreotide controls NET cells. CNDT2.5 cells were treated from 1 day up to 16 months with octreotide and then were profiled using Affymetrix microarray analysis. Quantitative real-time PCR and western blot analyses were used to validate microarray profiling in silico data. WST-1 cell proliferation assay was applied to evaluate cell growth of CNDT2.5 cells in the presence or absence of 1 µM octreotide at different time points. Moreover, laser capture microdissected tumour cells and paraffin embedded tissue slides from SI-NETs at different stages of disease were used to identify transcriptional and translational expression. Microarrays analyses did not reveal relevant changes in SSTR expression levels. Unexpectedly, six novel genes were found to be upregulated by octreotide: annexin A1 (ANXA1), rho GTPase-activating protein 18 (ARHGAP18), epithelial membrane protein 1 (EMP1), growth/differentiation factor 15 (GDF15), TGF-beta type II receptor (TGFBR2) and tumour necrosis factor (ligand) superfamily member 15 (TNFSF15). Furthermore, these novel genes were expressed in tumour tissues at transcript and protein levels. We suggest that octreotide may use a potential novel framework to exert its beneficial effect as a drug and to convey its action on neuroendocrine cells. Thus, six novel genes may regulate cell growth and differentiation in normal and tumour neuroendocrine cells and have a role in a novel octreotide mechanism system. PMID:23119007

  8. Redesign of negatively charged (111)In-DTPA-octreotide derivative to reduce renal radioactivity.

    PubMed

    Oshima, Nobuhiro; Akizawa, Hiromichi; Kawashima, Hidekazu; Zhao, Songji; Zhao, Yan; Nishijima, Ken-Ichi; Kitamura, Yoji; Arano, Yasushi; Kuge, Yuji; Ohkura, Kazue

    2017-05-01

    Radiolabeled octreotide derivatives have been studied as diagnostic and therapeutic agents for somatostatin receptor-positive tumors. To prevent unnecessary radiation exposure during their clinical application, the present study aimed to develop radiolabeled peptides which could reduce radioactivity levels in the kidney at both early and late post-injection time points by introducing a negative charge with an acidic amino acid such as L-aspartic acid (Asp) at a suitable position in (111)In-DTPA-conjugated octreotide derivatives. Biodistribution of the radioactivity was evaluated in normal mice after administration of a novel radiolabeled peptide by a counting method. The radiolabeled species remaining in the kidney were identified by comparing their HPLC data with those obtained by alternative synthesis. The designed and synthesized radiolabeled peptide (111)In-DTPA-d-Phe(-1)-Asp(0)-d-Phe(1)-octreotide exhibited significantly lower renal radioactivity levels than those of the known (111)In-DTPA-d-Phe(1)-octreotide at 3 and 24h post-injection. The radiolabeled species in the kidney at 24h after the injection of new octreotide derivative represented (111)In-DTPA-d-Phe-OH and (111)In-DTPA-d-Phe-Asp-OH as the metabolites. Their radiometabolites and intact (111)In-DTPA-conjugated octreotide derivative were observed in urine within 24h post-injection. The present study provided a new example of an (111)In-DTPA-conjugated octreotide derivative having the characteristics of both reduced renal uptake and shortened residence time of radioactivity in the kidney. It is considered that this kinetic control was achieved by introducing a negative charge on the octreotide derivative thereby suppressing the reabsorption in the renal tubules and affording the radiometabolites with appropriate lipophilicity. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Midodrine and octreotide in treatment of cirrhosis-related hemodynamic complications.

    PubMed

    Karwa, Rakhi; Woodis, C Brock

    2009-04-01

    To review studies evaluating the use of midodrine and octreotide in hemodynamic complications of cirrhosis, including ascites and hepatorenal syndrome. Searches of MEDLINE (1966-September 2008) and EMBASE (1974-September 2008) were conducted using the terms midodrine, octreotide, hepatorenal syndrome, ascites, cirrhosis, and paracentesis-induced circulatory dysfunction. Literature review was limited to English-language, human studies. Studies identified from data sources were considered for review. Studies were excluded if primary therapy involved any of the following: transjugular intrahepatic portosystemic shunt procedure, medications other than midodrine or octreotide, or patients included for treatment or prevention of portal hypertension and/or variceal bleeding. Pharmacokinetic/pharmacodynamic studies and studies using retrospective data collection were excluded. Seven studies were included in this review. Midodrine and octreotide in combination or alone have shown conflicting results for systemic and renal hemodynamics and renal function in patients with cirrhosis-related complications. Patients with ascites being treated with midodrine, alone or in combination with octreotide, showed significant changes in systemic hemodynamics, without a correlating change in renal perfusion. Studies comparing the use of midodrine with use of albumin for the prevention of paracentesis-induced circulatory dysfunction (PICD) showed no incidence of PICD in either treatment group. In hepatorenal syndrome, patients using midodrine with octreotide showed significant changes in systemic hemodynamics and improvements in renal perfusion. This regimen's effect on survival is yet to be determined. Available evidence shows inconsistent results for the effectiveness and safety of midodrine and octreotide use in cirrhotic patients. Because of the contradictory results, longer treatment duration and increased number of study participants are necessary to determine the proper use of

  10. Octreotide use in post-cardiac surgery chylothorax: a 12-year perspective.

    PubMed

    Aljazairi, Abdulrazaq Sheikh; Bhuiyan, Tauhid Ahmed; Alwadai, Abdullah Hasan; Almehizia, Rayd Abdulaziz

    2017-01-01

    Background Chylothorax following cardiothoracic surgery is a rare condition in pediatric patients with significant morbidity and mortality. Pharmacological management with octreotide suggests possible efficacy; however, current evidence is inadequate. The objective of this study was to assess the safety and efficacy of octreotide as a therapeutic option in this clinical setting. Methods This was a 12-year single-center retrospective cohort study of all patients (birth to 18-years old) who received octreotide for management of post-cardiac surgery chylothorax between January 2003 to August 2015. The primary efficacy endpoint was resolution of chylothorax, categorized as complete (<2 mL·kg(-1)·day(-1)), partial (based on physician's judgement), or failed. The primary safety endpoint was any significant adverse drug reaction leading to discontinuation of octreotide therapy. Of the 46 patients identified as receiving octreotide for post-cardiac surgery chylothorax, 29 were included in efficacy and safety analyses. Results Resolution of chylothorax was achieved in 62% (complete in 28%, partial in 34%) of the total sample. The 38% who did not respond to octreotide therapy required thoracic duct ligation. The mean initial dose and duration of octreotide was 4 ± 3 µg·kg(-1)·h(-1) and 10 ± 5 days, respectively. Besides minor side-effects including transient hyperglycemia (45%), abdominal distension (3%), and tachycardia (>150 beats·min(-1); 10%), no patient developed a significant side-effect that required discontinuation of therapy. Conclusions Pharmacological management of post-cardiac surgery induced chylothorax with octreotide shows promising benefits with an acceptable safety profile.

  11. Long-term use of short- and long-acting nitrates in stable angina pectoris.

    PubMed

    Kosmicki, Marek Antoni

    2009-05-01

    Long-acting nitrates are effective antianginal drugs during initial treatment. However, their therapeutic value is compromised by the rapid development of tolerance during sustained therapy, which means that their clinical efficacy is decreased during long-term use. Sublingual nitroglycerin (NTG), a short-acting nitrate, is suitable for the immediate relief of angina. In patients with stable angina treated with oral long-acting nitrates, NTG maintains its full anti-ischemic effect both after initial oral ingestion and after intermittent long-term oral administration. However, NTG attenuates this effect during continuous treatment, when tolerance to oral nitrates occurs, and this is called cross-tolerance. In stable angina long-acting nitrates are considered third-line therapy because a nitrate-free interval is required to avoid the development of tolerance. Nitrates vary in their potential to induce the development of tolerance. During long-lasting nitrate therapy, except pentaerythritol tetranitrate (PETN), one can observe the development of reactive oxygen species (ROS) inside the muscular cell of a vessel wall, and these bind with nitric oxide (NO). This leads to decreased NO activity, thus, nitrate tolerance. PETN has no tendency to form ROS, and therefore during long-term PETN therapy, there is probably no tolerance or cross-tolerance, as during treatment with other nitrates.

  12. How Do Dual Long-acting Bronchodilators Prevent Exacerbations of Chronic Obstructive Pulmonary Disease?

    PubMed

    Beeh, Kai M; Burgel, Pierre-Regis; Franssen, Frits M E; Lopez-Campos, Jose Luis; Loukides, Stelios; Hurst, John R; Fležar, Matjaž; Ulrik, Charlotte Suppli; Di Marco, Fabiano; Stolz, Daiana; Valipour, Arschang; Casserly, Brian; Ställberg, Björn; Kostikas, Konstantinos; Wedzicha, Jadwiga A

    2016-12-06

    Decreasing the frequency and severity of exacerbations is one of the main goals of treatment for patients with chronic obstructive pulmonary disease (COPD). Several studies have documented that long-acting bronchodilators (LABDs) can reduce exacerbation rate and/or severity, and others have shown that combinations of long-acting β2-adrenergic agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) provide greater reductions in exacerbation frequency than either their monocomponents or LABA/inhaled corticosteroids (LABA/ICS) combinations in patients at low and high risk for these events. In this review, small groups of experts critically evaluated mechanisms potentially responsible for the increased benefit of LABA/LAMA combinations over single LABDs or LABA/ICS in decreasing exacerbation. These included effects on lung hyperinflation and mechanical stress, inflammation, excessive mucus production with impaired mucociliary clearance, and symptom severity. The data assembled and analyzed by each group were reviewed by all authors and combined into this manuscript. Available clinical results support the possibility that effects of LABA/LAMA combinations on hyperinflation, mucociliary clearance, and symptom severity may all contribute to decreasing exacerbations. While preclinical studies suggest LABAs and LAMAs have anti-inflammatory effects, such effects have not been demonstrated yet in patients with COPD.

  13. Preparation, characterization and related in vivo release, safety and toxicity studies of long acting lanreotide microspheres.

    PubMed

    Wang, Shuang; Wu, Mingsheng; Li, Dan; Jiao, Mingli; Wang, Lan; Zhang, Haifeng; Liu, Huaiyu; Wang, Daifeng; Han, Bing

    2012-01-01

    The goal of this project was to prepare long-acting lanreotide acetate poly(lactic-co-glycolic acid) (PLGA) microspheres and to analyze the in vivo and in vitro release, safety and toxicology of these preparations. Long-acting lanreotide acetate PLGA microspheres that exhibited a 5-week slow-release period were prepared by a multiple-emulsion solvent evaporation method. Physical characterization, as well as the analysis of the in vivo and in vitro release, safety, acute toxicity and chronic toxicity of the lanreotide microspheres, were conducted in animal models in rats, guinea pigs, rabbits and beagle dogs. The lanreotide acetate PLGA microspheres prepared by multiple-emulsion solvent evaporation had smooth surfaces, uniform particle size and stable lanreotide loading. In vivo and in vitro experiments showed that the lanreotide acetate PLGA microspheres could continuously release lanreotide for 5 weeks. The safety of these long acting lanreotide microspheres was good in the following animal models: active systemic anaphylaxis test in guinea pigs, passive cutaneous anaphylaxis test in rats, hemolytic test in rabbits, local skin irritation test after subcutaneous administration in rabbits and muscle stimulation test in rabbits. Furthermore, no significant acute toxicity or chronic toxicity was observed after administration of lanreotide acetate PLGA microspheres in beagle dogs at dosages up to 22 mg/kg. The lanreotide acetate PLGA microspheres that were prepared in this study exhibited beneficial characteristics in apparent property and structural stability, as well as in release trends in vivo and in vitro.

  14. The Promise and Pitfalls of Long Acting Injectable Agents for HIV Prevention

    PubMed Central

    Kofron, Ryan; McCauley, Marybeth

    2016-01-01

    Purpose of review Pre-exposure prophyalxis (PrEP) for HIV prevention is highly effective when taken as prescribed. Adherence to required dosing regimens for protection may pose challenges. Long Acting agents for HIV prevention may have the potential to improve adherence via favorable pharmacokinetics supportive of infrequent dosing. This review focuses on the potential benefits and considerations for the study and use of two long acting injectable agents, cabotegravir (GSK1265744 LA, CAB LA) and rilpivirine (TMC278 LA, RPV LA), for use as chemoprophylaxis for HIV prevention. Recent findings Oral RPV is FDA approved for HIV treatment (in combination with other antiretrovirals). Both CAB LA and RPV LA are currently in Phase 2a safety/tolerability/pharmacokinetic studies in anticipation and support of future efficacy evaluation. Both agents have favorable pharmacokinetics, and use is complicated by injection site reactions. Summary Long acting injectable formulations, if safe and well tolerated, may improve pharmacokinetic coverage of exposures to HIV infection. Complexities around safety, tolerability, and starting/stopping protocols require careful consideration. PMID:26633643

  15. Pharmacokinetics of oxytetracycline in goats: modifications induced by a long-acting formulation.

    PubMed

    Escudero, E; Carceles, C M; Serrano, J M

    1994-12-03

    The pharmacokinetics of oxytetracycline were studied in goats, after the intravenous and intramuscular injection of a conventional and long-acting formulation. The antibiotic was distributed according to an open two-compartment model. The apparent volume of distribution (Vz) and the central compartment volume (Vc) were 1.443 litres/kg and 0.453 litre/kg, respectively, and the total body clearance was 0.156 litre/kg/hour. The mean half-lives (T1/2 lambda z) of the conventional formulation after intravenous and intramuscular administration were six hours 28 minutes and 10 hours 38 minutes, respectively, whereas the long-acting formulation had half-lives of six hours 36 seconds and 29 hours, respectively, after intravenous and intramuscular injection. From the results of these single administrations two intramuscular dosage regimens can be proposed that achieve minimum concentrations of over 0.5 mg/litre (the minimum inhibitory concentration for most susceptible pathogens): with the conventional formulation by administering an initial dose of 10 mg/kg and a maintenance dose of 8.5 mg/kg every 24 hours, and with the long-acting formulation by administering an initial dose of 20 mg/kg and a maintenance dose of 14 mg/kg every 48 hours.

  16. A case of suicide attempt with long-acting methylphenidate (Concerta).

    PubMed

    Ozdemir, Esra; Karaman, Mehmet Goksin; Yurteri, Nihal; Erdogan, Ayten

    2010-11-01

    The prescribed use of methylphenidate in the treatment of attention deficit hyperactivity disorder (ADHD) is widespread. The intranasal and parenteral abuse of methylphenidate (Ritalin) among teenagers is becoming increasingly more common, and deaths have been reported. Newer medical treatment options of long-acting stimulants offer effective treatment with a lower risk of abuse potential. We describe a case of a 17-year-old girl who had attempted suicide by ingesting 270 mg of Concerta. During the third years of treatment with Concerta, parents of patient reported that the patient had a depressive mood in the last week, and had attempted suicide with five tablets of Concerta 54 mg. She was sent to a local hospital with a diagnosis of long-acting methylphenidate overdose. All of vital and laboratory findings were normal except heart rate, which was 132 beats/min. Since more than 3 h have elapsed after the time of ingestion, activated charcoal administration was not carried out at the hospital. She was only observed for 12 h at the emergency department and later discharged from the hospital. While long-acting stimulants offer lower risk of abuse, their greater availability increases the likelihood of ingestion of this nature. Education of clinicians and families to be aware of this risk should reduce the frequency of this complication of treatment.

  17. Long-acting Injectable Risperidone Use in an 11-Years-Old Bipolar Child

    PubMed Central

    KARAKOÇ DEMİRKAYA, Sevcan; ZOROĞLU, Süleyman Salih

    2016-01-01

    Early-onset bipolar disorder is difficult for child psychiatrists in terms of both diagnosis and treatment. The proper diagnostic evaluation is negatively impacted by the atypical clinical manifestation and rapid cycling pattern of the disease, together with common comorbidity with attention-deficit hyperactivity disorder and anxiety disorder. In addition to poor insight, nonadherence to treatment, poor family coping skills, and insufficient child psychiatric inpatient units make clinicians unsuccessful in following up and treating such patients. Risperidone is a commonly used atypical antipsychotic it has been approved for the treatment of manic and mixed episodes of bipolar disorder even in 10–17-year-old patients, and it is commonly used. It has a long-acting injectable formulation. Studies on its long-acting form in younger children are limited. In this case presentation, the diagnostic procedure in an 11-year old child with bipolar disorder will be presented. Long-acting injectable risperidone use in the case of nonadherence to treatment and observed side effects will be discussed. PMID:28360814

  18. Factors associated with relapse in schizophrenia despite adherence to long-acting injectable antipsychotic therapy.

    PubMed

    Alphs, Larry; Nasrallah, Henry A; Bossie, Cynthia A; Fu, Dong-Jing; Gopal, Srihari; Hough, David; Turkoz, Ibrahim

    2016-07-01

    Many patients with schizophrenia will relapse despite uninterrupted antipsychotic (AP) long-acting therapy (LAT). This exploratory analysis examined variables associated with relapse despite ensured adherence to LAT. This was a post-hoc exploratory analysis of a 1-year study of risperidone long-acting injection in patients with stable schizophrenia or schizoaffective disorder (NCT00297388; N=323). Patients were discontinued from previous oral APs and randomly assigned to biweekly intramuscular injections of risperidone long-acting injectable 50 (n=163) or 25 mg (n=161) for 52 weeks. Cox proportional hazards regression models examined variables putatively associated with relapse. A total of 59/323 (18.3%) patients relapsed over 12 months despite continuous AP LAT. Variables associated with the risk of relapse included illness duration (6.0% increase each year; P=0.0003) and country (Canada vs. USA, 4.7-fold risk increase; P=0.0008). When illness duration was further categorized as ≤5, 6-10, and >10 years, patients with an illness duration of >10 versus ≤5 years were at greatest risk of relapse (>10 vs. ≤5 years associated with a 4.4-fold increase in the risk of relapse; P=0.0181). Findings suggest that patients with more chronic illness have a greater risk of relapse despite ensured treatment adherence, supporting the need for early intervention to prevent the deleterious effects of chronicity.

  19. Long-acting Injectable Risperidone Use in an 11-Years-Old Bipolar Child.

    PubMed

    Karakoç Demirkaya, Sevcan; Zoroğlu, Süleyman Salih

    2016-12-01

    Early-onset bipolar disorder is difficult for child psychiatrists in terms of both diagnosis and treatment. The proper diagnostic evaluation is negatively impacted by the atypical clinical manifestation and rapid cycling pattern of the disease, together with common comorbidity with attention-deficit hyperactivity disorder and anxiety disorder. In addition to poor insight, nonadherence to treatment, poor family coping skills, and insufficient child psychiatric inpatient units make clinicians unsuccessful in following up and treating such patients. Risperidone is a commonly used atypical antipsychotic it has been approved for the treatment of manic and mixed episodes of bipolar disorder even in 10-17-year-old patients, and it is commonly used. It has a long-acting injectable formulation. Studies on its long-acting form in younger children are limited. In this case presentation, the diagnostic procedure in an 11-year old child with bipolar disorder will be presented. Long-acting injectable risperidone use in the case of nonadherence to treatment and observed side effects will be discussed.

  20. A clinical trial of long-acting local anesthetics for periodontal surgery.

    PubMed Central

    Crout, R. J.; Koraido, G.; Moore, P. A.

    1990-01-01

    The efficacy of long-acting local anesthetics for anesthesia during periodontal surgery and for analgesia during the immediate postoperative period was evaluated. The rationale for using long-acting local anesthetics such as etidocaine and bupivacaine is that they can provide surgical anesthesia and, because of their long duration, prevent discomfort that may occur for 4-6 hours postoperatively. Two clinical trials were performed. The first enrolled patients requiring bilateral periodontal surgery. Using a matched pair design and double-blind randomized study conditions, 2% lidocaine 1/100,000 epinephrine was compared with 1.5% etidocaine 1/200,000 epinephrine for periodontal surgery. The time until complete recovery and the time until pain onset were found to be longer for the etidocaine surgeries. Postoperative pain appeared more severe, and the need for oral analgesics was greater for the lidocaine surgeries. Surgeons' rating of surgical bleeding was significantly greater for the etidocaine procedures. When matched bilateral surgeries were not available, a second double-blind randomized parallel trial was performed that compared 1.5% etidocaine 1/200,000 epinephrine to 0.5% bupivacaine 1/200,000 epinephrine. No significant differences were seen in the quality of anesthesia, degree of bleeding, or postoperative pain between these two long-acting anesthetics. PMID:2096742

  1. A prospective study on the role of octreotide in management of chyle fistula neck.

    PubMed

    Jain, Avani; Singh, Shashank Nath; Singhal, Pawan; Sharma, Man Prakash; Grover, Mohnish

    2015-07-01

    To study the effectiveness of octreotide in managing chyle fistula neck and its effect on duration of hospitalization. Prospective study. A total of 19 patients with chyle fistula following neck dissection over a period of 10 years were included in the study. All the patients first underwent conservative management of the chyle leak, including suction drainage, pressure dressings, bed rest, and nutritional modifications. In all of the cases, chyle leak persisted despite conservative management. Octreotide was started in a dose of 100 µg subcutaneously every 8 hours for 5 days in cases with low-output leaks and for 7 days in cases with high-output leaks. In all of the cases, the duration of chyle leak after starting treatment with octreotide and the duration of hospitalization was recorded. Chyle leak stopped in all the cases using octreotide. The mean duration of hospitalization was 13.8 days. Chyle leak stopped within 5 days of starting octreotide in the low-output cases and within 7 days in the high-output cases. This permitted early resumption of a regular oral diet and reduced morbidity associated with chyle fistula. The rapid response and minimal side effect profile make octreotide a promising addition to the medical management of a chyle fistula. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  2. Budget Impact of Long-Acting Insulin Analogues: The Case in Brazil

    PubMed Central

    da Silva, Everton Nunes; Pereira, Maurício G

    2016-01-01

    Background Long-acting insulin analogues for type 1 diabetes (T1D) treatment have been available on the Brazilian market since 2002. However, the population cannot access the analogues through the public health system. Objective To estimate the incremental budget impact of long-acting insulin analogues coverage for T1D patients in the Brazilian public health system compared to NPH insulin. Methods We performed a budget impact analysis of a five-year period. The eligible population was projected using epidemiological data from the International Diabetes Federation estimates for patients between 0–14 and 20–79 years old. The prevalence of T1D was estimated in children, and the same proportion was applied to the 15-19-year-old group due to a gap in epidemiological information. We considered 4,944 new cases per year and a 34.61/100,000 inhabitants mortality rate. Market share for long-acting insulin analogues was assumed as 20% in the first year, reaching 40% in the fifth year. The mean daily dose was taken from clinical trials. We calculated the bargaining power of the Ministry of Health by dividing the price paid for human insulin in the last purchase by the average regulated price. We performed univariate and multivariate sensitivity analyses. Results The incremental budget impact of long-acting insulin analogues was US$ 28.6 million in the first year, and reached US$ 58.7 million in the fifth year. The total incremental budget impact was US$ 217.9 million over the five-year period. The sensitivity analysis showed that the percentage of T1D among diabetic adults and the insulin analogue price were the main factors that affected the budget impact. Conclusions The cost of the first year of long-acting insulin analogue coverage would correspond to 0.03% of total public health expenditure. The main advantage of this study is that it identifies potential bargaining power because it features more realistic profiles of resource usage, once centralized purchasing is

  3. Budget Impact of Long-Acting Insulin Analogues: The Case in Brazil.

    PubMed

    Laranjeira, Fernanda O; Silva, Everton Nunes da; Pereira, Maurício G

    2016-01-01

    Long-acting insulin analogues for type 1 diabetes (T1D) treatment have been available on the Brazilian market since 2002. However, the population cannot access the analogues through the public health system. To estimate the incremental budget impact of long-acting insulin analogues coverage for T1D patients in the Brazilian public health system compared to NPH insulin. We performed a budget impact analysis of a five-year period. The eligible population was projected using epidemiological data from the International Diabetes Federation estimates for patients between 0-14 and 20-79 years old. The prevalence of T1D was estimated in children, and the same proportion was applied to the 15-19-year-old group due to a gap in epidemiological information. We considered 4,944 new cases per year and a 34.61/100,000 inhabitants mortality rate. Market share for long-acting insulin analogues was assumed as 20% in the first year, reaching 40% in the fifth year. The mean daily dose was taken from clinical trials. We calculated the bargaining power of the Ministry of Health by dividing the price paid for human insulin in the last purchase by the average regulated price. We performed univariate and multivariate sensitivity analyses. The incremental budget impact of long-acting insulin analogues was US$ 28.6 million in the first year, and reached US$ 58.7 million in the fifth year. The total incremental budget impact was US$ 217.9 million over the five-year period. The sensitivity analysis showed that the percentage of T1D among diabetic adults and the insulin analogue price were the main factors that affected the budget impact. The cost of the first year of long-acting insulin analogue coverage would correspond to 0.03% of total public health expenditure. The main advantage of this study is that it identifies potential bargaining power because it features more realistic profiles of resource usage, once centralized purchasing is established as an economically sustainable strategy

  4. Self-assembled platinum nanochains based on octreotide acetate

    NASA Astrophysics Data System (ADS)

    Zhao, Xiaoning; Gao, Dawei; Gao, Faming; Li, Na; Zhou, Jing; Hao, Jikui

    2013-09-01

    Biological scaffolds are used for the synthesis of inorganic materials due to their ability to self-assemble and nucleate crystal formation. We reported a facile method for preparing self-assembled Pt nanochains by using octreotide acetate (AOC) as bio-template in aqueous environment. The influence of solution pH was examined to define the optimal conditions for the formation of the AOC bio-templated Pt nanoparticles (PtNPs) arrays, the AOC has diameter about 55 nm at pH 2.0, for comparison, at pH 9.0, the diameter of AOC is about 25 nm. After 24-h incubation of AOC (pH 2.0) with PtCl4 and chemical reduction with borane-dimethyl-amine, uniform platinum nanoparticles (mean diameter 2.5 ± 0.5 nm) directed by AOC were formed. Preliminary characterizations of the synthesized PtNPs were performed using transmission electron microscopy, high-resolution transmission electron microscopy, energy dispersive spectroscopy, and selected area of electron diffraction. The cytotoxicity of Pt/octreotide acetate complexes (PtNPs-AOC) and AOC was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The results indicated that the antiproliferative effect of PtNPs-AOC is as high as AOC. In addition, the nano-design architecture of the Pt particles plays a crucial role in a strong enhancement of the biological efficiency of radiations, making PtNPs-AOC a promising material for anticancer drug delivery in the future.

  5. Bevacizumab plus octreotide and metronomic capecitabine in patients with metastatic well-to-moderately differentiated neuroendocrine tumors: the xelbevoct study

    PubMed Central

    2014-01-01

    Background We assessed the activity and toxicity of the XELBEVOCT regimen in patients with metastatic well-to-moderately differentiated neuroendocrine neoplasms (WMD-NEN). Ancillary studies evaluated hypertension, proteinuria, and vascular endothelial growth factor (VEGF) polymorphisms in predicting progression-free survival (PFS) and the predictive role of serum vitamin D in progression-free survival and proteinuria onset. Methods This prospective phase 2 study included 45 patients with WMD-NEN arising from various primary sites. The treatment regimen was octreotide long-acting release (LAR), 20 mg monthly, metronomic capecitabine, 2000 mg/daily, and intravenous bevacizumab, 5 mg/kg every 2 weeks, without interruption for 9 months. Bevacizumab was continued until disease progression. Results Partial response was obtained in 8 patients (17.8%, 95% confidence interval [CI], 6.4%-28.2%); tumor response was more frequent in pancreatic than in non-pancreatic malignancies. The median PFS was 14.9 months; median overall survival was not attained. Biochemical and symptomatic responses were observed in 52.9% and 82.3% of cases, respectively. The treatment was well tolerated. Grade 3 toxicities included hand and foot syndrome (11.1%), proteinuria (4.4%), and renal toxicity (2.2%). Proteinuria (all grades) was correlated with longer PFS (p = 0.017). There was an inverse relationship between proteinuria and vitamin D levels. VEGF polymorphisms were not associated with patient outcome. Conclusion The XELBEVOCT regimen is active and well tolerated in patients with metastatic WMD-NEN. Proteinuria correlated with hypovitaminosis D status and was the best predictive factor of treatment efficacy. Trial registration Trial registration number NCT01203306. PMID:24628963

  6. Cross-sectional comparison of first-generation antipsychotic long-acting injections vs risperidone long-acting injection: patient-rated attitudes, satisfaction and tolerability

    PubMed Central

    Singh, Sourabh Moti; Haddad, Peter M.; Husain, Nusrat; Heaney, Eamonn; Tomenson, Barbara; Chaudhry, Imran B.

    2016-01-01

    Objectives: The objective of this study was to compare patients’ attitudes and satisfaction with medication and patient-rated tolerability between those prescribed a first-generation antipsychotic long-acting injection (FGA-LAI) and those prescribed risperidone long-acting injection (RLAI). Method: A cross-sectional study of a representative sample of outpatients prescribed an FGA-LAI or RLAI for a minimum of 6 months and attending a depot clinic. Attitudes to medication were assessed by the Drug Attitude Inventory (DAI-30), tolerability was measured by the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS) and satisfaction with antipsychotic medication was assessed by the Satisfaction with Antipsychotic Medication (SWAM) scale. Results: The RLAI (n = 28) and FGA-LAI (n = 39) groups did not differ in terms of mean age, sex, diagnosis and ethnicity. All individual LAIs were prescribed within British National Formulary limits. The most commonly prescribed FGA-LAI was flupentixol decanoate (n = 22). There was no significant difference between the RLAI and FGA-LAI groups in terms of mean total scores on the DAI-30, LUNSERS and SWAM or the tolerability subscales of the LUNSERS or the two subscales (treatment acceptability and medication insight) of the SWAM. In both LAI groups there was a low level of side effects (LUNSERS) and a generally positive attitude (DAI-30) and reasonable satisfaction (SWAM) with medication. Conclusions: Patients treated with FGA-LAI and RLAI for at least 6 months did not differ in terms of patient-rated tolerability, attitudes and satisfaction with medication. The current design cannot determine whether differences would have been evident earlier on during treatment. These results should be regarded as preliminary and are subject to prescribing bias. Randomized studies avoid prescribing bias and are a superior way to compare specific LAIs. Ideally randomized studies should include patient-rated outcome measures including

  7. Comparative efficacy of fixed-dose combinations of long-acting muscarinic antagonists and long-acting β2-agonists: a systematic review and network meta-analysis.

    PubMed

    Schlueter, Max; Gonzalez-Rojas, N; Baldwin, Michael; Groenke, Lars; Voss, Florian; Reason, Tim

    2016-04-01

    A number of long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) fixed-dose combinations (FDCs) for treatment of moderate-to-very severe chronic obstructive pulmonary disease (COPD) have recently become available, but none have been directly compared in head-to-head randomized controlled trials (RCTs). The purpose of this study was to assess the relative clinical benefit of all currently available LAMA/LABA FDCs using a Bayesian network meta-analysis (NMA). A systematic literature review identified RCTs investigating the efficacy, safety and quality of life associated with licensed LAMA/LABA FDCs for the treatment of moderate-to-very severe COPD. RCTs were screened for inclusion in the NMA using prespecified eligibility criteria. Data were extracted for outcomes of interest, including change in trough forced expiratory volume in 1 second (tFEV1) from baseline, St. George Respiratory Questionnaire (SGRQ) percentage of responders, Transition Dyspnea Index (TDI) percentage of responders, change in SGRQ score from baseline, change in TDI focal score from baseline, moderate-to-severe exacerbations, all-cause discontinuation, and discontinuation due to adverse events. Following screening, a total of 27 trials from 26 publications with 30,361 subjects were eligible for inclusion in the NMA. Nonsignificant results were seen in most analyses comparing efficacy, exacerbations and discontinuation rates of included LAMA/LABA FDCs (i.e. aclidinium/formoterol 400/12 µg, glycopyrronium/indacaterol 110/50 µg, tiotropium + olodaterol 5/5 µg, umeclidinium/vilanterol 62.5/25 µg). Meta-regression controlling for post-bronchodilator percentage of tFEV1 predicted at baseline as well as meta-regression adjusting for concomitant use of inhaled corticosteroids at baseline was performed to assess the magnitude of effect modification and produced similar results as observed in the base case analysis. All LAMA/LABA FDCs were found to have similar efficacy and safety

  8. Demand for long acting and permanent contraceptive methods and associated factors among family planning service users, Batu town, Central Ethiopia.

    PubMed

    Haile, Anley; Fantahun, Mesganaw

    2012-01-01

    Evidence suggests a high unsatisfied demand for long acting and permanent contraceptive methods in sub-Saharan Africa. However, there is limited knowledge on demand for long acting and permanent contraceptive methods and associated factors in Ethiopia. The objective of this study was to assess demand for long acting and permanent contraceptive methods and associated factors among women of age group 18-49 years in Batu town, East Shoa Zone, Ethiopia. A facility based cross-sectional survey was conducted in six service delivery points from March to April 2009 on 398 women of age 18-49 years old. Thirteen (3%) were using long acting and permanent contraceptive methods and 89 (22.4%) wanted no more child in the future making the total demand of long acting and permanent contraceptive methods 24.4%. Older age group, multiparty, that the provider asked about reproductive intention, and the provider explained side effects of method selected were significantly associated with using LA and MPs (P < 0.05). There is high total demand and several socio demographic and family planning service quality related factors were associated with demand for long acting and permanent contraceptive methods indicating that multi-dimensional measures are needed to improve the use of long acting and permanent contraceptive methods.

  9. Long-acting muscarinic antagonists vs. long-acting β 2 agonists in COPD exacerbations: a systematic review and meta-analysis.

    PubMed

    Maia, Israel Silva; Pincelli, Mariângela Pimentel; Leite, Victor Figueiredo; Amadera, João; Buehler, Anna Maria

    2017-07-31

    To determine whether long-acting muscarinic antagonists (LAMAs) provide superior therapeutic effects over long-acting β2 agonists (LABAs) for preventing COPD exacerbations. This was a systematic review and meta-analysis of randomized clinical trials involving patients with stable, moderate to severe COPD according to the Global Initiative for Chronic Obstructive Lung Disease criteria, treated with a LAMA (i.e., tiotropium bromide, aclidinium, or glycopyrronium), followed for at least 12 weeks and compared with controls using a LABA in isolation or in combination with a corticosteroid. A total of 2,622 studies were analyzed for possible inclusion on the basis of their title and abstract; 9 studies (17,120 participants) were included in the analysis. In comparison with LABAs, LAMAs led to a greater decrease in the exacerbation rate ratio (relative risk [RR] = 0.88; 95% CI: 0.84-0.93]; a lower proportion of patients who experienced at least one exacerbation (RR = 0.90; 95% CI: 0.87-0.94; p < 0.00001); a lower risk of exacerbation-related hospitalizations (RR = 0.78; 95% CI: 0.69-0.87; p < 0.0001); and a lower number of serious adverse events (RR = 0.81; 95% CI: 0.67-0.96; p = 0.0002). The overall quality of evidence was moderate for all outcomes. The major findings of this systematic review and meta-analysis were that LAMAs significantly reduced the exacerbation rate (exacerbation episodes/year), as well as the number of exacerbation episodes, of hospitalizations, and of serious adverse events. Determinar se long-acting muscarinic antagonists (LAMAs, antagonistas muscarínicos de longa duração) são superiores a long-acting β2 agonists (LABAs, β2-agonistas de longa duração) na prevenção de exacerbações da DPOC. Revisão sistemática e meta-análise de ensaios clínicos controlados aleatórios com pacientes com DPOC estável, de moderada a grave, conforme os critérios da Global Initiative for Chronic Obstructive Lung Disease, tratados com LAMA (brometo de

  10. Pregnancy Intentions, Long-Acting Contraceptive Use, and Rapid Subsequent Pregnancies among Adolescent and Adult First-Time Mothers

    PubMed Central

    Waggoner, Miranda R.; Lanzi, Robin Gaines; Klerman, Lorraine V.

    2012-01-01

    Problem Greater understanding is needed related to qualitatively-assessed pregnancy intentions and rapid subsequent pregnancies among adolescent and adult mothers. Methods 4-site prospective study of 227 adolescent and adult mothers. Data analyzed to understand the relationship between pregnancy intentions, adolescent status, and use of long-acting contraceptives and rapid subsequent pregnancy. Findings The findings from this study provide evidence of the importance of goal-oriented pregnancy intentions, long-acting contraceptive use, and older age in delaying a second pregnancy. Conclusion Findings reveal the need for clinician awareness of the qualitative pregnancy intentions of young women and potential desired use of long-acting contraceptives. PMID:22512527

  11. Pregnancy intentions, long-acting contraceptive use, and rapid subsequent pregnancies among adolescent and adult first-time mothers.

    PubMed

    Waggoner, Miranda R; Lanzi, Robin Gaines; Klerman, Lorraine V

    2012-05-01

    Greater understanding is needed related to qualitatively assess pregnancy intentions and rapid subsequent pregnancies among adolescent and adult mothers. Four-site prospective study of 227 adolescent and adult mothers. Data were analyzed to understand the relationship between pregnancy intentions, adolescent status, and use of long-acting contraceptives and rapid subsequent pregnancy. The findings from this study provide evidence of the importance of goal-oriented pregnancy intentions, long-acting contraceptive use, and older age in delaying a second pregnancy. Findings reveal the need for clinician awareness of the qualitative pregnancy intentions of young women and potential desired use of long-acting contraceptives. © 2012 Wiley Periodicals, Inc.

  12. Long-acting injectable aripiprazole: how might it fit in our tool box?

    PubMed

    Gopalakrishna, Ganesh; Aggarwal, Arpit; Lauriello, John

    2013-01-01

    Schizophrenia is a severe mental illness with a lifetime prevalence of approximately one percent worldwide. Maintenance antipsychotic treatment has been effective in preventing relapses in long-term follow-up studies. Logically it can be proposed that long-acting injectable antipsychotics (LAI) might reduce both unintentional and intentional nonadherence. Long-acting injectable aripiprazole was approved for the treatment of schizophrenia by the U.S. FDA on 28th February 2013 and will be marketed under the name Abilify Maintena. Aripiprazole LAI (ALAI) is a lyophilized powder that needs to be reconstituted with sterile water to form an injectable suspension without affecting the original molecule. The monthly injection interval is very attractive since patients prefer fewer injections. From a tolerability perspective, ALAI appears to be both weight neutral and lacking metabolic side effects. This can confer an advantage over the other currently available second-generation antipsychotic LAIs. Simple constitution with sterile water and no requirement to refrigerate make storage and administration easier. Like all medications, there are always potential disadvantages to ALAI. There is a period of oral coverage, while not as long as for long-acting risperidone microspheres (RLAI), that is required. Care must be taken to review concomitant medications for the presence of metabolic inducers and inhibitors. One would also expect some patients to be sensitive to extrapyramidal symptoms, especially akathisia which is well documented in the oral preparation. All things considered, we welcome our new tool, ALAI, to our work-place and predict both clinical practice and post marketing analysis and studies will discover its true value.

  13. Two unusual cases of intractable hyperthyroidism responsive to octreotide: Munchausen syndrome or not?

    PubMed

    Liu, Jian-Min; Gu, Li-Qun; Zhao, Lin; Tang, Zheng-Yi; Sun, Li-Hao; Hong, Jie; Wang, Wei-Qing; Luo, Bang-Yao; Zhao, Yong-Ju; Xu, Man-Yin; Chen, Xi; Jiang, Xu-Feng; Zhu, Chen-Mo; Jin, Xiao-Long; Chen, Hong-Zhuan; Tan, Yu-Yan; Ning, Guang; Chen, Jia-Lun

    2011-05-12

    The effective treatment for patients with resistant hyperthyroidism is difficult. In this case report with 4-year follow-up data, we present 2 unusual cases of hyperthyroidism that were unresponsive to almost all antithyroid treatments including total thyroidectomy, but both were controlled with octreotide. Cases 1 and 2 were both middle-aged women. They presented thyrotoxicosis with a low serum concentration of TSH and thyroidal radioactive iodine uptake (RAIU). The underlying causes, such as thyroiditis, metastatic thyroid cancer and struma ovarii were explored. Iodine-induced hyperthyroidism, particularly factitious hyperthyroidism was highly suspected, but there was no direct evidence to establish these diagnoses. In spite of good compliance, their thyrotoxicosis could not be controlled with large doses of PTU or MMI. β-blocker, methylprednisolone, radio-iodine therapy and even thyroidectomy were all attempted and failed. Short-acting octreotide was first administered to case 1 and then to case 2. Thyroid function improved greatly within 3 days in both cases. The doses of octreotide were tapered down to twice a week with consistent efficacy. During the follow-up periods, case 1 required octreotide 0.1mg twice per week and case 2 is on thyroid replacement therapy due to hypothyroidism. The recurrences of hyperthyroidism in both cases were again rapidly controlled with the increased dose of octreotide in case 1 and re-started the usage of octreotide in case 2. The etiology of thyrotoxicosis in these 2 cases is not clear. In the absence of struma ovarii or wide-spread follicular thyroid cancer, factitious hyperthyroidism due to Munchausen syndrome should be considered first. The efficacy of the off-label use of octreotide in hyperthyroidism was highly effective (only) in these 2 cases. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Effect of Octreotide on Enteric Motor Neurons in Experimental Acute Necrotizing Pancreatitis

    PubMed Central

    Zou, Duowu; Wu, Wenbin; Li, Zhaoshen

    2012-01-01

    Background/Aims Amelioration of intestinal dysmotility and stasis during the early period of acute necrotizing pancreatitis (ANP) appears to be important to reduce the risks of secondary pancreatic infection. We aimed to characterize the association between the neuropathy of the enteric nervous system and gut dysfunction and to examine the effect of octreotide on motor innervation in the early stage of ANP. Methodology/Principal Findings The rats were randomly divided into eight groups: control+saline; control+octreotide; ANP+saline and ANP+octreotide (24 h, 48 h, 72 h). The spontaneous activity of ileal segments and the response to ACh, l-NNA were recorded. The alterations of myenteric neuronal nitric oxide synthase (nNOS), choline acetyltransferase (CHAT), PGP9.5 and somatostatin receptor 2 (SSTR2) immunoreactive cells were evaluated by immunofluorescence and the protein expression of nNOS and CHAT were evaluated by western blot. We found the amplitude of spontaneous contractions at 48 h and the response to ACh at 24 h declined in the ANP+saline rats. A higher contractile response to both ACh and to l-NNA was observed in the ANP+octreotide group, compared with the ANP+saline rats at 24 h. A significant reduction in the nNOS and cholinergic neurons was observed in ANP+saline rats at the three time points. However, this reduction was greatly ameliorated in the presence of octreotide at 24 h and 48 h. The protein expression of CHAT neurons at 24 h and the nNOS neurons at 48 h in the ANP+octreotide rats was much higher than the ANP+saline rats. Conclusion The pathogenesis of ileus in the early stage of ANP may be related to the neuropathy of the enteric nervous system. Octreotide may reduce the severity of ileus by lessening the damage to enteric motor innervation. PMID:23300603

  15. Cost-effectiveness comparison of prophylactic octreotide and pasireotide for prevention of fistula after pancreatic surgery.

    PubMed

    Welsch, Thilo; Müssle, Benjamin; Distler, Marius; Knoth, Holger; Weitz, Jürgen; Häckl, Dennis

    2016-11-01

    Postoperative pancreatic fistula (POPF) is a major determinant of pancreatic surgery outcome, and prevention of POPF is a relevant clinical challenge. The aim of the present study is to compare the cost-effectiveness of octreotide and pasireotide for POPF prophylaxis. A systematic literature review and meta-analysis and a retrospective patient cohort provided the data. Cost-effectiveness was calculated by the incremental cost-effectiveness ratio (ICER) and by decision tree modelling of hospital stay duration. Six randomised trials on octreotide (1255 patients) and one trial on pasireotide (300 patients) were included. The median POPF incidence without prophylaxis was 19.6 %. The relative risks for POPF after octreotide or pasireotide prophylaxis were 0.54 or 0.45. Octreotide prophylaxis (21 × 0.1 mg) costs were 249.69 Euro, compared with 728.84 Euro for pasireotide (14 × 0.9 mg) resulting in an ICER of 266.19 Euro for an additional 1.8 % risk reduction with pasireotide. Decision tree modelling revealed no significant reduction of median hospital stay duration if pasireotide was used instead of octreotide. Prophylactic octreotide is almost as effective as pasireotide but incurs significantly fewer drug costs per case. However, the data quality is limited, because the effect of octreotide on clinically relevant POPF is unclear. Together with the lack of multicentric data on pasireotide and its effectiveness, a current off-label use of pasireotide does not appear to be justified.

  16. The role of inhaled long-acting beta-2 agonists in the management of asthma.

    PubMed Central

    Kelly, H. William; Harkins, Michelle S.; Boushey, Homer

    2006-01-01

    The role of inhaled beta-2 agonists in the management of asthma has changed significantly over the last several years. This review outlines the most recent understanding of the pathophysiology of asthma and the studies that define the roles that both short- and long-acting beta-2 agonists play in therapy for this disease. A concentration on the clinical pharmacology and genetic implications for clinical use of this class of drugs in accordance with the national and international guidelines are described. PMID:16532973

  17. Prevention of unintended pregnancy: a focus on long-acting reversible contraception.

    PubMed

    Pickle, Sarah; Wu, Justine; Burbank-Schmitt, Edith

    2014-06-01

    This article summarizes the literature regarding the epidemiology and prevention of unintended pregnancy in the United States. Because of the Affordable Care Act and its accompanying contraceptive provision, there is a need for more primary care clinicians to provide family planning services. Office-based interventions to incorporate family planning services in primary care are presented, including clinical tools and electronic health record use. Special attention is paid to long-acting reversible contraceptive methods (the subdermal implant and intrauterine devices); these highly effective and safe methods have the greatest potential to decrease the rate of unintended pregnancy, but have been underused.

  18. Long-Acting Reversible Contraception: An Essential Guide for Pediatric Primary Care Providers.

    PubMed

    Allen, Suzanne; Barlow, Erin

    2017-04-01

    Long-acting reversible contraception (LARC) methods are 20% more effective than traditional contraceptives and are recommended by the American Academy of Pediatrics and American College of Obstetrics and Gynecology as first-line contraception for adolescent girls. Large studies show that LARC use reduces unintended pregnancies, increases user satisfaction, and prolongs duration of use. This article prepares the primary care provider (PCP) with knowledge on safety, efficacy, eligibility, confidentiality, anticipatory guidance, how to find a LARC provider, and guidance on common side effects so the PCP can confidently counsel adolescent patients on LARC methods.

  19. Therapeutic Options for Unscheduled Bleeding Associated with Long-Acting Reversible Contraception.

    PubMed

    Friedlander, EmmaKate; Kaneshiro, Bliss

    2015-12-01

    Long-acting reversible contraception (LARC) is the most effective form of reversible contraception. Although most women are satisfied with LARC methods, unscheduled bleeding and spotting are common reasons for method dissatisfaction and discontinuation. This systematic analysis of the current literature delineates treatment options for unscheduled bleeding related to LARC use. Although consistent results are lacking, all devices seem to have the best response to nonsteroidal antiinflammatory drugs for 5 to 7 days or the antifibrinolytic agent tranexamic acid. Additional studies are necessary to identify improved treatment interventions for unscheduled bleeding with LARC use.

  20. [Guidelines on long-acting injectable atypical antipsychotics for first-episode schizophrenia].

    PubMed

    Azorin, J-M

    2013-09-01

    The current review raises the question of the place of long-acting injectable (LAI) atypical antipsychotics for the treatment of first-episode schizophrenia in current and future guidelines. After exposing the different points of view adopted in the former, the author presents the clinical trials conducted with LAI atypicals in this indication, as well as the surveys related to psychiatrists'opinion regarding the use of these drugs in early schizophrenia. Pros and cons of this therapeutic option are discussed and suggestions are made for further guidelines.

  1. A review of the effects of long-acting progestogen-only contraceptives on ovarian activity.

    PubMed

    Li, X F; Davies, G C; Newton, J

    1992-03-01

    Progestogen-only contraception acts mainly by blocking cervical mucus and preventing sperm penetration through it does have a variable pattern of contraceptive effects on the endometrium and ovary. In contrast with the complete suppression of ovarian function with combined pill or injectable use, a variable degree of endocrine activity is demonstrated in women choosing a long-acting progestogen-only contraceptive. This degree of suppression of ovarian activity explains the decrease in systemic side-effects, the rapid resumption of ovulation and recovery of fertility following the discontinuation of the method. New delivery systems of progestogens, the vaginal ring and implant, offer better and more consistent contraceptive effects.

  2. Permeation enhancement of octreotide by specific bile salts in rats and human subjects: in vitro, in vivo correlations.

    PubMed Central

    Fricker, G.; Fahr, A.; Beglinger, C.; Kissel, T.; Reiter, G.; Drewe, J.

    1996-01-01

    1. The potential of bile salts to improve the enteral absorption of octreotide, an orally active somatostatin analogue, was investigated by a combination of in vitro, in situ and in vivo experiments. 2. Incorporation of octreotide into lipid monolayers (as measured by area increase of the monolayer at constant surface pressure using a Langmuir-Blodgett trough set-up) depended on the type of bile salt used for monolayer pre-treatment. Addition of 20 microM octreotide to the subphase containing 20 microM of the dihydroxylated bile salt ursodeoxycholate (UDCA) causes a 9% increase in area, whereas addition of octreotide to the subphase containing the 7 alpha-enantiomer of UDCA, chenodeoxycholate (CDCA), resulted in an area increase of the lipid monolayer of 20%. Area increase by octreotide alone was not significantly different from the increase of octreotide and UDCA in combination. 3. CDCA and UDCA in combination with octreotide increased the permeability of liposomal membranes for rubidium ions, whereas octreotide alone did not significantly change the permeability. This indicates membrane distortion as a possible cause for the enhanced absorption of octreotide by bile salts. 4. In polarized Caco-2 cell monolayers octreotide exhibited a permeation coefficient of 0.008 +/- 0.004 cm h-1. Addition of 0.2-1% of UDCA to the apical incubation medium had no significant effect upon the permeation coefficient. In contrast, 0.2-1% CDCA in the incubation medium resulted in a significant increase (P < 0.05) of the monolayer permeability of octreotide (0.015-0.037 cm h-1). 5. Octreotide was absorbed as the intact peptide from the gastrointestinal tract in rats with an absorption efficiency of 0.26%. Coadministration of bile salt resulted in a dose-dependent increase in absorption efficiency of the peptide up to 20.2%. The observed effect was more pronounced for CDCA than for UDCA. 6. The effect of CDCA and UDCA on octreotide absorption in vivo was assessed in a pharmacokinetic

  3. In vitro and in vivo evaluation of an in situ gel forming system for the delivery of PEGylated octreotide.

    PubMed

    Erfani Jabarian, Laleh; Rouini, Mohammad Reza; Atyabi, Fatemeh; Foroumadi, Alireza; Nassiri, Seyed Mahdi; Dinarvand, Rassoul

    2013-01-23

    The objective of this study was to develop a controlled delivery system for PEGylated octreotide using a Poloxamer based in situ gel forming polymer. PEGylated octreotide kept its full biological activity and higher serum half-life compared to the original octreotide. The designed drug delivery system contained low concentration of Poloxamer 407 (P407) (<0.16%) with polyvinyl alcohol (PVA) as a polymeric additive. Rheological measurements of gel vehicle formulations indicated that the in situ gel forming system with optimum sol-gel transition temperature of 28.7°C could be formed using a combination of P407 and PVA at ratio of 15-10% (w/v). The effect of formulation additives such as buffering agents on rheological behavior demonstrated that sodium bicarbonate and lactic acid have opposite effect on sol-gel transition temperature of the system. Using buffering agents, it was possible to shift the sol-gel transition to lower or higher temperatures. The in vitro release profiles of octreotide and PEGylated octreotide from the selected P407/PVA formulations were measured using a membrane-less device. PEGylated octreotide showed slower release rate from the gel system with different release kinetic compared to octreotide. In animal studies, a sustained release rate was achieved with both PEGylated and non-PEGylated octreotide, but longer delivery was observed for PEGylated octreotide. Tissue histopathological studies confirmed the biocompatibility of the delivery system for PEGylated octreotide, supporting the suitability of P407/PVA mixture as an injectable drug delivery system. The total effects of increasing PEGylated peptide half-life and prolonged release from thermoresponsive gel system offer the potential for sustained delivery of PEGylated octreotide.

  4. Effectiveness of long-acting risperidone in a patient with comorbid intellectual disability, catatonic schizophrenia, and oneiroid syndrome.

    PubMed

    Serata, Daniele; Rapinesi, Chiara; Kotzalidis, Georgios Demetrios; Alessi, Maria Chiara; Janiri, Delfina; Massolo, Anna Claudia; Ferri, Vittoria Rachele; Criscuolo, Silvia; Callovini, Gemma; Angeletti, Gloria; Girardi, Paolo; Del Casale, Antonio

    2015-01-01

    A patient with comorbid intellectual disability, catatonic schizophrenia, and recurrent oneiroid state of consciousness improved on long-acting risperidone and remains well at the three-year follow-up. We report a case treated with 50 mg long-acting risperidone administered every 14 days, who has been followed-up for three years. We studied his regional cerebral blood flow through technetium-99 m hexamethylpropyleneamine oxime single-photon emission computed tomography after two years of treatment. Symptoms of catatonic schizophrenia improved after two months of treatment, followed suit by oneiroid syndrome remission. Two years later, his brain perfusion was normal. No side effect has occurred since the patient was started on long-acting risperidone. Long-acting risperidone proved to be safe and effective in treating symptoms of catatonia and oneiroid syndrome. © The Author(s) 2015.

  5. Narcotic tapering in pregnancy using long-acting morphine: an 18-month prospective cohort study in northwestern Ontario.

    PubMed

    Dooley, Roisin; Dooley, Joe; Antone, Irwin; Guilfoyle, John; Gerber-Finn, Lianne; Kakekagumick, Kara; Cromarty, Helen; Hopman, Wilma; Muileboom, Jill; Brunton, Nicole; Kelly, Len

    2015-02-01

    To document the management of and outcomes for patients receiving narcotic replacement and tapering with long-acting morphine preparations during pregnancy. A prospective cohort study over 18 months. Northwestern Ontario. All 600 births at Meno Ya Win Health Centre in Sioux Lookout, Ont, from January 1, 2012, to June 30, 2013, including 166 narcotic-exposed pregnancies. Narcotic replacement and tapering of narcotic use with long-acting morphine preparations. Prenatal management of maternal narcotic use, incidence of neonatal abstinence syndrome, and other neonatal outcomes. The incidence of neonatal abstinence syndrome fell significantly to 18.1% of pregnancies exposed to narcotics (from 29.5% in a previous 2010 study, P = .003) among patients using narcotic replacement and tapering with long-acting morphine preparations. Neonatal outcomes were otherwise equivalent to those of the nonexposed pregnancies. In many patients, long-acting morphine preparations can be safely used and tapered in pregnancy, with a subsequent decrease in observed neonatal withdrawal symptoms.

  6. Aripiprazole once-monthly long-acting injectable for the treatment of schizophrenia.

    PubMed

    Potkin, Steven G; Preda, Adrian

    2016-01-01

    Patient non-adherence increases the risk for relapse and the long-term care of schizophrenia. Long-acting injectable (LAI) antipsychotics can decrease this risk by ensuring adherence. An extended formulation, aripiprazole 400 mg once-monthly (AOM 400) LAI (AOM LAI), received regulatory approval in the year 2013 for the treatment of schizophrenia. AOM LAI is the first dopamine D2 partial agonist available in a long-acting formulation for the treatment of schizophrenia. This review covers data on the efficacy and tolerability/safety of AOM LAI. AOM LAI is a lyophilized powder of aripiprazole, with an elimination half-life of 29.9 - 46.5 days, allowing for a 4-week injection interval. Antipsychotic efficacy was documented in a 12-week double-blind trial (n = 340) and in two maintenance-of-effect trials: a 38-week trial (n = 662) and a 52-week trial (n = 403). The side effect profile is similar to that of oral aripiprazole. Adverse events (≥5% and at least twice that for placebo) were typically mild or moderate and did not lead to discontinuation: increased weight, akathisia, injection site pain and sedation. The 400 mg dose is tolerated by >90% of patients. Injection does not require additional training of health personnel or post-injection observation. AOM LAI is an efficacious and well-tolerated antipsychotic treatment for schizophrenia.

  7. [Intravenous regional anesthesia with long-acting local anesthetics. An update].

    PubMed

    Atanassoff, P G; Lobato, A; Aguilar, J L

    2014-02-01

    Intravenous regional anesthesia is a widely used technique for brief surgical interventions, primarily on the upper limbs and less frequently, on the lower limbs. It began being used at the beginning of the 20th century, when Bier injected procaine as a local anesthetic. The technique to accomplish anesthesia has not changed much since then, although different drugs, particularly long-acting local anesthetics, such as ropivacaine and levobupivacaine in low concentrations, were introduced. Additionally, drugs like opioids, muscle relaxants, paracetamol, neostigmine, magnesium, ketamine, clonidine, and ketorolac, have all been investigated as adjuncts to intravenous regional anesthesia, and were found to be fairly useful in terms of an increased onset of operative anesthesia and longer lasting perioperative analgesia. The present article provides an overview of current knowledge with emphasis on long-acting local anesthetic drugs. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

  8. A long-acting GH receptor antagonist through fusion to GH binding protein

    PubMed Central

    Wilkinson, Ian R.; Pradhananga, Sarbendra L.; Speak, Rowena; Artymiuk, Peter J.; Sayers, Jon R.; Ross, Richard J.

    2016-01-01

    Acromegaly is a human disease of growth hormone (GH) excess with considerable morbidity and increased mortality. Somatostatin analogues are first line medical treatment but the disease remains uncontrolled in up to 40% of patients. GH receptor (GHR) antagonist therapy is more effective but requires frequent high-dose injections. We have developed an alternative technology for generating a long acting potent GHR antagonist through translational fusion of a mutated GH linked to GH binding protein and tested three candidate molecules. All molecules had the amino acid change (G120R), creating a competitive GHR antagonist and we tested the hypothesis that an amino acid change in the GH binding domain (W104A) would increase biological activity. All were antagonists in bioassays. In rats all antagonists had terminal half-lives >20 hours. After subcutaneous administration in rabbits one variant displayed a terminal half-life of 40.5 hours. A single subcutaneous injection of the same variant in rabbits resulted in a 14% fall in IGF-I over 7 days. In conclusion: we provide proof of concept that a fusion of GHR antagonist to its binding protein generates a long acting GHR antagonist and we confirmed that introducing the W104A amino acid change in the GH binding domain enhances antagonist activity. PMID:27731358

  9. Second-generation long-acting injectable antipsychotic agents: an overview.

    PubMed

    2012-09-01

    For over 40 years, antipsychotic drugs have been used as long-term maintenance treatment to control symptoms and reduce relapse rates in patients with schizophrenia. 'First-generation' oral agents such as haloperidol and chlorpromazine are associated with high levels of unwanted neurological effects and poor rates of patient adherence.1,2 Long-acting ('depot') injections of antipsychotics were developed to try to improve adherence. 'Second-generation' antipsychotic agents (also known as atypical antipsychotics) were introduced into clinical practice over 16 years ago. Although these agents have a lower propensity to cause extrapyramidal side effects, they are associated with a range of other unwanted effects (e.g. weight gain and its sequelae).1,3,4 Initially, second-generation agents were only available as orally administered medicines. Three long-acting injectable formulations of second-generation antipsychotics are now available in the UK: olanzapine embonate injection (ZypAdhera), paliperidone injection (Xeplion) and risperidone injection (Risperdal Consta). In this article we review the evidence for these agents and discuss the practical implications of their use.

  10. Cost and carbon burden of long-acting injections: a sustainable evaluation

    PubMed Central

    Maughan, Daniel L.; Lillywhite, Rob; Cooke, Matthew

    2016-01-01

    Aims and method This study explores the economic cost and carbon footprint associated with current patterns of prescribing long-term flupentixol decanoate long-acting injections. We conducted an analysis of prescription data from a mental health trust followed by economic and carbon cost projections using local and national data. Results A reduction of £300 000 could be achieved across England by improving prescribing behaviour, which equates to £250 per patient per year and 170 000 kg CO2e. These savings are unlikely to be released as cash from the service, but will lead to higher-value service provision at the same or lower cost. Most of these carbon emissions are attributable to the carbon footprint of the appointment – 88 000 kg CO2e (including energy use and materials used) and the overprescribing of medication – 66 000 kg CO2e. Clinical implications Psychiatrists need to review their prescribing practice of long-acting injections to reduce their impact on the National Health Service financial budget and the environment. PMID:27280033

  11. Rational design of a fully active, long-acting PEGylated factor VIII for hemophilia A treatment.

    PubMed

    Mei, Baisong; Pan, Clark; Jiang, Haiyan; Tjandra, Hendri; Strauss, Jonathan; Chen, Yaoqi; Liu, Tongyao; Zhang, Xin; Severs, Joanne; Newgren, Jim; Chen, Jianmin; Gu, Jian-Ming; Subramanyam, Babu; Fournel, Michael A; Pierce, Glenn F; Murphy, John E

    2010-07-15

    A long-acting factor VIII (FVIII) as a replacement therapy for hemophilia A would significantly improve treatment options for patients with hemophilia A. To develop a FVIII with an extended circulating half-life, but without a reduction in activity, we have engineered 23 FVIII variants with introduced surface-exposed cysteines to which a polyethylene glycol (PEG) polymer was specifically conjugated. Screening of variant expression level, PEGylation yield, and functional assay identified several conjugates retaining full in vitro coagulation activity and von Willebrand factor (VWF) binding.PEGylated FVIII variants exhibited improved pharmacokinetics in hemophilic mice and rabbits. In addition, pharmacokinetic studies in VWF knockout mice indicated that larger molecular weight PEG may substitute for VWF in protecting PEGylated FVIII from clearance in vivo. In bleeding models of hemophilic mice, PEGylated FVIII not only exhibited prolonged efficacy that is consistent with the improved pharmacokinetics but also showed efficacy in stopping acute bleeds comparable with that of unmodified rFVIII. In summary site-specifically PEGylated FVIII has the potential to be a long-acting prophylactic treatment while being fully efficacious for on-demand treatment for patients with hemophilia A.

  12. Pharmacokinetic study of an injectable long-acting parenteral formulation of doxycycline hyclate in calves.

    PubMed

    Vargas-Estrada, D; Gracia-Mora, J; Sumano, H

    2008-06-01

    Doxycycline hyclate (DOX-h) can be regarded as a time-dependant antibacterial. Hence, a parenteral long-acting formulation may be regarded as more pharmacologically sound. A poloxamer-based matrix was used to produce a long-acting injectable preparation (DOX-h-LA) and its serum concentrations vs. time profile investigated after its s.c. injection to calves. Serum concentrations profiles for such a prepartion were compared to the corresponding profiles obtained with an aqueous formulation of DOX-h injected either i.m. or i.v. in 10 calves in a crossover study at dose of 10mg/kg, with washout periods. DOX-h-LA showed the greatest values for bioavailability (602%); maximum serum concentration (C(max)) value was 1.99microg/mL with a time to reach C(max) (T(max)) of 25h and an elimination half-life of 40.81h. Considering minimum effective serum concentration of 0.5microg/mL a dose-interval of 80h can be achieved for DOX-h-LA, and only 9.7h and 17h after the i.v. or i.m. administration of DOX-h, respectively.

  13. Adjunctive and Long-Acting Nanoformulated Antiretroviral Therapies for HIV-associated neurocognitive disorders

    PubMed Central

    Gendelman, Howard E.; Gelbard, Harris A.

    2014-01-01

    Purpose of review This review focuses on current and future strategies to modulate neuroinflammation while reducing residual viral burden in the central nervous system (CNS). This has been realized by targeted long acting antiretroviral nano- and adjunctive therapies being developed for HIV infected people. Our ultimate goal is to eliminate virus from its CNS reservoirs and, in so doing, reverse the cognitive and motor dysfunctions seen in HIV-associated neurocognitive disorders (HAND). Recent findings Herein, we highlight our laboratories development of adjunctive and nanomedicine therapies for HAND. An emphasis is placed on drug-drug interactions that target both the viral life cycle and secretory pro-inflammatory neurotoxic factors and signaling pathways. Summary Antiretroviral therapy (ART) has improved the quality and duration of life for people living with HIV-1. A significant long-term comorbid illness is HAND. Symptoms, while reduced in severity, are common. Disease occurs, in part, through continued low-level viral replication inducing secondary glial neuroinflammatory activities. Our recent works and those of others have seen disease attenuated in animal models through the use of adjunctive and long-acting reservoir targeted nanoformulated ART. The translation of these inventions from animals to humans is the focus of this review. PMID:25226025

  14. A Systemic Review and Experts’ Consensus for Long-acting Injectable Antipsychotics in Bipolar Disorder

    PubMed Central

    Chou, Yuan Hwa; Chu, Po-Chung; Wu, Szu-Wei; Lee, Jen-Chin; Lee, Yi-Hsuan; Sun, I-Wen; Chang, Chen-Lin; Huang, Chien-Liang; Liu, I-Chao; Tsai, Chia-Fen; Yen, Yung-Chieh

    2015-01-01

    Bipolar disorder (BD) is a major psychiatric disorder that is easily misdiagnosed. Patient adherence to a treatment regimen is of utmost importance for successful outcomes in BD. Several trials of antipsychotics suggested that depot antipsychotics, including long-acting first- and second-generation agents, are effective in preventing non-adherence, partial adherence, and in reducing relapse in BD. Various long-acting injectable (LAI) antipsychotics are available, including fluphenazine decanoate, haloperidol decanoate, olanzapine pamoate, risperidone microspheres, paliperidone palmitate, and aripiprazole monohydrate. Due to the increasing number of BD patients receiving LAI antipsychotics, treatment guidelines have been developed. However, the clinical applicability of LAI antipsychotics remains a global cause for concern, particularly in Asian countries. Expert physicians from Taiwan participated in a consensus meeting, which was held to review key areas based on both current literature and clinical practice. The purpose of this meeting was to generate a practical and implementable set of recommendations for LAI antipsychotic use to treat BD; target patient groups, dosage, administration, and adverse effects were considered. Experts recommended using LAI antipsychotics in patients with schizophrenia, rapid cycling BD, BD I, and bipolar-type schizoaffective disorder. LAI antipsychotic use was recommended in BD patients with the following characteristics: multiple episodes and low adherence; seldom yet serious episodes; low adherence potential per a physician’s clinical judgment; preference for injectable agents over oral agents; and multiple oral agent users still experiencing residual symptoms. PMID:26243837

  15. Long-acting injectable formulations of new-generation antipsychotics: a review from a clinical perspective.

    PubMed

    Rauch, Anna-Sophia; Fleischhacker, W Wolfgang

    2013-08-01

    Antipsychotics are the mainstay of the long-term treatment of patients with schizophrenia. In this context, the evidence also supports the effectiveness of long-acting injections (LAIs) or depots of antipsychotics regarding their relapse-preventing properties. When a LAI formulation of risperidone was launched as the first second-generation depot, there was a renaissance of interest in these formulations. In the meantime, olanzapine, paliperidone, and aripiprazole have been approved by regulatory authorities as LAIs in various countries. All studies using the new-generation depots have shown a clear advantage over placebo regarding relapse prevention and symptom reduction. Safety profiles of the long-acting compounds are comparable to their oral formulations with the exception of olanzapine pamoate injections, which can sometimes lead to a post-injection delirium. Despite the fact that many treatment guidelines recommend LAI antipsychotics as an important treatment option for the long-term management of schizophrenia, they are still most frequently used in chronically ill patients with considerable compliance problems. It is imperative to overcome this indication bias in order to be able to utilize all available treatment options in the long-term management of schizophrenia. There is little evidence on comparisons between LAIs and their oral mother compounds, and even less concerning effectiveness comparisons between different depots. The purpose of this manuscript is to review the recent clinical evidence on new-generation depot antipsychotics.

  16. The Pharmacokinetics of Second-Generation Long-Acting Injectable Antipsychotics: Limitations of Monograph Values.

    PubMed

    Lee, Lik Hang N; Choi, Charles; Collier, Abby C; Barr, Alasdair M; Honer, William G; Procyshyn, Ric M

    2015-12-01

    Product monographs (also known by terms such as Summary of Product Characteristics and Highlights of Prescribing Information, depending on the jurisdiction) provide essential information to ensure the safe and effective use of a drug. Medical practitioners often rely on these monographs for guidance on matters related to pharmacokinetics as well as indications, contraindications, clinical pharmacology, and adverse reactions. The clinical and scientific information found within these documents, forming the basis for decision making, are presumed to be derived from well-designed studies. The objective of this review is to examine the source and validity of the pharmacokinetic data used in establishing the half-lives and times to steady-state reported in the product monographs of second-generation long-acting injectable antipsychotics. Thus, we have critically evaluated the clinical trials from which the pharmacokinetic parameters listed in the product monographs were determined. In many cases, the pharmacokinetic information presented in product monographs is of limited use to clinicians wishing to optimize the effectiveness and tolerability of second-generation long-acting injectable antipsychotics. Under such circumstances, off-label prescribing practices may actually produce better clinical outcomes than if decisions were made based on the product monographs alone.

  17. A Systemic Review and Experts' Consensus for Long-acting Injectable Antipsychotics in Bipolar Disorder.

    PubMed

    Chou, Yuan Hwa; Chu, Po-Chung; Wu, Szu-Wei; Lee, Jen-Chin; Lee, Yi-Hsuan; Sun, I-Wen; Chang, Chen-Lin; Huang, Chien-Liang; Liu, I-Chao; Tsai, Chia-Fen; Yen, Yung-Chieh

    2015-08-31

    Bipolar disorder (BD) is a major psychiatric disorder that is easily misdiagnosed. Patient adherence to a treatment regimen is of utmost importance for successful outcomes in BD. Several trials of antipsychotics suggested that depot antipsychotics, including long-acting first- and second-generation agents, are effective in preventing non-adherence, partial adherence, and in reducing relapse in BD. Various long-acting injectable (LAI) antipsychotics are available, including fluphenazine decanoate, haloperidol decanoate, olanzapine pamoate, risperidone microspheres, paliperidone palmitate, and aripiprazole monohydrate. Due to the increasing number of BD patients receiving LAI antipsychotics, treatment guidelines have been developed. However, the clinical applicability of LAI antipsychotics remains a global cause for concern, particularly in Asian countries. Expert physicians from Taiwan participated in a consensus meeting, which was held to review key areas based on both current literature and clinical practice. The purpose of this meeting was to generate a practical and implementable set of recommendations for LAI antipsychotic use to treat BD; target patient groups, dosage, administration, and adverse effects were considered. Experts recommended using LAI antipsychotics in patients with schizophrenia, rapid cycling BD, BD I, and bipolar-type schizoaffective disorder. LAI antipsychotic use was recommended in BD patients with the following characteristics: multiple episodes and low adherence; seldom yet serious episodes; low adherence potential per a physician's clinical judgment; preference for injectable agents over oral agents; and multiple oral agent users still experiencing residual symptoms.

  18. A randomised, double blind, multicentre trial of octreotide in moderate to severe acute pancreatitis

    PubMed Central

    Uhl, W; Buchler, M; Malfertheiner, P; Beger, H; Adler, G; Gaus, W; the, G

    1999-01-01

    BACKGROUND—The pharmacological inhibition of exocrine pancreatic secretion with the somatostatin analogue octreotide has been advocated as a specific treatment of acute pancreatitis.
AIM—To investigate the efficacy of octreotide in acute pancreatitis in a randomised, placebo controlled trial.
METHODS—302 patients from 32 hospitals, fulfilling the criteria for moderate to severe acute pancreatitis within 96 hours of the onset of symptoms, were randomly assigned to one of three treatment groups: group P (n=103) received placebo, while groups O1 (n=98) and O2 (n=101) received 100 and 200 µg of octreotide, respectively, by subcutaneous injection three times daily for seven days. The primary outcome variable was a score composed of mortality and 15 typical complications of acute pancreatitis.
RESULTS—The three groups were well matched with respect to pretreatment characteristics. An intent to treat analysis of all 302 patients revealed no significant differences among treatment groups with respect to mortality (P: 16%; O1: 15%; O2: 12%), the rate of newly developed complications, the duration of pain, surgical interventions, or the length of the hospital stay. A valid for efficacy analysis (251 patients) also revealed no significant differences.
CONCLUSIONS—This trial shows no benefit of octreotide in the treatment of acute pancreatitis.


Keywords: acute pancreatitis; somatostatin; octreotide; randomised controlled multicentre trial PMID:10369711

  19. Octreotide prevents liver failure through upregulating 5'-methylthioadenosine in extended hepatectomized rats.

    PubMed

    Du, Zhenggui; Zhou, Yongjie; Lu, Xufeng; Li, Lei; Lu, Changli; Li, Li; Li, Bo; Bu, Hong; Yang, Jiayin; Shi, Yujun

    2016-02-01

    Insufficient liver regeneration and hepatocyte injury caused by excessive portal perfusion are considered to be responsible for post-hepatectomy liver failure (PLF) or small-for-size syndrome in living-donor liver transplantation. Somatostatin can decrease portal vein pressure (PVP) but simultaneously inhibits liver regeneration. This interesting paradox motivated us to investigate the outcome of PLF in response to somatostatin treatment. Rats receiving extended partial hepatectomy (90% PH) were treated with octreotide, a somatostatin analogue, or placebo. Animal survival, serum parameters and hepatic histology were evaluated. Metabolomic analysis was performed to investigate the effect of octreotide on hepatocyte metabolism. Despite significantly inhibiting early regeneration, octreotide application noticeably improved the hepatic histology, liver function and survival after PH but did not decrease the PVP level. Metabolomic analysis exhibited that octreotide profoundly and exclusively altered the levels of five metabolites that participate in or closely associate with the methionine cycle, a biochemical reaction that uniquely produces S-adenosylmethionine (SAMe), an active methyl residual donor for methyltransferase reactions. Among these metabolites, 5'-methylthioadenosine (MTA), a derivate of SAMe, increased three-fold and was found independently improve the hepatic histology and reduce inflammatory cytokines in hepatectomized rats. Octreotide exclusively regulates the methionine cycle reaction and augments the MTA level in hepatocytes. MTA prominently protects hepatocytes against shear stress injury and reduces the secondary inflammation, thereby protecting rats from PLF. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Effect of β2-adrenergic receptor gene (ADRB2) 3′ untranslated region polymorphisms on inhaled corticosteroid/long-acting β2-adrenergic agonist response

    PubMed Central

    2012-01-01

    Background Evidence suggests that variation in the length of the poly-C repeat in the 3′ untranslated region (3′UTR) of the β2-adrenergic receptor gene (ADRB2) may contribute to interindividual variation in β-agonist response. However, methodology in previous studies limited the assessment of the effect of sequence variation in the context of poly-C repeat length. The objectives of this study were to design a novel genotyping method to fully characterize sequence variation in the ADRB2 3′UTR poly-C repeat in asthma patients treated with inhaled corticosteroid and long-acting β2-adrenergic agonist (ICS/LABA) combination therapy, and to analyze the effect of the poly-C repeat polymorphism on clinical response. Methods In 2,250 asthma patients randomized to treatment with budesonide/formoterol or fluticasone/salmeterol in a six-month study (AstraZeneca study code: SD-039-0735), sequence diversity in the ADRB2 poly-C repeat region was determined using a novel sequencing-based genotyping method. The relationship between the poly-C repeat polymorphism and the incidence of severe asthma exacerbations, and changes in pulmonary function and asthma symptoms from baseline to the average during the treatment period, were analyzed. Results Poly-C repeat genotypes were assigned in 97% (2,192/2,250) of patients. Of the 13 different poly-C repeat alleles identified, six alleles occurred at a frequency of >5% in one or more population in this study. The repeat length of these six common alleles ranged from 10 to 14 nucleotides. Twelve poly-C repeat genotypes were observed at a frequency of >1%. No evidence of an association between poly-C repeat genotype and the incidence of severe asthma exacerbations was observed. Patients’ pulmonary function measurements improved and asthma symptoms declined when treated with ICS/LABA combination therapy regardless of poly-C repeat genotype. Conclusions The extensive sequence diversity present in the poly-C repeat region of the ADRB2

  1. A multicentre randomised trial comparing octreotide and injection sclerotherapy in the management and outcome of acute variceal haemorrhage

    PubMed Central

    Jenkins, S; Shields, R; Davies, M; Elias, E; Turnbull, A; Bassendine, M; James, O; Iredale, J; Vyas, S; Arthur, M; Kingsnorth, A; Sutton, R

    1997-01-01

    Background—Few studies have compared vasoactive drugs with endoscopic sclerotherapy in the control of acute variceal haemorrhage. Octreotide is widely used for this purpose, but its value remains undetermined. 
Aims—To compare octreotide with endoscopic sclerotherapy for acute variceal haemorrhage. 
Patients—Consecutive patients with acute variceal haemorrhage. 
Methods—Patients were randomised at endoscopy to receive either a 48 hour intravenous infusion of 50 µg/h octreotide (n=73), or emergency sclerotherapy (n=77). 
Results—Overall control of bleeding and mortality was not significantly different between octreotide (85%, 62 patients) and sclerotherapy (82%, 63 patients) over the 48 hour trial period (relative risk of rebleeding 0.83; 95% confidence interval (CI) 0.38 to 1.82), irrespective of Child's grading or active bleeding at endoscopy. One major complication was observed in the sclerotherapy group (aspiration) and two in the octreotide group (pulmonary oedema, severe paralytic ileus). During 60 days of follow up there was an overall trend towards an increased mortality in the octreotide group which was not statistically significant (relative risk of dying at 60 days 1.91, 95% CI 0.97 to 3.78, p=0.06). 
Conclusions—The results of this study indicate that intravenous octreotide is as effective as injection sclerotherapy in the control of acute variceal bleeding, but further controlled trials are necessary to evaluate the safety of this treatment. 

 Keywords: variceal haemorrhage; octreotide; injection sclerotherapy PMID:9391254

  2. Dramatic volume reduction of a large GH/TSH secreting pituitary tumor with short term Octreotide therapy.

    PubMed

    Atkinson, John L D; Abboud, Charles F; Lane, John I

    2005-01-01

    A case is presented of a huge GH/TSH secreting tumor and marked volumetric reduction in size with only one week of Octreotide therapy. To our knowledge, this is the first reported case of such a dramatic volumetric response to short-term Octreotide therapy.

  3. Use of long-acting risperidone in psychiatric disorders: focus on efficacy, safety and cost-effectiveness.

    PubMed

    Keith, Samuel

    2009-01-01

    Schizophrenia is a chronic disorder, usually necessitating lifelong treatment. Although atypical antipsychotic agents have improved outcomes in schizophrenia, their clinical potential remains limited by patients' nonadherence to medication. Long-acting antipsychotics were developed in the 1960s to enhance treatment adherence and simplify the medication process. However, although conventional long-acting agents assure medication delivery, they are associated with similar side effects to their oral equivalents. The need for an agent combining the advantages of a long-acting formulation with those of an atypical antipsychotic was highlighted in 1997 by the American Psychiatric Association's Practice Guideline for the Treatment of Patients with Schizophrenia. The first long-acting injectable atypical antipsychotic, long-acting risperidone (Risperdal Consta, Johnson & Johnson), has since been developed. This article discusses the efficacy, tolerability and cost-effectiveness of long-acting risperidone in schizophrenia and bipolar disorder patients, and suggests possibilities for how its role in clinical practice may change over the next 5 years.

  4. Application of Implementation Science Methodology to Immediate Postpartum Long-Acting Reversible Contraception Policy Roll-Out Across States.

    PubMed

    Rankin, Kristin M; Kroelinger, Charlan D; DeSisto, Carla L; Pliska, Ellen; Akbarali, Sanaa; Mackie, Christine N; Goodman, David A

    2016-11-01

    Purpose Providing long-acting reversible contraception (LARC) in the immediate postpartum period is an evidence-based strategy for expanding women's access to highly effective contraception and for reducing unintended and rapid repeat pregnancy. The purpose of this article is to demonstrate the application of implementation science methodology to study the complexities of rolling-out policies that promote immediate postpartum LARC use across states. Description The Immediate Postpartum LARC Learning Community, sponsored by the Association of State and Territorial Health Officials (ASTHO), is made up of multi-disciplinary, multi-agency teams from 13 early-adopting states with Medicaid reimbursement policies promoting immediate postpartum LARC. Partners include federal agencies and maternal and child health organizations. The Learning Community discussed barriers, opportunities, strategies, and promising practices at an in-person meeting. Implementation science theory and methods, including the Consolidated Framework for Implementation Research (CFIR), and a recent compilation of implementation strategies, provide useful tools for studying the complexities of implementing immediate postpartum LARC policies in birthing facilities across early adopting states. Assessment To demonstrate the utility of this framework for guiding the expansion of immediate postpartum LARC policies, illustrative examples of barriers and strategies discussed during the in-person ASTHO Learning Community meeting are organized by the five CFIR domains-intervention characteristics, outer setting, inner setting, characteristics of the individuals involved, and process. Conclusion States considering adopting policies can learn from ASTHO's Immediate Postpartum LARC Learning Community. Applying implementation science principles may lead to more effective statewide scale-up of immediate postpartum LARC and other evidence-based strategies to improve women and children's health.

  5. Low-factor consumption for major surgery in haemophilia B with long-acting recombinant glycoPEGylated factor IX.

    PubMed

    Escobar, M A; Tehranchi, R; Karim, F A; Caliskan, U; Chowdary, P; Colberg, T; Giangrande, P; Giermasz, A; Mancuso, M E; Serban, M; Tsay, W; Mahlangu, J N

    2017-01-01

    Surgery in patients with haemophilia B carries a high risk of excessive bleeding and requires adequate haemostatic control until wound healing. Nonacog beta pegol, a long-acting recombinant glycoPEGylated factor IX (FIX), was used in the perioperative management of patients undergoing major surgery. To evaluate the efficacy and safety of nonacog beta pegol in patients with haemophilia B who undergo major surgery. This was an open-label, multicentre, non-controlled surgery trial aimed at assessing peri- and postoperative efficacy and safety of nonacog beta pegol in 13 previously treated patients with haemophilia B. All patients received a preoperative nonacog beta pegol bolus injection of 80 IU kg(-1) . Postoperatively, the patients received fixed nonacog beta pegol doses of 40 IU kg(-1) , repeated at the investigator's discretion. Safety assessments included monitoring of immunogenicity and adverse events. Intraoperative haemostatic effect was rated 'excellent' or 'good' in all 13 cases. Apart from the preoperative injection, none of the patients needed additional doses of nonacog beta pegol on the day of surgery. The median number of postoperative doses of nonacog beta pegol was 2.0 from days 1 to 6 and 1.5 from days 7 to 13. No unexpected intra- or postoperative complications were observed including deaths or thromboembolic events. No patients developed inhibitors. These results indicated that nonacog beta pegol was safe and effective in the perioperative setting, allowing major surgical interventions in patients with haemophilia B with minimal peri- and postoperative concentrate consumption and infrequent injections as reported with standard FIX products. © 2016 John Wiley & Sons Ltd.

  6. Strengthening Postabortion Family Planning Services in Ethiopia: Expanding Contraceptive Choice and Improving Access to Long-Acting Reversible Contraception.

    PubMed

    Samuel, Melaku; Fetters, Tamara; Desta, Demeke

    2016-08-11

    Where unmet need for the safest, most effective, and long-acting reversible contraceptives (LARCs) is very high, the health system and partners need to implement problem-solving, locally feasible, and comprehensive family planning delivery strategies. Because young and unmarried women are most at risk for unintended pregnancy and repeat abortion due to poor access to contraceptive services, postabortion family planning (PAFP) is a key component in such strategies. In Southern Nations, Nationalities, and People's Region, Ethiopia, Ipas implemented health system strengthening efforts from fiscal year (FY) 2010 (July 2009 to June 2010) to FY 2014 (July 2013 to June 2014) to improve the quality of PAFP services and expand method choice in 101 public facilities. The intervention significantly improved PAFP uptake at the project sites. Specifically, the proportion of abortion clients receiving LARCs progressively improved during the intervention period. The proportion of abortion clients who left the facilities with a contraceptive method increased from 58% in FY 2010 to 83% in FY 2014. The share of method mix for LARCs rose from 2% in FY 2010 to 55% in FY 2014, while the share for condoms, injectables, and oral contraceptives declined from 98% to 45%. Implant use rose from 2% in FY 2010 to 43% in FY 2014, while the use of intrauterine devices increased from 0.1% in FY 2010 to 12% in FY 2014. A larger proportion of PAFP users received LARCs at health centers, where midwives and nurses are the primary providers, than at hospitals (59% versus 37%, respectively). A broader method mix can satisfy clients with a variety of needs, a key factor for higher uptake of more effective methods and program success. Further evidence-based interventions need to be implemented to improve the quality of PAFP in a feasible and replicable strategy that addresses unmet need for modern contraceptive methods.

  7. Strengthening Postabortion Family Planning Services in Ethiopia: Expanding Contraceptive Choice and Improving Access to Long-Acting Reversible Contraception

    PubMed Central

    Samuel, Melaku; Fetters, Tamara; Desta, Demeke

    2016-01-01

    ABSTRACT Where unmet need for the safest, most effective, and long-acting reversible contraceptives (LARCs) is very high, the health system and partners need to implement problem-solving, locally feasible, and comprehensive family planning delivery strategies. Because young and unmarried women are most at risk for unintended pregnancy and repeat abortion due to poor access to contraceptive services, postabortion family planning (PAFP) is a key component in such strategies. In Southern Nations, Nationalities, and People’s Region, Ethiopia, Ipas implemented health system strengthening efforts from fiscal year (FY) 2010 (July 2009 to June 2010) to FY 2014 (July 2013 to June 2014) to improve the quality of PAFP services and expand method choice in 101 public facilities. The intervention significantly improved PAFP uptake at the project sites. Specifically, the proportion of abortion clients receiving LARCs progressively improved during the intervention period. The proportion of abortion clients who left the facilities with a contraceptive method increased from 58% in FY 2010 to 83% in FY 2014. The share of method mix for LARCs rose from 2% in FY 2010 to 55% in FY 2014, while the share for condoms, injectables, and oral contraceptives declined from 98% to 45%. Implant use rose from 2% in FY 2010 to 43% in FY 2014, while the use of intrauterine devices increased from 0.1% in FY 2010 to 12% in FY 2014. A larger proportion of PAFP users received LARCs at health centers, where midwives and nurses are the primary providers, than at hospitals (59% versus 37%, respectively). A broader method mix can satisfy clients with a variety of needs, a key factor for higher uptake of more effective methods and program success. Further evidence-based interventions need to be implemented to improve the quality of PAFP in a feasible and replicable strategy that addresses unmet need for modern contraceptive methods. PMID:27540126

  8. The Impact of Balanced Counseling on Contraceptive Method Choice and Determinants of Long Acting and Reversible Contraceptive Continuation in Nepal.

    PubMed

    Sapkota, Sabitri; Rajbhandary, Ruchita; Lohani, Shilpa

    2016-03-08

    Introduction Long-acting reversible contraceptives (LARCs) reduce rates of unintended pregnancies and repeat abortion. Uptake and continuation rates of LARCs are very low in Nepal, despite free provision from most health facilities. We sought to establish the effectiveness of a new approach to LARC promotion in Nepal. Methods We examined change in contraceptive method mix in Nepal using service data resulting from introduction of a balanced counseling (BC) approach to family planning (FP). All staff located at nine randomly selected FP sites were trained and began applying BC in April and May 2014. Women who accepted LARCs from a participating facility were re-contacted at 1, 3, 6 and 12 months. We estimated the LARC continuation rate and assessed determinants of continuation using descriptive analysis, Kaplan-Meier survival curves and univariate and multivariate Cox proportional hazard analysis. Results A total of 5744 women received BC between April and July 2014. 1580 women (27.5 %) took up LARCs, raising its contribution to contraceptive method mix at [organization] to 40 %, significantly higher than the 15 % recorded in 2013. 913 women were followed-up, and the LARC continuation rate at 12 months was 82 %. Women's reported satisfaction with LARC [AHR 0.23; 95 % CI 0.14-0.39, p = 0.000] was the single strongest determinant of LARC continuation after adjusting for all background characteristics. Discussion The findings suggest BC is an effective approach for increasing LARC uptake in Nepal. The rate of LARC continuation and its determinants are important inputs to strategies for improved delivery of FP services.

  9. Amelioration of the cardiovascular effects of cocaine in rhesus monkeys by a long-acting mutant form of cocaine esterase.

    PubMed

    Collins, Gregory T; Carey, Kathy A; Narasimhan, Diwahar; Nichols, Joseph; Berlin, Aaron A; Lukacs, Nicholas W; Sunahara, Roger K; Woods, James H; Ko, Mei-Chuan

    2011-04-01

    A long-acting mutant form of a naturally occurring bacterial cocaine esterase (T172R/G173Q CocE; double mutant CocE (DM CocE)) has previously been shown to antagonize the reinforcing, convulsant, and lethal effects of cocaine in rodents. However, the effectiveness and therapeutic characteristics of DM CocE in nonhuman primates, in a more clinically relevant context, are unknown. The current studies were aimed at (1) characterizing the cardiovascular effects of cocaine in freely moving rhesus monkeys, (2) evaluating the capacity of DM CocE to ameliorate these cocaine-induced cardiovascular effects when administered 10 min after cocaine, and (3) assessing the immunological responses of monkeys to DM CocE following repeated administration. Intravenous administration of cocaine produced dose-dependent increases in mean arterial pressure (MAP) and heart rate (HR) that persisted throughout the 2-h observation period following a dose of 3.2 mg/kg cocaine. Cocaine failed to produce reliable changes in electrocardiograph (ECG) parameters, body temperature, and locomotor activity. DM CocE produced a rapid and dose-dependent amelioration of the cardiovascular effects, with saline-like MAP measures restored within 5-10 min, and saline-like HR measures restored within 20-40 min of DM CocE administration. Although administration of DM CocE produced increases in anti-CocE antibodies, they did not appear to have a neutralizing effect on the capacity of DM CocE to reverse the cardiovascular effects of cocaine. In conclusion, these findings in monkeys provide strong evidence to suggest that highly efficient cocaine esterases, such as DM CocE, can provide a potential therapeutic option for treatment of acute cocaine intoxication in humans.

  10. The cost associated with administering risperidone long-acting injections in the Australian community

    PubMed Central

    2011-01-01

    Background Risperidone long-acting injection (LAI) is mostly administered twice weekly to people with schizophrenia by nurses at community mental health centres (CMHC) or through mobile outreach visits. This study estimates the cost of resource utilisation associated with the administration of risperidone LAI and the potential savings from substituting two-weekly injections with a longer interval product of therapeutic equivalence. Methods A survey of mental health staff overseeing the administration of risperidone LAI at 253 distinct Australian CMHCs was undertaken in November 2009. For the two-week period prior to the survey, respondents were asked questions on injection time (and related tasks) and, for mobile outreach visits, distance and time travelled as well as reduction in visits. Results were stratified by Australian Standard Geographical Classification (ASGC) region. Resource use was quantified and valued in Australian dollars. Results Results are derived from 74 CMHCs, representing approximately 26% of the national average risperidone LAI unit two-week sales. Stratified average injection time (including related tasks) for risperidone LAI ranged from 18-29 minutes, with a national average of 20.12 minutes. For mobile outreach visits, average distance per patient ranged from 19.4 to 55.5 km for One Staff Visits and 15.2 to 218.1 km for More Than One Staff Visits, and average time travelled ranged from 34.1 to 54.5 minutes for One Staff Visits and 29.2 to 136.3 minutes for More Than One Staff visits. The upper range consistently reflected greater resource utilisation in rural areas compared to urban areas. If administration of risperidone LAI had not been required, 20% fewer mobile outreach visits would have occurred. Conclusions The national average saving per two-weekly risperidone long-acting injection avoided is $75.14. In 2009 in Australia, this would have saved ~$11 million for injection administration costs alone if all patients taking two

  11. Successful management of intractable cryptosporidial diarrhea with intravenous octreotide, a somatostatin analogue.

    PubMed

    Kreinik, G; Burstein, O; Landor, M; Bernstein, L; Weiss, L M; Wittner, M

    1991-06-01

    A 38-year-old man with AIDS and intractable large-volume diarrhea due to a cryptosporidial infection was successfully treated with intravenous octreotide, a somatostatin analogue. The volume of diarrhea, 10-12 liters with 8-13 movements per day, was reduced to three to four semi-formed to formed stools per day when the patient was treated with 400 micrograms intravenous octreotide daily. The patient's intravenous hyperalimentation was discontinued and he returned to oral feeding. He quickly regained his normal weight and has now resumed his normal activities. For those patients who cannot tolerate subcutaneous administration, intravenous octreotide therapy may not only be life-saving but may also markedly increase the quality of life. Roxithromycin, a macrolide antibiotic, was also administered to this patient with cryptosporidiosis but efficacy was not demonstrated.

  12. A critical appraisal of long acting injectable antipsychotics: Translating research to clinics.

    PubMed

    Sreeraj, Vanteemar S; Shivakumar, Venkataram; Rao, Naren P; Venkatasubramanian, Ganesan

    2017-08-01

    Long acting injections (LAI) are an effective alternative mode of administration of antipsychotics, less commonly used in clinical practice. Gap in knowledge base is an important source of attitudinal bias. Current article is focused on reviewing the literature for the principles underlying the choice, initiation, maintenance, switch and termination of an LAI; historical, pharmacological and clinical factors implicating the rationale of using LAI against oral agents and older against newer LAIs. Evidences available in clinical and basic psychopharmacological researches are critically appraised, highlighting the lacunae in our understanding. It is endeavored to open the window for the studies to be carried forward in the future answering critical questions which could lay a stronger base for clinical utility of different LAIs. Thus, this article tries to acquaint clinicians with the translatable knowledge imparted from the research and riposte queries for the researchers to explore in relation to LAI. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. The use of long-acting opioids in chronic pain management.

    PubMed

    Vallerand, April Hazard

    2003-09-01

    The consensus statement from the American Pain Society and American Academy of Pain Medicine states that the undertreatment of pain is unjustified [6]. It has been suggested that opioid therapy can be used effectively to treat noncancer pain in a subset of patients [26], and this is becoming more acceptable [3]. Providing sustained analgesia is an important aspect of therapy, and medications should be administered on an around-the-clock basis, because regular administration of doses maintains a constant level of drug in the body and helps prevent recurrence of pain. Ideal treatment for persistent pain is a long-acting opioid administered around the clock to prevent baseline pain, with the use of short-acting opioids as supplemental agents for breakthrough pain. Controlled-release formulations can lessen the inconvenience associated with around-the-clock administration of short-acting opioids. Sustained analgesia also can be achieved with transdermal fentanyl, which combines a strong opioid with a 72-hour release profile and the benefits of a parenteral route, avoiding first-pass metabolism. Controlled-release formulations of morphine and oxycodone are available in the United States, and hydromorphone preparations are being reviewed for approval. Clinical experience with these formulations and transdermal fentanyl indicates that these agents are equally effective in controlling pain. Studies have demonstrated improved quality of life with the transdermal route and with controlled-release morphine and oxycodone. Because of patch reapplication every 72 hours, the transdermal route also enhances compliance. Use of an opioid without the need for oral or intravenous administration and the opportunity to improve compliance are among the advantages of the transdermal route in clinical practice. The nurse has an important role in the management of patients receiving long-acting opioids for chronic noncancer pain, Facilitation of the conversion from short-acting to long-acting

  14. Physiologically-Based Pharmacokinetic Modelling to Inform Development of Intramuscular Long Acting Nanoformulations for HIV

    PubMed Central

    Rajoli, Rajith KR; Back, David J; Rannard, Steve; Meyers, Caren Freel; Flexner, Charles; Owen, Andrew; Siccardi, Marco

    2014-01-01

    Background and Objectives Antiretrovirals (ARVs) are currently used for the treatment and prevention of HIV infection. Poor adherence and low tolerability of some existing oral formulations can hinder their efficacy. Long-acting (LA) injectable nanoformulations could help address these complications by simplifying ARV administration. The aim of this study is to inform the optimisation of intramuscular LA formulations for eight ARVs through physiologically-based pharmacokinetic (PBPK) modelling. Methods A whole-body PBPK model was constructed using mathematical descriptions of molecular, physiological and anatomical processes defining pharmacokinetics. These models were validated against available clinical data and subsequently used to predict the pharmacokinetics of injectable LA formulations Results The predictions suggest that monthly intramuscular injections are possible for dolutegravir, efavirenz, emtricitabine, raltegravir, rilpivirine and tenofovir provided that technological challenges to control release rate can be addressed. Conclusions These data may help inform the target product profiles for LA ARV reformulation strategies. PMID:25523214

  15. Side effects of pharmacotherapy on bone with long-acting gonadorelin agonist triptorelin for paraphilia.

    PubMed

    Hoogeveen, John; Van der Veer, Eveline

    2008-03-01

    There have been limited research studies concerning the use of libido inhibitors for the treatment of patients with a paraphilia. Observational studies suggest that agents that lower testosterone are an effective treatment for paraphilia. We report a case of hormonal treatment of paraphilia that was associated with side effects. A 35-year-old man with a paraphilia was treated with long-acting gonadorelin. The desired result was reduced preoccupation with sexuality, but there were various side effects including a serious amount of bone loss. We believe that more attention should be given to the adverse effects of long-term treatment with triptorelin. In our view the drug regime needs to be revised.

  16. Reversible Contraception Update: The Importance of Long-Acting Reversible Contraception

    PubMed Central

    Mestad, Renee E.; Kenerson, Jessica; Peipert, Jeffrey F.

    2011-01-01

    The past several years have seen an expansion in contraception options. Emerging data support the use of long-acting reversible contraception (LARC) such as the intrauterine device and subdermal implant as the most effective methods of contraception with the highest continuation rates and very high levels of patient satisfaction. In addition, the appropriate target population for the use of the intrauterine device now includes nulliparous women and adolescents. When a patient considers initiating a new contraceptive method, it is important to consider the characteristics of each method, including the side effects, effectiveness, and patient acceptability. Additionally, medical comorbidities must also be evaluated prior to choosing a method. In this article, we provide a brief overview of available reversible contraceptive methods, with an emphasis on LARC. PMID:19641264

  17. Long-Acting Muscarinic Antagonists for Difficult-to-Treat Asthma: Emerging Evidence and Future Directions.

    PubMed

    Bulkhi, Adeeb; Tabatabaian, Farnaz; Casale, Thomas B

    2016-07-01

    Asthma is a complex disease where many patients remain symptomatic despite guideline-directed therapy. This suggests an unmet need for alternative treatment approaches. Understanding the physiological role of muscarinic receptors and the parasympathetic nervous system in the respiratory tract will provide a foundation of alternative therapeutics in asthma. Currently, several long-acting muscarinic antagonists (LAMAs) are on the market for the treatment of respiratory diseases. Many studies have shown the effectiveness of tiotropium, a LAMA, as add-on therapy in uncontrolled asthma. These studies led to FDA approval for tiotropium use in asthma. In this review, we discuss how the neurotransmitter acetylcholine itself contributes to inflammation, bronchoconstriction, and remodeling in asthma. We further describe the current clinical studies evaluating LAMAs in adult and adolescent patients with asthma, providing a comprehensive review of the current known physiological benefits of LAMAs in respiratory disease.

  18. Shared Decision Aids: Increasing Patient Acceptance of Long-Acting Reversible Contraception

    PubMed Central

    George, Tracy P.; DeCristofaro, Claire; Dumas, Bonnie P.; Murphy, Pamela F.

    2015-01-01

    Unintended pregnancies are an important public health issue. Long-acting reversible contraceptive methods (LARCs) are reliable, safe, highly effective methods for most women; however they are underutilized in the United States. Shared decision aids were added to usual care in five public health family planning clinics in the Southeastern United States, staffed by advance practice nurses and registered nurses. All five sites showed an increase in the use of LARCs during the time period that shared decision aids were used (results statistically significant to p < 0.001). It is important for women to make informed choices about contraception, and shared decision aids can be utilized to support this decision making. This resource has been adopted for statewide use in all public health clinics, and implications for practice suggest that the use of shared decision aids is an effective method to support informed patient decision making and acceptance of LARC methods of contraception. PMID:27417757

  19. Potential anti-obesity effects of a long-acting cocaine hydrolase.

    PubMed

    Zheng, Xirong; Deng, Jing; Zhang, Ting; Yao, Jianzhuang; Zheng, Fang; Zhan, Chang-Guo

    2016-11-25

    A long-acting cocaine hydrolase, known as CocH3-Fc(M3), engineered from human butyrylcholinesterase (BChE) was tested, in this study, for its potential anti-obesity effects. Mice on a high-fat diet gained significantly less body weight when treated weekly with 1 mg/kg CocH3-Fc(M3) compared to control mice, though their food intake was similar. There is no correlation between the average body weight and the average food intake, which is consistent with the previously reported observation in BChE knockout mice. In addition, molecular modeling was carried out to understand how ghrelin binds with CocH3, showing that ghrelin binds with CocH3 in a similar mode as ghrelin binding with wild-type human BChE. The similar binding structures explains why CocH3 and BChE have similar catalytic activity against ghrelin.

  20. Characteristics of physicians who frequently prescribe long-acting benzodiazepines for the elderly.

    PubMed

    Monette, J; Tamblyn, R M; McLeod, P J; Gayton, D C

    1997-06-01

    Long-acting benzodiazepines (LABZs) are relatively contraindicated for elderly patients because they increase the risk of impaired cognitive function, falls, and hip fractures. The purpose of this study was to identify the characteristics of physicians who frequently prescribe LABZs for elderly patients. The authors examined the prescribing profile of 4,976 physicians who saw at least 20 elderly Quebec medicare registrants in 1990. Physicians who frequently prescribed LABZs for their elderly patients were more likely to have graduated before 1979, to be general practitioners as opposed to specialists, to practice in long-term care settings, and to have graduated from a medical school in Quebec as opposed to other schools in Quebec, in other provinces, or in other countries. The authors have identified several characteristics of physicians who frequently prescribed LABZs for the elderly. Strategies to improve prescribing in this field should target this group of physicians.

  1. Let's talk about sex (again): advancing the conversation around long-acting reversible contraception for teenagers.

    PubMed

    Satterwhite, Catherine Lindsey; Ramaswamy, Megha

    2015-11-01

    Long-acting reversible contraception (LARC) has incredible potential for decreasing teenage pregnancy rates in the USA, but use among adolescents remains low. LARC methods, including intrauterine devices and implants, are recommended as first-line choices for teenagers by multiple medical professional associations. Barriers at the system, provider and patient level persist, but new demonstration projects, in addition to provisions of the Affordable Care Act, show great promise in facilitating LARC use. A renewed national discourse should acknowledge the reality that many US teenagers have sex, that LARC is safe and effective and that LARC offers an opportunity to prevent teenage pregnancy. By encouraging widespread access and use, a large, positive impact across multiple health and economic sectors can be achieved.

  2. Barriers and Facilitators to Adolescents' Use of Long-Acting Reversible Contraceptives.

    PubMed

    Pritt, Nicole M; Norris, Alison H; Berlan, Elise D

    2017-02-01

    Most pregnancies among teenagers are unintended and many can be attributed to contraception misuse or nonuse. The etonogestrel implant and intrauterine devices, referred to as long-acting reversible contraceptives, or LARCs, are the most effective reversible contraceptive methods. These methods are safe for use by adolescents, yet the number of LARC users remains low among adolescents in the United States. In this review we examine recent literature about barriers and facilitators to LARC use among adolescent women. Factors that influence decision-making and provision are organized into 4 categories: (1) cost and clinical operations; (2) adolescent awareness and attitudes; (3) confidentiality, consent, and parental attitudes; and (4) health care provider knowledge, attitudes, and counseling. Knowledge deficits and misconceptions among adolescents and their health care providers are key barriers to adolescent LARC use.

  3. The role of long-acting injectable antipsychotics in schizophrenia: a critical appraisal.

    PubMed

    Brissos, Sofia; Veguilla, Miguel Ruiz; Taylor, David; Balanzá-Martinez, Vicent

    2014-10-01

    Despite their widespread use, long-acting injectable (LAI) antipsychotics (APs) are often regarded with some negativity because of the assumption of punishment, control and insufficient evolution towards psychosocial development of patients. However, LAI APs have proved effective in schizophrenia and other severe psychotic disorders because they assure stable blood levels, leading to a reduction of the risk of relapse. Therapeutic opportunities have also arisen after introduction of newer, second-generation LAI APs in recent years. Newer LAI APs are more readily dosed optimally, may be better tolerated and are better suited to integrated rehabilitation programmes. This review outlines the older and newer LAI APs available for the treatment of schizophrenia, with considerations of past and present pharmacological and therapeutic issues. Traditional, evidence-based approaches to systematic reviews and randomized clinical trials are of limited utility in this area so this paper's blending of experimental trials with observational research is particularly appropriate and effective.

  4. Aripiprazole long-acting injectable formulations for schizophrenia: aripiprazole monohydrate and aripiprazole lauroxil.

    PubMed

    Citrome, Leslie

    2016-01-01

    Aripiprazole monohydrate (AM) and aripiprazole lauroxil (AL) are two different long-acting injectable formulations of aripiprazole. AM 400 mg administered once monthly demonstrated efficacy in an acute, double-blind, placebo-controlled, randomized clinical trial, as well as in a double-blind, placebo-controlled, randomized-withdrawal maintenance study, and in two non-inferiority maintenance studies. AL is a prodrug of aripiprazole and available in 441 mg, 662 mg or 882 mg strengths. AL 441 mg and 882 mg administered once monthly demonstrated efficacy in an acute, double-blind, placebo-controlled, randomized clinical trial. The pharmacokinetic profile of AL also led to approval of dosing intervals of every 6 weeks for the 882 mg dose. The overall tolerability profiles of both products are consistent with what is known about oral aripiprazole.

  5. Clinicians' attitudes toward the use of long-acting injectable antipsychotics.

    PubMed

    Samalin, Ludovic; Charpeaud, Thomas; Blanc, Olivier; Heres, Stephan; Llorca, Pierre-Michel

    2013-07-01

    Depot formulations are not widely used in everyday practice. This study aimed to assess psychiatrists' attitudes toward the use of long-acting injectable (LAI) antipsychotics in schizophrenia. We interviewed 113 French psychiatrists about the factors that influenced their prescription of LAI antipsychotics. Multidimensional and cluster analyses were used to detect correlations. The most important factor against the use of LAI antipsychotics is a sufficient estimated compliance with the oral formulation. For first-generation LAI, the main factor is the risk for extrapyramidal symptoms; and for second-generation LAI, it is the unavailability of the equivalent oral formulation. Four factors incite the psychiatrists to prescribe LAI. Two different clusters of patients can also be identified. Most factors influencing the clinicians' attitudes toward the use of LAI antipsychotics are shared in many countries. Conversely, some attitudes related to organizational aspects, particularly the relevance of health care costs, may vary from one country to another.

  6. The role of long-acting injectable antipsychotics in schizophrenia: a critical appraisal

    PubMed Central

    Veguilla, Miguel Ruiz; Taylor, David; Balanzá-Martinez, Vicent

    2014-01-01

    Despite their widespread use, long-acting injectable (LAI) antipsychotics (APs) are often regarded with some negativity because of the assumption of punishment, control and insufficient evolution towards psychosocial development of patients. However, LAI APs have proved effective in schizophrenia and other severe psychotic disorders because they assure stable blood levels, leading to a reduction of the risk of relapse. Therapeutic opportunities have also arisen after introduction of newer, second-generation LAI APs in recent years. Newer LAI APs are more readily dosed optimally, may be better tolerated and are better suited to integrated rehabilitation programmes. This review outlines the older and newer LAI APs available for the treatment of schizophrenia, with considerations of past and present pharmacological and therapeutic issues. Traditional, evidence-based approaches to systematic reviews and randomized clinical trials are of limited utility in this area so this paper’s blending of experimental trials with observational research is particularly appropriate and effective. PMID:25360245

  7. A critical appraisal of paliperidone long-acting injection in the treatment of schizoaffective disorder.

    PubMed

    Chue, Pierre; Chue, James

    2016-01-01

    Schizoaffective disorder (SCA) is a chronic and disabling mental illness that presents with mixed symptoms of schizophrenia and affective disorders. SCA is recognized as a discrete disorder, but with greater heterogeneity and symptom overlap, leading to difficulty and delay in diagnosis. Although the overall prognosis is intermediate between schizophrenia and mood disorders, SCA is associated with higher rates of suicide and hospitalization than schizophrenia. No treatment guidelines exist for SCA, and treatment is frequently complex, involving off-label use and polypharmacy (typically combinations of antipsychotics, mood stabilizers, and antidepressants). Oral paliperidone extended-release was the first agent to be approved for the treatment of SCA. As in schizophrenia and bipolar disorder, adherence to oral medications is poor, further contributing to suboptimal outcomes. The use of an antipsychotic in a long-acting injection (LAI) addresses adherence issues, thus potentially reducing relapse. Paliperidone palmitate represents the LAI formulation of paliperidone. In a long-term, double-blind, randomized, controlled trial of adult patients (n=334; intent-to-treat [ITT]) with SCA, paliperidone long-acting injection (PLAI) significantly delayed risk of relapse compared to placebo (hazard ratio 2.49, 95% confidence interval, 1.55-3.99; P<0.001). This study demonstrated the efficacy and safety of PLAI when used as either monotherapy or adjunctive therapy for the maintenance treatment of SCA. The results are consistent with a similarly designed study conducted in patients with schizophrenia, which suggests a benefit in the long-term control of not only psychotic but also affective symptoms. No new safety signals were observed. When used in monotherapy, PLAI simplifies treatment by reducing complex pharmacotherapy and obviating the necessity for daily oral medications. PLAI is the second agent, and the first LAI, to be approved for the treatment of SCA; as an LAI

  8. A critical appraisal of paliperidone long-acting injection in the treatment of schizoaffective disorder

    PubMed Central

    Chue, Pierre; Chue, James

    2016-01-01

    Schizoaffective disorder (SCA) is a chronic and disabling mental illness that presents with mixed symptoms of schizophrenia and affective disorders. SCA is recognized as a discrete disorder, but with greater heterogeneity and symptom overlap, leading to difficulty and delay in diagnosis. Although the overall prognosis is intermediate between schizophrenia and mood disorders, SCA is associated with higher rates of suicide and hospitalization than schizophrenia. No treatment guidelines exist for SCA, and treatment is frequently complex, involving off-label use and polypharmacy (typically combinations of antipsychotics, mood stabilizers, and antidepressants). Oral paliperidone extended-release was the first agent to be approved for the treatment of SCA. As in schizophrenia and bipolar disorder, adherence to oral medications is poor, further contributing to suboptimal outcomes. The use of an antipsychotic in a long-acting injection (LAI) addresses adherence issues, thus potentially reducing relapse. Paliperidone palmitate represents the LAI formulation of paliperidone. In a long-term, double-blind, randomized, controlled trial of adult patients (n=334; intent-to-treat [ITT]) with SCA, paliperidone long-acting injection (PLAI) significantly delayed risk of relapse compared to placebo (hazard ratio 2.49, 95% confidence interval, 1.55–3.99; P<0.001). This study demonstrated the efficacy and safety of PLAI when used as either monotherapy or adjunctive therapy for the maintenance treatment of SCA. The results are consistent with a similarly designed study conducted in patients with schizophrenia, which suggests a benefit in the long-term control of not only psychotic but also affective symptoms. No new safety signals were observed. When used in monotherapy, PLAI simplifies treatment by reducing complex pharmacotherapy and obviating the necessity for daily oral medications. PLAI is the second agent, and the first LAI, to be approved for the treatment of SCA; as an LAI

  9. Long-Acting Injectable Antipsychotics for Schizophrenia: Sociodemographic Characteristics and Treatment Adherence.

    PubMed

    McCreath, James; Larson, Essie; Bharatiya, Purabi; Labanieh, Hisham A; Weiss, Zvi; Lozovatsky, Michael

    2017-02-23

    Long-acting injectable (LAI) antipsychotic medications are employed universally for the treatment of schizophrenia. This study retrospectively assessed the variables that factor into an individual's adherence to LAIs. The data sample was obtained from the adult ambulatory services of a large general hospital mental health center located in Elizabeth, New Jersey. Reports were run in November 2015 to identify patients who had received at least 1 LAI between January 1, 2014, and October 14, 2015. In September 2016, an additional report was run to collect follow-up data. The sample included 120 women and 178 men, ranging in age from 18-81 years, who received at least 1 LAI during a 23-month period. A hazard analysis for single-decrement, nonrepeatable events was used to assess the risk of discontinuation of LAIs during the study period. Separate χ² analyses were conducted to assess differences in discontinuation rates for sociodemographic variables, program type variables, type of long-acting medication, and time effects. The cumulative continuation rate across the study period was 73%. Main effect differences were found in continuation rates for program type (χ²₂undefined= 10.252, P = .006), LAI type (χ²₅ = 23.365, P < .000), and prescribed frequency of LAI (χ²₂ = 7.622, P = .022). In addition, multiple time-dependent effect differences were found. No significant main effect results were found for LAI continuation rates and patient age (χ²₃ = 3.689, P = .297), sex (χ²₁ = 0.904, P = .342), race (χ²₃ = 5.785, P = .123), or enrollment in involuntary outpatient commitment (χ²₁ = 2.989, P = .084). The findings of the current research suggest that medication type, frequency of medication appointments, and program type may be key in increasing and maintaining LAI adherence.

  10. Pharmacokinetics of Injectable, Long-Acting Nevirapine for HIV Prophylaxis in Breastfeeding Infants

    PubMed Central

    Cortez, John M.; Quintero, Rafaela; Moss, John A.; Beliveau, Martin; Smith, Thomas J.

    2014-01-01

    Mother-to-child transmission (MTCT) of HIV-1 remains a global health problem. The World Health Organization (WHO) recommendations advise the administration of a once-daily, oral, prophylactic regimen of the nonnucleoside reverse transcriptase inhibitor nevirapine (NVP) from birth until 4 to 6 weeks of age for infants born to HIV-infected mothers in regions without access to safe and nutritionally adequate alternatives to breast milk. A critical factor driving the successful implementation of the WHO guidelines involves sustaining high adherence to the frequent dosing. With these challenges in mind, we have developed the first injectable, sustained-release NVP formulations with the goal of providing, for 6 weeks or longer, preventative plasma drug levels from a single subcutaneous administration at birth. The long-acting NVP consists of large (>50 μm), monodisperse NVP particles coated with biocompatible polymers that control the drug release kinetics. Two lead formulations exhibiting burst-free, sustained-release kinetics for up to 75 days in vitro were developed. Subsequent in vivo studies in rats demonstrated no toxicity related to the formulations. Rat plasma NVP concentrations were above the analytical assay's limit of quantification for up to 28 days. Pharmacokinetic analysis of the rat plasma NVP concentration-time data allowed absorption rate constants to be calculated. These data then were used to simulate infant NVP exposure from a single injected dose (<200 mg) of our long-acting formulations, demonstrating preliminary feasibility of the technology to maintain safe, preventative NVP plasma levels (0.2 to 3.0 μg ml−1) for 6 weeks or longer. PMID:25313219

  11. Long-acting muscarinic receptor antagonists for the treatment of respiratory disease.

    PubMed

    Cazzola, Mario; Page, Clive; Matera, Maria Gabriella

    2013-06-01

    The use of muscarinic receptor antagonists in the treatment of chronic obstructive pulmonary disease (COPD) is well established. More recently, the potential for long-acting muscarinic receptor antagonists (LAMAs) in the treatment of asthma has also been investigated. While LAMAs offer advantages over short-acting muscarinic receptor antagonists, in terms of a reduced dosing frequency, there remains a need for therapies that improve symptom control throughout both the day and night, provide better management of exacerbations and deliver improved health-related quality of life. Furthermore, the potential for unwanted anticholinergic side effects, particularly cardiovascular effects, remains a concern for this class of compounds. Novel LAMAs in clinical development for the treatment of respiratory disease include: aclidinium bromide, NVA237 (glycopyrronium bromide), GP-MDI, EP-101, CHF-5259, umeclidinium bromide, CHF-5407, TD-4208, AZD8683 and V-0162. These compounds offer potential advantages in terms of onset of action, symptom control and safety. In addition, a number of LAMAs are also being developed as combination treatments with long-acting β2-agonists (LABAs) or inhaled glucocorticosteroids, potentially important treatment options for patients who require combination therapy to achieve an optimal therapeutic response as their disease progresses. More recently, compounds such as GSK961081 and THRX-198321 have been identified that combine LAMA and LABA activity in the same molecule, and have the potential to offer the benefits of combination therapy in a single compound. Here, we review novel LAMAs and dual action compounds in clinical development, with a particular focus on how they may address the current unmet clinical needs in the treatment of respiratory disease, particularly COPD. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Pharmacokinetics of injectable, long-acting nevirapine for HIV prophylaxis in breastfeeding infants.

    PubMed

    Cortez, John M; Quintero, Rafaela; Moss, John A; Beliveau, Martin; Smith, Thomas J; Baum, Marc M

    2015-01-01

    Mother-to-child transmission (MTCT) of HIV-1 remains a global health problem. The World Health Organization (WHO) recommendations advise the administration of a once-daily, oral, prophylactic regimen of the nonnucleoside reverse transcriptase inhibitor nevirapine (NVP) from birth until 4 to 6 weeks of age for infants born to HIV-infected mothers in regions without access to safe and nutritionally adequate alternatives to breast milk. A critical factor driving the successful implementation of the WHO guidelines involves sustaining high adherence to the frequent dosing. With these challenges in mind, we have developed the first injectable, sustained-release NVP formulations with the goal of providing, for 6 weeks or longer, preventative plasma drug levels from a single subcutaneous administration at birth. The long-acting NVP consists of large (>50 μm), monodisperse NVP particles coated with biocompatible polymers that control the drug release kinetics. Two lead formulations exhibiting burst-free, sustained-release kinetics for up to 75 days in vitro were developed. Subsequent in vivo studies in rats demonstrated no toxicity related to the formulations. Rat plasma NVP concentrations were above the analytical assay's limit of quantification for up to 28 days. Pharmacokinetic analysis of the rat plasma NVP concentration-time data allowed absorption rate constants to be calculated. These data then were used to simulate infant NVP exposure from a single injected dose (<200 mg) of our long-acting formulations, demonstrating preliminary feasibility of the technology to maintain safe, preventative NVP plasma levels (0.2 to 3.0 μg ml(-1)) for 6 weeks or longer.

  13. Safety of the long-acting neuraminidase inhibitor laninamivir octanoate hydrate in post-marketing surveillance.

    PubMed

    Kashiwagi, Seizaburo; Yoshida, Sanae; Yamaguchi, Hiroki; Niwa, Shinpei; Mitsui, Noriko; Tanigawa, Masatoshi; Shiosakai, Kazuhito; Yamanouchi, Naoki; Shiozawa, Tomoo; Yamaguchi, Fumie

    2012-11-01

    Laninamivir octanoate hydrate (laninamivir) is a long-acting neuraminidase inhibitor (NAI) that completes treatment with only a single inhalation. It was launched in Japan in October 2010 as an anti-influenza agent. A post-marketing surveillance study was conducted in the 2010/2011 influenza season to assess the safety of this drug in clinical settings. Adverse drug reactions (ADRs) were observed in 50 patients (59 events) out of 3542 patients subjected to safety evaluation (incidence 1.41%). Commonly reported ADRs were psychiatric disorders (abnormal behaviour, etc.), gastrointestinal disorders (diarrhoea, nausea, etc.) and nervous system disorders (dizziness, etc.), with incidences of 0.48% (n=17), 0.45% (n=16) and 0.17% (n=6), respectively. No serious ADRs occurred. ADRs usually emerged on the day on which laninamivir was inhaled (52.5%) and ADRs emerged within 3 days after inhalation in >90% of adversely affected patients. ADRs resolved or improved within 3 days in >85% of patients. The incidence of adverse events involving abnormal behaviour was 3.1% (30/959) among patients <10 years of age, 0.7% (8/1088) among patients aged 10-19 years, 0.1% (2/1431) among adult patients aged 20-64 years and 0.0% (0/64) among patients aged ≥65 years. It was confirmed that laninamivir is unlikely to cause delayed ADRs or a prolonged duration of ADRs despite this drug being a long-acting NAI. Furthermore, the incidence of ADRs was not found to have increased compared with that observed during clinical trials, and the types of ADR observed during this study were similar to those previously observed. Thus, laninamivir octanoate hydrate was confirmed to have no noticeable problem with safety. Copyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  14. Differential pharmacology and clinical utility of long-acting bronchodilators in COPD – focus on olodaterol

    PubMed Central

    Matera, Maria Gabriella; Ora, Josuel; Cazzola, Mario

    2015-01-01

    Olodaterol (BI 1744 CL) is a novel, once-daily long-acting β2-agonist (LABA) designed with the aim of improving β2-adrenoreceptor selectivity and intrinsic activity. Phase III pivotal trials have documented that olodaterol Respimat Soft Mist inhaler 5 μg induces fast onset of bronchodilation, comparable with formoterol at day 1. Moreover, significant lung function improvements have been documented up to 48 weeks in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). Olodaterol was generally well tolerated and had an acceptable cardiovascular and respiratory adverse event profile. Regrettably, the clinical development of olodaterol is however still too partial to draw any firm conclusions on the positioning of this ultra-LABA as monotherapy in the management of COPD. Waiting for further data on the impact of olodaterol on different patient-reported outcomes, which however are widely available for indacaterol, and mainly for a head-to-head comparison between these two ultra-LABAs and between olodaterol long-acting antimuscarinic antagonists other than tiotropium, we believe it is correct to follow the clinical indications of indacaterol also for olodaterol. In any case, the parallel bronchodilating modes of action of olodaterol and tiotropium make them an attractive combination in COPD. The results from the ongoing large TOviTO Phase III trial program have documented the efficacy and safety of olodaterol/tiotropium fixed-dose combination as maintenance therapy in patients with moderate to very severe COPD. In particular, olodaterol/tiotropium fixed-dose combination provides a convincing alternative for patients remaining symptomatic with olodaterol monotherapy. PMID:26676161

  15. Biocompatible riboflavin laurate long-acting injectable nanosuspensions allowing sterile filtration.

    PubMed

    Hu, Xi; Lin, Xia; Gu, Yuechen; Liu, Zitong; Tang, Yilin; Zhang, Yu; Chen, Xi; Wang, Yanjiao; Tang, Xing

    2014-08-01

    The aim of this research was to prepare biocompatible riboflavin laurate (RFL) long-acting injectable nanosuspensions for intramuscular injection with a small particle size allowing sterile filtration. RFL nanosuspensions were manufactured by a precipitation-combined high-pressure homogenization method. Three kinds of mixed stabilizers-d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a primary stabilizer, and egg lecithin (PL-100M), Kollidon VA64, Kollidon S-630 as a secondary stabilizer, were separately applied to avoid further aggregation. In the three optimized formulations, the mean particle size of the RFL nanosuspensions was about 170 nm allowing sterilization by filtration. Results from transmission electron microscopy, differential scanning calorimeter, powder X-ray diffraction and Fourier transform infrared reflectance spectroscopy revealed that RFL existed as rod-like crystals. However, a few nano-spheres under 100 nm were found only when PL-100 was used as a secondary stabilizer, possibly due to TPGS and PL-100, which inserted into RFL during the process of crystallization and homogenization. In irritation testing, RFL long-acting injection (LAI) stabilized by TPGS and PL-100 led to mild paw-licking responses and a slight inflammatory reaction, which returned to normal by 14 d after administration. The endogenous PL-100 and nano-spheres with a small size may have contributed to the excellent biocompatibility. As a result, TPGS and PL-100 were selected as blended stabilizers to prepare the irritation-free RFL-LAI that could be sterilized by passage through a 0.22 μm millipore membrane filter.

  16. Second-generation long-acting injectable antipsychotics in schizophrenia: patient functioning and quality of life

    PubMed Central

    Montemagni, Cristiana; Frieri, Tiziana; Rocca, Paola

    2016-01-01

    Long-acting injectable antipsychotics (LAIs) were developed to make treatment easier, improve adherence, and/or signal the clinician when nonadherence occurs. Second-generation antipsychotic LAIs (SGA-LAIs) combine the advantages of SGA with a long-acting formulation. The purpose of this review is to evaluate the available literature concerning the impact of SGA-LAIs on patient functioning and quality of life (QOL). Although several studies regarding schizophrenia patients’ functioning and QOL have been performed, the quantity of available data still varies greatly depending on the SGA-LAI under investigation. After reviewing the literature, it seems that SGA-LAIs are effective in ameliorating patient functioning and/or QOL of patients with schizophrenia, as compared with placebo. However, while methodological design controversy exists regarding the superiority of risperidone LAI versus oral antipsychotics, the significant amount of evidence in recently published research demonstrates the beneficial influence of risperidone LAI on patient functioning and QOL in stable patients and no benefit over oral treatment in unstable patients. However, the status of the research on SGA-LAIs is lacking in several aspects that may help physicians in choosing the correct drug therapy. Meaningful differences have been observed between SGA-LAIs in the onset of their clinical efficacy and in the relationships between symptoms and functioning scores. Moreover, head-to-head studies comparing the effects of SGA-LAIs on classical measures of psychopathology and functioning are available mainly on risperidone LAI, while those comparing olanzapine LAI with other SGA-LAIs are still lacking. Lastly, some data on their use, especially in first-episode or recent-onset schizophrenia and in refractory or treatment-resistant schizophrenia, is available. PMID:27143893

  17. Long-acting muscarinic antagonist (LAMA) plus long-acting beta-agonist (LABA) versus LABA plus inhaled corticosteroid (ICS) for stable chronic obstructive pulmonary disease (COPD).

    PubMed

    Horita, Nobuyuki; Goto, Atsushi; Shibata, Yuji; Ota, Erika; Nakashima, Kentaro; Nagai, Kenjiro; Kaneko, Takeshi

    2017-02-10

    Three classes of inhaler medications are used to manage chronic obstructive pulmonary disease (COPD): long-acting beta-agonists (LABA), long-acting muscarinic antagonists (LAMA), and inhaled corticosteroids (ICS). When two classes of medications are required, LAMA plus LABA (LAMA+LABA) and LABA plus ICS (LABA+ICS) are often selected because these combinations can be administered via a single medication device. The previous Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidance recommended LABA+ICS as the first-line treatment for managing stable COPD in high-risk people of categories C and D. However, the updated GOLD 2017 guidance recommends LAMA+LABA over LABA+ICS. To compare the benefits and harms of LAMA+LABA versus LABA+ICS for treatment of people with stable COPD. We performed an electronic search of the Cochrane Airways Group Specialised Register (2 February 2016), ClinicalTrials.gov (4 June 2016), and the World Health Organization Clinical Trials Search Portal (4 June 2016), followed by a handsearch (5 June 2016). Two review authors screened and scrutinised the selected articles. We included individual randomised controlled trials, parallel-group trials, and cross-over trials comparing LAMA+LABA and LABA+ICS for stable COPD. The minimum accepted trial duration was one month and trials should have been conducted in an outpatient setting. Two review authors independently extracted data and evaluated risk of bias. We resolved any discrepancies through discussion. We analysed dichotomous data as odds ratios (OR), and continuous data as mean differences (MD), with 95% confidence interval (CI) using Review Manager 5. Exacerbations were measured by counting the number of people experiencing one or more exacerbation. We included 11 studies comprising 9839 participants in our quantitative analysis. Most studies included people with moderate to severe COPD, without recent exacerbations. One pharmaceutical sponsored trial that included only people with

  18. Treatment of postural tachycardia syndrome: a comparison of octreotide and midodrine.

    PubMed

    Hoeldtke, Robert D; Bryner, Kimberly D; Hoeldtke, Martin E; Hobbs, Gerald

    2006-12-01

    We assessed the potency of octreotide and midodrine, and their combination, in the treatment of the postural tachycardia syndrome (POTS) and orthostatic intolerance (OI). Nine patients with POTS and six patients with OI stood for up to 1 hour while their HR and BP were monitored. Patients received on separate days, midodrine 10 mg 1 hour before testing, octreotide 0.9 micro g/kg 8 minutes before testing or combination therapy. Standing time in the patients with POTS was 41.2 +/- 8.4 minutes and not improved by midodrine or octreotide, but increased to 56.3 +/- 2.7 (P < 0.01) minutes following combination therapy. The standing heart rate in POTS, 114 +/- 0.7 bpm, was suppressed by midodrine 92.8 +/- 0.7 (P < 0.001), octreotide 90.6 +/- 0.78 (P < 0.001), and combination therapy 84.7 +/- 0.7 (P < 0.001). Combination therapy was better than monotherapy (P < 0.001) but only for the first 10 minutes of standing. Standing time of 36.3 +/- 3.5 minutes in the patients with OI improved with midodrine, octreotide and combination therapy (55.5 +/- 3.1, 56.5 +/- 3.5, and 56.6 +/- 3.3, respectively, P < 0.05 for each). Standing heart rate in OI was 100 +/- .76 bpm; following midodrine it was 80.3 +/- .69 (P < 0.05), following octreotide it was 84.8 +/- .86, and following combination therapy it was 71.2 +/- .9 (P < 0.01). The RR interval versus time area under the curve (The Orthostatic Index) was 21.1 +/- 4 in patients with OI. After midodrine it was 41.4 +/- 3.5 (P < 0.01), after octreotide 40.3 +/- 3.8 (P < 0.01) and after the combination it was 47.3 +/- 4.6 (P < 0.001). Midodrine and octreotide suppressed tachycardia in POTS and improved standing times in OI. The two drugs had similar potencies; combination therapy was not significantly better than monotherapy.

  19. Esthesioneuroblastoma (olfactory neuroblastoma) treated with 111In-octreotide and 177Lu-DOTATATE PRRT.

    PubMed

    Makis, William; McCann, Karey; McEwan, Alexander J B

    2015-04-01

    A 51-year-old man with a recurrent metastatic esthesioneuroblastoma (olfactory neuroblastoma) was referred for peptide receptor radionuclide therapy (PRRT). He received 4 treatments of 111In-octreotide over 8 months and 3 treatments of 177Lu-DOTATATE over 4 months, which helped alleviate his symptoms and improved his quality of life; however, the tumor ultimately progressed and he passed away shortly thereafter. PRRT with 111In-octreotide or 177Lu-DOTATATE could play a role in the management of esthesioneuroblastoma.

  20. ( sup 111 In-DTPA-D-Phe sup 1 )-octreotide, a potential radiopharmaceutical for imaging of somatostatin receptor-positive tumors: Synthesis, radiolabeling and in vitro validation

    SciTech Connect

    Bakker, W.H.; Albert, R.; Bruns, C.; Breeman, W.A.P.; Hofland, L.J.; Marbach, P.; Pless, J.; Pralet, D.; Stolz, B.; Koper, J.W.; Lamberts, S.W.J.; Visser, T.J.; Krenning, E.P. Sandoz Pharma AG, Basel )

    1991-01-01

    As starting material for a potentially convenient radiopharmaceutical, a diethylenetriaminopentaacetic acid (DTPA) conjugated derivative of octreotide (SMS 201-995) was prepared. This peptide, (DTPA-D-Phe{sup 1})-octreotide (SDZ 215-811) binds more than 95% of added {sup 111}In in an easy, single-step labeling procedure without necessity of further purification. The specific somatostatin-like biologic effect of these analogues was proven by the inhibition of growth hormone secretion by cultured rat pituitary cells in a dose-dependent fashion by octreotide, (DTPA-D-Phe{sup 1})-octreotide and non-radioactive ({sup 115}In-DTPA-D-Phe{sup 1})-octreotide. The binding of ({sup 111}In-DTPA-D-Phe{sup 1})-octreotide to rat brain cortex membranes proved to be displaced similarly by natural somatosatin as well as by octreotide, suggesting specific binding of ({sup 111}In-DTPA-D-Phe{sup 1})-octreotide to somatostatin receptors. The binding of the indium-labeled compound showed a somewhat lower affinity when compared with the iodinated (Tyr{sup 3})-octreotide, but indium-labeled (DTPA-D-Phe{sup 1})-octreotide still binds with nanomolar affinity. In conjunction with in vivo studies, these results suggest that ({sup 111}In-DTPA-D-Phe{sup 1})-octreotide is a promising radiopharmaceutical for scintigraphic imaging of somatostatin receptor-positive tumors.

  1. Neuroprotective effects of octreotide on diabetic neuropathy in rats.

    PubMed

    Solmaz, Volkan; Çınar, Bilge Piri; Yiğittürk, Gürkan; Özlece, Hatice Köse; Avni Eroglu, Hüseyin; Tekatas, Aslan; Erbaş, Oytun; Taşkıran, Dilek

    2017-02-26

    The purpose of the present study is to investigate the possible healing effects of octreotide (OCT) on motor performance, electrophysiological and histopathological findings of diabetic neuropathy in a rat model of diabetes mellitus (DM). To induce diabetes, rats were administered a single dose (60mg/kg) of streptozotocin (STZ). Diabetic rats were treated either with saline (1ml/kg/day, n=7) or OCT (0.1mg/kg/day, n=7) for four weeks. Seven rats served as control group and received no treatment. At the end of the study, electromyography (EMG), gross motor function (inclined plate test), general histology and the perineural thickness of sciatic nerve were evaluated. At the end of study, weight loss was significantly lower in OCT treated rats than that of saline treated ones (p<0.001). Electrophysiologically, compound muscle action potential (CMAP) amplitudes of the saline treated DM group were significantly reduced than those of controls (p<0.0001). Also, distal latency and CMAP durations were significantly prolonged in saline treated DM group (p<0.05) compared to control. However, treatment of diabetic rats with OCT significantly counteracted these alterations in EMG. Furthermore, OCT significantly improved the motor performance scores in diabetic rats (p<0.05). Histomorphometric assessment of the sciatic nerve demonstrated a significant reduction in perineural thickness in OCT treated group compared to saline group. In conclusion, OCT possesses beneficial effects against STZ-induced diabetic neuropathy, which promisingly support the use of OCT as a neuroprotective agent in patients with diabetic neuropathy.

  2. Free somatostatin receptor fraction predicts the antiproliferative effect of octreotide in a neuroendocrine tumor model: implications for dose optimization.

    PubMed

    Heidari, Pedram; Wehrenberg-Klee, Eric; Habibollahi, Peiman; Yokell, Daniel; Kulke, Matthew; Mahmood, Umar

    2013-12-01

    Somatostatin receptors (SSTR) are highly expressed in well-differentiated neuroendocrine tumors (NET). Octreotide, an SSTR agonist, has been used to suppress the production of vasoactive hormones and relieve symptoms of hormone hypersecretion with functional NETs. In a clinical trial, an empiric dose of octreotide treatment prolonged time to tumor progression in patients with small bowel neuroendocrine (carcinoid) tumors, irrespective of symptom status. However, there has yet to be a dose optimization study across the patient population, and methods are currently lacking to optimize dosing of octreotide therapy on an individual basis. Multiple factors such as total tumor burden, receptor expression levels, and nontarget organ metabolism/excretion may contribute to a variation in SSTR octreotide occupancy with a given dose among different patients. In this study, we report the development of an imaging method to measure surface SSTR expression and occupancy level using the PET radiotracer (68)Ga-DOTATOC. In an animal model, SSTR occupancy by octreotide was assessed quantitatively with (68)Ga-DOTATOC PET, with the finding that increased occupancy resulted in decreased tumor proliferation rate. The results suggested that quantitative SSTR imaging during octreotide therapy has the potential to determine the fractional receptor occupancy in NETs, thereby allowing octreotide dosing to be optimized readily in individual patients. Clinical trials validating this approach are warranted.

  3. Therapy using labelled somatostatin analogues: comparison of the absorbed doses with 111In-DTPA-D-Phe1-octreotide and yttrium-labelled DOTA-D-Phe1-Tyr3-octreotide.

    PubMed

    Barone, Raffaella; Walrand, Stéphan; Konijnenberg, Mark; Valkema, Roelf; Kvols, Larry K; Krenning, Eric P; Pauwels, Stanislas; Jamar, François

    2008-03-01

    We estimated the absorbed doses for (111)In-DTPA-D-Phe(1)-octreotide and (90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide in the same patients in order to compare the potential effectiveness (tumour dose) and safety (kidney and red marrow dose) of these drugs for peptide-targeted radiotherapy of somatostatin receptor positive tumours. Six patients with neuroendocrine tumours underwent quantitative (111)In-DTPA-D-Phe(1)-octreotide SPECT and (86)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide PET scan at intervals of 1 week. All studies were performed with a co-infusion of amino acids for renal protection. PET and SPECT were reconstructed using iterative algorithms, incorporating attenuation and scatter corrections. Tissue uptakes (IA%) were measured and used to calculate residence times. Absorbed doses to tissues were estimated and the maximal allowed activity, defined as either the activity delivering 23 Gy to the kidneys (MAA(K)) or 2 Gy to the red marrow (MAA(RM)), was calculated and the resulting tumour absorbed doses were computed. For the MAA(K) the mean absorbed dose to the red marrow was lower for (90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide than for (111)In-DTPA-D-Phe(1)-octreotide (1.8+/-0.9 Gy vs. 6.4+/-1.6 Gy; P<0.001). The median absorbed dose to tumours for the MAA(K) was two-fold higher for (90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide as compared to (111)In-DTPA-D-Phe(1)-octreotide (30.1 vs. 12.6 Gy; P<0.05). The median absorbed dose to tumours estimated for the MAA(RM) was 10-fold higher for (90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide than for (111)In-DTPA-D-Phe(1)-octreotide (35.1 Gy vs. 3.9 Gy; P<0.05). This direct intra-patient comparison confirms that the use of (90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide is more appropriate for therapy of somatostatin receptor bearing tumours. When using (111)In-DTPA-D-Phe(1)-octreotide, the red marrow represents the major critical organ; this can result in significant toxicity if high activities have to be administered to obtain efficient tumour irradiation.

  4. The role of somatostatin (octreotide) in the regulation of melatonin secretion in healthy volunteers and in patients with primary hypothyroidism.

    PubMed

    Wikner, J; Wetterberg, L; Röjdmark, S

    1999-01-01

    Somatostatin has been found in the pineal gland of several animal species, which suggests that it may be involved in the regulation of melatonin secretion. Whether somatostatin has regulatory influence on melatonin secretion in man has never been unequivocally shown. We studied the nocturnal melatonin secretion in 8 healthy volunteers, and 6 women with untreated primary hypothyroidism, a disease state that is associated with increased nocturnal secretion of melatonin. The participants were given subcutaneous injections at 18:00 h and 23:00 h of either saline or octreotide (Sandostatin; each injection 50 microg). During the nights when the healthy volunteers were given octreotide, melatonin secretion was similar to that recorded during administration of saline. Also the urinary excretion of melatonin was of similar magnitude at these two occasions. By contrast, the GH secretion was significantly lower the nights the healthy controls were given octreotide (GH AUC 22.6+/-5.4 mU/l x h during octreotide and 126.6+/-21.9 mU/l x h during saline; p<0.01). The patients with hypothyroidism also showed similar nocturnal melatonin secretion during octreotide and saline. Urinary excretion of melatonin also remained unchanged, as did GH secretion. The total nocturnal secretion of TSH was, however, significantly reduced by octreotide (TSH AUC 562+/-136 mU/l x h during octreotide and 851+/-185 mU/l x h during saline; p<0.05), thus suggesting that 100 microg of octreotide should be sufficient to inhibit also the pinealocytes if their function were regulated by somatostatin. Since exogenous somatostatin--in the form of octreotide--fails to influence nocturnal secretion and urinary excretion of melatonin in normal subjects and in patients with primary hypothyroidism, it is reasonable to assume that endogenous somatostatin may not be an important regulator of melatonin secretion in man.

  5. Roles of gall bladder emptying and intestinal transit in the pathogenesis of octreotide induced gall bladder stones.

    PubMed Central

    Hussaini, S H; Pereira, S P; Veysey, M J; Kennedy, C; Jenkins, P; Murphy, G M; Wass, J A; Dowling, R H

    1996-01-01

    BACKGROUND--Octreotide treatment of acromegalic patients increases the % deoxycholic acid conjugates and the cholesterol saturation of gall bladder bile, and induces gall stone formation. AIMS--To study the roles of gall bladder emptying and intestinal transit in these phenomena. METHODS AND PATIENTS--Gall bladder emptying and mouth to caecum transit was measured in (a) control subjects and acromegalic patients given saline or 50 micrograms of octreotide, and (b) acromegalic patients taking long term octreotide. In the second group, large bowel transit was also measured. RESULTS--A single dose of octreotide inhibited meal stimulated gall bladder emptying, the ejection fraction falling from mean (SEM) 66.0 (2.3)% to 7.0 (5.3)% in controls (p < 0.001); from 72.5 (2.1) to 16.6 (5.1)% in untreated acromegalic patients (p < 0.001), and to 30.4 (9.5)% in acromegalic patients taking long term octreotide (p < 0.001 v untreated acromegalic group). Octreotide prolonged mouth to caecum transit time, from 112 (15) min to 237 (13) min in controls (p < 0.001), from 170 (13) min to 282 (11) min in untreated acromegalic patients (p < 0.001), and to 247 (10) min in acromegalic patients taking long term octreotide (p < 0.001 v untreated acromegalic patients). The mean large bowel transit in octreotide untreated compared with treated acromegalic patients remained unchanged (40 (6) h v 47 (6) h). CONCLUSIONS--Prolongation of intestinal transit and impaired gall bladder emptying may contribute to lithogenic changes in bile composition and gall stone formation in patients receiving long term octreotide. PMID:8707128

  6. “Set it and forget it”: Women’s perceptions and opinions of long-acting topical vaginal gels

    PubMed Central

    van den Berg, Jacob J.; Rosen, Rochelle K.; Bregman, Dana E.; Thompson, Lara A.; Jensen, Kathleen M.; Kiser, Patrick F.; Katz, David F.; Buckheit, Karen; Buckheit, Robert W.; Morrow, Kathleen M.

    2014-01-01

    Women’s initial understandings and anticipated acceptability of long-acting vaginal gels as potential anti-HIV microbicides was investigated by exploring the perceptibility variables associated with prototype formulations. Four focus groups with 29 women, aged 18–45, were conducted to consider gel prototypes with varied physicochemical and rheological properties. Participants responded favorably to the concept of long-acting vaginal gels as microbicides. Distinctions in understandings and stated needs regarding product dosing, characteristics, and effectiveness offer valuable insights into product design. Long-acting vaginal gels capable of protecting against HIV/STIs will be a viable option among potential users, with dosing frequency being an important factor in willingness to use. PMID:24248674

  7. Long-Acting Injectable Risperidone for Relapse Prevention and Control of Breakthrough Symptoms After a Recent First Episode of Schizophrenia

    PubMed Central

    Subotnik, Kenneth L.; Casaus, Laurie R.; Ventura, Joseph; Luo, John S.; Hellemann, Gerhard S.; Gretchen-Doorly, Denise; Marder, Stephen; Nuechterlein, Keith H.

    2016-01-01

    IMPORTANCE Long-acting, injectable, second-generation antipsychotic medication has tremendous potential to bring clinical stability to persons with schizophrenia. However, long-acting medications are rarely used following a first episode of schizophrenia. OBJECTIVE To compare the clinical efficacy of the long-acting injectable formulation of risperidone with the oral formulation in the early course of schizophrenia. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial performed at a university-based research clinic, between 2005 and 2012. Eighty-six patients with recent onset of schizophrenia were randomized to receive long-acting injectable risperidone or oral risperidone. Half of each group was simultaneously randomized to receive cognitive remediation to improve cognitive functioning or healthy-behaviors training to improve lifestyle habits and well-being. An intent-to-treat analysis was performed between October 4, 2012, and November 12, 2014. INTERVENTIONS A 12-month trial comparing the long-acting injectable vs oral risperidone and cognitive remediation vs healthy-behaviors training. MAIN OUTCOMES AND MEASURES Psychotic relapse and control of breakthrough psychotic symptoms. RESULTS Of the 86 patients randomized, 3 refused treatment in the long-acting injectable risperidone group. The psychotic exacerbation and/or relapse rate was lower for the long-acting risperidone group compared with the oral group (5% vs 33%; χ21 = 11.1; P < .001; relative risk reduction, 84.7%). Long-acting injectable risperidone better controlled mean levels of hallucinations and delusions throughout follow-up (β = −0.30; t68 = −2.6, P = .01). The cognitive remediation and healthy-behaviors training groups did not differ significantly regarding psychotic relapse, psychotic symptom control, or hospitalization rates, and there were no significant interactions between the 2 medications and the 2 psychosocial treatments. Discontinuations owing to inadequate clinical response

  8. Long-acting injectable antipsychotics and the development of postinjection delirium/sedation syndrome (PDSS).

    PubMed

    Novakovic, Vladan; Adel, Tymaz; Peselow, Eric; Lindenmayer, Jean-Pierre

    2013-01-01

    Five long-acting injectable (LAI) antipsychotics are currently available in the United States for the treatment of schizophrenia: fluphenazine decanoate, haloperidol decanoate, risperidone microspheres, paliperidone palmitate, and olanzapine pamoate. Additionally, aripiprazole LAI is currently under FDA review. However, research into the safety and tolerability of these LAIs, with particular regard to the development of postinjection delirium/sedation syndrome (PDSS), is limited and has been focused mainly on olanzapine pamoate. This proposal seeks to review data regarding all currently available LAI antipsychotics to determine if a significant association exists between these depot formulations and the development of PDSS. A review of all published literature from 2005 to the present was obtained via a PubMed search for current data regarding the topic of LAIs and the development of PDSS. Keywords used for the search were "long-acting injectable antipsychotics" in association with one of the following: "post-injection delirium/sedation syndrome," "PDSS, " "side effects, " and "tolerability." References to key articles were further explored for relevancy to this proposal. A case analysis based on all 8 olanzapine LAI clinical trials conducted between August 2000 and October 2008 showed an occurrence of PDSS in approximately 0.07% of injections or 1.4% of patients (30 cases in 29 patients). A second case analysis reviewing the clinical trial databases for 15 completed studies and the postmarketing safety database for risperidone LAI versus 10 completed clinical trials of paliperidone palmitate failed to demonstrate an occurrence of PDSS events in patients receiving either LAI treatment. However, one case of PDSS was identified in a placebo group. In 4 randomized, double-blind, placebo-controlled trials, treatment-emergent adverse events leading to treatment discontinuation were similar for paliperidone palmitate and placebo; however, among the most frequently

  9. Long-acting beta-agonists and their association with inhaled corticosteroids in COPD.

    PubMed

    Fuso, L; Mores, N; Valente, S; Malerba, M; Montuschi, P

    2013-01-01

    Inhaled bronchodilators, including beta(2)-agonists and antimuscaric receptor antagonists, are the mainstay of pharmacotherapy in chronic obstructive pulmonary disease (COPD). The short-acting beta(2)-agonists, including salbutamol, and fenoterol, have a rapid onset of action, a bronchodilating effect for 3-6 h and are used on demand. The long-acting beta(2)-agonists (LABAs), including salmeterol and formoterol, have 12-hour duration of action and are used with a twice-daily dosing regimen for long-term COPD treatment. Unlike salmeterol, formoterol has a rapid onset of action. Pharmacological characteristics required by novel inhaled LABAs include 24 h bronchodilator effect in vivo which would make them suitable for once daily administration (ultra-LABA), high potency and selectivity for beta(2)-adrenoceptors, rapid onset of action, low oral bioavailability (< 5%) after inhalation, and high systemic clearance. Indacaterol, which has been approved for long-term treatment of COPD in Europe and in the USA, has a 24-h duration of action and a once-daily dosing regimen. Newer ultra-LABAs, including olodaterol, vilanterol, milveterol, carmoterol, and abediterol, are in development. Combination with ICS (fluticasone/salmeterol, budesonide/formoterol, beclomethasone/formoterol) appears to provide an additional benefit over the monocomponent therapy, although the extent of this benefit is variable and often not clinically significant in all the endpoints assessed. In patients with COPD, treatment with ICS is associated with increased risk of pneumonia which should be carefully considered when assessing the risk/benefit ratio of ICS/LABA combinations. Subphenotyping of patients with COPD (e.g., frequent exacerbations, sputum eosinophilia, mixed asthma/COPD phenotype) might help identify those patients who are most likely to benefit from addition of ICS to bronchodilating treatment. Ultra-LABA/ long-acting muscarinic receptor antagonist (LAMA) combination treatment is under

  10. Long-acting beta-agonists: a review of formoterol safety data from asthma clinical trials.

    PubMed

    Sears, M R; Ottosson, A; Radner, F; Suissa, S

    2009-01-01

    The safety of long-acting beta(2)-agonist (LABA) treatment in asthma has been questioned following reported increased respiratory deaths when salmeterol was added to usual pharmacotherapy. The aim of this study was to examine whether asthma, cardiac or all-cause mortality and morbidity were increased with formoterol use. The analysis included all AstraZeneca randomised controlled parallel-group asthma trials of 3-12-months duration involving formoterol. Risks associated with formoterol use compared with non-LABA treatment, overall and in combination with inhaled corticosteroids (ICS), were assessed using an intention-to-treat analysis of the rates and rate ratios of deaths and serious adverse events (SAEs). The main objective of this study was to compare asthma-related mortality in patients using formoterol and those not using formoterol. There were eight asthma-related deaths (0.34 per 1,000 person-yrs) among 49,906 formoterol-randomised patients (92% using ICS), and two (0.22 per 1,000 person-yrs) among 18,098 patients (83% using ICS) not randomised to formoterol, which was nonsignificant. Asthma-related SAEs (>90% of which were hospitalisations) were significantly fewer among formoterol-randomised patients (0.75 versus 1.10%). There was no increase in asthma-related SAEs with increased daily doses of formoterol (9, 18 or 36 microg). There was no significant difference in cardiac mortality or noncardiac nonasthma-related mortality in formoterol-randomised compared to non-LABA-treated patients. All-cause mortality was similar. In the data set in which all subjects were prescribed ICS at baseline, there were seven asthma-related deaths (0.32 per 1,000 person-yrs) among 46,003 formoterol-randomised patients and one (0.14 per 1,000 person-yrs) among 13,905 patients not randomised to formoterol, which was also nonsignificant. There were few asthma-related or cardiac-related deaths among patients randomised to formoterol, and all differences were nonsignificant

  11. [A history of antipsychotic long-acting injections in the treatment of schizophrenia].

    PubMed

    Crocq, M-A

    2015-02-01

    From a historical perspective, this article describes the use of antipsychotic long-acting injections (LAI) in the treatment of schizophrenia, a disorder that was defined in the final years of the 19th century. An efficient treatment for schizophrenia was discovered only in 1952 with the introduction of chlorpromazine, a phenothiazine derivative. Fairly soon, antipsychotics became available as LAI. The first compounds were fluphenazine enanthate (1966) and decanoate (1968) whose development is attributed to G.R. Daniel, a medical director at Squibb & Sons. Other first-generation antipsychotics long-acting injections (FGA-LAIs) were introduced in a rapid succession in the 1960s and 1970s. FGA-LAIs made a key contribution to the development of community psychiatry. As neuroleptics emptied psychiatric hospitals, it was important to ensure that patients could be taken care of in outpatient facilities. FGA-LAIs prevented covert non-compliance. Compliance was further reinforced by the social and psychological support of patients. The introduction of second-generation antipsychotics (SGA) led to a loss of interest in FGA-LAIs. This is evidenced by a drop in the number of papers published on this topic. The interest in LAI was revived with the introduction of the first SGA-LAI in 2003. Four different preparations have been approved in the decade between 2003 and 2013. SGA-LAIs differ from FGA-LAIs in the technology that is used to produce the depot effect, and also in the treatment objectives. The rationale for using SGA-LAIs is not only to prevent relapses due to treatment interruption, but also to achieve more constant plasma levels in order to reduce side effects due to excessive plasma levels and loss of efficacy due to insufficient plasma levels. Also, treatment objectives are no longer limited to controlling acute symptoms. Treatment objectives now include the alleviation of negative symptoms and cognitive deficits that are key prognostic factors. Copyright © 2014

  12. Effect of octreotide on 24-h blood pressure profile in acromegaly.

    PubMed

    Fallo, F; Barzon, L; Boscaro, M; Casiglia, E; Sonino, N

    1998-05-01

    The aim of the study was to investigate the effect of octreotide, a somatostatin analog drug potentially able to inhibit growth hormone (GH), on the circadian blood pressure profile in a group of patients with acromegaly. Ten patients with GH-secreting pituitary adenoma were studied before and 6 months after treatment with subcutaneous octreotide 0.2 to 0.6 mg/day. Twenty-four hour blood pressure and heart rate were measured every 15 min at daytime (07:00 to 22:59) and every 30 min at nighttime (23:00 to 06:59) using a TM-2420 recorder. No correlation was found between GH levels and 24-h blood pressure in baseline conditions. Untreated patients had a significant nocturnal decrease of both systolic and diastolic blood pressure (P < .01), and all showed a circadian systolic or diastolic blood pressure rhythm. During octreotide treatment, 24 h as well as nighttime systolic and diastolic blood pressures significantly increased (P < .05), whereas daytime systolic and diastolic blood pressures did not change. Treated patients did not have a nocturnal decline in both systolic and diastolic blood pressures (P = NS), and eight lost their systolic or diastolic blood pressure rhythm. In conclusion, blood pressure circadian rhythm seems to be maintained in acromegaly. Octreotide treatment is associated with an increase of 24-h and nighttime blood pressure, and with loss of circadian blood pressure rhythm. Splanchnic vasoconstriction by this drug, shifting blood to peripheral vessels, may explain this phenomenon.

  13. Comparison of the effect of midodrine versus octreotide on hemodynamic status in cirrhotic patients with ascites

    PubMed Central

    Minakari, Mohammad; Faiiaz, Leila; Rowshandel, Mehdi; Shavakhi, Ahmad

    2011-01-01

    BACKGROUND: In cirrhotic patients peripheral vasodilatation may decrease renal blood flow and subsequently raises plasma renin activity. Octreotide with several mechanisms causes peripheral arterial vasoconstriction. Midodrine is an alpha agonist and acts as a peripheral vasoconstrictor; therefore it may reduce plasma renin activity and improve renal function. In this study the effects of these two agents were compared on cirrhotic patients to determine their ability to reduce plasma renin activity and increase GFR. METHODS: This study was a randomized clinical trial and was performed in Al-Zahra hospital in 2008-2009; 34 patients with CHILD C cirrhosis enrolled in this study. They were randomly divided into two groups. First group were treated by 3 days of subcutaneous octreotide 50 μg tid (n = 17). For the second group oral midodrine 7.5 mg tid was administrated for 3 days. Plasma renin activity, blood pressure, glomerular filtration rate, and body weight were measured and compared before and after therapy in both groups. RESULTS: In both groups, plasma rennin activity decreased significantly after treatment. The present study showed that both midodrine and octreotide can reduce plasma renin activity but midodrine can reduce PRA and increase GFR more potently than octreotide. CONCLUSIONS: Midodrine has a favorable hemodynamic effect in nonazotemic cirrhotic patients by decreasing plasma renin activity and increasing GFR. PMID:21448389

  14. Doppler waveform study as indicator of change of portal pressure after administration of octreotide.

    PubMed

    Haider, Shahbaz; Hussain, Qurban; Tabassum, Sumera; Hussain, Bilal; Durrani, Muhammad Rasheed; Ahmed, Fayyaz

    2016-01-01

    To estimate the effect of portal pressure lowering drug 'octreotide', by observing the Doppler waveform before and after the administration of intravenous bolus of octreotide and thus to assess indirectly its efficacy to lower the portal pressure. This quassi experimental study was carried out in Medical Department in collaboration with Radiology Department of Jinnah Postgraduate Medical Center Karachi Pakistan from September 10, 2015 to February 5, 2016. Cases were selected from patients admitted in Medical Wards and those attending Medical OPD. Diagnosis of cirrhosis was confirmed by Clinical Examination and Lab & Imaging investigation in Medical Department. Doppler waveform study was done by experienced radiologist in Radiology Department before and after administration of octreotide. Doppler signals were obtained from the right hepatic vein. Waveform tracings were recorded for five seconds and categorized as 'monophasic', 'biphasic' and 'triphasic'. Waveform changes from one waveform to other were noted and analyzed. Significant change i.e. from 'monophasic' to 'biphasic' or 'biphasic' to 'triphasic' was seen in 56% cases while 'monophasic' to 'triphasic' was seen in 20% cases. No change was seen in 24% cases. Improvement in waveform reflects lowering of portal vein pressure. Non invasive Hepatic vein Doppler waveform study showed improvement in Doppler waveform after administration of octreotide in 76% cases. Doppler waveform study has the potential of becoming non invasive 'follow up tool' of choice for assessing portal pressure in patients having variceal bleed due to portal hypertension.

  15. Octreotide and pasireotide (dis)similarly inhibit pituitary tumor cells in vitro.

    PubMed

    Ibáñez-Costa, Alejandro; Rivero-Cortés, Esther; Vázquez-Borrego, Mari C; Gahete, Manuel D; Jiménez-Reina, Luis; Venegas-Moreno, Eva; de la Riva, Andrés; Arráez, Miguel Ángel; González-Molero, Inmaculada; Schmid, Herbert A; Maraver-Selfa, Silvia; Gavilán-Villarejo, Inmaculada; García-Arnés, Juan Antonio; Japón, Miguel A; Soto-Moreno, Alfonso; Gálvez, María A; Luque, Raúl M; Castaño, Justo P

    2016-11-01

    Somatostatin analogs (SSA) are the mainstay of pharmacological treatment for pituitary adenomas. However, some patients escape from therapy with octreotide, a somatostatin receptor 2 (sst2)-preferring SSA, and pasireotide, a novel multi-sst-preferring SSA, may help to overcome this problem. It has been proposed that correspondence between sst1-sst5 expression pattern and SSA-binding profile could predict patient's response. To explore the cellular/molecular features associated with octreotide/pasireotide response, we performed a parallel comparison of their in vitro effects, evaluating sst1-sst5 expression, intracellular Ca(2+) signaling ([Ca(2+)]i), hormone secretion and cell viability, in a series of 85 pituitary samples. Somatotropinomas expressed sst5>sst2, yet octreotide reduced [Ca(2+)]i more efficiently than pasireotide, while both SSA similarly decreased growth hormone release/expression and viability. Corticotropinomas predominantly expressed sst5, but displayed limited response to pasireotide, while octreotide reduced functional endpoints. Non-functioning adenomas preferentially expressed sst3 but, surprisingly, both SSA increased cell viability. Prolactinomas mainly expressed sst1 but were virtually unresponsive to SSA. Finally, both SSA decreased [Ca(2+)]i in normal pituitaries. In conclusion, both SSA act in vitro on pituitary adenomas exerting both similar and distinct effects; however, no evident correspondence was found with the sst1-sst5 profile. Thus, it seems plausible that additional factors, besides the simple abundance of a given sst, critically influence the SSA response. © 2016 Society for Endocrinology.

  16. Growth hormone excess and the effect of octreotide in cats with diabetes mellitus.

    PubMed

    Slingerland, L I; Voorhout, G; Rijnberk, A; Kooistra, H S

    2008-11-01

    In this prospective study 16 cats with diabetes mellitus were examined for concurrent acromegaly by measuring plasma growth hormone (GH) and insulin-like growth factor-I concentrations, and magnetic resonance imaging (MRI) of the pituitary fossa. Additionally, the effects of octreotide administration on the plasma concentrations of glucose, GH, alpha-melanocyte-stimulating hormone (alpha-MSH), adrenocorticotrophic hormone (ACTH), and cortisol were measured. Five cats were diagnosed with hypersomatotropism. The pituitary was enlarged in these 5 cats and in 2 other cats. Six cats that required a maximum lente insulin dosage >or=1.5 IU/kg body weight per injection had pituitary enlargement and 5 of these cats had acromegaly. Plasma concentrations of GH, ACTH, and cortisol decreased significantly after single intravenous administration of the somatostatin analogue octreotide in the acromegalic cats. The effect on GH concentrations was more pronounced in some of the acromegalic cats than in others. In the non-acromegalic cats only ACTH concentrations decreased significantly. In both groups plasma glucose concentrations increased slightly but significantly, whereas alpha-MSH concentrations were not significantly affected. In conclusion, the incidence of hypersomatotropism with concomitant pituitary enlargement appears to be high among diabetic cats with severe insulin resistance. Some of these cats responded to octreotide administration with a pronounced decrease in the plasma GH concentration, which suggests that octreotide administration could be used as a pre-entry test for treatment with somatostatin analogues.

  17. Somatostatin analogue, octreotide, reduces increased glomerular filtration rate and kidney size in insulin-dependent diabetes

    SciTech Connect

    Serri, O.; Beauregard, H.; Brazeau, P.; Abribat, T.; Lambert, J.; Harris, A.; Vachon, L. Sandoz Canada Inc., Dorval, Quebec )

    1991-02-20

    To determine whether treatment with a somatostatin analogue can reduce kidney hyperfiltration and hypertrophy in insulin-dependent diabetes mellitus, the authors studied 11 patients with insulin-dependent diabetes mellitus and glomerular hyperfiltration. The patients were assigned randomly to receive continuous subcutaneous infusion of either octreotide, 300 {mu}g/24 h (five patients) or placebo (six patients) for 12 weeks. At baseline, mean glomerular filtration rate and mean total kidney volume were not significantly different in the two groups. However, after 12 weeks of treatment, the mean glomerular filtration rate was significantly lower in the octreotide group than in the placebo group. Furthermore, the mean total kidney volume was significantly lower after treatment in the octreotide group than in the placebo group. Glycemic control did not change significantly in either group. They conclude that subcutaneous infusion of octreotide for 12 weeks reduces increased glomerular filtration rate and kidney size in patients with insulin-dependent diabetes mellitus despite the fact that glycemic control remains unchanged.

  18. Long-acting anticholinesterases for myasthenia gravis: synthesis and activities of quaternary phenylcarbamates of neostigmine, pyridostigmine and physostigmine

    PubMed Central

    Yu, Qian-sheng; Holloway, Harold W.; Luo, Weiming; Lahiri, Debomoy K.; Brossi, Arnold; Greig, Nigel H.

    2010-01-01

    The N-monophenylcarbamate analogues of neostigmine methyl sulfate (6) and pyridostigmine bromide (8) together with their precursors (5), (7), and the N(1)-methylammonium analogues of (−)-phenserine (12), (−)-tolserine (14), (−)-cymserine (16) and (−)-phenethylcymserine (18) were synthesized to produce long-acting peripheral inhibitors of acetylcholinesterase or butyrylcholinesterase. Evaluation of their cholinesterase inhibition against human enzyme ex vivo demonstrated that, whereas compounds 5–8 possessed only marginal activity, 12, 14, 16 and 18 proved to be potent anticholinesterases. An extended duration of cholinesterase inhibition was determined in rodent, making them of potential interest as long-acting agents for myasthenia gravis. PMID:20627738

  19. Global trends in use of long-acting reversible and permanent methods of contraception: Seeking a balance.

    PubMed

    Joshi, Ritu; Khadilkar, Suvarna; Patel, Madhuri

    2015-10-01

    The global trend shows that the use of permanent contraception to prevent unintended pregnancy is high. Although the trend also shows a rise in the use of long-acting reversible methods, these are still underutilized despite having contraceptive as well as non-contraceptive benefits. Lack of knowledge among women, dependence on the provider for information, and provider bias for permanent contraception are cited as reasons for this reduced uptake. Training of healthcare providers and increased patient awareness about the effectiveness of long-acting reversible contraceptive methods will increase their uptake and help prevent unintended pregnancies.

  20. Combined corticosteroid and long-acting beta2-agonist in one inhaler versus long-acting beta2-agonists for chronic obstructive pulmonary disease

    PubMed Central

    Nannini, Luis Javier; Lasserson, Toby J; Poole, Phillippa

    2014-01-01

    Background Both inhaled steroids (ICS) and long-acting beta2-agonists (LABA) are used in the management of chronic obstructive pulmonary disease (COPD). This updated review compared compound LABA plus ICS therapy (LABA/ICS) with the LABA component drug given alone. Objectives To assess the efficacy of ICS and LABA in a single inhaler with mono-component LABA alone in adults with COPD. Search methods We searched the Cochrane Airways Group Specialised Register of trials. The date of the most recent search was November 2011. Selection criteria We included randomised, double-blind controlled trials. We included trials comparing compound ICS and LABA preparations with their component LABA preparations in people with COPD. Data collection and analysis Two authors independently assessed study risk of bias and extracted data. The primary outcomes were exacerbations, mortality and pneumonia, while secondary outcomes were health-related quality of life (measured by validated scales), lung function, withdrawals due to lack of efficacy, withdrawals due to adverse events and side-effects. Dichotomous data were analysed as random-effects model odds ratios or rate ratios with 95% confidence intervals (CIs), and continuous data as mean differences and 95% CIs. We rated the quality of evidence for exacerbations, mortality and pneumonia according to recommendations made by the GRADE working group. Main results Fourteen studies met the inclusion criteria, randomising 11,794 people with severe COPD. We looked at any LABA plus ICS inhaler (LABA/ICS) versus the same LABA component alone, and then we looked at the 10 studies which assessed fluticasone plus salmeterol (FPS) and the four studies assessing budesonide plus formoterol (BDF) separately. The studies were well-designed with low risk of bias for randomisation and blinding but they had high rates of attrition, which reduced our confidence in the results for outcomes other than mortality. Primary outcomes There was low quality

  1. Enhancing adherence, subjective well-being and quality of life in patients with schizophrenia: which role for long-acting risperidone?

    PubMed Central

    Niolu, Cinzia; Bianciardi, Emanuela; Di Lorenzo, Giorgio; Marchetta, Claudia; Barone, Ylenia; Sterbini, Nicoletta; Ribolsi, Michele; Reggiardo, Giorgio; Siracusano, Alberto

    2015-01-01

    Aim: This study evaluated adherence to treatment, quality of life and subjective well-being in patients with psychosis treated with long-acting injectable risperidone. Subjects enrolled were part of a larger study where patients were observed in an adherence to treatment program of the University of Rome Tor Vergata. Materials and methods: A total of 27 nonadherent patients (21 men, six women; mean age: 36.1 years; range: 23–63 years) were enrolled. Maximum observational period was 30 months. Results: A total of 12 patients were under treatment for 30 months (44.44%) but only nine had a valid 30-month follow up, while the remaining three patients initially treated at our unit continued long-acting risperidone at their local centre. Reductions of monthly mean values of Scale for the Assessment of Positive Symptoms (SAPS) [repeated measures analysis of variance (rm-ANOVA): p < 0.0001] and Scale for Assessment of Negative Symptoms (SANS) (p < 0.0001), increase of monthly mean values of Subjective Well-Being Under Neuroleptic Treatment Scale (SWN) (p < 0.0001) and Schizophrenia Quality of Life Scale (S-QoL) (p < 0.01) were observed. Significant differences with respect to SAPS baseline values from the sixth month, SANS baseline values from the seventh month, SWN baseline values from the eighth month, S-QoL baseline values from the eighteenth month were shown in post hoc tests. Reduction of SAPS mean values was associated with increase of SWN (p < 0.0001) and S-QoL (p < 0.0001) mean values as demonstrated by correlation analysis. The same inverse correlation was found between reduction of SANS mean values and increases of SWN (p < 0.0001) and S-QoL (p = 0.0001) mean values. Conclusions: Long-term treatment with long-acting risperidone may be associated with improvement to adherence to therapy and quality of life. Patients may show improvement in psychopathological symptoms, subjective well-being and quality of life. PMID:26557984

  2. Motivational Interviewing to Promote Long-Acting Reversible Contraception in Postpartum Teenagers.

    PubMed

    Tomlin, Kristl; Bambulas, Tammalynn; Sutton, Maureen; Pazdernik, Vanessa; Coonrod, Dean V

    2017-06-01

    To determine if teenage patients receiving prenatal care in an adolescent-focused clinic, emphasizing long-acting reversible contraception (LARC) using motivational interviewing techniques, had higher rates of uptake of postpartum LARC than a control group. Retrospective cohort study comparing young women who received prenatal care in an adolescent-focused setting with those enrolled in standard prenatal care. Adolescents between the ages of 13 and 17 years receiving prenatal care within the Maricopa Integrated Health safety-net system between 2007 and 2014. Motivational interviewing within the context of adolescent-focused prenatal care. Rates of uptake of LARC within 13 postpartum weeks. The adjusted rate of LARC for adolescent-focused prenatal care participants by 13 weeks postpartum was 38% (95% confidence interval [CI], 29%-47%) compared with 18% (95% CI, 11%-28%) for standard care participants, with an adjusted odds ratio of LARC use of 2.8 (95% CI, 1.5-5.2). Among patients who received adolescent-focused prenatal care, most (27% vs 12.7%) were using an intrauterine device as opposed to an implantable contraceptive device. Participation in an adolescent-focused antepartum setting using motivational interviewing to emphasize postpartum LARC resulted in nearly 3 times higher rates of uptake compared with standard prenatal care. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  3. The use of academic detailing to improve evidence based prescribing of risperidone long acting injection.

    PubMed

    Paton, Carol; Adebowale, Olubunmi; Okocha, Chike I

    2008-01-01

    Objective. It takes 6 weeks for plasma levels of risperidone long-acting injection (RLAI) to reach steady state, and randomised controlled trials demonstrate a flat dose-response curve. In clinical practice, the dose of RLAI is often increased rapidly at the start of treatment and many patients receive a dose above 25 mg/2 weeks. We sought to understand why and to use academic detailing as a catalyst for change. Method. (1) Semi-structured interview of and academic detailing visit to psychiatrists. (2) Number of pharmacy issues or each strength of RLAI issues before and after the academic detailing visit. Results. Understanding of the pharmacokinetics of RLAI and the flat dose-response curve were poor. After a single visit from an academic detailer, the proportion of 50-mg doses issued decreased from 44 to 31%. Conclusion. Academic detailing was effective in changing prescribing practice; patients are likely to benefit through receiving treatment that has a better risk-benefit ratio, and the healthcare organization is likely to benefit, in terms of more cost-effective prescribing.

  4. Contraceptive implants: long acting and provider dependent contraception raises concerns about freedom of choice.

    PubMed Central

    Thompson, M. S.

    1996-01-01

    David Bromham's editorial on contraceptive implants ignores the wider issues to voice concern that trial by media could limit contraceptive choice by jeopardising research into new methods. However, it is more beneficial to the public for points of conflict to be debated openly. Furthermore, the impetus for research into new contraceptive technology is driven by profit and political motives and is only marginally affected by the media. Implanted contraceptives may increase the choice of contraceptive methods, but they put control of fertility increasingly into the hands of the medical profession. Herein lies their greatest problem: their potential to increase providers' control over clients' choice. There is the danger that certain groups of women may be targeted for their use: in the United States the coercive use of Norplant for mothers receiving welfare benefit has been suggested. Long acting contraceptives are a contraceptive of choice only when they are available without pressure, as part of a wider menu; when instant removal on request is guaranteed; and when there is an open and free flow of information and opinions between users, health professionals, and special interest groups. Images p1394-a PMID:8956712

  5. Long-acting protein drugs for the treatment of ocular diseases

    PubMed Central

    Ghosh, Joy G.; Nguyen, Andrew A.; Bigelow, Chad E.; Poor, Stephen; Qiu, Yubin; Rangaswamy, Nalini; Ornberg, Richard; Jackson, Brittany; Mak, Howard; Ezell, Tucker; Kenanova, Vania; de la Cruz, Elisa; Carrion, Ana; Etemad-Gilbertson, Bijan; Caro, Roxana Garcia; Zhu, Kan; George, Vinney; Bai, Jirong; Sharma-Nahar, Radhika; Shen, Siyuan; Wang, Yiqin; Subramanian, Kulandayan K.; Fassbender, Elizabeth; Maker, Michael; Hanks, Shawn; Vrouvlianis, Joanna; Leehy, Barrett; Long, Debby; Prentiss, Melissa; Kansara, Viral; Jaffee, Bruce; Dryja, Thaddeus P.; Roguska, Michael

    2017-01-01

    Protein drugs that neutralize vascular endothelial growth factor (VEGF), such as aflibercept or ranibizumab, rescue vision in patients with retinal vascular diseases. Nonetheless, optimal visual outcomes require intraocular injections as frequently as every month. Here we report a method to extend the intravitreal half-life of protein drugs as an alternative to either encapsulation or chemical modifications with polymers. We combine a 97-amino-acid peptide of human origin that binds hyaluronan, a major macromolecular component of the eye's vitreous, with therapeutic antibodies and proteins. When administered to rabbit and monkey eyes, the half-life of the modified proteins is increased ∼3–4-fold relative to unmodified proteins. We further show that prototype long-acting anti-VEGF drugs (LAVAs) that include this peptide attenuate VEGF-induced retinal changes in animal models of neovascular retinal disease ∼3–4-fold longer than unmodified drugs. This approach has the potential to reduce the dosing frequency associated with retinal disease treatments. PMID:28332616

  6. [Evaluating the efficacy of long acting injectable antipsychotics through clinical trials].

    PubMed

    Fakra, E; Azorin, J-M; Belzeaux, R; Adida, M; Blin, O; Kaladjian, A

    2016-12-01

    After reminding the various phases of the development of molecules, this article will state the stages of commercialisation of treatments, underlining the FDA (Food and Drug Administration) and the EMA (European Medicine Agency) requirements. Like all the other treatments available in Europe and in the United States, the long acting injectable antipsychotics (LAI) have to prove their efficacy compared to placebo and their non-inferiority compared to a treatment of reference, usually the same molecule in the oral form. These criteria of efficacy have evolved over time. If initially classical criteria of symptomatic intensity (score on scale PANSS) were considered, criteria more adequate from a clinical perspective, such as relapse, but also related to functioning, quality of life and, more recently, costs-effectiveness have appeared. This evolution is probably due to several factors: vision on mental illness, progress in patient's rights and aspirations, but also the pregnant place of health costs recently taken in the evaluation of treatments. These modifications are also based on the indications of L.A.I., i.e. stabilized patients for whom the challenge is rehabilitation care more than the control of symptoms. © L’Encéphale, Paris, 2016.

  7. Safety of long-acting beta agonists and inhaled corticosteroids in children and adolescents with asthma

    PubMed Central

    Xia, Ying; Kelton, Christina M. L.; Xue, Liang; Bian, Boyang; Wigle, Patricia R.

    2013-01-01

    The introduction of long-acting beta agonists (LABAs) was considered a major advance in bronchodilator therapy for adult, as well as pediatric, patients with asthma. However, the use of LABAs has raised safety concerns, especially the potential for severe asthma exacerbations (SAEs) resulting in hospitalizations or even death. Meanwhile, the use of inhaled corticosteroids (ICSs), a cornerstone in the treatment of mild-to-severe persistent asthma, has been associated with growth suppression in children. The purpose of this review was to identify and discuss the major published safety studies surrounding LABA, ICS, and combined LABA/ICS usage in children. By way of a critical search for influential published clinical trials, meta-analyses, and observational studies, six studies relevant to the safety of LABA monotherapy, seven studies relevant to ICS monotherapy, and four studies on the subject of LABA/ICS combination usage were identified and reviewed. Based on the reviewed literature, the controversy surrounding these anti-asthma medications was clearly exposed. On the one hand, there is some evidence that LABA monotherapy may be associated with SAEs and asthma-related death, while ICS monotherapy may be associated with a higher risk of growth suppression. On the other hand, the concurrent use of a LABA with an ICS has been associated with positive outcomes including symptom reduction and reduced rate and severity of exacerbations. Further clinical research is warranted and has been called for by the US Food and Drug Administration. PMID:25114786

  8. A systematic review and combined analysis of therapeutic drug monitoring studies for long-acting risperidone.

    PubMed

    Schoretsanitis, Georgios; Spina, Edoardo; Hiemke, Christoph; de Leon, Jose

    2017-09-01

    This systematic review of therapeutic drug monitoring (TDM) identifies three long-acting injectable (LAI) risperidone formulations. Areas covered: Limited data is available on two formulations (RBP-7000 and in Situ Microparticle), but 20 TDM articles on the microsphere formulation were found. Risperidone TDM includes the serum concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone, used for calculating: 1) the risperidone/9-hydroxyrisperidone (R/9-OH-R) ratio (a measure of CYP2D6; values >1 are indicative of a CYP2D6 poor metabolizer) and 2) the total risperidone concentration-to-dose (C/D) ratio (a measure of risperidone clearance with a normal value around 7 in oral risperidone). The weighted mean R/9-OH-R ratio was 0.48 (approximately twice that of oral risperidone TDM) in a combined analysis from 329 patients in 6 risperidone LAI studies without major confounders. The total C/D ratios from 297 patients in 6 risperidone LAI studies ranged from 7.4 to 9.7 ng/ml/mg/day with a weighted mean of 8.8 ng/ml/mg/day. Expert commentary: Clinicians using TDM for risperidone LAI microsphere formulation need to: 1) consider steady state to be reached ≥ 6 weeks after the first injection, 2) pay attention to a) co-medications with inducers/inhibitors, b) severe inflammations/infections, and c) hepatic/renal impairment, and 3) use Castberg's recommendation to calculate risperidone dosing.

  9. A long-acting GH receptor antagonist through fusion to GH binding protein.

    PubMed

    Wilkinson, Ian R; Pradhananga, Sarbendra L; Speak, Rowena; Artymiuk, Peter J; Sayers, Jon R; Ross, Richard J

    2016-10-12

    Acromegaly is a human disease of growth hormone (GH) excess with considerable morbidity and increased mortality. Somatostatin analogues are first line medical treatment but the disease remains uncontrolled in up to 40% of patients. GH receptor (GHR) antagonist therapy is more effective but requires frequent high-dose injections. We have developed an alternative technology for generating a long acting potent GHR antagonist through translational fusion of a mutated GH linked to GH binding protein and tested three candidate molecules. All molecules had the amino acid change (G120R), creating a competitive GHR antagonist and we tested the hypothesis that an amino acid change in the GH binding domain (W104A) would increase biological activity. All were antagonists in bioassays. In rats all antagonists had terminal half-lives >20 hours. After subcutaneous administration in rabbits one variant displayed a terminal half-life of 40.5 hours. A single subcutaneous injection of the same variant in rabbits resulted in a 14% fall in IGF-I over 7 days.

  10. Injectable long-acting in situ forming systems for Radix Ophiopogonis polysaccharide.

    PubMed

    Shi, XiaoLi; Lin, Xiao; Yao, ChunXia; Shen, Lan; Feng, Yi

    2015-01-01

    In the area of injectable long-acting formulations, the in situ forming system (ISFS) is an attractive alternative for its various superiorities. In this study, both hydrophilic and hydrophobic in situ forming systems, using Poloxamer and sucrose acetate isobutyrate (SAIB) or poly(D,L-lactide-co-glycolide) copolymer (PLGA) as carrier, respectively, were investigated for Radix Ophiopogonis polysaccharide (ROP), a natural anti-myocardial ischemic fructan. A reasonable and applicable range of formulations were selected from each carrier for in vivo study by investigating their rheological property. The results from in vivo evaluation show that relatively promising sustained behaviors were achieved by formulations 24% P407/10% P188, 40% PLGA30k/NMP, and 30% PLGA50k/NMP. Significant differences of drug release kinetics were observed between in situ thermally-induced Poloxamer-based hydrogels and in situ solvent exchange-induced hydrophobic PLGA depots. This suggests that different ISFS could be chosen to provide different application purpose for polysaccharide drugs. In the case of ROP, Poloxamer-based ISFS is promising for short-term acute therapies; however, PLGA-based ISFS might be promising for long-term precaution or/and cure of myocardial ischemia.

  11. Bioequivalence study of two long-acting oxytetracycline formulations in sheep.

    PubMed

    Ozdemir, N; Yildirim, M

    2006-11-01

    Two commercially available long-acting oxytetracycline hydrochloride formulations (Primamycin LA (Pfizer) and Terralent 20% LA (I.E. Ulagay)) were administered by the intramuscular route to 20 clinically healthy sheep at a dose of 20 mg/kg. The study was performed in a two-period crossover design. Plasma samples were analysed by high-pressure liquid chromatography. The mean maximum concentrations (C (max)) was 8.00 +/- 2.05 microg/ml and 8.61 +/- 1.42 micro/ml, respectively. The mean area under the concentration time curve (AUC) values were 154.95 +/- 50.37(microg h)/ml and 161.70 +/- 47.02(microg h)/ml, respectively. The 90%confidence intervals for the ratio of C (max) and AUC values for the test and reference product are with in the interval 70-143% for C (max) and interval 80--125% for AUC proposed by EMEA. It was concluded that Primamycin LA and Terralent 20% LA formulations are bioequivalent in their rate and extent of drug absorbtion.

  12. Long Acting Single Injection Caudal Anesthesia—1,208 Obstetrical Deliveries with Mepivacaine

    PubMed Central

    Gunther, Ronald E.; Harer, W. Benson

    1966-01-01

    Long acting, single injection caudal anesthesia with mepivacaine was studied in 1,208 obstetrical cases. A 1 per cent solution was used in 671 patients and compared with a 1.5 per cent concentration in 537. No remarkable differences were found between the two groups. The 1 per cent solution provided relief of labor discomfort for from 60 to 180 minutes with an average of 110 minutes. In contrast, the 1.5 per cent solution provided an average of 115 minutes with a range of 80 to 210 minutes. A total volume of 30 ml of anesthetic agent yielded anesthesia to a level of the tenth thoracic vertebra or higher in 91 per cent of patients. Significant alterations in blood pressure were uncommon. About 1 per cent of patients required a vasopressor because of a drop in systolic blood pressure below 80 mm of mercury. Another 8 per cent had a drop of over 20 points in systolic pressure but from high enough levels that they did not require a vasopressor. Toxic effects similar to those of lidocaine were found in slightly more than 1 per cent of cases. This anesthesia requires a higher incidence of operative intervention for delivery. PMID:5980717

  13. Demand for long-acting and permanent contraceptive methods among Kurdish women in Mahabad, Iran.

    PubMed

    Hosseini, Hatam; Torabi, Fatemeh; Bagi, Balal

    2014-11-01

    It is anticipated that the demand for contraceptives in Iran will increase in the near future as the number of women of reproductive age increases and with women wanting smaller families. The aim of this paper was to study the demand for long-acting and permanent contraceptive methods (LAPCMs), and its determinants, among Kurdish women in Mahabad city, Iran. Data were taken from the Mahabad Fertility Survey (MFS) conducted on a sample of over 700 households in April 2012. The results show that the demand for LAPCMs was 71.35% at the time of survey, although only 27.7% of women were using these methods. Thus, the number of unintended pregnancies is likely to increase in the future if this gap is not reduced. The multivariate analysis showed significant impacts on the dependent variables of the number of children ever born, perceived contraceptive costs and childbearing intentions. Moreover, women at the end of their reproductive lives and those with higher education were more likely to desire LAPCMs. It is concluded that despite a growing use of contraceptive methods in Iran in recent decades, the development of reproductive health services and promotion of the quality of family planning services remains a necessity.

  14. Young women's attitudes towards, and experiences of, long-acting reversible contraceptives.

    PubMed

    Bracken, Jennifer; Graham, Cynthia A

    2014-08-01

    To identify factors involved in women's decisions to choose particular contraceptive methods and more specifically, incentives and disincentives to use three long-acting reversible contraceptive (LARC) methods: injectables, implants, and intrauterine devices/systems (IUDs/IUSs). A total of 502 women aged 18 to 30 completed a cross-sectional online questionnaire. The three most important factors in choosing a contraceptive method were: high efficacy at preventing pregnancy, protection against sexually transmitted infections, and non-interference with sexual intercourse. The most common incentives for LARC use were the high efficacy and long duration of action. Disincentives included the possibility of irregular bleeding and concerns about effects on fertility; fear of needles and pain was a particular disincentive for IUD/IUS use. Only 93 (18%) of the participants reported ever having used a LARC. Reported disincentives to LARC use (e.g., concern about effects on future fertility) indicated that many young women hold inaccurate beliefs about these methods. The relatively high proportions of women who held neutral attitudes about LARCs (21-40%, depending on the method) highlight the importance of education and contraceptive counselling to improve knowledge about the advantages of these methods.

  15. Eliminating Health Disparities in Unintended Pregnancy with Long-Acting Reversible Contraception (LARC)

    PubMed Central

    PARKS, Caitlin; PEIPERT, Jeffrey F.

    2016-01-01

    Significant public health disparities exist surrounding teen and unplanned pregnancy in the U.S. Women of color and those with lower education and socioeconomic status are at much greater risk of unplanned pregnancy and the resulting adverse outcomes. Unplanned pregnancies reduce educational and career opportunities and may contribute to socioeconomic deprivation and widening income disparities. Long-acting reversible contraception (LARC), including intrauterine devices (IUDs) and implants, offer the opportunity to change the default from drifting into parenthood to planned conception. LARC methods are forgettable; once placed they offer highly effective, long-term pregnancy prevention. Increasing evidence in the medical literature demonstrates the population benefits of use of these methods. However, barriers to more widespread use of LARC methods persist, and include educational, access, and cost barriers. With increasing insurance coverage under the Affordable Care Act, and more widespread, no-cost coverage of methods, more and more women are choosing IUDs and the contraceptive implant. Increasing the use of highly effective contraceptive methods may provide one solution to the persistent problem of the health disparities of unplanned and teen pregnancies in the U.S., and improve women and children's health. PMID:26875950

  16. Cost of unintended pregnancy in Norway: a role for long-acting reversible contraception

    PubMed Central

    Henry, Nathaniel; Schlueter, Max; Lowin, Julia; Lekander, Ingrid; Filonenko, Anna; Trussell, James; Skjeldestad, Finn Egil

    2015-01-01

    Objectives The objective of this study was to quantify the cost burden of unintended pregnancies (UPs) in Norway, and to estimate the proportion of costs due to imperfect contraceptive adherence. Potential cost savings that could arise from increased uptake of long-acting reversible contraception (LARC) were also investigated. Methods An economic model was constructed to estimate the total number of UPs and associated costs in women aged 15–24 years. Adherence-related UP was estimated using ‘perfect use’ and ‘typical use’ contraceptive failure rates. Potential savings from increased use of LARC were projected by comparing current costs to projected costs following a 5% increase in LARC uptake. Results Total costs from UP in women aged 15–24 years were estimated to be 164 million Norwegian Kroner (NOK), of which 81.7% were projected to be due to imperfect contraceptive adherence. A 5% increase in LARC uptake was estimated to generate cost savings of NOK 7.2 million in this group. Conclusions The cost of UP in Norway is substantial, with a large proportion of this cost arising from imperfect contraceptive adherence. Increased LARC uptake may reduce the UP incidence and generate cost savings for both the health care payer and contraceptive user. PMID:25537792

  17. Adherence challenges and long-acting injectable antipsychotic treatment in patients with schizophrenia.

    PubMed

    Kirk Morton, N; Zubek, Donna

    2013-03-01

    Medication nonadherence has been associated with persistence of psychotic symptoms, relapse, and hospitalization in patients with schizophrenia. Patients with untreated psychosis are significantly less likely to achieve remission, whereas antipsychotic drug adherence has been associated with recovery. As such, adherence to antipsychotic drug treatment is a key issue for nurses and treatment team members caring for patients who typically are on chronic, progressive disease course. Long-acting injectable (LAI) anti-psychotic drugs, developed to improve adherence and provide and alternative antipsychotic drug treatment fro schizophrenia, have been associated with improved treatment outcomes including reduction of relapse rates approximately 30% and reduction in hospitalizations. However, LAI antipsychotic drugs remain underutilized in the United States despite a growing body of literature supporting positive outcomes of LAI versus oral antipsychotic drugs. Mental health nurses are in a key position to support improved adherence inpatients with schizophrenia through use of practical educational strategies that help patients, family members, and health care providers better understand and manage treatment.

  18. Long-acting beta-agonists and the risk of intensive care unit admission in children.

    PubMed

    Jacobs, Tammy S; Jones, Bobby L; MacGinnitie, Andrew J

    2012-06-01

    A possible association between long-acting beta-agonists (LABA) and severe asthma exacerbations including death remains controversial. We examined whether LABA in the setting of combination therapy with inhaled corticosteroids (ICS) increase the risk of near-fatal asthma in children using a case-control study design. Medical records from admissions for asthma exacerbations in children 4-18 years of age during the 2005 calendar year at Children's Hospital of Pittsburgh of UPMC were reviewed. Cases and controls were determined by pediatric intensive care unit (PICU) and floor admission, respectively. Exposure was defined by LABA use in combination with ICS versus ICS alone. Records from 85 PICU and 96 pediatric floor admissions were reviewed. LABA use in combination with ICS did not increase the risk of PICU admission (odds ratio 1.07, 95% CI 0.46-2.52) compared to ICS only without LABA. After adjusting for demographics, asthma severity, history of PICU admissions, and concurrent infection, LABA/ICS use still did not increase the risk of PICU admission (adjusted odds ratio 0.84, 95% CI 0.26-2.76) compared to ICS alone. There were no deaths and five intubations within the study period. The combination of LABA and ICS did not appear to increase the risk of near-fatal asthma in children.

  19. Manufacturing process used to produce long-acting recombinant factor VIII Fc fusion protein.

    PubMed

    McCue, Justin; Kshirsagar, Rashmi; Selvitelli, Keith; Lu, Qi; Zhang, Mingxuan; Mei, Baisong; Peters, Robert; Pierce, Glenn F; Dumont, Jennifer; Raso, Stephen; Reichert, Heidi

    2015-07-01

    Recombinant factor VIII Fc fusion protein (rFVIIIFc) is a long-acting coagulation factor approved for the treatment of hemophilia A. Here, the rFVIIIFc manufacturing process and results of studies evaluating product quality and the capacity of the process to remove potential impurities and viruses are described. This manufacturing process utilized readily transferable and scalable unit operations and employed multi-step purification and viral clearance processing, including a novel affinity chromatography adsorbent and a 15 nm pore size virus removal nanofilter. A cell line derived from human embryonic kidney (HEK) 293H cells was used to produce rFVIIIFc. Validation studies evaluated identity, purity, activity, and safety. Process-related impurity clearance and viral clearance spiking studies demonstrate robust and reproducible removal of impurities and viruses, with total viral clearance >8-15 log10 for four model viruses (xenotropic murine leukemia virus, mice minute virus, reovirus type 3, and suid herpes virus 1). Terminal galactose-α-1,3-galactose and N-glycolylneuraminic acid, two non-human glycans, were undetectable in rFVIIIFc. Biochemical and in vitro biological analyses confirmed the purity, activity, and consistency of rFVIIIFc. In conclusion, this manufacturing process produces a highly pure product free of viruses, impurities, and non-human glycan structures, with scale capabilities to ensure a consistent and adequate supply of rFVIIIFc. Copyright © 2015 Biogen. Published by Elsevier Ltd.. All rights reserved.

  20. Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations.

    PubMed

    Christiansen, Jens Sandahl; Backeljauw, Philippe F; Bidlingmaier, Martin; Biller, Beverly M K; Boguszewski, Margaret C S; Casanueva, Felipe F; Chanson, Philippe; Chatelain, Pierre; Choong, Catherine S; Clemmons, David R; Cohen, Laurie E; Cohen, Pinchas; Frystyk, Jan; Grimberg, Adda; Hasegawa, Yukihiro; Haymond, Morey W; Ho, Ken; Hoffman, Andrew R; Holly, Jeff M P; Horikawa, Reiko; Höybye, Charlotte; Jorgensen, Jens Otto L; Johannsson, Gudmundur; Juul, Anders; Katznelson, Laurence; Kopchick, John J; Lee, K O; Lee, Kuk-Wha; Luo, Xiaoping; Melmed, Shlomo; Miller, Bradley S; Misra, Madhusmita; Popovic, Vera; Rosenfeld, Ron G; Ross, Judith; Ross, Richard J; Saenger, Paul; Strasburger, Christian J; Thorner, Michael O; Werner, Haim; Yuen, Kevin

    2016-06-01

    The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry. Current literature was reviewed for gaps in knowledge. Expert opinion was used to suggest studies required to address potential safety and efficacy issues. Following plenary presentations summarizing the literature, breakout groups discussed questions framed by the planning committee. Attendees reconvened after each breakout session to share group reports. A writing team compiled the breakout session reports into a draft document that was discussed and revised in an open forum on the concluding day. This was edited further and then circulated to attendees from academic institutions for review after the meeting. Participants from pharmaceutical companies did not participate in the planning, writing, or in the discussions and text revision on the final day of the workshop. Scientists from industry and regulatory agencies reviewed the manuscript to identify any factual errors. LAGH compounds may represent an advance over daily GH injections because of increased convenience and differing phamacodynamic properties, providing the potential for improved adherence and outcomes. Better methods to assess adherence must be developed and validated. Long-term surveillance registries that include assessment of efficacy, cost-benefit, disease burden, quality of life, and safety are essential for understanding the impact of sustained exposure to LAGH preparations. © 2016 The authors.

  1. Clinical Decision-Making in the Treatment of Schizophrenia: Focus on Long-Acting Injectable Antipsychotics

    PubMed Central

    Samalin, Ludovic; Garnier, Marion; Auclair, Candy; Llorca, Pierre-Michel

    2016-01-01

    The purpose of this study was to identify clinician characteristics associated with higher prescription rates of long-acting injectable (LAI) antipsychotics, as well as the sources that influence medical decision-making regarding the treatment of schizophrenia. We surveyed 202 psychiatrists during six regional French conferences (Bordeaux, Lyon, Marseille, Nice, Paris, and Strasbourg). Data on the characteristics of practice, prescription rates of antipsychotic, and information sources about their clinical decisions were collected. Most psychiatrists used second-generation antipsychotics (SGAs), and preferentially an oral formulation, in the treatment of schizophrenia. LAI SGAs were prescribed to 30.4% of schizophrenic patients. The duration and type of practice did not influence the class or formulation of antipsychotics used. The clinicians following the higher percentage of schizophrenic patients were associated with a higher use of LAI antipsychotics and a lower use of oral SGAs. Personal experience, government regulatory approval, and guidelines for the treatment of schizophrenia were the three main contributing factors guiding clinicians’ decision-making regarding the treatment of schizophrenia. The more clinicians follow schizophrenic patients, the more they use LAI antipsychotics. The development of specialized programs with top specialists should lead to better use of LAI antipsychotics in the treatment of schizophrenia. PMID:27869767

  2. Disposition of oxytetracycline in pigs after i.m. administration of two long-acting formulations.

    PubMed

    El Korchi, G; Prats, C; Arboix, M; Pérez, B

    2001-08-01

    Two commercially available long-acting oxytetracycline (OTC) formulations were administered by the intramuscular (i.m.) route to six healthy pigs at the recommended dose of 30 mg/kg. After 2 h the mean maximum concentration (C(max)) reached values of 8.1 +/- 2.2 and 15.4 +/- 11.1 microg/mL, respectively. These concentrations remained higher than 0.5 microg/mL for more than 5 days after drug administration. The area under the concentration time curve (AUC09 days) of each formulation was 255 +/- 76.5 and 399.2 +/- 123 microg. h/mL, respectively, and the mean residence time (MRT) was around 3 days for both formulations. No significant differences were observed between the pharmacokinetic parameters of the two formulations, showing the bioequivalence of the two formulations studied according to the criteria established by the Food and Drug Administration (FDA) and the Committee for Veterinary Medicinal Products (CVMP).

  3. Effects of long-acting beta adrenergic agonists on vocal fold ion transport.

    PubMed

    Sivasankar, Mahalakshmi; Blazer-Yost, Bonnie

    2009-03-01

    Inhaled medications prescribed for the hypersensitive airway typically combine corticosteroids and long-acting beta2 adrenergic agonists (LABAs). The phonatory side effects of these combination treatments are widely recognized. However, there is limited understanding of the physiological changes induced by these medications that underlie the phonatory side effects. The objective of this study was to investigate the distinct effects of corticosteroids and LABAs on vocal fold mucosal physiology. Understanding the physiological changes to the vocal folds after corticosteroid and LABA treatments is necessary to prevent the prevalent vocal decrement associated with these medications. Experimental in vitro design with treatment and control groups. Native porcine vocal fold mucosae (N = 38) were exposed to corticosteroid or LABA treatments. Ion transport was measured continuously at baseline and after treatment. To quantify the nature of ion transport, vocal folds were also treated with chloride and sodium channel inhibitors. Corticosteroid treatment did not alter ion transport. Conversely, exposure to LABAs significantly increased ion transport. This increase in ion transport was transient, observed immediately after treatment in all tissue and associated with increased chloride secretion. The distinct effects of corticosteroids and LABAs on vocal fold physiology have not been examined to date. This study demonstrates that short-term treatment with LABAs, but not corticosteroids, significantly increases ion transport. These findings suggest that one underlying physiological mechanism for phonatory changes associated with inhaled treatments may be related to acute alterations in vocal fold ion transport and surface hydration.

  4. Pharmacological, pharmacokinetic, and clinical properties of benidipine hydrochloride, a novel, long-acting calcium channel blocker.

    PubMed

    Yao, Kozo; Nagashima, Ken; Miki, Hiroyuki

    2006-04-01

    Benidipine is a dihydropyridine-derived calcium channel blocker developed in Japan, with several unique mechanisms of action, that is, triple calcium channels (L, N, and T) blocking action with a membrane approach. Benidipine has relatively high vascular selectivity and is expected to show protective effects on vascular endothelial cells. Renal protective effects of benidipine also have been shown in several basic and clinical studies. Moreover, anti-oxidative action and enhancing nitric oxide production have been noted with this drug, following its cardio-protective effects in patients with ischemic heart diseases. In fact, benidipine exerted a better prognostic effect than other calcium channel blockers in the therapy for patients with vasospastic angina. In addition, benidipine showed reliable antihypertensive, renoprotective effects if used in combination with angiotensin II type 1 receptor blockers (ARBs) when adequate anti-hypertensive effects are not achieved by ARBs alone, indicating that benidipine is an useful calcium channel blocker in combination therapy for hypertension. Benidipine was launched on the Japanese market 14 years ago, but few severe side effects have been reported, suggesting that this is a drug with established safety and long-acting pharmacological effects.

  5. Pharmacodynamics of long-acting folic acid-receptor targeted ritonavir boosted atazanavir nanoformulations

    PubMed Central

    Puligujja, Pavan; Balkundi, Shantanu; Kendrick, Lindsey; Baldridge, Hannah; Hilaire, James; Bade, Aditya N.; Dash, Prasanta K.; Zhang, Gang; Poluektova, Larisa; Gorantla, Santhi; Liu, Xin-Ming; Ying, Tianlei; Feng, Yang; Wang, Yanping; Dimitrov, Dimiter S.; McMillan, JoEllyn M.; Gendelman, Howard E.

    2014-01-01

    Long-acting nanoformulated antiretroviral therapy (nanoART) that target monocyte-macrophage could improve the drug’s half-life and protein binding capacities while facilitating cell and tissue depots. To this end, ART nanoparticles that target the folic acid (FA) receptor and permit cell-based drug depots were examined using pharmacokinetic and pharmacodynamic (PD) tests. FA receptor-targeted poloxamer 407 nanocrystals, containing ritonavir-boosted atazanavir (ATV/r), significantly affected several therapeutic factors: drug bioavailability increased as much as 5 times and PD activity improved as much as 100 times. Drug particles administered to human peripheral blood lymphocyte reconstituted NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ mice and infected with HIV-1ADA at a tissue culture infective dose50 of 104 infectious viral particles/ml led to ATV/r drug concentrations that paralleled FA receptor beta staining in both the macrophage-rich parafollicular areas of spleen and lymph nodes. Drug levels were higher in these tissues than what could be achieved by either native drug or untargeted nanoART particles. The data also mirrored potent reductions in viral loads, tissue viral RNA and numbers of HIV-1p24+ cells in infected and treated animals. We conclude that FA-P407 coating of ART nanoparticles readily facilitate drug carriage and facilitate antiretroviral responses. PMID:25522973

  6. Pharmacodynamics of long-acting folic acid-receptor targeted ritonavir-boosted atazanavir nanoformulations.

    PubMed

    Puligujja, Pavan; Balkundi, Shantanu S; Kendrick, Lindsey M; Baldridge, Hannah M; Hilaire, James R; Bade, Aditya N; Dash, Prasanta K; Zhang, Gang; Poluektova, Larisa Y; Gorantla, Santhi; Liu, Xin-Ming; Ying, Tianlei; Feng, Yang; Wang, Yanping; Dimitrov, Dimiter S; McMillan, JoEllyn M; Gendelman, Howard E

    2015-02-01

    Long-acting nanoformulated antiretroviral therapy (nanoART) that targets monocyte-macrophages could improve the drug's half-life and protein-binding capacities while facilitating cell and tissue depots. To this end, ART nanoparticles that target the folic acid (FA) receptor and permit cell-based drug depots were examined using pharmacokinetic and pharmacodynamic (PD) tests. FA receptor-targeted poloxamer 407 nanocrystals, containing ritonavir-boosted atazanavir (ATV/r), significantly increased drug bioavailability and PD by five and 100 times, respectively. Drug particles administered to human peripheral blood lymphocyte reconstituted NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ mice and infected with HIV-1ADA led to ATV/r drug concentrations that paralleled FA receptor beta staining in both the macrophage-rich parafollicular areas of spleen and lymph nodes. Drug levels were higher in these tissues than what could be achieved by either native drug or untargeted nanoART particles. The data also mirrored potent reductions in viral loads, tissue viral RNA and numbers of HIV-1p24+ cells in infected and treated animals. We conclude that FA-P407 coating of ART nanoparticles readily facilitates drug carriage and antiretroviral responses.

  7. The long-acting beta-agonist controversy: a clinical dilemma.

    PubMed

    Lang, David M; Davis, Ray S

    2007-01-01

    The Food and Drug Administration approved new safety labeling on March 2, 2006 for medication containing salmeterol, a long-acting beta-agonist (LABA), because of data suggesting an increased risk of fatal or potentially fatal asthma episodes. The "black box" warning, public health advisory, and label change for salmeterol, salmeterol-fluticasone combination, and formoterol has heightened public and physician concern over the risk-to-benefit ratio and the medicolegal implications of prescribing these agents for patients with asthma. A problem-based learning (PBL) case was presented to several breakout groups at the Eastern Allergy Conference, May 6, 2006, in Naples, FL, focusing on the LABA controversy in the context of an actual patient. The consensus of opinion during the interactive group sessions among approximately 100 allergists was that (1) the patient had poorly controlled asthma on inhaled corticosteroid (ICS) monotherapy and that warranted a change of therapy; (2) each physician must choose which option presents the best benefit-to-risk ratio after a thorough and open discussion with the patient; (3) of the several choices for step-up therapy when a patient is not well controlled on an ICS alone, the best choice based on current evidence is combined ICS plus LABA. After the PBL case discussion, a didactic lecture was presented describing the evidence pertaining to the LABA controversy, which is detailed in this article.

  8. Update on ultra-long-acting β agonists in chronic obstructive pulmonary disease.

    PubMed

    Zafar, Muhammad Ahsan; Droege, Christopher; Foertsch, Madeline; Panos, Ralph J

    2014-12-01

    For the last two decades, long-acting β agonists (LABAs) have been a cornerstone in the management of chronic obstructive pulmonary disease (COPD). They relax airway smooth muscle and augment expiratory airflow, which reduces hyperinflation and improves dyspnea, functional capacity and quality of life. In recent years, Indacaterol, a LABA with an ultra-long duration of action (ultra-LABA), which only requires once-daily dosing, was approved by the FDA. The clinical efficacy of indacaterol is comparable, and, in some aspects better, than the currently available LABAs. This article reviews the pharmacological properties, clinical efficacy, safety and potential role of the ultra-LABAs in COPD management. Ultra-LABAs are effective bronchodilators with a prolonged duration of action. By decreasing dosing frequency, ultra-LABAs potentially may improve respiratory medication adherence, which is associated with better survival and less healthcare utilization. In addition to their salubrious benefits, β agonists may produce untoward effects. Increased mortality and hospitalizations among patients with left ventricular heart failure, who were treated with β agonists, has caused concern about their use in patients with COPD and heart disease. Further experience and testing will determine the optimal role of ultra-LABAs in the management of COPD.

  9. Design and synthesis of HIV-1 protease inhibitors for a long-acting injectable drug application.

    PubMed

    Kesteleyn, Bart; Amssoms, Katie; Schepens, Wim; Hache, Geerwin; Verschueren, Wim; Van De Vreken, Wim; Rombauts, Klara; Meurs, Greet; Sterkens, Patrick; Stoops, Bart; Baert, Lieven; Austin, Nigel; Wegner, Jörg; Masungi, Chantal; Dierynck, Inge; Lundgren, Stina; Jönsson, Daniel; Parkes, Kevin; Kalayanov, Genadiy; Wallberg, Hans; Rosenquist, Asa; Samuelsson, Bertil; Van Emelen, Kristof; Thuring, Jan Willem

    2013-01-01

    The design and synthesis of novel HIV-1 protease inhibitors (PIs) (1-22), which display high potency against HIV-1 wild-type and multi-PI-resistant HIV-mutant clinical isolates, is described. Lead optimization was initiated from compound 1, a Phe-Phe hydroxyethylene peptidomimetic PI, and was directed towards the discovery of new PIs suitable for a long-acting (LA) injectable drug application. Introducing a heterocyclic 6-methoxy-3-pyridinyl or a 6-(dimethylamino)-3-pyridinyl moiety (R(3)) at the para-position of the P1' benzyl fragment generated compounds with antiviral potency in the low single digit nanomolar range. Halogenation or alkylation of the metabolic hot spots on the various aromatic rings resulted in PIs with high stability against degradation in human liver microsomes and low plasma clearance in rats. Replacing the chromanolamine moiety (R(1)) in the P2 protease binding site by a cyclopentanolamine or a cyclohexanolamine derivative provided a series of high clearance PIs (16-22) with EC(50)s on wild-type HIV-1 in the range of 0.8-1.8 nM. PIs 18 and 22, formulated as nanosuspensions, showed gradual but sustained and complete release from the injection site over two months in rats, and were therefore identified as interesting candidates for a LA injectable drug application for treating HIV/AIDS.

  10. Subcutaneous implants for long-acting drug therapy in laboratory animals may generate unintended drug reservoirs

    PubMed Central

    Guarnieri, Michael; Tyler, Betty M.; DeTolla, Louis; Zhao, Ming; Kobrin, Barry

    2014-01-01

    Background: Long-acting therapy in laboratory animals offers advantages over the current practice of 2-3 daily drug injections. Yet little is known about the disintegration of biodegradable drug implants in rodents. Objective: Compare bioavailability of buprenorphine with the biodegradation of lipid-encapsulated subcutaneous drug pellets. Methods: Pharmacokinetic and histopathology studies were conducted in BALB/c female mice implanted with cholesterol-buprenorphine drug pellets. Results: Drug levels are below the level of detection (0.5 ng/mL plasma) within 4-5 days of implant. However, necroscopy revealed that interstitial tissues begin to seal implants within a week. Visual inspection of the implant site revealed no evidence of inflammation or edema associated with the cholesterol-drug residue. Chemical analyses demonstrated that the residues contained 10-13% of the initial opiate dose for at least two weeks post implant. Discussion: The results demonstrate that biodegradable scaffolds can become sequestered in the subcutaneous space. Conclusion: Drug implants can retain significant and unintended reservoirs of drugs. PMID:24459402

  11. Clinical Decision-Making in the Treatment of Schizophrenia: Focus on Long-Acting Injectable Antipsychotics.

    PubMed

    Samalin, Ludovic; Garnier, Marion; Auclair, Candy; Llorca, Pierre-Michel

    2016-11-19

    The purpose of this study was to identify clinician characteristics associated with higher prescription rates of long-acting injectable (LAI) antipsychotics, as well as the sources that influence medical decision-making regarding the treatment of schizophrenia. We surveyed 202 psychiatrists during six regional French conferences (Bordeaux, Lyon, Marseille, Nice, Paris, and Strasbourg). Data on the characteristics of practice, prescription rates of antipsychotic, and information sources about their clinical decisions were collected. Most psychiatrists used second-generation antipsychotics (SGAs), and preferentially an oral formulation, in the treatment of schizophrenia. LAI SGAs were prescribed to 30.4% of schizophrenic patients. The duration and type of practice did not influence the class or formulation of antipsychotics used. The clinicians following the higher percentage of schizophrenic patients were associated with a higher use of LAI antipsychotics and a lower use of oral SGAs. Personal experience, government regulatory approval, and guidelines for the treatment of schizophrenia were the three main contributing factors guiding clinicians' decision-making regarding the treatment of schizophrenia. The more clinicians follow schizophrenic patients, the more they use LAI antipsychotics. The development of specialized programs with top specialists should lead to better use of LAI antipsychotics in the treatment of schizophrenia.

  12. Feline diabetes mellitus: clinical use of long-acting glargine and detemir.

    PubMed

    Bloom, Carly Anne; Rand, Jacquie

    2014-03-01

    Diabetes mellitus is a common endocrine disorder in feline practice, affecting approximately 1 in 200 cats. The majority of diabetic cats have type 2 diabetes mellitus, which results from a combination of peripheral insulin resistance and a progressive reduction in insulin production. While usually easy to diagnose, management of diabetes mellitus presents a number of challenges for practitioners and clients alike. Practitioners must decide on diet, insulin type and dose, monitoring method and intensity, and concomitant therapy, which will vary based on individual patient and client needs, and geographic location. Practitioners may also encounter patients with diabetic ketoacidosis or other diabetic complications, and patients with multiple concurrent diseases. Clients may be challenged by the substantial time and financial commitment involved in owning a diabetic cat. Understanding the pathophysiology, optimal treatment protocols and current goals of diabetes management will benefit practitioners managing diabetic cats. This article reviews the most current management plans for feline diabetics. It places particular emphasis on best practice for achieving diabetic remission, which is an attainable goal in the majority of newly diagnosed diabetic cats. The information in this article is drawn from the recent human and veterinary literature, including prospective and retrospective studies. The body of prospective clinical data on the use of newer, long-acting insulins (glargine and especially detemir) in cats is limited, but growing.

  13. Eliminating health disparities in unintended pregnancy with long-acting reversible contraception (LARC).

    PubMed

    Parks, Caitlin; Peipert, Jeffrey F

    2016-06-01

    Significant public health disparities exist surrounding teen and unplanned pregnancy in the United States. Women of color and those with lower education and socioeconomic status are at much greater risk of unplanned pregnancy and the resulting adverse outcomes. Unplanned pregnancies reduce educational and career opportunities and may contribute to socioeconomic deprivation and widening income disparities. Long-acting reversible contraception (LARC), including intrauterine devices and implants, offer the opportunity to change the default from drifting into parenthood to planned conception. LARC methods are forgettable; once placed, they offer highly effective, long-term pregnancy prevention. Increasing evidence in the medical literature demonstrates the population benefits of use of these methods. However, barriers to more widespread use of LARC methods persist and include educational, access, and cost barriers. With increasing insurance coverage under the Affordable Care Act and more widespread, no-cost coverage of methods, more and more women are choosing intrauterine devices and the contraceptive implant. Increasing the use of highly effective contraceptive methods may provide one solution to the persistent problem of the health disparities of unplanned and teen pregnancies in the United States and improve women's and children's health.

  14. Suicide Prevention in Schizophrenia: Do Long-Acting Injectable Antipsychotics (LAIs) have a role?

    PubMed

    Pompili, Maurizio; Orsolini, Laura; Lamis, Dorian A; Goldsmith, David R; Nardella, Adele; Falcone, Giulia; Corigliano, Valentina; Luciano, Mario; Fiorillo, Andrea

    2017-02-23

    Suicide risk is a major cause of death among patients with schizophrenia. Death by suicide has been reported in approximately 5% of schizophrenia patients although such figure appears an underestimation of the problem. A number of risk factors are routinely reported as associated with suicide risk among these patients, some of which are modifiable by targeted therapeutic strategies. Clozapine is the only compound that gathered evidence as an effective treatment for reducing suicide risk in schizophrenia. Long-Acting Injectable Antipsychotics (LAIs) have a range of advantages in terms of efficacy, safety and tolerability in the treatment of schizophrenia, and one area of interest is whether LAI-treatment may decrease suicidality by indirectly acting on a range of risk factors for suicide specific to schizophrenia patients. This background encouraged the present, review of research pertaining to LAI in relation to modifiable risk factors for suicide in schizophrenia. We viewed our task as gathering, speculatingand critically appraising the available research relevant to the topic, with the aim of formulating a hypothesis to be tested with further research.

  15. Four years' experience with the TCu 220C, a long-acting multisleeved copper intrauterine device.

    PubMed

    Thiery, M; Van Der Pas, H; Van Kets, H; Boogers, W; Haspels, A; Amy J-j

    1979-01-01

    4 years of experience with the TCu 220C (901 women; 28,071 woman months of use) - a long-acting multisleeved copper IUD - are analyzed. Event rates were calculated by life-table analysis with a computer program on an IBM 370/148-OS/VS1. Net cumulative rates at 4 years were as follows: pregnancy 3.3, expulsion 5.2, removal for bleeding, pain and other medical reasons 7.7, and 4.3 respectively. The incidence of pregnancy, expulsions, and removal for bleeding/pain decreases with time. Parity influences the performance of the TCu 220C. It seems to affect the pregnancy rate only marginally, but the expulsion and removal rates (for bleeding, pain, or other medical reasons) are higher in the nulliparae, and the same trends appear to be present for women of lower age groups. The IUD insertion technique seems to be important when determining the effectiveness of the method. The expulsion rate is significantly higher when the push-in technique (without sounding) is used, and the same tendency is present for pregnancies and removals for bleeding/pain, albeit to a lesser degree. Refraining from sounding the uterus and pushing-in the TCu 220C introduces the risk of not inserting the IUD high enough into the uterine cavity and therefore increases the risk of expulsion.

  16. Successful treatment of canine necrolytic migratory erythema (superficial necrolytic dermatitis) due to metastatic glucagonoma with octreotide.

    PubMed

    Oberkirchner, Ursula; Linder, Keith E; Zadrozny, Leah; Olivry, Thierry

    2010-10-01

    Necrolytic migratory erythema (NME; also known as superficial necrolytic dermatitis) is a syndrome most often associated with certain chronic liver diseases or pancreatic glucagonomas. In humans with glucagonoma-associated NME, skin lesions usually respond to octreotide, a somatostatin analogue that inhibits glucagon release. In this report an 11-year-old golden retriever dog with pancreatic glucagonoma and metastasis to the regional lymph nodes, spleen and liver was diagnosed with NME. The dog exhibited erosions, ulcers and crusts on the paws, pressure points, muzzle, periocular area and prepuce. The dog was also anorexic and had difficulty walking. Because metastasis precluded surgery, treatment was initiated with subcutaneous octreotide (2 μg/kg twice daily). Skin lesions and systemic clinical signs improved markedly within 5 days. The dosage was increased to nearly 3 μg/kg twice daily and signs almost completely resolved within 10 days. Anorexia was the major adverse effect observed. During the following month, both dosage (1-3.7 μg/kg) and frequency (two to four times daily) of the octreotide injections were adjusted to permit control of clinical signs while maintaining adequate appetite. Temporary cessation of octreotide administration resulted in the rapid recurrence of skin lesions. Resuming injections led to improvement of clinical signs within 48 h. The dog was later euthanized because of progressive metastatic disease. In conclusion, subcutaneous octreotide injections were beneficial in this dog with glucagonoma-associated NME. This somatostatin analogue could be a valuable option to treat canine patients with non-resectable or relapsing pancreatic glucagonoma-associated NME.

  17. Additive effect of ketoconazole and octreotide in the treatment of severe adrenocorticotropin-dependent hypercortisolism.

    PubMed

    Vignati, F; Loli, P

    1996-08-01

    Over the last few years ketoconazole and octreotide have been employed in the treatment of pituitary-dependent or ectopic Cushing's syndrome. In four patients (two men and two women, aged 25-64 yr) with severe ACTH-dependent hypercortisolism in whom medical treatment with ketoconazole showed limited effectiveness and/or tolerability, we tried the association with octreotide. In all patients ketoconazole (200-1000 mg) induced a marked decrease in urinary free cortisol (UFC) excretion, but normalization could not be achieved. After ketoconazole discontinuation, three patients received octreotide alone (300-1500 micrograms/day, sc). This drug caused a dramatic decrease in UFC excretion, although not normalization; in all patients, escape from treatment occurred. Combined treatment was carried out for 10-180 days. Urinary cortisol excretion normalized and remained steadily within normal limits in three of four patients in whom normal UFC excretion had never been attained with both single drug regimens; in the fourth patient, UFC excretion decreased to levels lower than those achieved with ketoconazole or octreotide alone. The association with octreotide allowed a reduction in the daily dose of ketoconazole in three patients. Consistent with the steady reduction of cortisol production, a striking clinical improvement occurred in all patients after starting combined treatment. The normalization of UFC in three of four patients treated with both agents suggests that this approach may be useful in the long term treatment of severe forms of hypercortisolism of both pituitary and ectopic origin. In contrast to the limited effectiveness of each drug taken singularly at the same or higher doses, the association of the two drugs had an additive effect in the attainment of normal urinary cortisol excretion.

  18. In vitro structure-activity relationship of Re-cyclized octreotide analogues.

    PubMed

    Dannoon, Shorouk F; Bigott-Hennkens, Heather M; Ma, Lixin; Gallazzi, Fabio; Lewis, Michael R; Jurisson, Silvia S

    2010-07-01

    Development of radiolabeled octreotide analogues is of interest for targeting somatostatin receptor (SSTR)-positive tumors for diagnostic and therapeutic purposes. We are investigating a direct labeling approach for incorporation of a Re ion into octreotide analogues, where the peptide sequences are cyclized via coordination to Re rather than through a disulfide bridge. Various octreotide analogue sequences and coordination systems (e.g., S(2)N(2) and S(3)N) were synthesized and cyclized with nonradioactive Re. In vitro competitive binding assays with (111)In-DOTA-Tyr(3)-octreotide in AR42J rat pancreatic tumor cells yielded IC(50) values as a measure of SSTR affinity of the Re-cyclized analogues. Three-dimensional structures of Re-cyclized Tyr(3)-octreotate and its disulfide-bridged analogue were calculated from two-dimensional NMR experiments to visualize the effect of metal cyclization on the analogue's pharmacophore. Only two of the 11 Re-cyclized analogues investigated showed moderate in vitro binding affinity toward somatostatin subtype 2 receptors. Three-dimensional molecular structures of Re- and disulfide-cyclized Tyr(3)-octreotate were calculated, and both of their pharmacophore turns appear to be very similar with minor differences due to metal coordination to the amide nitrogen of one of the pharmacophore amino acids. Various Re-cyclized analogues were developed and analogue 4 had moderate affinity toward somatostatin subtype 2 receptors. In vitro stable studies that are in progress showed stable radiometal cyclization of octreotide analogues via NS(3) and N(2)S(2) coordination forming five- and six-membered chelate rings. In vivo biodistribution studies are underway of (99m)Tc-cyclized analogue 4. Copyright 2010 Elsevier Inc. All rights reserved.

  19. In Vitro Structure-Activity Relationship of Re-cyclized Octreotide Analogues

    PubMed Central

    Dannoon, Shorouk F.; Bigott-Hennkens, Heather M.; Ma, Lixin; Gallazzi, Fabio; Lewis, Michael R.; Jurisson, Silvia S.

    2010-01-01

    Introduction Development of radiolabeled octreotide analogues is of interest for targeting somatostatin receptor-positive tumors for diagnostic and therapeutic purposes. We are investigating a direct labeling approach for incorporation of a Re ion into octreotide analogues, where the peptide sequences are cyclized via coordination to Re rather than through a disulfide bridge. Methods Various octreotide analogue sequences and coordination systems (e.g., S2N2 and S3N) were synthesized and cyclized with non-radioactive Re. In vitro competitive binding assays with 111In-DOTA-Tyr3-octreotide in AR42J rat pancreatic tumor cells yielded IC50 values as a measure of somatostatin receptor affinity of the Re-cyclized analogues. Three-dimensional structures of Re-cyclized Tyr3-octreotate and its disulfide-bridged analogue were calculated from two-dimensional NMR experiments to visualize the effect of metal cyclization on the analogue’s pharmacophore. Results Only two of the eleven Re-cyclized analogues investigated showed moderate in vitro binding affinity toward somatostatin subtype 2 receptors. Three-dimensional molecular structures of Re- and disulfide-cyclized Tyr3-octreotate were calculated, and both of their pharmacophore turns appear to be very similar with minor differences due to metal coordination to the amide nitrogen of one of the pharmacophore amino acids. Conclusions Various Re-cyclized analogues were developed and analogue 4 had moderate affinity toward somatostatin subtype 2 receptors. In vitro stable studies that are in progress showed stable radiometal-cyclization of octreotide analogues via NS3 and N2S2 coordination forming 5- and 6- membered chelate rings. In vivo biodistribution studies are underway of 99m Tc- cyclized analogue 4. PMID:20610157

  20. The discovery of potent and long-acting oral factor Xa inhibitors with tetrahydroisoquinoline and benzazepine P4 motifs.

    PubMed

    Watson, Nigel S; Adams, Carl; Belton, David; Brown, David; Burns-Kurtis, Cynthia L; Chaudry, Laiq; Chan, Chuen; Convery, Máire A; Davies, David E; Exall, Anne M; Harling, John D; Irvine, Stephanie; Irving, Wendy R; Kleanthous, Savvas; McLay, Iain M; Pateman, Anthony J; Patikis, Angela N; Roethke, Theresa J; Senger, Stefan; Stelman, Gary J; Toomey, John R; West, Robert I; Whittaker, Caroline; Zhou, Ping; Young, Robert J

    2011-03-15

    The discovery and evaluation of potent and long-acting oral sulfonamidopyrrolidin-2-one factor Xa inhibitors with tetrahydroisoquinoline and benzazepine P4 motifs are described. Unexpected selectivity issues versus tissue plasminogen activator in the former series were addressed in the later, delivering a robust candidate for progression towards clinical studies. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Antipsychotic-induced metabolic effects in the female rat: Direct comparison between long-acting injections of risperidone and olanzapine.

    PubMed

    Ersland, Kari M; Skrede, Silje; Røst, Therese H; Berge, Rolf K; Steen, Vidar M

    2015-12-01

    Several antipsychotics have well-known adverse metabolic effects. Studies uncovering molecular mechanisms of such drugs in patients are challenging due to high dropout rates, previous use of antipsychotics and restricted availability of biological samples. Rat experiments, where previously unexposed animals are treated with antipsychotics, allow for direct comparison of different drugs, but have been hampered by the short half-life of antipsychotics in rodents. The use of long-acting formulations of antipsychotics could significantly increase the value of rodent models in the molecular characterization of therapeutic and adverse effects of these agents. However, as long-acting formulations have rarely been used in rodents, there is a need to characterize the basic metabolic phenotype of different antipsychotics. Using long-acting olanzapine injections as a positive control, the metabolic effects of intramuscular long-acting risperidone in female rats were investigated for the first time. Like olanzapine, risperidone induced rapid, significant hyperphagia and weight gain, with concomitant increase in several plasma lipid species. Both drugs also induced weight-independent upregulation of several genes encoding enzymes involved in lipogenesis, but this activation was not confirmed at the protein level. Our findings shed light on the role of drug administration, drug dose and nutritional status in the development of rodent models for adverse metabolic effects of antipsychotic agents. © The Author(s) 2015.

  2. Role of indacaterol and the newer very long-acting β2-agonists in patients with stable COPD: a review

    PubMed Central

    Ridolo, Erminia; Montagni, Marcello; Olivieri, Elisa; Riario-Sforza, Gian Galeazzo; Incorvaia, Cristoforo

    2013-01-01

    Bronchodilators are central drugs in the management of patients with chronic obstructive pulmonary disease (COPD). Indacaterol was the first agent of the novel family of very long-acting β2-agonists to be used as an inhaled bronchodilator for COPD and provides 24-hour therapeutic action, thus allowing once-daily administration. Data from clinical trials show that indacaterol has a bronchodilator effect similar to that of the anticholinergic tiotropium bromide and slightly higher efficacy compared with the long-acting β2-agonists, salmeterol and formoterol. Moreover, the safety profile is excellent and comparable with that of placebo. Concerning adherence with drug treatment and real-life management in respect to long-acting β2-agonists, once-daily dosing makes indacaterol more convenient for COPD patients and is likely to enhance patient adherence. Other very long-acting β2-agonists currently in development include vilanterol, olodaterol, and carmoterol, and these have shown good characteristics for clinical use in the studies reported thus far. PMID:24082783

  3. New approaches to antiretroviral drug delivery: challenges and opportunities associated with the use of long-acting injectable agents.

    PubMed

    Boffito, Marta; Jackson, Akil; Owen, Andrew; Becker, Stephen

    2014-01-01

    Research on improved treatment of HIV infection and pre-exposure prophylaxis continues. Poor adherence to treatment is the critical risk factor for virological failure and resistance development, and long-acting formulations of anti-HIV medications that need only infrequent dosing may facilitate long-term therapeutic responses. Importantly, long-acting formulations of therapeutic agents have been used to avoid missing doses or treatment fatigue to prescribed lifelong medications in a number of different medical fields, with demonstrable success. However, such formulations are associated with challenges, such as the prolongation of adverse events with the persistence of drug concentrations and concerns over the development of resistance as a result of selective pressure as drug concentrations decline. Furthermore, long-acting injectable formulations of antiretroviral (ARV) agents with infrequent dosing may be advantageous over daily oral drug intake to prevent transmission of HIV. However, the knowledge on protective drug concentrations and frequency of dosing is poor to date and implementation globally is challenging. Importantly, if nanoformulations of ARVs requiring lower drug doses become available globally, the potential for treatment cost reductions is high, as, especially in resource-limited settings, the active pharmaceutical ingredient accounts for the greater proportion of the total cost of the medicine. In conclusion, different long-acting ARVs are being studied in phase I/II for both the treatment and prevention of HIV infection, and research on administering these agents in combination has started.

  4. Optimization and evaluation of MALDI TOF mass spectrometric imaging for quantification of orally dosed octreotide in mouse tissues.

    PubMed

    Rao, Tai; Shen, Boyu; Zhu, Zhangpei; Shao, Yuhao; Kang, Dian; Li, Xinuo; Yin, Xiaoxi; Li, Haofeng; Xie, Lin; Wang, Guangji; Liang, Yan

    2017-04-01

    Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry imaging (MALDI-TOF-MSI) has received considerable attention in recent years since it allows molecular mapping of diverse bimolecular in animal/plant tissue sections, although some barriers still exist in absolute pixel-to-pixel quantification. Octreotide, a synthetic somatostatin analogue, has been widely used to prevent gastrointestine bleeding in the clinic. The aim of the present study is to develop a MALDI-TOF-MSI method for quantitatively visualizing spatial distribution of octreotide in mouse tissues. In this process, a structurally similar internal standard was spotted onto tissue section together with matrix solution to minimize signal variation and give excellent quantitative results. The 2,5-dihydroxybenzoic acid was chosen as the most suitable matrix via comparing the signal/noise generated by MALDI-TOF-MSI after cocrystallization of octreotide with different matrix candidates. The reliability of MALDI-TOF-MSI, with respect to linearity, sensitivity and precision, was tested via measuring octreotide in fresh tissue slices at different concentrations. The validated method was then successfully applied to visualize the distribution of octreotide in mouse tissues after oral administration of octreotide at 20mg/kg. The results demonstrated that MALDI-TOF-MSI could not only clearly visualize the spatial distribution of octreotide, but also make the calculation of the key pharmacokinetic parameters (Tmax and t1/2) possible. More importantly, the tissue concentration-time curves of octreotide determined by MALDI-TOF-MSI agreed well with those measured based on LC-MS/MS.These findings illustrate the potential of MALDI-TOF-MSI in pharmacokinetic profiling during drug development.

  5. Prescription coverage in indigent patients affects the use of long-acting opiates in the management of cancer pain

    PubMed Central

    Wieder, Robert; DeLaRosa, Nila; Bryan, Margarette; Hill, Ann Marie; Amadio, William J.

    2013-01-01

    Purpose We tested the hypothesis that prescription coverage affects the prescribing of long-acting opiates to indigent inner city minority patients with cancer pain. Materials and Methods We conducted a chart review of 360 patients treated in the Oncology Practice at UMDNJ-University Hospital, who were prescribed opiate pain medications. Half the patients were Charity Care or Self Pay (CC/SP), without the benefit of prescription coverage, and half had Medicaid, with unlimited prescription coverage. We evaluated patients discharged from a hospitalization, who had three subsequent outpatient follow up visits. We compared demographics, pain intensity, the type and dose of opiates, adherence to prescribed pain regimen, unscheduled Emergency Department (ED) visits and unscheduled hospitalizations. Results There was a significantly greater use of long-acting opiates in the Medicaid group than in the CC/SP group. The Medicaid group had significantly more African American patients and a greater rate of smoking and substance use and the CC/SP group disproportionately more Hispanic and Asian patients and less smoking and substance use. Hispanic and Asian patients were less likely to have long-acting opiates prescribed to them. Pain levels and adherence were equivalent in both groups and were not affected by any of these variables except stage of disease, which was equally distributed in the two groups. Conclusion Appropriate use of long-acting opiates for equivalent levels of cancer pain are influenced only by the availability of prescription coverage. The group without prescription coverage and receiving fewer long-acting opiates had disproportionately more Hispanic and Asian patients. PMID:24106748

  6. Long acting injectable versus oral naltrexone maintenance therapy with psychosocial intervention for heroin dependence: A quasi-experiment

    PubMed Central

    Brooks, Adam C.; Comer, Sandra D.; Sullivan, Maria A.; Bisaga, Adam; Carpenter, Kenneth; Raby, Wilfrid M.; Yu, Elmer; O’Brien, Charles P.; Nunes, Edward V.

    2009-01-01

    Objective To conduct a quasi-experimental comparison of early clinical outcomes between injectable, sustained release, depot naltrexone formulation versus oral naltrexone maintenance therapy. Method Early retention and urine results were compared between patients participating in two concurrently run randomized clinical trials of oral (N = 69) and long acting injectable naltrexone maintenance therapy with psychosocial therapy (N = 42). Retention in treatment and opiate use in the first 8-weeks post-detoxification were compared. Results Long acting injectable naltrexone produced significantly better outcome than oral naltrexone on days retained in treatment and one measure of opiate use; other measures were not significantly different, but differences were in the same direction. In subanalyses, there were interaction effects between baseline heroin severity and type of treatment. In subanalyses, heroin users with more severe baseline use showed better retention in oral naltrexone maintenance combined with intensive psychotherapy (Behavior Naltrexone Therapy) as compared to retention of severe users treated with long acting naltrexone injections combined with standard cognitive-behavioral psychotherapy; less severe heroin users evidenced better outcomes when treated with long acting injectable naltrexone. Conclusions This quasi-experimental analysis provides tentative indications of superior outcomes for heroin dependent patients treated with long acting injectable naltrexone compared to oral naltrexone. The finding that heroin users with more severe baseline use achieved better outcomes with oral naltrexone is most probably attributable to the intensive nature of the psychosocial treatments provided, and points to the opportunity for continued research in augmenting injectable naltrexone with psychosocial strategies to further improve outcome especially in more severe users. The results should be considered exploratory given the quasi-experimental nature of the

  7. Prescription coverage in indigent patients affects the use of long-acting opioids in the management of cancer pain.

    PubMed

    Wieder, Robert; Delarosa, Nila; Bryan, Margarette; Hill, Ann Marie; Amadio, William J

    2014-01-01

    We tested the hypothesis that prescription coverage affects the prescribing of long-acting opiates to indigent inner city minority patients with cancer pain. We conducted a chart review of 360 patients treated in the Oncology Practice at University of Medicine and Dentistry of New Jersey University Hospital, who were prescribed opiate pain medications. Half the patients were charity care or self-pay (CC/SP), without the benefit of prescription coverage, and half had Medicaid, with unlimited prescription coverage. We evaluated patients discharged from a hospitalization, who had three subsequent outpatient follow-up visits. We compared demographics, pain intensity, the type and dose of opiates, adherence to prescribed pain regimen, unscheduled emergency department visits, and unscheduled hospitalizations. There was a significantly greater use of long-acting opiates in the Medicaid group than in the CC/SP group. The Medicaid group had significantly more African American patients and a greater rate of smoking and substance use, and the CC/SP group disproportionately more Hispanic and Asian patients and less smoking and substance use. Hispanic and Asian patients were less likely to have long-acting opiates prescribed to them. Pain levels and adherence were equivalent in both groups and were not affected by any of these variables except stage of disease, which was equally distributed in the two groups. Appropriate use of long-acting opiates for equivalent levels of cancer pain was influenced only by the availability of prescription coverage. The group without prescription coverage and receiving fewer long-acting opiates had disproportionately more Hispanic and Asian patients. Wiley Periodicals, Inc.

  8. Meta-analysis of the efficacy and safety of long-acting non-ergot dopamine agonists in Parkinson's disease.

    PubMed

    Zhou, Chang-Qing; Zhang, Jiang-Wei; Wang, Min; Peng, Guo-Guang

    2014-07-01

    A meta-analysis of randomized controlled trials (RCT) was performed to evaluate the efficacy and safety of long-acting non-ergot dopamine agonists (NEDA) versus placebo in Parkinson's disease (PD). A comprehensive literature search up to February 2013 was performed, and the weighted mean differences (WMD) and relative risks (RR) with 95% confidence intervals (CI) were calculated. Nine RCT (n=2857) which assessed the rotigotine transdermal patch, extended-release pramipexole, and ropinirole prolonged-release, were included. Compared with placebo, long-acting NEDA achieved greater improvements in Unified Parkinson's Disease Rating Scale activities of daily living (ADL) score (WMD -1.77, 95% CI -2.13 to -1.41), motor score (WMD -4.18, 95% CI -4.94 to -3.43) and the ADL and motor subtotal score (WMD -5.12, 95% CI -6.16 to -4.07), as well as a reduction in "off" time (WMD -1.29, 95% CI -1.64 to -0.93) and an increase in "on" time without troublesome dyskinesia (WMD 1.55, 95% CI 1.06 to 2.04). Compared with placebo, long-acting NEDA were associated with a higher risk of nausea, but no difference was found in headache incidence. Higher risks of dizziness, somnolence, constipation, vomiting, and insomnia were only found in early PD while higher risks of dyskinesia and hallucination were only found in advanced PD. The results of our meta-analysis showed that the use of long-acting NEDA can reduce the symptoms of PD patients. However, long-acting NEDA were also associated with a higher incidence of adverse events, especially in early PD patients, compared with placebo.

  9. [Effect of barnidipine hydrochloride on the autonomic nervous system: difference between short- and long-acting components of calcium antagonist].

    PubMed

    Soejima, K; Akaishi, M; Oyamada, K; Mitamura, H; Ogawa, S

    1997-07-01

    Short-acting calcium antagonists have a deleterious effect on the prognosis for patients with myocardial ischemia, possibly caused by overactivation of sympathetic nerves due to vasodilatation, negative inotropism, or coronary steal. However, there is considerable debate about whether long-acting calcium antagonists as well as the short-acting calcium antagonists have the same effect. Barnidipine-HCl is a newly-developed calcium antagonist with 1:2 short- and long-acting particles. This study evaluated the changes of autonomic tone due to barnidipine. Both the short- and long-acting effect of the calcium antagonist was evaluated. Eleven patients with primary hypertension underwent 24-hour ambulatory electrocardiogram and blood pressure monitoring before and after the treatment with barnidipine. Heart rate and blood pressure were compared before and after the medication. Heart rate variability was analyzed with a Marquette 8000/T. High frequency power (HF), as a parameter of vagal tone, and the ratio to low frequency power (LF), as a parameter of sympathetic tone, were obtained. Twenty-four-hour average blood pressure decreased significantly during the day, but nocturnal hypotension was not observed. Heart rate did not increase. HF decreased at the peak of the short- and long-acting components. LF/HF increased at the peak of the short-acting component. Short-acting particles of barnidipine had a deleterious effect on the autonomic tone, that is overactivation of sympathetic tone and suppression of vagal tone. Long-acting particles of barnidipine suppressed the vagal tone. These findings suggest that short-acting calcium antagonists may cause arrhythmia or deterioration of coronary ischemia.

  10. Risperidone long-acting injectable monotherapy in the maintenance treatment of bipolar I disorder.

    PubMed

    Quiroz, Jorge A; Yatham, Lakshmi N; Palumbo, Joseph M; Karcher, Keith; Kushner, Stuart; Kusumakar, Vivek

    2010-07-15

    Treatment adherence is a significant problem in patients with bipolar disorder. This study was designed to determine the efficacy of risperidone long-acting injectable (LAI) in the maintenance treatment of bipolar I disorder. Eligible patients with current or recent manic or mixed episodes (n = 559, aged 18-65 years) were treated with open-label oral risperidone for 3 weeks (period II) and open-label risperidone LAI for 26 weeks (n = 501; period III). Patients who maintained response (n = 303) were randomly allocated 1:1 to placebo injections (n = 149) or to continue risperidone LAI (n = 154) for up to 24 months (period IV). Most (77%) patients on risperidone LAI received a dose of 25 mg every 2 weeks during period IV. Time to recurrence for any mood episode (primary outcome variable) was significantly longer in the risperidone LAI group versus placebo (p < .001); the difference was significant for time to recurrence of elevated-mood episode (p < .001) but not time to recurrence of depressive episode (p = .805). Weight gains > or = 7% (compared with the period's baseline) occurred in 15% of patients in period III; in 12% of patients on risperidone LAI and 3% of patients on placebo in period IV. Risperidone LAI monotherapy significantly delayed the time to recurrence of mood episodes, versus placebo, in this controlled, randomized study in patients with bipolar I disorder. Risperidone LAI was tolerable and no new safety concerns emerged compared with previous studies of risperidone LAI. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  11. Combination treatment with risperidone long-acting injection and psychoeducational approaches for preventing relapse in schizophrenia.

    PubMed

    Zhao, Yueren; Kishi, Taro; Iwata, Nakao; Ikeda, Manabu

    2013-01-01

    A recent meta-analysis showed that long-acting injectable (LAI) antipsychotics were not superior to oral antipsychotics for preventing relapse in patients with schizophrenia. We therefore designed a treatment strategy combining risperidone LAI and COMPASS (COMprehensive Psycho-educational Approach and Scheme Set), an original psychoeducational program supporting treatment with risperidone LAI and evaluating subjective treatment satisfaction, transition of symptoms, and effectiveness in preventing symptomatic relapse. The aim of this study was to examine whether addition of COMPASS to risperidone LAI was more effective in preventing relapse in schizophrenia patients than risperidone LAI alone, with the latter group consisting of patients enrolled in a Phase III trial of risperidone LAI in Japan. Patients were followed up for 6 months, with COMPASS continuously implemented from the transition to the observation phase. The primary efficacy measurements were relapse rate (rates of rehospitalization and discontinuation due to inefficacy). Secondary efficacy measurements were the Brief Psychiatric Rating Scale (BPRS) and Global Assessment of Functioning (GAF) scores. Of the 96 patients originally enrolled, 19 (19.8%) were discontinued from all causes. During the 6-month study period, ten of the 96 patients (10.4%) relapsed, compared with a 12.2% relapse rate in patients enrolled in a Phase III trial of risperidone LAI in Japan. Patients showed significant improvements in BPRS total scores (P = 0.0031), BPRS positive (P = 0.0451), BRPS negative (P < 0.0001), and general subscale scores (P = 0.0031), and GAF (P < 0.0001) from baseline to 6 months. In conclusion, the lower relapse rate observed in patients treated with COMPASS plus risperidone LAI than in patients treated with risperidone LAI alone suggests that COMPASS may have benefits in the treatment of schizophrenia, indicating a need for randomized, controlled trials in larger numbers of patients.

  12. Pharmacokinetics of Long-Acting Tenofovir Alafenamide (GS-7340) Subdermal Implant for HIV Prophylaxis

    PubMed Central

    Gunawardana, Manjula; Remedios-Chan, Mariana; Miller, Christine S.; Fanter, Rob; Yang, Flora; Marzinke, Mark A.; Hendrix, Craig W.; Beliveau, Martin; Moss, John A.; Smith, Thomas J.

    2015-01-01

    Oral or topical daily administration of antiretroviral (ARV) drugs to HIV-1-negative individuals in vulnerable populations is a promising strategy for HIV-1 prevention. Adherence to the dosing regimen has emerged as a critical factor determining efficacy outcomes of clinical trials. Because adherence to therapy is inversely related to the dosing period, sustained release or long-acting ARV formulations hold significant promise for increasing the effectiveness of HIV-1 preexposure prophylaxis (PrEP) by reducing dosing frequency. A novel, subdermal implant delivering the potent prodrug tenofovir alafenamide (TAF) with controlled, sustained, zero-order (linear) release characteristics is described. A candidate device delivering TAF at 0.92 mg day−1 in vitro was evaluated in beagle dogs over 40 days for pharmacokinetics and preliminary safety. No adverse events related to treatment with the test article were noted during the course of the study, and no significant, unusual abnormalities were observed. The implant maintained a low systemic exposure to TAF (median, 0.85 ng ml−1; interquartile range [IQR], 0.60 to 1.50 ng ml−1) and tenofovir (TFV; median, 15.0 ng ml−1; IQR, 8.8 to 23.3 ng ml−1), the product of in vivo TAF hydrolysis. High concentrations (median, 512 fmol/106 cells over the first 35 days) of the pharmacologically active metabolite, TFV diphosphate, were observed in peripheral blood mononuclear cells at levels over 30 times higher than those associated with HIV-1 PrEP efficacy in humans. Our report on the first sustained-release nucleoside reverse transcriptase inhibitor (NRTI) for systemic delivery demonstrates a successful proof of principle and holds significant promise as a candidate for HIV-1 prophylaxis in vulnerable populations. PMID:25896688

  13. Pediatricians' Attitudes and Beliefs about Long-Acting Reversible Contraceptives Influence Counseling.

    PubMed

    Berlan, Elise D; Pritt, Nicole M; Norris, Alison H

    2017-02-01

    Adolescents are at high risk for unintended pregnancy. Because of pediatricians' potential role in contraceptive counseling, understanding their attitudes and beliefs and counseling practices about use of long-acting reversible contraceptives (LARC; ie, etonogestrel implant and intrauterine devices [IUDs]) is vital. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: We interviewed primary care pediatricians (N = 23) in a Midwestern city in June-August 2014. We transcribed the interviews, developed a coding schema, and analyzed these qualitative data using a priori and open coding of transcripts. Few pediatricians had favorable views on adolescent IUD use and most did not include IUDs in routine contraception counseling. Pediatricians perceived IUDs to impose significant risks for adverse reproductive outcomes and to be poorly tolerated by adolescents. Poor and/or outdated knowledge influenced inaccurate beliefs and unsupportive attitudes. Whereas some pediatricians were advocates for adolescent use of IUDs, many others had concerns that IUDs were not appropriate and not favored by adolescents. In contrast, participants viewed the etonogestrel implant more favorably and often included it in routine counseling. Some pediatricians focused on the familiar and readily available methods (injectable and oral contraceptives) or assumed patients had predetermined expectations for those methods. Time spent counseling on LARC was also perceived as a barrier. Pediatricians described how education and increased familiarity with LARC changed viewpoints. A variety of beliefs and attitudes, as well as factors such as time and personal habits, influence pediatricians' contraceptive counseling practices. Until knowledge deficits are addressed, uninformed viewpoints and unfavorable attitudes will limit adolescents' access to LARC, especially IUDs. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All

  14. Aripiprazole Lauroxil: Pharmacokinetic Profile of This Long-Acting Injectable Antipsychotic in Persons With Schizophrenia.

    PubMed

    Hard, Marjie L; Mills, Richard J; Sadler, Brian M; Turncliff, Ryan Z; Citrome, Leslie

    2017-06-01

    Aripiprazole lauroxil is an extended-release prodrug of aripiprazole for intramuscular injection, approved for schizophrenia treatment. We developed a population pharmacokinetic (PopPK) model to characterize aripiprazole lauroxil PK and evaluate dosing scenarios likely to be encountered in clinical practice. Data from 616 patients with schizophrenia, collected from 5 clinical studies, were used to construct the PopPK model. The model was subsequently used to evaluate various dose levels and frequency and the impact of dosing delay on aripiprazole concentrations. The results of the model indicate that aripiprazole is released into the systemic circulation after 5 to 6 days, and release continues for an additional 36 days. The slow increase in aripiprazole concentration after injection necessitates the coadministration of oral aripiprazole for 21 days with the first injection. Based on the PopPK model simulations, a dosing interval of 882 mg every 6 weeks results in aripiprazole concentrations that fall within the concentration range associated with the efficacious aripiprazole lauroxil dose range (441-882 mg dosed monthly). A 662-mg monthly dose also resulted in aripiprazole concentrations within the efficacious dose range. Aripiprazole lauroxil administration results in prolonged exposure, such that dose delays of 2 to 4 weeks, depending on the dose regimen, do not require oral aripiprazole supplementation upon resumption of dosing. This PopPK model and model-based simulations were effective means for evaluating aripiprazole lauroxil dosing regimens and management of missed doses. Such analyses play an important role in determining the use of this long-acting antipsychotic in clinical practice.

  15. Provision of no-cost, long-acting contraception and teenage pregnancy.

    PubMed

    Secura, Gina M; Madden, Tessa; McNicholas, Colleen; Mullersman, Jennifer; Buckel, Christina M; Zhao, Qiuhong; Peipert, Jeffrey F

    2014-10-02

    The rate of teenage pregnancy in the United States is higher than in other developed nations. Teenage births result in substantial costs, including public assistance, health care costs, and income losses due to lower educational attainment and reduced earning potential. The Contraceptive CHOICE Project was a large prospective cohort study designed to promote the use of long-acting, reversible contraceptive (LARC) methods to reduce unintended pregnancy in the St. Louis region. Participants were educated about reversible contraception, with an emphasis on the benefits of LARC methods, were provided with their choice of reversible contraception at no cost, and were followed for 2 to 3 years. We analyzed pregnancy, birth, and induced-abortion rates among teenage girls and women 15 to 19 years of age in this cohort and compared them with those observed nationally among U.S. teens in the same age group. Of the 1404 teenage girls and women enrolled in CHOICE, 72% chose an intrauterine device or implant (LARC methods); the remaining 28% chose another method. During the 2008-2013 period, the mean annual rates of pregnancy, birth, and abortion among CHOICE participants were 34.0, 19.4, and 9.7 per 1000 teens, respectively. In comparison, rates of pregnancy, birth, and abortion among sexually experienced U.S. teens in 2008 were 158.5, 94.0, and 41.5 per 1000, respectively. Teenage girls and women who were provided contraception at no cost and educated about reversible contraception and the benefits of LARC methods had rates of pregnancy, birth, and abortion that were much lower than the national rates for sexually experienced teens. (Funded by the Susan Thompson Buffett Foundation and others.).

  16. Pharmacokinetics of an injectable long-acting parenteral formulation of doxycycline hyclate in pigs.

    PubMed

    Gutiérrez, L; Ocampo, L; Espinosa, F; Sumano, H

    2014-02-01

    Based on its ideal PK/PD ratios, doxycycline hyclate (DOX-h), a time-dependant antibacterial, is ideally expected to achieve sustained plasma drug concentrations at or slightly above the MIC level for as long as possible between dosing intervals. Pursuing this end, a poloxamer-based matrix was used to produce a 10% long-acting injectable preparation (DOX-h-LA) and its serum concentrations vs. time profile investigated after its injection to pigs in the pericaudal s.c. by parallel design. Results were compared with the forced oral bolus dose and i.v. pharmacokinetics of DOX-h. For this study, 12 recently weaned pigs per group were included in this trial, and a dose of 20 mg/kg was injected in all cases. DOX-h-LA showed the greatest values for bioavailability (115.38%); maximum serum concentration (Cmax) value was 1.5 ± 0.2 with a time to reach Cmax of 3.41 ± 0.04 h and an elimination rate constant of 70.93 ± 0.87( ) h. Considering minimum effective serum concentration of 0.5 μg/mL, a dose interval of at least 5 days can be achieved for DOX-h-LA, whereas p.o. and i.v. dosing of DOX-h may only last 11 and 15 h, respectively. Pigs were slaughtered on day 30 after this trial, and no visible remnants of the preparation were detected neither fibrosis was observed after a thorough macroscopic and histopathological analysis.

  17. Physician and patient benefit–risk preferences from two randomized long-acting injectable antipsychotic trials

    PubMed Central

    Katz, Eva G; Hauber, Brett; Gopal, Srihari; Fairchild, Angie; Pugh, Amy; Weinstein, Rachel B; Levitan, Bennett S

    2016-01-01

    Purpose To quantify clinical trial participants’ and investigators’ judgments with respect to the relative importance of efficacy and safety attributes of antipsychotic treatments for schizophrenia, and to assess the impact of formulation and adherence. Methods Discrete-choice experiment surveys were completed by patients with schizophrenia and physician investigators participating in two phase-3 clinical trials of paliperidone palmitate 3-month long-acting injectable (LAI) antipsychotic. Respondents were asked to choose between hypothetical antipsychotic profiles defined by efficacy, safety, and mode of administration. Data were analyzed using random-parameters logit and probit models. Results Patients (N=214) and physicians (N=438) preferred complete improvement in positive symptoms (severe to none) as the most important attribute, compared with improvement in any other attribute studied. Both respondents preferred 3-month and 1-month injectables to oral formulation (P<0.05), irrespective of prior adherence to oral antipsychotic treatment, with physicians showing greater preference for a 3-month over a 1-month LAI for nonadherent patients. Physicians were willing to accept treatments with reduced efficacy for patients with prior poor adherence. The maximum decrease in efficacy (95% confidence interval [CI]) that physicians would accept for switching a patient from daily oral to 3-month injectable was as follows: adherent: 9.8% (95% CI: 7.2–12.4), 20% nonadherent: 25.4% (95% CI: 21.0–29.9), and 50% nonadherent: >30%. For patients, adherent: 10.1% (95% CI: 6.1–14.1), nonadherent: the change in efficacy studied was regarded as unimportant. Conclusion Improvement in positive symptoms was the most important attribute. Patients and physicians preferred LAIs over oral antipsychotics, with physicians showing a greater preference for 3-month over 1-month LAI. Physicians and patients were willing to accept reduced efficacy in exchange for switching a patient from

  18. Effects of long-acting somatostatin analogues on redox systems in rat lens in experimental diabetes

    PubMed Central

    Kunjara, Sirilaksana; Greenbaum, A Leslie; Sochor, Milena; Flyvbjerg, Allan; Grønbaek, Henning; McLean, Patricia

    2014-01-01

    The effects of long-acting somatostatin analogues, angiopeptin (AGP) and Sandostatin (SMS), on the early decline in the lens content of glutathione (GSH), ATP and NADPH and increase in sorbitol were studied in STZ diabetic rats, and comparison was made with the effect of insulin. Three factors prompted this study: (i) the known increase in IGF-1 in ocular tissue in diabetes and antagonistic effect of somatostatins, (ii) the known effect of IGF-1 in increasing lens aldose reductase and (iii) the lack of effect of somatostatins on diabetic hyperglycaemia, the latter enabling a differentiation to be made between effects of hyperglycaemia per se and site(s) of IGF-1/somatostatins. All four metabolites studied showed a significant restoration towards the normal control level after 7 days of treatment with AGP and SMS, and AGP was more effective on levels of GSH and ATP. A significant correlation was found between GSH and ATP across all groups at 7 days treatment. The redox state changes in diabetes include both NADP+/NADPH and NAD+/NADH in the conversion of glucose to sorbitol and via sorbitol dehydrogenase to fructose with a linked decrease in ATP formation via NAD+/NADH regulation of the glycolytic pathway. The interlinked network of change includes the requirement for ATP in the synthesis of GSH. The present study points to possible loci of action of somatostatins in improving metabolic parameters in the diabetic rat lens via effects on aldose reductase and/or glucose transport at GLUT 3. PMID:24602114

  19. Blood eosinophils and inhaled corticosteroid/long-acting β-2 agonist efficacy in COPD

    PubMed Central

    Pavord, Ian D; Lettis, Sally; Locantore, Nicholas; Pascoe, Steve; Jones, Paul W; Wedzicha, Jadwiga A; Barnes, Neil C

    2016-01-01

    Objective We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels ≥2% were associated with a greater reduction in exacerbation rates with ICS therapy. Methods Three studies of ≥1-year duration met the inclusion criteria. Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs ≥2%). At baseline, 57–75% of patients had ≥2% blood eosinophils. Changes in FEV1 and St George's Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level. Results For patients with ≥2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001). No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively). In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo). No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ. Discussion Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations. PMID:26585525

  20. Knowledge and attitudes about long-acting reversible contraception among Latina women who desire sterilization

    PubMed Central

    White, Kari; Hopkins, Kristine; Potter, Joseph E.; Grossman, Daniel

    2013-01-01

    Background There is growing interest in increasing the use of long-acting reversible contraception (LARC), and suggestions that such methods may serve as an alternative to sterilization. However, there is little information about whether women who do not want more children would be interested in using LARC methods. Methods We conducted semi-structured interviews with 120 parous Latina women in El Paso, Texas who wanted a sterilization but had not obtained one. We assessed women’s awareness of and interest in using the copper intrauterine device (IUD), levonorgestrel intrauterine system (LNG-IUS), and etonogestrel implant. Findings Overall, 51%, 23% and 47% of women reported they had heard of the copper IUD, LNG-IUS and implant, respectively. More women stated they would use the copper IUD (24%) than the LNG-IUS (14%) or implant (9%). Among women interested in LARC, the most common reasons were that, relative to their current method, LARC methods were more convenient, effective, and provided longer-term protection against pregnancy. Those who had reservations about LARC were primarily concerned with menstrual changes. Women also had concerns about side effects and the methods' effectiveness in preventing pregnancy, preferring to use a familiar method. Conclusions Although these findings indicate many Latina women in this setting do not consider LARC an alternative to sterilization, they point to an existing demand among some who wish to end childbearing. Efforts are needed to improve women’s knowledge and access to a range of methods so they can achieve their childbearing goals. PMID:23816156

  1. Long-acting Reversible Contraception for Adolescents and Young Adults: Patient and Provider Perspectives

    PubMed Central

    Kavanaugh, Megan L.; Frohwirth, Lori; Jerman, Jenna; Popkin, Ronna; Ethier, Kathleen

    2013-01-01

    Study objective To describe and explore provider- and patient-level perspectives regarding long-acting reversible contraception (LARC) for teens and young adults (ages 16-24). Methods Data collection occurred between June – December 2011. We first conducted telephone interviews with administrative directors at 20 publicly funded facilities that provide family planning services. At six of these sites, we conducted a total of six focus group discussions (FGDs) with facility staff and forty-eight in-depth interviews (IDIs) with facility clients ages 16-24. Results Staff in the FGDs did not generally equate being a teen with ineligibility for IUDs. In contrast to staff, one quarter of the young women did perceive young age as rendering them ineligible. Clients and staff agreed that the “forgettable” nature of the methods and their duration were some of LARC’s most significant advantages. They also agreed that fear of pain associated with both insertion and removal and negative side effects were disadvantages. Some aspects of IUDs and implants were perceived as advantages by some clients but disadvantages by others. Common challenges to providing LARC-specific services to younger patients included extra time required to counsel young patients about LARC methods, outdated clinic policies requiring multiple visits to obtain IUDs, and a perceived higher removal rate among young women. The most commonly cited strategy for addressing many of these challenges was securing supplementary funding to support the provision of these services to young patients. Conclusion Incorporating young women’s perspectives on LARC methods into publicly funded family planning facilities’ efforts to provide these methods to a younger population may increase their use among young women. PMID:23287602

  2. Early Impact of the Affordable Care Act on Uptake of Long-acting Reversible Contraceptive Methods.

    PubMed

    Pace, Lydia E; Dusetzina, Stacie B; Keating, Nancy L

    2016-09-01

    The Affordable Care Act (ACA) required most private insurance plans to cover contraceptive services without patient cost-sharing as of January 2013 for most plans. Whether the ACA's mandate has impacted long-acting reversible contraceptives (LARC) use is unknown. The aim of this article is to assess trends in LARC cost-sharing and uptake before and one year after implementation of the ACA's contraceptive mandate. A retrospective cohort study using Truven Health MarketScan claims data from January 2010 to December 2013. Women aged 18-45 years with continuous insurance coverage with claims for oral contraceptive pills, patches, rings, injections, or LARC during 2010-2013 (N=3,794,793). Descriptive statistics were used to assess trends in LARC cost-sharing and uptake from 2010 through 2013. Interrupted time series models were used to assess the association of time, ACA, and time after the ACA on LARC cost-sharing and initiation rates, adjusting for patient and plan characteristics. The proportion of claims with $0 cost-sharing for intrauterine devices and implants, respectively, rose from 36.6% and 9.3% in 2010 to 87.6% and 80.5% in 2013. The ACA was associated with a significant increase in these proportions and in their rate of increase (level and slope change both P<0.001). LARC uptake increased over time with no significant change in level of LARC use after ACA implementation in January 2013 (P=0.44) and a slightly slower rate of growth post-ACA than previously reported (β coefficient for trend, -0.004; P<0.001). The ACA has significantly decreased LARC cost-sharing, but during its first year had not yet increased LARC initiation rates.

  3. Complications and continuation rates associated with two types of long-acting contraception

    PubMed Central

    Berenson, Abbey B.; Tan, Alai; Hirth, Jacqueline M.

    2015-01-01

    Objectives To compare complication and continuation rates of the levonorgestrel intrauterine system (LNG-IUS) with the subdermal etonogestrel (ENG) implant across the US among women 15 – 44 years of age. Study Design A retrospective study of health insurance claims records from 2007–2011 identified a cohort of women who had LNG-IUS (n=79,920) or ENG implants (n=7,374) inserted and had insurance coverage for 12 months post-insertion. Claims for complications were examined 12 months after insertion, or until removal of either device within each of three age groups. Results After its introduction in 2007, the frequency of ENG implants increased each year and almost 1/3 of all insertions were in teenagers. However, among women ≤ 24 years old who had delivered an infant in the prior 8 weeks, a LNG-IUS was more likely to be inserted than an ENG implant (P < .05). The most frequent complications with both methods were related to abnormal menstruation, which was more likely to occur among ENG implant users. Overall, 83–88% of the entire sample used their chosen method for at least 12 months. The odds of continuation were similar for both methods among teenagers, but ENG implants were more likely to be removed prematurely among women 20 – 24 years old (OR 1.21, 95% CI: 1.06–1.39) and 25 – 44 years old (OR 1.49, 95% CI: 1.35–1.64). Conclusions Both of these long-acting contraceptive methods are well tolerated among women of all ages, and demonstrate high continuation rates. PMID:25555662

  4. Combination treatment with risperidone long-acting injection and psychoeducational approaches for preventing relapse in schizophrenia

    PubMed Central

    Zhao, Yueren; Kishi, Taro; Iwata, Nakao; Ikeda, Manabu

    2013-01-01

    A recent meta-analysis showed that long-acting injectable (LAI) antipsychotics were not superior to oral antipsychotics for preventing relapse in patients with schizophrenia. We therefore designed a treatment strategy combining risperidone LAI and COMPASS (COMprehensive Psycho-educational Approach and Scheme Set), an original psychoeducational program supporting treatment with risperidone LAI and evaluating subjective treatment satisfaction, transition of symptoms, and effectiveness in preventing symptomatic relapse. The aim of this study was to examine whether addition of COMPASS to risperidone LAI was more effective in preventing relapse in schizophrenia patients than risperidone LAI alone, with the latter group consisting of patients enrolled in a Phase III trial of risperidone LAI in Japan. Patients were followed up for 6 months, with COMPASS continuously implemented from the transition to the observation phase. The primary efficacy measurements were relapse rate (rates of rehospitalization and discontinuation due to inefficacy). Secondary efficacy measurements were the Brief Psychiatric Rating Scale (BPRS) and Global Assessment of Functioning (GAF) scores. Of the 96 patients originally enrolled, 19 (19.8%) were discontinued from all causes. During the 6-month study period, ten of the 96 patients (10.4%) relapsed, compared with a 12.2% relapse rate in patients enrolled in a Phase III trial of risperidone LAI in Japan. Patients showed significant improvements in BPRS total scores (P = 0.0031), BPRS positive (P = 0.0451), BRPS negative (P < 0.0001), and general subscale scores (P = 0.0031), and GAF (P < 0.0001) from baseline to 6 months. In conclusion, the lower relapse rate observed in patients treated with COMPASS plus risperidone LAI than in patients treated with risperidone LAI alone suggests that COMPASS may have benefits in the treatment of schizophrenia, indicating a need for randomized, controlled trials in larger numbers of patients. PMID:24194642

  5. Systems Approach to targeted and long-acting HIV/AIDS therapy.

    PubMed

    Ho, Rodney J Y; Yu, Jesse; Li, Bowen; Kraft, John C; Freeling, Jennifer P; Koehn, Josefin; Shao, Jingwei

    2015-12-01

    Medication adherence and insufficient drug levels are central to HIV/AIDS disease progression. Recently, Fletcher et al. confirmed that HIV patients on oral antiretroviral therapy had lower intracellular drug concentrations in lymph nodes than in blood. For instance, in the same patient, multiple lymph node drug concentrations were as much as 99 % lower than in blood. This study built upon our previous finding that HIV patients taking oral indinavir had 3-fold lower mononuclear cell drug concentrations in lymph nodes than in blood. As a result, an association between insufficient lymph node drug concentrations in cells and persistent viral replication has now been validated. Lymph node cells, particularly CD4 T lymphocytes, host HIV infection and persistence; CD4 T cell depletion in blood correlates with AIDS progression. With established drug targets to overcome drug insufficiency in lymphoid cells and tissues, we have developed and employed a "Systems Approach" to engineer multi-drug-incorporated particles for HIV treatment. The goal is to improve lymphatic HIV drug exposure to eliminate HIV drug insufficiency and disease progression. We found that nano-particulate drugs that absorb, transit, and retain in the lymphatic system after subcutaneous dosing improve intracellular lymphatic drug exposure and overcome HIV lymphatic drug insufficiency. The composition, physical properties, and stability of the drug nanoparticles contribute to the prolonged and enhanced drug exposure in lymphoid cells and tissues. In addition to overcoming lymphatic drug insufficiency and potentially reversing HIV infection, targeted drug nanoparticle properties may extend drug concentrations and enable the development of long-acting HIV drug therapy for enhanced patient compliance.

  6. Atypical molecular pharmacology of a new long-acting beta 2-adrenoceptor agonist, TA 2005.

    PubMed

    Voss, H P; Donnell, D; Bast, A

    1992-12-01

    The molecular pharmacology of a new putative long-acting bronchodilator TA 2005 (8-hydroxy-5-[(1R)-1-hydroxy-2-[N-[(1R)-2-(p-methoxy-phenyl)- 1-methylethyl]amino]ethyl]carbostyril hydrochloride) has been compared with that of the reference compounds isoprenaline and salbutamol in both methacholine (3 x 10(-6) M) precontracted guinea pig tracheal smooth muscle relaxation and in bovine trapezium muscle binding experiments. TA 2005 appeared very potent compared with isoprenaline and salbutamol (pD2 values of 9.29 vs. 7.65 and 7.10 respectively). For isoprenaline and salbutamol a shallow displacement curve was observed and addition of the non-hydrolysable GTP analogue guanylyl-imidodiphosphate (GppNHp) gave a rightward shift (pKd,high and pKd,low values of 7.3 and 6.1 vs. 7.0 and 5.4 respectively). For TA 2005 a steep displacement curve was found with only one binding state even without GppNHp (pKd,high value of 8.2). The long duration of action of TA 2005 might be explained by tight binding of this compound to the beta 2-adrenoceptor. The extent of tight binding for TA 2005 was extremely large. The molecular basis of the tight agonist binding phenomenon for TA 2005 seems to be of different origin than for isoprenaline. It is hypothesized that a different mechanism of activation of the beta 2-adrenoceptor may be involved for TA 2005.

  7. Long-acting glucose-dependent insulinotropic polypeptide ameliorates obesity-induced adipose tissue inflammation.

    PubMed

    Varol, Chen; Zvibel, Isabel; Spektor, Lior; Mantelmacher, Fernanda Dana; Vugman, Milena; Thurm, Tamar; Khatib, Marian; Elmaliah, Elinor; Halpern, Zamir; Fishman, Sigal

    2014-10-15

    Obesity induces low-grade chronic inflammation, manifested by proinflammatory polarization of adipose tissue innate and adaptive resident and recruited immune cells that contribute to insulin resistance (IR). The glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone that mediates postprandial insulin secretion and has anabolic effects on the adipose tissue. Importantly, recent evidence suggested that GIP is a potential suppressor of inflammation in several metabolic models. In this study, we aimed to investigate the immunoregulatory role of GIP in a murine model of diet-induced obesity (DIO) using the long-acting GIP analog [d-Ala(2)]GIP. Administration of [d-Ala(2)]GIP resulted in adipocytes of increased size, increased levels of adipose tissue lipid droplet proteins, indicating better lipid storage capacity, and reduced adipose tissue inflammation. Flow cytometry analysis revealed reduced numbers of inflammatory Ly6C(hi) monocytes and F4/80(hi)CD11c(+) macrophages, associated with IR. In addition, [d-Ala(2)]GIP reduced adipose tissue infiltration of IFN-γ-producing CD8(+) and CD4(+) T cells. Furthermore, [d-Ala(2)]GIP treatment induced a favorable adipose tissue adipokine profile, manifested by a prominent reduction in key inflammatory cytokines (TNF-α, IL-1β, IFN-γ) and chemokines (CCL2, CCL8, and CCL5) and an increase in adiponectin. Notably, [d-Ala(2)]GIP also reduced the numbers of circulating neutrophils and proinflammatory Ly6C(hi) monocytes in mice fed regular chow or a high-fat diet. Finally, the beneficial immune-associated effects were accompanied by amelioration of IR and improved insulin signaling in liver and adipose tissue. Collectively, our results describe key beneficial immunoregulatory properties for GIP in DIO and reveal that its augmentation ameliorates adipose tissue inflammation and improves IR. Copyright © 2014 by The American Association of Immunologists, Inc.

  8. Long-acting reversible contraception: Findings from the Understanding Fertility Management in Contemporary Australia survey.

    PubMed

    Holton, Sara; Rowe, Heather; Kirkman, Maggie; Jordan, Lynne; McNamee, Kathy; Bayly, Chris; McBain, John; Sinnott, Vikki; Fisher, Jane

    2016-01-01

    The aim of this research was to investigate awareness, perceived reliability and consideration of use of long-acting reversible contraception (LARC) among Australians of reproductive age. A sample of 18- to 50-year-old women and men (N = 2235) was randomly recruited from the Australian electoral roll in 2013. Respondents completed a self-administered, anonymous questionnaire. Data were weighted to reduce non-response bias. Factors associated with perceived reliability and consideration of use of LARC were identified in multivariable analyses. Most respondents had heard of implants (76.5%) and intrauterine contraception (63.7%). However, most did not think implants (56.3%) or IUDs (63.9%) were reliable and would not consider using implants (71.6%) or IUDs (77.5%). Those significantly more likely to perceive LARC as reliable were younger, did not regard religion as important in fertility choices, had private health insurance, had been pregnant and had had an abortion; and women who had a partner. Those more likely to consider using LARC were younger and did not regard religion as important in fertility choices; women who had private health insurance, lived in an area of socioeconomic advantage and had had an abortion; and men without a partner, born in Australia and comfortable talking to a health care provider about contraceptive matters. Despite high awareness of LARC among Australian adults, its perceived reliability and willingness to use it remain low in certain groups. Targeted interventions that aim to increase knowledge of the benefits and reliability of LARC and allow informed use are recommended.

  9. Post-abortion initiation of long-acting reversible contraception in New Zealand.

    PubMed

    Rose, Sally B; Garrett, Susan M

    2015-07-01

    Post-abortion initiation of long-acting reversible contraception (LARC) reduces subsequent abortion rates within 24 months, but the prevalence of post-abortion LARC use in New Zealand is unknown. To describe post-abortion initiation of intrauterine and implantable LARC methods in New Zealand between 2007 and 2012, and to determine what impact the introduction of government-funded (free) levonorgestrel (LNG) implants in August 2010 had on overall LARC use. Retrospective observational study involving New Zealand abortion clinic data. Nationally collated data on post-abortion LARC insertions were obtained for the period 2007-2012, and individual-level discharge data for patients attending a large urban hospital abortion clinic were analysed using descriptive statistics to describe annual uptake rates, and the demographic profile of LARC users during this period. Logistic regression analyses examined whether LARC use differed by parity and/or age over time. Post-abortion LARC use increased from 20.2% in 2007 to 45.6% in 2012. Intrauterine device use increased from 20.2% to 31.8% during this period, with implants contributing a further 14% to the overall use of LARC methods by 2012. Clinic data showed that LARC use increased among most demographic subgroups between 2009 and 2012, with the greatest increase among nulliparous under-20-year-olds (from 17.2% to 42.0%). Post-abortion LARC use has been steadily increasing in New Zealand since 2007. Overall LARC use significantly increased following the introduction of government-funded implants, particularly among young and nulliparous women. Improving access to alternative methods of LARC may further increase uptake and reduce unwanted pregnancy rates. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  10. Factors influencing the provision of long-acting reversible contraception in California.

    PubMed

    Biggs, M Antonia; Harper, Cynthia C; Malvin, Jan; Brindis, Claire D

    2014-03-01

    To assess long-acting reversible contraception (LARC) beliefs and practices among site directors who represent the family planning services delivered in their practices. Medical directors from 1,000 sites listed in the Family Planning Access Care and Treatment program (California's family planning Medicaid program) provider database were mailed a survey in the fall of 2011 regarding their LARC beliefs and practices. Participants responded by mail, online, or telephone. Data on family planning clients served and LARC dispensing were obtained from administrative claims data. All analyses were limited to advanced practice clinician respondents. General estimating equation models identified the respondent and practice characteristics associated with LARC provision. After three follow-up mailings and telephone calls, 68% of eligible sites responded to the survey (636/939). Most respondents were physicians (448/587). They were most likely to consider women with a history of pelvic inflammatory disease unsuitable for hormonal (27%, n=161) and copper (26%, n=154) intrauterine devices. Smokers were the most likely to be considered unsuitable for the implant (16%, n=96). Nearly three fourths of respondents routinely discussed intrauterine devices (413/561) and half (271/558) discussed implants with their contraceptive patients. Characteristics that predicted onsite LARC provision included LARC training, beliefs, and health care provider type. Although there has been significant progress in expanding access and understanding about LARC, many clinicians from sites offering family planning services held beliefs limiting the provision of intrauterine devices and were unfamiliar with the implant, suggesting the need for targeted trainings aimed at informing clinicians of recent developments in LARC recommendations.

  11. Changes in body composition in women using long-acting reversible contraception.

    PubMed

    Silva Dos Santos, Priscilla de Nazaré; Madden, Tessa; Omvig, Karen; Peipert, Jeffrey F

    2017-04-01

    Users of hormonal long-acting reversible contraception (LARC) report weight gain as a side effect, but few studies have assessed body composition change among LARC users. We evaluated weight and body composition of healthy women using the levonorgestrel intrauterine system (LNG-IUS), copper intrauterine device (copper IUD) or etonogestrel implant (ENG implant). We hypothesized that weight gain and body composition over 12 months would not differ between copper IUD, LNG-IUS and ENG implant users. We performed a prospective cohort study of a subgroup of women enrolled in the Contraceptive CHOICE Project who initiated the LNG-IUS, copper IUD or ENG implant. Inclusion criteria included lack of metabolic and eating disorders or change in body weight of more than 5% in the 6 months before enrollment. We measured changes in weight and body composition (body fat percentage, total body fat mass, total lean mass and total body mass) in women who continued their method for 12 months. We analyzed data from 149 participants: 85 LNG-IUS users, 31 copper IUD users and 33 ENG implant users. The mean age was 25.9 years, 56.4% were White, 82.5% had some college education and 67.6% were nulliparous. Although lean body mass increased over 12 months in LNG-IUS and copper IUD users but not in ENG implant users, changes in body weight and body composition did not differ between the groups. In the adjusted model, Black race was associated with change in total body mass (p<.05). Among those who continued the method for 12 months, changes in body weight and composition did not differ between copper IUD, LNG-IUS and ENG implant users. Changes in body weight and composition over 12 months did not differ between copper IUD users and LNG-IUS and ENG implant users among those with 12 months of continuous use. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Projections and opinions from 100 experts in long-acting reversible contraception.

    PubMed

    Foster, Diana Greene; Barar, Rana; Gould, Heather; Gomez, Ivette; Nguyen, Deborah; Biggs, M Antonia

    2015-12-01

    This survey of published researchers of long-acting reversible contraceptives (LARCs) examines their opinions about important barriers to LARC use in the United States (US), projections for LARC use in the absence of barriers and attitudes toward incentives for clinicians to provide and women to use LARC methods. We identified 182 authors of 59 peer-reviewed papers on LARC use published since 2013. A total of 104 completed an internet survey. We used descriptive and multivariate analyses to assess LARC use barriers and respondent characteristics associated with LARC projections and opinions. The most commonly identified barrier was the cost of the device (63%), followed by women's knowledge of safety, method acceptability and expectations about use. A shortage of trained providers was a commonly cited barrier, primarily of primary care providers (49%). Median and modal projections of LARC use in the absence of these barriers were 25-29% of contracepting women. There was limited support for provider incentives and almost no support for incentives for women to use LARC methods, primarily out of concern about coercion. Clinical and social science LARC experts project at least a doubling of the current US rate of LARC use if barriers to method provision and adoption are removed. While LARC experts recognize the promise of LARC methods to better meet women's contraceptive needs, they anticipate that the majority of US women will not choose LARC methods. Reducing unintended pregnancy rates will depend on knowledge, availability and use of a wider range of methods of contraception to meet women's individual needs. Efforts to increase LARC use need to meet the dual goals of increasing access to LARC methods and protecting women's reproductive autonomy. To accomplish this, we need reasonable expectations for use, provider training, low-cost devices and noncoercive counseling, rather than incentives for provision or use. Copyright © 2015 The Authors. Published by Elsevier

  13. Obstetrician-gynecologists and contraception: long-acting reversible contraception practices and education.

    PubMed

    Luchowski, Alicia T; Anderson, Britta L; Power, Michael L; Raglan, Greta B; Espey, Eve; Schulkin, Jay

    2014-06-01

    Long-acting reversible contraception (LARC) - the copper and levonorgestrel intrauterine devices (IUDs) and the single-rod implant - are safe and effective but account for a small proportion of contraceptive use by US women. This study examined obstetrician-gynecologists' knowledge, training, practice and beliefs regarding LARC methods. A survey questionnaire was mailed to 3000 Fellows of the American College of Obstetricians and Gynecologists. After exclusions, 1221 eligible questionnaires were analyzed (45.8% response rate, accounting for exclusions). Almost all obstetrician-gynecologists reported providing IUDs (95.8%). Most obstetrician-gynecologists reported requiring two or more visits for IUD insertion (86.9%). Respondents that reported IUD insertion in a single visit reported inserting a greater number of IUDs in the last year. About half reported offering the single-rod implant (51.3%). A total of 92.0% reported residency training on IUDs, and 50.8% reported residency training on implants. Residency training and physician age correlated with the number of IUDs inserted in the past year. A total of 59.6% indicated receiving continuing education on at least one LARC method in the past 2years. Recent continuing education was most strongly associated with implant insertion, and 31.7% of respondents cited lack of insertion training as a barrier. Barriers to LARC provision could be reduced if more obstetrician-gynecologists received implant training and provided same-day IUD insertion. Continuing education will likely increase implant provision. This study shows that obstetrician-gynecologists generally offer IUDs, but fewer offer the single-rod contraceptive implant. Recent continuing education strongly predicted whether obstetrician-gynecologists inserted implants and was also associated with other practices that encourage LARC use. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Relevance of dosage in adherence to treatment with long-acting anticholinergics in patients with COPD

    PubMed Central

    Izquierdo, José Luis; Paredero, José Manuel; Piedra, Raul

    2016-01-01

    Introduction The aim of this study was to assess the degree of adherence for two standard regimens for administrating anticholinergic drugs (12 and 24 hours) in patients with chronic obstruction of the airflow and to establish whether the use of a once-daily dose improves the level of treatment adherence. Methods We used long-acting anticholinergics (LAMAs) as a study variable, and included the entire health area of Castile-La Mancha, numbering 2,100,998 inhabitants, as the study population. We analyzed a total of 16,446 patients who had been prescribed a LAMA between January 1, 2013 and December 31, 2013. The follow-up period, based on a centralized system of electronic prescription management, was extended until December 2014. Results During 2013, the medication collected was 7.4%–10.7% higher than indicated by labeling. This was very similar for all LAMAs, irrespective of the patient’s sex, the molecule, the device, and the drug dosage. We did not observe seasonal variations in the consumption of LAMAs, nor did we detect differences between prescription drugs for once-daily (every 24 hours) versus twice-daily (every 12 hours) administration, between the different molecules, or between different types of inhalers for the same molecule. The results were similar in 2014. Conclusion The principal conclusion of this study is that, in an area with a centralized management system of pharmacological prescriptions, adherence to treatment with LAMAs is very high, irrespective of the molecules or inhalation device. We did not find that patients who used twice-daily medication had a lower adherence. PMID:26929614

  15. Physician and patient benefit-risk preferences from two randomized long-acting injectable antipsychotic trials.

    PubMed

    Katz, Eva G; Hauber, Brett; Gopal, Srihari; Fairchild, Angie; Pugh, Amy; Weinstein, Rachel B; Levitan, Bennett S

    2016-01-01

    To quantify clinical trial participants' and investigators' judgments with respect to the relative importance of efficacy and safety attributes of antipsychotic treatments for schizophrenia, and to assess the impact of formulation and adherence. Discrete-choice experiment surveys were completed by patients with schizophrenia and physician investigators participating in two phase-3 clinical trials of paliperidone palmitate 3-month long-acting injectable (LAI) antipsychotic. Respondents were asked to choose between hypothetical antipsychotic profiles defined by efficacy, safety, and mode of administration. Data were analyzed using random-parameters logit and probit models. Patients (N=214) and physicians (N=438) preferred complete improvement in positive symptoms (severe to none) as the most important attribute, compared with improvement in any other attribute studied. Both respondents preferred 3-month and 1-month injectables to oral formulation (P<0.05), irrespective of prior adherence to oral antipsychotic treatment, with physicians showing greater preference for a 3-month over a 1-month LAI for nonadherent patients. Physicians were willing to accept treatments with reduced efficacy for patients with prior poor adherence. The maximum decrease in efficacy (95% confidence interval [CI]) that physicians would accept for switching a patient from daily oral to 3-month injectable was as follows: adherent: 9.8% (95% CI: 7.2-12.4), 20% nonadherent: 25.4% (95% CI: 21.0-29.9), and 50% nonadherent: >30%. For patients, adherent: 10.1% (95% CI: 6.1-14.1), nonadherent: the change in efficacy studied was regarded as unimportant. Improvement in positive symptoms was the most important attribute. Patients and physicians preferred LAIs over oral antipsychotics, with physicians showing a greater preference for 3-month over 1-month LAI. Physicians and patients were willing to accept reduced efficacy in exchange for switching a patient from an oral formulation to a LAI.

  16. Pharmacokinetics of an injectable long-acting formulation of doxycycline hyclate in dogs.

    PubMed

    Gutiérrez, Lilia; Velasco, Zazil-Ha; Vázquez, Carlos; Vargas, Dinorah; Sumano, Héctor

    2012-06-08

    Based on its PK/PD ratios, doxycycline hyclate (DOX-h), a time-dependant antibacterial, is ideally expected to achieve both sustained plasma drug concentrations at or slightly above the MIC level for as long as possible between dosing intervals. Pursuing this end, a poloxamer-based matrix was used to produce a long-acting injectable preparation (DOX-h-LA) and its serum concentrations vs. time profile investigated after its SC injection to dogs (≤ 0.3 mL per injection site), and results compared with the oral (PO) and IV pharmacokinetics of DOX-h, prepared as tablet or as freshly made solution. A crossover (4 x 4 x 4) study design was employed with 12 Mongrel dogs, with washout periods of 21 days, and at dose of 10 mg/kg in all cases. DOX-h-LA showed the greatest values for bioavailability (199.48%); maximum serum concentration (Cmax) value was 2.8 ± 0.3 with a time to reach Cmax (Tmax) of 2.11 ± 0.12 h and an elimination half-life of 133.61 ± 6.32 h. Considering minimum effective serum concentration of 0.5 μg/mL, a dose-interval of at least 1 week h can be achieved for DOX-h-LA, and only 48 h and 24 h after the IV or PO administration of DOX-h as a solution or as tablets, respectively. A non-painful small bulge, apparently non-inflammatory could be distinguished at injection sites. These lumps dissipated completely in 30 days in all cases.

  17. Development and comparison of intramuscularly long-acting paliperidone palmitate nanosuspensions with different particle size.

    PubMed

    Leng, Donglei; Chen, Hongming; Li, Guangjing; Guo, Mengran; Zhu, Zhaolu; Xu, Lu; Wang, Yongjun

    2014-09-10

    The main purpose of this study was to develop and compare the pharmacokinetic behavior of two paliperidone palmitate (PP) nanosuspensions with different particle size after intramuscular (i.m.) administration. PP nanosuspensions were prepared by wet media milling method and the mean particle size of nanosuspension was controlled as 1,041 ± 6 nm (A) and 505 ± 9 nm (B), respectively. The morphology of nanosuspensions was observed by scanning electron microscope (SEM). Differential scanning calorimeter (DSC) and powder X-ray diffraction (PXRD) confirmed the crystallinity of PP in nanosuspensions. The physical and chemical stabilities of nanosuspensions A and B were investigated by particle analyzer and HPLC after storage for 2 months at 25°C, 4°C and mechanical shaking condition. No obvious change in particle size and chemical degradation of drug were observed. Following single-dose i.m. administration to beagle dogs, the release of paliperidone lasted for nearly 1 month. The Tmax of nanosuspensions A and B was 6 (d) and 10 (d). The AUC0-t and Cmax of nanosuspensions A was 2.0-fold and 1.8-fold higher than nanosuspensions B (p<0.05). The results demonstrated that PP nanosuspensions formulation had long-acting effect. Nanosuspension A with a larger particle size performed better than nanosuspension B. As a result, it is important to design appropriate particle size of nanosuspensions for i.m. administration in order to produce larger therapeutic effect. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Long-acting beta2-agonists in asthma: not so SMART?

    PubMed

    Currie, Graeme P; Lee, Daniel K C; Lipworth, Brian J

    2006-01-01

    Asthma is a worldwide chronic disorder that is characterised by airway inflammation and hyper-responsiveness, which results in intermittent airflow obstruction and subsequent perception of symptoms and exacerbations. Inhaled corticosteroids are a fundamental component in the prevention of the short- and long-term complications associated with inadequately controlled asthma. However, many individuals experience persistent symptoms and exacerbations despite receiving low-to-medium doses of an inhaled corticosteroid (400-800 microg/day of beclometasone or equivalent). In these symptomatic asthmatic patients, guidelines advocate the initiation of a long-acting beta2-adrenoceptor agonist (LABA) as additional second-line controller therapy. The recent SMART (Salmeterol Multi-centre Asthma Research Trial) study was designed to compare the effects of add-on salmeterol 42 microg (ex-actuator) twice daily with placebo over 28 weeks in a randomised, double-blind, parallel-group fashion, with the intention to enrol 60,000 asthmatic patients. However, the study was halted prematurely because preliminary data revealed an increased mortality associated with regular use of salmeterol. Moreover, concerning rates of respiratory-related deaths, asthma-related deaths and life-threatening events were observed among African Americans, who constituted up to 18% of the study population. This in turn prompted the US FDA to announce important safety information regarding inhalers containing LABAs and advise that new labelling be produced outlining the "small but significant risk in asthma-related deaths" associated with their regular use. This evidence-based review discusses the data from SMART and highlights potentially important drawbacks with regular use of LABAs in persistent asthma.

  19. Pharmacokinetics and Disposition of Rilpivirine (TMC278) Nanosuspension as a Long-Acting Injectable Antiretroviral Formulation▿

    PubMed Central

    van ′t Klooster, Gerben; Hoeben, Eva; Borghys, Herman; Looszova, Adriana; Bouche, Marie-Paule; van Velsen, Frans; Baert, Lieven

    2010-01-01

    The next-generation human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase inhibitor rilpivirine (TMC278) was administered in rats and dogs as single intramuscular (IM) or subcutaneous (SC) injections, formulated as a 200-nm nanosuspension. The plasma pharmacokinetics, injection site concentrations, disposition to lymphoid tissues, and tolerability were evaluated in support of its potential use as a once-monthly antiretroviral agent in humans. Rilpivirine plasma concentration-time profiles showed sustained and dose-proportional release over 2 months in rats and over 6 months in dogs. The absolute bioavailability approached 100%, indicating a complete release from the depot, in spite of rilpivirine concentrations still being high at the injection site(s) 3 months after administration in dogs. For both species, IM administration was associated with higher initial peak plasma concentrations and a more rapid washout than SC administration, which resulted in a stable plasma-concentration profile over at least 6 weeks in dogs. The rilpivirine concentrations in the lymph nodes draining the IM injection site exceeded the plasma concentrations by over 100-fold 1 month after administration, while the concentrations in the lymphoid tissues decreased to 3- to 6-fold the plasma concentrations beyond 3 months. These observations suggest uptake of nanoparticles by macrophages, which generates secondary depots in these lymph nodes. Both SC and IM injections were generally well tolerated and safe, with observations of a transient inflammatory response at the injection site. The findings support clinical investigations of rilpivirine nanosuspension as a long-acting formulation to improve adherence during antiretroviral therapy and for preexposure prophylaxis. PMID:20160045

  20. Seasonal changes in prescribing of long-acting beta-2-agonists-containing drugs.

    PubMed

    Rottenkolber, M; Voogd, E; van Dijk, L; Primatesta, P; Becker, C; de Groot, M C H; Plana, E; Alvarez, Y; Durand, J; Slattery, J; Afonso, A; Requena, G; Huerta, C; Alvarez, A; de Abajo, F; Tauscher, M; Hasford, J; Fischer, R; Reynolds, R; Schmiedl, S

    2015-07-01

    For patients with asthma, COPD, or asthma-COPD overlap syndrome (ACOS), inter-country comparisons of seasonal changes in drug prescriptions are scarce or missing. Hence, we aimed to compare seasonal changes in prescription rates of long-acting beta-2-agonist (LABA) in four European countries. A common study protocol was applied to six health care databases (Germany, Spain, the Netherlands (2), and the UK (2)) to calculate age- and sex-standardized point prevalence rates (PPRs) of LABA-containing prescriptions by the 1st of March, June, September, and December of each year during the study period 2002-2009. Seasonal variation of PPRs was quantified using seasonal indexes (SIs; based on the ratio-to-moving-average-method) and SIs averaged over the study period (aSI) stratified by sex, age, and indication (asthma, COPD, or ACOS). There was a moderate seasonal change in LABA-containing prescriptions which was more pronounced in asthma or COPD patients compared to ACOS patients. For asthma and ACOS patients, highest seasonal variation was found for patients living in Spain (aSI: 87.3-110.7, aSI: 93.2-103.1) whereas for COPD highest seasonal variation was revealed for the NPCRD database (the Netherlands) (aSI: 92.2-105.6). Regarding age and sex, highest seasonal variation was found in Spanish boys under 10 years of age having a diagnosis of asthma. By applying a common analysis in six databases, we could observe moderate overall seasonal changes in LABA-containing prescription rates in patients with asthma, COPD, or ACOS. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Cardiopulmonary effects of sufentanil long acting on sevoflurane anaesthesia in dogs.

    PubMed

    Polis, Ingeborgh; Moens, Yves; Hoeben, Dagmar; Tshamala, Mulenda; Hoybergs, Yves; Gasthuys, Frank

    2006-03-01

    To evaluate the cardiopulmonary effects of sufentanil long acting (SLA) in sevoflurane-anaesthetized dogs. Randomized prospective study. Animals Forty female dogs (beagles) aged 1-2 years, weighing 11.97 +/- 1.40 kg. The dogs were divided into five groups of eight. Two control groups were used: group A received intramuscular (IM), SLA (50 microg kg(-1)) alone, while group B received the SLA vehicle followed by sevoflurane anaesthesia for 90 minutes. In the other groups, SLA (50 microg kg(-1) IM) was given immediately before (group C(0)), 15 minutes before (group D(15)) or 30 minutes (group E(30)) before induction [with intravenous (IV) thiopental] of sevoflurane anaesthesia lasting for 90 minutes. Heart rate, arterial blood pressure, respiratory rate (f(r)), arterial oxygen haemoglobin saturation and end-tidal sevoflurane concentration (Fe'SEVO) were measured every 10 minutes during anaesthesia and at 2, 4 and 24 hours after induction (not Fe'SEVO). Acid-base and blood gas analyses were performed. Sufentanil LA reduced heart rate and increased arterial CO(2) tensions during anaesthesia. Respiratory depression was least in group E(30) compared with groups C(0) and D(15). Bradycardia was present for at least 24 hours. Respiratory rate was least in group B although arterial O(2) and CO(2) tension values were acceptable up to 24 hours after anaesthesia. Pre-anaesthetic medication with SLA moderately aggravated the cardiopulmonary effects of sevoflurane. In spite of a moderate depressant effect on cardiorespiratory parameters, SLA may be of use as pre-anaesthetic medication before sevoflurane anaesthesia in dogs. Intermittent positive pressure ventilation may occasionally be necessary.

  2. Provider and Health System Factors Associated with Usage of Long-Acting Reversible Contraception in Adolescents.

    PubMed

    Bodurtha Smith, Anna Jo; Harney, Kathleen F; Singh, Tara; Hurwitz, Anita Gupta

    2017-05-11

    Long-acting reversible contraception (LARC) is recommended as first-line contraception for adolescents. Surveys of primary care providers suggest that physician and clinic factors may influence LARC counseling, but their impact on usage is unknown. Our objective was to explore provider and clinic characteristics associated with LARC usage in adolescents. We conducted a cross-sectional study of 5363 women ages 15-21 years receiving primary care within a large health system in Massachusetts in 2015. We used data abstracted from electronic medical records to characterize rates of LARC usage. We analyzed the association of provider (specialty, degree, gender, resident status, LARC credentialing) and clinic (Title X funding, onsite LARC provision, onsite obstetrician-gynecologist) factors with adolescents' LARC usage through multivariate logistic regression. Overall, 3.4% (95%CI 2.9-3.9) of adolescents were documented as currently using a LARC method. Older adolescents were significantly more likely to use a LARC method (adjusted OR 2.41, 95%CI 1.62-3.58 for women ages 20-21 years compared to ages 15-17). Adolescents whose primary care provider was a resident were significantly more likely to use a LARC method (adjusted OR 1.65, 95%CI 1.02-2.68). Provider specialty, degree, gender, onsite LARC provision, and onsite obstetrician-gynecologist were not significantly associated with LARC usage in adolescents. Being older and having a primary care provider early in their training increased the odds of LARC usage among adolescents in a large Massachusetts health system. Across primary care specialties, educating providers about the appropriate uses of LARC methods in nulliparous adolescents may facilitate LARC usage. Copyright © 2017. Published by Elsevier Inc.

  3. Provision of No-Cost, Long-Acting Contraception and Teenage Pregnancy

    PubMed Central

    Secura, Gina M.; Madden, Tessa; McNicholas, Colleen; Mullersman, Jennifer; Buckel, Christina M.; Zhao, Qiuhong; Peipert, Jeffrey F.

    2014-01-01

    Background The rate of teenage pregnancy in the United States is higher than in other developed nations. Teenage births result in substantial costs, including public assistance, health care costs, and income losses due to lower educational attainment and reduced earning potential. Methods The Contraceptive CHOICE Project was a large prospective cohort study designed to promote the use of long-acting, reversible contraceptive (LARC) methods to reduce unintended pregnancy in the St. Louis region. Participants were educated about reversible contraception, with an emphasis on the benefits of LARC methods, were provided with their choice of reversible contraception at no cost, and were followed for 2 to 3 years. We analyzed pregnancy, birth, and induced-abortion rates among teenage girls and women 15 to 19 years of age in this cohort and compared them with those observed nationally among U.S. teens in the same age group. Results Of the 1404 teenage girls and women enrolled in CHOICE, 72% chose an intrauterine device or implant (LARC methods); the remaining 28% chose another method. During the 2008–2013 period, the mean annual rates of pregnancy, birth, and abortion among CHOICE participants were 34.0, 19.4, and 9.7 per 1000 teens, respectively. In comparison, rates of pregnancy, birth, and abortion among sexually experienced U.S. teens in 2008 were 158.5, 94.0, and 41.5 per 1000, respectively. Conclusions Teenage girls and women who were provided contraception at no cost and educated about reversible contraception and the benefits of LARC methods had rates of pregnancy, birth, and abortion that were much lower than the national rates for sexually experienced teens. (Funded by the Susan Thompson Buffett Foundation and others.) PMID:25271604

  4. Pharmacokinetics of an injectable long-acting formulation of doxycycline hyclate in dogs

    PubMed Central

    2012-01-01

    Based on its PK/PD ratios, doxycycline hyclate (DOX-h), a time-dependant antibacterial, is ideally expected to achieve both sustained plasma drug concentrations at or slightly above the MIC level for as long as possible between dosing intervals. Pursuing this end, a poloxamer-based matrix was used to produce a long-acting injectable preparation (DOX-h-LA) and its serum concentrations vs. time profile investigated after its SC injection to dogs (≤ 0.3 mL per injection site), and results compared with the oral (PO) and IV pharmacokinetics of DOX-h, prepared as tablet or as freshly made solution. A crossover (4 x 4 x 4) study design was employed with 12 Mongrel dogs, with washout periods of 21 days, and at dose of 10 mg/kg in all cases. DOX-h-LA showed the greatest values for bioavailability (199.48%); maximum serum concentration (Cmax) value was 2.8 ± 0.3 with a time to reach Cmax (Tmax) of 2.11 ± 0.12 h and an elimination half-life of 133.61 ± 6.32 h. Considering minimum effective serum concentration of 0.5 μg/mL, a dose-interval of at least 1 week h can be achieved for DOX-h-LA, and only 48 h and 24 h after the IV or PO administration of DOX-h as a solution or as tablets, respectively. A non-painful small bulge, apparently non-inflammatory could be distinguished at injection sites. These lumps dissipated completely in 30 days in all cases. PMID:22682068

  5. Pharmacokinetics, Pharmacodynamics, and Efficacy of a Novel Long-Acting Human Growth Hormone: Fc Fusion Protein.

    PubMed

    Kim, Su Jin; Kwak, Hyun-Hee; Cho, Sung Yoon; Sohn, Young Bae; Park, Sung Won; Huh, Rimm; Kim, Jinsup; Ko, Ah-Ra; Jin, Dong-Kyu

    2015-10-05

    The current recombinant human growth hormone (rhGH) therapy requires daily subcutaneous (sc) injections, which results in poor patient compliance, especially in young children. To reduce the dosing frequency, we generated a chimeric protein of rhGH and the Fc-domain of immunoglobulin G (IgG) (rhGH-Fc). The pharmacokinetics and pharmacodynamics of sc-injected rhGH-Fc were assessed in male Sprague-Dawley rats and hypophysectomized rats, respectively. A single sc injection of rhGH-Fc at a dose of 0.2 mg/kg slowly reached a Cmax of 16.80 ng/mL and remained for 7 days with a half-life of 51.1 h. Conversely, a single sc injection of rhGH 0.2 mg/kg rapidly reached a Cmax of 46.88 ng/mL and declined with a half-life of 0.55 h to baseline values in 4 h. In the efficacy study, the sc-injected rhGH-Fc induced rapid weight gain and tibial width growth at a dose of 240 μg/animal. The effect of two injections of rhGH-Fc separated by 1 week was comparable to that of the same dose of 14 daily injections of rhGH. The rhGH-Fc is a novel candidate for long-acting rhGH therapy with more convenient weekly administration, as it reduces glomerular filtration and receptor-mediated clearance while allowing for the rapid reversal of potential adverse events.

  6. Efficacy and Safety of Long-Acting Reversible Contraception in Women With Cardiovascular Conditions.

    PubMed

    Vu, Quyen; Micks, Elizabeth; McCoy, Erin; Prager, Sarah

    2016-01-15

    The physiological changes that occur during pregnancy can be deleterious to women with a cardiovascular condition. Evidence-based contraceptive counseling and provision is essential in this patient population. Although long-acting reversible contraception (LARCs), which include the intrauterine device (IUD) and the etonogestrel contraceptive implant, have been found to be safe and effective in healthy women, there are inadequate data regarding LARC use in patients with cardiovascular conditions. We conducted a retrospective chart review of women diagnosed with cardiovascular disease who had a copper IUD, levonorgestrel-releasing intrauterine system or contraceptive implant placed at the University of Washington Medical Center from 2007 to 2012. We abstracted and analyzed patient demographic characteristics, medical conditions, indications for LARC placement, and complications. The sample included 470 women with cardiovascular conditions. The mean age was 34.6 years. One hundred twenty-four patients (26.11%) were nulligravid and 169 patients (35.58%) were nulliparous. Four hundred ten chose the levonorgestrel-releasing intrauterine system (87.23%), 33 patients (7.02%) opted for the copper IUD, and 23 patients (4.89%) chose the etonogestrel implant. Eighteen patients (3.83%) had a confirmed IUD expulsion, 2 patients (0.43%) became pregnant, and there were 4 cases of pelvic inflammatory disease (0.85%). There were no cases of perforation. There were no confirmed cases of infective endocarditis associated with LARC insertion. In conclusion, LARC devices appear safe with few complications for women with cardiovascular conditions. Clinicians can be reassured that LARC may be offered as an appropriate option when counseling women with cardiovascular disease on safe contraceptive methods.

  7. Pharmacokinetics of long-acting tenofovir alafenamide (GS-7340) subdermal implant for HIV prophylaxis.

    PubMed

    Gunawardana, Manjula; Remedios-Chan, Mariana; Miller, Christine S; Fanter, Rob; Yang, Flora; Marzinke, Mark A; Hendrix, Craig W; Beliveau, Martin; Moss, John A; Smith, Thomas J; Baum, Marc M

    2015-07-01

    Oral or topical daily administration of antiretroviral (ARV) drugs to HIV-1-negative individuals in vulnerable populations is a promising strategy for HIV-1 prevention. Adherence to the dosing regimen has emerged as a critical factor determining efficacy outcomes of clinical trials. Because adherence to therapy is inversely related to the dosing period, sustained release or long-acting ARV formulations hold significant promise for increasing the effectiveness of HIV-1 preexposure prophylaxis (PrEP) by reducing dosing frequency. A novel, subdermal implant delivering the potent prodrug tenofovir alafenamide (TAF) with controlled, sustained, zero-order (linear) release characteristics is described. A candidate device delivering TAF at 0.92 mg day(-1) in vitro was evaluated in beagle dogs over 40 days for pharmacokinetics and preliminary safety. No adverse events related to treatment with the test article were noted during the course of the study, and no significant, unusual abnormalities were observed. The implant maintained a low systemic exposure to TAF (median, 0.85 ng ml(-1); interquartile range [IQR], 0.60 to 1.50 ng ml(-1)) and tenofovir (TFV; median, 15.0 ng ml(-1); IQR, 8.8 to 23.3 ng ml(-1)), the product of in vivo TAF hydrolysis. High concentrations (median, 512 fmol/10(6) cells over the first 35 days) of the pharmacologically active metabolite, TFV diphosphate, were observed in peripheral blood mononuclear cells at levels over 30 times higher than those associated with HIV-1 PrEP efficacy in humans. Our report on the first sustained-release nucleoside reverse transcriptase inhibitor (NRTI) for systemic delivery demonstrates a successful proof of principle and holds significant promise as a candidate for HIV-1 prophylaxis in vulnerable populations.

  8. Comparison of SGA oral medications and a long-acting injectable SGA: the PROACTIVE study.

    PubMed

    Buckley, Peter F; Schooler, Nina R; Goff, Donald C; Hsiao, John; Kopelowicz, Alexander; Lauriello, John; Manschreck, Theo; Mendelowitz, Alan J; Miller, Del D; Severe, Joanne B; Wilson, Daniel R; Ames, Donna; Bustillo, Juan; Mintz, Jim; Kane, John M

    2015-03-01

    Until relatively recently, long-acting injectable (LAI) formulations were only available for first-generation antipsychotics and their utilization decreased as use of oral second-generation antipsychotics (SGA) increased. Although registry-based naturalistic studies show LAIs reduce rehospitalization more than oral medications in clinical practice, this is not seen in recent randomized clinical trials. PROACTIVE (Preventing Relapse Oral Antipsychotics Compared to Injectables Evaluating Efficacy) relapse prevention study incorporated efficacy and effectiveness features. At 8 US academic centers, 305 patients with schizophrenia or schizoaffective disorder were randomly assigned to LAI risperidone (LAI-R) or physician's choice oral SGAs. Patients were evaluated during the 30-month study by masked, centralized assessors using 2-way video, and monitored biweekly by on-site clinicians and assessors who knew treatment assignment. Relapse was evaluated by a masked Relapse Monitoring Board. Differences between LAI-R and oral SGA treatment in time to first relapse and hospitalization were not significant. Psychotic symptoms and Brief Psychiatric Rating Scale total score improved more in the LAI-R group. In contrast, the LAI group had higher Scale for Assessment of Negative Symptoms Alogia scale scores. There were no other between-group differences in symptoms or functional improvement. Despite the advantage for psychotic symptoms, LAI-R did not confer an advantage over oral SGAs for relapse or rehospitalization. Biweekly monitoring, not focusing specifically on patients with demonstrated nonadherence to treatment and greater flexibility in changing medication in the oral treatment arm, may contribute to the inability to detect differences between LAI and oral SGA treatment in clinical trials.

  9. Multicentre, open-label, randomised, parallel-group, superiority study to compare the efficacy of octreotide therapy 40 mg monthly versus standard of care in patients with refractory anaemia due to gastrointestinal bleeding from small bowel angiodysplasias: a protocol of the OCEAN trial

    PubMed Central

    van Geenen, E J M; Drenth, J P H

    2016-01-01

    Introduction Gastrointestinal angiodysplasias are an important cause of difficult-to-manage bleeding, especially in older patients. Endoscopic coagulation of angiodysplasias is the mainstay of treatment, but may be difficult for small bowel angiodysplasias because of the inability to reach them for endoscopic intervention. Some patients are red blood cell (RBC) transfusion dependent due to frequent rebleeding despite endoscopic treatment. In small cohort studies, octreotide appears to decrease the number of bleeding episodes in patients with RBC transfusion dependency due to gastrointestinal angiodysplasias. This trial will assess the efficacy of octreotide in decreasing the need for RBC transfusions and parenteral iron in patients with anaemia due to gastrointestinal bleeding of small bowel angiodysplasias despite endoscopic intervention. Study design Randomised controlled, superiority, open-label multicentre trial. Participants 62 patients will be included with refractory anaemia due to small bowel angiodysplasias, who are RBC transfusion or iron infusion dependent despite endoscopic intervention and oral iron supplementation. Intervention Patients will be randomly assigned (1:1) to standard care or 40 mg long-acting octreotide once every 4 weeks for 52 weeks, in addition to standard care. The follow-up period is 8 weeks. Main outcome measures The primary outcome is the difference in the number of blood and iron infusions between the year prior to inclusion and the treatment period of 1 year. Important secondary outcomes are the per cent change in the number of rebleeds from baseline to end point, adverse events and quality of life. Ethics and dissemination The trial received ethical approval from the Central Committee on Research Involving Human Subjects and from the local accredited Medical Research Ethics Committee of the region Arnhem-Nijmegen, the Netherlands (reference number: 2014-1433). Results will be published in a peer-reviewed journal and

  10. (111)In-DTPA-d-Phe(-1)-Asp(0)-d-Phe(1)-octreotide exhibits higher tumor accumulation and lower renal radioactivity than (111)In-DTPA-d-Phe(1)-octreotide.

    PubMed

    Oshima, Nobuhiro; Akizawa, Hiromichi; Kitaura, Hirotake; Kawashima, Hidekazu; Zhao, Songji; Zhao, Yan; Nishijima, Ken-Ichi; Kitamura, Yoji; Arano, Yasushi; Kuge, Yuji; Ohkura, Kazue

    2017-07-12

    (111)In-DTPA-d-Phe(1)-octreotide scintigraphy is an important method of detecting neuroendocrine tumors. We previously reported that a new derivative of (111)In-DTPA-d-Phe(1)-octreotide, (111)In-DTPA-d-Phe(-1)-Asp(0)-d-Phe(1)-octreotide, accomplished the reduction of prolonged renal accumulation of radioactivity. The aim of this study was to evaluate the tumor accumulation of (111)In-DTPA-d-Phe(-1)-Asp(0)-d-Phe(1)-octreotide in vitro and in vivo by comparing it with (111)In-DTPA-d-Phe(1)-octreotide. The tumor accumulation of this octreotide derivative was determined by measuring its uptake using cultured AR42J cells in vitro and biodistribution studies in vivo. The distribution of the radiotracer and the extent of somatostatin receptor-specific uptake in the tumor were estimated by a counting method using AR42J tumor-bearing mice. The radioactive metabolite species in the tumor and kidney were identified by HPLC analyses at 3 and 24h post-injection of the (111)In-DTPA-conjugated peptide. In both cases, in vitro and in vivo, the tumor radioactivity levels of (111)In-DTPA-d-Phe(-1)-Asp(0)-d-Phe(1)-octreotide were approximately 2-4 times higher than those of (111)In-DTPA-d-Phe(1)-octreotide. On in vitro cellular uptake inhibition and radioreceptor assay, (111)In-DTPA-d-Phe(-1)-Asp(0)-d-Phe(1)-octreotide exhibited a binding affinity to somatostatin receptor highly similar to that of (111)In-DTPA-d-Phe(1)-octreotide. As the additional cellular uptake of (111)In-DTPA-d-Phe(-1)-Asp(0)-d-Phe(1)-octreotide was significantly lower at low temperature than at 37°C, it was considered that a cellular uptake pathway is involved in energy-dependent endocytotic processes. In the radiometabolite analysis of (111)In-DTPA-d-Phe(-1)-Asp(0)-d-Phe(1)-octreotide, (111)In-DTPA-d-Phe-Asp-OH was a major metabolite in the tumor at 24h post-injection. (111)In-DTPA-d-Phe(-1)-Asp(0)-d-Phe(1)-octreotide exhibited higher tumor accumulation and persistence of tumor radioactivity than (111)In

  11. Circulating ghrelin levels are suppressed by meals and octreotide therapy in children with Prader-Willi syndrome.

    PubMed

    Haqq, Andrea M; Stadler, Diane D; Rosenfeld, Ron G; Pratt, Katherine L; Weigle, David S; Frayo, R Scott; LaFranchi, Stephen H; Cummings, David E; Purnell, Jonathan Q

    2003-08-01

    Prader-Willi syndrome (PWS) is characterized by severe obesity, hyperphagia, hypogonadism, and GH deficiency. Unlike individuals with common obesity, who have low fasting-plasma ghrelin concentrations, those with PWS have high fasting-ghrelin concentrations that might contribute to their hyperphagia. Treatment with octreotide, a somatostatin agonist, decreases ghrelin concentrations in healthy and acromegalic adults and induces weight loss in children with hypothalamic obesity. This pilot study was performed to determine whether octreotide administration (5 microg/kg.d) for 5-7 d lowers ghrelin concentrations and affects body composition, resting energy expenditure, and GH markers in children with PWS. Octreotide treatment decreased mean fasting plasma ghrelin concentration by 67% (P < 0.05). Meal-related ghrelin suppression (-35%; P < 0.001) was still present after intervention but was blunted (-11%; P = 0.19). Body weight, body composition, leptin, insulin, resting energy expenditure, and GH parameters did not change. However, one subject's parent noted fewer tantrums over denial of food during octreotide intervention. In conclusion, short-term octreotide treatment markedly decreased fasting ghrelin concentrations in children with PWS but did not fully ablate the normal meal-related suppression of ghrelin. Further investigation is warranted to determine whether long-term octreotide treatment causes sustained ghrelin suppression, changes eating behavior, and induces weight loss in this population.

  12. Comparison of the efficacy and pharmacokinetics of conventional propranolol and a long acting preparation of propranolol

    PubMed Central

    Leahey, W. J.; Neill, J. D.; Varma, M. P. S.; Shanks, R. G.

    1980-01-01

    1 Plasma levels of propranolol were measured at intervals after the oral administration of 160 mg propranolol and 160 mg L.A. propranolol in ten subjects who received both drugs on separate occasions. 2 Mean peak plasma concentration of propranolol occurred 2 h after propranolol and 10 h after the L.A. formulation; the peak concentration with the former was four times that with the latter. At 24 h the plasma level was significantly higher after L.A. propranolol. 3 Observations were made in nine healthy volunteers who exercised before and at intervals after the oral administration of 160 mg propranolol and 160 mg L.A. propranolol. 4 Propranolol produced a maximum reduction (27.84 ± 2.4%) in the exercise tachycardia at 3 h and L.A. propranolol a maximum reduction (22.00 ± 1.73%) at 6 h. The effects at 24 h were 9.24 ± 1.55 and 16.79 ± 2.16% respectively. 5 Five subjects were given 160 mg propranolol as a single dose daily for 8 days and on a separate occasion similar treatment with L.A. propranolol. Subjects were exercised and blood samples were taken before and 3 h after each dose on days 1 to 5 and on day 8. 6 The reduction in the exercise tachycardia 3 h after propranolol ranged from 33.0 to 36.9% and 24 h after propranolol from 12.2 to 20.8%. The corresponding values after L.A. propranolol were 26.8 and 31.4 (3 h values) and 20.4 and 25.0 (trough values). 7 The trough plasma levels of propranolol during administration of propranolol ranged from 10.2 to 19.4 ng/ml and peak values from 202.2 to 245.0 ng/ml. The corresponding values after L.A. propranolol were 12.5 to 17.5 (trough values) and 18.4 to 50.0 (peak values) ng/ml. 8 These observations show that the new long acting formulation of propranolol produces a significant reduction of an exercise tachycardia throughout a 24 h period without a very high initial effect during single and multiple dosing. This formulation should be suitable for once a day administration. PMID:7356891

  13. The Use of Long-Acting Injectable Antipsychotics in Schizophrenia: Evaluating the Evidence.

    PubMed

    Correll, Christoph U; Citrome, Leslie; Haddad, Peter M; Lauriello, John; Olfson, Mark; Calloway, Stephen M; Kane, John M

    2016-01-01

    Long-acting injectable antipsychotics (LAIs) are among the most effective treatments in psychiatry, yet they remain underutilized in clinical practice. Although LAIs are typically used to maintain treatment adherence in patients with chronic schizophrenia, recent research has suggested that they may also provide an effective treatment strategy for patients with early-phase or first-episode disease. In October 2015, a group of 8 experts on the management of schizophrenia and LAIs met to evaluate the evidence surrounding the efficacy, safety, and cost-effectiveness of LAIs and to develop practical recommendations regarding the clinical use, education, and unmet needs related to LAIs. Participants were also asked to rate the importance of several patient characteristics when choosing an LAI versus an oral antipsychotic, from the perspectives of 4 different stakeholder groups: patients, health care professionals, families, and payers. The evidence review demonstrated that LAIs are superior to placebo for acute and maintenance treatment of schizophrenia and, in general, appear to be similar to one another in terms of schizophrenia relapse prevention. Study design impacts the demonstrated efficacy of LAIs versus oral antipsychotics, but recent database and randomized controlled studies favor the use of LAIs in early-phase schizophrenia patients. LAIs vary considerably in their propensity to cause certain adverse effects, including weight gain, metabolic effects, extrapyramidal symptoms, and prolactin elevation, and these differences can be used to help guide LAI selection. Some studies, but not all, have demonstrated significant reductions in health care utilization or overall costs with LAIs. The expert panel identified several barriers to LAI use in current practice, including clinician lack of knowledge, negative attitudes about LAIs, and resource and cost issues. The participants also identified a number of additional factors that should be considered when weighing

  14. [Application of half-dose depot long-acting triptorelin in postoperative adjuvant therapy for endometriosis].

    PubMed

    Liu, Xia; Zhang, Hong-xia; Wang, Li-ping; Fu, Wei-ping

    2013-01-15

    To evaluate the efficacy and adverse effects of half-dose depot long-acting triptorelin in the therapy of endometriosis. The efficacy and adverse effects of routine-dose or half-dose triptorelin in postoperative endometriosis patients were prospectively observed. A total of 186 postoperative patients with moderate or severe endometriosis received an intramuscular injection of triptorelin every 28 days for 6 times. They were randomly divided into 3 groups, i.e. half-dose group (n = 99): 1.875 mg each time; "draw-back" group (n = 52): 3.75 mg first time, then 1.875 mg each time; and routine-dose group (n = 35): 3.75 mg each time. Amenorrhea was effectively induced in all patients after the second injection. There was no significant difference in the rate of serum E2 level at Day 28 of every injection below the upper limit of "estrogen threshold (110 - 146 pmol/L)" not stimulating ectopic endometrium proliferation among half-dose group, "draw-back" group and routine-dose group (99% vs 100% and 99.0%, P > 0.05), the percentage of E2 < 37 pmol/L in E2 < 110 pmol/L in half-dose group was significantly lower than that in "draw-back" and routine-dose groups after 2-5(th) injection (69% vs 79% and 85%, P < 0.01), but there was no significant difference after first half-dose and routine-dose injection (71% vs 73%, P > 0.05). No significant difference existed in the rate of pelvic pain relief during the first returning menstruation and the recurrence rate of endometriosis within 1 year postoperation among three groups (both P > 0.05). However, the incidences of menopausal syndrome and severe menopausal syndrome in half-dose group were significantly lower than those in "draw-back" and routine-dose groups (both P < 0.01). And the incompletion rate of six-time drug for severe menopause syndrome was also significantly lower (P < 0.05) while the completion rate of six-time drug use in half-dose group was significantly higher (P < 0.05). As a postoperative adjuvant, half-dose depot

  15. Attitudes towards the administration of long-acting antipsychotics: a survey of physicians and nurses

    PubMed Central

    2013-01-01

    Background Discontinuation of antipsychotic treatment for schizophrenia can interrupt improvement and exacerbate the illness. Reasons for discontinuing treatment are multifactorial and include adherence, efficacy and tolerability issues. Poor adherence may be addressed through non-pharmacological approaches as well as through pharmacological ones, ie ensured delivery of medication, such as that achieved with long-acting injectable (LAI) antipsychotics. However, attitudes of healthcare professionals (HCPs) towards LAI antipsychotics may influence their prescribing decisions and may influence medication choices offered to patients. We therefore conducted a survey to investigate factors driving LAI use as well as physician and nurse attitudes to LAI antipsychotics and to different injection sites. Methods An independent market research agency conducted the survey of HCPs across Europe. Participants were recruited by telephone and completed the survey online. Using conjoint analyses (a multivariate statistical technique analysing preferences on the basis of ranking a limited number of attributes which are presented repetitively), attitudes to oral versus LAI medication and gluteal versus deltoid injection routes were assessed. Results A total of 891 HCPs across Europe were surveyed. Of these, 40% would choose LAI antipsychotics for first episode patients whereas 90% would select LAI antipsychotics for chronic patients with two to five psychotic episodes. Dominant elements in antipsychotic choice were low sedation but no tardive dyskinesia, no or mild pain at injection and low risk of embarrassment or impact upon therapeutic alliance. Eighty-six per cent of respondents considered that having the choice of a deltoid as well as gluteal administration site was beneficial over not having that choice. Two thirds of respondents said they agreed that medication administration via the deltoid muscle may reduce social embarrassment associated with LAI antipsychotics and most

  16. Achieving cost-neutrality with long-acting reversible contraceptive methods⋆

    PubMed Central

    Trussell, James; Hassan, Fareen; Lowin, Julia; Law, Amy; Filonenko, Anna

    2014-01-01

    Objectives This analysis aimed to estimate the average annual cost of available reversible contraceptive methods in the United States. In line with literature suggesting long-acting reversible contraceptive (LARC) methods become increasingly cost-saving with extended duration of use, it aimed to also quantify minimum duration of use required for LARC methods to achieve cost-neutrality relative to other reversible contraceptive methods while taking into consideration discontinuation. Study design A three-state economic model was developed to estimate relative costs of no method (chance), four short-acting reversible (SARC) methods (oral contraceptive, ring, patch and injection) and three LARC methods [implant, copper intrauterine device (IUD) and levonorgestrel intrauterine system (LNG-IUS) 20 mcg/24 h (total content 52 mg)]. The analysis was conducted over a 5-year time horizon in 1000 women aged 20–29 years. Method-specific failure and discontinuation rates were based on published literature. Costs associated with drug acquisition, administration and failure (defined as an unintended pregnancy) were considered. Key model outputs were annual average cost per method and minimum duration of LARC method usage to achieve cost-savings compared to SARC methods. Results The two least expensive methods were copper IUD ($304 per women, per year) and LNG-IUS 20 mcg/24 h ($308). Cost of SARC methods ranged between $432 (injection) and $730 (patch), per women, per year. A minimum of 2.1 years of LARC usage would result in cost-savings compared to SARC usage. Conclusions This analysis finds that even if LARC methods are not used for their full durations of efficacy, they become cost-saving relative to SARC methods within 3 years of use. Implications Previous economic arguments in support of using LARC methods have been criticized for not considering that LARC methods are not always used for their full duration of efficacy. This study calculated that cost-savings from LARC

  17. Guidelines for the use and management of long-acting injectable antipsychotics in serious mental illness

    PubMed Central

    2013-01-01

    Background Long-acting injectable (LAI) formulations are not widely used in routine practice even though they offer advantages in terms of relapse prevention. As part of a process to improve the quality of care, the French Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) elaborated guidelines for the use and management of antipsychotic depots in clinical practice. Methods Based on a literature review, a written survey was prepared that asked about 539 options in 32 specific clinical situations concerning 3 fields: target-population, prescription and use, and specific populations. We contacted 53 national experts, 42 of whom (79%) completed the survey. The options were scored using a 9-point scale derived from the Rand Corporation and the University of California in the USA. According to the answers, a categorical rank (first-line/preferred choice, second-line/alternate choice, third-line/usually inappropriate) was assigned to each option. The first-line option was defined as a strategy rated as 7–9 (extremely appropriate) by at least 50% of the experts. The following results summarize the key recommendations from the guidelines after data analysis and interpretation of the results of the survey by the scientific committee. Results LAI antipsychotics are indicated in patients with schizophrenia, schizoaffective disorder, delusional disorder and bipolar disorder. LAI second-generation antipsychotics are recommended as maintenance treatment after the first episode of schizophrenia. LAI first-generation antipsychotics are not recommended in the early course of schizophrenia and are not usually appropriate in bipolar disorder. LAI antipsychotics have long been viewed as a treatment that should only be used for a small subgroup of patients with non-compliance, frequent relapses or who pose a risk to others. The panel considers that LAI antipsychotics should be considered and systematically proposed to any patients for whom maintenance

  18. Bioequivalence Study of Two Long-Acting Formulations of Oxytetracycline Following Intramuscular Administration in Bovines.

    PubMed

    Mestorino, Nora; Marchetti, María Laura; Lucas, Mariana Florencia; Modamio, Pilar; Zeinsteger, Pedro; Fernández Lastra, Cecilia; Segarra, Ignacio; Mariño, Eduardo Luis

    2016-01-01

    The aim of this study was to evaluate the bioequivalence of two commercial long-acting formulations based on oxytetracycline (OTC) hydrochloride between the reference formulation (Terramycin LA, Pfizer) and a test formulation (Cyamicin LA, Fort Dodge Saude Animal). Both formulations were administered in a single intramuscular route at a dose of 20 mg OTC/kg of body weight in clinically healthy bovines. The study was carried out according to a one-period parallel design. Plasma samples were analyzed by high-pressure liquid chromatography. The limit of quantitation was 0.050 μg/mL with an accuracy of 101.67% with a coefficient of variation of 13.15%. Analysis of variance and 90% confidence interval tests were used to compare the bioavailability parameters (maximum plasma concentration, C max, and the area under the concentration-versus-time curve extrapolated to infinity, AUC0-∞) of both products. In the case of the time to maximum concentration (T max), non-parametric tests based on Wilcoxon's signed rank test were preferred. The comparison of the mean AUC0-∞ values did not reveal any significant differences (311.40 ± 93.05 μg h/mL and 287.71 ± 45.31 μg h/mL, respectively). The results were similar for the T max (3.58 ± 0.90 h versus 3.42 ± 0.51 h). However, when comparing the mean C max some significant differences were found (8.73 ± 3.66 μg/mL and 10.43 ± 3.84 μg/mL, respectively). The 90% confidence intervals for the ratio of AUC0-∞ and T max values for the reference and test product are within the interval 80-125%, but the 90% confidence intervals for the ratio of C max falls outside the proposed interval. It was concluded that C max of test product are not within the 20% of those of the reference, thus suggesting that test OTC is not bioequivalent to the reference formulation.

  19. Achieving cost-neutrality with long-acting reversible contraceptive methods.

    PubMed

    Trussell, James; Hassan, Fareen; Lowin, Julia; Law, Amy; Filonenko, Anna

    2015-01-01

    This analysis aimed to estimate the average annual cost of available reversible contraceptive methods in the United States. In line with literature suggesting long-acting reversible contraceptive (LARC) methods become increasingly cost-saving with extended duration of use, it aimed to also quantify minimum duration of use required for LARC methods to achieve cost-neutrality relative to other reversible contraceptive methods while taking into consideration discontinuation. A three-state economic model was developed to estimate relative costs of no method (chance), four short-acting reversible (SARC) methods (oral contraceptive, ring, patch and injection) and three LARC methods [implant, copper intrauterine device (IUD) and levonorgestrel intrauterine system (LNG-IUS) 20 mcg/24 h (total content 52 mg)]. The analysis was conducted over a 5-year time horizon in 1000 women aged 20-29 years. Method-specific failure and discontinuation rates were based on published literature. Costs associated with drug acquisition, administration and failure (defined as an unintended pregnancy) were considered. Key model outputs were annual average cost per method and minimum duration of LARC method usage to achieve cost-savings compared to SARC methods. The two least expensive methods were copper IUD ($304 per women, per year) and LNG-IUS 20 mcg/24 h ($308). Cost of SARC methods ranged between $432 (injection) and $730 (patch), per women, per year. A minimum of 2.1 years of LARC usage would result in cost-savings compared to SARC usage. This analysis finds that even if LARC methods are not used for their full durations of efficacy, they become cost-saving relative to SARC methods within 3 years of use. Previous economic arguments in support of using LARC methods have been criticized for not considering that LARC methods are not always used for their full duration of efficacy. This study calculated that cost-savings from LARC methods relative to SARC methods, with discontinuation rates

  20. The relationship between long-acting reversible contraception and insurance coverage: a retrospective analysis.

    PubMed

    Broecker, Jane; Jurich, Joan; Fuchs, Robin

    2016-03-01

    The objective was to determine if there is a relationship between patients' financial responsibility (out-of-pocket expenses) and placement of long-acting, reversible contraceptive (LARC) methods among girls and women living in Appalachia who expressed interest in LARC device placement. A retrospective chart analysis of patients prescribed an intrauterine device (IUD) or an etonogestrel implant between December 2011 and July 2013 in an Appalachian private practice was performed. Of the 571 identified patients aged 13 to 50, the majority were Caucasian (98.7%) and using Medicaid (53.2%). Outcomes measured the patients' decision regarding whether to use LARC after being informed of out-of-pocket expenses. There was a dramatic increase in the proportion of patients who had LARC methods placed if expense was under $200 (p<.001). Placement rate for privately insured patients was 86.6% for those who paid less than $200 compared to 27.8% for those who paid $200 or more. Medicaid patients, for whom the device was free, had a 78.0% placement rate. For every additional $100 patients had to pay out of pocket, the odds of deciding to use the prescribed LARC method decreased. LARC methods are utilized significantly more often when out-of-pocket cost is low. Cost appears to be a significant barrier to device placement for the group of privately insured Appalachian patients with out-of-pocket expenses over $200. Despite the improvements in coverage for many women provided under the Affordable Care Act, cost may remain a barrier for privately insured women who are required to pay some or all of the cost of LARC methods. Unintended pregnancy rates in the United States remain high, especially in Appalachia. One contributing factor is reliance on user-dependent methods which have significantly high typical use failure rates. Placement of LARC methods for more patients could decrease unintended pregnancy, but device costs may be one barrier to utilization, even for those with private

  1. The Clinical Role and Cost-Effectiveness of Long-Acting Antiretroviral Therapy

    PubMed Central

    Ross, Eric L.; Weinstein, Milton C.; Schackman, Bruce R.; Sax, Paul E.; Paltiel, A. David; Walensky, Rochelle P.; Freedberg, Kenneth A.; Losina, Elena

    2015-01-01

    Background. Long-acting antiretroviral therapy (LA-ART) is currently under development and could improve outcomes for human immunodeficiency virus (HIV)-infected individuals with poor daily ART adherence. Methods. We used a computer simulation model to evaluate the cost-effectiveness of 3 LA-ART strategies vs daily oral ART for all: (1) LA-ART for patients with multiple ART failures; (2) second-line LA-ART for those failing first-line therapy; and (3) first-line LA-ART for ART-naive patients. We calculated the maximum annual cost of LA-ART at which each strategy would be cost-effective at a willingness to pay of $100 000 per quality-adjusted life-year. We assumed HIV RNA suppression on daily ART ranged from 0% to 91% depending on adherence, vs 91% suppression on LA-ART regardless of daily ART adherence. In sensitivity analyses, we varied adherence, efficacy of LA-ART and daily ART, and loss to follow-up. Results. Relative to daily ART, LA-ART increased overall life expectancy by 0.15–0.24 years, and by 0.51–0.89 years among poorly adherent patients, depending on the LA-ART strategy. LA-ART after multiple failures became cost-effective at an annual drug cost of $48 000; in sensitivity analysis, this threshold varied from $40 000–$70 000. Second-line LA-ART and first-line LA-ART became cost-effective at an annual drug cost of $26 000–$31 000 and $24 000–$27 000, vs $28 000 and $25 000 for current second-line and first-line regimens. Conclusions. LA-ART could improve survival of HIV patients, especially those with poor daily ART adherence. At an annual cost of $40 000–$70 000, LA-ART will offer good value for patients with multiple prior failures. To be a viable option for first- or second-line therapy, however, its cost must approach that of currently available regimens. PMID:25583979

  2. Vouchers in Fragile States: Reducing Barriers to Long-Acting Reversible Contraception in Yemen and Pakistan

    PubMed Central

    Boddam-Whetham, Luke; Gul, Xaher; Al-Kobati, Eman; Gorter, Anna C

    2016-01-01

    ABSTRACT In conflict-affected states, vouchers have reduced barriers to reproductive health services and have enabled health programs to use targeted subsidies to increase uptake of specific health services. Vouchers can also be used to channel funds to public- and private-service providers and improve service quality. The Yamaan Foundation for Health and Social Development in Yemen and the Marie Stopes Society (MSS) in Pakistan—both working with Options Consultancy Services—have developed voucher programs that subsidize voluntary access to long-acting reversible contraceptives (LARCs) and permanent methods (PMs) of family planning in their respective fragile countries. The programs focus on LARCs and PMs because these methods are particularly difficult for poor women to access due to their cost and to provider biases against offering them. Using estimates of expected voluntary uptake of LARCs and PMs for 2014 based on contraceptive prevalence rates, and comparing these with uptake of LARCs and PMs through the voucher programs, we show the substantial increase in service utilization that vouchers can enable by contributing to an expanded method choice. In the governorate of Lahj, Yemen, vouchers for family planning led to an estimated 38% increase in 2014 over the expected use of LARCs and PMs (720 vs. 521 expected). We applied the same approach in 13 districts of Punjab, Khyber Pakhtunkhwa (KPK), and Sindh provinces in Pakistan. Our calculations suggest that vouchers enabled 10 times more women than expected to choose LARCs and PMs in 2014 in those areas of Pakistan (73,639 vs. 6,455 expected). Voucher programs can promote and maintain access to family planning services where existing health systems are hampered. Vouchers are a flexible financing approach that enable expansion of contraceptive choice and the inclusion of the private sector in service delivery to the poor. They can keep financial resources flowing where the public sector is prevented from

  3. Lessons from the contraceptive CHOICE project: the Hull long-acting reversible contraception (LARC) initiative.

    PubMed

    Trussell, James; Guthrie, Kate

    2015-01-01

    To discover whether a hand-out explaining the benefits of intrauterine contraceptives (IUCs) and implants could increase their uptake in Hull, UK. We developed a simple double-sided A4 hand-out. On one side was a script with pictures of copper and levonorgestrel IUCs next to a 20 pence coin and of an implant beside a hairgrip. On the other side was the three-tiered effectiveness chart published in the textbook Contraceptive Technology. We implemented the project in family planning (FP), abortion and antenatal clinics and general practitioner (GP) surgeries. The plan was that the receptionist would give the hand-out to every woman and ask her to read it before seeing a clinician. We evaluated the hand-out in FP clinics and GP practices because routine electronic monitoring reports were available only for these locations. There was no impact in GP practices. There was no overall impact in FP clinics, with the exception of the service hub, in which there was an increase in the proportion of women receiving IUCs or implants of 15.0% between the periods October 2011-April 2012 and May 2012-November 2012 (p=0.0002). This clinic is open 6 days per week and has permanent sexual health staff on the reception desk. The proportion of women receiving IUCs or implants returned to baseline in December 2012-November 2013, when a change in clinic procedure to reduce waiting times caused staff to stop dispensing hand-outs. This was not a formal study, so there was no research coordinator to monitor the project. We think that there was no impact among GPs because the project was not implemented by them. The project was poorly implemented at the four satellite FP clinics. Only the service hub implemented the project, where it had a clear impact. We conclude that when implemented as intended, this simple, very low-cost long-acting reversible contraception intervention was highly effective and also extremely cost effective. Published by the BMJ Publishing Group Limited. For

  4. Bioequivalence Study of Two Long-Acting Formulations of Oxytetracycline Following Intramuscular Administration in Bovines

    PubMed Central

    Mestorino, Nora; Marchetti, María Laura; Lucas, Mariana Florencia; Modamio, Pilar; Zeinsteger, Pedro; Fernández Lastra, Cecilia; Segarra, Ignacio; Mariño, Eduardo Luis

    2016-01-01

    The aim of this study was to evaluate the bioequivalence of two commercial long-acting formulations based on oxytetracycline (OTC) hydrochloride between the reference formulation (Terramycin LA, Pfizer) and a test formulation (Cyamicin LA, Fort Dodge Saude Animal). Both formulations were administered in a single intramuscular route at a dose of 20 mg OTC/kg of body weight in clinically healthy bovines. The study was carried out according to a one-period parallel design. Plasma samples were analyzed by high-pressure liquid chromatography. The limit of quantitation was 0.050 μg/mL with an accuracy of 101.67% with a coefficient of variation of 13.15%. Analysis of variance and 90% confidence interval tests were used to compare the bioavailability parameters (maximum plasma concentration, Cmax, and the area under the concentration-versus-time curve extrapolated to infinity, AUC0–∞) of both products. In the case of the time to maximum concentration (Tmax), non-parametric tests based on Wilcoxon’s signed rank test were preferred. The comparison of the mean AUC0–∞ values did not reveal any significant differences (311.40 ± 93.05 μg h/mL and 287.71 ± 45.31 μg h/mL, respectively). The results were similar for the Tmax (3.58 ± 0.90 h versus 3.42 ± 0.51 h). However, when comparing the mean Cmax some significant differences were found (8.73 ± 3.66 μg/mL and 10.43 ± 3.84 μg/mL, respectively). The 90% confidence intervals for the ratio of AUC0–∞ and Tmax values for the reference and test product are within the interval 80–125%, but the 90% confidence intervals for the ratio of Cmax falls outside the proposed interval. It was concluded that Cmax of test product are not within the 20% of those of the reference, thus suggesting that test OTC is not bioequivalent to the reference formulation. PMID:27446938

  5. Effect of treatment with depot somatostatin analogue octreotide on primary hyperparathyroidism (PHP) in multiple endocrine neoplasia type 1 (MEN1) patients.

    PubMed

    Faggiano, Antongiulio; Tavares, Lidice Brandao; Tauchmanova, Libuse; Milone, Francesco; Mansueto, Gelsomina; Ramundo, Valeria; De Caro, Maria Laura Del Basso; Lombardi, Gaetano; De Rosa, Gaetano; Colao, Annamaria

    2008-11-01

    In patients with multiple endocrine neoplasia type 1 (MEN1), expression of somatostatin receptor (SST) in parathyroid adenomas and effectiveness of therapy with somatostatin analogues on primary hyperparathyroidism (PHP) have been scarcely investigated. To evaluate the effects of depot long acting octreotide (OCT-LAR) in patients with MEN1-related PHP. Eight patients with a genetically confirmed MEN1, presenting both PHP and duodeno-pancreatic neuroendocrine tumours (NET), were enrolled. The initial treatment was OCT-LAR 30 mg every 4 weeks. This therapy was established to stabilize the duodeno-pancreatic NET before to perform parathyroidectomy for PHP. Before OCT-LAR therapy, a SST scintigraphy was performed in all patients. SST subtype 2A immunohistochemistry was performed on parathyroid tumour samples from three patients undergone parathyroidectomy after OCT-LAR therapy. Serum concentrations of PTH, calcium and phosphorus as well as the 24-h urine calcium : creatinine ratio and the renal threshold phosphate concentration were evaluated before and after OCT-LAR. After OCT-LAR therapy, hypercalcaemia and hypercalciuria normalized in 75% and 62.5% of patients, respectively, and serum phosphorus and renal threshold phosphate significantly increased. Serum PTH concentrations significantly decreased in all patients and normalized in two of them. SST subtype 2A immunostaining was found in all parathyroid adenomas investigated, while SST scintigraphy showed a positive parathyroid tumour uptake in three of eight patients (37.5%). Six months of OCT-LAR therapy controlled hypercalcaemia and hypercalciuria in two-thirds of patients with MEN1-related PHP. Direct OCT-LAR effects mediated by binding to SST expression on parathyroid tumour cells are likely the main mechanism to explain the activity of this compound on calcium and phosphorus abnormalities in MEN1 PHP.

  6. The effect of octreotide treatment on somatic and psychological symptoms of acromegaly.

    PubMed

    Ruchala, Marek; Stangierska, Izabela; Gurgul, Edyta; Stangierski, Adam; Fajfer, Jolanta; Sowinski, Jerzy

    2010-01-01

    Acromegaly is a chronic disease caused by excessive growth hormone secretion resulting in bone and soft tissue overgrowth. Body image changes as well as systemic complications may considerably influence patients' psychological health and disturb everyday activities. The aim of this study was to determine the effect of octreotide treatment on somatic and psychological symptoms of acromegaly, and thus on patients' quality of life. The study was conducted on 15 patients with acromegaly. The average duration of octreotide therapy was 5.6 years (1-10 years). The respondents created a list of subjective signs and symptoms of acromegaly before treatment and reported changes observed during therapy. The psychological examination was performed with appropriate test scales assessed patients' self-efficacy, emotional control, psychological gender and their life satisfaction. The most important changes observed during octreotide therapy were associated with head and joint pain relief and reduction of physical limitations. The patients also noticed the improvement of cognitive functions and interpersonal relations. The study revealed average life satisfaction in the group. The patients on the one hand demonstrated high self-efficacy and on the other hand - intensive repression of emotions. The undifferentiated sex-role schema dominated in group. The study proved a significance of octreotide therapy in acromegalic patients' life. In spite of chronic disease, all the respondents reported good quality of life (average life satisfaction). Additionally, their high self-efficacy helps to cope with the disease. Nevertheless, undifferentiated sex role schema in the study group suggests lack of behavioral flexibility and high emotional repression predicts negative somatic consequences.

  7. Pasireotide and octreotide antiproliferative effects and sst2 trafficking in human pancreatic neuroendocrine tumor cultures.

    PubMed

    Mohamed, Amira; Blanchard, Marie-Pierre; Albertelli, Manuela; Barbieri, Federica; Brue, Thierry; Niccoli, Patricia; Delpero, Jean-Robert; Monges, Genevieve; Garcia, Stephane; Ferone, Diego; Florio, Tullio; Enjalbert, Alain; Moutardier, Vincent; Schonbrunn, Agnes; Gerard, Corinne; Barlier, Anne; Saveanu, Alexandru

    2014-10-01

    Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) raise difficult therapeutic problems despite the emergence of targeted therapies. Somatostatin analogs (SSA) remain pivotal therapeutic drugs. However, the tachyphylaxis and the limited antitumoral effects observed with the classical somatostatin 2 (sst2) agonists (octreotide and lanreotide) led to the development of new SSA, such as the pan sst receptor agonist pasireotide. Our aim was to compare the effects of pasireotide and octreotide on cell survival, chromogranin A (CgA) secretion, and sst2 phosphorylation/trafficking in pancreatic NET (pNET) primary cells from 15 tumors. We established and characterized the primary cultures of human pancreatic tumors (pNETs) as powerful preclinical models for understanding the biological effects of SSA. At clinically relevant concentrations (1-10 nM), pasireotide was at least as efficient as octreotide in inhibiting CgA secretion and cell viability through caspase-dependent apoptosis during short treatments, irrespective of the expression levels of the different sst receptors or the WHO grade of the parental tumor. Interestingly, unlike octreotide, which induces a rapid and persistent partial internalization of sst2 associated with its phosphorylation on Ser341/343, pasireotide did not phosphorylate sst2 and induced a rapid and transient internalization of the receptor followed by a persistent recycling at the cell surface. These results provide the first evidence, to our knowledge, of striking differences in the dynamics of sst2 trafficking in pNET cells treated with the two SSAs, but with similar efficiency in the control of CgA secretion and cell viability.

  8. Noradrenalin Versus the Combination of Midodrine and Octreotide in Patients with Hepatorenal Syndrome: Randomized Clinical Trial

    PubMed Central

    Tavakkoli, Hamid; Yazdanpanah, Kambiz; Mansourian, Marjan

    2012-01-01

    Background: Hepatorenal syndrome (HRS) is known as development of acute renal failure in a patient who usually has advanced liver disease. The aim of the present study was to determine the safety and the efficacy of noradrenalin in comparison with midodrine-octreotide in patients with HRS. Methods: This study was registered to the Iranian Registry of Clinical trials (IRCT). This study was a single-center, randomized, clinical trial that performed in Alzahra hospital, Isfahan, Iran. Since March 2011 to January 2012, twenty-three patients were enrolled in the study. Eligible patients were allocated in 2 groups. In the first group, patients received infusion of NA with the dose of 0.1–0.7 μg/kg/min, and in the other groups, patients received octreotide 100-200 μg subcutaneously 3 times daily and midodrine 5-15 mg orally 3 times daily. In both study groups, patient received albumin infusion in addition to noradrenalin or midodrine-octreotide. Results: Complete response of HRS was observed in 8 of the 11 patients (73%) treated with noradrenalin and in 9 of the 12 patients (75%) treated with midodrine-octreotide (P > 0.05). HRS recurred after treatment withdrawal in 2 of 11 in NA and 3 of 12 in MO group. That shows no significant difference between 2 groups (P > 0.05). Conclusion: We deduce that NA has the same efficacy and safety with MO and can induce a complete response in high percentage of the patients. Moreover, we observed no significant differences in the recurrence rate and outcomes after 3 months among the patients in both study groups; this result could support the use of NA in HRS management. The IRCT ID is: IRCT201107217085N1. PMID:23189227

  9. Effects of diclofenac sodium and octreotide on treatment of caerulein-induced acute pancreatitis in mice

    PubMed Central

    Ozer Cakir, Ozlem; Esen, Hasan; Toker, Aysun; Ataseven, Huseyin; Demir, Ali; Polat, Hakki

    2015-01-01

    Background: Research continues to develop novel therapeutic modalities that particularly focus on the pathogenesis of acute pancreatitis. This study aimed to assess the effects of diclofenac sodium and octreotide, alone or in combination, on pancreatic enzymes, pancreatic myeloperoxidase activity, histopathology and apoptosis of pancreas cells, using a model of experimentally induced acute pancreatitis. Objectives: We aimed to demonstrate effects of diclofenac sodium, octreotide and their combined use on pancreatic enzymes, activity of pancreatic myeloperoxidase (MPO) activity, histopathology and apoptosis of pancreas on treatment of caerulin-induced experimental acute pancreatitis. Materials and methods: Caerulin-induced acute pancreatitis model was created using a total of 58 male BALB-C mice of 25 gr in seven groups. Serum amylase, lipase levels and pancreatic myeloperoxidase activity were examined as well as apoptotic values in pancreatic acinar cells through TUNNEL method. Histopathology of pancreas was evaluated for presence of edema, hemorrhage, parenchymal necrosis, fat necrosis, leukocyte infiltration, and fibrosis. Results: In the diclofenac sodium group, apoptotic values in the pancreatic acinar cells were found to be statistically lower than in the acute pancreatitis group in terms of parenchymal necrosis and hemorrhage scores (P = 0.007, P = 0.002, and P = 0.052, respectively). No statistically significant differences were found in serum level of amylase, lipase, pancreatic myeloperoxidase activity and the other histopathological scores (P > 0.05). Conclusion: Diclofenac sodium, a cost-effective agent with a favorable side-effect profile, may represent a novel therapeutic agent for the treatment of acute pancreatitis. Findings of this study suggest a better efficacy for diclofenac sodium monotherapy as compared to octreotide alone or octreotide/diclofenac combination. PMID:26770346

  10. Metformin with everolimus and octreotide in pancreatic neuroendocrine tumor patients with diabetes.

    PubMed

    Pusceddu, Sara; Buzzoni, Roberto; Vernieri, Claudio; Concas, Laura; Marceglia, Sara; Giacomelli, Luca; Milione, Massimo; Leuzzi, Livia; Femia, Daniela; Formisano, Barbara; Mazzaferro, Vincenzo; de Braud, Filippo

    2016-05-01

    A bidirectional relationship seems to exist between diabetes mellitus and development of pancreatic tumors. Metformin, the most widely used drug in the treatment of Type 2 diabetes mellitus, has recently emerged as a potentially active agent in cancer chemoprevention and treatment. In this article, we discuss the potential correlation between glycemic status, administration of antiglycemic treatments, such as metformin or insulin, and prognosis of pancreatic neuroendocrine tumors patients treated with everolimus and octreotide, on the basis of existing evidence and our experience.

  11. Effect of octreotide, a somatostatin analog, on sleep apnea in patients with acromegaly.

    PubMed

    Grunstein, R R; Ho, K K; Sullivan, C E

    1994-10-01

    To determine the effects of octreotide, a somatostatin analog, on the severity of sleep apnea and on growth hormone levels in patients with acromegaly. Open-label, prospective study. Tertiary referral hospital. 19 patients with active acromegaly. Octreotide in a 6-month, stepwise incremental dosage. Sleep studies and indices of hormonal activity (levels of insulin-like growth factor 1 [IGF-1] and growth hormone). A 50% decrease occurred in the respiratory disturbance index (baseline compared with 6 months, 39 events/h compared with 19 events/h; P = 0.0002), and a 40% decrease occurred in total apnea time (27.6% of total sleep time compared with 15.1%; P = 0.001). Indices of oxygen desaturation, sleep quality, and subjective sleepiness improved after 6 months of octreotide. A parallel decrease was noted in mean levels of growth hormone (40.0 micrograms/L compared with 9.1 micrograms/L; P = 0.003) and IGF-1 (107 nmol/L compared with 47 nmol/L; P = 0.0001). However, no correlation was noted between the decrease in the total amount of sleep time spent in apnea and the decrease in growth hormone levels (rho = -0.35; P > 0.2). The residual respiratory disturbance index after 6 months of treatment was similar in patients who improved, regardless of whether or not biochemical remission (IGF-1 < 35 nmol/L) occurred. Improvement in indices of sleep apnea severity occurs in association with octreotide treatment in patients with sleep apnea and acromegaly. However, sleep apnea may either persist despite normalization of growth hormone levels or may improve markedly even if there is only partial biochemical remission.

  12. Multispecies resistance of cattle gastrointestinal nematodes to long-acting avermectin formulations in Mato Grosso do Sul.

    PubMed

    Borges, Fernando de Almeida; Borges, Dyego Gonçalves Lino; Heckler, Rafael Pereira; Neves, Juliana Paniago Lordello; Lopes, Fernando Gonçalves; Onizuka, Marcel Kenzo Vilalba

    2015-09-15

    The use of long-acting avermectins (AVMs) in cattle to treat infections with gastrointestinal nematodes was common in Brazil until its prohibition by state authorities. The prohibition; however, was rescinded in 2015, but a scientific discussion of the pros and cons of the use of these formulations is necessary. We evaluated the levels of resistance to 1.0 and 3.5% doramectin and to 3.15% ivermectin in cattle. The worms in animals treated with 3.5% doramectin were characterized by the suppression of oviposition and by a higher proportion of adult females carrying no eggs. Haemonchus placei, Cooperia punctata, C. pectinata, C. spatulata, and Oesophagostomum radiatum were resistant to the above compositions. The administration of long-acting AVM formulations did not result in a higher efficacy against these helminth populations.

  13. Chemical Conjugation of Evans Blue Derivative: A Strategy to Develop Long-Acting Therapeutics through Albumin Binding.

    PubMed

    Chen, Haojun; Wang, Guohao; Lang, Lixin; Jacobson, Orit; Kiesewetter, Dale O; Liu, Yi; Ma, Ying; Zhang, Xianzhong; Wu, Hua; Zhu, Lei; Niu, Gang; Chen, Xiaoyuan

    2016-01-01

    The efficacy of therapeutic drugs is highly dependent on their optimal in vivo pharmacokinetics. Albumin conjugation is considered to be one of the most effective means of protracting the short lifespan of peptides and proteins. In this study, we proposed a novel platform for developing long lasting therapeutics by conjugating a small molecular albumin binding moiety, truncated Evans blue, to either peptides or proteins. Using the anti-diabetic peptide drug Exendin-4 as a model peptide, we synthesized a new long-acting Exendin-4 derivative (denoted as Abextide). Through complexation with albumin in situ, the biological half-life of Abextide was significantly extended. The hypoglycemic effect of Abextide was also improved remarkably over Exendin-4. Thus, Abextide has considerable potential to treat type 2 diabetes. This strategy as a general technology platform can be applied to other small molecules and biologics for the development of long-acting therapeutic drugs.

  14. Chemical Conjugation of Evans Blue Derivative: A Strategy to Develop Long-Acting Therapeutics through Albumin Binding

    PubMed Central

    Chen, Haojun; Wang, Guohao; Lang, Lixin; Jacobson, Orit; Kiesewetter, Dale O.; Liu, Yi; Ma, Ying; Zhang, Xianzhong; Wu, Hua; Zhu, Lei; Niu, Gang; Chen, Xiaoyuan

    2016-01-01

    The efficacy of therapeutic drugs is highly dependent on their optimal in vivo pharmacokinetics. Albumin conjugation is considered to be one of the most effective means of protracting the short lifespan of peptides and proteins. In this study, we proposed a novel platform for developing long lasting therapeutics by conjugating a small molecular albumin binding moiety, truncated Evans blue, to either peptides or proteins. Using the anti-diabetic peptide drug Exendin-4 as a model peptide, we synthesized a new long-acting Exendin-4 derivative (denoted as Abextide). Through complexation with albumin in situ, the biological half-life of Abextide was significantly extended. The hypoglycemic effect of Abextide was also improved remarkably over Exendin-4. Thus, Abextide has considerable potential to treat type 2 diabetes. This strategy as a general technology platform can be applied to other small molecules and biologics for the development of long-acting therapeutic drugs. PMID:26877782

  15. Octreotide improves early dumping syndrome potentially through incretins: a case report.

    PubMed

    Sato, Daisuke; Morino, Katsutaro; Ohashi, Natsuko; Ueda, Emi; Ikeda, Kazuhiro; Yamamoto, Hideka; Ugi, Satoshi; Yamamoto, Hiroshi; Araki, Shinichi; Maegawa, Hiroshi

    2013-01-01

    Dumping syndrome, or rapid gastric emptying, is a frequent complication after gastric surgery. In this case, the patient was a 47-year-old woman who 10 years previously had undergone distal gastrectomy with Billroth I reconstruction for early-stage gastric cancer. She presented with symptoms of weakness, headache, palpitation, sweating, dizziness and significant fatigue between one and two hours after a meal. Because a 75 g oral glucose tolerance test (75 g-OGTT) induced both acute postprandial tachycardia (within 1 hour) and postprandial hypoglycemia, we diagnosed this patient with early and late dumping syndrome. Dietary measures and acarbose improved symptoms of late dumping syndrome but did not prevent the symptoms of early dumping syndrome such as postprandial tachycardia, weakness, headache, palpitation, and dizziness. We therefore used the somatostatin analogue octreotide, which has been reported as an effective therapy for early dumping syndrome. Octreotide prevented the symptoms of early dumping syndrome, especially postprandial tachycardia, but caused postprandial hyperglycemia. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) were completely suppressed during the 75 g-OGTT following subcutaneous injection of octreotide. No change was observed in vasoactive intestinal polypeptide (VIP), which is the gastrointestinal peptide hormone generally responsible for early dumping syndrome, suggesting possible contribution of incretins in early dumping syndrome of this patient.

  16. Successful use of octreotide as a chemoprotectant for prevention of PEG-asparaginase-induced pancreatitis.

    PubMed

    Buie, Larry W; Moore, Joseph; van Deventer, Hank

    2014-08-01

    l-asparaginase is an aminohydrolase that deprives leukemia cells of l-asparagine required for protein synthesis. Although studies in patients with acute lymphoblastic leukemia have shown that the addition of l-asparaginase improved the overall remission rate, life-threatening acute pancreatitis has occurred in 0.5-4% of patients. We describe the first adult case report, to our knowledge, of the successful use of octreotide as a chemoprotectant for the prevention of recurrent pegylated asparaginase (PEG-ASP)-induced pancreatitis in a 21-year-old man with Philadelphia chromosome-negative acute lymphoblastic leukemia. After recurrent PEG-ASP administration during induction chemotherapy, he developed necrotizing pancreatitis, confirmed by abdominal computed tomography, and further asparaginase therapy was withheld. Currently, there are no specific treatment recommendations for the management of asparaginase-induced pancreatitis other than drug discontinuation. After disease relapse, a pediatric PEG-ASP-containing regimen was initiated, and PEG-ASP therapy was resumed due to its potential clinical benefit. Octreotide 100 μg subcutaneously 3 times/day, utilized as a chemoprotectant, was found to prevent pancreatitis recurrence. The patient completed therapy and was able to receive a bone marrow transplant without further complications from PEG-ASP therapy. Based on this patient's experience, we believe it is reasonable to reincorporate PEG-ASP after an episode of pancreatitis with use of octreotide as a chemoprotectant; however, this conclusion will need to be substantiated in a randomized clinical trial with a larger group of patients.

  17. Treatment of Gastrin-Secreting Tumor With Sustained-Release Octreotide Acetate in a Dog.

    PubMed

    Kim, Sangho; Hosoya, Kenji; Takagi, Satoshi; Okumura, Masahiro

    2015-01-01

    An 8 yr old, intact male Shiba Inu was presented with loose stool, polydipsia, hematuria, vomiting, and anorexia. On abdominal ultrasonography, numerous nodules were detected in the hepatic parenchyma distributed diffusely throughout all lobes. Excisional biopsy of one of the nodules was performed via exploratory laparotomy. A histopathological diagnosis of the lesion was carcinoid, and the tumor cells stained positive to chromogranin A and gastrin. The serum gastrin level of the dog was 45,613 pg/mL (reference range: 160-284). In addition to medical treatment with omeprazole(c) and famotidine(e), suppression of gastrin secretion was attempted with octreotide acetate. A test dose of octreotide acetate significantly decreased the serum gastrin level to approximately one third of the baseline in 2 hr and the effect lasted approximately for 6 hr. On day 21, treatment with sustained-release formulation of octreotide acetate(a) (5 mg intramuscular, q 4 wk) was initiated. The serum gastrin concentration gradually decreased over 32 days and then progressively increased in parallel with the progression of the hepatic nodules. The dog gradually developed recurrence of initial clinical signs, and was lost to follow-up on day 510.

  18. (89)Zr-labeled paramagnetic octreotide-liposomes for PET-MR imaging of cancer.

    PubMed

    Abou, Diane S; Thorek, Daniel L J; Ramos, Nicholas N; Pinkse, Martijn W H; Wolterbeek, Hubert T; Carlin, Sean D; Beattie, Bradley J; Lewis, Jason S

    2013-03-01

    Dual-modality PET/MR platforms add a new dimension to patient diagnosis with high resolution, functional, and anatomical imaging. The full potential of this emerging hybrid modality could be realized by using a corresponding dual-modality probe. Here, we report pegylated liposome (LP) formulations, housing a MR T(1) contrast agent (Gd) and the positron-emitting (89)Zr (half-life: 3.27 days), for simultaneous PET and MR tumor imaging capabilities. (89)Zr oxophilicity was unexpectedly found advantageous for direct radiolabeling of preformed paramagnetic LPs. LPs were conjugated with octreotide to selectively target neuroendocrine tumors via human somatostatin receptor subtype 2 (SSTr2). (89)Zr-Gd-LPs and octreotide-conjugated homolog were physically, chemically and biologically characterized. (89)Zr-LPs showed reasonable stability over serum proteins and chelator challenges for proof-of-concept in vitro and in vivo investigations. Nuclear and paramagnetic tracking quantified superior SSTr2-recognition of octreotide-LP compared to controls. This study demonstrated SSTr2-targeting specificity along with direct chelator-free (89)Zr-labeling of LPs and dual PET/MR imaging properties.

  19. 89Zr-Labeled Paramagnetic Octreotide-Liposomes for PET-MR Imaging of Cancer

    PubMed Central

    Abou, Diane S.; Thorek, Daniel L. J.; Ramos, Nicholas N.; Pinkse, Martijn W. H.; Wolterbeek, Hubert T.; Carlin, Sean D.; Beattie, Bradley J.

    2013-01-01

    Purpose Dual-modality PET/MR platforms add a new dimension to patient diagnosis with high resolution, functional, and anatomical imaging. The full potential of this emerging hybrid modality could be realized by using a corresponding dual-modality probe. Here, we report pegylated liposome (LP) formulations, housing a MR T1 contrast agent (Gd) and the positron-emitting 89Zr (half-life: 3.27 days), for simultaneous PET and MR tumor imaging capabilities. Methods 89Zr oxophilicity was unexpectedly found advantageous for direct radiolabeling of preformed paramagnetic LPs. LPs were conjugated with octreotide to selectively target neuroendocrine tumors via human somatostatin receptor subtype 2 (SSTr2). 89Zr-Gd-LPs and octreotide-conjugated homolog were physically, chemically and biologically characterized. Results 89Zr-LPs showed reasonable stability over serum proteins and chelator challenges for proof-of-concept in vitro and in vivo investigations. Nuclear and paramagnetic tracking quantified superior SSTr2-recognition of octreotide-LP compared to controls. Conclusions This study demonstrated SSTr2-targeting specificity along with direct chelator-free 89Zr-labeling of LPs and dual PET/MR imaging properties. PMID:23224977

  20. Prescribing patterns and purchasing costs of long-acting opioids over nine years at an academic oncology hospital.

    PubMed

    Curry, Eardie A; Palla, Shana; Hung, Frank; Arbuckle, Rebecca; Bruera, Eduardo

    2007-08-01

    The prescribing patterns and purchasing costs of long-acting opioids over nine years at an academic oncology hospital were studied. Data were collected for doses of transdermal fentanyl, methadone (all routes of administration), and oral sustained-release morphine and oxycodone dispensed for individual inpatient use for the month of October for each year between 1996 and 2004. The dates included in the retrieval were selected to document long-acting opioid use before and after the establishment of the palliative care and rehabilitation medicine department. For each opioid the number of milligrams dispensed daily per patient was determined and converted into a morphine-equivalent daily dose (MEDD). The average wholesale price per dosing unit of each drug during each period studied was obtained from internal databases. Costs were calculated by multiplying the number of units dispensed by the average wholesale price per unit and then normalized to 1996 U.S. dollars. The mean aggregate cost for a single MEDD in a month was determined by multiplying the mean cost per MEDD for each agent by that agent's percent contribution to the total MEDDs dispensed in that month. Long-acting opioid and methadone usage increased from 1996 to 2004. Between 1996 and 2004, the mean cost of a single MEDD dropped from $0.0738 to $0.0330. During the study period, the median daily cost to treat one patient dropped from $5.96 to $2.80. Long-acting opioid use increased and cost per MEDD decreased at an academic oncology hospital between 1996 and 2004. The decreased cost of purchasing opioids was attributed to the increased proportional use of methadone.

  1. [Side effects of treatment with the long-acting gonadorelin agonist triptorelin in a case of paraphilia].

    PubMed

    Hoogeveen, J H; van der Veer, E

    2007-01-01

    A 35-year-old man with a paraphilia was treated with long-acting gonadorelin. The desired result was reduced preoccupation with sexuality, but there were various side effects including a serious amount of bone loss. We believe that more attention should be given to the adverse effects of long-term treatment with triptorelin. In our view the drug regimen needs to be revised.

  2. Risperidone long-acting injectable (Risperdal Consta®) for maintenance treatment in patients with bipolar disorder.

    PubMed

    Bobo, William V; Shelton, Richard C

    2010-11-01

    Poor adherence to pharmacotherapy during maintenance-phase treatment of bipolar disorder is a common occurrence, exposing patients to a high risk of illness relapses, rehospitalization and other negative outcomes. In view of this, there has been a reawakening of interest in the potential of long-acting injectable antipsychotic medications to improve treatment outcome during bipolar maintenance therapy. Indeed, long-acting injectable medications have practical advantages of assuring delivery of medication at a prescribed dose, and perhaps also making it easier to monitor adherence, at least to the long-acting drug. However, there are important limitations to the long-term use of depot typical neuroleptics in patients with bipolar disorder, including risk of extrapyramidal side effects and tardive dyskinesia, which may exceed that of patients with schizophrenia, and the potential for treatment-emergent exacerbation of depressive symptoms. Long-acting injectable risperidone (RLAI) has recently been approved for maintenance treatment in patients with bipolar I disorder. Evidence supporting the use of RLAI for this indication consists of several nonrandomized, open-label studies; one randomized, open-label trial; and two adequately powered randomized, double-blind trials. In general, these studies have shown RLAI to be effective for the prevention of relapse or hospitalization during bipolar maintenance treatment. In the double-blind studies, RLAI was associated with reduced relapse rates, increased time to relapse and greater control of clinical symptoms during maintenance treatment following initial stabilization, compared with oral medication treatment or placebo injection. RLAI appeared to be more effective for preventing manic/mixed episodes than depressive episodes. RLAI showed good tolerability across studies; however, dose-related extrapyramidal effects, sedation, weight gain and prolactin elevation may occur during long-term treatment. Responder

  3. Severe COPD Exacerbation Risk and Long-Acting Bronchodilator Treatments: Comparison of Three Observational Data Analysis Methods.

    PubMed

    Roberts, Melissa H; Mapel, Douglas W; Borrego, Matthew E; Raisch, Dennis W; Georgopoulos, Larry; van der Goes, David

    2015-06-01

    Results from three observational methods for assessing effectiveness of long-acting bronchodilator therapies for reducing severe exacerbations of chronic obstructive pulmonary disease (COPD) were compared: intent-to-treat (ITT), as protocol (AP), and an as-treated analysis that utilized a marginal structural model (MSM) incorporating time-varying covariates related to treatment adherence and moderate exacerbations. Severe exacerbation risk was assessed over a 2-year period using claims data for patients aged ≥40 years who initiated long-acting muscarinic antagonist (LAMA), inhaled corticosteroid/long-acting beta-agonist (ICS/LABA), or triple therapy (LAMA + ICS/LABA). A total of 5475 COPD patients met inclusion criteria. Six months post-initiation, 53.5 % of patients discontinued using any therapy. The ITT analysis found an increased severe exacerbation risk for triple therapy treatment (hazard ratio [HR] 1.24; 95 % confidence interval [CI] 1.00-1.53). No increased risk was found in the AP (HR 1.00; 95 % CI 0.73-1.36), or MSM analyses (HR 1.11; 95 % CI 0.68-1.81). The MSM highlighted important associations among post-index events. Neglecting to adjust for treatment discontinuation may produce biased risk estimates. The MSM approach is a promising tool to compare chronic disease management by illuminating relationships between treatment decisions, adherence, patient choices, and outcomes.

  4. Knowledge and perception on long acting and permanent contraceptive methods in adigrat town, tigray, northern ethiopia: a qualitative study.

    PubMed

    Gebremariam, Alem; Addissie, Adamu

    2014-01-01

    Background. Long acting and permanent contraceptive methods have the potential to reduce unintended pregnancies but the contraceptive choice and utilization in Ethiopia are highly dominated by short term contraceptives. Objective. To assess the knowledge and perception on long acting and permanent contraceptives of married women and men in Northern Ethiopia. Method. A qualitative method was conducted in Adigrat on January, 2012. Four focus group discussions with married women and men and six in-depth interviews with family planning providers were conducted. Content analysis was used to synthesize the data. Result. Participants' knowledge on long acting and permanent contraceptives is limited to recognizing the name of the methods. Most of the participants are not able to identify permanent methods as a method of contraception. They lack basic information on how these methods work and how they can use it. Women had fears and rumors about each of these methods. They prefer methods which do not require any procedure. Family planning providers stated as they have weakness on counseling of all contraceptive choices. Conclusion. There are personal barriers and knowledge gaps on these contraceptive methods. Improving the counseling service program can help women to increase knowledge and avoid misconceptions of each contraceptive choice.

  5. Creation of a Long-Acting Nanoformulated 2′,3′-Dideoxy-3′-Thiacytidine

    PubMed Central

    Guo, Dongwei; Zhou, Tian; Araínga, Mariluz; Palandri, Diana; Gautam, Nagsen; Bronich, Tatiana; Alnouti, Yazen; McMillan, JoEllyn; Edagwa, Benson

    2017-01-01

    Background: Antiretroviral drug discovery and formulation design will facilitate viral clearance in infectious reservoirs. Although progress has been realized for selected hydrophobic integrase and nonnucleoside reverse transcriptase inhibitors, limited success has been seen to date with hydrophilic nucleosides. To overcome these limitations, hydrophobic long-acting drug nanoparticles were created for the commonly used nucleoside reverse transcriptase inhibitor, lamivudine (2′,3′-dideoxy-3′-thiacytidine, 3TC). Methods: A 2-step synthesis created a slow-release long-acting hydrophobic 3TC. Conjugation of 3TC to a fatty acid created a myristoylated prodrug which was encased into a folate-decorated poloxamer 407. Both in vitro antiretroviral efficacy in human monocyte-derived macrophages and pharmacokinetic profiles in mice were evaluated for the decorated nanoformulated drug. Results: A stable drug formulation was produced by poloxamer encasement that improved monocyte–macrophage uptake, antiretroviral activities, and drug pharmacokinetic profiles over native drug formulations. Conclusions: Sustained release of long-acting antiretroviral therapy is a new therapeutic frontier for HIV/AIDS. 3TC depot formation in monocyte-derived macrophages can be facilitated through stable subcellular internalization and slow drug release. PMID:27559685

  6. A prospective study on the efficacy of octreotide in the management of malignant bowel obstruction in gynecologic cancer.

    PubMed

    Watari, Hidemichi; Hosaka, Masayoshi; Wakui, Yukio; Nomura, Eiji; Hareyama, Hitoshi; Tanuma, Fumie; Hattori, Rifumi; Azuma, Masaki; Kato, Hidenori; Takeda, Naoki; Ariga, Satoshi; Sakuragi, Noriaki

    2012-05-01

    Malignant bowel obstruction (MBO), of which symptoms lead to a poor quality of life, is a common and distressing clinical complication in advanced gynecologic cancer. The aim of this study was to prospectively assess the clinical efficacy of octreotide to control vomiting in patients with advanced gynecologic cancer with inoperable gastrointestinal obstruction. Patients with advanced gynecologic cancer, who presented at least one episode of vomiting per day due to MBO, were enrolled in this prospective study from 2006 to 2009. Octreotide was administered when necessary at doses starting with 300 μg up to 600 μg a day by continuous infusion for 2 weeks. Primary end point was vomiting control, which was evaluated by common terminology criteria for adverse events version 3 (CTCAE v3.0). Adverse events were also evaluated by CTCAE v3.0. Twenty-two cases were enrolled in this study. Octreotide controlled vomiting in 15 cases (68.2%) to grade 0 and 3 cases (13.6%) to grade 1 on CTCAE v3.0. Overall response rate to octreotide treatment was 81.8% in our patients' cohort. Among 14 cases without nasogastric tube, the overall response rate was 93.1% (13/14). Among 8 cases with nasogastric tube, 4 cases were free of tube with decrease of drainage, and overall response rate was 62.5% (5/8). No major adverse events related to octreotide were reported. We conclude that 300-μg/d dose of octreotide was effective and safe for Japanese patients with MBO by advanced gynecologic cancer. Octreotide could contribute to better quality of life by avoiding placement of nasogastric tube.

  7. Daily average consumption of 2 long-acting opioids: an interrupted time series analysis.

    PubMed

    Puenpatom, R Amy; Szeinbach, Sheryl L; Ma, Larry; Ben-Joseph, Rami H; Summers, Kent H

    2012-01-01

    Oxycodone controlled release (CR) and oxymorphone extended release (ER) are frequently prescribed long-acting opioids, which are approved for twice-daily dosing. The US Food and Drug Administration approved a reformulated crush-resistant version of oxycodone CR in April 2010. To compare the daily average consumption (DACON) for oxycodone CR and for oxymorphone ER before and after the introduction of the reformulated, crush-resistant version of oxycodone CR. This was a retrospective claims database analysis using pharmacy claims from the MarketScan database for the period from January 2010 through March 2011. The interrupted time series analysis was used to evaluate the impact of the introduction of reformulated oxycodone CR on the DACON of the 2 drugs-oxycodone CR and oxymorphone ER. The source of the databases included private-sector health data from more than 150 medium and large employers. All prescription claims containing oxycodone CR and oxymorphone ER dispensed to members from January 1, 2010, to March 31, 2011, were included in the analysis. Prescription claims containing duplicate National Drug Codes, missing member identification, invalid quantities or inaccurate days supply of either drug, and DACON values of <1 and >500 were removed. The database yielded 483,063 prescription claims for oxycodone CR and oxymorphone ER from January 1, 2010, to March 31, 2011. The final sample consisted of 411,404 oxycodone CR prescriptions (traditional and reformulated) dispensed to 85,150 members and 62,656 oxymorphone ER prescriptions dispensed to 11,931 members. Before the introduction of reformulated oxycodone CR, DACON values for the highest strength available for each of the 2 drugs were 0.51 tablets higher for oxycodone CR than for oxymorphone ER, with mean DACON values of 3.5 for oxycodone CR and 3.0 for oxymorphone ER (P <.001). The differences of mean DACON between the 2 drugs for all lower strengths were 0.46 tablets, with mean DACON values of 2.7 for oxycodone

  8. Long-acting calcium channel antagonist pranidipine prevents ventricular remodeling after myocardial infarction in rats.

    PubMed

    Takeuchi, K; Omura, T; Yoshiyama, M; Yoshida, K; Otsuka, R; Shimada, Y; Ujino, K; Yoshikawa, J

    1999-01-01

    The purpose of this study was to examine the effects of the long-acting calcium channel antagonist pranidipine on ventricular remodeling, systolic and diastolic cardiac function, circulating humoral factors, and cardiac mRNA expression in myocardial infarcted rats. Myocardial infarction (MI) was produced by ligation of the coronary artery in Wistar rats. Three mg/kg per day of pranidipine was randomly administered to the infarcted rats. Hemodynamic measurements, Doppler echocardiographic examinations, analyses of the plasma levels of humoral factors, and myocardial mRNA expression were performed at 4 weeks after myocardial infarction. Left ventricular end-diastolic pressure (LVEDP) and central venous pressure (CVP) increased to 24.2 +/- 1.2mmHg and 5.4 +/- 0.6 mmHg. Pranidipine reduced LVEDP and CVP to 13.6 +/- 1.4mmHg (P < 0.01) and 2.5 +/- 0.4mmHg (P < 0.01). The weight of the left and right ventricles in MI was significantly higher than in the sham-operated rats (sham, 2.02 +/- 0.04 and 0.47 +/- 0.02g/kg; MI, 2.18 +/- 0.05 and 0.79 +/- 0.04g/ kg; P < 0.01). Left ventricular end-diastolic dimension (LVDd) in MI increased to 10.3 +/- 0.3mm (P < 0.01) (sham, 6.4 +/- 0.3mm). Pranidipine prevented an increase in the weight of the left and right ventricles (2.02 +/- 0.04 and 0.6 +/- 0.03g/kg, P < 0.01) and LVDd (7.9 +/-0.2mm, P < 0.01 to MI). Plasma renin activity (PRA), and plasma epinephrine, norepinephrine, and dopamine concentrations in MI were higher than those of the sham-operated rats. Pranidipine decreased the PRA and plasma cathecolamine levels of the myocardial infarcted rats to the level of the sham-operated rats. Moreover, the rats in MI showed systolic dysfunction, shown by decreased fractional shortening (sham, 31 +/- 2% vs MI, 15 +/- 1%; P < 0.01) and diastolic dysfunction shown by the E-wave deceleration rate (sham, 12.8 +/- 1.1 m/s2; MI, 32.6 +/- 2.1 m/s2; P < 0.01). Pranidipine significantly prevented systolic and diastolic dysfunction. The increases

  9. Repeated nightmares

    MedlinePlus

    ... different from night terrors . Alternative Names Nightmares - repeated; Dream anxiety disorder References American Academy of Family Physicians. Information from your family doctor. Nightmares and night terrors in children. ...

  10. Long-acting beta-agonists in the management of chronic obstructive pulmonary disease: current and future agents

    PubMed Central

    2010-01-01

    Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and debilitating symptoms. For patients with moderate-to-severe COPD, long-acting bronchodilators are the mainstay of therapy; as symptoms progress, guidelines recommend combining bronchodilators from different classes to improve efficacy. Inhaled long-acting β2-agonists (LABAs) have been licensed for the treatment of COPD since the late 1990s and include formoterol and salmeterol. They improve lung function, symptoms of breathlessness and exercise limitation, health-related quality of life, and may reduce the rate of exacerbations, although not all patients achieve clinically meaningful improvements in symptoms or health related quality of life. In addition, LABAs have an acceptable safety profile, and are not associated with an increased risk of respiratory mortality, although adverse effects such as palpitations and tremor may limit the dose that can be tolerated. Formoterol and salmeterol have 12-hour durations of action; however, sustained bronchodilation is desirable in COPD. A LABA with a 24-hour duration of action could provide improvements in efficacy, compared with twice-daily LABAs, and the once-daily dosing regimen could help improve compliance. It is also desirable that a new LABA should demonstrate fast onset of action, and a safety profile at least comparable to existing LABAs. A number of novel LABAs with once-daily profiles are in development which may be judged against these criteria. Indacaterol, a LABA with a 24-hour duration of bronchodilation and fast onset of action, is the most advanced of these. Preliminary results from large clinical trials suggest indacaterol improves lung function compared with placebo and other long-acting bronchodilators. Other LABAs with a 24-hour duration of bronchodilation include carmoterol, vilanterol trifenatate and oldaterol, with early results indicating potential for once-daily dosing in humans. The introduction of

  11. Use and Outcomes Associated with Long-acting Bronchodilators among Patients Hospitalized for Chronic Obstructive Pulmonary Disease

    PubMed Central

    Shieh, Meng-Shiou; Pekow, Penelope S.; Stefan, Mihaela S.

    2014-01-01

    Rationale: Long-acting β-adrenergic agonists and long-acting anticholinergic agents are recommended for the management of patients with stable chronic obstructive pulmonary disease (COPD); however, their role in the acute setting is uncertain. Objectives: To describe the use and outcomes associated with long-acting bronchodilator therapy (LABD) among patients hospitalized with exacerbations of COPD. Methods: We conducted a retrospective cohort study at 421 U.S. hospitals of patients hospitalized with exacerbations of COPD between January 1, 2010, and June 30, 2011. We used propensity score methods to compare the risk of a composite measure of treatment failure, length of stay, and hospital costs in patients who were treated with an LABD to those who did not receive treatment. Measurements and Main Results: Of the 77,378 patients included in the analysis, 31,725 (41%) were treated with an LABD on Hospital Day 1 or Day 2, including 15,356 (48.4%) who received a long-acting β-agonist, 6,665 (21%) who received a long-acting anticholinergic, and 9,704 (30.6%) who received both. When compared with patients who were not treated with an LABD, treated patients tended to be younger and had a modestly lower comorbidity burden but were more likely to have had prior admission for COPD and to be treated with inhaled corticosteroids. The incidence of treatment failure was similar among those who were or were not treated with LABDs (13.1 vs. 13.6%, P = 0.06). In propensity-matched analyses we found no difference in the risk of treatment failure associated with exposure to LABDs (relative risk [RR], 1.00; 95% confidence interval [CI], 0.96–1.04), minimal differences in hospital cost (RR, 1.02; 95% CI, 1.01–1.03), and no difference in length of stay (RR, 1.01; 95% CI, 1.00–1.02). Conclusions: Despite a lack of evidence, LABDs are commonly prescribed to patients hospitalized for exacerbations of COPD but are not associated with better clinical or economic outcomes. Clinical

  12. [Construction of yeast strains expressing long-acting glucagon-like peptide-1 (GLP-1) and their therapeutic effects on type 2 diabetes mellitus mouse model].

    PubMed

    Ri, Wu; Chao, Ma; Xiaodan, Li; Huikun, Duan; Yanli, Ji; Yu, Wang; Pingzhe, Jiang; Haisong, Wang; Peipei, Tu; Miao, Li; Ganggang, Ni; Baicheng, Ma; Minggang, Li

    2015-02-01

    Probiotics, i.e., bacteria expressing therapeutic peptides (protein), are used as a new type of orally administrated biologic drugs to treat diseases. To develop yeast strains which could effectively prevent and treat type 2 diabetes mellitus, we firstly constructed the yeast integrating plasmid pNK1-PGK which could successfully express green fluorescent protein (GFP) in Saccharomyces cerevisiae. The gene encoding ten tandem repeats of glucagon-like peptide-1(10 × GLP-1) was cloned into the vector pNK1-PGK and the resulting plasmids were then transformed into the S. cerevisiae INVSc1. The long-acting GLP-1 hypoglycemic yeast (LHY) which grows rapidly and expresses 10 × GLP-1 stably was selected by nutrition screening and Western blotting. The amount of 10 × GLP-1 produced by LHY reached 1.56 mg per gram of wet cells. Moreover, the oral administration of LHY significantly reduced blood glucose level in type 2 diabetic mice induced by streptozotocin plus high fat and high sugar diet.

  13. 99mTc-exendin(9-39)/octreotide: biokinetics and radiation dosimetry in healthy individuals.

    PubMed

    Ocampo-García, Blanca E; Santos-Cuevas, Clara L; Luna-Gutiérrez, Myrna A; Ignacio-Alvarez, Eleazar; Pedraza-López, Martha; Manzano-Mayoral, Cesar

    2017-09-25

    About 90% of insulinomas are benign and 5-15% are malignant. Benign insulinomas express the glucagon-like peptide-1 receptor (GLP-1R, which recognizes exendin-4 and low levels of the somatostatin receptor (SSTR, which recognizes octreotide), whereas malignant insulinomas overexpress SSTR and low levels of GLP-1R. Recently, Lys(Tc-EDDA/HYNIC)-exendin(9-39)/Tc-EDDA/HYNIC-Tyr-octreotide was formulated to detect 100% of insulinomas. The aim of this study was to estimate the biokinetics and dosimetry of Tc-exendin(9-39)/octreotide in four healthy individuals. Tc-exendin(9-39)/octreotide was obtained from a lyophilized formulation with radiochemical purities of more than 97%, determined by reversed-phase high-performance liquid chromatography. Whole-body images from four healthy individuals were acquired at 20 min, 2, 6, and 24 h after Tc-exendin(9-39)/octreotide administration. Regions of interest were drawn around the source organs on each time frame. Each region of interest was corrected by background, attenuation, scattered radiation, and physical decay. The image sequence was used to extrapolate the Tc-exendin(9-39)/octreotide time-activity curves of each organ to adjust the biokinetic model and calculate the total number of disintegrations (N) that occurred in the source regions. N data were the input for the OLINDA/EXM code to calculate internal radiation doses. Furthermore, in a patient suspicious of harboring an insulinoma, whole-body single-photon emission computed tomography/computed tomography images were obtained at 3 h. For four healthy individuals, the blood activity showed a half-life value of 1.20 min for the fast component (T1/2 α=ln 2/34.71), 8.7 min for the first slow component (T1/2 β=ln 2/4.76), and 1.7 h for the second slow component (T1/2 γ=ln 2/0.401). The average equivalent doses calculated for a study using 555 MBq were 15.10, 4.13, 3.08, 2.61, and 1.90 mSv for the kidneys, upper large intestinal wall, lower large

  14. A New Level A Type IVIVC for the Rational Design of Clinical Trials Toward Regulatory Approval of Generic Polymeric Long-Acting Injectables.

    PubMed

    Somayaji, Mahadevabharath R; Das, Debarun; Przekwas, Andrzej

    2016-10-01

    Chronic neuropsychiatric disorders and diabetes mellitus affect millions of patients and require long-term supervision and expensive medical care. Although repeated drug administration can help manage these diseases, relapses and re-hospitalization owing to patient non-adherence and reduced therapeutic efficacy remain challenging. In response, long-acting injectables, which provide sustained drug release over longer periods at concentrations close to therapeutic ranges, have been proposed. Recent advancements include polymeric long-acting injectables (pLAIs), in which the active pharmaceutical ingredient (API) is encapsulated within U.S. Food and Drug Administration (FDA)-approved biocompatible polymers, such as poly(lactic-co-glycolic acid), or PLGA. Despite significant progress and development in the global pLAI market, FDA guidance for the approval of complex drug products, such as generic pLAIs, is not clearly defined. Although in vitro to in vivo correlation (IVIVC) can facilitate the identification of critical quality attributes (CQAs), drug formulations, and in vitro test platforms for evaluating drug performance in vivo, the application of IVIVC in order to shortlist time- and resource-intensive clinical trials for generic pLAIs has not been reported. Here, we propose a new Level A Type IVIVC that directly correlates the in vitro outcomes, such as drug dissolution, of candidate generic formulations with the clinical characteristics, such as drug absorption, of a reference listed drug (RLD), to help identify the specific generic pLAI formulations with clinical absorptions that are likely to be similar to that of the RLD, thereby reducing the number of clinical trials required for evaluation of clinical bioequivalence (BE). Therefore, the scope of the proposed method is intended only for the rational design of clinical trials, i.e., to shortlist the specific pLAI generic formulations for clinical BE evaluation, and not necessarily to analyze drug performances

  15. In Vitro and in Vivo Characterization of MOD-4023, a Long-Acting Carboxy-Terminal Peptide (CTP)-Modified Human Growth Hormone.

    PubMed

    Hershkovitz, Oren; Bar-Ilan, Ahuva; Guy, Rachel; Felikman, Yana; Moschcovich, Laura; Hwa, Vivian; Rosenfeld, Ron G; Fima, Eyal; Hart, Gili

    2016-02-01

    MOD-4023 is a novel long-acting version of human growth hormone (hGH), containing the carboxy-terminal peptide (CTP) of human chorionic gonadotropin (hCG). MOD-4023 is being developed as a treatment for adults and children with growth hormone deficiency (GHD), which would require fewer injections than currently available GH formulations and thus reduce patient discomfort and increase compliance. This study characterizes MOD-4023's binding affinities for the growth hormone receptor, as well as the pharmacokinetic and pharmacodynamics, toxicology, and safety profiles of repeated dosing of MOD-4023 in Sprague-Dawley rats and Rhesus monkeys. Although MOD-4023 exhibited reduced in vitro potency and lower affinity to the GH receptor than recombinant hGH (rhGH), administration of MOD-4023 every 5 days in rats and monkeys resulted in exposure comparable to daily rhGH, and the serum half-life of MOD-4023 was significantly longer. Repeated administration of MOD-4023 led to elevated levels of insulin-like growth factor 1 (IGF-1), and twice-weekly injections of MOD-4023 resulted in larger increase in weight gain with fewer injections and a lower accumulative hGH dose. Thus, the increased half-life of MOD-4023 in comparison to hGH may increase the frequency of protein-receptor interactions and compensate for its decreased in vitro potency. MOD-4023 was found to be well-tolerated in rats and monkeys, with minimal adverse events, suggesting an acceptable safety profile. These results provide a basis for the continued clinical development of MOD-4023 as a novel treatment of GHD in children and adults.

  16. Effectiveness of long-acting antipsychotics in clinical practice : 1. A retrospective, 18-month follow up and comparison between paliperidone palmitate, risperidone long-acting injection and zuclopenthixol decanoate

    PubMed Central

    Cordiner, Matthew; Shajahan, Polash; McAvoy, Sarah; Bashir, Muhammad; Taylor, Mark

    2016-01-01

    Objectives: In the UK, nine different compounds are available as long-acting antipsychotic injections (LAIs). There are few clinical guidelines for determining which LAIs are most effective in specific patient groups. To measure the clinical effectiveness of LAIs we aimed to determine the now-established concept of antipsychotic discontinuation rates and measure Clinical Global Impression (CGI) outcomes. Method: The population (n was approximately 560,000) was a secondary care NHS adult mental health service in Lanarkshire, Scotland, UK. This was a retrospective, electronic case note search of LAI-naïve patients commenced on paliperidone palmitate (n = 31), risperidone long-acting injection (RLAI) (n = 102) or zuclopenthixol decanoate (n = 105), with an 18-month follow up. Kaplan–Meier survival statistics for discontinuation rates and hospital admission were calculated. CGI severity and improvement scores were retrospectively assigned by the investigating team. Results: Paliperidone palmitate performed less favourably than risperidone long-acting injection (RLAI) or zuclopenthixol decanoate. Paliperidone palmitate had higher discontinuation rates due to any cause, inefficacy and increased hospitalization risk. Paliperidone palmitate had the smallest proportion of patients assigned a clinically desirable CGI-I score of 1 (very much improved) or 2 (much improved). Conclusions: Paliperidone palmitate had less favourable discontinuation and CGI outcomes compared with RLAI and zuclopenthixol decanoate. This could not be adequately explained by patients in the paliperidone group being more chronically or severely unwell, nor by the presence of comorbidities such as alcohol or substance misuse, or by the use of lower mean dosages compared with RLAI or zuclopenthixol decanoate. We considered that prescribers are familiarizing themselves with paliperidone and outcomes may improve over time. PMID:26913175

  17. Addition of long-acting beta-agonists to inhaled corticosteroids for chronic asthma in children

    PubMed Central

    Ni Chroinin, Muireann; Lasserson, Toby J; Greenstone, Ilana; Ducharme, Francine M

    2014-01-01

    Background Long-acting ß2-agonists (LABA) in combination with inhaled corticosteroids (ICS) are increasingly prescribed in asthmatic children. Objectives To compare the safety and benefit of adding LABA to ICS with the same or an increased dose of ICS in children with persistent asthma. Search methods We searched the Cochrane Airways Group Asthma Trials Register (May 2008). Selection criteria We included randomised controlled trials testing the combination of LABA and ICS versus the same or an increased dose of ICS for minimum of at least 28 days in children and adolescents with asthma. The main outcome was the rate of exacerbations requiring rescue oral steroids. Secondary outcomes included pulmonary function, symptoms, adverse events, and withdrawals. Data collection and analysis Studies were assessed independently by two review authors for methodological quality and data extraction. Confirmation was obtained from the trialists when possible. Main results A total of 25 trials representing 31 control-intervention comparisons were included in the review randomising 5572 children. Most of the participants were inadequately controlled on current ICS dose. We assessed the addition of LABA to the same dose of ICS and to an increased dose of ICS: (1)The addition of LABA to ICS was compared to same dose ICS, namely 400 mcg/day of beclomethasone or less in 16 of the 24 studies. The mean age of participants was 10 years and males accounted for 64% of the study populations. The mean FEV1 at baseline was 80% of predicted or above in 10 studies; FEV1 61% to 79% of predicted in eight studies; and unreported in the remaining study. Participants were inadequately controlled before randomisation in all but seven studies. Compared to ICS alone, the addition of LABA to ICS was not associated with a significant reduction in exacerbations requiring oral steroids (seven studies, RR 0.92 95% CI 0.60 to 1.40). Compared to ICS alone, there was a significantly greater improvement in FEV1

  18. Prevalence and factors affecting use of long acting and permanent contraceptive methods in Jinka town, Southern Ethiopia: a cross sectional study

    PubMed Central

    Mekonnen, Getachew; Enquselassie, Fikre; Tesfaye, Gezahegn; Semahegn, Agumasie

    2014-01-01

    Introduction In Ethiopia, knowledge of contraceptive methods is high though there is low contraceptive prevalence rate. This study was aimed to assess prevalence and associated factors of long acting and permanent contraceptive methods in Jinka town, southern Ethiopia. Methods Community based cross sectional survey was conducted to assess the prevalence and factors affecting long acting and permanent methods of contraceptives utilization from March to April 2008. Eight hundred child bearing age women were participated in the quantitative study and 32 purposively selected focus group discussants were participated in the qualitative study. Face to face interview was used for data collection. Data were analyzed by SPSS version 13.0 statistical software. Descriptive statistics and logistic regression were computed to analyze the data. Results The prevalence of long acting and permanent contraceptive method was 7.3%. Three fourth (76.1%) of the women have ever heard about implants and implant 28 (50%) were the most widely used method. Almost two third of women had intention to use long acting and permanent methods. Knowledge of contraceptive and age of women have significant association with the use of long acting and permanent contraceptive methods. Conclusion The overall prevalence of long acting and permanent contraceptive method was low. Knowledge of contraceptive and age of women have significant association with use of long acting and permanent contraceptive. Extensive health information should be provided. PMID:25404960

  19. Prevalence and factors affecting use of long acting and permanent contraceptive methods in Jinka town, Southern Ethiopia: a cross sectional study.

    PubMed

    Mekonnen, Getachew; Enquselassie, Fikre; Tesfaye, Gezahegn; Semahegn, Agumasie

    2014-01-01

    In Ethiopia, knowledge of contraceptive methods is high though there is low contraceptive prevalence rate. This study was aimed to assess prevalence and associated factors of long acting and permanent contraceptive methods in Jinka town, southern Ethiopia. Community based cross sectional survey was conducted to assess the prevalence and factors affecting long acting and permanent methods of contraceptives utilization from March to April 2008. Eight hundred child bearing age women were participated in the quantitative study and 32 purposively selected focus group discussants were participated in the qualitative study. Face to face interview was used for data collection. Data were analyzed by SPSS version 13.0 statistical software. Descriptive statistics and logistic regression were computed to analyze the data. The prevalence of long acting and permanent contraceptive method was 7.3%. Three fourth (76.1%) of the women have ever heard about implants and implant 28 (50%) were the most widely used method. Almost two third of women had intention to use long acting and permanent methods. Knowledge of contraceptive and age of women have significant association with the use of long acting and permanent contraceptive methods. The overall prevalence of long acting and permanent contraceptive method was low. Knowledge of contraceptive and age of women have significant association with use of long acting and permanent contraceptive. Extensive health information should be provided.

  20. Comparison of inhaled long-acting β-agonist and anticholinergic effectiveness in older patients with chronic obstructive pulmonary disease: a cohort study.

    PubMed

    Gershon, Andrea; Croxford, Ruth; To, Teresa; Stanbrook, Matthew B; Upshur, Ross; Sanchez-Romeu, Paula; Stukel, Thérèse

    2011-05-03

    Chronic obstructive pulmonary disease (COPD), a largely preventable and manageable respiratory condition, affects an estimated 12% to 20% of adults. Long-acting inhaled β-agonists and anticholinergics have both been shown to improve COPD outcomes and are recommended for moderate to severe disease; however, little is known about their comparative effectiveness. To compare survival in older patients with COPD who initially receive inhaled long-acting β-agonists with that of patients who receive anticholinergics. Population-based, retrospective cohort study. Ontario, Canada. Patients aged 66 years or older (who carry the largest burden of COPD and for whom data were available) who met a validated case definition of COPD on the basis of health administrative data and were newly prescribed an inhaled long-acting β-agonist or a long-acting anticholinergic (but not both) between 2003 and 2007. Patients were followed for up to 5.5 years. The primary outcome was all-cause mortality. A total of 46 403 patients with COPD (mean age, 77 years; 49% women) were included. Overall mortality was 38.2%. Mortality was higher in patients initially prescribed a long-acting anticholinergic than in those initially prescribed a long-acting inhaled β-agonist (adjusted hazard ratio, 1.14 [95% CI, 1.09 to 1.19]). Rates of hospitalizations and emergency department visits were also higher in those initially prescribed a long-acting anticholinergic. Patients were classified as having COPD on the basis of health administrative records, which did not contain information about lung function. Older adults initially prescribed long-acting inhaled β-agonists for the management of moderate COPD seem to have lower mortality than those initially prescribed long-acting anticholinergics. Further research is needed to confirm these findings in younger patients and in a randomized, controlled trial. Government of Ontario, Canada.

  1. Long-Acting Injectable Risperidone for Relapse Prevention and Control of Breakthrough Symptoms After a Recent First Episode of Schizophrenia. A Randomized Clinical Trial.

    PubMed

    Subotnik, Kenneth L; Casaus, Laurie R; Ventura, Joseph; Luo, John S; Hellemann, Gerhard S; Gretchen-Doorly, Denise; Marder, Stephen; Nuechterlein, Keith H

    2015-08-01

    Long-acting, injectable, second-generation antipsychotic medication has tremendous potential to bring clinical stability to persons with schizophrenia. However, long-acting medications are rarely used following a first episode of schizophrenia. To compare the clinical efficacy of the long-acting injectable formulation of risperidone with the oral formulation in the early course of schizophrenia. A randomized clinical trial performed at a university-based research clinic, between 2005 and 2012. Eighty-six patients with recent onset of schizophrenia were randomized to receive long-acting injectable risperidone or oral risperidone. Half of each group was simultaneously randomized to receive cognitive remediation to improve cognitive functioning or healthy-behaviors training to improve lifestyle habits and well-being. An intent-to-treat analysis was performed between October 4, 2012, and November 12, 2014. A 12-month trial comparing the long-acting injectable vs oral risperidone and cognitive remediation vs healthy-behaviors training. Psychotic relapse and control of breakthrough psychotic symptoms. Of the 86 patients randomized, 3 refused treatment in the long-acting injectable risperidone group. The psychotic exacerbation and/or relapse rate was lower for the long-acting risperidone group compared with the oral group (5% vs 33%; χ21 = 11.1; P < .001; relative risk reduction, 84.7%). Long-acting injectable risperidone better controlled mean levels of hallucinations and delusions throughout follow-up (β = -0.30; t68 = -2.6, P = .01). The cognitive remediation and healthy-behaviors training groups did not differ significantly regarding psychotic relapse, psychotic symptom control, or hospitalization rates, and there were no significant interactions between the 2 medications and the 2 psychosocial treatments. Discontinuations owing to inadequate clinical response were more common in the oral group than in the long-acting risperidone group (χ21 = 6.1; P = .01

  2. Long-Acting Injectable Antipsychotics for Prevention of Relapse in Bipolar Disorder: A Systematic Review and Meta-Analyses of Randomized Controlled Trials

    PubMed Central

    Oya, Kazuto; Iwata, Nakao

    2016-01-01

    Background: This meta-analysis of randomized controlled trials aimed to examine the advantages of long-acting injectable antipsychotics over placebo or oral medications regarding efficacy and safety for patients with bipolar disorder. Methods: Two categorical meta-analyses of randomized controlled trials were performed to compare study-defined relapse rate (primary), discontinuation rates, and individual adverse events: (1) risperidone-long-acting injectable vs placebo, and (2) long-acting injectable antipsychotics vs oral medications. Results: We identified 7 randomized controlled trials (n=1016; long-acting injectable antipsychotics [flupenthixol (1 randomized controlled trial) and risperidone (6 randomized controlled trials)=449]; oral medications [mood stabilizers, antidepressants, antipsychotic, or any combination of these agents=283]; and placebo=284). Risperidone-long-acting injectable antipsychotic was superior to placebo for study-defined relapse rate (risk ratio=0.63, P<.0001), relapse of manic symptoms (risk ratio=0.42, P<.00001), and all-cause discontinuation (risk ratio=0.75, P=.007). Risperidone-long-acting injectable was associated with higher incidence of prolactin-related adverse events (risk ratio=4.82, P=.001) and weight gain (risk ratio=3.80, P<.0001) than placebo. The pooled long-acting injectable antipsychotics did not outperform oral medications regarding primary outcome but with significant heterogeneity (I2=74%). Sensitivity analysis, including only studies with rapid cycling or high frequency of relapse patients, revealed that long-acting injectable antipsychotics were superior compared to oral medications (I2=0%, RR=0.58, P=.0004). However, the comparators in this sensitivity analysis did not include second-generation antipsychotic monotherapy. In sensitivity analysis, including only studies with second-generation antipsychotic monotherapy as the comparator, long-acting injectable antipsychotics did not outperform second

  3. Effect of theophylline on exercise capacity in COPD patients treated with combination long-acting bronchodilator therapy: a pilot study

    PubMed Central

    Voduc, Nha; Alvarez, Gonzalo G; Amjadi, Kayvan; Tessier, Caroline; Sabri, Elham; Aaron, Shawn D

    2012-01-01

    Background Many patients with chronic obstructive pulmonary disease continue to experience significant functional limitation despite the use of both long-acting anticholinergic and beta-agonist inhalers. Theophylline is a widely available medication which may further improve lung function and exercise performance. Previous studies evaluating the effects of theophylline on exercise capacity in chronic obstructive pulmonary disease (COPD) have demonstrated heterogeneous results. Methods We performed a randomized placebo-controlled double-blind pilot study assessing the effects of theophylline on constant load exercise duration and lung function, involving 24 COPD patients already treated with long-acting inhaled beta-agonist and long-acting anti-cholinergic bronchodilator therapy. Results Analyzable data was available in 10 of 12 subjects in the treatment arm and 11 of 12 subjects in the control arm. Theophylline was associated with a 26.1% (95% confidence interval [CI]: −17.3–69.5) improvement in exercise duration compared to placebo. Four of 10 treated patients demonstrated an improvement in exercise duration exceeding the minimum clinically important difference of 33%, compared to 1 of 11 controls (P = 0.15). Furthermore, peak ventilation was reduced by 11.1%, (95% CI: 0.77–21.5) which may suggest improvements in gas exchange. There were no significant observed differences in resting lung function nor measures of dyspnea between the two treatment groups. Conclusions Our study demonstrated a trend, but not a statistically significant improvement in exercise duration and a reduction in peak ventilation with theophylline. Based on the observed mean differences and standard deviations in this pilot study, a randomized controlled trial would require 45 subjects in each arm to detect a significant change in exercise duration. PMID:22563244

  4. Long-Acting Anticoagulant Rodenticide (Superwarfarin) Poisoning: A Review of Its Historical Development, Epidemiology, and Clinical Management.

    PubMed

    King, Nathan; Tran, Minh-Ha

    2015-10-01

    Long-acting anticoagulant rodenticides (LAARs) inhibit vitamin K epoxide reductase (VKOR). Related bleeding may present a diagnostic challenge and require administration of blood component therapy, hemostatic agents, and vitamin K. This article intends to provide the reader a comprehensive understanding of LAAR poisoning. An exhaustive literature search of PubMed, Science Direct, US National Library of Medicine Toxicology Data Network, and Google Scholar yielded 174 reported cases of LAAR poisoning from which clinical data were extracted and reviewed. In addition, 25 years of epidemiologic data from the American Association of Poison Control Centers was reviewed. In the United States, on average, there were 10413 exposures reported with 2750 patients treated annually. For 25 years, there were 315951 exposures reported with nearly 90% among children and more than 100000 patients treated in a health care facility. Fortunately, only 2% of all exposures result in morbidity or mortality. Inhalational, transcutaneous, and oral routes of exposure have been documented. Most exposures are unintentional. The most frequently reported bleeding sites are mucocutaneous, with hematuria being the most common feature. Deaths were most commonly associated with intracranial hemorrhage. Long-acting anticoagulant rodenticide-induced paradoxical thrombosis and thrombotic complications accompanying hemostatic therapy have also been observed. Most patients present with coagulation assay values beyond measurable limits. Long-acting anticoagulant rodenticides have an extremely high affinity for VKOR compared with warfarin, characterized by rebound coagulopathy and bleeding after initial treatment and the need for high-dose, long-term therapy with vitamin K1. Treatment of acute hemorrhagic symptoms often required intravenous vitamin K1 in excess of 50 to 100 mg; chronic maintenance with 100 mg PO vitamin K1 daily was the most frequently used dose required to suppress coagulopathy. Treatment

  5. Prescribing of opioid analgesics and related mortality before and after the introduction of long-acting oxycodone

    PubMed Central

    Dhalla, Irfan A.; Mamdani, Muhammad M.; Sivilotti, Marco L.A.; Kopp, Alex; Qureshi, Omar; Juurlink, David N.

    2009-01-01

    Introduction Opioid-related mortality appears to be increasing in Canada. We examined the true extent of the problem and the impact of the introduction of long-acting oxycodone. Methods We examined trends in the prescribing of opioid analgesics in the province of Ontario from 1991 to 2007. We reviewed all deaths related to opioid use between 1991 and 2004. We linked 3271 of these deaths to administrative data to examine the patients’ use of health care services before death. Using time-series analysis, we determined whether the addition of long-acting oxycodone to the provincial drug formulary in January 2000 was associated with an increase in opioid-related mortality. Results From 1991 to 2007, annual prescriptions for opioids increased from 458 to 591 per 1000 individuals. Opioid-related deaths doubled, from 13.7 per million in 1991 to 27.2 per million in 2004. Prescriptions of oxycodone increased by 850% between 1991 and 2007. The addition of long-acting oxycodone to the drug formulary was associated with a 5-fold increase in oxycodone-related mortality (p < 0.01) and a 41% increase in overall opioid-related mortality (p = 0.02). The manner of death was deemed unintentional by the coroner in 54.2% and undetermined in 21.9% of cases. Use of health care services in the month before death was common: for example, of the 3066 patients for whom data on physician visits were available, 66.4% had visited a physician in the month before death; of the 1095 patients for whom individual-level prescribing data were available, 56.1% had filled a prescription for an opioid in the month before death. Interpretation Opioid-related deaths in Ontario have increased markedly since 1991. A significant portion of the increase was associated with the addition of long-acting oxycodone to the provincial drug formulary. Most of the deaths were deemed unintentional. The frequency of visits to a physician and prescriptions for opioids in the month before death suggests a missed

  6. Efficacy of long-acting oxytetracycline alone or in combination with streptomycin for treatment of Brucella ovis infection of rams.

    PubMed

    Marín, C M; Jiménez de Bagués, M P; Barberán, M; Blasco, J M

    1989-04-01

    Twenty-four rams inoculated with Brucella ovis by conjunctival and preputial routes were treated with a long-acting oxytetracycline