Extended-release hydrocodone – gift or curse?

PubMed Central

Krashin, Daniel; Murinova, Natalia; Trescot, Andrea M

2013-01-01

Hydrocodone is a semisynthetic opioid, which has been used for decades as a short-acting analgesic combined with acetaminophen (or less commonly ibuprofen). Several long-acting, non-acetaminophen-containing hydrocodone formulations are undergoing trials in the US under the auspices of the US Food and Drug Administration, and may be available shortly. This article reviews some of the advantages (including drug familiarity and lack of acetaminophen toxicity) and potential disadvantages (including altered use patterns and high morphine equivalent dosing) of such a medication formulation. We also discuss the abuse potential of long-acting versus short-acting opioids in general and hydrocodone specifically, as well as the metabolism of hydrocodone. PMID:23358452

[Pharmacokinetic interactions of telaprevir with other drugs].

PubMed

Berenguer Berenguer, Juan; González-García, Juan

2013-07-01

Telaprevir is a new direct-acting antiviral drug for the treatment of hepatitis C virus (HCV) infection and is both a substrate and an inhibitor of cytochrome P450 (CYP450) isoenzymes. With the introduction of this new drug, assessment of drug-drug interactions has become a key factor in the evaluation of patients under treatment for HCV infection. During the treatment of this infection, many patients require other drugs to mitigate the adverse effects of anti-HCV drugs and to control other comorbidities. Moreover, most patients coinfected with HIV and HCV require antiretroviral therapy during treatment for HCV. Physicians should therefore be familiar with the pharmacokinetic properties of direct-acting antivirals for HCV treatment and their potential drug-drug interactions. The present article reviews the available information to date on the interactions of telaprevir with other drugs and provides recommendations for daily clinical practice. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Increasing Access to Subsidized Artemisinin-based Combination Therapy through Accredited Drug Dispensing Outlets in Tanzania

PubMed Central

2011-01-01

Background In Tanzania, many people seek malaria treatment from retail drug sellers. The National Malaria Control Program identified the accredited drug dispensing outlet (ADDO) program as a private sector mechanism to supplement the distribution of subsidized artemisinin-based combination therapies (ACTs) from public facilities and increase access to the first-line antimalarial in rural and underserved areas. The ADDO program strengthens private sector pharmaceutical services by improving regulatory and supervisory support, dispenser training, and record keeping practices. Methods The government's pilot program made subsidized ACTs available through ADDOs in 10 districts in the Morogoro and Ruvuma regions, covering about 2.9 million people. The program established a supply of subsidized ACTs, created a price system with a cost recovery plan, developed a plan to distribute the subsidized products to the ADDOs, trained dispensers, and strengthened the adverse drug reactions reporting system. As part of the evaluation, 448 ADDO dispensers brought their records to central locations for analysis, representing nearly 70% of ADDOs operating in the two regions. ADDO drug register data were available from July 2007-June 2008 for Morogoro and from July 2007-September 2008 for Ruvuma. This intervention was implemented from 2007-2008. Results During the pilot, over 300,000 people received treatment for malaria at the 448 ADDOs. The percentage of ADDOs that dispensed at least one course of ACT rose from 26.2% during July-September 2007 to 72.6% during April-June 2008. The number of malaria patients treated with ACTs gradually increased after the start of the pilot, while the use of non-ACT antimalarials declined; ACTs went from 3% of all antimalarials sold in July 2007 to 26% in June 2008. District-specific data showed substantial variation among the districts in ACT uptake through ADDOs, ranging from ACTs representing 10% of all antimalarial sales in Kilombero to 47% in Morogoro Rural. Conclusions The intervention increased access to affordable ACTs for underserved populations. Indications are that antimalarial monotherapies are being "crowded out" of the market. Importantly, the transition to ACTs has been accomplished in an environment where the safety and efficacy of the drugs and the quality of services are being monitored and regulated. This paper presents a description of the pilot program implementation, results of the program evaluation, and a discussion of the challenges and recommendations that will be used to guide rollout of subsidized ACT in ADDOs in the rest of Tanzania and possibly in other countries. PMID:21658259

Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria

PubMed Central

2011-01-01

Quinine remains an important anti-malarial drug almost 400 years after its effectiveness was first documented. However, its continued use is challenged by its poor tolerability, poor compliance with complex dosing regimens, and the availability of more efficacious anti-malarial drugs. This article reviews the historical role of quinine, considers its current usage and provides insight into its appropriate future use in the treatment of malaria. In light of recent research findings intravenous artesunate should be the first-line drug for severe malaria, with quinine as an alternative. The role of rectal quinine as pre-referral treatment for severe malaria has not been fully explored, but it remains a promising intervention. In pregnancy, quinine continues to play a critical role in the management of malaria, especially in the first trimester, and it will remain a mainstay of treatment until safer alternatives become available. For uncomplicated malaria, artemisinin-based combination therapy (ACT) offers a better option than quinine though the difficulty of maintaining a steady supply of ACT in resource-limited settings renders the rapid withdrawal of quinine for uncomplicated malaria cases risky. The best approach would be to identify solutions to ACT stock-outs, maintain quinine in case of ACT stock-outs, and evaluate strategies for improving quinine treatment outcomes by combining it with antibiotics. In HIV and TB infected populations, concerns about potential interactions between quinine and antiretroviral and anti-tuberculosis drugs exist, and these will need further research and pharmacovigilance. PMID:21609473

78 FR 21613 - Prescription Drug User Fee Act Patient-Focused Drug Development; Announcement of Disease Areas...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-11

... syndrome; narcolepsy; neurological manifestations of inborn errors of metabolism; Parkinson's disease and... available therapies. Patients who live with a disease have a direct stake in the outcome of FDA's decisions... of applications for new drugs in certain disease areas. For FDA's review divisions, this kind of...

Risperidone long-acting injection: a review of its long term safety and efficacy

PubMed Central

Rainer, Michael K

2008-01-01

A long-acting form of the second-generation antipsychotic drug risperidone is now broadly available for the treatment of schizophrenia and closely related psychiatric conditions. It combines the advantage of previously available depot formulations for first-generation drugs with the favorable characteristics of the modern “atypical” antipsychotics, namely higher efficacy in the treatment of the negative symptoms of schizophrenia and reduced motor disturbances. Published clinical studies show an objective clinical efficacy (as per psychiatric symptom scores and relapse data) that exceeds that of oral atypical antipsychotics when patients are switched to the long-acting injectable form, a low incidence of treatment-emergent extrapyramidal side effects, and very good acceptance by patients. Available data for maintenance treatment of bipolar disorder show equivalence with the oral form instead of superiority, but are still limited. As it seems likely that efficacy benefits are mostly due to the fact that the injectable form reduces the demand for patient compliance to one physician visit every 2 weeks instead of self-administration on a daily or twice-daily basis, additional potential could exist in other psychiatric disorders where atypical antipsychotic drugs are of benefit but where patient adherence to treatment schedules is typically low. PMID:19183782

Has Tanzania embraced the green leaf? Results from outlet and household surveys before and after implementation of the Affordable Medicines Facility-malaria.

PubMed

Thomson, Rebecca; Festo, Charles; Johanes, Boniface; Kalolella, Admirabilis; Bruxvoort, Katia; Nchimbi, Happy; Tougher, Sarah; Cairns, Matthew; Taylor, Mark; Kleinschmidt, Immo; Ye, Yazoume; Mann, Andrea; Ren, Ruilin; Willey, Barbara; Arnold, Fred; Hanson, Kara; Kachur, S Patrick; Goodman, Catherine

2014-01-01

The Affordable Medicines Facility-malaria (AMFm) is primarily an artemisinin combination therapy (ACT) subsidy, aimed at increasing availability, affordability, market share and use of quality-assured ACTs (QAACTs). Mainland Tanzania was one of eight national scale programmes where AMFm was introduced in 2010. Here we present findings from outlet and household surveys before and after AMFm implementation to evaluate its impact from both the supply and demand side. Outlet surveys were conducted in 49 randomly selected wards throughout mainland Tanzania in 2010 and 2011, and data on outlet characteristics and stocking patterns were collected from outlets stocking antimalarials. Household surveys were conducted in 240 randomly selected enumeration areas in three regions in 2010 and 2012. Questions about treatment seeking for fever and drugs obtained were asked of individuals reporting fever in the previous two weeks. The availability of QAACTs increased from 25.5% to 69.5% among all outlet types, with the greatest increase among pharmacies and drug stores, together termed specialised drug sellers (SDSs), where the median QAACT price fell from $5.63 to $0.94. The market share of QAACTs increased from 26.2% to 42.2%, again with the greatest increase in SDSs. Household survey results showed a shift in treatment seeking away from the public sector towards SDSs. Overall, there was no change in the proportion of people with fever obtaining an antimalarial or ACT from baseline to endline. However, when broken down by treatment source, ACT use increased significantly among clients visiting SDSs. Unchanged ACT use overall, despite increases in QAACT availability, affordability and market share in the private sector, reflected a shift in treatment seeking towards private providers. The reasons for this shift are unclear, but likely reflect both persistent stockouts in public facilities, and the increased availability of subsidised ACTs in the private sector.

21 CFR 184.1695 - Riboflavin.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Academy Press, 2101 Constitution Ave. NW., Washington, DC 20418, or available for inspection at the... at NARA, call 202-741-6030, or go to: http://www.archives.gov/federal_register/code_of_federal... the Federal Food, Drug, and Cosmetic Act (the Act) or with regulations promulgated under section 412(a...

21 CFR 184.1695 - Riboflavin.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Academy Press, 2101 Constitution Ave. NW., Washington, DC 20418, or available for inspection at the... at NARA, call 202-741-6030, or go to: http://www.archives.gov/federal_register/code_of_federal... the Federal Food, Drug, and Cosmetic Act (the Act) or with regulations promulgated under section 412(a...

[Why do good drugs disappear?].

PubMed

Brezis, Mayer; Tomer, Ron; Klang, Samuel; Hammerman, Ariel

2010-10-01

Old drugs, with proved efficacy and safety, are disappearing from the market. For instance, nitrofurantoin, an inexpensive effective agent for urinary tract infections with low incidence of bacterial resistance in comparison to other antibiotics, is becoming unavailable. Alpha-methyldopa and hydraLazine, drugs of choice for pregnancy hypertension, are no longer available. Chlorthalidone, a Long acting thiazide with best evidence on efficacy, is no Longer marketed in Israel. Switching to newer agents increases costs and is often associated with relative uncertainty about safety and efficacy. The reason for the disappearance of old drugs is a combination of market failures and failures in production and regulatory processes. System revisions are needed to allow continued availability of old, safe and effective drugs.

21 CFR 184.1535 - Niacinamide.

Code of Federal Regulations, 2013 CFR

2013-04-01

... reference. Copies are available from the National Academy Press, 2101 Constitution Ave. NW., Washington, DC.../federal_register/code_of_federal_regulations/ibr_locations.html. (c) In accordance with § 184.1(b)(1), the... infant formula in accordance with section 412(g) of the Federal Food, Drug, and Cosmetic Act (the act) or...

21 CFR 184.1535 - Niacinamide.

Code of Federal Regulations, 2012 CFR

2012-04-01

... reference. Copies are available from the National Academy Press, 2101 Constitution Ave. NW., Washington, DC.../federal_register/code_of_federal_regulations/ibr_locations.html. (c) In accordance with § 184.1(b)(1), the... infant formula in accordance with section 412(g) of the Federal Food, Drug, and Cosmetic Act (the act) or...

76 FR 17136 - Medical Devices; Availability of Safety and Effectiveness Summaries for Premarket Approval...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-28

... section 515(d)(4) and (e)(2) of the Federal Food, Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C. 360e(d......... Dako Denmark A/S..... HercepTest kit Approved October 20, 2010. P080009 Ethicon Endo-Surgery, SEDASYS...

Drugs in the Pipeline for the Obesity Market

PubMed Central

Klonoff, David C.; Greenway, Frank

2008-01-01

Obesity is a major public health problem. For many obese patients, diet and exercise are an inadequate treatment and bariatric surgery may be too extreme of a treatment. As with many other chronic diseases, pharmacologic treatment may be an attractive option for selected obese patients. Antiobesity drugs may potentially work through one of three mechanisms: (1) appetite suppression, (2) interference with absorption of nutrients, and (3) increased metabolism of nutrients. The three most widely prescribed drugs approved to treat obesity are phentermine, sibutramine, and orlistat. Drugs approved for treating obesity usually result in an additional weight loss of approximately 2–5 kg in addition to placebo. For pharmacologic therapy in obesity to be widely utilized, greater effectiveness and safety will be needed. Four types of single-agent drugs are in late stage development, including (1) selective central cannabinoid-1 receptor blockers, (2) selective central 5-hydroxytryptamine 2C serotonin receptor agonists, (3) an intestinal lipase blocker, and (4) central-acting incretin mimetic drugs. Four combination agent compounds in late stage development include (1) Contrave, which combines long-acting versions of naltrexone and bupropion; (2) Empatic, which combines long-acting bupropion and long-acting zonisamide; (3) Qnexa, which combines phentermine with controlled release topiramate; and (4) an injectable combination of leptin and pramlintide. Peptide YY and melanin-concentrating hormone receptor-1 antagonists are centrally acting agents in early stage development. It is expected that several new drug products for obesity will become available over the next few years. Their role in managing this disease remains to be determined. PMID:19885278

Drugs in the pipeline for the obesity market.

PubMed

Klonoff, David C; Greenway, Frank

2008-09-01

Obesity is a major public health problem. For many obese patients, diet and exercise are an inadequate treatment and bariatric surgery may be too extreme of a treatment. As with many other chronic diseases, pharmacologic treatment may be an attractive option for selected obese patients. Antiobesity drugs may potentially work through one of three mechanisms: (1) appetite suppression, (2) interference with absorption of nutrients, and (3) increased metabolism of nutrients. The three most widely prescribed drugs approved to treat obesity are phentermine, sibutramine, and orlistat. Drugs approved for treating obesity usually result in an additional weight loss of approximately 2-5 kg in addition to placebo. For pharmacologic therapy in obesity to be widely utilized, greater effectiveness and safety will be needed. Four types of single-agent drugs are in late stage development, including (1) selective central cannabinoid-1 receptor blockers, (2) selective central 5-hydroxytryptamine 2C serotonin receptor agonists, (3) an intestinal lipase blocker, and (4) central-acting incretin mimetic drugs. Four combination agent compounds in late stage development include (1) Contrave, which combines long-acting versions of naltrexone and bupropion; (2) Empatic, which combines long-acting bupropion and long-acting zonisamide; (3) Qnexa, which combines phentermine with controlled release topiramate; and (4) an injectable combination of leptin and pramlintide. Peptide YY and melanin-concentrating hormone receptor-1 antagonists are centrally acting agents in early stage development. It is expected that several new drug products for obesity will become available over the next few years. Their role in managing this disease remains to be determined.

Medical devices; hematology and pathology devices; classification of the Factor V Leiden DNA mutation detection systems devices. Final rule.

PubMed

2004-03-16

The Food and Drug Administration (FDA) is classifying the Factor V Leiden deoxyribonucleic acid (DNA) mutation detections systems device into class II (special controls). The special control that will apply to the device is the guidance document entitled "Class II Special Controls Guidance Document: Factor V Leiden DNA Mutation Detection Systems." The agency is taking this action in response to a petition submitted under the Federal Food, Drug, and Cosmetic Act (the act) as amended by the Medical Device Amendments of 1976 (the 1976 amendments), the Safe Medical Devices Act of 1990 (SMDA), the Food and Drug Administration Modernization Act of 1997 (FDAMA), and the Medical Device User Fee and Modernization Act of 2002. The agency is classifying this device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device. Elsewhere in this issue of the Federal Register, FDA is publishing a notice of availability of a guidance document that is the special control for this device.

Medical devices; reclassification of the topical oxygen chamber for extremities. Final rule.

PubMed

2011-04-25

The Food and Drug Administration (FDA) is reclassifying the topical oxygen chamber for extremities (TOCE) from class III to class II. This device is intended to surround a patient's limb and apply humidified oxygen topically at a pressure slightly greater than atmospheric pressure to aid healing of chronic skin ulcers, such as bedsores. This reclassification is on the Secretary of Health and Human Services's own initiative based on new information. This action is being taken under the Federal Food, Drug, and Cosmetic Act (the FD&C Act) as amended by the Medical Device Amendments of 1976 (the 1976 Amendments), the Safe Medical Devices Act of 1990 (the SMDA), and the Food and Drug Administration Modernization Act of 1997 (FDAMA). Elsewhere in this issue of the Federal Register, FDA is announcing the availability of the guidance document entitled ``Class II Special Controls Guidance Document: Topical Oxygen Chamber for Extremities,'' which will serve as the special control for this device.

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.

21 CFR 184.1301 - Ferric phosphate.

Code of Federal Regulations, 2012 CFR

2012-04-01

.... Copies are available from the National Academy Press, 2101 Constitution Ave. NW., Washington, DC 20418.../federal_register/code_of_federal_regulations/ibr_locations.html. (c) In accordance with § 184.1(b)(1), the... in accordance with section 412(g) of the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C...

21 CFR 184.1307d - Ferrous fumarate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... National Academy Press, 2101 Constitution Ave NW., Washington, DC 20418, or available for inspection at the... at NARA, call 202-741-6030, or go to: http://www.archives.gov/federal_register/code_of_federal... section 412(g) of the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 350a(g)), or with...

21 CFR 184.1307d - Ferrous fumarate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... National Academy Press, 2101 Constitution Ave NW., Washington, DC 20418, or available for inspection at the... at NARA, call 202-741-6030, or go to: http://www.archives.gov/federal_register/code_of_federal... section 412(g) of the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 350a(g)), or with...

21 CFR 184.1304 - Ferric pyrophosphate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... reference. Copies are available from the National Academy Press, 2101 Constitution Ave. NW., Washington, DC.../federal_register/code_of_federal_regulations/ibr_locations.html. (c) In accordance with § 184.1(b)(1), the... in accordance with section 412(g) of the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C...

21 CFR 184.1304 - Ferric pyrophosphate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... reference. Copies are available from the National Academy Press, 2101 Constitution Ave. NW., Washington, DC.../federal_register/code_of_federal_regulations/ibr_locations.html. (c) In accordance with § 184.1(b)(1), the... in accordance with section 412(g) of the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C...

21 CFR 184.1301 - Ferric phosphate.

Code of Federal Regulations, 2013 CFR

2013-04-01

.... Copies are available from the National Academy Press, 2101 Constitution Ave. NW., Washington, DC 20418.../federal_register/code_of_federal_regulations/ibr_locations.html. (c) In accordance with § 184.1(b)(1), the... in accordance with section 412(g) of the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C...

42 CFR 403.902 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., repackagers, relabelers, and kit assemblers) that do not hold title to any covered drug, device, biological or... sister corporations. Covered device means any device for which payment is available under Title XVIII of the Act or under a State plan under Title XIX or XXI of the Act (or a waiver of such plan), either...

42 CFR 403.902 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., repackagers, relabelers, and kit assemblers) that do not hold title to any covered drug, device, biological or... sister corporations. Covered device means any device for which payment is available under Title XVIII of the Act or under a State plan under Title XIX or XXI of the Act (or a waiver of such plan), either...

78 FR 11204 - Accreditation and Reaccreditation Process for Firms Under the Third Party Review Program: Part I...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-15

...] Accreditation and Reaccreditation Process for Firms Under the Third Party Review Program: Part I; Draft Guidance... announcing the availability of the draft guidance entitled ``Accreditation and Reaccreditation Process for... Act), as amended by the Food and Drug Administration Safety and Innovation Act (FDASIA), requires FDA...

Polypharmacology of Approved Anticancer Drugs.

PubMed

Amelio, Ivano; Lisitsa, Andrey; Knight, Richard A; Melino, Gerry; Antonov, Alexey V

2017-01-01

The major drug discovery efforts in oncology have been concentrated on the development of selective molecules that are supposed to act specifically on one anticancer mechanism by modulating a single or several closely related drug targets. However, a bird's eye view on data from multiple available bioassays implies that most approved anticancer agents do, in fact, target many more proteins with different functions. Here we will review and systematize currently available information on the targets of several anticancer drugs along with revision of their potential mechanisms of action. Polypharmacology of the current antineoplastic agents suggests that drug clinical efficacy in oncology can be achieved only via modulation of multiple cellular mechanisms. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Orthopedic devices; classification for the resorbable calcium salt bone void filler device. Final rule.

PubMed

2003-06-02

The Food and Drug Administration (FDA) is classifying the resorbable calcium salt bone void filler device intended to fill bony voids or gaps of the extremities, spine, and pelvis that are caused by trauma or surgery and are not intrinsic to the stability of the bony structure into class II (special controls). Elsewhere in this issue of the Federal Register, FDA is announcing the availability of a class II special controls guidance entitled "Class II Special Controls Guidance Document: Resorbable Calcium Salt Bone Void Filler Device; Guidance for Industry and FDA." This action is being undertaken based on new information submitted in a classification proposal from Wright Medical Technology under the Federal Food, Drug, and Cosmetic Act as amended by the Medical Device Amendments of 1976, the Safe Medical Devices Act of 1990, and the Food and Drug Administration Modernization Act of 1997.

Expanding the domain of drug delivery for HIV prevention: exploration of the transdermal route.

PubMed

Puri, Ashana; Sivaraman, Arunprasad; Zhang, Wei; Clark, Meredith R; Banga, Ajay K

2017-01-01

Constant efforts for HIV prevention using antiretroviral drugs, pre- and postexposure prophylactic agents, and microbicides are being made by researchers. Drug-delivery systems such as oral tablets and coitally dependent vaginal gels are short acting, require daily application, and are associated with user adherence issues, whereas the coitally independent systems such as injectables and biodegradable implants are long acting, lasting several months, during which time the termination of prophylaxis is impractical in case of adverse effects. An effective drug-delivery system to be used for an intermediate duration, if available, would be an attractive alternative option for users in terms of adherence. Transdermal delivery systems, overcoming most of the limitations of the other routes of administration and aiming to provide sustained delivery of drugs through skin, may be explored for HIV prevention. Passive and physical enhancement techniques may be designed strategically to improve the transdermal delivery of HIV preventive agents.

The clinical impact of artemisinin resistance in Southeast Asia and the potential for future spread

PubMed Central

Woodrow, Charles J.; White, Nicholas J.

2017-01-01

Abstract Artemisinins are the most rapidly acting of currently available antimalarial drugs. Artesunate has become the treatment of choice for severe malaria, and artemisinin-based combination therapies (ACTs) are the foundation of modern falciparum malaria treatment globally. Their safety and tolerability profile is excellent. Unfortunately, Plasmodium falciparum infections with mutations in the ‘K13’ gene, with reduced ring-stage susceptibility to artemisinins, and slow parasite clearance in patients treated with ACTs, are now widespread in Southeast Asia. We review clinical efficacy data from the region (2000–2015) that provides strong evidence that the loss of first-line ACTs in western Cambodia, first artesunate-mefloquine and then DHA-piperaquine, can be attributed primarily to K13 mutated parasites. The ring-stage activity of artemisinins is therefore critical for the sustained efficacy of ACTs; once it is lost, rapid selection of partner drug resistance and ACT failure are inevitable consequences. Consensus methods for monitoring artemisinin resistance are now available. Despite increased investment in regional control activities, ACTs are failing across an expanding area of the Greater Mekong subregion. Although multiple K13 mutations have arisen independently, successful multidrug-resistant parasite genotypes are taking over and threaten to spread to India and Africa. Stronger containment efforts and new approaches to sustaining long-term efficacy of antimalarial regimens are needed to prevent a global malaria emergency. PMID:27613271

Obesity and Pediatric Drug Development.

PubMed

Vaughns, Janelle D; Conklin, Laurie S; Long, Ying; Zheng, Panli; Faruque, Fahim; Green, Dionna J; van den Anker, John N; Burckart, Gilbert J

2018-05-01

There is a lack of dosing guidelines for use in obese children. Moreover, the impact of obesity on drug safety and clinical outcomes is poorly defined. The paucity of information needed for the safe and effective use of drugs in obese patients remains a problem, even after drug approval. To assess the current incorporation of obesity as a covariate in pediatric drug development, the pediatric medical and clinical pharmacology reviews under the Food and Drug Administration (FDA) Amendments Act of 2007 and the FDA Safety and Innovation Act (FDASIA) of 2012 were reviewed for obesity studies. FDA labels were also reviewed for statements addressing obesity in pediatric patients. Forty-five drugs studied in pediatric patients under the FDA Amendments Act were found to have statements and key words in the medical and clinical pharmacology reviews and labels related to obesity. Forty-four products were identified similarly with pediatric studies under FDASIA. Of the 89 product labels identified, none provided dosing information related to obesity. The effect of body mass index on drug pharmacokinetics was mentioned in only 4 labels. We conclude that there is little information presently available to provide guidance related to dosing in obese pediatric patients. Moving forward, regulators, clinicians, and the pharmaceutical industry should consider situations in drug development in which the inclusion of obese patients in pediatric trials is necessary to facilitate the safe and effective use of new drug products in the obese pediatric population. © 2018, The American College of Clinical Pharmacology.

75 FR 20441 - Authorization of Emergency Use of Certain In Vitro Diagnostic Devices; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-19

...The Food and Drug Administration (FDA) is announcing the issuance of 10 Emergency Use Authorizations (EUAs) (the Authorizations) several of which were amended after initial issuance, for certain in vitro diagnostic devices. FDA also is announcing an amendment to the EUA for the Centers for Disease Control and Prevention (CDC) Swine Influenza Virus Real-time RT-PCR Detection Panel authorized on April 27, 2009. FDA is issuing the Authorizations and amendments thereto under the Federal Food, Drug, and Cosmetic Act (the act). The Authorizations contain, among other things, conditions on the emergency use of the authorized in vitro diagnostics. The Authorizations follow the determination by the Acting Secretary of the U.S. Department of Health and Human Services, Charles E. Johnson (the Acting Secretary), that a public health emergency exists involving Swine Influenza A (now known as 2009 H1N1 Influenza A, or 2009 H1N1 flu) that affects, or has the significant potential to affect, national security. On the basis of such determination, the Acting Secretary declared an emergency justifying the authorization of the emergency use of certain in vitro diagnostics, accompanied by emergency use information subject to the terms of any authorization issued under the Federal Food, Drug, and Cosmetic Act (the act). The Authorizations, which include explanations of the reasons for their issuance or reissuance, are reprinted in this document.

77 FR 74852 - Draft Guidance for Industry on Certification of Designated Medical Gases; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-18

... the availability of a draft guidance for industry entitled ``Certification Process for Designated Medical Gases.'' This draft guidance describes the new certification process created by the Food and Drug Administration Safety and Innovation Act (FDASIA) for certain medical gases and explains how FDA plans to...

American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part I--evidence assessment.

PubMed

Manchikanti, Laxmaiah; Abdi, Salahadin; Atluri, Sairam; Balog, Carl C; Benyamin, Ramsin M; Boswell, Mark V; Brown, Keith R; Bruel, Brian M; Bryce, David A; Burks, Patricia A; Burton, Allen W; Calodney, Aaron K; Caraway, David L; Cash, Kimberly A; Christo, Paul J; Damron, Kim S; Datta, Sukdeb; Deer, Timothy R; Diwan, Sudhir; Eriator, Ike; Falco, Frank J E; Fellows, Bert; Geffert, Stephanie; Gharibo, Christopher G; Glaser, Scott E; Grider, Jay S; Hameed, Haroon; Hameed, Mariam; Hansen, Hans; Harned, Michael E; Hayek, Salim M; Helm, Standiford; Hirsch, Joshua A; Janata, Jeffrey W; Kaye, Alan D; Kaye, Adam M; Kloth, David S; Koyyalagunta, Dhanalakshmi; Lee, Marion; Malla, Yogesh; Manchikanti, Kavita N; McManus, Carla D; Pampati, Vidyasagar; Parr, Allan T; Pasupuleti, Ramarao; Patel, Vikram B; Sehgal, Nalini; Silverman, Sanford M; Singh, Vijay; Smith, Howard S; Snook, Lee T; Solanki, Daneshvari R; Tracy, Deborah H; Vallejo, Ricardo; Wargo, Bradley W

2012-07-01

Opioid abuse has continued to increase at an alarming rate since the 1990 s. As documented by different medical specialties, medical boards, advocacy groups, and the Drug Enforcement Administration, available evidence suggests a wide variance in chronic opioid therapy of 90 days or longer in chronic non-cancer pain. Part 1 describes evidence assessment. The objectives of opioid guidelines as issued by the American Society of Interventional Pain Physicians (ASIPP) are to provide guidance for the use of opioids for the treatment of chronic non-cancer pain, to produce consistency in the application of an opioid philosophy among the many diverse groups involved, to improve the treatment of chronic non-cancer pain, and to reduce the incidence of abuse and drug diversion. The focus of these guidelines is to curtail the abuse of opioids without jeopardizing non-cancer pain management with opioids. 1) There is good evidence that non-medical use of opioids is extensive; one-third of chronic pain patients may not use prescribed opioids as prescribed or may abuse them, and illicit drug use is significantly higher in these patients. 2) There is good evidence that opioid prescriptions are increasing rapidly, as the majority of prescriptions are from non-pain physicians, many patients are on long-acting opioids, and many patients are provided with combinations of long-acting and short-acting opioids. 3) There is good evidence that the increased supply of opioids, use of high dose opioids, doctor shoppers, and patients with multiple comorbid factors contribute to the majority of the fatalities. 4) There is fair evidence that long-acting opioids and a combination of long-acting and short-acting opioids contribute to increasing fatalities and that even low-doses of 40 mg or 50 mg of daily morphine equivalent doses may be responsible for emergency room admissions with overdoses and deaths. 5) There is good evidence that approximately 60% of fatalities originate from opioids prescribed within the guidelines, with approximately 40% of fatalities occurring in 10% of drug abusers. 6) The short-term effectiveness of opioids is fair, whereas the long-term effectiveness of opioids is limited due to a lack of long-term (> 3 months) high quality studies, with fair evidence with no significant difference between long-acting and short-acting opioids. 7) Among the individual drugs, most opioids have fair evidence for short-term and limited evidence for long-term due to a lack of quality studies. 8) The evidence for the effectiveness and safety of chronic opioid therapy in the elderly for chronic non-cancer pain is fair for short-term and limited for long-term due to lack of high quality studies; limited in children and adolescents and patients with comorbid psychological disorders due to lack of quality studies; and the evidence is poor in pregnant women. 9) There is limited evidence for reliability and accuracy of screening tests for opioid abuse due to lack of high quality studies. 10) There is fair evidence to support the identification of patients who are non-compliant or abusing prescription drugs or illicit drugs through urine drug testing and prescription drug monitoring programs, both of which can reduce prescription drug abuse or doctor shopping. The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."

Illicit Internet availability of drugs subject to recall and patient safety consequences.

PubMed

Mackey, Tim K; Aung, Phyo; Liang, Bryan A

2015-12-01

Permanently recalled drugs are a public health concern if they remain accessible in violation of applicable regulation. Illicit online pharmacies act as an alternative form of access and have been associated with the sale to patients of counterfeit/falsified/fraudulent/substandard drugs. We wished to determine if permanently recalled and significantly restricted drugs were illegally marketed for sale online. The study was conducted in two phases with two objectives. The first phase attempted to identify drugs subject to permanent recall in certain major pharmaceutical markets as well as those listed as recalled or significantly restricted by the United Nations. We also examined the market authorization status of identified drugs in China and India. The second phase used structured searches on the Internet to determine if identified drugs were marketed for sale online. The World Wide Web. After identification of permanently recalled and restricted drugs we conducted Internet searches for illegal "no prescription" marketing events. We assessed the form of marketing, whether a site offered direct-to-patient sale, use of social media marketing, and the site's compliance status with external monitoring bodies. Number of recalled drugs marketed as available for purchase on the Internet. We identified 16 class I equivalent permanently recalled or restricted drugs, 56.3 % (n = 9) of which maintained market authorization in either China or India. Half (n = 8) were marketed for sale online without a prescription direct-to-patient. Use of social media marketing was mixed, with only 18.8 % (n = 3) of recalled drugs having a presence on Facebook, though 50.0 % (n = 8) had content on Twitter. We also found the majority (68.8 %, n = 11) were available and marketed for sale by vendors on the wholesale/business-to-business website alibaba.com primarily as active pharmaceutical ingredient. Despite efforts in several countries to restrict access to these drugs or permanently remove them from the market, our study indicates that various sources actively market recalled drugs for sale online. Drug regulators, public health agencies, and law enforcement officials should act with urgency to appropriately restrict and regulate these sales to protect global patients and consumers.

Adolescent dosing and labeling since the Food and Drug Administration Amendments Act of 2007.

PubMed

Momper, Jeremiah D; Mulugeta, Yeruk; Green, Dionna J; Karesh, Alyson; Krudys, Kevin M; Sachs, Hari C; Yao, Lynn P; Burckart, Gilbert J

2013-10-01

During pediatric drug development, dedicated pharmacokinetic studies are generally performed in all relevant age groups to support dose selection for subsequent efficacy trials. To our knowledge, no previous assessments regarding the need for an intensive pharmacokinetic study in adolescents have been performed. To compare U.S. Food and Drug Administration (FDA)-approved adult and adolescent drug dosing and to assess the utility of allometric scaling for the prediction of drug clearance in the adolescent population. Adult and adolescent dosing and drug clearance data were obtained from FDA-approved drug labels and publicly available databases containing reviews of pediatric trials submitted to the FDA. Dosing information was compared for products with concordant indications for adolescent and adult patients. Adolescent drug clearance was predicted from adult pharmacokinetic data by using allometric scaling and compared with observed values. Adolescent and adult dosing information and drug clearance. There were 126 unique products with pediatric studies submitted to the FDA since the FDA Amendments Act of 2007, of which 92 had at least 1 adolescent indication concordant with an adult indication. Of these 92 products, 87 (94.5%) have equivalent dosing for adults and adolescent patients. For 18 of these 92 products, a minimum weight or body surface area threshold is recommended for adolescents to receive adult dosing. Allometric scaling predicted adolescent drug clearance with an overall mean absolute percentage error of 17.0%. Approved adult and adolescent drug dosing is equivalent for 94.5% of products with an adolescent indication studied since the FDA Amendments Act of 2007. Allometric scaling may be a useful tool to avoid unnecessary dedicated pharmacokinetic studies in the adolescent population during pediatric drug development, although each development program in adolescents requires a full discussion of drug dosing with the FDA.

Protein Complex Production from the Drug Discovery Standpoint.

PubMed

Moarefi, Ismail

2016-01-01

Small molecule drug discovery critically depends on the availability of meaningful in vitro assays to guide medicinal chemistry programs that are aimed at optimizing drug potency and selectivity. As it becomes increasingly evident, most disease relevant drug targets do not act as a single protein. In the body, they are instead generally found in complex with protein cofactors that are highly relevant for their correct function and regulation. This review highlights selected examples of the increasing trend to use biologically relevant protein complexes for rational drug discovery to reduce costly late phase attritions due to lack of efficacy or toxicity.

Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals.

PubMed

Ahmed, Asma; Felmlee, Daniel J

2015-12-18

There has been a remarkable transformation in the treatment of chronic hepatitis C in recent years with the development of direct acting antiviral agents targeting virus encoded proteins important for viral replication including NS3/4A, NS5A and NS5B. These agents have shown high sustained viral response (SVR) rates of more than 90% in phase 2 and phase 3 clinical trials; however, this is slightly lower in real-life cohorts. Hepatitis C virus resistant variants are seen in most patients who do not achieve SVR due to selection and outgrowth of resistant hepatitis C virus variants within a given host. These resistance associated mutations depend on the class of direct-acting antiviral drugs used and also vary between hepatitis C virus genotypes and subtypes. The understanding of these mutations has a clear clinical implication in terms of choice and combination of drugs used. In this review, we describe mechanism of action of currently available drugs and summarize clinically relevant resistance data.

2010 drug packaging review: identifying problems to prevent errors.

PubMed

2011-06-01

Prescrire's analyses showed that the quality of drug packaging in 2010 still left much to be desired. Potentially dangerous packaging remains a significant problem: unclear labelling is source of medication errors; dosing devices for some psychotropic drugs create a risk of overdose; child-proof caps are often lacking; and too many patient information leaflets are misleading or difficult to understand. Everything that is needed for safe drug packaging is available; it is now up to regulatory agencies and drug companies to act responsibly. In the meantime, health professionals can help their patients by learning to identify the pitfalls of drug packaging and providing safe information to help prevent medication errors.

Preclinical assessment of abuse liability of biologics: In defense of current regulatory control policies.

PubMed

Gauvin, David V; Zimmermann, Zachary J; Baird, Theodore J

2015-10-01

Current regulatory policies of both the US Food and Drug Administration and Drug Enforcement Administration do not delineate automatic exceptions for biologics with respect to preclinical assessments for abuse liability of all new entities. As defined in current guidance documents and drug control policies, an exception may be given upon thorough review of available data, therapeutic target and in consultation with the Controlled Substances Staff within the Center for Drug Evaluation and Research of the FDA, but a blanket exception for all biological entities is not currently available. We review the abuse liability testing of four known biologics with definitive positive abuse liability signals in the three core abuse liability assays, self-administration, drug discrimination, and dependence potential described in the FDA draft guidance document. Interestingly, while all four examplars have positive abuse liability signals in all three assays, two of these biologics are controlled under the Comprehensive Drug Abuse and Control Act (CSA, 1970) and the other two are not currently controlled. Admittedly, these four biologics are small molecule entities. However, there is no reference to "molecular size" in the legally-binding statutory definition of biologics under the FD&C act or in the Controlled Substances Act. Neither of these drug control policy mandates have a bifurcated control status in which to make exceptions based solely on molecular size. With the current pharmaceutical focus on new technologies, such as "Trojan Horses", targeting the active transport of large molecule entities directly into the CNS, an argument to automatically exempt new molecular entities solely on molecular size is untenable. We argue that for the safety and health of general public the current regulatory control status be maintained until definitive criteria for exceptions can be identified and amended to both the FD&CA and CSA, if warranted. Copyright © 2015 Elsevier Inc. All rights reserved.

Neuronal plasticity and neurotrophic factors in drug responses

PubMed Central

Castrén, Eero; Antila, Hanna

2017-01-01

Neurotrophic factors, particularly brain-derived neurotrophic factor (BDNF) and other members of the neurotrophin family, are central mediators of the activity-dependent plasticity through which environmental experiences, such as sensory information are translated into the structure and function of neuronal networks. Synthesis, release and action of BDNF is regulated by neuronal activity and BDNF in turn leads to trophic effects such as formation, stabilization and potentiation of synapses through its high-affinity TrkB receptors. Several clinically available drugs directly activate neurotrophins and neuronal plasticity. In particular, antidepressant drugs rapidly activate TrkB signaling and gradually increase BDNF expression, and the behavioral effects of antidepressants are mediated by and dependent on BDNF signaling through TrkB at least in rodents. These findings indicate that antidepressants, widely used drugs, effectively act as TrkB activators. They further imply that neuronal plasticity is a central mechanism in the action of antidepressant drugs. Indeed, it was recently discovered that antidepressants reactivate a state of plasticity in the adult cerebral cortex that closely resembles the enhanced plasticity normally observed during postnatal critical periods. This state of induced plasticity, known as iPlasticity, allows environmental stimuli to beneficially reorganize networks abnormally wired during early life. iPlasticity has been observed in cortical as well as subcortical networks and is induced by several pharmacological and non-pharmacological treatments. iPlasticity is a new pharmacological principle where drug treatment and rehabilitation cooperate: the drug acts permissively to enhance plasticity and rehabilitation provides activity to guide the appropriate wiring of the plastic network. Optimization of iPlastic drug treatment with novel means of rehabilitation may help improve the efficacy of available drug treatments and expand the use of currently existing drugs into new indications. PMID:28397840

Effect of the market withdrawal of carisoprodol on use of other prescribed drugs with abuse potential.

PubMed

Bramness, J G; Furu, K; Skurtveit, S; Engeland, A

2012-03-01

Carisoprodol, a centrally acting muscle relaxant indicated for acute lower back pain, has been available in Europe and the United States since 1959. Studies indicating increased risk of abuse or addiction led to withdrawal of the drug from the market in Norway and other EU countries in 2008. In this nationwide longitudinal prescription study of 53,116 individuals in Norway, previous users of carisoprodol switched, to a limited extent, to other prescribed drugs with abuse potential after the withdrawal.

The use of paediatric artemisinin combinations in sub-Saharan Africa: a snapshot questionnaire survey of health care personnel

PubMed Central

2011-01-01

Background Paediatric drug formulations for artemisinin combination therapy (P-ACT) have been developed over the past few years and have been shown to improve the therapeutic management of young children with uncomplicated falciparum malaria. This process was however not equally paralleled by a timely adoption of P-ACT in national and international treatment recommendations. National malaria programmes in sub-Saharan Africa have not yet widely embraced this new therapeutic tool. To which extent P-ACT is used in the field in sub-Saharan Africa is not known to date. Methods This snapshot questionnaire survey aimed to provide an overview on the current routine practices for the availability and use of P-ACT as anti-malarial treatment for young children in sub-Saharan Africa. Health care personnel in seven countries in West-, Central, and East-Africa were invited to answer a structured questionnaire assessing use and availability of P-ACT. Results A total of 71 respondents including doctors, nurses and pharmacy personnel responsible for the anti-malarial treatment of young children were interviewed. P-ACT was used by 83% (95% confidence interval: 73-90%; n = 59) as first-line treatment for young children. Use of 15 different P-ACT products was reported among which only two have received WHO prequalification status and approval by a stringent registration authority. Use of a specific P-ACT product was not linked to consumer prices or availability of supporting clinical trial data, but may depend more on the marketing capacity of the manufacturer. Major differences in frequency and dosing of anti-malarial regimens with identical anti-malarial compounds and the marketing of loose combinations were recorded. Conclusion Paediatric ACT is widely used for the treatment of uncomplicated malaria in young children. However, the majority of P-ACT formulations in use do not meet highest international quality standards evoking concerns for patients' safety and the induction of drug resistance. Improving the quality of currently marketed P-ACT should constitute a public health priority besides their adoption into official treatment recommendations. PMID:22168234

19 CFR 147.23 - Compliance with Plant Quarantine Act and Federal Food, Drug, and Cosmetic Act.

Code of Federal Regulations, 2010 CFR

2010-04-01

... the plant quarantine regulations. (b) Federal Food, Drug, and Cosmetic Act. The entry of food products... Food, Drug, and Cosmetic Act. 147.23 Section 147.23 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION... Laws § 147.23 Compliance with Plant Quarantine Act and Federal Food, Drug, and Cosmetic Act. (a) Plant...

19 CFR 147.23 - Compliance with Plant Quarantine Act and Federal Food, Drug, and Cosmetic Act.

Code of Federal Regulations, 2011 CFR

2011-04-01

... the plant quarantine regulations. (b) Federal Food, Drug, and Cosmetic Act. The entry of food products... Food, Drug, and Cosmetic Act. 147.23 Section 147.23 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION... Laws § 147.23 Compliance with Plant Quarantine Act and Federal Food, Drug, and Cosmetic Act. (a) Plant...

19 CFR 147.23 - Compliance with Plant Quarantine Act and Federal Food, Drug, and Cosmetic Act.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Food, Drug, and Cosmetic Act. 147.23 Section 147.23 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION... Laws § 147.23 Compliance with Plant Quarantine Act and Federal Food, Drug, and Cosmetic Act. (a) Plant... the plant quarantine regulations. (b) Federal Food, Drug, and Cosmetic Act. The entry of food products...

19 CFR 147.23 - Compliance with Plant Quarantine Act and Federal Food, Drug, and Cosmetic Act.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Food, Drug, and Cosmetic Act. 147.23 Section 147.23 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION... Laws § 147.23 Compliance with Plant Quarantine Act and Federal Food, Drug, and Cosmetic Act. (a) Plant... the plant quarantine regulations. (b) Federal Food, Drug, and Cosmetic Act. The entry of food products...

19 CFR 147.23 - Compliance with Plant Quarantine Act and Federal Food, Drug, and Cosmetic Act.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Food, Drug, and Cosmetic Act. 147.23 Section 147.23 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION... Laws § 147.23 Compliance with Plant Quarantine Act and Federal Food, Drug, and Cosmetic Act. (a) Plant... the plant quarantine regulations. (b) Federal Food, Drug, and Cosmetic Act. The entry of food products...

Current Drug Targets in Obesity Pharmacotherapy - A Review.

PubMed

Bhat, Sangeeta P; Sharma, Arun

2017-01-01

Obesity, an impending global pandemic, is not being effectively controlled by current measures such as lifestyle modifications, bariatric surgery or available medications. Its toll on health and economy compels us to look for more effective measures. Fortunately, the advances in biology and molecular technology have been in our favour for delineating new pathways in the pathophysiology of obesity and have led to subsequent development of new drug targets. Development of antiobesity drugs has often been riddled with problems in the past. Some of the recently approved drugs for pharmacotherapy of obesity have been lorcaserin, phentermine/topiramate and naltrexone/ bupropion combinations. Several promising new targets are currently being evaluated, such as amylin analogues (pramlintide, davalintide), leptin analogues (metreleptin), GLP-1 analogues (exenatide, liraglutide, TTP-054), MC4R agonists (RM-493), oxyntomodulin analogues, neuropeptide Y antagonists (velneperit), cannabinoid type-1 receptor blockers (AM-6545), MetAP2 inhibitors (beloranib), lipase inhibitors (cetilistat) and anti-obesity vaccines (ghrelin, somatostatin, Ad36). Many of these groups of drugs act as "satiety signals" while others act by antagonizing orexigenic signals, increasing fat utilisation and decreasing absorption of fats. Since these targets act through various pathways, the possibility of combined use of two or more classes of these drugs unlocks numerous therapeutic avenues. Hence, the dream of personalized management of obesity might be growing closer to reality. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Evidence for Pyronaridine as a Highly Effective Partner Drug for Treatment of Artemisinin-Resistant Malaria in a Rodent Model

PubMed Central

Henrich, Philipp P.; O'Brien, Connor; Sáenz, Fabián E.; Cremers, Serge; Kyle, Dennis E.

2014-01-01

The increasing prevalence in Southeast Asia of Plasmodium falciparum infections with delayed parasite clearance rates, following treatment of malaria patients with the artemisinin derivative artesunate, highlights an urgent need to identify which of the currently available artemisinin-based combination therapies (ACTs) are most suitable to treat populations with emerging artemisinin resistance. Here, we demonstrate that the rodent Plasmodium berghei SANA strain has acquired artemisinin resistance following drug pressure, as defined by reduced parasite clearance and early recrudescence following daily exposure to high doses of artesunate or the active metabolite dihydroartemisinin. Using the SANA strain and the parental drug-sensitive N strain, we have interrogated the antimalarial activity of five ACTs, namely, artemether-lumefantrine, artesunate-amodiaquine, artesunate-mefloquine, dihydroartemisinin-piperaquine, and the newest combination artesunate-pyronaridine. By monitoring parasitemia and outcome for 30 days following initiation of treatment, we found that infections with artemisinin-resistant P. berghei SANA parasites can be successfully treated with artesunate-pyronaridine used at doses that are curative for the parental drug-sensitive N strain. No other partner drug combination was as effective in resolving SANA infections. Of the five partner drugs tested, pyronaridine was also the most effective at suppressing the recrudescence of SANA parasites. These data support the potential benefit of implementing ACTs with pyronaridine in regions affected by artemisinin-resistant malaria. PMID:24145526

Subsidising artemisinin-based combination therapy in the private retail sector

PubMed Central

Opiyo, Newton; Yamey, Gavin; Garner, Paul

2016-01-01

Background Malaria causes ill health and death in Africa. Treating illness promptly with artemisinin-based combination therapy (ACT) is likely to cure people and avoid the disease progressing to more severe forms and death. In many countries, ACT use remains low. Part of the problem is that most people seek treatment from the retail sector where ACTs are expensive; this expense is a barrier to their use. The Global Fund and other international organisations are subsidising the cost of ACTs for private retail providers to improve access to ACTs. The subsidy was initially organised through a stand-alone initiative, called the Affordable Medicines Facility-malaria (AMFm), but has since been integrated into the Global Fund core grant management and financial processes. Objectives To assess the effect of programmes that include ACT price subsidies for private retailers on ACT use, availability, price and market share. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 1, The Cochrane Library, including the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register); MEDLINE (OvidSP), EMBASE (OvidSP), CINAHL (EbscoHost), EconLit (ProQuest), Global Health (OvidSP), Regional Indexes (Global Health Library, WHO), LILACS (Global Health Library, WHO), Science Citation Index and Social Sciences Citation Index (ISI Web of Science) and Health Management (ProQuest). All databases were searched February 2015, except for Health Management which was searched November 2013, without any date, language or publication status restrictions. We also searched the International Clinical Trials Registry Platform (ICTRP; WHO), ClinicalTrials.gov (NIH) and various grey literature sources. We also conducted a cited reference search for all included studies in ISI Web of Knowledge, checked references of identified articles and contacted authors to identify additional studies. Selection criteria Randomised trials, non-randomised trials, controlled before-after studies and interrupted-time-series studies that compared the effects of ACT price subsidies for private retailers to no subsidies or alternative ACT financing mechanisms were eligible for inclusion. Two authors independently screened and selected studies for inclusion. Data collection and analysis Two review authors independently extracted data, assessed study risk of bias and confidence in effect estimates (certainty of evidence) using Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Main results We included four trials (two cluster-randomised trials reported in three articles and two non-randomised cluster trials). Three trials assessed retail sector ACT subsidies combined with supportive interventions (retail outlet provider training, community awareness and mass media campaigns). One trial assessed vouchers provided to households to purchase subsidised ACTs. Price subsidies ranged from 80% to 95%. One trial enrolled children under five years of age; the other three trials studied people of all age groups. The studies were done in rural districts in East Africa (Kenya, Uganda and Tanzania). In this East Africa setting, these ACT subsidy programmes increased the percentage of children under five years of age receiving ACTs on the day, or following day, of fever onset by 25 percentage points (95% confidence interval (CI) 14.1 to 35.9 percentage points; 1 study, high certainty evidence). This suggests that in practice, among febrile children under five years of age with an ACT usage rate of 5% without a subsidy, subsidy programmes would increase usage by between 19% and 41% over a one year period. The ACT subsidy programmes increased the percentage of retail outlets stocking ACTs for children under five years of age by 31.9 percentage points (95% CI 26.3 to 37.5 percentage points; 1 study, high certainty evidence). Effects on ACT stocking for patients of any age is unknown because the certainty of evidence was very low. The ACT subsidy programmes decreased the median cost of ACTs for children under five years of age by US$ 0.84 (median cost per ACT course without subsidy: US$ 1.08 versus with subsidy: US$ 0.24; 1 study, high certainty evidence). The ACT subsidy programmes increased the market share of ACTs for children under five years of age by between 23.6 and 63.0 percentage points (1 study, high certainty evidence). The ACT subsidy programmes decreased the use of older antimalarial drugs (such as amodiaquine and sulphadoxine-pyrimethamine) among children under five years of age by 10.4 percentage points (95% CI 3.9 to 16.9 percentage points; 1 study, high certainty evidence). None of the three studies of ACT subsidies reported the number of patients treated who had confirmed malaria. Vouchers increased the likelihood that an illness is treated with an ACT by 16 to 23 percentage points; however, vouchers were associated with a high rate of over-treatment of malaria (only 56% of patients taking ACTs from the drug shop tested positive for malaria under the 92% subsidy; 1 study, high certainty evidence). Authors' conclusions Programmes that include substantive subsidies for private sector retailers combined with training of providers and social marketing improved use and availability of ACTs for children under five years of age with suspected malaria in research studies from three countries in East Africa. These programmes also reduced prices of ACTs, improved market share of ACTs and reduced the use of older antimalarial drugs among febrile children under five years of age. The research evaluates drug delivery but does not assess whether the patients had confirmed (parasite-diagnosed) malaria. None of the included studies assessed patient outcomes; it is therefore not known whether the effects seen in the studies would translate to an impact on health. PLAIN LANGUAGE SUMMARY Subsidising artemisinin-based combination therapy in drug shops and pharmacies We conducted a review of the effect of subsidising artemisinin-based combination therapy (ACT) drugs for malaria. We searched for all relevant studies up to February 2015 and identified four. Our findings are summarised below. Background Malaria causes ill health and death in Africa, particularly in children under five years of age and poor rural populations. The World Health Organization recommends that people use ACT to treat malaria. ACT drugs are available at shops and pharmacies, but these drugs are expensive and people often choose cheaper, older, less effective drugs instead. The Global Fund and other international organisations have therefore decided to subsidise the cost of ACT drugs so that people can buy them from shops and pharmacies at prices similar to, or lower than, those of the older, less effective drugs. What is the effect of delivery programmes that subsidise ACT prices? We included four studies. One study looked at the effect of subsidising ACT drugs for children under five years of age and three studies looked at subsidising ACT drugs for people of all ages. All studies were from rural districts in East Africa (Kenya, Uganda and Tanzania). ACT price subsidies were accompanied with activities (such as staff training at shops and pharmacies, community awareness and mass media campaigns) to promote appropriate use of antimalarial drugs in all except one study. In all four studies, the effect of subsidising the drugs was compared to not subsidising the drugs. Price subsidies ranged from 80% to 95% of the actual price; vouchers to households were used in one study. The findings from these studies indicate that ACT subsidy programmes: lead to a substantial increase in the number of children under five years of age who used ACTs when they had a fever (high certainty evidence); lead to a substantial increase in the number of shops that stocked ACTs for children under five years of age (high certainty evidence); we could not draw any conclusion on the effect on the number of shops that stocked ACTs for patients of any age because the quality of evidence was very low; lead to a substantial decrease in the price of ACTs for children under five years of age (high certainty evidence); lead to a substantial increase in the market share of ACTs for children under five years of age (high certainty evidence); and lead to a decrease in the use of older, less effective antimalarials among children under five years of age (high certainty evidence). None of the studies measured whether the subsidy programmes led to any harmful effects (such as the inappropriate use of ACTs, in other words people who receive ACTs but do not actually have malaria). The review findings also showed that subsidising ACT prices using vouchers lead to an increase in the likelihood that an illness was treated with an ACT among people seeking treatment for fever or suspected malaria. However, vouchers also lead to an increase in inappropriate use of ACTs (high certainty evidence). PMID:26954551

Shortage of Peritoneal Dialysis Solution and the Food and Drug Administration's Response.

PubMed

Jensen, Valerie; Throckmorton, Douglas C

2015-08-07

Although the number of new drug shortages has been lower in recent years than in the past, severe shortages have occurred that have affected large numbers of patients. A new law entitled the Food and Drug Administration Safety and Innovation Act was enacted in July of 2012, which requires companies to notify the Food and Drug Administration of anticipated shortages. This notification requirement has allowed the Food and Drug Administration to work closely with manufacturers earlier to mitigate and, often, prevent shortages. However, not all shortages are able to be prevented, and the shortage of peritoneal dialysis solution is one that has had a significant effect on patients. The Food and Drug Administration continues to use all available tools to address this shortage with manufacturers, including temporary availability of imported peritoneal dialysis solution from Ireland. Mitigating shortages is a top priority for the Food and Drug Administration, and communication with all stakeholders is essential. Copyright © 2015 by the American Society of Nephrology.

21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. 1310.11 Section 1310.11 Food and Drugs DRUG ENFORCEMENT... Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. (a) The...

21 CFR 1310.10 - Removal of the exemption of drugs distributed under the Food, Drug and Cosmetic Act.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Removal of the exemption of drugs distributed under the Food, Drug and Cosmetic Act. 1310.10 Section 1310.10 Food and Drugs DRUG ENFORCEMENT... Removal of the exemption of drugs distributed under the Food, Drug and Cosmetic Act. (a) The Administrator...

21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. 1310.11 Section 1310.11 Food and Drugs DRUG ENFORCEMENT... Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. (a) The...

21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. 1310.11 Section 1310.11 Food and Drugs DRUG ENFORCEMENT... Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. (a) The...

21 CFR 1310.10 - Removal of the exemption of drugs distributed under the Food, Drug and Cosmetic Act.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Removal of the exemption of drugs distributed under the Food, Drug and Cosmetic Act. 1310.10 Section 1310.10 Food and Drugs DRUG ENFORCEMENT... Removal of the exemption of drugs distributed under the Food, Drug and Cosmetic Act. (a) The Administrator...

21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. 1310.11 Section 1310.11 Food and Drugs DRUG ENFORCEMENT... Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. (a) The...

21 CFR 21.20 - Procedures for notice of Food and Drug Administration Privacy Act Record Systems.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Administration Privacy Act Record Systems. 21.20 Section 21.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROTECTION OF PRIVACY Food and Drug Administration Privacy Act Record Systems § 21.20 Procedures for notice of Food and Drug Administration Privacy Act Record...

Innovations: Alcohol & drug abuse: Narcotics on the net: the availability of Web sites selling controlled substances.

PubMed

Forman, Robert F

2006-01-01

The Internet is not only a vital medium for communication, entertainment, and commerce, but it is also an outlet for illicit drug sales. Although the U.S. Controlled Substances Act regulates access to certain drugs by requiring prescriptions, unique characteristics of the Internet create significant challenges for the enforcement of U.S. drug policies. In the late 1990s "no prescription Web sites" (NPWs) began to emerge, which allow persons to purchase drugs, such as opiates, without a prescription. Given the likely role of NPWs in increasing prescription drug abuse, health care professionals must develop and disseminate strategies for helping patients who are affected by these Web sites.

Long-acting injectable antipsychotics update: lengthening the dosing interval and expanding the diagnostic indications.

PubMed

Citrome, Leslie

2017-10-01

Long-acting injectable (LAI) antipsychotics are a useful but underutilized option in the management of schizophrenia. Areas covered: This is a narrative review of newer LAI antipsychotics approved by the US Food and Drug Administration and is an update to a previously published review from 2013. Emphasized are new indications and new dosing intervals. Expert commentary: Ensuring that persons receiving oral antipsychotics are aware that LAI antipsychotics are available is important. The use of LAI antipsychotics can decrease the risk of relapse in both first-episode and chronic schizophrenia. Available treatments differ in terms of specific indications, approved injection sites, needle gauge, injection volume, injection interval, requirements for oral supplementation, availability of pre-filled syringes, storage needs, and post-injection observation period, as well as potential drug-drug interactions and commonly encountered adverse reactions. Approved indications have expanded beyond schizophrenia to also include bipolar maintenance (risperidone microspheres and aripiprazole monohydrate) and schizoaffective disorder (paliperidone palmitate monthly). Intervals between injections can be longer than one month (six-week or two-month aripiprazole lauroxil, and three-month paliperidone palmitate). After a review of the evidence-base, guidance is offered on the appropriate selection among the LAI formulations of both first and second-generation antipsychotics.

21 CFR 1310.10 - Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act. 1310.10 Section 1310.10 Food and Drugs DRUG ENFORCEMENT... Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act. (a) The...

21 CFR 1310.10 - Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act. 1310.10 Section 1310.10 Food and Drugs DRUG ENFORCEMENT... Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act. (a) The...

21 CFR 1310.10 - Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act. 1310.10 Section 1310.10 Food and Drugs DRUG ENFORCEMENT... Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act. (a) The...

21 CFR 21.20 - Procedures for notice of Food and Drug Administration Privacy Act Record Systems.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Administration Privacy Act Record Systems. 21.20 Section 21.20 Food and Drugs FOOD AND DRUG ADMINISTRATION... Act Record Systems § 21.20 Procedures for notice of Food and Drug Administration Privacy Act Record... of each year a notice concerning each Privacy Act Record System as defined in § 21.3(c) that is not...

21 CFR 21.20 - Procedures for notice of Food and Drug Administration Privacy Act Record Systems.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Administration Privacy Act Record Systems. 21.20 Section 21.20 Food and Drugs FOOD AND DRUG ADMINISTRATION... Act Record Systems § 21.20 Procedures for notice of Food and Drug Administration Privacy Act Record... of each year a notice concerning each Privacy Act Record System as defined in § 21.3(c) that is not...

21 CFR 21.20 - Procedures for notice of Food and Drug Administration Privacy Act Record Systems.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Administration Privacy Act Record Systems. 21.20 Section 21.20 Food and Drugs FOOD AND DRUG ADMINISTRATION... Act Record Systems § 21.20 Procedures for notice of Food and Drug Administration Privacy Act Record... of each year a notice concerning each Privacy Act Record System as defined in § 21.3(c) that is not...

21 CFR 21.20 - Procedures for notice of Food and Drug Administration Privacy Act Record Systems.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Administration Privacy Act Record Systems. 21.20 Section 21.20 Food and Drugs FOOD AND DRUG ADMINISTRATION... Act Record Systems § 21.20 Procedures for notice of Food and Drug Administration Privacy Act Record... of each year a notice concerning each Privacy Act Record System as defined in § 21.3(c) that is not...

Treatment options for chronic pain management: opioids revisited.

PubMed

Lipman, Arthur G

2007-02-01

Pain is a public health disaster. Although it remains largely undertreated, pharmacists and pharmacy managers can do much to correct the problem. Change will require the education of patients and health care professionals on the facts pertaining to addiction, drug dependence, and drug tolerance. Evidence-based resources, including guidelines published by the APS, should be consulted. A variety of short- and long-acting drugs are available, not the least of which are the opioids. Fears regarding addiction and uncertainty about tolerance have precluded the comprehensive use of these drugs, and varying dose requirements complicate the picture. What is known, however, is that dose titration must be performed with the goal of preventing breakthrough pain. Fortunately, sufficient drug formulae have been developed to accommodate this need. Pain is the primary reason why people come into the health care system, and it is incumbent upon health care professionals to eliminate insufficient pain control, using the drugs available to the patient's best advantage.

21 CFR 872.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 872.9 Section 872.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES DENTAL DEVICES General...

21 CFR 872.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 872.9 Section 872.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES DENTAL DEVICES General...

21 CFR 866.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 866.9 Section 866.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY...

21 CFR 866.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 866.9 Section 866.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY...

21 CFR 866.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 866.9 Section 866.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY...

21 CFR 866.9 - Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act).

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). 866.9 Section 866.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY...

Characterization and comparison of SGLT2 inhibitors: Part 3. Effects on diabetic complications in type 2 diabetic mice.

PubMed

Tahara, Atsuo; Takasu, Toshiyuki; Yokono, Masanori; Imamura, Masakazu; Kurosaki, Eiji

2017-08-15

In this study, we investigated and compared the effects of all six sodium-glucose cotransporter (SGLT) 2 inhibitors commercially available in Japan on diabetes-related diseases and complications in type 2 diabetic mice. Following 4-week repeated administration to diabetic mice, all SGLT2 inhibitors showed significant improvement in diabetes-related diseases and complications, including obesity; abnormal lipid metabolism; steatohepatitis; inflammation; endothelial dysfunction; and nephropathy. While all SGLT2 inhibitors exerted comparable effects in reducing hyperglycemia, improvement of these diabetes-related diseases and complications was more potent with the two long-acting drugs (ipragliflozin and dapagliflozin) than with the four intermediate-acting four drugs (tofogliflozin, canagliflozin, empagliflozin, and luseogliflozin), albeit without statistical significance. These findings demonstrate that SGLT2 inhibitors alleviate various diabetic pathological conditions in type 2 diabetic mice, and suggest that SGLT2 inhibitors, particularly long-acting drugs, might be useful not only for hyperglycemia but also in diabetes-related diseases and complications, including nephropathy in type 2 diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

76 FR 71042 - Scott S. Reuben: Debarment Order

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-16

... drug product under the Federal Food, Drug, and Cosmetic Act. Dr. Reuben was given notice of the... conduct relating to the regulation of a drug product under the Federal Food, Drug, and Cosmetic Act. This... of a drug product under the Federal Food, Drug, and Cosmetic Act. As a result of the foregoing...

Artemisinin-resistant Plasmodium falciparum malaria

PubMed Central

Fairhurst, Rick M.; Dondorp, Arjen M.

2016-01-01

For more than five decades, Southeast Asia (SEA) has been fertile ground for the emergence of drug-resistant Plasmodium falciparum malaria. After generating parasites resistant to chloroquine, sulfadoxine, pyrimethamine, quinine, and mefloquine, this region has now spawned parasites resistant to artemisinins – the world's most potent antimalarial drugs. In areas where artemisinin resistance is prevalent, artemisinin combination therapies (ACTs) – the first-line treatments for malaria – are failing fast. This worrisome development threatens to make malaria practically untreatable in SEA, and threatens to compromise global endeavors to eliminate this disease. A recent series of clinical, in-vitro, genomics, and transcriptomics studies in SEA have defined in-vivo and in-vitro phenotypes of artemisinin resistance; identified its causal genetic determinant; explored its molecular mechanism; and assessed its clinical impact. Specifically, these studies have established that artemisinin resistance manifests as slow parasite clearance in patients and increased survival of early ring-stage parasites in vitro; is caused by single nucleotide polymorphisms in the parasite's ‘K13’ gene; is associated with an upregulated “unfolded protein response” pathway that may antagonize the pro-oxidant activity of artemisinins; and selects for partner drug resistance that rapidly leads to ACT failures. In SEA, clinical studies are urgently needed to monitor ACT efficacy where K13 mutations are prevalent; test whether new combinations of currently-available drugs cure ACT failures; and advance new antimalarial compounds through preclinical pipelines and into clinical trials. Intensifying these efforts should help to forestall the spread of artemisinin and partner drug resistance from SEA to Sub-Saharan Africa, where the world's malaria transmission, morbidity, and mortality rates are highest. PMID:27337450

Artemisinin-Resistant Plasmodium falciparum Malaria.

PubMed

Fairhurst, Rick M; Dondorp, Arjen M

2016-06-01

For more than five decades, Southeast Asia (SEA) has been fertile ground for the emergence of drug-resistant Plasmodium falciparum malaria. After generating parasites resistant to chloroquine, sulfadoxine, pyrimethamine, quinine, and mefloquine, this region has now spawned parasites resistant to artemisinins, the world's most potent antimalarial drugs. In areas where artemisinin resistance is prevalent, artemisinin combination therapies (ACTs)-the first-line treatments for malaria-are failing fast. This worrisome development threatens to make malaria practically untreatable in SEA, and threatens to compromise global endeavors to eliminate this disease. A recent series of clinical, in vitro, genomics, and transcriptomics studies in SEA have defined in vivo and in vitro phenotypes of artemisinin resistance, identified its causal genetic determinant, explored its molecular mechanism, and assessed its clinical impact. Specifically, these studies have established that artemisinin resistance manifests as slow parasite clearance in patients and increased survival of early-ring-stage parasites in vitro; is caused by single nucleotide polymorphisms in the parasite's K13 gene, is associated with an upregulated "unfolded protein response" pathway that may antagonize the pro-oxidant activity of artemisinins, and selects for partner drug resistance that rapidly leads to ACT failures. In SEA, clinical studies are urgently needed to monitor ACT efficacy where K13 mutations are prevalent, test whether new combinations of currently available drugs cure ACT failures, and advance new antimalarial compounds through preclinical pipelines and into clinical trials. Intensifying these efforts should help to forestall the spread of artemisinin and partner drug resistance from SEA to sub-Saharan Africa, where the world's malaria transmission, morbidity, and mortality rates are highest.

Pharmacokinetic considerations for use of artemisinin-based combination therapies against falciparum malaria in different ethnic populations.

PubMed

Sugiarto, Sri Riyati; Davis, Timothy M E; Salman, Sam

2017-11-01

Artemisinin-based combination therapy (ACT) is used extensively as first-line treatment for uncomplicated falciparum malaria. There has been no rigorous assessment of the potential for racial/ethnic differences in the pharmacokinetic properties of ACTs that might influence their efficacy. Areas covered: A comprehensive literature search was performed that identified 72 publications in which the geographical origin of the patients could be ascertained and the key pharmacokinetic parameters maximum drug concentration (C max ), area under the plasma concentration-time curve (AUC) and elimination half-life (t ½β ) were available for one or more of the five WHO-recommended ACTs (artemether-lumefantrine, artesunate-amodiaquine, artesunate-mefloquine, dihydroartemisinin-piperaquine and artesunate-sulfadoxine-pyrimethamine). Comparisons of each of the three pharmacokinetic parameters of interest were made by drug (artemisinin derivative and long half-life partner), race/ethnicity (African, Asian, Caucasian, Melanesian, South American) and patient categories based on age and pregnancy status. Expert opinion: The review identified no evidence of a clinically significant influence of race/ethnicity on the pharmacokinetic properties of the nine component drugs in the five ACTs currently recommended by WHO for first-line treatment of uncomplicated falciparum malaria. This provides reassurance for health workers in malaria-endemic regions that ACTs can be given in recommended doses with the expectation of adequate blood concentrations regardless of race/ethnicity.

Misuse of OTC drugs in Poland.

PubMed

Zaprutko, Tomasz; Koligat, Dorota; Michalak, Michał; Wieczorek, Marta; Józiak, Malwina; Ratajczak, Monika; Szydłowska, Kinga; Miazek, Joanna; Kus, Krzysztof; Nowakowska, Elżbieta

2016-08-01

The misuse of over-the-counter (OTC) drugs became a global public health concern. Although abuse with dextrometorphan (DXM), pseudoefedrine (PSD), codeine (COD) or benzydamine (BND) may lead even to psychosis, drugs containing these substances are relatively cheap and freely available. In Poland the Act on Counteracting Drug Addiction was amended in 2015, however it seems that there are still some points which could be improved. Study was conducted between October 2014 and June 2015 using a specially designed questionnaire delivered to pharmacists from the Greater Poland region. Questionnaire consisting of 11 closed questions was distributed by direct contact and via the Internet. From over 2500 distributed questionnaires, we received 761 sheets and 680 were included. The misuse of OTC drugs is increasing in Poland from pharmacists point of view. The most popular substance was PSD followed by COD and DXM. The main reason of misuse of these drugs could be related to the use of Internet and free access to these medications. In respondents (58.2%) opinion OTC drugs containing analyzed substances should be moved into the prescription status. The misuse of OTC drugs should be considered as a very dangerous phenomenon. Although the Act on Counteracting Drug Addiction was amended in Poland in 2015, there are some facets requiring improvement. Social education may play a key role in the limitation of misuse of OTC drugs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Preparing a prescription drug monitoring program data set for research purposes.

PubMed

O'Kane, Nicole; Hallvik, Sara E; Marino, Miguel; Van Otterloo, Joshua; Hildebran, Christi; Leichtling, Gillian; Deyo, Richard A

2016-09-01

To develop a complete and consistent prescription drug monitoring program (PDMP) data set for use by drug safety researchers in evaluating patterns of high-risk use and potential abuse of scheduled drugs. Using publically available data references from the US Food and Drug Administration and the Centers for Disease Control and Prevention, we developed a strategic methodology to assign drug categories based on pharmaceutical class for the majority of prescriptions in the PDMP data set. We augmented data elements required to calculate morphine milligram equivalents and assigned duration of action (short-acting or long acting) properties for a majority of opioids in the data set. About 10% of prescriptions in the PDMP data set did not have a vendor-assigned drug category, and 20% of opioid prescriptions were missing data needed to calculate risk metrics. Using inclusive methods, 19 133 167 (>99.9%) of prescriptions in the PDMP data set were assigned a drug category. For the opioid category, augmenting data elements resulted in 10 760 669 (99.8%) having required values to calculate morphine milligram equivalents and evaluate duration of action properties. Drug safety researchers who require a complete and consistent PDMP data set can use the methods described here to ensure that prescriptions of interest are assigned consistent drug categories and complete opioid risk variable values. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Antihypertensive drugs.

PubMed

Laurent, Stéphane

2017-10-01

Successful treatment of hypertension is possible with limited side effects given the availability of multiple antihypertensive drug classes. This review describes the various pharmacological classes of antihypertensive drugs, under two major aspects: their mechanisms of action and side effects. The mechanism of action is analysed through a pharmacological approach, i.e. the molecular receptor targets, the various sites along the arterial system, and the extra-arterial sites of action, in order to better understand in which type of hypertension a given pharmacological class of antihypertensive drug is most indicated. In addition, side effects are described and explained through their pharmacological mechanisms, in order to better understand their mechanism of occurrence and in which patients drugs are contra-indicated. This review does not address the effectiveness of monotherapies in large randomized clinical trials and combination therapies, since these are the matters of other articles of the present issue. Five major pharmacological classes of antihypertensive drugs are detailed here: beta-blockers, diuretics, angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, and calcium channel blockers. Four additional pharmacological classes are described in a shorter manner: renin inhibitors, alpha-adrenergic receptor blockers, centrally acting agents, and direct acting vasodilators. Copyright © 2017. Published by Elsevier Ltd.

Working together: Expanding the availability of naloxone for peer administration to prevent opioid overdose deaths in the Australian Capital Territory and beyond.

PubMed

Lenton, Simon; Dietze, Paul; Olsen, Anna; Wiggins, Nicole; McDonald, David; Fowlie, Carrie

2015-07-01

Since the mid-1990s, there have been calls to make naloxone, a prescription-only medicine in many countries, available to heroin and other opioid users and their peers and family members to prevent overdose deaths. In Australia there were calls for a trial of peer naloxone in 2000, yet at the end of that year, heroin availability and harm rapidly declined, and a trial did not proceed. In other countries, a number of peer naloxone programs have been successfully implemented. Although a controlled trial had not been conducted, evidence of program implementation demonstrated that trained injecting drug-using peers and others could successfully administer naloxone to reverse heroin overdose, with few, if any, adverse effects. In 2009 Australian drug researchers advocated the broader availability of naloxone for peer administration in cases of opioid overdose. Industrious local advocacy and program development work by a number of stakeholders, notably by the Canberra Alliance for Harm Minimisation and Advocacy, a drug user organisation, contributed to the rollout of Australia's first prescription naloxone program in the Australian Capital Territory (ACT). Over the subsequent 18 months, prescription naloxone programs were commenced in four other Australian states. The development of Australia's first take-home naloxone program in the ACT has been an 'ice-breaker' for development of other Australian programs. Issues to be addressed to facilitate future scale-up of naloxone programs concern scheduling and cost, legal protections for lay administration, prescribing as a barrier to scale-up; intranasal administration, administration by service providers and collaboration between stakeholders. © 2014 Australasian Professional Society on Alcohol and other Drugs.

Factors Affecting Drug Use During Incarceration: A Cross-Sectional Study of Opioid-Dependent Persons from India.

PubMed

Rao, Ravindra; Mandal, Piyali; Gupta, Rishab; Ramshankar, Prashanth; Mishra, Ashwani; Ambekar, Atul; Jhanjee, Sonali; Dhawan, Anju

2016-02-01

Substance abuse and criminality share a complex relationship. The rates of substance use among the prisoners, and that of criminal acts among substance users in community setting are high. Data from South Asian countries, including from India are inadequate. This study aimed to assess the pattern of criminal acts among opioid-dependent subjects and their substance use pattern in the month before, during and after imprisonment. Using a cross-sectional study design and purposive sampling, opioid-dependent subjects (n=101) attending two community drug treatment clinics who have had any contact with the law were assessed using a specifically-designed tool to record criminal acts and substance use before, during and after last imprisonment. Most subjects (93%) had committed illegal acts in their lifetime. Physical assault was the most common illegal act, while 23% reported selling drugs and 9% reported committing serious crimes. About 95% were arrested and 92% had spent time in police lockups. About 29% were arrested for drugs possession or drug use, and 3% of injecting drug users arrested for carrying injection equipment. About 85% had been imprisoned at least once, of whom 88% used psychoactive substances in the 1-month period before their last imprisonment. Opioids were the most common substances used daily (68%), followed by cannabis (34%) and alcohol (22%). Ninety-seven percent reported the availability of substances in prisons, and 65% also used substances during their last imprisonment. Cannabis (35%) was the most common substances used in prison followed by opioids (19%). Seventy-six percent used substances soon after prison release, and 13% of opioid users experienced opioid overdose soon after prison release. Use of cannabis, injecting drugs, and opioid use before imprisonment were predictors of substance use in prison. Opioid-dependent people have various contacts with the law, including imprisonment. Many users are dependent on substances during prison-entry, which is an important reason for their continued substance use in prisons. There is a need to provide substance abuse treatment across all stages of criminal justice system. Copyright © 2015 Elsevier Inc. All rights reserved.

21 CFR 1210.2 - Scope of act.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Scope of act. 1210.2 Section 1210.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER... MILK ACT General Provisions § 1210.2 Scope of act. The provisions of the act apply to all milk and...

21 CFR 1210.2 - Scope of act.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Scope of act. 1210.2 Section 1210.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER... MILK ACT General Provisions § 1210.2 Scope of act. The provisions of the act apply to all milk and...

The drug-drug interaction potential of antiviral agents for the treatment of chronic hepatitis C infection.

PubMed

Garrison, Kimberly L; German, Polina; Mogalian, Erik; Mathias, Anita

2018-04-25

Several safe and highly-effective directly-acting antiviral drugs for chronic hepatitis C virus (HCV) have been developed and greatly increase the number of treatment options available to successfully treat HCV infection. However, as treatment regimens contain at least two drugs (e.g., sofosbuvir with daclatasvir, simeprevir, ledipasvir, or velpatasvir; elbasvir and grazoprevir) and up to five drugs (ombitasvir/paritaprevir/ritonavir+dasabuvir+ribavirin), the potential for drug-drug interactions (DDI) becomes an important consideration for HCV-infected individuals with comorbidities that require concomitant medications, such as HIV/HCV co-infection or immunosuppression following liver transplantation. This review details the pharmacokinetics and DDI potential of approved DAAs for the treatment of HCV infection. The American Society for Pharmacology and Experimental Therapeutics.

76 FR 79195 - Animal Drug User Fee Act; Reopening of the Comment Period

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0656] Animal Drug User Fee Act; Reopening of the Comment Period AGENCY: Food and Drug Administration, HHS... notice, FDA requested comments on the Animal Drug User Fee Act (ADUFA) program to date and solicited...

The challenges of treating epilepsy with 25 antiepileptic drugs.

PubMed

Santulli, Lia; Coppola, Antonietta; Balestrini, Simona; Striano, Salvatore

2016-05-01

Nowadays a substantial armamentarium of antiepileptic drugs (AEDs) is available, including drugs with different mechanisms of action, pharmacokinetics, efficacy and tolerability; therefore the choice for the right treatment is often challenging. The specific characteristic of the drug, the epileptic syndrome, seizure types and the patient's features need to be taken into consideration driving the choice through available evidence-based studies, which are often lacking for older AEDs. Besides, study conditions in registered clinical trials (RCTs) are quite different from daily clinical practice, which is more complex and various. When dealing with first diagnosed epilepsy, monotherapy is widely accepted as the gold standard option. Likewise, alternative monotherapy should be considered when the first drug treatment fails. However, the association of different AEDs in polytherapy is a common practice. The choice of AEDs used in association is often based on clinical experience or anecdotal observations or small clinical studies. Polytherapy should be as "rational" as possible and consider the mechanism of action, the pharmacokinetic characteristics and the safety of each drug. When dealing with drug resistant patients, clinicians should never give up and consider the use of AEDs acting on new targets. An attempt to come back to a monotherapy or simpler therapeutic regimen should be pursued even in patients who were previously drug resistant. This review will focus on the strategies to treat epilepsy by choosing among 25 available drugs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Medicare and state health care programs: fraud and abuse; safe harbor for federally qualified health centers arrangements under the anti-kickback statute. Final rule.

PubMed

2007-10-04

In accordance with section 431 of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA), this final rule sets forth a safe harbor under the anti-kickback statute to protect certain arrangements involving goods, items, services, donations, and loans provided by individuals and entities to certain health centers funded under section 330 of the Public Health Service Act. The goods, items, services, donations, or loans must contribute to the health center's ability to maintain or increase the availability, or enhance the quality, of services available to a medically underserved population.

A dual drug regimen synergistically blocks human parainfluenza virus infection

NASA Astrophysics Data System (ADS)

Bailly, Benjamin; Dirr, Larissa; El-Deeb, Ibrahim M.; Altmeyer, Ralf; Guillon, Patrice; von Itzstein, Mark

2016-04-01

Human parainfluenza type-3 virus (hPIV-3) is one of the principal aetiological agents of acute respiratory illness in infants worldwide and also shows high disease severity in the elderly and immunocompromised, but neither therapies nor vaccines are available to treat or prevent infection, respectively. Using a multidisciplinary approach we report herein that the approved drug suramin acts as a non-competitive in vitro inhibitor of the hPIV-3 haemagglutinin-neuraminidase (HN). Furthermore, the drug inhibits viral replication in mammalian epithelial cells with an IC50 of 30 μM, when applied post-adsorption. Significantly, we show in cell-based drug-combination studies using virus infection blockade assays, that suramin acts synergistically with the anti-influenza virus drug zanamivir. Our data suggests that lower concentrations of both drugs can be used to yield high levels of inhibition. Finally, using NMR spectroscopy and in silico docking simulations we confirmed that suramin binds HN simultaneously with zanamivir. This binding event occurs most likely in the vicinity of the protein primary binding site, resulting in an enhancement of the inhibitory potential of the N-acetylneuraminic acid-based inhibitor. This study offers a potentially exciting avenue for the treatment of parainfluenza infection by a combinatorial repurposing approach of well-established approved drugs.

Quality of antimalarial drugs and antibiotics in Papua New Guinea: a survey of the health facility supply chain.

PubMed

Hetzel, Manuel W; Page-Sharp, Madhu; Bala, Nancy; Pulford, Justin; Betuela, Inoni; Davis, Timothy M E; Lavu, Evelyn K

2014-01-01

Poor-quality life-saving medicines are a major public health threat, particularly in settings with a weak regulatory environment. Insufficient amounts of active pharmaceutical ingredients (API) endanger patient safety and may contribute to the development of drug resistance. In the case of malaria, concerns relate to implications for the efficacy of artemisinin-based combination therapies (ACT). In Papua New Guinea (PNG), Plasmodium falciparum and P. vivax are both endemic and health facilities are the main source of treatment. ACT has been introduced as first-line treatment but other drugs, such as primaquine for the treatment of P. vivax hypnozoites, are widely available. This study investigated the quality of antimalarial drugs and selected antibiotics at all levels of the health facility supply chain in PNG. Medicines were obtained from randomly sampled health facilities and selected warehouses and hospitals across PNG and analysed for API content using validated high performance liquid chromatography (HPLC). Of 360 tablet/capsule samples from 60 providers, 9.7% (95% CI 6.9, 13.3) contained less, and 0.6% more, API than pharmacopoeial reference ranges, including 29/37 (78.4%) primaquine, 3/70 (4.3%) amodiaquine, and one sample each of quinine, artemether, sulphadoxine-pyrimethamine and amoxicillin. According to the package label, 86.5% of poor-quality samples originated from India. Poor-quality medicines were found in 48.3% of providers at all levels of the supply chain. Drug quality was unrelated to storage conditions. This study documents the presence of poor-quality medicines, particularly primaquine, throughout PNG. Primaquine is the only available transmission-blocking antimalarial, likely to become important to prevent the spread of artemisinin-resistant P. falciparum and eliminating P. vivax hypnozoites. The availability of poor-quality medicines reflects the lack of adequate quality control and regulatory mechanisms. Measures to stop the availability of poor-quality medicines should include limiting procurement to WHO prequalified products and implementing routine quality testing.

Quality of Antimalarial Drugs and Antibiotics in Papua New Guinea: A Survey of the Health Facility Supply Chain

PubMed Central

Hetzel, Manuel W.; Page-Sharp, Madhu; Bala, Nancy; Pulford, Justin; Betuela, Inoni; Davis, Timothy M. E.; Lavu, Evelyn K.

2014-01-01

Background Poor-quality life-saving medicines are a major public health threat, particularly in settings with a weak regulatory environment. Insufficient amounts of active pharmaceutical ingredients (API) endanger patient safety and may contribute to the development of drug resistance. In the case of malaria, concerns relate to implications for the efficacy of artemisinin-based combination therapies (ACT). In Papua New Guinea (PNG), Plasmodium falciparum and P. vivax are both endemic and health facilities are the main source of treatment. ACT has been introduced as first-line treatment but other drugs, such as primaquine for the treatment of P. vivax hypnozoites, are widely available. This study investigated the quality of antimalarial drugs and selected antibiotics at all levels of the health facility supply chain in PNG. Methods and Findings Medicines were obtained from randomly sampled health facilities and selected warehouses and hospitals across PNG and analysed for API content using validated high performance liquid chromatography (HPLC). Of 360 tablet/capsule samples from 60 providers, 9.7% (95% CI 6.9, 13.3) contained less, and 0.6% more, API than pharmacopoeial reference ranges, including 29/37 (78.4%) primaquine, 3/70 (4.3%) amodiaquine, and one sample each of quinine, artemether, sulphadoxine-pyrimethamine and amoxicillin. According to the package label, 86.5% of poor-quality samples originated from India. Poor-quality medicines were found in 48.3% of providers at all levels of the supply chain. Drug quality was unrelated to storage conditions. Conclusions This study documents the presence of poor-quality medicines, particularly primaquine, throughout PNG. Primaquine is the only available transmission-blocking antimalarial, likely to become important to prevent the spread of artemisinin-resistant P. falciparum and eliminating P. vivax hypnozoites. The availability of poor-quality medicines reflects the lack of adequate quality control and regulatory mechanisms. Measures to stop the availability of poor-quality medicines should include limiting procurement to WHO prequalified products and implementing routine quality testing. PMID:24828338

Portugal's 2001 Drugs Liberalisation Policy: A UK Service Provider's Perspective on the Psychoactive Substances Act (2016)

ERIC Educational Resources Information Center

Banbury, Samantha; Lusher, Joanne; Guedelha, Francisco

2018-01-01

The Misuse of Drugs Act (1971) and the Psychoactive Substances Act (2016) both reinforce the criminalisation of drug use in the UK. The Psychoactive Substances Act (2016) has been developed to control and monitor the use of legal highs, particularly in institutions. This study aimed to establish drug service providers' viewpoints on how effective…

Bringing New PET Drugs to Clinical Practice - A Regulatory Perspective

PubMed Central

Hung, Joseph C.

2013-01-01

The regulatory framework for radioactive drugs, in particular those used in positron emission tomography (PET) scans, has been gradually established since the release of the Food and Drug Administration Modernization Act in 1997. Various guidances specially tailored to accommodate special properties of PET drugs have been issued by the Food and Drug Administration (FDA) in order to ensure this valuable technology (i.e., PET molecular imaging) will continue to be available to patients and yet the safety and efficacy of PET drugs are well regulated so that public health will be protected. This article presents several key elements of this regulatory framework for PET drugs. New regulatory avenues proposed by the FDA to facilitate the research and development process to bring more new PET drugs to clinical practice, as well as to foster the opportunity of using “orphan” PET drugs in clinical practice are also discussed in this paper. PMID:24312157

76 FR 32362 - Agency Information Collection Activities: Proposed Collection; Reports and Records Under...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-06

... Drug Marketing Act of 1987 AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food... recordkeeping requirements contained in the regulations implementing the Prescription Drug Marketing Act of 1987... appropriate, and other forms of information technology. Prescription Drug Marketing Act of 1987...

Provisions of Anti-Drug Abuse Amendments Act of 1988 Relating to Drug Law Enforcement. Information Memorandum 89-1.

ERIC Educational Resources Information Center

Matthias, Mary

This document describes major provisions of the Anti-Drug Abuse Amendments Act of 1988, a federal law relating to enforcement of controlled substances laws which authorizes over two billion dollars for anti-drug activities. Provisions of the Act relating primarily to drug abuse education, prevention or treatment and regulation of the manufacture,…

ILLICIT DOPAMINE TRANSIENTS: RECONCILING ACTIONS OF ABUSED DRUGS

PubMed Central

Covey, Dan P.; Roitman, Mitchell F.; Garris, Paul A.

2014-01-01

Phasic increases in brain dopamine are required for cue-directed reward seeking. While compelling within the framework of appetitive behavior, the view that illicit drugs hijack reward circuits by hyper-activating these dopamine transients is inconsistent with established psychostimulant pharmacology. However, recent work reclassifying amphetamine (AMPH), cocaine, and other addictive dopamine-transporter inhibitors (DAT-Is) supports transient hyper-activation as a unifying hypothesis of abused drugs. We argue here that reclassification also identifies generating burst firing by dopamine neurons as a keystone action. Unlike natural rewards, which are processed by sensory systems, drugs act directly on the brain. Consequently, to mimic natural reward and exploit reward circuits, dopamine transients must be elicited de novo. Of available drug targets, only burst firing achieves this essential outcome. PMID:24656971

21 CFR 172.665 - Gellan gum.

Code of Federal Regulations, 2010 CFR

2010-04-01

... used in food in accordance with the following prescribed conditions: (a) The additive is a high... and Records Administration (NARA). For information on the availability of this material at NARA, call... container shall bear, in addition to other information required by the Federal Food, Drug, and Cosmetic Act...

A cross-sectional study of the availability and price of anti-malarial medicines and malaria rapid diagnostic tests in private sector retail drug outlets in rural Western Kenya, 2013.

PubMed

Kioko, Urbanus; Riley, Christina; Dellicour, Stephanie; Were, Vincent; Ouma, Peter; Gutman, Julie; Kariuki, Simon; Omar, Ahmeddin; Desai, Meghna; Buff, Ann M

2016-07-12

Although anti-malarial medicines are free in Kenyan public health facilities, patients often seek treatment from private sector retail drug outlets. In mid-2010, the Affordable Medicines Facility-malaria (AMFm) was introduced to make quality-assured artemisinin-based combination therapy (ACT) accessible and affordable in private and public sectors. Private sector retail drug outlets stocking anti-malarial medications within a surveillance area of approximately 220,000 people in a malaria perennial high-transmission area in rural western Kenya were identified via a census in September 2013. A cross-sectional study was conducted in September-October 2013 to determine availability and price of anti-malarial medicines and malaria rapid diagnostic tests (RDTs) in drug outlets. A standardized questionnaire was administered to collect drug outlet and personnel characteristics and availability and price of anti-malarials and RDTs. Of 181 drug outlets identified, 179 (99 %) participated in the survey. Thirteen percent were registered pharmacies, 25 % informal drug shops, 46 % general shops, 13 % homesteads and 2 % other. One hundred sixty-five (92 %) had at least one ACT type: 162 (91 %) had recommended first-line artemether-lumefantrine (AL), 22 (12 %) had recommended second-line dihydroartemisinin-piperaquine (DHA-PPQ), 85 (48 %) had sulfadoxine-pyrimethamine (SP), 60 (34 %) had any quinine (QN) formulation, and 14 (8 %) had amodiaquine (AQ) monotherapy. The mean price (range) of an adult treatment course for AL was $1.01 ($0.35-4.71); DHA-PPQ was $4.39 ($0.71-7.06); QN tablets were $2.24 ($0.12-4.71); SP was $0.62 ($0.24-2.35); AQ monotherapy was $0.42 ($0.24-1.06). The mean AL price with or without the AMFm logo did not differ significantly ($1.01 and 1.07, respectively; p = 0.45). Only 17 (10 %) drug outlets had RDTs; 149 (84 %) never stocked RDTs. The mean RDT price was $0.92 ($0.24-2.35). Most outlets never stocked RDTs; therefore, testing prior to treatment was unlikely for customers seeking treatment in the private retail sector. The recommended first-line treatment, AL, was widely available. Although SP and AQ monotherapy are not recommended for treatment, both were less expensive than AL, which might have caused preferential use by customers. Interventions that create community demand for malaria diagnostic testing prior to treatment and that increase RDT availability should be encouraged.

New DEA rules expand options for controlled substance disposal.

PubMed

Peterson, David M

2015-03-01

Prescription drug abuse and overdose are rapidly growing problems in the United States. The United States federal Disposal of Controlled Substances Rule became effective 9 October 2014, implementing the Secure and Responsible Drug Disposal Act of 2010 (Disposal Act). These regulations target escalating prescription drug misuse by reducing accumulation of unused controlled substances that may be abused, diverted or accidentally ingested. Clinical areas that can now participate in collecting unused controlled substances include retail pharmacies, hospitals or clinics with an onsite pharmacy, and narcotic treatment programs. Collection methods include placing a controlled substance collection receptacle or instituting a mail-back program. Because prompt onsite destruction of collected items is required of mail-back programs, collection receptacles are more likely to be used in clinical areas. Retail pharmacies and hospitals or clinics with an onsite pharmacy may also place and maintain collection receptacles at long-term care facilities. The Act and Rule are intended to increase controlled substance disposal methods and expand local involvement in collection of unused controlled substances. Potential barriers to participating in controlled substance collection include acquisition of suitable collection receptacles and liners, lack of available space meeting the necessary criteria, lack of employee time for verification and inventory requirements, and program costs.

21 CFR 1210.28 - Permits waiving clause 4, section 2 of the Federal Import Milk Act.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Import Milk Act. 1210.28 Section 1210.28 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION REGULATIONS UNDER THE FEDERAL IMPORT MILK ACT Permit Control § 1210.28 Permits...

21 CFR 1210.28 - Permits waiving clause 4, section 2 of the Federal Import Milk Act.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Import Milk Act. 1210.28 Section 1210.28 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION REGULATIONS UNDER THE FEDERAL IMPORT MILK ACT Permit Control § 1210.28 Permits...

Sign my e-petition to make changes to misuse of drugs act.

PubMed

Griffiths, Matt

2012-02-29

My medicines management article (reflections February 8) highlighted legal muddles over the prescription of controlled drugs. The Medicines Act was amended four years ago to allow independent nurse prescribers to prescribe almost all controlled drugs. But the Misuse of Drugs Act needs to amended to make this legally possible.

77 FR 72359 - Animal Generic Drug User Fee Act; Public Meeting; Request for Comments

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-05

... increase the revenue stream stability and reduce application fee costs. III. What information should you...] Animal Generic Drug User Fee Act; Public Meeting; Request for Comments AGENCY: Food and Drug... announcing the following meeting: Animal Generic Drug User Fee Act. The topic to be discussed is proposed...

28 CFR 0.177 - Applications for orders under the Comprehensive Drug Abuse Prevention and Control Act.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Comprehensive Drug Abuse Prevention and Control Act. 0.177 Section 0.177 Judicial Administration DEPARTMENT OF... the Comprehensive Drug Abuse Prevention and Control Act. Notwithstanding the delegation of functions... authorized to exercise the authority vested in the Attorney General by section 514 of the Comprehensive Drug...

28 CFR 0.177 - Applications for orders under the Comprehensive Drug Abuse Prevention and Control Act.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Comprehensive Drug Abuse Prevention and Control Act. 0.177 Section 0.177 Judicial Administration DEPARTMENT OF... the Comprehensive Drug Abuse Prevention and Control Act. Notwithstanding the delegation of functions... authorized to exercise the authority vested in the Attorney General by section 514 of the Comprehensive Drug...

28 CFR 0.177 - Applications for orders under the Comprehensive Drug Abuse Prevention and Control Act.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Comprehensive Drug Abuse Prevention and Control Act. 0.177 Section 0.177 Judicial Administration DEPARTMENT OF... the Comprehensive Drug Abuse Prevention and Control Act. Notwithstanding the delegation of functions... authorized to exercise the authority vested in the Attorney General by section 514 of the Comprehensive Drug...

28 CFR 0.177 - Applications for orders under the Comprehensive Drug Abuse Prevention and Control Act.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Comprehensive Drug Abuse Prevention and Control Act. 0.177 Section 0.177 Judicial Administration DEPARTMENT OF... the Comprehensive Drug Abuse Prevention and Control Act. Notwithstanding the delegation of functions... authorized to exercise the authority vested in the Attorney General by section 514 of the Comprehensive Drug...

28 CFR 0.177 - Applications for orders under the Comprehensive Drug Abuse Prevention and Control Act.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Comprehensive Drug Abuse Prevention and Control Act. 0.177 Section 0.177 Judicial Administration DEPARTMENT OF... the Comprehensive Drug Abuse Prevention and Control Act. Notwithstanding the delegation of functions... authorized to exercise the authority vested in the Attorney General by section 514 of the Comprehensive Drug...

21 CFR 184.1945 - Vitamin B 12..

Code of Federal Regulations, 2013 CFR

2013-04-01

... incorporated by reference. Copies are available from the National Academy Press, 2101 Constitution Ave. NW....archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html. (c) In accordance with § 184... used in infant formula in accordance with section 412(g) of the Federal Food, Drug, and Cosmetic Act...

21 CFR 184.1945 - Vitamin B12.

Code of Federal Regulations, 2012 CFR

2012-04-01

... incorporated by reference. Copies are available from the National Academy Press, 2101 Constitution Ave. NW....archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html. (c) In accordance with § 184... used in infant formula in accordance with section 412(g) of the Federal Food, Drug, and Cosmetic Act...

The Implementation of Buprenorphine/Naloxone in College Health Practice

ERIC Educational Resources Information Center

DeMaria, Peter A., Jr.; Patkar, Ashwin A.

2008-01-01

Opiate abuse and dependence have become important concerns for college healthcare providers. The passage of the Drug Addiction Treatment Act of 2000 and the approval of the combination buprenorphine/naloxone for office-based treatment of opiate dependence have increased the options available for college students and their healthcare providers. The…

Making the leap from daily oral dosing to long-acting injectables: lessons from the antipsychotics.

PubMed

Remenar, Julius F

2014-06-02

There are now long-acting versions of six antipsychotic drugs on the U.S. market, and with them, five unique combinations of molecular form and delivery strategy long-acting-injectable-antipsychotics (LAIAs) show evidence of reduced relapses of schizophrenia, but their introduction has been slow, taking at least nine years after the approval of each oral drug. Oily solutions of lipophilic prodrugs were the first to enter the LAIA market, but they relied on esterification of a hydroxyl handle that was lost with the emergence of the atypical antipsychotics. A review of the literature and patents shows that companies tested many different approaches before reaching the currently marketed versions, including aqueous suspensions of poorly soluble salts, polymeric microspheres, and new approaches to making prodrugs. Yet, very little has been published to support faster development of safe long-acting injectables (LAIs). This review introduces some of the critical considerations in creating an LAI; then it analyzes the existing products and discusses areas where further research is needed. The available literature suggests that lipophilic prodrugs may be inherently safer than poorly soluble salts as LAIs. Other areas needing additional study include (1) the range of physical properties acceptable for LAIs and the effect of prodrug tail length in achieving them, and (2) the role of physiological responses at the injection site in the release of drug from a depot.

21 CFR 1210.27 - Permits waiving clauses 2 and 5, section 2 of the Federal Import Milk Act.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Federal Import Milk Act. 1210.27 Section 1210.27 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION REGULATIONS UNDER THE FEDERAL IMPORT MILK ACT Permit Control § 1210.27...

21 CFR 1210.27 - Permits waiving clauses 2 and 5, section 2 of the Federal Import Milk Act.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Federal Import Milk Act. 1210.27 Section 1210.27 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION REGULATIONS UNDER THE FEDERAL IMPORT MILK ACT Permit Control § 1210.27...

78 FR 60288 - Agency Information Collection Activities: Proposed Collection; Comment Request; Guidance for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-01

..., and Cosmetic Act AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug... Cosmetic Act (FD&C Act). DATES: Submit either electronic or written comments on the collection of... Petitions for Stay of Action Subject to Section 505(q) of the Federal Food, Drug, and Cosmetic Act--(OMB...

Implementation of the 2011 Reimbursement Act in Poland: Desired and undesired effects of the changes in reimbursement policy.

PubMed

Kawalec, Paweł; Sagan, Anna; Stawowczyk, Ewa; Kowalska-Bobko, Iwona; Mokrzycka, Anna

2016-04-01

The Act of 12 May 2011 on the Reimbursement of Medicines, Foodstuffs Intended for Particular Nutritional Uses and Medical Devices constitutes a major change of the reimbursement policy in Poland. The main aims of this Act were to rationalize the reimbursement policy and to reduce spending on reimbursed drugs. The Act seems to have met these goals: reimbursement policy (including pricing of reimbursed drugs) was overhauled and the expenditure of the National Health Fund on reimbursed drugs saw a significant decrease in the year following the Act's introduction. The annual savings achieved since then (mainly due to the introduction of risk sharing schemes), have made it possible to include new drugs into the reimbursement list and improve access to innovative drugs. However, at the same time, the decrease in prices of reimbursed drugs, that the Act brought about, led to an uncontrolled outflow of some of these drugs abroad and shortages in Poland. This paper analyses the main changes introduced by the Reimbursement Act and their implications. Since the Act came into force relatively recently, its full impact on the reimbursement policy is not yet possible to assess. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

The drug regulatory and review process in Guyana.

PubMed

Woo-Ming, R B

1993-01-01

After the old "Sale of Food and Drugs" Ordinance, Cap. 144 was repealed, the new Food and Drugs Act was enacted in 1971. This new Act has considerable flexibility and gives the Minister extensive authority to make Regulations (for carrying out the purposes and provisions of the Act). The Act controls the manufacture, importation, sale, advertising, labeling, packaging, and distribution of drug samples, and the testing of drugs. The Act also controls raw materials and finished products of drugs at the point of entry into the country, with a single agency coordinating both the inspection and analytical services. Developing countries could ensure the procurement of safe, good quality, and effective drugs and devices with the enactment of a similar Food and Drugs Act only. Rapid assessment of Drug Safety, Quality and Efficacy is done through Guyana's participation in the WHO Certification Scheme on the Quality of Pharmaceutical Products moving in International Commerce. This certification scheme is highly commendable especially to third-world countries. The Food and Drug Regulations (1977) have several unique features for drug, cosmetic and device control and they allow for a system of centralized control with limited staff to enforce the legislation. In summary, enforcement of legislative control of imported pharmaceuticals and product evaluation can be considered strong points in the drug regulatory and review process in Guyana. A cautious attitude is observed so as to ensure efficacy, safety, and quality of drugs entering the market. This Drug Regulatory and Review Process is recommended for implementation by third-world countries with outdated drug legislation.(ABSTRACT TRUNCATED AT 250 WORDS)

High-mix insulins

PubMed Central

Kalra, Sanjay; Farooqi, Mohammad Hamed; El-Houni, Ali E.

2015-01-01

Premix insulins are commonly used insulin preparations, which are available in varying ratios of different molecules. These drugs contain one short- or rapid-acting, and one intermediate- or long-acting insulin. High-mix insulins are mixtures of insulins that contain 50% or more than 50% of short-acting insulin. This review describes the clinical pharmacology of high-mix insulins, including data from randomized controlled trials. It suggests various ways, in which high-mix insulin can be used, including once daily, twice daily, thrice daily, hetero-mix, and reverse regimes. The authors provide a rational framework to help diabetes care professionals, identify indications for pragmatic high-mix use. PMID:26425485

Treatment of hypopituitarism in patients receiving antiepileptic drugs.

PubMed

Paragliola, Rosa Maria; Prete, Alessandro; Kaplan, Peter W; Corsello, Salvatore Maria; Salvatori, Roberto

2015-02-01

Evidence suggests that there may be drug interactions between antiepileptic drugs and hormonal therapies, which can present a challenge to endocrinologists dealing with patients who have both hypopituitarism and neurological diseases. Data are scarce for this subgroup of patients; however, data for the interaction of antiepileptic drugs with the pituitary axis have shown that chronic use of many antiepileptic drugs, such as carbamazepine, oxcarbazepine, and topiramate, enhances hepatic cytochrome P450 3A4 (CYP3A4) activity, and can decrease serum concentrations of sex hormones. Other antiepileptic drugs increase sex hormone-binding globulin, which reduces the bioactivity of testosterone and estradiol. Additionally, the combined oestrogen-progestagen contraceptive pill might decrease lamotrigine concentrations, which could worsen seizure control. Moreover, sex hormones and their metabolites can directly act on neuronal excitability, acting as neurosteroids. Because carbamazepine and oxcarbazepine can enhance the sensitivity of renal tubules, a reduction in desmopressin dose might be necessary in patients with central diabetes insipidus. Although the effects of antiepileptic drugs in central hypothyroidism have not yet been studied, substantial evidence indicates that several antiepileptic drugs can increase thyroid hormone metabolism. However, although it is reasonable to expect a need for a thyroxine dose increase with some antiepileptic drugs, the effect of excessive thyroxine in lowering seizure threshold should also be considered. There are no reports of significant interactions between antiepileptic drugs and the efficacy of human growth hormone therapy, and few data are available for the effects of second-generation antiepileptic drugs on hypopituitarism treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

The effects of heroin administration and drug cues on impulsivity.

PubMed

Jones, Jermaine D; Vadhan, Nehal P; Luba, Rachel R; Comer, Sandra D

2016-08-01

Drug addiction is a chronic relapsing disorder characterized by compulsive drug seeking and continued use despite negative consequences. Behavioral impulsivity is a strong predictor of the initiation and maintenance of drug addiction. Preclinical data suggest that heroin may exacerbate impulsive characteristics in an individual but this has yet to be assessed in clinical samples. The current secondary data analysis sought to investigate the effects of heroin on impulsivity along with the effects of exposure to drug cues. Using the current data set, we also tentatively assessed the etiological relationship between impulsivity and heroin abuse. Sixteen heroin-dependent participants were recruited to complete Immediate Memory Task/Delayed Memory Task (IMT/DMT) and GoStop tasks following repeated heroin administration, following acute heroin administration, and following a drug cue exposure session. Four preceding days of active heroin availability, compared to four preceding days of placebo drug availability, increased impulsivity assessed using the IMT and DMT. Presentation of drug cues similarly acted to increase impulsivity assessments on all three tasks. It also appears that heavier users were more susceptible to the influence of drug cues on impulsivity. The present study represents a step toward a more comprehensive understanding of the interaction between opioid abuse and impulsivity. A better understanding of these factors could provide critical insight into the maintenance of heroin use and relapse.

Illicit dopamine transients: reconciling actions of abused drugs.

PubMed

Covey, Dan P; Roitman, Mitchell F; Garris, Paul A

2014-04-01

Phasic increases in brain dopamine are required for cue-directed reward seeking. Although compelling within the framework of appetitive behavior, the view that illicit drugs hijack reward circuits by hyperactivating these dopamine transients is inconsistent with established psychostimulant pharmacology. However, recent work reclassifying amphetamine (AMPH), cocaine, and other addictive dopamine-transporter inhibitors (DAT-Is) supports transient hyperactivation as a unifying hypothesis of abused drugs. We argue here that reclassification also identifies generating burst firing by dopamine neurons as a keystone action. Unlike natural rewards, which are processed by sensory systems, drugs act directly on the brain. Consequently, to mimic natural rewards and exploit reward circuits, dopamine transients must be elicited de novo. Of available drug targets, only burst firing achieves this essential outcome. Copyright © 2014 Elsevier Ltd. All rights reserved.

75 FR 78249 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-15

... 505(q) of the Federal Food, Drug, and Cosmetic Act AGENCY: Food and Drug Administration, HHS. ACTION... Petitions for Stay of Action Subject to Section 505(q) of the Federal Food, Drug, and Cosmetic Act.'' Also... Petitions for Stay of Action Subject to Section 505(q) of the Federal Food, Drug, and Cosmetic Act In the...

The Two Faces of Social Interaction Reward in Animal Models of Drug Dependence.

PubMed

El Rawas, Rana; Saria, Alois

2016-03-01

Drug dependence is a serious health and social problem. Social factors can modify vulnerability to developing drug dependence, acting as risk factors or protective factors. Whereas stress and peer environment that encourage substance use may increase drug taking, strong attachments between family members and peer environment that do not experience drug use may protect against drug taking and, ultimately, drug dependence. The rewarding effects of drug abuse and social interaction can be evaluated using animal models. In this review we focus on evaluating social interaction reward in the conditioned place preference paradigm. We give an overview of how social interaction, if made available within the drug context, may facilitate, promote and interact with the drug's effects. However, social interaction, if offered alternatively outside the drug context, may have pronounced protective effects against drug abuse and relapse. We also address the importance of the weight difference parameter between the social partners in determining the positive or "agonistic" versus the hostile or "antagonistic" social interaction. We conclude that understanding social interaction reward and its subsequent effects on drug reward is sorely needed for therapeutic interventions against drug dependence.

77 FR 69488 - Medical Devices; Custom Devices; Request for Comments

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-19

...: Notice; request for comments. SUMMARY: The Food and Drug Administration Safety and Innovation Act (FDASIA... Act). The Food and Drug Administration (FDA) is in the process of developing an implementation... electronically at http://www.regulations.gov . 1. The Food and Drug Administration Safety and Innovation Act...

Safety of the breast-feeding infant after maternal anesthesia.

PubMed

Dalal, Priti G; Bosak, Jodi; Berlin, Cheston

2014-04-01

There has been an increase in breast-feeding supported by the recommendations of the American Academy of Pediatrics and the World Health Organization. An anesthesiologist may be presented with a well-motivated breast-feeding mother who wishes to breast-feed her infant in the perioperative period. Administration of anesthesia entails acute administration of drugs with potential for sedation and respiratory effects on the nursing infant. The short-term use of these drugs minimizes the possibility of these effects. The aim should be to minimize the use of narcotics and benzodiazepines, use shorter acting agents, use regional anesthesia where possible and avoid agents with active metabolites. Frequent clinical assessments of the nursing infant are important. Available literature does suggest that although the currently available anesthetic and analgesic drugs are transferred in the breast milk, the amounts transferred are almost always clinically insignificant and pose little or no risk to the nursing infant. © 2013 John Wiley & Sons Ltd.

Metabolite characterization of a novel sedative drug, remimazolam in human plasma and urine using ultra high-performance liquid chromatography coupled with synapt high-definition mass spectrometry.

PubMed

Zhou, Ying; Hu, Pei; Jiang, Ji

2017-04-15

Remimazolam is a new chemical entity belonging to the benzodiazepine class of sedative drugs, which shows faster-acting onset and recovery than currently available short-acting sedatives. In the present study, ultra high performance liquid chromatography with synapt high-definition mass spectrometry method combined with MassLynx software was established to characterize metabolites of remimazolam in human plasma and urine. In total, 5 human metabolites were detected, including 3 phase I and 2 phase II metabolites. There was no novel human metabolite detected compared to that in rat. Hydrolysis, glucuronidation and oxidation were the major metabolic reactions. To our knowledge, this is the first report of the human metabolic profile of remimazolam. Copyright © 2017 Elsevier B.V. All rights reserved.

Food labeling; nutrition labeling of standard menu items in restaurants and similar retail food establishments. Final rule.

PubMed

2014-12-01

To implement the nutrition labeling provisions of the Patient Protection and Affordable Care Act of 2010 (Affordable Care Act or ACA), the Food and Drug Administration (FDA or we) is requiring disclosure of certain nutrition information for standard menu items in certain restaurants and retail food establishments. The ACA, in part, amended the Federal Food, Drug, and Cosmetic Act (the FD&C Act), among other things, to require restaurants and similar retail food establishments that are part of a chain with 20 or more locations doing business under the same name and offering for sale substantially the same menu items to provide calorie and other nutrition information for standard menu items, including food on display and self-service food. Under provisions of the ACA, restaurants and similar retail food establishments not otherwise covered by the law may elect to become subject to these Federal requirements by registering every other year with FDA. Providing accurate, clear, and consistent nutrition information, including the calorie content of foods, in restaurants and similar retail food establishments will make such nutrition information available to consumers in a direct and accessible manner to enable consumers to make informed and healthful dietary choices.

Naphyrone: a "legal high" not legal any more.

PubMed

Vardakou, Ioanna; Pistos, Constantinos; Dona, Artemis; Spiliopoulou, Chara; Athanaselis, Sotiris

2012-10-01

Naphyrone, also known as naphthylpyrovalerone and O-2482, is a cathinone derivative that has been recently advertized for purchase on a number of websites. Naphyrone belongs to a new class of "designer drugs" that has emerged on the drugs abuse market and has gained popularity as the new "legal high." Legal highs have been circulating for a number of years in Europe and are becoming popular in the United States. They are affordable, widely available, legal to use and possess, and legal to supply. This review presents any available information about safety profile, clinical data, analytical profile, and legislation of this legal high, which is not legal any more. Any available information has been collected by various literature search engines and the World Wide Web. The structure of naphyrone is similar to that of pyrovalerone, a monoamine uptake inhibitor. This new designer drug does not have a long history of use, so there is little evidence of its long-term effects or on the risks from its use. Because of its similarity to other cathinone derivatives, naphyrone is likely to share the same risks, such as anxiety, paranoia, and overstimulation of the heart and circulatory system. Naphyrone was classified as a controlled drug under the UK Misuse of Drugs Act of 1971 (Amendment No. 2) Regulation 2010.

78 FR 15019 - Food and Drug Administration Prescription Drug User Fee Act V Benefit-Risk Plan; Request for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-08

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0196] Food and Drug Administration Prescription Drug User Fee Act V Benefit-Risk Plan; Request for Comments AGENCY: Food and Drug Administration, HHS. ACTION: Notice, request for comments. SUMMARY: The Food and...

21 CFR 341.80 - Labeling of nasal decongestant drug products.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of nasal decongestant drug products. 341.80 Section 341.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN..., subject to the provisions of section 502 of the Federal Food, Drug, and Cosmetic Act (the act) relating to...

21 CFR 341.80 - Labeling of nasal decongestant drug products.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Labeling of nasal decongestant drug products. 341.80 Section 341.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN..., subject to the provisions of section 502 of the Federal Food, Drug, and Cosmetic Act (the act) relating to...

40 CFR 23.10 - Timing of Administrator's action under the Federal Food, Drug, and Cosmetic Act.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Timing of Administrator's action under the Federal Food, Drug, and Cosmetic Act. 23.10 Section 23.10 Protection of Environment ENVIRONMENTAL... action under the Federal Food, Drug, and Cosmetic Act. Unless the Administrator otherwise explicitly...

40 CFR 23.10 - Timing of Administrator's action under the Federal Food, Drug, and Cosmetic Act.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Timing of Administrator's action under the Federal Food, Drug, and Cosmetic Act. 23.10 Section 23.10 Protection of Environment ENVIRONMENTAL... action under the Federal Food, Drug, and Cosmetic Act. Unless the Administrator otherwise explicitly...

40 CFR 23.10 - Timing of Administrator's action under the Federal Food, Drug, and Cosmetic Act.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Timing of Administrator's action under the Federal Food, Drug, and Cosmetic Act. 23.10 Section 23.10 Protection of Environment ENVIRONMENTAL... action under the Federal Food, Drug, and Cosmetic Act. Unless the Administrator otherwise explicitly...

40 CFR 23.10 - Timing of Administrator's action under the Federal Food, Drug, and Cosmetic Act.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Timing of Administrator's action under the Federal Food, Drug, and Cosmetic Act. 23.10 Section 23.10 Protection of Environment ENVIRONMENTAL... action under the Federal Food, Drug, and Cosmetic Act. Unless the Administrator otherwise explicitly...

76 FR 25542 - Information Required in Prior Notice of Imported Food

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-05

..., Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 381(m)) to require that additional information be provided... Subjects in 21 CFR Part 1 Cosmetics, Drugs, Exports, Food labeling, Imports, Labeling, Reporting and recordkeeping requirements. Therefore, under the Federal Food, Drug, and Cosmetic Act and under authority...

40 CFR 23.10 - Timing of Administrator's action under the Federal Food, Drug, and Cosmetic Act.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Timing of Administrator's action under the Federal Food, Drug, and Cosmetic Act. 23.10 Section 23.10 Protection of Environment ENVIRONMENTAL... action under the Federal Food, Drug, and Cosmetic Act. Unless the Administrator otherwise explicitly...

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 opportunity for prevention. PMID:19969578

Administrative Destruction of Certain Drugs Refused Admission to the United States. Final rule.

PubMed

2015-09-15

The Food and Drug Administration (FDA or Agency) is implementing its authority to destroy a drug valued at $2,500 or less (or such higher amount as the Secretary of the Treasury may set by regulation) that has been refused admission into the United States under the Federal Food, Drug, and Cosmetic Act (the FD&C Act), by issuing a rule that provides to the owner or consignee notice and an opportunity to appear and introduce testimony to the Agency prior to destruction. This regulation is authorized by amendments made to the FD&C Act by the Food and Drug Administration Safety and Innovation Act (FDASIA). Implementation of this authority will allow FDA to better protect the public health by providing an administrative process for the destruction of certain refused drugs, thus increasing the integrity of the drug supply chain.

The US Orphan Drug Act: rare disease research stimulator or commercial opportunity?

PubMed

Wellman-Labadie, Olivier; Zhou, Youwen

2010-05-01

This study investigates issues associated with the United States Orphan Drug Act. A comprehensive orphan drug database was compiled from FDA data and corporate annual reports of major pharmaceutical companies. Analysis allowed the generation of a descriptive orphan drug portrait as well as documentation of orphan drugs along their lifecycle. Currently, 2002 products have obtained orphan drug designation with 352 drugs obtaining FDA approval. Approximately 33% of orphan drugs are oncology products. On average, products obtain 1.7 orphan designations with approximately 70% obtaining a single designation. At least 9% of orphan drugs have reached blockbuster status with two-thirds having two or more designations. An additional 25 orphan drugs had sales exceeding US$ 100 million in 2008 alone. Since 1983, at least 14 previously discontinued products have been recycled as orphan drugs. The United States Orphan Drug Act has created issues which, in some cases, have led to commercial and ethical abuses. Orphan Drug Act reform is necessary but current incentives, including 7 year market exclusivity, should be maintained in order to favour patients as well as economic prosperity. Suggested reforms include price regulation, subsidy paybacks for profitable drugs and the establishment of an International Orphan Drug Office. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

78 FR 21085 - Establishment of a Public Docket for Administrative Detention Under the Food and Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-09

... Administration Safety and Innovation Act AGENCY: Food and Drug Administration, HHS. ACTION: Establishment of... authority with respect to drugs under the Food and Drug Administration Safety and Innovation Act (FDASIA....regulations.gov . Submit written comments to the Division of Dockets Management (HFA- 305), Food and Drug...

76 FR 41434 - Removal of Certain Requirements Related to the Prescription Drug Marketing Act; Opportunity for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-14

.... FDA-2011-N-0446] Removal of Certain Requirements Related to the Prescription Drug Marketing Act... Food and Drug Administration (FDA) is proposing to remove a section of the Prescription Drug Marketing... prescription drug marketing and distribution. The primary purpose of the PDMA was to increase safeguards to...

21 CFR 17.1 - Scope.

Code of Federal Regulations, 2010 CFR

2010-04-01

... act that relate to prescription drug marketing practices. (b) Section 303(f)(1) of the act authorizing... mitigation strategies for drugs. (d) Section 303(g)(1) of the act authorizing civil money penalties for...

76 FR 62073 - Guidance for Industry on Implementation of the Fee Provisions of the FDA Food Safety...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0721] Guidance for Industry on Implementation of the Fee Provisions of the FDA Food Safety Modernization Act... Administration (FDA) is announcing the availability of a guidance for industry entitled ``Implementation of the...

Socially-marketed rapid diagnostic tests and ACT in the private sector: ten years of experience in Cambodia.

PubMed

Yeung, Shunmay; Patouillard, Edith; Allen, Henrietta; Socheat, Duong

2011-08-18

Whilst some populations have recently experienced dramatic declines in malaria, the majority of those most at risk of Plasmodium falciparum malaria still lack access to effective treatment with artemisinin combination therapy (ACT) and others are already facing parasites resistant to artemisinins.In this context, there is a crucial need to improve both access to and targeting of ACT through greater availability of good quality ACT and parasitological diagnosis. This is an issue of increasing urgency notably in the private commercial sector, which, in many countries, plays an important role in the provision of malaria treatment. The Affordable Medicines Facility for malaria (AMFm) is a recent initiative that aims to increase the provision of affordable ACT in public, private and NGO sectors through a manufacturer-level subsidy. However, to date, there is little documented experience in the programmatic implementation of subsidized ACT in the private sector. Cambodia is in the unique position of having more than 10 years of experience not only in implementing subsidized ACT, but also rapid diagnostic tests (RDT) as part of a nationwide social marketing programme. The programme includes behaviour change communication and the training of private providers as well as the sale and distribution of Malarine, the recommended ACT, and Malacheck, the RDT. This paper describes and evaluates this experience by drawing on the results of household and provider surveys conducted since the start of the programme. The available evidence suggests that providers' and consumers' awareness of Malarine increased rapidly, but that of Malacheck much less so. In addition, improvements in ACT and RDT availability and uptake were relatively slow, particularly in more remote areas.The lack of standardization in the survey methods and the gaps in the data highlight the importance of establishing a clear system for monitoring and evaluation for similar initiatives. Despite these limitations, a number of important lessons can still be learnt. These include the importance of a comprehensive communications strategy and of a sustained and reliable supply of products, with attention to the geographical reach of both. Other important challenges relate to the difficulty in incentivising providers and consumers not only to choose the recommended drug, but to precede this with a confirmatory blood test and ensure that providers adhere to the test results and patients to the treatment regime. In Cambodia, this is particularly complicated due to problems inherent to the drug itself and the emergence of artemisinin resistance.

Socially-marketed rapid diagnostic tests and ACT in the private sector: ten years of experience in Cambodia

PubMed Central

2011-01-01

Whilst some populations have recently experienced dramatic declines in malaria, the majority of those most at risk of Plasmodium falciparum malaria still lack access to effective treatment with artemisinin combination therapy (ACT) and others are already facing parasites resistant to artemisinins. In this context, there is a crucial need to improve both access to and targeting of ACT through greater availability of good quality ACT and parasitological diagnosis. This is an issue of increasing urgency notably in the private commercial sector, which, in many countries, plays an important role in the provision of malaria treatment. The Affordable Medicines Facility for malaria (AMFm) is a recent initiative that aims to increase the provision of affordable ACT in public, private and NGO sectors through a manufacturer-level subsidy. However, to date, there is little documented experience in the programmatic implementation of subsidized ACT in the private sector. Cambodia is in the unique position of having more than 10 years of experience not only in implementing subsidized ACT, but also rapid diagnostic tests (RDT) as part of a nationwide social marketing programme. The programme includes behaviour change communication and the training of private providers as well as the sale and distribution of Malarine, the recommended ACT, and Malacheck, the RDT. This paper describes and evaluates this experience by drawing on the results of household and provider surveys conducted since the start of the programme. The available evidence suggests that providers' and consumers' awareness of Malarine increased rapidly, but that of Malacheck much less so. In addition, improvements in ACT and RDT availability and uptake were relatively slow, particularly in more remote areas. The lack of standardization in the survey methods and the gaps in the data highlight the importance of establishing a clear system for monitoring and evaluation for similar initiatives. Despite these limitations, a number of important lessons can still be learnt. These include the importance of a comprehensive communications strategy and of a sustained and reliable supply of products, with attention to the geographical reach of both. Other important challenges relate to the difficulty in incentivising providers and consumers not only to choose the recommended drug, but to precede this with a confirmatory blood test and ensure that providers adhere to the test results and patients to the treatment regime. In Cambodia, this is particularly complicated due to problems inherent to the drug itself and the emergence of artemisinin resistance. PMID:21851625

American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part 2--guidance.

PubMed

Manchikanti, Laxmaiah; Abdi, Salahadin; Atluri, Sairam; Balog, Carl C; Benyamin, Ramsin M; Boswell, Mark V; Brown, Keith R; Bruel, Brian M; Bryce, David A; Burks, Patricia A; Burton, Allen W; Calodney, Aaron K; Caraway, David L; Cash, Kimberly A; Christo, Paul J; Damron, Kim S; Datta, Sukdeb; Deer, Timothy R; Diwan, Sudhir; Eriator, Ike; Falco, Frank J E; Fellows, Bert; Geffert, Stephanie; Gharibo, Christopher G; Glaser, Scott E; Grider, Jay S; Hameed, Haroon; Hameed, Mariam; Hansen, Hans; Harned, Michael E; Hayek, Salim M; Helm, Standiford; Hirsch, Joshua A; Janata, Jeffrey W; Kaye, Alan D; Kaye, Adam M; Kloth, David S; Koyyalagunta, Dhanalakshmi; Lee, Marion; Malla, Yogesh; Manchikanti, Kavita N; McManus, Carla D; Pampati, Vidyasagar; Parr, Allan T; Pasupuleti, Ramarao; Patel, Vikram B; Sehgal, Nalini; Silverman, Sanford M; Singh, Vijay; Smith, Howard S; Snook, Lee T; Solanki, Daneshvari R; Tracy, Deborah H; Vallejo, Ricardo; Wargo, Bradley W

2012-07-01

Part 2 of the guidelines on responsible opioid prescribing provides the following recommendations for initiating and maintaining chronic opioid therapy of 90 days or longer. 1. A) Comprehensive assessment and documentation is recommended before initiating opioid therapy, including documentation of comprehensive history, general medical condition, psychosocial history, psychiatric status, and substance use history. ( good) B) Despite limited evidence for reliability and accuracy, screening for opioid use is recommended, as it will identify opioid abusers and reduce opioid abuse. ( limited) C) Prescription monitoring programs must be implemented, as they provide data on patterns of prescription usage, reduce prescription drug abuse or doctor shopping. ( good to fair) D) Urine drug testing (UDT) must be implemented from initiation along with subsequent adherence monitoring to decrease prescription drug abuse or illicit drug use when patients are in chronic pain management therapy. ( good) 2. A) Establish appropriate physical diagnosis and psychological diagnosis if available prior to initiating opioid therapy. ( good) B) Caution must be exercised in ordering various imaging and other evaluations, interpretation and communication with the patient, to avoid increased fear, activity restriction, requests for increased opioids, and maladaptive behaviors. ( good) C) Stratify patients into one of the 3 risk categories - low, medium, or high risk. D) A pain management consultation, may assist non-pain physicians, if high-dose opioid therapy is utilized. ( fair) 3. Essential to establish medical necessity prior to initiation or maintenance of opioid therapy. ( good) 4. Establish treatment goals of opioid therapy with regard to pain relief and improvement in function. ( good) 5. A) Long-acting opioids in high doses are recommended only in specific circumstances with severe intractable pain that is not amenable to short-acting or moderate doses of long-acting opioids, as there is no significant difference between long-acting and short-acting opioids for their effectiveness or adverse effects. ( fair) B) The relative and absolute contraindications to opioid use in chronic non-cancer pain must be evaluated including respiratory instability, acute psychiatric instability, uncontrolled suicide risk, active or history of alcohol or substance abuse, confirmed allergy to opioid agents, coadministration of drugs capable of inducing life-limiting drug interaction, concomitant use of benzodiazepines, active diversion of controlled substances, and concomitant use of heavy doses of central nervous system depressants. ( fair to limited) 6. A robust agreement which is followed by all parties is essential in initiating and maintaining opioid therapy as such agreements reduce overuse, misuse, abuse, and diversion. ( fair) 7. A) Once medical necessity is established, opioid therapy may be initiated with low doses and short-acting drugs with appropriate monitoring to provide effective relief and avoid side effects. ( fair for short-term effectiveness, limited for long-term effectiveness) B) Up to 40 mg of morphine equivalent is considered as low dose, 41 to 90 mg of morphine equivalent as a moderate dose, and greater than 91 mg of morphine equivalence as high dose. ( fair) C) In reference to long-acting opioids, titration must be carried out with caution and overdose and misuse must be avoided. ( good) 8. A) Methadone is recommended for use in late stages after failure of other opioid therapy and only by clinicians with specific training in the risks and uses. ( limited) B) Monitoring recommendation for methadone prescription is that an electrocardiogram should be obtained prior to initiation, at 30 days and yearly thereafter. ( fair) 9. In order to reduce prescription drug abuse and doctor shopping, adherence monitoring by UDT and PMDPs provide evidence that is essential to the identification of those patients who are non-compliant or abusing prescription drugs or illicit drugs. ( fair) 10. Constipation must be closely monitored and a bowel regimen be initiated as soon as deemed necessary. ( good) 11. Chronic opioid therapy may be continued, with continuous adherence monitoring, in well-selected populations, in conjunction with or after failure of other modalities of treatments with improvement in physical and functional status and minimal adverse effects. ( fair). The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."

Pharmacology of stimulants prohibited by the World Anti-Doping Agency (WADA)

PubMed Central

Docherty, J R

2008-01-01

This review examines the pharmacology of stimulants prohibited by the World Anti-Doping Agency (WADA). Stimulants that increase alertness/reduce fatigue or activate the cardiovascular system can include drugs like ephedrine available in many over-the-counter medicines. Others such as amphetamines, cocaine and hallucinogenic drugs, available on prescription or illegally, can modify mood. A total of 62 stimulants (61 chemical entities) are listed in the WADA List, prohibited in competition. Athletes may have stimulants in their body for one of three main reasons: inadvertent consumption in a propriety medicine; deliberate consumption for misuse as a recreational drug and deliberate consumption to enhance performance. The majority of stimulants on the list act on the monoaminergic systems: adrenergic (sympathetic, transmitter noradrenaline), dopaminergic (transmitter dopamine) and serotonergic (transmitter serotonin, 5-HT). Sympathomimetic describes agents, which mimic sympathetic responses, and dopaminomimetic and serotoninomimetic can be used to describe actions on the dopamine and serotonin systems. However, many agents act to mimic more than one of these monoamines, so that a collective term of monoaminomimetic may be useful. Monoaminomimietic actions of stimulants can include blockade of re-uptake of neurotransmitter, indirect release of neurotransmitter, direct activation of monoaminergic receptors. Many of the stimulants are amphetamines or amphetamine derivatives, including agents with abuse potential as recreational drugs. A number of agents are metabolized to amphetamine or metamphetamine. In addition to the monoaminomimetic agents, a small number of agents with different modes of action are on the list. A number of commonly used stimulants are not considered as Prohibited Substances. PMID:18500382

16 CFR § 1500.81 - Exemptions for food, drugs, cosmetics, and fuels.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Exemptions for food, drugs, cosmetics, and... REGULATIONS § 1500.81 Exemptions for food, drugs, cosmetics, and fuels. (a) Food, drugs, and cosmetics. Substances subject to the Federal Food, Drug, and Cosmetic Act are exempted by section 2(f)(2) of the act...

16 CFR 1500.81 - Exemptions for food, drugs, cosmetics, and fuels.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Exemptions for food, drugs, cosmetics, and... § 1500.81 Exemptions for food, drugs, cosmetics, and fuels. (a) Food, drugs, and cosmetics. Substances subject to the Federal Food, Drug, and Cosmetic Act are exempted by section 2(f)(2) of the act; but where...

16 CFR 1500.81 - Exemptions for food, drugs, cosmetics, and fuels.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Exemptions for food, drugs, cosmetics, and... § 1500.81 Exemptions for food, drugs, cosmetics, and fuels. (a) Food, drugs, and cosmetics. Substances subject to the Federal Food, Drug, and Cosmetic Act are exempted by section 2(f)(2) of the act; but where...

16 CFR 1500.81 - Exemptions for food, drugs, cosmetics, and fuels.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Exemptions for food, drugs, cosmetics, and... § 1500.81 Exemptions for food, drugs, cosmetics, and fuels. (a) Food, drugs, and cosmetics. Substances subject to the Federal Food, Drug, and Cosmetic Act are exempted by section 2(f)(2) of the act; but where...

16 CFR 1500.81 - Exemptions for food, drugs, cosmetics, and fuels.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Exemptions for food, drugs, cosmetics, and... § 1500.81 Exemptions for food, drugs, cosmetics, and fuels. (a) Food, drugs, and cosmetics. Substances subject to the Federal Food, Drug, and Cosmetic Act are exempted by section 2(f)(2) of the act; but where...

Malaria treatment in the retail sector: Knowledge and practices of drug sellers in rural Tanzania

PubMed Central

Hetzel, Manuel W; Dillip, Angel; Lengeler, Christian; Obrist, Brigit; Msechu, June J; Makemba, Ahmed M; Mshana, Christopher; Schulze, Alexander; Mshinda, Hassan

2008-01-01

Background Throughout Africa, the private retail sector has been recognised as an important source of antimalarial treatment, complementing formal health services. However, the quality of advice and treatment at private outlets is a widespread concern, especially with the introduction of artemisinin-based combination therapies (ACTs). As a result, ACTs are often deployed exclusively through public health facilities, potentially leading to poorer access among parts of the population. This research aimed at assessing the performance of the retail sector in rural Tanzania. Such information is urgently required to improve and broaden delivery channels for life-saving drugs. Methods During a comprehensive shop census in the districts of Kilombero and Ulanga, Tanzania, we interviewed 489 shopkeepers about their knowledge of malaria and malaria treatment. A complementary mystery shoppers study was conducted in 118 retail outlets in order to assess the vendors' drug selling practices. Both studies included drug stores as well as general shops. Results Shopkeepers in drug stores were able to name more malaria symptoms and were more knowledgeable about malaria treatment than their peers in general shops. In drug stores, 52% mentioned the correct child-dosage of sulphadoxine-pyrimethamine (SP) compared to only 3% in general shops. In drug stores, mystery shoppers were more likely to receive an appropriate treatment (OR = 9.6), but at an approximately seven times higher price. Overall, adults were more often sold an antimalarial than children (OR = 11.3). On the other hand, general shopkeepers were often ready to refer especially children to a higher level if they felt unable to manage the case. Conclusion The quality of malaria case-management in the retail sector is not satisfactory. Drug stores should be supported and empowered to provide correct malaria-treatment with drugs they are allowed to dispense. At the same time, the role of general shops as first contact points for malaria patients needs to be re-considered. Interventions to improve availability of ACTs in the retail sector are urgently required within the given legal framework. PMID:18471299

Cost-effectiveness analysis of introducing malaria diagnostic testing in drug shops: A cluster-randomised trial in Uganda.

PubMed

Hansen, Kristian Schultz; Clarke, Siân E; Lal, Sham; Magnussen, Pascal; Mbonye, Anthony K

2017-01-01

Private sector drug shops are an important source of malaria treatment in Africa, yet diagnosis without parasitological testing is common among these providers. Accurate rapid diagnostic tests for malaria (mRDTs) require limited training and present an opportunity to increase access to correct diagnosis. The present study was a cost-effectiveness analysis of the introduction of mRDTs in Ugandan drug shops. Drug shop vendors were trained to perform and sell subsidised mRDTs and artemisinin-based combination therapies (ACTs) in the intervention arm while vendors offered ACTs following presumptive diagnosis of malaria in the control arm. The effect on the proportion of customers with fever 'appropriately treated of malaria with ACT' was captured during a randomised trial in drug shops in Mukono District, Uganda. Health sector costs included: training of drug shop vendors, community sensitisation, supervision and provision of mRDTs and ACTs to drug shops. Household costs of treatment-seeking were captured in a representative sample of drug shop customers. The introduction of mRDTs in drug shops was associated with a large improvement of diagnosis and treatment of malaria, resulting in low incremental costs for the health sector at US$0.55 per patient appropriately treated of malaria. High expenditure on non-ACT drugs by households contributed to higher incremental societal costs of US$3.83. Sensitivity analysis showed that mRDTs would become less cost-effective compared to presumptive diagnosis with increasing malaria prevalence and lower adherence to negative mRDT results. mRDTs in drug shops improved the targeting of ACTs to malaria patients and are likely to be considered cost-effective compared to presumptive diagnosis, although the increased costs borne by households when the test result is negative are a concern.

Novel anticoagulants for stroke prevention in patients with atrial fibrillation.

PubMed

Jalota, A; Scarabelli, T M; Saravolatz, L; Bakhsh, M U; Agrawal, P; Jalota, R; Chen-Scarabelli, C; Fuster, V; Halperin, J

2014-06-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia that can potentially result in stroke. Vitamin K antagonists (VKA) like warfarin were for many decades the only oral anticoagulants available for stroke prevention in patients with non-valvular atrial fibrillation (AF) at high risk of stroke. Recently, new oral anticoagulants (NOACS) have been introduced that act via direct inhibition of thrombin (dabigatran) or activated factor X (edoxaban, rivaroxaban and apixaban). Unlike VKAs, these anticoagulants do not require routine INR monitoring and posses favorable pharmacological properties. NOACs act rapidly, and have a stable and predictable dose-related anticoagulant effect with few clinically relevant drug-drug interactions. Phase III trials comparing these agents to warfarin for stroke prevention in patients with non-valvular AF demonstrated that they are at least as efficacious and safe as warfarin. Evolution of clinical guidelines to incorporate the new anticoagulants for stroke prevention in non-valvular AF may result in a reduction in the incidence of AF-related strokes. Safe and effective use of these new drugs in clinical practice requires understanding of their distinct pharmacological properties.

Is orphan drug status beneficial to tropical disease control? Comparison of the American and future European orphan drug acts.

PubMed

Trouiller, P; Battistella, C; Pinel, J; Pecoul, B

1999-06-01

OBJECTIVES To quantify past outcomes of tropical pharmacology research and development (R & D) and to assess past benefits of the American orphan drug act and potential benefits of the future European orphan drug regulation on tropical diseases. This paper presents two analyses: a 1983-97 retrospective study of the United States Orphan Drug Act concerning rare diseases and a prospective study of the European Proposal for a Regulation Concerning Orphan Drugs and its possible impact on tropical diseases. Different programmes have in the past tried to stimulate R & D in this area, but results remain limited. Of 1450 new chemical entities marketed between 1972 and 1997, 13 were specifically for tropical diseases and considered as essential drugs. Between 1983 & 1997, the US Orphan Drug Act approved 837 drugs and marketing of 152 new molecular entities (NMEs). Three NMEs have been designated for malaria and human African trypanosomiasis. Seven others, already commonly used in tropical diseases, received either orphan designation or an orphan approval for another indication. Pharmaceutical companies benefit from the US framework only when the US market exclusivity clause was applicable. Future European orphan drug regulation appears to be similar to the US Orphan Drug Act. CONCLUSION The orphan drug programmes relating to rare diseases have met with some success. Considering tropical diseases rare diseases seems inadequate to boost pharmaceutical R & D. However, some provisions of the European text may be relevant to tropical diseases, admitting the need for a more specific rule for evaluations of this kind of drug and recognizing the existence of 'diseases of exception'.

21 CFR 25.1 - Purpose.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Purpose. 25.1 Section 25.1 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ENVIRONMENTAL IMPACT... Federal Food, Drug, and Cosmetic Act and the Public Health Service Act. This part also supplements the...

21 CFR 807.3 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Definitions. 807.3 Section 807.3 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES... Provisions § 807.3 Definitions. (a) Act means the Federal Food, Drug, and Cosmetic Act. (b) Commercial...

21 CFR 807.3 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Definitions. 807.3 Section 807.3 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES... Provisions § 807.3 Definitions. (a) Act means the Federal Food, Drug, and Cosmetic Act. (b) Commercial...

21 CFR 3.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Definitions. 3.2 Section 3.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PRODUCT JURISDICTION... this part: (a) Act means the Federal Food, Drug, and Cosmetic Act. (b) Agency component means the...

21 CFR 3.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Definitions. 3.2 Section 3.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PRODUCT JURISDICTION... this part: (a) Act means the Federal Food, Drug, and Cosmetic Act. (b) Agency component means the...

Long-Acting Antiretrovirals: Where Are We now?

PubMed

Nyaku, Amesika N; Kelly, Sean G; Taiwo, Babafemi O

2017-04-01

Current HIV treatment options require daily use of combination antiretroviral drugs. Many persons living with HIV experience treatment fatigue and suboptimal adherence as a result. Long-acting antiretroviral drugs are being developed to expand options for HIV treatment. Here, we review the agents in development, and evaluate data from recent clinical trials. In addition, we anticipate challenges to successful widespread use of long-acting antiretrovirals. Parenteral nanosuspensions of cabotegravir and rilpivirine, and dapivirine vaginal ring are the farthest in clinical development. Long-acting modalities in earlier development stages employ drug-loaded implants, microparticles, or targeted mutagenesis, among other innovations. Long-acting antiretroviral drugs promise new options for HIV prevention and treatment, and ways to address poor adherence and treatment fatigue. Further studies will identify the long-acting agents or combinations that are suitable for routine use. Creative solutions will be needed for anticipated implementation challenges.

78 FR 72901 - Draft Guidance; Pharmacy Compounding of Human Drug Products Under Section 503A of the Federal...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-04

... the Drug Quality and Security Act to remove the unconstitutional advertising, promotion, and... 503A are met. The conditions of section 503A of the FD&C Act included restrictions on the advertising or promotion of the compounding of any particular drug, class of drug, or type of drug, and the...

Calcium channel antagonists in the treatment of hypertension.

PubMed

Weber, Michael A

2002-01-01

Calcium channel antagonists are widely used antihypertensive agents. Their popularity among primary care physicians is not only due to their blood pressure-lowering effects, but also because they appear to be effective regardless of the age or ethnic background of the patients. The first available calcium channel antagonists utilized immediate-release formulations which, although effective in patients with angina pectoris, were not approved by the US FDA for use in hypertension. When long-acting once-daily formulations were approved in this indication, the short-acting preparations--which had by then become generic and inexpensive--retained some residual unapproved use for hypertension. An observational case-controlled trial, based on such usage, noted that these agents were associated with a greater risk of myocardial infarctions than conventional agents such as diuretics and beta-adrenoceptor antagonists. Further case-controlled trials showed, in fact, that the dangers of calcium channel antagonists were confined to the short-acting agents and that approved long-acting agents were at least as well tolerated and effective as other antihypertensive drugs. Cardiovascular outcomes during treatment with calcium channel antagonists have been examined in randomized, controlled trials. Compared with placebo, the calcium channel antagonists clearly prevented strokes and other cardiovascular events and reduced mortality. The effects of these agents on survival and clinical outcomes were similar to those with other antihypertensive drugs. There is a slight tendency for the calcium channel antagonists to be more effective than other drug types in preventing stroke, but slightly less effective in preventing coronary events. These observations extend to high-risk patients with hypertension including those with diabetes mellitus. Even so, patients with evidence of nephropathy should not receive monotherapy with calcium channel antagonists. Such patients are optimally treated with angiotensin receptor antagonists or ACE inhibitors, although addition of other drugs, including calcium channel antagonists, is often required to achieve the tight blood pressure control necessary to provide adequate renal protection. Calcium channel antagonists have a highly acceptable tolerability profile and careful reviews of available data have shown that their use is not associated with increased bleeding or promotion of tumor formation. It is now recognized that reduction of blood pressure in patients with hypertension to levels often <130/85 mm Hg should be undertaken in presence of other cardiovascular risk factors or evidence of end organ damage. Because of this important concept, calcium channel antagonists, like the other antihypertensive drug classes, are progressively being prescribed less often as monotherapy, but more typically as part of combination regimens.

37 CFR 1.740 - Formal requirements for application for extension of patent term; correction of informalities.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Virus-Serum-Toxin Act; and (C) The date the license issued; (iv) For a patent claiming a food or color... or use under the Federal Food, Drug, and Cosmetic Act, the Public Health Service Act, or the Virus... patent claiming a new animal drug: (A) The date a major health or environmental effects test on the drug...

37 CFR 1.740 - Formal requirements for application for extension of patent term; correction of informalities.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Virus-Serum-Toxin Act; and (C) The date the license issued; (iv) For a patent claiming a food or color... or use under the Federal Food, Drug, and Cosmetic Act, the Public Health Service Act, or the Virus... patent claiming a new animal drug: (A) The date a major health or environmental effects test on the drug...

37 CFR 1.740 - Formal requirements for application for extension of patent term; correction of informalities.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Virus-Serum-Toxin Act; and (C) The date the license issued; (iv) For a patent claiming a food or color... or use under the Federal Food, Drug, and Cosmetic Act, the Public Health Service Act, or the Virus... patent claiming a new animal drug: (A) The date a major health or environmental effects test on the drug...

37 CFR 1.740 - Formal requirements for application for extension of patent term; correction of informalities.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Virus-Serum-Toxin Act; and (C) The date the license issued; (iv) For a patent claiming a food or color... or use under the Federal Food, Drug, and Cosmetic Act, the Public Health Service Act, or the Virus... patent claiming a new animal drug: (A) The date a major health or environmental effects test on the drug...

40 CFR 2.308 - Special rules governing certain information obtained under the Federal Food, Drug and Cosmetic Act.

Code of Federal Regulations, 2012 CFR

2012-07-01

... information obtained under the Federal Food, Drug and Cosmetic Act. 2.308 Section 2.308 Protection of... § 2.308 Special rules governing certain information obtained under the Federal Food, Drug and Cosmetic... Cosmetic Act, as amended, 21 U.S.C. 301 et seq. (2) Petition means a petition for the issuance of a...

40 CFR 2.308 - Special rules governing certain information obtained under the Federal Food, Drug and Cosmetic Act.

Code of Federal Regulations, 2013 CFR

2013-07-01

... information obtained under the Federal Food, Drug and Cosmetic Act. 2.308 Section 2.308 Protection of... § 2.308 Special rules governing certain information obtained under the Federal Food, Drug and Cosmetic... Cosmetic Act, as amended, 21 U.S.C. 301 et seq. (2) Petition means a petition for the issuance of a...

40 CFR 2.308 - Special rules governing certain information obtained under the Federal Food, Drug and Cosmetic Act.

Code of Federal Regulations, 2014 CFR

2014-07-01

... information obtained under the Federal Food, Drug and Cosmetic Act. 2.308 Section 2.308 Protection of... § 2.308 Special rules governing certain information obtained under the Federal Food, Drug and Cosmetic... Cosmetic Act, as amended, 21 U.S.C. 301 et seq. (2) Petition means a petition for the issuance of a...

40 CFR 2.308 - Special rules governing certain information obtained under the Federal Food, Drug and Cosmetic Act.

Code of Federal Regulations, 2011 CFR

2011-07-01

... information obtained under the Federal Food, Drug and Cosmetic Act. 2.308 Section 2.308 Protection of... § 2.308 Special rules governing certain information obtained under the Federal Food, Drug and Cosmetic... Cosmetic Act, as amended, 21 U.S.C. 301 et seq. (2) Petition means a petition for the issuance of a...

40 CFR 2.308 - Special rules governing certain information obtained under the Federal Food, Drug and Cosmetic Act.

Code of Federal Regulations, 2010 CFR

2010-07-01

... information obtained under the Federal Food, Drug and Cosmetic Act. 2.308 Section 2.308 Protection of... § 2.308 Special rules governing certain information obtained under the Federal Food, Drug and Cosmetic... Cosmetic Act, as amended, 21 U.S.C. 301 et seq. (2) Petition means a petition for the issuance of a...

The Two Faces of Social Interaction Reward in Animal Models of Drug Dependence

PubMed Central

Rawas, Rana El

2016-01-01

Drug dependence is a serious health and social problem. Social factors can modify vulnerability to developing drug dependence, acting as risk factors or protective factors. Whereas stress and peer environment that encourage substance use may increase drug taking, strong attachments between family members and peer environment that do not experience drug use may protect against drug taking and, ultimately, drug dependence. The rewarding effects of drug abuse and social interaction can be evaluated using animal models. In this review we focus on evaluating social interaction reward in the conditioned place preference paradigm. We give an overview of how social interaction, if made available within the drug context, may facilitate, promote and interact with the drug’s effects. However, social interaction, if offered alternatively outside the drug context, may have pronounced protective effects against drug abuse and relapse. We also address the importance of the weight difference parameter between the social partners in determining the positive or “agonistic” versus the hostile or “antagonistic” social interaction. We conclude that understanding social interaction reward and its subsequent effects on drug reward is sorely needed for therapeutic interventions against drug dependence. PMID:26088685

NF-κB-IKKβ pathway as a target for drug development: realities, challenges and perspectives.

PubMed

Freitas, Rosana H C N; Fraga, Carlos A M

2018-02-19

Nuclear factor κB (NF-κB) comprises a family of proteins that act as transcription factors promoting the expression of many genes. Activation of NF-κB biochemical cascades is associated with the regulation of innate and adaptive immune responses and inflammation, among other physiological responses. However, genetic abnormalities and continuous stimulation of the NF-κB-IKKβ pathway are directly related to many types of inflammatory and autoimmune diseases, as well as to the genesis and survival of tumor cells. Inhibition of the NF-κB-IKKβ cascade can be considered an attractive therapeutic method for the genesis of new prototypes to combat these chronic multifactorial diseases. This review describes some prototypes and drugs that act to inhibit the NF-κB-IKKβ pathway, highlighting the realities, challenges and perspectives for therapeutic use. Although only proteasome inhibitors, such as bortezomib and carfilzomib, are a reality as therapeutically useful drugs among the known modulators of possible targets in the NF-κB-IKKβ pathway, some other prototypes described as IKKβ inhibitors have entered clinical stages as drug candidates for the control of inflammatory diseases. It is important to note that some classical drugs available on the pharmaceutical market, such as acetylsalicylic acid, were also described more recently as NF-κB pathway modulators as IKKβ inhibitors. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

76 FR 30727 - Food and Drug Administration Food Safety Modernization Act: Focus on Inspections and Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0366] Food and Drug Administration Food Safety Modernization Act: Focus on Inspections and Compliance AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public meeting; request for comments. SUMMARY: The...

76 FR 64354 - Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-18

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0529] Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small Business; Extension of Comment Period AGENCY: Food and Drug Administration, HHS. ACTION: Notice; extension of comment...

16 CFR 1702.16 - Petitions requesting an exemption for a drug or a new drug.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Petitions requesting an exemption for a drug or a new drug. 1702.16 Section 1702.16 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION POISON PREVENTION PACKAGING ACT OF 1970 REGULATIONS PETITIONS FOR EXEMPTIONS FROM POISON PREVENTION PACKAGING ACT...

16 CFR 1702.16 - Petitions requesting an exemption for a drug or a new drug.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Petitions requesting an exemption for a drug or a new drug. 1702.16 Section 1702.16 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION POISON PREVENTION PACKAGING ACT OF 1970 REGULATIONS PETITIONS FOR EXEMPTIONS FROM POISON PREVENTION PACKAGING ACT...

16 CFR 1702.16 - Petitions requesting an exemption for a drug or a new drug.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Petitions requesting an exemption for a drug or a new drug. 1702.16 Section 1702.16 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION POISON PREVENTION PACKAGING ACT OF 1970 REGULATIONS PETITIONS FOR EXEMPTIONS FROM POISON PREVENTION PACKAGING ACT...

16 CFR 1702.16 - Petitions requesting an exemption for a drug or a new drug.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Petitions requesting an exemption for a drug or a new drug. 1702.16 Section 1702.16 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION POISON PREVENTION PACKAGING ACT OF 1970 REGULATIONS PETITIONS FOR EXEMPTIONS FROM POISON PREVENTION PACKAGING ACT...

21 CFR 821.3 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Definitions. 821.3 Section 821.3 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES... terms apply to this part: (a) Act means the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. 321 et seq...

21 CFR 821.3 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Definitions. 821.3 Section 821.3 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES... terms apply to this part: (a) Act means the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. 321 et seq...

21 CFR 821.3 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Definitions. 821.3 Section 821.3 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES... terms apply to this part: (a) Act means the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. 321 et seq...

Case management of malaria fever in Cambodia: results from national anti-malarial outlet and household surveys

PubMed Central

2011-01-01

Background Continued progress towards global reduction in morbidity and mortality due to malaria requires scale-up of effective case management with artemisinin-combination therapy (ACT). The first case of artemisinin resistance in Plasmodium falciparum was documented in western Cambodia. Spread of artemisinin resistance would threaten recent gains in global malaria control. As such, the anti-malarial market and malaria case management practices in Cambodia have global significance. Methods Nationally-representative household and outlet surveys were conducted in 2009 among areas in Cambodia with malaria risk. An anti-malarial audit was conducted among all public and private outlets with the potential to sell anti-malarials. Indicators on availability, price and relative volumes sold/distributed were calculated across types of anti-malarials and outlets. The household survey collected information about management of recent "malaria fevers." Case management in the public versus private sector, and anti-malarial treatment based on malaria diagnostic testing were examined. Results Most public outlets (85%) and nearly half of private pharmacies, clinics and drug stores stock ACT. Oral artemisinin monotherapy was found in pharmacies/clinics (9%), drug stores (14%), mobile providers (4%) and grocery stores (2%). Among total anti-malarial volumes sold/distributed nationally, 6% are artemisinin monotherapies and 72% are ACT. Only 45% of people with recent "malaria fever" reportedly receive a diagnostic test, and the most common treatment acquired is a drug cocktail containing no identifiable anti-malarial. A self-reported positive diagnostic test, particularly when received in the public sector, improves likelihood of receiving anti-malarial treatment. Nonetheless, anti-malarial treatment of reportedly positive cases is low among people who seek treatment exclusively in the public (61%) and private (42%) sectors. Conclusions While data on the anti-malarial market shows favourable progress towards replacing artemisinin monotherapies with ACT, the widespread use of drug cocktails to treat malaria is a barrier to effective case management. Significant achievements have been made in availability of diagnostic testing and effective treatment in the public and private sectors. However, interventions to improve case management are urgently required, particularly in the private sector. Evidence-based interventions that target provider and consumer behaviour are needed to support uptake of diagnostic testing and treatment with full-course first-line anti-malarials. PMID:22039922

Kratom, an Emerging Drug of Abuse: A Case Report of Overdose and Management of Withdrawal.

PubMed

Diep, Jack; Chin, David Tian; Gupta, Somdatta; Syed, Faraz; Xiong, Ming; Cheng, Jianguo

2018-04-15

Kratom is an herb indigenous to Southeast Asia with psychoactive opioid compounds, often used as a treatment for chronic pain or opiate withdrawal symptoms. It is legally and readily available via Internet sales and has been identified as an emerging drug of abuse in the United States. Kratom use has been associated with psychosis, seizures, and even death. At lower doses, kratom acts as a stimulant, while at higher doses, it produces analgesia and euphoria. Here, we describe the successful management of kratom overdose and withdrawal in a young man with negative toxicology screens.

Kratom, an Emerging Drug of Abuse: A Case Report of Overdose and Management of Withdrawal.

PubMed

Diep, Jack; Chin, David Tian; Gupta, Somdatta; Syed, Faraz; Xiong, Ming; Cheng, Jianguo

2017-10-26

Kratom is an herb indigenous to Southeast Asia with psychoactive opioid compounds, often used as a treatment for chronic pain or opiate withdrawal symptoms. It is legally and readily available via Internet sales and has been identified as an emerging drug of abuse in the United States. Kratom use has been associated with psychosis, seizures, and even death. At lower doses, kratom acts as a stimulant, while at higher doses, it produces analgesia and euphoria. Here, we describe the successful management of kratom overdose and withdrawal in a young man with negative toxicology screens.

Argemone mexicana decoction versus artesunate-amodiaquine for the management of malaria in Mali: policy and public-health implications.

PubMed

Graz, Bertrand; Willcox, Merlin L; Diakite, Chiaka; Falquet, Jacques; Dackuo, Florent; Sidibe, Oumar; Giani, Sergio; Diallo, Drissa

2010-01-01

A classic way of delaying drug resistance is to use an alternative when possible. We tested the malaria treatment Argemone mexicana decoction (AM), a validated self-prepared traditional medicine made with one widely available plant and safe across wide dose variations. In an attempt to reflect the real situation in the home-based management of malaria in a remote Malian village, 301 patients with presumed uncomplicated malaria (median age 5 years) were randomly assigned to receive AM or artesunate-amodiaquine [artemisinin combination therapy (ACT)] as first-line treatment. Both treatments were well tolerated. Over 28 days, second-line treatment was not required for 89% (95% CI 84.1-93.2) of patients on AM, versus 95% (95% CI 88.8-98.3) on ACT. Deterioration to severe malaria was 1.9% in both groups in children aged 5 years) and 0% had coma/convulsions. AM, now government-approved in Mali, could be tested as a first-line complement to standard modern drugs in high-transmission areas, in order to reduce the drug pressure for development of resistance to ACT, in the management of malaria. In view of the low rate of severe malaria and good tolerability, AM may also constitute a first-aid treatment when access to other antimalarials is delayed.

Non-prescription (OTC) oral analgesics for acute pain - an overview of Cochrane reviews.

PubMed

Moore, R Andrew; Wiffen, Philip J; Derry, Sheena; Maguire, Terry; Roy, Yvonne M; Tyrrell, Laila

2015-11-04

Non-prescription (over-the-counter, or OTC) analgesics (painkillers) are used frequently. They are available in various brands, package sizes, formulations, and dose. They can be used for a range of different types of pain, but this overview reports on how well they work for acute pain (pain of short duration, usually with rapid onset). Thirty-nine Cochrane reviews of randomised trials have examined the analgesic efficacy of individual drug interventions in acute postoperative pain. To examine published Cochrane reviews for information about the efficacy of pain medicines available without prescription using data from acute postoperative pain. We identified OTC analgesics available in the UK, Australia, Canada, and the USA by examining online pharmacy websites. We also included some analgesics (diclofenac potassium, dexketoprofen, dipyrone) of importance in parts of the world, but not currently available in these jurisdictions.We identified systematic reviews by searching the Cochrane Database of Systematic Reviews (CDSR) on The Cochrane Library through a simple search strategy. All reviews were overseen by a single review group, had a standard title, and had as their primary outcome numbers of participants with at least 50% pain relief over four to six hours compared with placebo. From individual reviews we extracted the number needed to treat for an additional beneficial outcome (NNT) for this outcome for each drug/dose combination, and also calculated the success rate to achieve at least 50% of maximum pain relief. We also examined the number of participants experiencing any adverse event, and whether the incidence was different from placebo. We found information on 21 different OTC analgesic drugs, doses, and formulations, using information from 10 Cochrane reviews, supplemented by information from one non-Cochrane review with additional information on ibuprofen formulations (high quality evidence). The lowest (best) NNT values were for combinations of ibuprofen plus paracetamol, with NNT values below 2. Analgesics with values close to 2 included fast acting formulations of ibuprofen 200 mg and 400 mg, ibuprofen 200 mg plus caffeine 100 mg, and diclofenac potassium 50 mg. Combinations of ibuprofen plus paracetamol had success rates of almost 70%, with dipyrone 500 mg, fast acting ibuprofen formulations 200 mg and 400 mg, ibuprofen 200 mg plus caffeine 100 mg, and diclofenac potassium 50 mg having success rates above 50%. Paracetamol and aspirin at various doses had NNT values of 3 or above, and success rates of 11% to 43%. We found no information on many of the commonly available low dose codeine combinations.The proportion of participants experiencing an adverse event were generally not different from placebo, except for aspirin 1000 mg and (barely) ibuprofen 200 mg plus caffeine 100 mg. For ibuprofen plus paracetamol, adverse event rates were lower than with placebo. There is a body of reliable evidence about the efficacy of some of the most commonly available drugs and doses widely available without prescription. The postoperative pain model is predominantly pain after third molar extraction, which is used as the industry model for everyday pain. The proportion of people with acute pain who get good pain relief with any of them ranges from around 70% at best to less than 20% at worst; low doses of some drugs in fast acting formulations were among the best. Adverse events were generally no different from placebo. Consumers can make an informed choice based on this knowledge, together with availability and price. Headache and migraine were not included in this overview.

Perioperative Use of Clevidipine: A Systematic Review and Meta-Analysis.

PubMed

Espinosa, Angel; Ripollés-Melchor, Javier; Casans-Francés, Rubén; Abad-Gurumeta, Alfredo; Bergese, Sergio D; Zuleta-Alarcon, Alix; López-Timoneda, Francisco; Calvo-Vecino, José María

2016-01-01

Clevidipine is an ultrashort-acting drug for rapid reduction of blood pressure by selectively acting on the L-type Ca2+ channels on arteriolar smooth muscle. The drug's ultrashort action in reducing the blood pressure is due to its rapid hydrolysis by blood and extravascular tissue esterases, which does not depend on hepato-renal metabolism and excretion. An analysis of the perioperative management of blood pressure should be considered to compare with other intravenous antihypertensive agents. Analyses of the available evidence in randomized clinical trials following the PRISMA methodology as well as clinical significance according to the GRADE system were conducted. Placebo versus other antihypertensive drugs studies were included. Statistical assessments were done using the X2 and I2 tests. Clevidipine was more effective in maintaining the blood pressure within pre-specified ranges compared with other antihypertensive drugs (MD, -17.87 CI 95%: -29.02 to -6.72; p = 0.02). The use of Clevidipine versus placebo and rescue antihypertensive intravenous drug showed a clear reduction in rates of treatment failure (RR 0.10; IC 95%; 0.05-0.18; p <0.0001). There was no difference in the incidence of adverse events compared with placebo (RR 1.47; 95% CI 0.89 to 2.43, p = 0.14) and with other antihypertensive drugs (RR 0.78, 95% CI 0.45 to 1.35; p = 0.37). In addition, there was no difference in the incidence of atrial fibrillation (AF) between clevidipine and control groups (RR 1.09, IC del 95%: 0.65 a 1.83; p = 0.73). Clevidipine is an ultrafast-acting drug that is highly effective for management of perioperative arterial hypertension. It is devoid of adverse effects associated with the use of other IV antihypertensives. Its favorable pharmacodynamic and pharmacokinetic properties make clevidipine the drug of choice for the management of acute perioperative hypertension. It is important to emphasize the need for further studies with a larger number of patients to confirm these findings and increase the degree of evidence.

Permanent Discontinuance or Interruption in Manufacturing of Certain Drug or Biological Products. Final rule.

PubMed

2015-07-08

The Food and Drug Administration (FDA or the Agency) is amending its regulations to implement certain drug shortages provisions of the Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended by the Food and Drug Administration Safety and Innovation Act (FDASIA). The rule requires all applicants of covered approved drugs or biological products--including certain applicants of blood or blood components for transfusion and all manufacturers of covered drugs marketed without an approved application--to notify FDA electronically of a permanent discontinuance or an interruption in manufacturing of the product that is likely to lead to a meaningful disruption in supply (or a significant disruption in supply for blood or blood components) of the product in the United States.

Do anti-malarials in Africa meet quality standards? The market penetration of non quality-assured artemisinin combination therapy in eight African countries.

PubMed

Newton, Paul N; Hanson, Kara; Goodman, Catherine

2017-05-25

Quality of artemisinin-based combination therapy (ACT) is important for ensuring malaria parasite clearance and protecting the efficacy of artemisinin-based therapies. The extent to which non quality-assured ACT (non-QAACT), or those not granted global regulatory approval, are available and used to treat malaria in endemic countries is poorly documented. This paper uses national and sub-national medicine outlet surveys conducted in eight study countries (Benin, Kinshasa and Kantanga [Democratic Republic of the Congo, DRC], Kenya, Madagascar, Nigeria, Tanzania, Uganda and Zambia) between 2009 and 2015 to describe the non-QAACT market and to document trends in availability and distribution of non-QAACT in the public and private sector. In 2014/15, non-QAACT were most commonly available in Kinshasa (83%), followed by Katanga (53%), Nigeria (48%), Kenya (42%), and Uganda (33%). Non-QAACT accounted for 20% of the market share in the private sector in Kenya, followed by Benin and Uganda (19%), Nigeria (12%) and Zambia (8%); this figure was 27% in Katanga and 40% in Kinshasa. Public sector non-QAACT availability and distribution was much lower, with the exception of Zambia (availability, 85%; market share, 32%). Diverse generics and formulations were available, but non-QAACT were most commonly artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DHA PPQ), in tablet formulation, imported, and distributed in urban areas at either pharmacies or drug stores. The number of unique manufacturers supplying non-QAACT to each country ranged from 9 in Uganda to 92 in Nigeria. Addressing the availability and distribution of non-QAACT will require effective private sector engagement and evidence-based strategies to address provider and consumer demand for these products. Given the variation in non-QAACT markets observed across the eight study countries, active efforts to limit registration, importation and distribution of non-QAACT must be tailored to the country context, and will involve addressing complex and challenging aspects of medicine registration, private sector pharmaceutical regulation, local manufacturing and drug importation. These efforts may be critical not only to patient health and safety, but also to effective malaria control and protection of artemisinin drug efficacy in the face of spreading resistance.

Restrictions for reimbursement of interferon-free direct-acting antiviral drugs for HCV infection in Europe.

PubMed

Marshall, Alison D; Cunningham, Evan B; Nielsen, Stine; Aghemo, Alessio; Alho, Hannu; Backmund, Markus; Bruggmann, Philip; Dalgard, Olav; Seguin-Devaux, Carole; Flisiak, Robert; Foster, Graham R; Gheorghe, Liana; Goldberg, David; Goulis, Ioannis; Hickman, Matthew; Hoffmann, Patrick; Jancorienė, Ligita; Jarcuska, Peter; Kåberg, Martin; Kostrikis, Leondios G; Makara, Mihály; Maimets, Matti; Marinho, Rui Tato; Matičič, Mojca; Norris, Suzanne; Ólafsson, Sigurður; Øvrehus, Anne; Pawlotsky, Jean-Michel; Pocock, James; Robaeys, Geert; Roncero, Carlos; Simonova, Marieta; Sperl, Jan; Tait, Michele; Tolmane, Ieva; Tomaselli, Stefan; van der Valk, Marc; Vince, Adriana; Dore, Gregory J; Lazarus, Jeffrey V; Grebely, Jason

2018-02-01

All-oral direct-acting antiviral drugs (DAAs) for hepatitis C virus, which have response rates of 95% or more, represent a major clinical advance. However, the high list price of DAAs has led many governments to restrict their reimbursement. We reviewed the availability of, and national criteria for, interferon-free DAA reimbursement among countries in the European Union and European Economic Area, and Switzerland. Reimbursement documentation was reviewed between Nov 18, 2016, and Aug 1, 2017. Primary outcomes were fibrosis stage, drug or alcohol use, prescriber type, and HIV co-infection restrictions. Among the 35 European countries and jurisdictions included, the most commonly reimbursed DAA was ombitasvir, paritaprevir, and ritonavir, with dasabuvir, and with or without ribavirin (33 [94%] countries and jurisdictions). 16 (46%) countries and jurisdictions required patients to have fibrosis at stage F2 or higher, 29 (83%) had no listed restrictions based on drug or alcohol use, 33 (94%) required a specialist prescriber, and 34 (97%) had no additional restrictions for people co-infected with HIV and hepatitis C virus. These findings have implications for meeting WHO targets, with evidence of some countries not following the 2016 hepatitis C virus treatment guidelines by the European Association for the Study of Liver. Copyright © 2018 Elsevier Ltd. All rights reserved.

Drug development strategies for the treatment of obesity: how to ensure efficacy, safety, and sustainable weight loss

PubMed Central

Barja-Fernandez, S; Leis, R; Casanueva, FF; Seoane, LM

2014-01-01

The prevalence of obesity has increased worldwide, and approximately 25%–35% of the adult population is obese in some countries. The excess of body fat is associated with adverse health consequences. Considering the limited efficacy of diet and exercise in the current obese population and the use of bariatric surgery only for morbid obesity, it appears that drug therapy is the only available method to address the problem on a large scale. Currently, pharmacological obesity treatment options are limited. However, new antiobesity drugs acting through central nervous system pathways or the peripheral adiposity signals and gastrointestinal tract are under clinical development. One of the most promising approaches is the use of peptides that influence the peripheral satiety signals and brain–gut axis such as GLP-1 analogs. However, considering that any antiobesity drug may affect one or several of the systems that control food intake and energy expenditure, it is unlikely that a single pharmacological agent will be effective as a striking obesity treatment. Thus, future strategies to treat obesity will need to be directed at sustainable weight loss to ensure maximal safety. This strategy will probably require the coadministration of medications that act through different mechanisms. PMID:25489237

Patent extension policy for paediatric indications: an evaluation of the impact within three drug classes in a state Medicaid programme.

PubMed

Nelson, Richard E; McAdam-Marx, Carrie; Evans, Megan L; Ward, Robert; Campbell, Benjamin; Brixner, Diana; Lafleur, Joanne

2011-05-01

The Food and Drug Administration Modernization Act (FDAMA) of 1997, Best Pharmaceuticals for Children Act (BPCA) of 2002 and Pediatric Research Equity Act of 2007 provide an extended period of 6 months of marketing exclusivity (i.e. patent extension) to prescription drug manufacturers that conduct paediatric studies. Branded drugs in the statin, ACE inhibitor and selective serotonin reuptake inhibitor (SSRI) classes were three of many classes with drugs granted patent extensions. We estimated the cost impact of the 6-month exclusivity extension policy on the Utah Medicaid drug programme by comparing actual costs to projected costs had the 6-month exclusivity extension not been granted for these drugs and thus less expensive generic alternatives been available sooner. Using these results, we then projected the cost impact of this policy on Medicaid programmes in the US during the 18 months following patent expiration. The Utah Medicaid prescription claims obtained for statins, ACE inhibitors and SSRIs included reimbursement amount, number of units dispensed, days supplied, date of service and drug strength. Actual expenditures for each drug were calculated for the 6 months before and 12 months after generic availability. The percentage difference between the brand name prescription reimbursement amount to Medicaid in the last 2 months of the 6-month extension and the generic prescription reimbursement amount to Medicaid in the first 2 months following exclusivity expiration was then calculated for each drug. This was done using data from the 5 months surrounding the exclusivity expiration by regressing the log-transformed Utah Medicaid reimbursement amount on an indicator for patent expiration, controlling for number of units, volume of sales, month filled and strength. This was used to estimate what the initial generic prescription price would have been without the 6-month patent extension and what costs would have been in the 18 months following the original expiration date if the patent extension had not been granted. Medicaid rebates were assumed to be 15.1% for branded products and 11% for generics. The 6-month extension policy was estimated to cost Utah's Medicaid $US2.2 (95% CI 1.9, 2.4) million for these three drug classes over the 18 months following the original patent expiration date (year 2007 values). Projected to the US Medicaid population, this cost was $US430 (95% CI 371, 475) million. For the individual drugs that we examined, the percentage cost decrease in reimbursement amount resulting from exclusivity expiration and generic entry ranged from 24.4% (p < 0.001) for enalapril to 3.8% (p = 0.0951) for pravastatin sodium. Makers of the branded drugs evaluated were given market exclusivity extensions for conducting studies of their medications in children. The costs found in this study are just a small portion of the total paid, which include those born by other payers. Whether the benefits of this policy outweigh these costs is an open question, but these results suggest that the costs to Medicaid and thus taxpayers are substantial.

21 CFR 1403.4 - Applicability.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND... National School Lunch Act: (i) School Lunch (section 4 of the Act), (ii) Commodity Assistance (section 6 of...), and (ii) School Breakfast (section 4 of the Act); (6) Entitlement grants for State Administrative...

21 CFR 1403.4 - Applicability.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND... National School Lunch Act: (i) School Lunch (section 4 of the Act), (ii) Commodity Assistance (section 6 of...), and (ii) School Breakfast (section 4 of the Act); (6) Entitlement grants for State Administrative...

21 CFR 1403.4 - Applicability.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND... National School Lunch Act: (i) School Lunch (section 4 of the Act), (ii) Commodity Assistance (section 6 of...), and (ii) School Breakfast (section 4 of the Act); (6) Entitlement grants for State Administrative...

21 CFR 1403.4 - Applicability.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND... National School Lunch Act: (i) School Lunch (section 4 of the Act), (ii) Commodity Assistance (section 6 of...), and (ii) School Breakfast (section 4 of the Act); (6) Entitlement grants for State Administrative...

21 CFR 1403.4 - Applicability.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND... National School Lunch Act: (i) School Lunch (section 4 of the Act), (ii) Commodity Assistance (section 6 of...), and (ii) School Breakfast (section 4 of the Act); (6) Entitlement grants for State Administrative...

[Biperiden abuse as a partial factor in polytoxicomania].

PubMed

Schulte, R M

1988-03-01

We found 16 patients (15%) taking the anticholinergic biperiden because of its psychotropic action, occasionally, rather frequently or regularly, among a subgroup of 120 drug-dependent patients (drugs of the barbiturate and amphetamin types) out of a studied total of 194 imprisoned male addicts. These biperiden abusers suffered without exception from polytoxicomania associated with drug dependence and alcoholism. Most prominent was drug dependence on drugs of the morphine type. We could not prove a case of an isolated "primary" abuse of biperiden. Direct medical prescription was a rather secondary factor in procuring this preparation, in contrast to analgesics, tranquilisers, barbiturates and clomethiazol. Increase of biperiden abuse is due, on the one hand, to a generally noticeable tendency to polytoxicomania, and on the other hand to a change in Federal German drug prescription rules effective 1 August 1986 according to which fenetylline hydrochloride, a sympathomimetic, is now subject to medical prescription. Other centrally acting anticholinergics were unknown among this group of patients and were not abused. The results are discussed on the basis of available literature.

Tragedy, transformation, and triumph: comparing the factors and forces that led to the adoption of the 1860 Adulteration Act in England and the 1906 Pure Food and Drug Act in the United States.

PubMed

London, Jillian

2014-01-01

The 1860 Adulteration Act in England and the 1906 Pure Food and Drug Act in the United States were two of the earliest pieces of legislation to provide generalized regulation of food and drugs on a national scale. While significant scholarly attention has been given to explaining the factors and forces that led to the passage of each Act independent of the other, few books or articles have directly compared the similar individuals and events that led to the adoption of both Acts. This paper attempts to fill that gap. Through a comparative examination, this paper reveals that four main components were key to the national pure food and drug movements in both countries: individuals who crusaded for national adulteration legislation; tragedies that shocked the public into calling for reform; press and publicity that was willing and able to bring the evils of adulteration to the forefront of the public mind; and a transformation of the social, political, and economic systems, which created atmospheres conducive to reform. This paper aims to shed new light on the 1860 Adulteration Act and the 1906 Pure Food and Drug Act--two acts that derive their importance not just from the effect that they directly had on the regulation of food and drugs but also as some of the earliest examples of western governments coming to recognize the need for national regulation to protect the public from harm and coming to embrace their changing role as spearheads of modern regulatory states.

Drug-Free Schools and Communities Act Compliance at Michigan Community Colleges

ERIC Educational Resources Information Center

Custer, Bradley D.

2018-01-01

In 1989, Congress passed the Drug-Free Schools and Communities Act Amendments to address illegal alcohol and drug abuse on college campuses. To receive federal funding, each college must comply by implementing an alcohol and drug prevention program, but the federal government and some colleges have paid little attention to this policy. Recently,…

77 FR 34388 - Determination of Regulatory Review Period for Purposes of Patent Extension; CYSVIEW (Previously...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-11

... Restoration Act of 1984 (Pub. L. 98-417) and the Generic Animal Drug and Patent Term Restoration Act (Pub. L... patented item (human drug product, animal drug product, medical device, food additive, or color additive... drug products, the testing phase begins when the exemption to permit the clinical investigations of the...

75 FR 17414 - Determination of Regulatory Review Period for Purposes of Patent Extension; TOVIAZ

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-06

... Restoration Act of 1984 (Public Law 98-417) and the Generic Animal Drug and Patent Term Restoration Act... as the patented item (human drug product, animal drug product, medical device, food additive, or... approval phase. For human drug products, the testing phase begins when the exemption to permit the clinical...

75 FR 18213 - Determination of Regulatory Review Period for Purposes of Patent Extension; MOZOBIL

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-09

... Restoration Act of 1984 (Public Law 98-417) and the Generic Animal Drug and Patent Term Restoration Act... as the patented item (human drug product, animal drug product, medical device, food additive, or... approval phase. For human drug products, the testing phase begins when the exemption to permit the clinical...

75 FR 19406 - Determination of Regulatory Review Period for Purposes of Patent Extension; AFINITOR

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-14

... Restoration Act of 1984 (Public Law 98-417) and the Generic Animal Drug and Patent Term Restoration Act... as the patented item (human drug product, animal drug product, medical device, food additive, or... approval phase. For human drug products, the testing phase begins when the exemption to permit the clinical...

76 FR 36929 - Determination of Regulatory Review Period for Purposes of Patent Extension; DEXILANT

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-23

... Restoration Act of 1984 (Pub. L. 98-417) and the Generic Animal Drug and Patent Term Restoration Act (Pub. L... patented item (human drug product, animal drug product, medical device, food additive, or color additive... drug products, the testing phase begins when the exemption to permit the clinical investigations of the...

75 FR 17415 - Determination of Regulatory Review Period for Purposes of Patent Extension; FANAPT

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-06

... Restoration Act of 1984 (Public Law 98-417) and the Generic Animal Drug and Patent Term Restoration Act... as the patented item (human drug product, animal drug product, medical device, food additive, or... approval phase. For human drug products, the testing phase begins when the exemption to permit the clinical...

[Drugs use in pregnancy in the Valencia Region and the risk of congenital anomalies].

PubMed

Cavero-Carbonell, Clara; Gimeno-Martos, Silvia; Páramo-Rodríguez, Lucía; Rabanaque-Hernández, María José; Martos-Jiménez, Carmen; Zurriaga, Óscar

2017-09-01

Despite the potential risks of drug use during pregnancy, consumption has increased in recent decades. To identify the risk of congenital anomalies (CA) associated with the use of drugs in primary care in pregnant women residents in the Valencia Region. A case-control study, considering a case as a less than one year old live birth in 2009-2010, diagnosed with a CA and resident in the Valencia Region, obtained from the CA population-based registry. Controls were selected from the Metabolic Disease Registry, and the drugs prescribed and dispensed from the Integral Management of Pharmaceutical Services. Crude odds ratio (OR) was calculated with its 95% confidence intervals and adjusted OR was calculated using logistic regression. A total of 1,913 cases and 3,826 controls were identified. The most frequently used drug groups were those acting on the musculoskeletal, nervous and respiratory systems, on the blood and blood forming organs, and anti-infection drugs. The most common drugs used were ibuprofen, dexketoprofen, paracetamol, amoxicillin, ferrous sulphate, and a combination of folic acid. A significantly increased risk of CA was identified for drugs acting on the musculoskeletal system (adjusted OR 1.14 [95% confidence interval 1.02-1.28]). A significantly decreased risk was observed for drugs acting on the blood and blood forming organs (adjusted OR 0.87 [95% confidence interval 0.78-0.98]). Associations between drugs and CA in pregnant women resident in the Valencia Region have been identified for drugs that act as risk factors of CA, and for drugs that act as protective factors of CA. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Co-loaded paclitaxel/rapamycin liposomes: Development, characterization and in vitro and in vivo evaluation for breast cancer therapy.

PubMed

Eloy, Josimar O; Petrilli, Raquel; Topan, José Fernando; Antonio, Heriton Marcelo Ribeiro; Barcellos, Juliana Palma Abriata; Chesca, Deise L; Serafini, Luciano Neder; Tiezzi, Daniel G; Lee, Robert J; Marchetti, Juliana Maldonado

2016-05-01

Paclitaxel and rapamycin have been reported to act synergistically to treat breast cancer. Albeit paclitaxel is available for breast cancer treatment, the most commonly used formulation in the clinic presents side effects, limiting its use. Furthermore, both drugs present pharmacokinetics drawbacks limiting their in vivo efficacy and clinic combination. As an alternative, drug delivery systems, particularly liposomes, emerge as an option for drug combination, able to simultaneously deliver co-loaded drugs with improved therapeutic index. Therefore, the purpose of this study is to develop and characterize a co-loaded paclitaxel and rapamycin liposome and evaluate it for breast cancer efficacy both in vitro and in vivo. Results showed that a SPC/Chol/DSPE-PEG (2000) liposome was able to co-encapsulate paclitaxel and rapamycin with suitable encapsulation efficiency values, nanometric particle size, low polydispersity and neutral zeta potential. Taken together, FTIR and thermal analysis evidenced drug conversion to the more bioavailable molecular and amorphous forms, respectively, for paclitaxel and rapamycin. The pegylated liposome exhibited excellent colloidal stability and was able to retain drugs encapsulated, which were released in a slow and sustained fashion. Liposomes were more cytotoxic to 4T1 breast cancer cell line than the free drugs and drugs acted synergistically, particularly when co-loaded. Finally, in vivo therapeutic evaluation carried out in 4T1-tumor-bearing mice confirmed the in vitro results. The co-loaded paclitaxel/rapamycin pegylated liposome better controlled tumor growth compared to the solution. Therefore, we expect that the formulation developed herein might be a contribution for future studies focusing on the clinical combination of paclitaxel and rapamycin. Copyright © 2016 Elsevier B.V. All rights reserved.

Simple Field Assays to Check Quality of Current Artemisinin-Based Antimalarial Combination Formulations

PubMed Central

Ioset, Jean-Robert; Kaur, Harparkash

2009-01-01

Introduction Malaria continues to be one of the major public health problems in Africa, Asia and Latin America. Artemisinin derivatives (ARTs; artesunate, artemether, and dihydroartemisinin) derived from the herb, Artemisia annua, are the most effective antimalarial drugs available providing rapid cures. The World Health Organisation (WHO) has recommended that all antimalarials must be combined with an artemisinin component (artemisinin-based combination therapy; ACT) for use as first line treatment against malaria. This class of drugs is now first-line policy in most malaria-endemic countries. Reports of ad hoc surveys from South East Asia show that up to 50% of the artesunate currently sold is counterfeit. Drug quality is rarely assessed in resource poor countries in part due to lack of dedicated laboratory facilities which are expensive to build, equip and maintain. With a view to address this unmet need we developed two novel colour reaction assays that can be used in the field to check the quality of ARTs. Methods and Findings Our assays utilise thin layer chromatography silica gel sheets and 2, 4 dinitrophenylhydrazine or 4-Benzoylamino-2, 5-dimethoxybenzenediazonium chloride hemi (zinc chloride) salt as the reagents showing a pink or blue product respectively only in the presence ARTs. We are able to detect as low as 10% of ARTs in ACTs (WINTHROP - artesunate/amodiaquine, Coartem®-artemether/lumefantrine and Duocortexcin - dihydroartemisinin/piperaquine). The assays have been validated extensively by testing eighty readily accessible and widely used drugs in malaria endemic countries. None of the other antimalarial drugs or a range of commonly used excipients, antiretroviral drugs or other frequently used drugs from the WHO essential drugs list such as analgesics or antibiotics are detected with our assays. Conclusions Our two independent assays requiring no specialist training are specific, simple to use, rapid, robust, reproducible, inexpensive and, have successfully resulted in detecting two counterfeit drugs within a small scale screening survey of over 100 declared artemisinin-containing drugs collected from various Asian and African countries. These promising results indicate that the assays will provide a useful first test to assure the quality of the ACTs formulations in resource poor malaria endemic areas when there is an absence of dedicated medicines quality laboratory facilities. PMID:19789707

Small-scale screening of anticancer drugs acting specifically on neural stem/progenitor cells derived from human-induced pluripotent stem cells using a time-course cytotoxicity test.

PubMed

Fukusumi, Hayato; Handa, Yukako; Shofuda, Tomoko; Kanemura, Yonehiro

2018-01-01

Since the development of human-induced pluripotent stem cells (hiPSCs), various types of hiPSC-derived cells have been established for regenerative medicine and drug development. Neural stem/progenitor cells (NSPCs) derived from hiPSCs (hiPSC-NSPCs) have shown benefits for regenerative therapy of the central nervous system. However, owing to their intrinsic proliferative potential, therapies using transplanted hiPSC-NSPCs carry an inherent risk of undesired growth in vivo . Therefore, it is important to find cytotoxic drugs that can specifically target overproliferative transplanted hiPSC-NSPCs without damaging the intrinsic in vivo stem-cell system. Here, we examined the chemosensitivity of hiPSC-NSPCs and human neural tissue-derived NSPCs (hN-NSPCs) to the general anticancer drugs cisplatin, etoposide, mercaptopurine, and methotrexate. A time-course analysis of neurospheres in a microsphere array identified cisplatin and etoposide as fast-acting drugs, and mercaptopurine and methotrexate as slow-acting drugs. Notably, the slow-acting drugs were eventually cytotoxic to hiPSC-NSPCs but not to hN-NSPCs, a phenomenon not evident in the conventional endpoint assay on day 2 of treatment. Our results indicate that slow-acting drugs can distinguish hiPSC-NSPCs from hN-NSPCs and may provide an effective backup safety measure in stem-cell transplant therapies.

Characteristics of drug use on sheep farms in Ontario, Canada

PubMed Central

Moon, Catherine S.; Berke, Olaf; Avery, Brent P.; McEwen, Scott A.; Reid-Smith, Richard J.; Scott, Lisa; Menzies, Paula

2010-01-01

This study examined characteristics of the use of drugs, especially antimicrobials, on Ontario sheep farms. Forty-nine sheep farms participated in a 12-month prospective study. Producers documented treatment events during the study period and drug use data from the records were summarized. The most frequently used drugs of the 15 drug categories used by producers belonged to the following categories: antimicrobial (40.7%, n = 2710), vitamin/mineral (12.0%), and biological (11.1%). Short-acting penicillin (27.2%, n = 1103), long-acting oxytetracycline (22.9%), and long-acting penicillin (21.9%) were the most frequently used antimicrobials. The drugs that were used most frequently on sheep farms were antimicrobials, of which 93% of treatments were extra-label. Extensive extra-label drug use may be the result of the limited number of drugs that are approved in Canada for use in sheep. PMID:21358930

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.

75 FR 24967 - Andean Trade Preference Act: Impact on the U.S. Economy and on Andean Drug Crop Eradication

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-06

...Section 206 of the ATPA (19 U.S.C. 3204) requires the Commission to report biennially to the Congress by September 30 of each reporting year on the economic impact of the Act on U.S. industries and U.S. consumers, as well as on the effectiveness of the Act in promoting drug related crop eradication and crop substitution efforts by beneficiary countries. The Commission prepares these reports under investigation No. 332-352, Andean Trade Preference Act: Impact on the U.S. Economy and on Andean Drug Crop Eradication.

77 FR 28620 - Andean Trade Preference Act: Impact on the U.S. Economy and on Andean Drug Crop Eradication

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-15

...Section 206 of the ATPA (19 U.S.C. 3204) requires the Commission to report biennially to the Congress by September 30 of each reporting year on the economic impact of the Act on U.S. industries and U.S. consumers, as well as on the effectiveness of the Act in promoting drug related crop eradication and crop substitution efforts by beneficiary countries. The Commission prepares these reports under investigation No. 332-352, Andean Trade Preference Act: Impact on the U.S. Economy and on Andean Drug Crop Eradication.

Sodium glucose co-transporter 2 (SGLT2) inhibitors: new among antidiabetic drugs.

PubMed

Opie, L H

2014-08-01

Type 2 diabetes is characterized by decreased insulin secretion and sensitivity. The available oral anti-diabetic drugs act on many different molecular sites. The most used of oral anti-diabetic agents is metformin that activates glucose transport vesicles to the cell surface. Others are: the sulphonylureas; agents acting on the incretin system; GLP-1 agonists; dipetidylpeptidase-4 inhibitors; meglinitide analogues; and the thiazolidinediones. Despite these many drugs acting by different mechanisms, glycaemic control often remains elusive. None of these drugs have a primary renal mechanism of action on the kidneys, where almost all glucose excreted is normally reabsorbed. That is where the inhibitors of glucose reuptake (sodium-glucose cotransporter 2, SGLT2) have a unique site of action. Promotion of urinary loss of glucose by SGLT2 inhibitors embodies a new principle of control in type 2 diabetes that has several advantages with some urogenital side-effects, both of which are evaluated in this review. Specific approvals include use as monotherapy, when diet and exercise alone do not provide adequate glycaemic control in patients for whom the use of metformin is considered inappropriate due to intolerance or contraindications, or as add-on therapy with other anti-hyperglycaemic medicinal products including insulin, when these together with diet and exercise, do not provide adequate glycemic control. The basic mechanisms are improved β-cell function and insulin sensitivity. When compared with sulphonylureas or other oral antidiabetic agents, SGLT2 inhibitors provide greater HbA1c reduction. Urogenital side-effects related to the enhanced glycosuria can be troublesome, yet seldom lead to discontinuation. On this background, studies are analysed that compare SGLT2 inhibitors with other oral antidiabetic agents. Their unique mode of action, unloading the excess glycaemic load, contrasts with other oral agents that all act to counter the effects of diabetic hyperglycaemia.

Diffusion of subsidized ACTs in accredited drug shops in Tanzania: determinants of stocking and characteristics of early and late adopters

PubMed Central

2013-01-01

Background Many households in sub-Saharan Africa utilize the private sector as a primary source of treatment for malaria episodes. Expanding access to effective treatment in private drug shops may help reduce incidence of severe disease and mortality. This research leveraged a longitudinal survey of stocking of subsidized artemisinin combination therapies (ACTs), an effective anti-malarial, in Accredited Drug Dispensing Outlets (ADDOs) in two regions of Tanzania. This provided a unique opportunity to explore shop and market level determinants of product diffusion in a developing country retail market. Methods 356 ADDOs in the Rukwa and Mtwara regions of Tanzania were surveyed at seven points between Feb 2011 and May 2012. Shop level audits were used to measure the availability of subsidized ACTs at each shop. Data on market and shop level factors were collected during the survey and also extracted from GIS layers. Regression and network based methodologies were used. Shops classified as early and late adopters, following Rogers’ model of product diffusion, were compared. The Bass model of product diffusion was applied to determine whether shops stocked ACTs out of a need to imitate market competitors or a desire to satisfy customer needs. Results Following the introduction of a subsidy for ACTs, stocking increased from 12% to nearly 80% over the seven survey rounds. Stocking was influenced by higher numbers of proximal shops and clinics, larger customer traffic and the presence of a licensed pharmacist. Early adopters were characterized by a larger percentage of customers seeking care for malaria, a larger catchment and sourcing from specific wholesalers/suppliers. The Bass model of product diffusion indicated that shops were adopting products in response to competitor behavior, rather than customer demand. Conclusions Decisions to stock new pharmaceutical products in Tanzanian ADDOs are influenced by a combination of factors related to both market competition and customer demand, but are particularly influenced by the behavior of competing shops. Efforts to expand access to new pharmaceutical products in developing country markets could benefit from initial targeting of high profile shops in competitive markets and wholesale suppliers to encourage faster product diffusion across all drug retailers. PMID:24350611

Diffusion of subsidized ACTs in accredited drug shops in Tanzania: determinants of stocking and characteristics of early and late adopters.

PubMed

Larson, Peter S; Yadav, Prashant; Alphs, Sarah; Arkedis, Jean; Massaga, Julius; Sabot, Oliver; Cohen, Jessica L

2013-12-18

Many households in sub-Saharan Africa utilize the private sector as a primary source of treatment for malaria episodes. Expanding access to effective treatment in private drug shops may help reduce incidence of severe disease and mortality. This research leveraged a longitudinal survey of stocking of subsidized artemisinin combination therapies (ACTs), an effective anti-malarial, in Accredited Drug Dispensing Outlets (ADDOs) in two regions of Tanzania. This provided a unique opportunity to explore shop and market level determinants of product diffusion in a developing country retail market. 356 ADDOs in the Rukwa and Mtwara regions of Tanzania were surveyed at seven points between Feb 2011 and May 2012. Shop level audits were used to measure the availability of subsidized ACTs at each shop. Data on market and shop level factors were collected during the survey and also extracted from GIS layers. Regression and network based methodologies were used. Shops classified as early and late adopters, following Rogers' model of product diffusion, were compared. The Bass model of product diffusion was applied to determine whether shops stocked ACTs out of a need to imitate market competitors or a desire to satisfy customer needs. Following the introduction of a subsidy for ACTs, stocking increased from 12% to nearly 80% over the seven survey rounds. Stocking was influenced by higher numbers of proximal shops and clinics, larger customer traffic and the presence of a licensed pharmacist. Early adopters were characterized by a larger percentage of customers seeking care for malaria, a larger catchment and sourcing from specific wholesalers/suppliers. The Bass model of product diffusion indicated that shops were adopting products in response to competitor behavior, rather than customer demand. Decisions to stock new pharmaceutical products in Tanzanian ADDOs are influenced by a combination of factors related to both market competition and customer demand, but are particularly influenced by the behavior of competing shops. Efforts to expand access to new pharmaceutical products in developing country markets could benefit from initial targeting of high profile shops in competitive markets and wholesale suppliers to encourage faster product diffusion across all drug retailers.

21 CFR 330.1 - General conditions for general recognition as safe, effective and not misbranded.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false General conditions for general recognition as safe, effective and not misbranded. 330.1 Section 330.1 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... product is labeled in compliance with chapter V of the Federal Food, Drug, and Cosmetic Act (the act) and...

75 FR 45632 - Animal Drug User Fee Rates and Payment Procedures for Fiscal Year 2011

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-03

... available to you after you submit a cover sheet. Click the ``Pay Now'' button.) On your check, bank draft... 2011, FDA is assuming that the number of applications that will pay fees in FY 2011 will equal the... applications subject to the criteria set forth is section 512(d)(4) of the act which pay half of the full fee...

77 FR 28604 - Agency Information Collection Activities; Proposed Collection; Comment Request; Guidance for...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-15

... Approved Application as Required by the Dietary Supplement and Nonprescription Drug Consumer Protection Act... Dietary Supplement and Nonprescription Drug Consumer Protection Act.'' DATES: Submit either electronic or... Nonprescription Human Drug Products Marketed Without an Approved Application as Required by the Dietary Supplement...

Cost-effectiveness analysis of introducing malaria diagnostic testing in drug shops: A cluster-randomised trial in Uganda

PubMed Central

Hansen, Kristian Schultz; Clarke, Siân E.; Lal, Sham; Magnussen, Pascal; Mbonye, Anthony K.

2017-01-01

Background Private sector drug shops are an important source of malaria treatment in Africa, yet diagnosis without parasitological testing is common among these providers. Accurate rapid diagnostic tests for malaria (mRDTs) require limited training and present an opportunity to increase access to correct diagnosis. The present study was a cost-effectiveness analysis of the introduction of mRDTs in Ugandan drug shops. Methods Drug shop vendors were trained to perform and sell subsidised mRDTs and artemisinin-based combination therapies (ACTs) in the intervention arm while vendors offered ACTs following presumptive diagnosis of malaria in the control arm. The effect on the proportion of customers with fever ‘appropriately treated of malaria with ACT’ was captured during a randomised trial in drug shops in Mukono District, Uganda. Health sector costs included: training of drug shop vendors, community sensitisation, supervision and provision of mRDTs and ACTs to drug shops. Household costs of treatment-seeking were captured in a representative sample of drug shop customers. Findings The introduction of mRDTs in drug shops was associated with a large improvement of diagnosis and treatment of malaria, resulting in low incremental costs for the health sector at US$0.55 per patient appropriately treated of malaria. High expenditure on non-ACT drugs by households contributed to higher incremental societal costs of US$3.83. Sensitivity analysis showed that mRDTs would become less cost-effective compared to presumptive diagnosis with increasing malaria prevalence and lower adherence to negative mRDT results. Conclusion mRDTs in drug shops improved the targeting of ACTs to malaria patients and are likely to be considered cost-effective compared to presumptive diagnosis, although the increased costs borne by households when the test result is negative are a concern. PMID:29244829

Long-acting atypical injectable antipsychotics in the treatment of schizophrenia: safety and tolerability review.

PubMed

Cañas, Fernando; Möller, Hans-Jürgen

2010-09-01

Although atypical antipsychotics have beneficial efficacy and tolerance, non-adherence and partial adherence remain in patients treated for schizophrenia. Long-acting injectable or depot atypical antipsychotics offer better medication adherence and tolerability advantages. Currently, two drugs are available for the treatment of schizophrenia, risperidone long-acting injectable (RLAI) and olanzapine pamoate (OP). Short- and long-term safety and tolerability data on RLAI and OP from January 2006 through September 2009 were reviewed by performing Medline and PubMed searches, reviewing abstracts and poster presentations, and viewing available material from the FDA and European Medicines Agency. RLAI and OP show good short- and long-term safety when treating patients with schizophrenia, with uncommon discontinuation due to adverse effects. RLAI and OP data show rare problems with injection site reactions and patients exposed to injectable treatments prefer to continue injections. Infrequent but serious post-injection delirium sedation syndrome occurred after 1% of OP injections. Weight gain was generally higher among patients treated with OP versus RLAI. Healthcare providers, patients and family members should be made aware of the safety and benefits of long-acting injectable atypical antipsychotics in order to diminish the unnecessary restrictions of these therapies for patients with schizophrenia.

Optimization of the Bacterial Cytochrome P450 BM3 System for the Production of Human Drug Metabolites

PubMed Central

Di Nardo, Giovanna; Gilardi, Gianfranco

2012-01-01

Drug metabolism in human liver is a process involving many different enzymes. Among them, a number of cytochromes P450 isoforms catalyze the oxidation of most of the drugs commercially available. Each P450 isoform acts on more than one drug, and one drug may be oxidized by more than one enzyme. As a result, multiple products may be obtained from the same drug, and as the metabolites can be biologically active and may cause adverse drug reactions (ADRs), the metabolic profile of a new drug has to be known before this can be commercialized. Therefore, the metabolites of a certain drug must be identified, synthesized and tested for toxicity. Their synthesis must be in sufficient quantities to be used for metabolic tests. This review focuses on the progresses done in the field of the optimization of a bacterial self-sufficient and efficient cytochrome P450, P450 BM3 from Bacillus megaterium, used for the production of metabolites of human enzymes. The progress made in the improvement of its catalytic performance towards drugs, the substitution of the costly NADPH cofactor and its immobilization and scale-up of the process for industrial application are reported. PMID:23443101

21 CFR 21.1 - Scope.

Code of Federal Regulations, 2010 CFR

2010-04-01

... the Food and Drug Administration and contained in Privacy Act Record Systems. (b) This part does not: (1) Apply to Food and Drug Administration record systems that are not Privacy Act Record Systems or... by his name or other personal identifier, whether or not contained in a Privacy Act Record System...

21 CFR 1210.31 - Hearing before prosecution.

Code of Federal Regulations, 2010 CFR

2010-04-01

....31 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... FEDERAL IMPORT MILK ACT Hearings § 1210.31 Hearing before prosecution. Before violation of the act is referred to the Department of Justice for prosecution under section 5 of the Federal Import Milk Act, an...

21 CFR 1210.31 - Hearing before prosecution.

Code of Federal Regulations, 2011 CFR

2011-04-01

....31 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... FEDERAL IMPORT MILK ACT Hearings § 1210.31 Hearing before prosecution. Before violation of the act is referred to the Department of Justice for prosecution under section 5 of the Federal Import Milk Act, an...

78 FR 63218 - Draft Guidance for Industry on Chronic Hepatitis C Virus Infection: Developing Direct-Acting...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-23

...] Draft Guidance for Industry on Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral... entitled ``Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Drugs for Treatment... antiviral (DAA) drugs for the treatment of chronic hepatitis C. This guidance revises and replaces a...

The Controlled Substances Act: how a "big tent" reform became a punitive drug law.

PubMed

Courtwright, David T

2004-10-05

The 1970 Controlled Substances Act was part of an omnibus reform package designed to rationalize, and in some respects to liberalize, American drug policy. While the legislation provided additional resources for law enforcement and a systematic means for regulating the use of most psychoactive drugs, it also did away with mandatory minimum sentences and provided more support for treatment and research. Over the next three decades, and in response to public alarm about drug abuse, the US Congress continuously amended the law to produce a more punitive system of drug control. The amendments, which gave the Drug Enforcement Administration greater control over scheduling and maintenance and which substantially increased penalties for illicit trafficking, transformed the law into the legal foundation of America's "drug war," as the stricter criminal approach came to be known. By the 1980s, the flexibility and innovative spirit of the original Controlled Substances Act (and that of Nixon-era drug strategy generally) had largely disappeared from American drug policy.

Maximising HIV prevention by balancing the opportunities of today with the promises of tomorrow: a modelling study.

PubMed

Smith, Jennifer A; Anderson, Sarah-Jane; Harris, Kate L; McGillen, Jessica B; Lee, Edward; Garnett, Geoff P; Hallett, Timothy B

2016-07-01

Many ways of preventing HIV infection have been proposed and more are being developed. We sought to construct a strategic approach to HIV prevention that would use limited resources to achieve the greatest possible prevention impact through the use of interventions available today and in the coming years. We developed a deterministic compartmental model of heterosexual HIV transmission in South Africa and formed assumptions about the costs and effects of a range of interventions, encompassing the further scale-up of existing interventions (promoting condom use, male circumcision, early antiretroviral therapy [ART] initiation for all [including increased HIV testing and counselling activities], and oral pre-exposure prophylaxis [PrEP]), the introduction of new interventions in the medium term (offering intravaginal rings, long-acting injectable antiretroviral drugs) and long term (vaccine, broadly neutralising antibodies [bNAbs]). We examined how available resources could be allocated across these interventions to achieve maximum impact, and assessed how this would be affected by the failure of the interventions to be developed or scaled up. If all interventions are available, the optimum mix would place great emphasis on the following: scale-up of male circumcision and early ART initiation with outreach testing, as these are available immediately and assumed to be low cost and highly efficacious; intravaginal rings targeted to sex workers; and vaccines, as these can achieve a large effect if scaled up even if imperfectly efficacious. The optimum mix would rely less on longer term developments, such as long-acting antiretroviral drugs and bNAbs, unless the costs of these reduced. However, if impossible to scale up existing interventions to the extent assumed, emphasis on oral PrEP, intravaginal rings, and long-acting antiretroviral drugs would increase. The long-term effect on the epidemic is most affected by scale-up of existing interventions and the successful development of a vaccine. With current information, a strategic approach in which limited resources are used to maximise prevention impact would focus on strengthening the scale-up of existing interventions, while pursuing a workable vaccine and developing other approaches that can be used if further scale-up of existing interventions is limited. Bill & Melinda Gates Foundation. Copyright © 2016 Smith et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

The Global Fund to Fight AIDS, Tuberculosis, and Malaria: Progress Report and Issues for Congress

DTIC Science & Technology

2006-04-25

artemisinin -based combination drug treatments (ACT). Artemisinin -based treatments have been found to be effective in dealing with drug-resistant...and have no observable resistance are considerably more expensive. The new drugs called, “ artemisinin -based combination therapies” (ACTs) cost about

76 FR 58020 - Prescription Drug User Fee Act IV Information Technology Plan

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-19

...] Prescription Drug User Fee Act IV Information Technology Plan AGENCY: Food and Drug Administration, HHS. ACTION... information technology (IT) plan entitled ``PDUFA IV Information Technology Plan'' (updated plan) to achieve... Information Technology Plan.'' This plan will meet one of the performance goals agreed to under the 2007...

Perioperative Use of Clevidipine: A Systematic Review and Meta-Analysis

PubMed Central

Espinosa, Angel; Ripollés–Melchor, Javier; Casans-Francés, Rubén; Abad-Gurumeta, Alfredo; Bergese, Sergio D.; Zuleta-Alarcon, Alix; López-Timoneda, Francisco; Calvo-Vecino, José María

2016-01-01

Background Clevidipine is an ultrashort-acting drug for rapid reduction of blood pressure by selectively acting on the L-type Ca2+ channels on arteriolar smooth muscle. The drug’s ultrashort action in reducing the blood pressure is due to its rapid hydrolysis by blood and extravascular tissue esterases, which does not depend on hepato-renal metabolism and excretion. An analysis of the perioperative management of blood pressure should be considered to compare with other intravenous antihypertensive agents. Methods Analyses of the available evidence in randomized clinical trials following the PRISMA methodology as well as clinical significance according to the GRADE system were conducted. Placebo versus other antihypertensive drugs studies were included. Statistical assessments were done using the X2 and I2 tests. Results Clevidipine was more effective in maintaining the blood pressure within pre-specified ranges compared with other antihypertensive drugs (MD, -17.87 CI 95%: -29.02 to -6.72; p = 0.02). The use of Clevidipine versus placebo and rescue antihypertensive intravenous drug showed a clear reduction in rates of treatment failure (RR 0.10; IC 95%; 0.05–0.18; p <0.0001). There was no difference in the incidence of adverse events compared with placebo (RR 1.47; 95% CI 0.89 to 2.43, p = 0.14) and with other antihypertensive drugs (RR 0.78, 95% CI 0.45 to 1.35; p = 0.37). In addition, there was no difference in the incidence of atrial fibrillation (AF) between clevidipine and control groups (RR 1.09, IC del 95%: 0.65 a 1.83; p = 0.73). Conclusions Clevidipine is an ultrafast-acting drug that is highly effective for management of perioperative arterial hypertension. It is devoid of adverse effects associated with the use of other IV antihypertensives. Its favorable pharmacodynamic and pharmacokinetic properties make clevidipine the drug of choice for the management of acute perioperative hypertension. It is important to emphasize the need for further studies with a larger number of patients to confirm these findings and increase the degree of evidence. PMID:27018586

Hepatitis C virus resistance to the new direct-acting antivirals.

PubMed

Esposito, Isabella; Trinks, Julieta; Soriano, Vicente

2016-10-01

The treatment of hepatitis C virus (HCV) infection has dramatically improved in recent years with the widespread use of interferon-free combination regimens. Despite the high sustained virological response (SVR) rates (over 90%) obtained with direct-acting antivirals (DAAs), drug resistance has emerged as a potential challenge. The high replication rate of HCV and the low fidelity of its RNA polymerase result in a high degree of genetic variability in the HCV population, which ultimately explains the rapid selection of drug resistance associated variants (RAVs). Results from clinical trials and real-world experience have both provided important information on the rate and clinical significance of RAVs. They can be present in treatment-naive patients as natural polymorphisms although more frequently they are selected upon treatment failure. In patients engaged in high-risk behaviors, RAVs can be transmitted. Although DAA failures generally occur in less than 10% of treated chronic hepatitis C patients, selection of drug resistance is the rule in most cases. HCV re-treatment options are available, but first-line therapeutic strategies should be optimized to efficiently prevent DAA failure due to baseline HCV resistance. Considerable progress is being made and next-generation DAAs are coming with pangenotypic activity and higher resistance barrier.

21 CFR 808.1 - Scope.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Product Radiation Control of the Federal Food, Drug, and Cosmetic Act (formerly the Radiation Control for... Administration issues specific requirements under the Federal Food, Drug, and Cosmetic Act applicable to these...

21 CFR 808.1 - Scope.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Product Radiation Control of the Federal Food, Drug, and Cosmetic Act (formerly the Radiation Control for... Administration issues specific requirements under the Federal Food, Drug, and Cosmetic Act applicable to these...

21 CFR 808.1 - Scope.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Product Radiation Control of the Federal Food, Drug, and Cosmetic Act (formerly the Radiation Control for... Administration issues specific requirements under the Federal Food, Drug, and Cosmetic Act applicable to these...

21 CFR 808.1 - Scope.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Product Radiation Control of the Federal Food, Drug, and Cosmetic Act (formerly the Radiation Control for... Administration issues specific requirements under the Federal Food, Drug, and Cosmetic Act applicable to these...

Computational methods in drug discovery

PubMed Central

Leelananda, Sumudu P

2016-01-01

The process for drug discovery and development is challenging, time consuming and expensive. Computer-aided drug discovery (CADD) tools can act as a virtual shortcut, assisting in the expedition of this long process and potentially reducing the cost of research and development. Today CADD has become an effective and indispensable tool in therapeutic development. The human genome project has made available a substantial amount of sequence data that can be used in various drug discovery projects. Additionally, increasing knowledge of biological structures, as well as increasing computer power have made it possible to use computational methods effectively in various phases of the drug discovery and development pipeline. The importance of in silico tools is greater than ever before and has advanced pharmaceutical research. Here we present an overview of computational methods used in different facets of drug discovery and highlight some of the recent successes. In this review, both structure-based and ligand-based drug discovery methods are discussed. Advances in virtual high-throughput screening, protein structure prediction methods, protein–ligand docking, pharmacophore modeling and QSAR techniques are reviewed. PMID:28144341

Computational methods in drug discovery.

PubMed

Leelananda, Sumudu P; Lindert, Steffen

2016-01-01

The process for drug discovery and development is challenging, time consuming and expensive. Computer-aided drug discovery (CADD) tools can act as a virtual shortcut, assisting in the expedition of this long process and potentially reducing the cost of research and development. Today CADD has become an effective and indispensable tool in therapeutic development. The human genome project has made available a substantial amount of sequence data that can be used in various drug discovery projects. Additionally, increasing knowledge of biological structures, as well as increasing computer power have made it possible to use computational methods effectively in various phases of the drug discovery and development pipeline. The importance of in silico tools is greater than ever before and has advanced pharmaceutical research. Here we present an overview of computational methods used in different facets of drug discovery and highlight some of the recent successes. In this review, both structure-based and ligand-based drug discovery methods are discussed. Advances in virtual high-throughput screening, protein structure prediction methods, protein-ligand docking, pharmacophore modeling and QSAR techniques are reviewed.

Unintended Effects of Orphan Product Designation for Rare Neurological Diseases

PubMed Central

Murphy, Sinéad M; Puwanant, Araya; Griggs, Robert C.

2012-01-01

Since the introduction of the Orphan Drug Act in 1983, designed to promote development of treatments for rare diseases, at least 378 orphan drugs have been approved. Incentives include financial support, tax credits and, perhaps most importantly, extended market exclusivity. These incentives have encouraged industry interest and accelerated research on rare diseases, allowing patients with orphan diseases access to treatments. However, extended market exclusivity has been associated with unacceptably high drug costs; both for newly developed drugs and even for drugs which were previously widely available. We suggest that a paradoxical effect of orphan product exclusivity can be reduced patient access to existing drugs. In addition, the costs of each new drug are arguably unsustainable for patients and for the American health care system. Of all the specialties, neurology has the third highest number of orphan product designations, and neurological diseases account for at least one fifth of rare diseases. Citing the use of tetrabenazine for chorea in Huntington’s disease, adrenocorticotropic hormone for infantile spasms and enzyme replacement therapy with alglucosidase alpha for Pompe’s disease we highlight these paradoxical effects. PMID:23109143

Nutraceutical phycocyanin nanoformulation for efficient drug delivery of paclitaxel in human glioblastoma U87MG cell line

NASA Astrophysics Data System (ADS)

Agrawal, Madhunika; Yadav, Sanjeev Kumar; Agrawal, Satyam Kumar; Karmakar, Surajit

2017-08-01

To enhance the therapeutic efficacy of chemotherapy on glioblastoma U87MG cell line, paclitaxel-loaded phycocyanin nanoparticles (PTX-PcNPs) were prepared by modified desolvation process. PTX-PcNPs were characterised in terms of size, zeta potential, drug loading efficiency and drug release. Confocal laser scanning microscopy showed PTX-PcNPs could be internalised by U87MG cells. The anti-cancer activity was investigated in vitro by 3-(4,5-dimethylthizol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay with and without photodynamic therapy. It was observed that formulation could significantly inhibit growth of U87MG cells as compared to PTX alone and also induced apoptosis, which was evidenced by presence of apoptotic bodies and nuclear fragmentation in treated cells. The present study suggests that PTX-PcNPs can act as a promising drug delivery system for cancer treatment. [Figure not available: see fulltext.

You are what you eat: influence of type and amount of food consumed on central dopamine systems and the behavioral effects of direct- and indirect-acting dopamine receptor agonists

PubMed Central

Baladi, Michelle G; Daws, Lynette C; France, Charles P

2012-01-01

The important role of dopamine (DA) in mediating feeding behavior and the positive reinforcing effects of some drugs is well recognized. Less widely studied is how feeding conditions might impact the sensitivity of drugs acting on DA systems. Food restriction, for example, has often been the focus of aging and longevity studies; however, other studies have demonstrated that mild food restriction markedly increases sensitivity to direct- and indirect-acting DA receptor agonists. Moreover, it is becoming clear that not only the amount of food, but the type of food, is an important factor in modifying the effects of drugs. Given the increased consumption of high fat and sugary foods, studies are exploring how consumption of highly palatable food impacts DA neurochemistry and the effects of drugs acting on these systems. For example, eating high fat chow increases sensitivity to some behavioral effects of direct- as well as indirect-acting DA receptor agonists. A compelling mechanistic possibility is that the central DA pathways that mediate the effects of some drugs are regulated by one or more of the endocrine hormones (e.g. insulin) that undergo marked changes during food restriction or after consuming high fat or sugary foods. Although traditionally recognized as an important signaling molecule in regulating energy homeostasis, insulin can also regulate DA neurochemistry. Because direct- and indirect-acting DA receptor drugs are used therapeutically and some are abused, a better understanding of how food intake impacts response to these drugs would likely facilitate improved treatment of clinical disorders and provide information that would be relevant to the causes of vulnerability to abuse drugs. PMID:22710441

The malaria testing and treatment market in Kinshasa, Democratic Republic of the Congo, 2013.

PubMed

Mpanya, Godéfroid; Tshefu, Antoinette; Likwela, Joris Losimba

2017-02-28

The Democratic Republic of Congo (DRC) is one of the two most leading contributors to the global burden of disease due to malaria. This paper describes the malaria testing and treatment market in the nation's capital province of Kinshasa, including availability of malaria testing and treatment and relative anti-malarial market share for the public and private sector. A malaria medicine outlet survey was conducted in Kinshasa province in 2013. Stratified multi-staged sampling was used to select areas for the survey. Within sampled areas, all outlets with the potential to sell or distribute anti-malarials in the public and private sector were screened for eligibility. Among outlets with anti-malarials or malaria rapid diagnostic tests (RDT) in stock, a full audit of all available products was conducted. Information collected included product information (e.g. active ingredients, brand name), amount reportedly distributed to patients in the past week, and retail price. In total, 3364 outlets were screened for inclusion across Kinshasa and 1118 outlets were eligible for the study. Among all screened outlets in the private sector only about one in ten (12.1%) were stocking quality-assured Artemisinin-based Combination Therapy (ACT) medicines. Among all screened public sector facilities, 24.5% had both confirmatory testing and quality-assured ACT available, and 20.2% had sulfadoxine-pyrimethamine (SP) available for intermittent preventive therapy during pregnancy (IPTp). The private sector distributed the majority of anti-malarials in Kinshasa (96.7%), typically through drug stores (89.1% of the total anti-malarial market). Non-artemisinin therapies were the most commonly distributed anti-malarial (50.1% of the total market), followed by non quality-assured ACT medicines (38.5%). The median price of an adult quality-assured ACT was $6.59, and more expensive than non quality-assured ACT ($3.71) and SP ($0.44). Confirmatory testing was largely not available in the private sector (1.1%). While the vast majority of anti-malarial medicines distributed to patients in Kinshasa province are sold within the private sector, availability of malaria testing and appropriate treatment for malaria is alarmingly low. There is a critical need to improve access to confirmatory testing and quality-assured ACT in the private sector. Widespread availability and distribution of non quality-assured ACT and non-artemisinin therapies must be addressed to ensure effective malaria case management.

Tools for studying drug transport and metabolism in the brain.

PubMed

Pitcher, Meagan R; Quevedo, João

2016-01-01

Development of xenobiotics that cross the blood-brain barrier in therapeutically-relevant quantities is an expensive and time-consuming undertaking. However, central nervous system diseases are an under-addressed cause of high mortality and morbidity, and drug development in this field is a worthwhile venture. We aim to familiarize the reader with available methodologies for studying drug transport into the brain. Current understanding of the blood-brain barrier structure has been well-described in other manuscripts, and first we briefly review the path that xenobiotics take through the brain - from bloodstream, to endothelial cells of the blood-brain barrier, to interstitial space, to brain parenchymal cells, and then to an exit point from the central nervous system. The second half of the review discusses research tools available to determine if xenobiotics are making the journey through the brain successfully and offers commentary on the translational utility of each methodology. Theoretically, non-human mammalian and human blood-brain barriers are similar in composition; however, some findings demonstrate important differences across species. Translational methodologies may provide more reliable information about how a drug may act across species. The recent finding of lymphatic vessels within the central nervous system may provide new tools and strategies for drug delivery to the brain.

Safety analysis of sofosbuvir and ledipasvir for treating hepatitis C.

PubMed

Fazel, Yousef; Lam, Brian; Golabi, Pegah; Younossi, Zobair

2015-08-01

The approval of sofosbuvir (SOF), a nucleotide analogue NS5B polymerase inhibitor, and ledipasvir (LDV), a NS5A inhibitor, marked a new chapter in IFN and ribavirin-free treatment of hepatitis C virus (HCV). This drug reduces adverse events associated with IFN therapy. The purpose of this paper is to evaluate the safety and efficacy of LDV/SOF. Clinical trials illustrating safety and efficacy of LDV/SOF are reviewed and compared to other IFN and ribavirin-free treatment options available. In trials enrolling more than 3000 patients, LDV/SOF is well tolerated with a good safety and side-effect profile in diverse cohorts, including previous direct-acting antiviral (DAA) treatment failures, liver transplant recipients, decompensated cirrhosis and HIV/HCV co-infection. As with all DAAs, the potential for drug-drug interactions must be carefully evaluated, as demonstrated by recent post-marketing reports of symptomatic bradycardia when LDV/SOF is co-administered with amiodarone. Currently, dose recommendations cannot be given for patients with advanced renal disease. Trials in this population are ongoing, more study is warranted. When surveying the DAA regimens available, efficacy, safety and tolerability of LDV/SOF is comparable or better, and LDV/SOF provides an option with convenient single-tablet, once daily, ribavirin-free dosing with relatively few significant drug-drug interactions.

GABAA receptor: Positive and negative allosteric modulators.

PubMed

Olsen, Richard W

2018-01-31

gamma-Aminobutyric acid (GABA)-mediated inhibitory neurotransmission and the gene products involved were discovered during the mid-twentieth century. Historically, myriad existing nervous system drugs act as positive and negative allosteric modulators of these proteins, making GABA a major component of modern neuropharmacology, and suggesting that many potential drugs will be found that share these targets. Although some of these drugs act on proteins involved in synthesis, degradation, and membrane transport of GABA, the GABA receptors Type A (GABA A R) and Type B (GABA B R) are the targets of the great majority of GABAergic drugs. This discovery is due in no small part to Professor Norman Bowery. Whereas the topic of GABA B R is appropriately emphasized in this special issue, Norman Bowery also made many insights into GABA A R pharmacology, the topic of this article. GABA A R are members of the ligand-gated ion channel receptor superfamily, a chloride channel family of a dozen or more heteropentameric subtypes containing 19 possible different subunits. These subtypes show different brain regional and subcellular localization, age-dependent expression, and potential for plastic changes with experience including drug exposure. Not only are GABA A R the targets of agonist depressants and antagonist convulsants, but most GABA A R drugs act at other (allosteric) binding sites on the GABA A R proteins. Some anxiolytic and sedative drugs, like benzodiazepine and related drugs, act on GABA A R subtype-dependent extracellular domain sites. General anesthetics including alcohols and neurosteroids act at GABA A R subunit-interface trans-membrane sites. Ethanol at high anesthetic doses acts on GABA A R subtype-dependent trans-membrane domain sites. Ethanol at low intoxicating doses acts at GABA A R subtype-dependent extracellular domain sites. Thus GABA A R subtypes possess pharmacologically specific receptor binding sites for a large group of different chemical classes of clinically important neuropharmacological agents. Copyright © 2018 Elsevier Ltd. All rights reserved.

Recent advances in the treatment of hepatitis C.

PubMed

Dhingra, Abhinav; Kapoor, Saloni; Alqahtani, Saleh A

2014-10-01

Hepatitis C virus (HCV) therapeutics is amidst a revolution. With the recent approval of sofosbuvir (Sovaldi) and simeprevir (Olysio), clinicians and patients started to recognize that for the first time in the history, hepatitis C can be cured in a majority of patients without interferon. These new regimens are safe, and have excellent efficacy and minimal adverse events. Sofosbuvir, a nucleotide analogue (NS5B polymerase inhibitor), is a potent drug with excellent tolerability and pan-genotypic activity with a high barrier to resistance. Simeprevir, a second-generation protease inhibitor which inhibits the initial cleavage of the HCV poly-protein by the NS3/4A protease. Simeprevir has been evaluated in clinical trials in combination with interferon and ribavirin based therapy and also in the COSMO trial in combination with sofosbuvir. More directly acting antiviral therapy drugs are in the pipeline with several drugs being expected to be approved by the FDA in late 2014. Although these drugs have excellent efficacy, they are more costly. The price of these drugs limits treatments of many patients in the world especially in countries with limited economic resources. However, with the availability of a variety of excellent directly acting antivirals (DAAs) in the near future, hopefully many patients would be able to afford the treatment. The future in HCV therapy will focus on special groups of patients who were excluded from initial HCV clinical trials such as post-liver transplant HCV recurrence, patients with HCV/HIV co-infection, and patients with advanced cirrhosis.

Indirect androgen doping by oestrogen blockade in sports

PubMed Central

Handelsman, D J

2008-01-01

Androgens can increase muscular mass and strength and remain the most frequently abused and widely available drugs used in sports doping. Banning the administration of natural or synthetic androgens has led to a variety of strategies to circumvent the ban of the most effective ergogenic agents for power sports. Among these, a variety of indirect androgen doping strategies aiming to produce a sustained rise in endogenous testosterone have been utilized. These include oestrogen blockade by drugs that act as oestrogen receptor antagonists (antioestrogen) or aromatase inhibitors. The physiological and pharmacological basis for the effects of oestrogen blockade in men, but not women, are reviewed. PMID:18500381

COPD - control drugs

MedlinePlus

Chronic obstructive pulmonary disease - control drugs; Bronchodilators - COPD - control drugs; Beta agonist inhaler - COPD - control drugs; Anticholinergic inhaler - COPD - control drugs; Long-acting inhaler - COPD - ...

Is the GAIN Act a turning point in new antibiotic discovery?

PubMed

Brown, Eric D

2013-03-01

The United States GAIN (Generating Antibiotic Incentives Now) Act is a call to action for new antibiotic discovery and development that arises from a ground swell of concern over declining activity in this therapeutic area in the pharmaceutical sector. The GAIN Act aims to provide economic incentives for antibiotic drug discovery in the form of market exclusivity and accelerated drug approval processes. The legislation comes on the heels of nearly two decades of failure using the tools of modern drug discovery to find new antibiotic drugs. The lessons of failure are examined herein as are the prospects for a renewed effort in antibiotic drug discovery and development stimulated by new investments in both the public and private sector.

21 CFR 312.120 - Foreign clinical studies not conducted under an IND.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE INVESTIGATIONAL NEW DRUG APPLICATION Miscellaneous § 312... the act or section 351 of the Public Health Service Act (the PHS Act) (42 U.S.C. 262)) a well-designed... this section, GCP is defined as a standard for the design, conduct, performance, monitoring, auditing...

Novel Treatments for Rare Cancers: The U.S. Orphan Drug Act Is Delivering-A Cross-Sectional Analysis.

PubMed

Stockklausner, Clemens; Lampert, Anette; Hoffmann, Georg F; Ries, Markus

2016-04-01

Rare cancers are a heterogeneous group of conditions with highly unmet medical needs. Although infrequent in individuals, rare cancers affect millions of people who deserve effective treatments. Therefore, we systematically analyzed the impact of the U.S. Orphan Drug Act of 1983 on delivery of novel treatments for rare cancers. Quantitative cross-sectional analysis was conducted on the U.S. Food and Drug Administration Orphan Drug Product database according to Strengthening the Reporting of Observational Studies in Epidemiology Statement criteria between 1983 and 2015. Since 1983, a total of 177 approvals have originated from 1,391 orphan drug designations to treat rare cancers, which represents 36% of all approvals within the U.S. orphan drug act (n = 492). Two compounds (1%) to treat rare cancer were withdrawn after approval. Median time from designation to approval was 2.49 years (interquartile range 1.13-4.64) and decreased significantly over time (p < .001, linear regression). Over the last decade, rare cancer treatments have been transformed from nonspecific cytotoxic agents toward targeted therapies, such as protein kinase inhibitors and monoclonal antibodies, representing the largest groups of innovative rare cancer treatments today. Most compounds were approved to treat solid tumors and hematological malignancies. The U.S. Orphan Drug Act and associated incentives, such as 7 years of marketing exclusivity, have fostered delivery of novel treatments for rare cancers. More than one-third of all orphan drug approvals address needs of patients suffering from rare cancers. Over the last decade, the understanding of tumorigenesis and genetic driver mutations in different tumor entities has produced innovative treatments, of which many were first approved within the U.S. Orphan Drug Act. Over the last 30 years, the U.S. Orphan Drug Act successfully delivered numerous novel treatments for rare cancers, of which some were subsequently used in other, nonorphan indications. The understanding of molecular mechanisms of diseases is directly connected to the search for novel therapies. The constant pursuit to translate basic research findings into clinical practice is a crucial prerequisite to address unmet medical needs in rare cancers, as in other rare diseases. Oncological drug development proves to be a major player in overall orphan drug research, displayed by more than one-third of all U.S. Food and Drug Administration-approved orphan drugs with oncological indications. ©AlphaMed Press.

Understanding artemisinin-resistant malaria: what a difference a year makes

PubMed Central

Fairhurst, Rick M.

2015-01-01

Purpose of review The emergence of artemisinin resistance in Southeast Asia, where artemisinin combination therapies (ACTs) are beginning to fail, threatens global endeavors to control and eliminate Plasmodium falciparum malaria. Future efforts to prevent the spread of this calamity to Africa will benefit from last year’s tremendous progress in understanding artemisinin resistance. Recent findings Multiple international collaborations have established that artemisinin resistance is associated with slow parasite clearance in patients; increased survival of early ring-stage parasites in vitro; single-nucleotide polymorphisms (SNPs) in the parasite’s ‘K13’ gene; parasite ‘founder’ populations sharing a genetic background of four additional SNPs; parasite transcriptional profiles reflecting an “unfolded protein response” and decelerated parasite development; and elevated parasite phosphatidylinositol-3-kinase activity. In Western Cambodia, where the K13 C580Y mutation is approaching fixation, the frontline ACT is failing to cure nearly half of patients, likely due to partner drug resistance. In Africa, where dozens of K13 mutations have been detected at low frequency, there is no evidence yet of artemisinin resistance. Summary In Southeast Asia, clinical and epidemiological investigations are urgently needed to stop the further spread of artemisinin resistance; monitor ACT efficacy where K13 mutations are prevalent; identify currently-available drug regimens that cure ACT failures; and rapidly advance new antimalarial compounds through clinical trials. PMID:26237549

Interactions between tafenoquine and artemisinin-combination therapy partner drug in asexual and sexual stage Plasmodium falciparum.

PubMed

Kemirembe, Karen; Cabrera, Mynthia; Cui, Liwang

2017-08-01

The 8-aminoquinoline tafenoquine (TFQ), a primaquine derivative, is currently in late-stage clinical development for the radical cure of P. vivax. Here drug interactions between TFQ and chloroquine and six artemisinin-combination therapy (ACT) partner drugs in P. falciparum asexual stages and gametocytes were investigated. TFQ was mostly synergistic with the ACT-partner drugs in asexual parasites regardless of genetic backgrounds. However, at fixed ratios of 1:3, 1:1 and 3:1, TFQ only interacted synergistically with naphthoquine, pyronaridine and piperaquine in gametocytes. This study indicated that TFQ and ACT-partner drugs will likely have increased potency against asexual stages of the malaria parasites, whereas some drugs may interfere with each other against the P. falciparum gametocytes. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Was Part D a giveaway to the pharmaceutical industry?

PubMed

Newhouse, Joseph P; Seiguer, Erica; Frank, Richard G

2007-01-01

The Medicare Modernization Act (MMA) prohibited the government from negotiating drug prices, a feature that the act's critics characterize as a giveaway to the drug industry. Instead of the government negotiating to keep prices down, the act relies on competition among drug companies to obtain business from private insurers; yet, competition cannot be effective when there are no close clinical substitutes. In the past few years, the rate of introduction of first-in-class drugs has been low; if this continues, the prohibition on negotiation may be only a minor problem. However, if the prior rate of introduction resumes, the government may find itself with unacceptable expenditure levels.

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

75 FR 75677 - Agency Information Collection Activities; Proposed Collection; Comment Request; Exports...

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2014-04-01

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2010-01-01

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Are there any reasons to change our behavior in necrotizing fasciitis with the advent of new antibiotics?

PubMed

Menichetti, Francesco; Giuliano, Simone; Fortunato, Simona

2017-04-01

The treatment of necrotizing fasciitis requires a multifaceted approach, consisting of surgical source control with immediate surgical debridement along with life support, clinical monitoring, and antimicrobial therapy. Many drugs are now available for the treatment of this life-threatening infectious disease, and the purpose of this review is to provide the reader with an updated overview of the newest therapeutic options. Because most necrotizing soft tissue infections are polymicrobial, broad-spectrum coverage is advisable. Acceptable monotherapy regimens include piperacillin-tazobactam or a carbapenem. However, drugs such as ceftolozane-tazobactam, ceftazidime-avibactam in association with an antianaerobic agent (metronidazole or clindamycin) are currently available as valuable alternatives. The new cephalosporins active against methicillin-resistant Staphylococcus aureus (MRSA), ceftaroline, and ceftobiprole share similar antibacterial activity against Gram-positive cocci, and they might be considered as an alternative to nonbetalactam anti-MRSA agents for necrotizing fasciitis management. Two new long-acting lypoglycopeptides - oritavancin and dalbavancin - share the indications for acute bacterial skin and skin structure infections and had similar activity against Gram-positive cocci including MRSA and streptococci. Carbapenem-sparing agents are particularly suitable for antimicrobial stewardship strategy. The new long-acting lypoglycopeptides are very effective in treating necrotizing fasciitis and are uttermost attractive for patients requiring short hospital stays and early discharge.

Emerging medication for the treatment of male hypogonadism.

PubMed

Aydogdu, Aydogan; Swerdloff, Ronald S

2016-09-01

Male hypogonadism is characterized by inadequate production of Testosterone (T) (hypoandrogenism) and deficiencies in spermatogenesis. The main treatment of male hypogonadism is T replacement therapy (TRT), but for some of the patients, alternative drugs may be more suitable. The available literature of T and alternative treatments for male hypogonadism are discussed. Transdermal application of T gels are the most commonly used route of T administration. Some oral T formulations are either associated with hepatic toxicity (i.e. methyltestosterone) or short half-lives that require multiple doses per day (i.e. oral testosterone undecanoate). Short acting, injectable T formulations are also available. If the patient prefers not to use daily drugs or short acting injectable formulations, depot formulations such as injectable testosterone undecanoate (TU) may be a good alternative. If the patient has hypogonadotropic hypogonadism and desires fertility or if he is adolescent, instead of TRT, gonadotropins can be started to stimulate testicular growth and spermatogenesis. In obese patients or for the patients having high risks for TRT, off label aromatase inhibitors (AI) and clomiphene citrate (CC), may be considered to stimulate LH, FSH and T levels. In patients with high prostate disease risk, selective androgen receptor modulators may be an alternative treatment but these latter treatments have not had high level evidence.

21 CFR 332.30 - Labeling of antiflatulent drug products.

Code of Federal Regulations, 2010 CFR

2010-04-01

... section 502 of the Federal Food, Drug, and Cosmetic Act (the act) relating to misbranding and the... accidental overdose, seek professional assistance or contact a poison control center immediately.” The...

21 CFR 332.30 - Labeling of antiflatulent drug products.

Code of Federal Regulations, 2014 CFR

2014-04-01

... section 502 of the Federal Food, Drug, and Cosmetic Act (the act) relating to misbranding and the... accidental overdose, seek professional assistance or contact a poison control center immediately.” The...

21 CFR 332.30 - Labeling of antiflatulent drug products.

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2013-04-01

... section 502 of the Federal Food, Drug, and Cosmetic Act (the act) relating to misbranding and the... accidental overdose, seek professional assistance or contact a poison control center immediately.” The...

21 CFR 332.30 - Labeling of antiflatulent drug products.

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21 CFR 332.30 - Labeling of antiflatulent drug products.

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2012-04-01

... section 502 of the Federal Food, Drug, and Cosmetic Act (the act) relating to misbranding and the... accidental overdose, seek professional assistance or contact a poison control center immediately.” The...

A Cluster Randomised Trial Introducing Rapid Diagnostic Tests into Registered Drug Shops in Uganda: Impact on Appropriate Treatment of Malaria

PubMed Central

Mbonye, Anthony K.; Magnussen, Pascal; Lal, Sham; Hansen, Kristian S.; Cundill, Bonnie; Chandler, Clare; Clarke, Siân E.

2015-01-01

Background Inappropriate treatment of malaria is widely reported particularly in areas where there is poor access to health facilities and self-treatment of fevers with anti-malarial drugs bought in shops is the most common form of care-seeking. The main objective of the study was to examine the impact of introducing rapid diagnostic tests for malaria (mRDTs) in registered drug shops in Uganda, with the aim to increase appropriate treatment of malaria with artemisinin-based combination therapy (ACT) in patients seeking treatment for fever in drug shops. Methods A cluster-randomized trial of introducing mRDTs in registered drug shops was implemented in 20 geographical clusters of drug shops in Mukono district, central Uganda. Ten clusters were randomly allocated to the intervention (diagnostic confirmation of malaria by mRDT followed by ACT) and ten clusters to the control arm (presumptive treatment of fevers with ACT). Treatment decisions by providers were validated by microscopy on a reference blood slide collected at the time of consultation. The primary outcome was the proportion of febrile patients receiving appropriate treatment with ACT defined as: malaria patients with microscopically-confirmed presence of parasites in a peripheral blood smear receiving ACT or rectal artesunate, and patients with no malaria parasites not given ACT. Findings A total of 15,517 eligible patients (8672 intervention and 6845 control) received treatment for fever between January-December 2011. The proportion of febrile patients who received appropriate ACT treatment was 72·9% versus 33·7% in the control arm; a difference of 36·1% (95% CI: 21·3 – 50·9), p<0·001. The majority of patients with fever in the intervention arm accepted to purchase an mRDT (97·8%), of whom 58·5% tested mRDT-positive. Drug shop vendors adhered to the mRDT results, reducing over-treatment of malaria by 72·6% (95% CI: 46·7– 98·4), p<0·001) compared to drug shop vendors using presumptive diagnosis (control arm). Conclusion Diagnostic testing with mRDTs compared to presumptive treatment of fevers implemented in registered drug shops substantially improved appropriate treatment of malaria with ACT. Trial Registration ClinicalTrials.gov NCT01194557. PMID:26200467

A Cluster Randomised Trial Introducing Rapid Diagnostic Tests into Registered Drug Shops in Uganda: Impact on Appropriate Treatment of Malaria.

PubMed

Mbonye, Anthony K; Magnussen, Pascal; Lal, Sham; Hansen, Kristian S; Cundill, Bonnie; Chandler, Clare; Clarke, Siân E

2015-01-01

Inappropriate treatment of malaria is widely reported particularly in areas where there is poor access to health facilities and self-treatment of fevers with anti-malarial drugs bought in shops is the most common form of care-seeking. The main objective of the study was to examine the impact of introducing rapid diagnostic tests for malaria (mRDTs) in registered drug shops in Uganda, with the aim to increase appropriate treatment of malaria with artemisinin-based combination therapy (ACT) in patients seeking treatment for fever in drug shops. A cluster-randomized trial of introducing mRDTs in registered drug shops was implemented in 20 geographical clusters of drug shops in Mukono district, central Uganda. Ten clusters were randomly allocated to the intervention (diagnostic confirmation of malaria by mRDT followed by ACT) and ten clusters to the control arm (presumptive treatment of fevers with ACT). Treatment decisions by providers were validated by microscopy on a reference blood slide collected at the time of consultation. The primary outcome was the proportion of febrile patients receiving appropriate treatment with ACT defined as: malaria patients with microscopically-confirmed presence of parasites in a peripheral blood smear receiving ACT or rectal artesunate, and patients with no malaria parasites not given ACT. A total of 15,517 eligible patients (8672 intervention and 6845 control) received treatment for fever between January-December 2011. The proportion of febrile patients who received appropriate ACT treatment was 72·9% versus 33·7% in the control arm; a difference of 36·1% (95% CI: 21·3 - 50·9), p<0·001. The majority of patients with fever in the intervention arm accepted to purchase an mRDT (97·8%), of whom 58·5% tested mRDT-positive. Drug shop vendors adhered to the mRDT results, reducing over-treatment of malaria by 72·6% (95% CI: 46·7- 98·4), p<0·001) compared to drug shop vendors using presumptive diagnosis (control arm). Diagnostic testing with mRDTs compared to presumptive treatment of fevers implemented in registered drug shops substantially improved appropriate treatment of malaria with ACT. ClinicalTrials.gov NCT01194557.

Use of computer-assisted drug therapy outside the operating room.

PubMed

Singh, Preet Mohinder; Borle, Anuradha; Goudra, Basavana G

2016-08-01

The number of procedures performed in the out-of-operating room setting under sedation has increased many fold in recent years. Sedation techniques aim to achieve rapid patient turnover through the use of short-acting drugs with minimal residual side-effects (mainly propofol and opioids). Even for common procedures, the practice of sedation delivery varies widely among providers. Computer-based sedation models have the potential to assist sedation providers and offer a more consistent and safer sedation experience for patients. Target-controlled infusions using propofol and other short-acting opioids for sedation have shown promising results in terms of increasing patient safety and allowing for more rapid wake-up times. Target-controlled infusion systems with real-time patient monitoring can titrate drug doses automatically to maintain optimal depth of sedation. The best recent example of this is the propofol-based Sedasys sedation system. Sedasys redefined individualized sedation by the addition of an automated clinical parameter that monitors depth of sedation. However, because of poor adoption and cost issues, it has been recently withdrawn by the manufacturer. Present automated drug delivery systems can assist in the provision of sedation for out-of-operating room procedures but cannot substitute for anesthesia providers. Use of the available technology has the potential to improve patient outcomes, decrease provider workload, and have a long-term economic impact on anesthesia care delivery outside of the operating room.

Deployment of ACT antimalarials for treatment of malaria: challenges and opportunities

PubMed Central

Whitty, Christopher JM; Chandler, Clare; Ansah, Evelyn; Leslie, Toby; Staedke, Sarah G

2008-01-01

Following a long period when the effectiveness of existing mono-therapies for antimalarials was steadily declining with no clear alternative, most malaria-endemic countries in Africa and Asia have adopted artemisinin combination therapy (ACT) as antimalarial drug policy. Several ACT drugs exist and others are in the pipeline. If properly targeted, they have the potential to reduce mortality from malaria substantially. The major challenge now is to get the drugs to the right people. Current evidence suggests that most of those who need the drugs do not get them. Simultaneously, a high proportion of those who are given antimalarials do not in fact have malaria. Financial and other barriers mean that, in many settings, the majority of those with malaria, particularly the poorest, do not access formal healthcare, so the provision of free antimalarials via this route has only limited impact. The higher cost of ACT creates a market for fake drugs. Addressing these problems is now a priority. This review outlines current evidence, possible solutions and research priorities. PMID:19091041

Commentary on recent therapeutic guidelines for osteoarthritis.

PubMed

Cutolo, Maurizio; Berenbaum, Francis; Hochberg, Marc; Punzi, Leonardo; Reginster, Jean-Yves

2015-06-01

Despite availability of international evidence-based guidelines for osteoarthritis (OA) management, agreement on the different treatment modalities is lacking. A symposium of European and US OA experts was held within the framework of the Annual European Congress of Rheumatology to discuss and compare guidelines and recommendations for the treatment of knee OA and to reach a consensus for management, particularly for areas in which there is no clear consensus: non-pharmacological therapy; efficacy and safety of analgesics and non-steroidal anti-inflammatory drugs (NSAIDs); intra-articular (i.a.) hyaluronates (HA); and the role of chondroitin sulfate (CS) and/or glucosamine sulfate (GS). All guidelines reviewed agree that knee OA is a progressive disease of the joint whose management requires non-pharmacological and pharmacological approaches. Discrepancies between guidelines are few and mostly reflect heterogeneity of expert panels involved, geographical differences in the availability of pharmacotherapies, and heterogeneity of the studies included. Panels chosen for guideline development should include experts with real clinical experience in drug use and patient management. Implementation of agreed guidelines can be thwarted by drug availability and reimbursement plans, resulting in optimal OA treatment being jeopardized, HA and symptomatic slow-acting drugs for osteoarthritis (SySADOAs) being clear examples of drugs whose availability and prescription can greatly vary geographically. In addition, primary care providers, often responsible for OA management (at least in early disease), may not adhere to clinical care guidelines, particularly for non-pharmacological OA treatment. Harmonization of the recommendations for knee OA treatment is challenging but feasible, as shown by the step-by-step therapeutic algorithm developed by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). More easily disseminated and implemented guidance for OA treatment in the primary care setting is key to improved management of OA. Copyright © 2015 Elsevier Inc. All rights reserved.

Piloting the global subsidy: the impact of subsidized artemisinin-based combination therapies distributed through private drug shops in rural Tanzania.

PubMed

Sabot, Oliver J; Mwita, Alex; Cohen, Justin M; Ipuge, Yahya; Gordon, Megumi; Bishop, David; Odhiambo, Moses; Ward, Lorrayne; Goodman, Catherine

2009-09-02

WHO estimates that only 3% of fever patients use recommended artemisinin-based combination therapies (ACTs), partly reflecting their high prices in the retail sector from where many patients seek treatment. To overcome this challenge, a global ACT subsidy has been proposed. We tested this proposal through a pilot program in rural Tanzania. Three districts were assigned to serve either as a control or to receive the subsidy plus a package of supporting interventions. From October 2007, ACTs were sold at a 90% subsidy through the normal private supply chain to intervention district drug shops. Data were collected at baseline and during intervention using interviews with drug shop customers, retail audits, mystery shoppers, and audits of public and NGO facilities. The proportion of consumers in the intervention districts purchasing ACTs rose from 1% at baseline to 44.2% one year later (p<0.001), and was significantly higher among consumers purchasing for children under 5 than for adults (p = 0.005). No change in ACT usage was observed in the control district. Consumers paid a mean price of $0.58 for ACTs, which did not differ significantly from the price paid for sulphadoxine-pyrimethamine, the most common alternative. Drug shops in population centers were significantly more likely to stock ACTs than those in more remote areas (p<0.001). A subsidy introduced at the top of the private sector supply chain can significantly increase usage of ACTs and reduce their retail price to the level of common monotherapies. Additional interventions may be needed to ensure access to ACTs in remote areas and for poorer individuals who appear to seek treatment at drug shops less frequently. Controlled-Trials.com ISRCTN39125414.

Piloting the Global Subsidy: The Impact of Subsidized Artemisinin-Based Combination Therapies Distributed through Private Drug Shops in Rural Tanzania

PubMed Central

Sabot, Oliver J.; Mwita, Alex; Cohen, Justin M.; Ipuge, Yahya; Gordon, Megumi; Bishop, David; Odhiambo, Moses; Ward, Lorrayne; Goodman, Catherine

2009-01-01

Background WHO estimates that only 3% of fever patients use recommended artemisinin-based combination therapies (ACTs), partly reflecting their high prices in the retail sector from where many patients seek treatment. To overcome this challenge, a global ACT subsidy has been proposed. We tested this proposal through a pilot program in rural Tanzania. Methods/Principal Findings Three districts were assigned to serve either as a control or to receive the subsidy plus a package of supporting interventions. From October 2007, ACTs were sold at a 90% subsidy through the normal private supply chain to intervention district drug shops. Data were collected at baseline and during intervention using interviews with drug shop customers, retail audits, mystery shoppers, and audits of public and NGO facilities. The proportion of consumers in the intervention districts purchasing ACTs rose from 1% at baseline to 44.2% one year later (p<0.001), and was significantly higher among consumers purchasing for children under 5 than for adults (p = 0.005). No change in ACT usage was observed in the control district. Consumers paid a mean price of $0.58 for ACTs, which did not differ significantly from the price paid for sulphadoxine-pyrimethamine, the most common alternative. Drug shops in population centers were significantly more likely to stock ACTs than those in more remote areas (p<0.001). Conclusions A subsidy introduced at the top of the private sector supply chain can significantly increase usage of ACTs and reduce their retail price to the level of common monotherapies. Additional interventions may be needed to ensure access to ACTs in remote areas and for poorer individuals who appear to seek treatment at drug shops less frequently. Trial Registration Controlled-Trials.com ISRCTN39125414. PMID:19724644

21 CFR 1005.25 - Service of process on manufacturers.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Subchapter C—Electronic Product Radiation Control of the Federal Food, Drug, and Cosmetic Act (formerly the Radiation Control for Health and Safety Act of 1968) (21 U.S.C. 360mm(d)) and this section. The agent may be... Radiation Control of the Federal Food, Drug, and Cosmetic Act (formerly the Radiation Control for Health and...

21 CFR 1005.25 - Service of process on manufacturers.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Subchapter C—Electronic Product Radiation Control of the Federal Food, Drug, and Cosmetic Act (formerly the Radiation Control for Health and Safety Act of 1968) (21 U.S.C. 360mm(d)) and this section. The agent may be... Subchapter C—Electronic Product Radiation Control of the Federal Food, Drug, and Cosmetic Act (formerly the...

21 CFR 1005.25 - Service of process on manufacturers.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Subchapter C—Electronic Product Radiation Control of the Federal Food, Drug, and Cosmetic Act (formerly the Radiation Control for Health and Safety Act of 1968) (21 U.S.C. 360mm(d)) and this section. The agent may be... Radiation Control of the Federal Food, Drug, and Cosmetic Act (formerly the Radiation Control for Health and...

21 CFR 1005.25 - Service of process on manufacturers.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Subchapter C—Electronic Product Radiation Control of the Federal Food, Drug, and Cosmetic Act (formerly the Radiation Control for Health and Safety Act of 1968) (21 U.S.C. 360mm(d)) and this section. The agent may be... Subchapter C—Electronic Product Radiation Control of the Federal Food, Drug, and Cosmetic Act (formerly the...

78 FR 61991 - Schedules of Controlled Substances: Temporary Placement of Three Synthetic Phenethylamines Into...

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... the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 355, for the substance. 21 U.S.C. 811(h... Institute on Drug Abuse (NIDA), FDA acts as the lead agency within HHS in carrying out the Assistant... grounds for his determination that it is [[Page 61993

BZP-party pills: a review of research on benzylpiperazine as a recreational drug.

PubMed

Cohen, Bruce M Z; Butler, Rachael

2011-03-01

BZP-party pills are yet another 'designer drug' which mimics the stimulant qualities of amphetamines and MDMA/Ecstasy. As legal markets for the substance have developed in the last decade (especially amongst young people) so has public and governmental concern. This article provides a summary of the available international research on benzylpiperazine (BZP) and its popular use in the compound form known as 'party pills'. Through performing an analysis of the available medical and social scientific literature, the review outlines current knowledge on the compound, the prevalence of usage of BZP-party pills, as well as the associated harms, risks and rationales for use of the drug. Despite moves towards legislative control of BZP-party pills, the evidence presented suggests limited social and health harms associated with the drug, although research on long term effects is a significant gap in the literature. It also remains inconclusive as to whether BZP-party pills act as a 'gateway' to illegal drugs or, conversely, play a role in harm reduction with illegal drug users turning to legal alternatives; there is some evidence for both positions. With increasing controls of BZP-party pills, and with the increasing numbers of 'legal highs' and new designer drugs on the market, we conclude that new legal alternatives will continue to surface to replace the drug in the future. Considering a harm reduction approach to drug taking, it is suggested that policy makers consider the creation of a legal holding category which restricts and regulates the market in legal highs whilst the social and health harms associated with each drug can be thoroughly investigated. Copyright © 2011 Elsevier B.V. All rights reserved.

Transdermal Drug Delivery: Opportunities and Challenges for Controlled Delivery of Therapeutic Agents Using Nanocarriers.

PubMed

Kurmi, Balak Das; Tekchandani, Pawan; Paliwal, Rishi; Paliwal, Shivani Rai

2017-01-01

Transdermal drug delivery represents an extremely attractive and innovative route across the skin owing to the possibility for achieving systemic effect of drugs. The present scenario demands a special focus on developing safe medicine with minimized toxic adverse effects related to most of the pharmacologically active agents. Transdermal drug delivery would be a focal paradigm which provides patient convenience, first-pass hepatic metabolism avoidance, local targeting and reduction in toxic effect related to various categories of drugs like, analgesics, antiinflammatory, antibiotics, antiviral, anaesthetic, anticancer etc. Even this route has challenges due to highly organized structure of skin which acts as a main barrier to penetration of drug via the skin. Several alternative possible strategies are available which overcome these barriers, including use of penetration enhancer, eletroporation, iontophoresis and various nanotechnologically developed nanocarrier systems. The latest one includes employing liposome, dendrimers, nanoparticles, ethosome, carbon nanotube and many more to avoid associated limitations of conventional formulations. Numerous transdermal products such as Estrasorb, Diractin, VivaGel®, Daytrana®, Aczone, Sileryst® are available in the market having a novel strategy to achieve higher penetration of drugs. This encourages formulation fraternity to develop structurally deformable and stable nanocarriers as an alternative approach for controlled and reliable drug delivery across the skin barrier. In this review, we will discuss nanocarriers mediated approaches that come-up with the solutions to the different challenges towards transdermal drug delivery, its clinical importance and latest insight to research in it. The reports presented in this review confirm the wide application of nanocarriers for transdermal delivery of drug/gene. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

NanoCrySP technology for generation of drug nanocrystals: translational aspects and business potential.

PubMed

Shete, Ganesh; Bansal, Arvind Kumar

2016-08-01

Drug nanocrystals have rapidly evolved into a mature drug delivery strategy in the last decade, with almost 16 products currently on the market. Several "top-down" technologies are available in the market for generation of nanocrystals. Despite several advantages, very few bottom-up technologies have been explored for commercial purpose. This short communication highlights a novel, bottom-up, spray drying based technology-NanoCrySP-to generate drug nanocrystals. Nanocrystals are generated in the presence of non-polymeric excipients that act as crystallization inducer for the drug. Excipients encourage crystallization of drug by plasticization, primary heterogeneous nucleation, and imparting physical barrier to crystal growth. Nanocrystals have shown significant improvement in dissolution and thereby oral bioavailability. NanoCrySP technology is protected through patents in India, the USA, and the European Union. NanoCrySP can be utilized for (i) pharmaceutical development of new chemical entities, (ii) differentiated products of existing molecules, and (iii) generic drug products. The aggregation of drug nanocrystals generated using NanoCrySP poses significant challenges in the nanocrystal-based product development. Addition of stabilizers either during spray drying or during dissolution has shown beneficial effects.

Exclusivity strategies and opportunities in view of the Biologics Price Competition and Innovation Act.

PubMed

Gaudry, Kate S

2011-01-01

Government-provided exclusivity periods provide pharmaceutical companies with incentives to invest in new drugs. Meanwhile, encouraging competition serves another worthy goal of improving the affordability of medications. Decades ago, the Hatch-Waxman Act set forth provisions attempting to balance these objectives in the context of small-molecule drugs. Recently, the Biologics Price Competition and Innovation Act was enacted to meet similar aims in the context of biologic drugs. This article presents a detailed comparison of these two Acts. While the Acts share many global similarities (e.g., providing exclusivity terms and abbreviated approval processes), many differences are also apparent when analyzing details of the provisions. One area of great departure between the Acts is the requirements of how a generic or follow-on applicant must address patents covering a reference product. After describing these differences, the article presents predictions of how reference product sponsors will adapt their patent-prosecution strategies in view of the new Biologics Act.

21 CFR 1.101 - Notification and recordkeeping.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., animal drug, food, cosmetic, and tobacco product exports under sections 801 or 802 of the Federal Food, Drug, and Cosmetic Act or (21 U.S.C. 381 and 382) or section 351 of the Public Health Service Act (42 U... drugs, foods, cosmetics, and tobacco products exported under or subject to section 801(e)(1) of the...

21 CFR 1.101 - Notification and recordkeeping.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., animal drug, food, cosmetic, and tobacco product exports under sections 801 or 802 of the Federal Food, Drug, and Cosmetic Act or (21 U.S.C. 381 and 382) or section 351 of the Public Health Service Act (42 U... drugs, foods, cosmetics, and tobacco products exported under or subject to section 801(e)(1) of the...

21 CFR 108.19 - Establishment of requirements for exemption from section 404 of the act.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Establishment of requirements for exemption from section 404 of the act. 108.19 Section 108.19 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION EMERGENCY PERMIT CONTROL General...

21 CFR 108.19 - Establishment of requirements for exemption from section 404 of the act.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Establishment of requirements for exemption from section 404 of the act. 108.19 Section 108.19 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION EMERGENCY PERMIT CONTROL General...

21 CFR 108.19 - Establishment of requirements for exemption from section 404 of the act.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Establishment of requirements for exemption from section 404 of the act. 108.19 Section 108.19 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION EMERGENCY PERMIT CONTROL General...

21 CFR 108.19 - Establishment of requirements for exemption from section 404 of the act.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Establishment of requirements for exemption from section 404 of the act. 108.19 Section 108.19 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION EMERGENCY PERMIT CONTROL General...

Piecing Together an Integrated Approach to Drug-Free Schools. 1992-93 Final Report.

ERIC Educational Resources Information Center

Wiehe, James A.

The federal Drug-Free Schools and Communities (DFSC) Act of 1986 provides funding to school districts to help eliminate drug and alcohol use on their campuses. In 1992-93, the Austin Independent School District (AISD) received $467,362 from the act. The funds supported a wide assortment of preventative and educational programs regarding the…

21 CFR 108.19 - Establishment of requirements for exemption from section 404 of the act.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Establishment of requirements for exemption from section 404 of the act. 108.19 Section 108.19 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION EMERGENCY PERMIT CONTROL General...

21 CFR 60.22 - Regulatory review period determinations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... drugs: (1) The testing phase begins on the date an exemption under section 505(i) of the Act becomes... Act and ends on the date the protocol is declared to be completed. (d) For animal drugs: (1) The... animal drug, whichever is earlier, and ends on the date a marketing application under section 512 of the...

21 CFR 60.22 - Regulatory review period determinations.

Code of Federal Regulations, 2014 CFR

2014-04-01

... drugs: (1) The testing phase begins on the date an exemption under section 505(i) of the Act becomes... Act and ends on the date the protocol is declared to be completed. (d) For animal drugs: (1) The... animal drug, whichever is earlier, and ends on the date a marketing application under section 512 of the...

21 CFR 60.22 - Regulatory review period determinations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... drugs: (1) The testing phase begins on the date an exemption under section 505(i) of the Act becomes... Act and ends on the date the protocol is declared to be completed. (d) For animal drugs: (1) The... animal drug, whichever is earlier, and ends on the date a marketing application under section 512 of the...

21 CFR 60.22 - Regulatory review period determinations.

Code of Federal Regulations, 2012 CFR

2012-04-01

... drugs: (1) The testing phase begins on the date an exemption under section 505(i) of the Act becomes... Act and ends on the date the protocol is declared to be completed. (d) For animal drugs: (1) The... animal drug, whichever is earlier, and ends on the date a marketing application under section 512 of the...

21 CFR 60.22 - Regulatory review period determinations.

Code of Federal Regulations, 2013 CFR

2013-04-01

... drugs: (1) The testing phase begins on the date an exemption under section 505(i) of the Act becomes... Act and ends on the date the protocol is declared to be completed. (d) For animal drugs: (1) The... animal drug, whichever is earlier, and ends on the date a marketing application under section 512 of the...

Reducing Prescriptions of Long-Acting Benzodiazepine Drugs in Denmark: A Descriptive Analysis of Nationwide Prescriptions during a 10-Year Period.

PubMed

Eriksen, Sophie Isabel; Bjerrum, Lars

2015-06-01

Prolonged consumption of benzodiazepine drugs (BZD) and benzodiazepine receptor agonists (zolpidem, zaleplon, zopiclone; altogether Z drugs) is related to potential physiological and psychological dependence along with other adverse effects. This study aimed to analyse the prescribing of long-acting BZD (half-life >10 hr), compared to short-acting BZD in Denmark during a 10-year period. Descriptive analysis of total sales data from the Danish Register of Medicinal Product Statistics, to individuals in the primary healthcare sector, of all BZD and Z drugs in the period of 2003-2013. Prescription data derive from all community and hospital pharmacies in Denmark. The prescribing of long-acting BZD was reduced from 25.8 defined daily doses (DDD)/1000 inhabitants/day in 2003 to 8.8 DDD/1000 inhabitants/day in 2013, a relative reduction of 66%. The prescribing of short-acting BZD was reduced from 26.1 DDD/1000 inhabitants/day in 2003 to 16.4 DDD/1000 inhabitants/day in 2013, a relative reduction of 37%. Prescription data in this study did not include information about indications for initiating treatments. In addition, due to compliance problems, some of the prescribed drugs may not have been consumed according to the prescription. The observed reduction in BZD use was correlated to the introduction of new national guidelines on prescription of addictive drugs, but this study was not designed to detect a causal relationship. The prescribing of long-acting BZD decreased considerably more than the prescribing of short-acting BZD in the 10-year period. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Trends in the use of antiasthmatic medications in Morocco (1999-2010).

PubMed

Ghanname, Imane; Ahid, Samir; Berrada, Ghizlane; Belaiche, Abdelmjid; Hassar, Mohamed; Cherrah, Yahya

2013-12-01

Asthma is a big public health problem in Morocco. The drug therapy existing in Morocco is currently insufficient because of the low purchasing power and the low health insurance coverage available to the average citizen in Morocco. In this study we evaluated the consumption of antiasthmatics in Morocco during the period 1999-2010, the classes of used drugs and the generics' market share. We used sales data from the Moroccan subsidiaries of the IMS Health "Intercontinental Marketing Service". The consumption volume was converted to Defined Daily Doses (DDDs). During 1999-2010, antiasthmatics's consumption increased from 3.91 to 14.47 DDD per 1000 inhabitants per day. In 2010, the association Beta-2-mimetic-Glucocorticosteroids were the most consumed (8.53 DDD/1000 Inhabitants/day) followed by the short-acting inhaled Beta-2-mimetic (4 DDD/1000 Inhabitants/day) and inhaled Glucocorticosteroids alone accounted for 1.13 DDD/1000 Inhabitants/day. The largest consumption share in volume was held by the short-acting inhaled Beta-2-mimetic (42%) followed by the combination Beta-2-mimetic-Glucocorticosteroids (38%). Between 1999 and 2010, the market for generic antiasthmatics increased from 1.84 to 2.18 DDD/1000 Inhabitants/day. The ratio of the monthly average cost of treatment to the minimum wage in Morocco decreased from 10.8% in 1999 to 7.11% in 2010. Antiasthmatics' consumption in Morocco has undergone significant changes between 1999 and 2010. However, the availability of these drugs expressed as the Average Monthly Expenditure/Guaranteed Minimum Wage ratio improved. Despite this, the use of antiasmathics in Morocco remains low.

Antimalarial drug resistance: linking Plasmodium falciparum parasite biology to the clinic

PubMed Central

Blasco, Benjamin; Leroy, Didier; Fidock, David A

2017-01-01

The global adoption of artemisinin-based combination therapies (ACTs) in the early 2000s heralded a new era in effectively treating drug-resistant Plasmodium falciparum malaria. However, several Southeast Asian countries have now reported the emergence of parasites that have decreased susceptibility to artemisinin (ART) derivatives and ACT partner drugs, resulting in increasing rates of treatment failures. Here we review recent advances in understanding how antimalarials act and how resistance develops, and discuss new strategies for effectively combatting resistance, optimizing treatment and advancing the global campaign to eliminate malaria. PMID:28777791

Rational management of epilepsy.

PubMed

Viswanathan, Venkataraman

2014-09-01

Management of epilepsies in children has improved considerably over the last decade, all over the world due to the advances seen in the understanding of the patho-physiology of epileptogenesis, availability of both structural and functional imaging studies along with better quality EEG/video-EEG recordings and the availability of a plethora of newer anti-epileptic drugs which are tailormade to act on specific pathways. In spite of this, there is still a long way to go before one is able to be absolutely rational about which drug to use for which type of epilepsy. There have been a lot of advances in the area of epilepsy surgery and is certainly gaining ground for specific cases. Better understanding of the genetic basis of epilepsies will hopefully lead to a more rational treatment plan in the future. Also, a lot of work needs to be done to dispel various misunderstandings and myths about epilepsy which still exists in our country.

[Impact Reimbursement Act on the pharmaceutical market in Poland].

PubMed

Giermaziak, Wojciech

2014-04-01

According to 12 may 2011 Reimbursement Act, the new regulations were introduced related to changes in so far in force rules on refunds of official prices and margins for drugs, foodstuffs of special purpose and medical products. After year of functioning of this regulation, in evaluation of the government, law gave measurable financial effects for public payer, sometimes through drastic actions, connected the of reduction of existing profits of manufacturers sector and importers drugs, as well wholesale and retail, both in treatment open and closed. Parallel to research and analysis of effects introduction in life act refund, conducted by government, to target current regulation possible negative phenomena can to be after-effects to regulation, systematically there are conducted analogous study to reputable companies specialized in evaluation and updating market Polish pharmaceutical, such as IMS Health Polska, Pharma Expert, Kamsoft, WHO and European a law firm. In their opinion to reimbursement act is the most serious regulation control system to introduced into Polish order legal, and first time for many years on such a large scale. Thoroughly changed policy of drugs State have important influence for all participants Polish pharmaceutical market, both those directly related to the drug trade, as the functioning doctors and health condition and financial Polish patient. Change in the way prices of drugs is determined as flexible to price formation mechanism, combining drugs similar profile pharmacological in so group limits and dependence of the level of refunds from application drug accordingly characteristics medicinal product, adaptation solutions to new law refund to the existing law about health services, gave measurable financial effect for the public payer. Rationalization expenses to NFZ, as main premise introduction refund act, created to broader than so far possibility to use new molecules of drugs, and the latest medical technology, even if in the revised or new drug programs. Important implications for even Polish image in Europe, especially from the point of view of cohesion policy and application to directive transparency EU have introduction refund act in context to introduction clear, transparent and verifiable procedures used with creating drug pricing mechanisms, foodstuffs of special purpose and medical product.

The Blood Brain Barrier and its Role in Alzheimer's Therapy: An Overview.

PubMed

Jakki, Satya Lavanya; Senthil, V; Yasam, Venkata Ramesh; Chandrasekar, M J N; Vijayaraghavan, C

2018-01-01

Alzheimer's disease (AD) is the most frequent age related neurodegenerative disorder. It represents 70% of all dementia. Millions of people have been affected by AD worldwide. It is a complex illness characterized pathologically by accumulation of protein aggregates of amyloid and neurofibrillary tangles containing hyperphosphorylated neuronal tau protein. AD requires drugs that can circumvent the blood-brain barrier (BBB) which is not a simple physical barrier between blood and brain, but acts as an iron curtain, allowing only selective molecules to enter the brain. Unfortunately, this dynamic barrier restricts transport of drugs to the brain; due to which, currently very few drugs are available for AD treatment. The present review focuses mainly on strategies used for administration of drug to the CNS by-passing BBB for the treatment of AD. Many studies have proved to be effective in overcoming BBB and targeting drugs to CNS by using different strategies. Here we have discussed some of the most important drug permeability and drug targeting approaches. In conclusion, concentrating solely in development of drug discovery programs is not enough but it is important to maintain balance between the drug discovery and drug delivery systems that are more specific and effective in targeting CNS of AD patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Convergence and divergence, a concept for explaining drug actions.

PubMed

Watanabe, Takehiko; Kamisaki, Yoshinori; Timmerman, Henk

2004-10-01

For the teaching and/or learning about drug actions and for the discovery and development of new drugs, it is important to understand how drugs act on living bodies. So far, there has been no clear description on the general principle of drug action in pharmacology textbooks. We propose two principles to depict the action mechanism of drugs. The first is that most, if not all, drugs act on proteins at the molecular level, that is, enzymes, receptors, ion channels, and transporters. The second is that a drug may cause divergent or convergent responses, resulting in changes of a physiological or pathological function of the human body. The concept of divergence and convergence can be used to explain the complex individuality of drug actions.

Doxycycline for Malaria Chemoprophylaxis and Treatment: Report from the CDC Expert Meeting on Malaria Chemoprophylaxis

PubMed Central

Tan, Kathrine R.; Magill, Alan J.; Parise, Monica E.; Arguin, Paul M.

2011-01-01

Doxycycline, a synthetically derived tetracycline, is a partially efficacious causal prophylactic (liver stage of Plasmodium) drug and a slow acting blood schizontocidal agent highly effective for the prevention of malaria. When used in conjunction with a fast acting schizontocidal agent, it is also highly effective for malaria treatment. Doxycycline is especially useful as a prophylaxis in areas with chloroquine and multidrug-resistant Plasmodium falciparum malaria. Although not recommended for pregnant women and children < 8 years of age, severe adverse events are rarely reported for doxycycline. This report examines the evidence behind current recommendations for the use of doxycycline for malaria and summarizes the available literature on its safety and tolerability. PMID:21460003

Closing the access barrier for effective anti-malarials in the private sector in rural Uganda: consortium for ACT private sector subsidy (CAPSS) pilot study.

PubMed

Talisuna, Ambrose O; Daumerie, Penny Grewal; Balyeku, Andrew; Egan, Timothy; Piot, Bram; Coghlan, Renia; Lugand, Maud; Bwire, Godfrey; Rwakimari, John Bosco; Ndyomugyenyi, Richard; Kato, Fred; Byangire, Maria; Kagwa, Paul; Sebisubi, Fred; Nahamya, David; Bonabana, Angela; Mpanga-Mukasa, Susan; Buyungo, Peter; Lukwago, Julius; Batte, Allan; Nakanwagi, Grace; Tibenderana, James; Nayer, Kinny; Reddy, Kishore; Dokwal, Nilesh; Rugumambaju, Sylvester; Kidde, Saul; Banerji, Jaya; Jagoe, George

2012-10-29

Artemisinin-based combination therapy (ACT), the treatment of choice for uncomplicated falciparum malaria, is unaffordable and generally inaccessible in the private sector, the first port of call for most malaria treatment across rural Africa. Between August 2007 and May 2010, the Uganda Ministry of Health and the Medicines for Malaria Venture conducted the Consortium for ACT Private Sector Subsidy (CAPSS) pilot study to test whether access to ACT in the private sector could be improved through the provision of a high level supply chain subsidy. Four intervention districts were purposefully selected to receive branded subsidized medicines - "ACT with a leaf", while the fifth district acted as the control. Baseline and evaluation outlet exit surveys and retail audits were conducted at licensed and unlicensed drug outlets in the intervention and control districts. A survey-adjusted, multivariate logistic regression model was used to analyse the intervention's impact on: ACT uptake and price; purchase of ACT within 24 hours of symptom onset; ACT availability and displacement of sub-optimal anti-malarial. At baseline, ACT accounted for less than 1% of anti-malarials purchased from licensed drug shops for children less than five years old. However, at evaluation, "ACT with a leaf" accounted for 69% of anti-malarial purchased in the interventions districts. Purchase of ACT within 24 hours of symptom onset for children under five years rose from 0.8% at baseline to 26.2% (95% CI: 23.2-29.2%) at evaluation in the intervention districts. In the control district, it rose modestly from 1.8% to 5.6% (95% CI: 4.0-7.3%). The odds of purchasing ACT within 24 hours in the intervention districts compared to the control was 0.46 (95% CI: 0.08-2.68, p=0.4) at baseline and significant increased to 6.11 (95% CI: 4.32-8.62, p<0.0001) at evaluation. Children less than five years of age had "ACT with a leaf" purchased for them more often than those aged above five years. There was no evidence of price gouging. These data demonstrate that a supply-side subsidy and an intensive communications campaign significantly increased the uptake and use of ACT in the private sector in Uganda.

Closing the access barrier for effective anti-malarials in the private sector in rural Uganda: consortium for ACT private sector subsidy (CAPSS) pilot study

PubMed Central

2012-01-01

Background Artemisinin-based combination therapy (ACT), the treatment of choice for uncomplicated falciparum malaria, is unaffordable and generally inaccessible in the private sector, the first port of call for most malaria treatment across rural Africa. Between August 2007 and May 2010, the Uganda Ministry of Health and the Medicines for Malaria Venture conducted the Consortium for ACT Private Sector Subsidy (CAPSS) pilot study to test whether access to ACT in the private sector could be improved through the provision of a high level supply chain subsidy. Methods Four intervention districts were purposefully selected to receive branded subsidized medicines - “ACT with a leaf”, while the fifth district acted as the control. Baseline and evaluation outlet exit surveys and retail audits were conducted at licensed and unlicensed drug outlets in the intervention and control districts. A survey-adjusted, multivariate logistic regression model was used to analyse the intervention’s impact on: ACT uptake and price; purchase of ACT within 24 hours of symptom onset; ACT availability and displacement of sub-optimal anti-malarial. Results At baseline, ACT accounted for less than 1% of anti-malarials purchased from licensed drug shops for children less than five years old. However, at evaluation, “ACT with a leaf” accounted for 69% of anti-malarial purchased in the interventions districts. Purchase of ACT within 24 hours of symptom onset for children under five years rose from 0.8% at baseline to 26.2% (95% CI: 23.2-29.2%) at evaluation in the intervention districts. In the control district, it rose modestly from 1.8% to 5.6% (95% CI: 4.0-7.3%). The odds of purchasing ACT within 24 hours in the intervention districts compared to the control was 0.46 (95% CI: 0.08-2.68, p=0.4) at baseline and significant increased to 6.11 (95% CI: 4.32-8.62, p<0.0001) at evaluation. Children less than five years of age had “ACT with a leaf” purchased for them more often than those aged above five years. There was no evidence of price gouging. Conclusions These data demonstrate that a supply-side subsidy and an intensive communications campaign significantly increased the uptake and use of ACT in the private sector in Uganda. PMID:23107021

"Creating hope" and other incentives for drug development for children.

PubMed

Connor, Edward; Cure, Pablo

2011-01-19

Enhancing drug development for pediatric disease is a priority and a public responsibility. The Creating Hope Act of 2010 is important new proposed legislation that adds drugs and biologics for treating rare diseases in children to those for neglected tropical diseases as eligible for a priority review voucher from the U.S. Food and Drug Administration. The Act enhances existing incentive programs through specific financial benefits to companies who seek a pediatric indication for a new drug to treat an orphan disease that occurs specifically in children.

21 CFR 860.95 - Exemptions from sections 510, 519, and 520(f) of the act.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Exemptions from sections 510, 519, and 520(f) of the act. 860.95 Section 860.95 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... (records and reports), and section 520(f) (good manufacturing practice requirements of the quality system...

Employing and Accommodating Individuals with Histories of Alcohol and Drug Abuse. Implementing the Americans with Disabilities Act Series.

ERIC Educational Resources Information Center

Weber, Ellen M.

One of a series of bulletins on implementing the Americans with Disabilities Act (ADA), this bulletin discusses protections for individuals with histories of alcohol and drug abuse. The material explains: (1) the ADA prohibits employment discrimination of individuals with past drug and alcohol problems and those who currently have alcohol problems…

Local Evaluation of Programs Funded under the Drug-Free Schools and Communities Act. Final Report.

ERIC Educational Resources Information Center

Tashjian, Michael D.; Elliott, Barbara

In September 1993 the U.S. Department of Education (ED) released a handbook to assist school- and community-based practitioners in designing and conducting evaluations of drug- and violence-prevention programs funded under the Drug Free Schools and Communities Act (DFSCA). A study was undertaken to assess the level of customer satisfaction with…

21 CFR 70.50 - Application of the cancer clause of section 721 of the act.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Application of the cancer clause of section 721 of the act. 70.50 Section 70.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... testing) suggest the possibility that the color additive including its components or impurities has...

21 CFR 70.50 - Application of the cancer clause of section 721 of the act.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Application of the cancer clause of section 721 of the act. 70.50 Section 70.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... testing) suggest the possibility that the color additive including its components or impurities has...

21 CFR 70.50 - Application of the cancer clause of section 721 of the act.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Application of the cancer clause of section 721 of the act. 70.50 Section 70.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... testing) suggest the possibility that the color additive including its components or impurities has...

You are what you eat: influence of type and amount of food consumed on central dopamine systems and the behavioral effects of direct- and indirect-acting dopamine receptor agonists.

PubMed

Baladi, Michelle G; Daws, Lynette C; France, Charles P

2012-07-01

The important role of dopamine (DA) in mediating feeding behavior and the positive reinforcing effects of some drugs is well recognized. Less widely studied is how feeding conditions might impact the sensitivity of drugs acting on DA systems. Food restriction, for example, has often been the focus of aging and longevity studies; however, other studies have demonstrated that mild food restriction markedly increases sensitivity to direct- and indirect-acting DA receptor agonists. Moreover, it is becoming clear that not only the amount of food, but the type of food, is an important factor in modifying the effects of drugs. Given the increased consumption of high fat and sugary foods, studies are exploring how consumption of highly palatable food impacts DA neurochemistry and the effects of drugs acting on these systems. For example, eating high fat chow increases sensitivity to some behavioral effects of direct- as well as indirect-acting DA receptor agonists. A compelling mechanistic possibility is that central DA pathways that mediate the effects of some drugs are regulated by one or more of the endocrine hormones (e.g. insulin) that undergo marked changes during food restriction or after consuming high fat or sugary foods. Although traditionally recognized as an important signaling molecule in regulating energy homeostasis, insulin can also regulate DA neurochemistry. Because direct- and indirect-acting DA receptor drugs are used therapeutically and some are abused, a better understanding of how food intake impacts response to these drugs would likely facilitate improved treatment of clinical disorders and provide information that would be relevant to the causes of vulnerability to abuse drugs. This article is part of a Special Issue entitled 'Central Control of Food Intake'. Copyright © 2012 Elsevier Ltd. All rights reserved.

Willingness-to-pay for a rapid malaria diagnostic test and artemisinin-based combination therapy from private drug shops in Mukono district, Uganda

PubMed Central

Hansen, Kristian Schultz; Pedrazzoli, Debora; Mbonye, Anthony; Clarke, Sian; Cundill, Bonnie; Magnussen, Pascal; Yeung, Shunmay

2013-01-01

In Uganda, as in many parts of Africa, the majority of the population seek treatment for malaria in drug shops as their first point of care; however, parasitological diagnosis is not usually offered in these outlets. Rapid diagnostic tests (RDTs) for malaria have attracted interest in recent years as a tool to improve malaria diagnosis, since they have proved accurate and easy to perform with minimal training. Although RDTs could feasibly be performed by drug shop vendors, it is not known how much customers would be willing to pay for an RDT if offered in these settings. We conducted a contingent valuation survey among drug shop customers in Mukono District, Uganda. Exit interviews were undertaken with customers aged 15 years and above after leaving a drug shop having purchased an antimalarial and/or paracetamol. The bidding game technique was used to elicit the willingness-to-pay (WTP) for an RDT and a course of artemisinin-based combination therapy (ACT) with and without RDT confirmation. Factors associated with WTP were investigated using linear regression. The geometric mean WTP for an RDT was US$0.53, US$1.82 for a course of ACT and US$2.05 for a course of ACT after a positive RDT. Factors strongly associated with a higher WTP for these commodities included having a higher socio-economic status, no fever/malaria in the household in the past 2 weeks and if a malaria diagnosis had been obtained from a qualified health worker prior to visiting the drug shop. The findings further suggest that the WTP for an RDT and a course of ACT among drug shop customers is considerably lower than prevailing and estimated end-user prices for these commodities. Increasing the uptake of ACTs in drug shops and restricting the sale of ACTs to parasitologically confirmed malaria will therefore require additional measures. PMID:22589226

Willingness-to-pay for a rapid malaria diagnostic test and artemisinin-based combination therapy from private drug shops in Mukono District, Uganda.

PubMed

Hansen, Kristian Schultz; Pedrazzoli, Debora; Mbonye, Anthony; Clarke, Sian; Cundill, Bonnie; Magnussen, Pascal; Yeung, Shunmay

2013-03-01

In Uganda, as in many parts of Africa, the majority of the population seek treatment for malaria in drug shops as their first point of care; however, parasitological diagnosis is not usually offered in these outlets. Rapid diagnostic tests (RDTs) for malaria have attracted interest in recent years as a tool to improve malaria diagnosis, since they have proved accurate and easy to perform with minimal training. Although RDTs could feasibly be performed by drug shop vendors, it is not known how much customers would be willing to pay for an RDT if offered in these settings. We conducted a contingent valuation survey among drug shop customers in Mukono District, Uganda. Exit interviews were undertaken with customers aged 15 years and above after leaving a drug shop having purchased an antimalarial and/or paracetamol. The bidding game technique was used to elicit the willingness-to-pay (WTP) for an RDT and a course of artemisinin-based combination therapy (ACT) with and without RDT confirmation. Factors associated with WTP were investigated using linear regression. The geometric mean WTP for an RDT was US$0.53, US$1.82 for a course of ACT and US$2.05 for a course of ACT after a positive RDT. Factors strongly associated with a higher WTP for these commodities included having a higher socio-economic status, no fever/malaria in the household in the past 2 weeks and if a malaria diagnosis had been obtained from a qualified health worker prior to visiting the drug shop. The findings further suggest that the WTP for an RDT and a course of ACT among drug shop customers is considerably lower than prevailing and estimated end-user prices for these commodities. Increasing the uptake of ACTs in drug shops and restricting the sale of ACTs to parasitologically confirmed malaria will therefore require additional measures.

Drug-facilitated sexual assault ('date rape').

PubMed

Schwartz, R H; Milteer, R; LeBeau, M A

2000-06-01

In the past few years, drug-facilitated sexual assaults have received widespread media coverage. In addition to alcohol, the most frequently used date-rape drug, flunitrazepam (Rohypnol), a fast-acting benzodiazepine, and gamma-hydroxybutyrate (GHB) and its congeners are among the most popular drugs used for this purpose. The latter drug is easily procured at some gymnasiums, popular bars, discos, and rave clubs, as well as over the Internet. Perpetrators choose these drugs because they act rapidly, produce disinhibition and relaxation of voluntary muscles, and cause the victim to have lasting anterograde amnesia for events that occur under the influence of the drug. Alcoholic beverages potentiate the drug effects. We review several date-rape drugs, provide information on laboratory testing for them, and offer guidelines for preventing drug-facilitated sexual assault.

Seizures as a Potential Complication of Treatment With Simeprevir and Sofosbuvir.

PubMed

Syal, Gaurav; Heldenbrand, Seth D; Duarte-Rojo, Andres

2016-01-01

Newer direct-acting antiviral agents have revolutionized the medical management of chronic hepatitis C. In addition to being extremely efficacious, they report very mild adverse drug reactions from experience in clinical trials. However, because they are relatively new on the horizon, postmarketing surveillance studies refining the safety profile are not yet available. We present a case of seizures as a potential side effect of antiviral therapy with sofosbuvir and simeprevir.

Does levonorgestrel emergency contraceptive have a post-fertilization effect? A review of its mechanism of action.

PubMed

Peck, Rebecca; Rella, Walter; Tudela, Julio; Aznar, Justo; Mozzanega, Bruno

2016-02-01

Recent studies have identified that levonorgestrel administered orally in emergency contraception (LNG-EC) is only efficacious when taken before ovulation. However, the drug does not consistently prevent follicular rupture or impair sperm function. The present systematic review is performed to analyze and more precisely define the extent to which pre-fertilization mechanisms of action may explain the drug's efficacy in pregnancy avoidance. We also examine the available evidence to determine if pre-ovulatory drug administration may be associated with post-fertilization effects. The mechanism of action of LNG-EC is reviewed. The drug has no ability to alter sperm function at doses used in vivo and has limited ability to suppress ovulation. Our analysis estimates that the drug's ovulatory inhibition potential could prevent less than 15 percent of potential conceptions, thus making a pre-fertilization mechanism of action significantly less likely than previously thought. Luteal effects (such as decreased progesterone, altered glycodelin levels, and shortened luteal phase) present in the literature may suggest a pre-ovulatory induced post-fertilization drug effect. Plan B is the most widely used emergency contraceptive available. It is important for patients and physicians to clearly understand the drug's mechanism of action (MOA). The drug was originally thought to work by preventing fertilization. Recent research has cast doubt on this. Our review of the research suggests that it could act in a pre-fertilization capacity, and we estimate that it could prevent ovulation in only 15 percent or less of cases. The drug has no ability to alter sperm function and limited ability to suppress ovulation. Further, data suggest that when administered pre-ovulation, it may have a post-fertilization MOA.

Perspectives on treatment options for mesial temporal lobe epilepsy with hippocampal sclerosis.

PubMed

Palleria, Caterina; Coppola, Antonietta; Citraro, Rita; Del Gaudio, Luigi; Striano, Salvatore; De Sarro, Giovambattista; Russo, Emilio

2015-01-01

Mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) is a syndrome that is often refractory to drug treatment. The effects on specific syndromes are not currently available from the pre-marketing clinical development of new AEDs; this does not allow the prediction of whether new drugs will be more effective in the treatment of some patients. We have reviewed all the existing literature relevant to the understanding of a potential effectiveness in MTLE-HS patients for the latest AEDs, namely brivaracetam, eslicarbazepine, lacosamide, perampanel and retigabine also including the most relevant clinical data and a brief description of their pharmacological profile. Records were identified using predefined search criteria using electronic databases (e.g., PubMed, Cochrane Library Database of Systematic Reviews). Primary peer-reviewed articles published up to the 15 June 2015 were included. All the drugs considered have the potential to be effective in the treatment of MTLE-HS; in fact, they possess proven efficacy in animal models; currently considered valuable tools for predicting drug efficacy in TLE. Furthermore, for some of these (e.g., lacosamide and eslicarbazepine) data are already available from post-marketing studies while brivaracetam acting on SV2A like levetiracetam might have the same potential effectiveness with the possibility to be more efficacious considering its ability to inhibit voltage gated sodium channels; finally, perampanel and retigabine are very effective drugs in animal models of TLE.

The Orphan Drug Act: Restoring the Mission to Rare Diseases.

PubMed

Daniel, Michael G; Pawlik, Timothy M; Fader, Amanda N; Esnaola, Nestor F; Makary, Martin A

2016-04-01

The Orphan Drug Act has fostered drug development for patients with rare cancers and other diseases; however, current data suggest that companies are gaming the system to use the law for mainstream drugs. We identify a pattern of pharmaceutical companies submitting drugs to the Food and Drug Administration (FDA) as orphan drugs but once approved, the drugs are used broadly off-label with the lucrative orphan drug protections and exclusivity benefits. Since the law was passed, the proportion of new FDA-approved drugs that were submitted as orphan drugs has increased with a peak last year of 41% of all FDA-approved drugs approved as orphan drugs. On the basis of the current data, we suggest that patients with rare cancers and other diseases may suffer due to dilution of the incentives and benefits. We propose reform to increase submission scrutiny, decrease benefits based on off-label use, and increase price transparency.

Inhibition of the multidrug resistance P-glycoprotein: time for a change of strategy?

PubMed

Callaghan, Richard; Luk, Frederick; Bebawy, Mary

2014-04-01

P-glycoprotein (P-gp) is a key player in the multidrug-resistant phenotype in cancer. The protein confers resistance by mediating the ATP-dependent efflux of an astonishing array of anticancer drugs. Its broad specificity has been the subject of numerous attempts to inhibit the protein and restore the efficacy of anticancer drugs. The general strategy has been to develop compounds that either compete with anticancer drugs for transport or act as direct inhibitors of P-gp. Despite considerable in vitro success, there are no compounds currently available to "block" P-gp-mediated resistance in the clinic. The failure may be attributed to toxicity, adverse drug interaction, and numerous pharmacokinetic issues. This review provides a description of several alternative approaches to overcome the activity of P-gp in drug-resistant cells. These include 1) drugs that specifically target resistant cells, 2) novel nanotechnologies to provide high-dose, targeted delivery of anticancer drugs, 3) compounds that interfere with nongenomic transfer of resistance, and 4) approaches to reduce the expression of P-gp within tumors. Such approaches have been developed through the pursuit of greater understanding of resistance mediators such as P-gp, and they show considerable potential for further application.

The role of the Pharmaceuticals and Medical Devices Agency and healthcare professionals in post-marketing safety.

PubMed

Mori, Kazuhiko; Watanabe, Meguru; Horiuchi, Naoya; Tamura, Atsushi; Kutsumi, Hiromu

2014-04-01

The development of drugs and medical devices is necessary for medical progress; however, safety measures need to be put in place to protect the health of the population. In order to ensure the safety of drugs and medical devices, it is important to determine measures for appropriate management of risks at any time during the development phase, the regulatory review and the post-marketing phase. Adverse events detected in clinical trials are limited due to the restricted numbers of patients enrolled in the trials. Therefore, it is almost impossible to predict rare serious adverse events during the post-marketing phase. The revised Pharmaceutical Affairs Act was established in Japan in November 20, 2013. The new act focuses on increased safety of drugs and medical devices. The Pharmaceuticals and Medical Devices Agency (PMDA) is the regulatory authority in Japan that promotes safety measures from the development phase through to the post-marketing phase. In the post-marketing phase, the PMDA collects information from the medical product companies and healthcare professionals, as well as instructing and advising them with regard to post-marketing safety measures for each drug and medical device. Since Japan has a national health insurance system, a new drug or a medical device is available throughout the country when the drug price or medical fee is listed in the National Health Insurance price list. Healthcare professionals in medical institutions must learn about the drugs and medical devices they handle, and should make an effort to maintain patient safety. The PMDA medi-navi is a very useful electronic mail delivery service that provides critical information for protecting patients from health hazards caused by adverse events. The 'risk management plan' is also important as it contains important information about safety profile and post-marketing measures of a new drug.

77 FR 51030 - Kelly Dean Shrum: Debarment Order

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-23

...The Food and Drug Administration (FDA) is issuing an order under the Federal Food, Drug, and Cosmetic Act (the FD&C Act) permanently debarring Kelly Dean Shrum, from providing services in any capacity to a person that has an approved or pending drug product application. FDA bases this order on a finding that Dr. Shrum was convicted of a felony under Federal law for conduct relating to the regulation of a drug product under the FD&C Act. Dr. Shrum was given notice of the proposed permanent debarment and an opportunity to request a hearing within the timeframe prescribed by regulation. Dr. Shrum failed to respond. Dr. Shrum's failure to respond constitutes a waiver of his right to a hearing concerning this action.

Quantifying antiviral activity optimizes drug combinations against hepatitis C virus infection.

PubMed

Koizumi, Yoshiki; Ohashi, Hirofumi; Nakajima, Syo; Tanaka, Yasuhito; Wakita, Takaji; Perelson, Alan S; Iwami, Shingo; Watashi, Koichi

2017-02-21

With the introduction of direct-acting antivirals (DAAs), treatment against hepatitis C virus (HCV) has significantly improved. To manage and control this worldwide infectious disease better, the "best" multidrug treatment is demanded based on scientific evidence. However, there is no method available that systematically quantifies and compares the antiviral efficacy and drug-resistance profiles of drug combinations. Based on experimental anti-HCV profiles in a cell culture system, we quantified the instantaneous inhibitory potential (IIP), which is the logarithm of the reduction in viral replication events, for both single drugs and multiple-drug combinations. From the calculated IIP of 15 anti-HCV drugs from different classes [telaprevir, danoprevir, asunaprevir, simeprevir, sofosbuvir (SOF), VX-222, dasabuvir, nesbuvir, tegobuvir, daclatasvir, ledipasvir, IFN-α, IFN-λ1, cyclosporin A, and SCY-635], we found that the nucleoside polymerase inhibitor SOF had one of the largest potentials to inhibit viral replication events. We also compared intrinsic antiviral activities of a panel of drug combinations. Our quantification analysis clearly indicated an advantage of triple-DAA treatments over double-DAA treatments, with triple-DAA treatments showing enhanced antiviral activity and a significantly lower probability for drug resistance to emerge at clinically relevant drug concentrations. Our framework provides quantitative information to consider in designing multidrug strategies before costly clinical trials.

47 CFR 1.2002 - Applicants required to submit information.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Grants by Random Selection Implementation of the Anti-Drug Abuse Act of 1988 § 1.2002 Applicants required... benefits that includes FCC benefits pursuant to section 5301 of the Anti-Drug Abuse Act of 1988. 21 U.S.C...

47 CFR 1.2002 - Applicants required to submit information.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Grants by Random Selection Implementation of the Anti-Drug Abuse Act of 1988 § 1.2002 Applicants required... benefits that includes FCC benefits pursuant to section 5301 of the Anti-Drug Abuse Act of 1988. 21 U.S.C...

47 CFR 1.2002 - Applicants required to submit information.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Grants by Random Selection Implementation of the Anti-Drug Abuse Act of 1988 § 1.2002 Applicants required... benefits that includes FCC benefits pursuant to section 5301 of the Anti-Drug Abuse Act of 1988. 21 U.S.C...

[Dissociated learning with GABAergic drugs].

PubMed

Azarashvili, A A; Kaĭmachnikova, I E

2008-01-01

The possibility of dissociated learning was investigated using drugs which act directly on GABAB receptors of the brain. The earlier proposed suggestion that the cholinergic system plays a key role in the mechanisms of dissociated learning was tested. It was shown in male Wistar rats that dissociated learning was possible with GABAergic drugs. The dissociated state was induced by injecting the animals with both GABA agonist Baclofen and GABA antagonist 5-aminovaleric acid. Thus, dissociated learning is possible with drugs which act on either cholinergic or GABAergic transmitter systems.

A qualitative study of the feasibility and community perception on the effectiveness of artemether-lumefantrine use in the context of home management of malaria in south-west Nigeria

PubMed Central

Ajayi, Ikeoluwapo O; Falade, Catherine O; Olley, Benjamin O; Yusuf, Bidemi; Gbotosho, Sola; Iyiola, Toyin; Olaniyan, Omobola; Happi, Christian; Munguti, Kaendi; Pagnoni, Franco

2008-01-01

Background In Nigeria ACT use at the community level has not been evaluated and the use of antimalarial drugs (commonly chloroquine (CQ)) at home has been shown to be largely incorrect. The treatment regimen of ACT is however more complicated than that of CQ. There is thus a need to determine the feasibility of using ACT at the home level and determine community perception on its use. Methods A before and after qualitative study using key informant interviews (KII) and focus group discussions (FGDs) was conducted in selected villages in Ona-Ara local government area. At baseline, 14 FGDs and 14 KIIs were conducted. Thereafter, community medicine distributors (CMDs) were trained in each village to dispense artemeter-lumenfantrine (AL) to febrile children aged 6–59 months presumed to have uncomplicated malaria. After one year of drug distribution, nine KIIs and 10 FGDs were conducted. Participants and key informants were mothers and fathers with children under five years, traditional heads of communities, opinion leaders and health workers. Results None of the participants have heard of AL prior to study. Participants were favourably disposed to introduction of AL into the community. Mothers/caregivers were said to have used AL in place of the orthodox drugs and herbs reported commonly used prior to study after commencement of AL distribution. The use of CMDs for drug distribution was acceptable to the participants and they were judged to be efficient as they were readily available, distributed correct dose of AL and mobilised the community effectively. AL was perceived to be very effective and no significant adverse event was reported. Major concerns to the sustainability of the program were the negative attitudes of health workers towards discharge of their duties, support to the CMDs and the need to provide CMDs incentives. In addition regular supply of drugs and adequate supervision of CMDs were advised. Conclusion Our findings showed that the use of AL at home and community level is feasible with adequate training of community medicine distributors and caregivers. Community members perceived AL to be effective thus fostering acceptability. The negative attitudes of the health workers and issue of incentives to CMDs need to be addressed for successful scaling-up of ACT use at community level. PMID:18513447

An in vivo strategy to counteract post-administration anticoagulant activity of azido-Warfarin

NASA Astrophysics Data System (ADS)

Ursuegui, Sylvain; Recher, Marion; Krężel, Wojciech; Wagner, Alain

2017-05-01

Drugs, usually long acting and metabolically stable molecules, might be the source of adverse effects triggered by complex drug interactions, anaphylaxis and drug-induced coagulopathy. To circumvent this growing drug safety issue, we herein investigate the opportunity offered by bio-orthogonal chemistry for in vivo drug neutralization. We design a small-molecule anticoagulant drug (Warfarin) containing an azide group that acts as a safety pin. It allows drug deactivation and restoration of physiological coagulation via in vivo click reaction with a suitable cyclooctyne-based neutralizing agent. In this strategy, the new molecule formed by reaction of the drug and the antidote is deprived of biological activity and prone to fast renal clearance. This `Click & Clear' approach lays ground for new strategies in designing drugs with switchable biophysical properties.

Combined bronchodilators (tiotropium plus olodaterol) for patients with chronic obstructive pulmonary disease.

PubMed

Ramadan, Wijdan H; Kabbara, Wissam K; El Khoury, Ghada M; Al Assir, Sarah A

2015-01-01

Chronic obstructive pulmonary disease (COPD), a respiratory disease characterized by a progressive decline in lung function, is considered to be a leading cause of morbidity and mortality. Long-acting inhaled bronchodilators, such as long-acting β2 agonists (LABAs) or long-acting muscarinic antagonists (LAMAs), are the cornerstone of maintenance therapy for patients with moderate-to-very-severe COPD. For patients not sufficiently controlled on a single long-acting bronchodilator, a combination of different bronchodilators has shown a significant increase in lung function. Tiotropium, a once-daily dosing LAMA, demonstrated sustained improvements in lung function as well as improved health-related quality of life, reduced exacerbations, and increased survival without altering the rate of decline in the mean forced expiratory volume in 1 second (FEV1) with fairly tolerable side effects. Olodaterol is a once-daily dosing LABA that has proven to be effective in improving lung function, reducing rescue medication use, and improving dyspnea and health-related quality of life, as well as improving exercise endurance with an acceptable safety profile. The combination of olodaterol and tiotropium provided additional improvements in lung function greater than monotherapy with each drug alone. Several well-designed randomized trials confirmed that the synergistic effect of both drugs in combination was able to improve lung function and health-related quality of life without a significant increase in adverse effects. The objective of this paper is to review available evidence on the clinical efficacy and safety of tiotropium, olodaterol, and their combination in patients with COPD.

Designating Additions to the Current List of Tropical Diseases in the Federal Food, Drug, and Cosmetic Act. Final order.

PubMed

2015-08-20

The Federal Food, Drug, and Cosmetic Act (the FD&C Act) authorizes the Food and Drug Administration (FDA or Agency) to award priority review vouchers (PRVs) to tropical disease product applicants when the applications meet certain criteria. The FD&C Act lists the diseases that are considered to be tropical diseases for purposes of obtaining PRVs, and also provides for Agency expansion of that list to include other diseases that satisfy the definition of ``tropical diseases'' as set forth in the FD&C Act. FDA has determined that Chagas disease and neurocysticercosis satisfy this definition, and therefore is adding them to the list of designated tropical diseases whose product applications may result in the award of PRVs. Sponsors submitting certain applications for the treatment of Chagas disease and neurocysticercosis may be eligible to receive a PRV if such applications are approved by FDA.

47 CFR 1.2002 - Applicants required to submit information.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Implementation of the Anti-Drug Abuse Act of 1988 § 1.2002 Applicants required to submit information. (a) In... benefits pursuant to section 5301 of the Anti-Drug Abuse Act of 1988. 21 U.S.C. 862. If a section 5301...

47 CFR 1.2002 - Applicants required to submit information.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Implementation of the Anti-Drug Abuse Act of 1988 § 1.2002 Applicants required to submit information. (a) In... benefits pursuant to section 5301 of the Anti-Drug Abuse Act of 1988. 21 U.S.C. 862. If a section 5301...

Review of the 2015 Drug Supply Chain Security Act

PubMed Central

Brechtelsbauer, Erich D.; Pennell, Benjamin; Durham, Mary; Hertig, John B.; Weber, Robert J.

2016-01-01

The integrity of the pharmaceutical supply chain is threatened by medication counterfeiting, importation of unapproved and substandard drugs, and grey markets – all of which have the potential to distribute drug products with the potential for serious harm. On November 27, 2013, President Obama signed into law Title II of the Drug Quality and Security Act, now known as the Drug Supply Chain Security Act (DSCSA). Over the next 10 years, the DSCSA will require the pharmaceutical supply chain to implement medication tracking and tracing; serialization, verification, and detection of suspicious products; and strict guidelines for wholesaler licensing and reporting. This article reviews the important aspects of the DSCSA and outlines the role of health-system pharmacy leaders in ensuring compliance to the DSCSA. By verifying that medication supplies are free from adulteration and tampering, the DSCSA serves as a foundational law to ensure quality in providing patient-centered pharmacy services. PMID:27354753

Do patients adhere to over-the-counter artemisinin combination therapy for malaria? evidence from an intervention study in Uganda

PubMed Central

2012-01-01

Background Increasing affordability of artemisinin combination therapy (ACT) in the African retail sector could be critical to expanding access to effective malaria treatment, but must be balanced by efforts to protect the efficacy of these drugs. Previous research estimates ACT adherence rates among public sector patients, but adherence among retail sector purchasers could differ substantially. This study aimed to estimate adherence rates to subsidized, over-the-counter ACT in rural Uganda. Methods An intervention study was conducted with four licensed drug shops in Eastern Uganda in December 2009. Artemether-lumefantrine (AL) was made available for sale at a 95% subsidy over-the counter. Customers completed a brief survey at the time of purchase and then were randomly assigned to one of three study arms: no follow-up, follow-up after two days or follow-up after three days. Surveyors recorded the number of pills remaining through blister pack observation or through self-report if the pack was unavailable. The purpose of the three-day follow-up arm was to capture non-adherence in the sense of an incomplete treatment course ("under-dosing"). The purpose of the two-day follow-up arm was to capture whether participants completed the full course too soon ("over-dosing"). Results Of the 106 patients in the two-day follow-up sample, 14 (13.2%) had finished the entire treatment course by the second day. Of the 152 patients in the three-day follow-up sample, 49 (32.2%) were definitely non-adherent, three (2%) were probably non-adherent and 100 (65.8%) were probably adherent. Among the 52 who were non-adherent, 31 (59.6%) had more than a full day of treatment remaining. Conclusions Overall, adherence to subsidized ACT purchased over-the-counter was found to be moderate. Further, a non-trivial fraction of those who complete treatment are taking the full course too quickly. Strategies to increase adherence in the retail sector are needed in the context of increasing availability and affordability of ACT in this sector. PMID:22443291

Harms and benefits associated with psychoactive drugs: findings of an international survey of active drug users

PubMed Central

Morgan, Celia JA; Noronha, Louise A; Muetzelfeldt, Mark; Fielding, Amanda

2013-01-01

There have been several recent efforts in the UK and the Netherlands to describe the harms of psychoactive substances based on ratings of either experts or drug users. This study aimed to assess the perceived benefits as well as harms of widely used recreational drugs, both licit and illicit, in an international sample of drug users. The survey was hosted at https://www.internationaldrugsurvey.org/ and was available in three languages. Residents reported their experience of 15 commonly used drugs or drug classes; regular users then rated their harms and benefits. In all, 5791 individuals from over 40 countries completed the survey, although the majority were from English speaking countries. Rankings of drugs differed across 10 categories of perceived benefits. Skunk and herbal cannabis were ranked consistently beneficial, whilst alcohol and tobacco fell below many classified drugs. There was no correlation at all between users’ harm ranking of drugs and their classification in schedules of the USA or ABC system in the UK. Prescription analgesics, alcohol and tobacco were ranked within the top 10 most harmful drugs. These findings suggest that neither the UK nor US classification systems act to inform users of the harms of psychoactive substances. It is hoped the results might inform health professionals and educators of what are considered to be both the harms and benefits of psychoactive substances to young people. PMID:23438502

Activation of 5-hydroxytryptamine1B/1D/1F receptors as a mechanism of action of antimigraine drugs.

PubMed

Ramírez Rosas, Martha B; Labruijere, Sieneke; Villalón, Carlos M; Maassen Vandenbrink, Antoinette

2013-08-01

The introduction of the triptans (5-hydroxytryptamine (5-HT)1B/1D receptor agonists) was a great improvement in the acute treatment of migraine. However, shortcomings of the triptans have prompted research on novel serotonergic targets for the treatment of migraine. In this review the different types of antimigraine drugs acting at 5-HT receptors, their discovery and development are discussed. The first specific antimigraine drugs were the ergot alkaloids, consisting of ergotamine, dihydroergotamine and methysergide, which are agonists at 5-HT receptors, but can also bind α-adrenoceptors and dopamine receptors. In the 1990s, the triptans became available on the market. They are 5-HT1B/1D receptor agonists, showing fewer side effects due to their receptor specificity. In the last years, compounds that bind specifically to 5-HT1D, 5-HT1F and 5-HT7 receptors have been explored for their antimigraine potential. Furthermore, the serotonergic system seems to act in tight connection with the glutamatergic as well as the CGRP-ergic systems, which may open novel therapeutic avenues. Although the triptans are very effective in treating migraine attacks, their shortcomings have stimulated the search for novel drugs. Currently, the focus is on 5-HT1F receptor agonists, which seem devoid of vascular side effects. Moreover, novel compounds that affect multiple transmitter and/or neuropeptide systems that are involved in migraine could be of therapeutic relevance.

Effects of oral and intravenous administration of buspirone on food-cocaine choice in socially housed male cynomolgus monkeys.

PubMed

Czoty, Paul W; Nader, Michael A

2015-03-13

Drugs acting at D3 dopamine receptors have been suggested as medications for cocaine dependence. These experiments examined the effects of intravenously and orally administered buspirone, a D2-like receptor antagonist with high affinity for D3 and D4 receptors, on the relative reinforcing strength of cocaine in group-housed male cynomolgus monkeys. Use of socially housed monkeys permitted the assessment of whether social status, known to influence D2-like receptor availability, modulates the behavioral effects of buspirone. Buspirone was administered acutely to monkeys self-administering cocaine under a food-drug choice procedure in which a cocaine self-administration dose-effect curve was determined daily. When administered by either route, buspirone significantly decreased cocaine choice in dominant-ranked monkeys. In subordinate monkeys, however, i.v. buspirone was ineffective on average, and oral buspirone increased choice of lower cocaine doses. The effects of buspirone only differed according to route of administration in subordinate monkeys. Moreover, it is noteworthy that the effects of buspirone were similar to those of the D3 receptor-selective antagonist PG01037 and qualitatively different than those of less selective drugs that act at D2-like or serotonin (5-HT)1A receptors, suggesting a D3 and possibly D4 receptor mechanism of action for buspirone. Taken together, the data support the utility of drugs targeting D3/D4 receptors as potential treatments for cocaine addiction, particularly in combination with enriching environmental manipulations.

Does levonorgestrel emergency contraceptive have a post-fertilization effect? A review of its mechanism of action

PubMed Central

Peck, Rebecca; Rella, Walter; Tudela, Julio; Aznar, Justo; Mozzanega, Bruno

2016-01-01

Background Recent studies have identified that levonorgestrel administered orally in emergency contraception (LNG-EC) is only efficacious when taken before ovulation. However, the drug does not consistently prevent follicular rupture or impair sperm function. Objective The present systematic review is performed to analyze and more precisely define the extent to which pre-fertilization mechanisms of action may explain the drug's efficacy in pregnancy avoidance. We also examine the available evidence to determine if pre-ovulatory drug administration may be associated with post-fertilization effects. Conclusion The mechanism of action of LNG-EC is reviewed. The drug has no ability to alter sperm function at doses used in vivo and has limited ability to suppress ovulation. Our analysis estimates that the drug's ovulatory inhibition potential could prevent less than 15 percent of potential conceptions, thus making a pre-fertilization mechanism of action significantly less likely than previously thought. Luteal effects (such as decreased progesterone, altered glycodelin levels, and shortened luteal phase) present in the literature may suggest a pre-ovulatory induced post-fertilization drug effect. Lay Summary Plan B is the most widely used emergency contraceptive available. It is important for patients and physicians to clearly understand the drug’s mechanism of action (MOA). The drug was originally thought to work by preventing fertilization. Recent research has cast doubt on this. Our review of the research suggests that it could act in a pre-fertilization capacity, and we estimate that it could prevent ovulation in only 15 percent or less of cases. The drug has no ability to alter sperm function and limited ability to suppress ovulation. Further, data suggest that when administered pre-ovulation, it may have a post-fertilization MOA. PMID:27833181

21 CFR 1210.24 - Temporary permits.

Code of Federal Regulations, 2011 CFR

2011-04-01

... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... FEDERAL IMPORT MILK ACT Permit Control § 1210.24 Temporary permits. A temporary permit will be granted... inspections required by the applicable provisions of section 2 of the Federal Import Milk Act. Temporary...

21 CFR 1210.24 - Temporary permits.

Code of Federal Regulations, 2010 CFR

2010-04-01

... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... FEDERAL IMPORT MILK ACT Permit Control § 1210.24 Temporary permits. A temporary permit will be granted... inspections required by the applicable provisions of section 2 of the Federal Import Milk Act. Temporary...

78 FR 14669 - Privacy Act of 1974; Implementation

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-07

... DEPARTMENT OF JUSTICE 28 CFR Part 16 [CPCLO Order No. 002-2013] Privacy Act of 1974; Implementation AGENCY: Drug Enforcement Administration, United States Department of Justice. ACTION: Final rule. SUMMARY: The Department of Justice (DOJ or Department), Drug Enforcement Administration (DEA) is issuing a...

21 CFR 21.70 - Disclosure and intra-agency use of records in Privacy Act Record Systems; no accounting required.

Code of Federal Regulations, 2010 CFR

2010-04-01

... requirements of this part under § 21.30. (b) No accounting is required for any disclosure or use under... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Disclosure and intra-agency use of records in Privacy Act Record Systems; no accounting required. 21.70 Section 21.70 Food and Drugs FOOD AND DRUG...

The safety and regulation of natural products used as foods and food ingredients.

PubMed

Abdel-Rahman, Ali; Anyangwe, Njwen; Carlacci, Louis; Casper, Steve; Danam, Rebecca P; Enongene, Evaristus; Erives, Gladys; Fabricant, Daniel; Gudi, Ramadevi; Hilmas, Corey J; Hines, Fred; Howard, Paul; Levy, Dan; Lin, Ying; Moore, Robert J; Pfeiler, Erika; Thurmond, T Scott; Turujman, Saleh; Walker, Nigel J

2011-10-01

The use of botanicals and dietary supplements derived from natural substances as an adjunct to an improved quality of life or for their purported medical benefits has become increasingly common in the United States. This review addresses the safety assessment and regulation of food products containing these substances by the U.S. Food and Drug Administration (FDA). The issue of safety is particularly critical given how little information is available on the toxicity of some of these products. The first section uses case studies for stevia and green tea extracts as examples of how FDA evaluates the safety of botanical and herbal products submitted for consideration as Generally Recognized as Safe under the Federal Food, Drug, and Cosmetics Act. The 1994 Dietary Supplement Health Education Act (DSHEA) created a regulatory framework for dietary supplements. The article also discusses the regulation of this class of dietary supplements under DSHEA and addresses the FDA experience in analyzing the safety of natural ingredients described in pre-market safety submissions. Lastly, we discuss an ongoing interagency collaboration to conduct safety testing of nominated dietary supplements.

Development of modified-release dosage forms containing loratadine and pseudoephedrine sulfate.

PubMed

Sznitowska, Małgorzata; Cal, Krzysztof; Kupiec, Katarzyna

2004-12-01

Pseudoephedrine sulfate (PES) is a short-acting sympathomimetic amine and decongestant. Loratadine (L) is a long-acting antihistamine, H1 blocker. These drugs administered together provide relief from a whole range of rhinitis (hay fever) symptoms. Combination of both drugs is available in the form of sugar-coated modified-release tablets Clarinase (Schering-Plough). In this product, 5 mg of L and 60 mg of PES is present in the sugar-coating layer ready for an immediate release, and the rest of PES (60 mg) is incorporated in the extended-release core of the tablet. This enables fast as well as prolonged release of PES over 6-8 h. Because the sugar coating technologies are troublesome and rarely used nowadays, the aim of this study was to develop alternative oral dosage forms containing L (5 mg) and PES (120 mg). It was assumed that, similarly to the original product, the total dose of L and the half dose of PES should be released during 1 h and the remaining dose of PES ought to be gradually released for up to 8 h.

Drug delivery strategies for Alzheimer's disease treatment.

PubMed

Di Stefano, Antonio; Iannitelli, Antonio; Laserra, Sara; Sozio, Piera

2011-05-01

Current Alzheimer's disease (AD) therapy is based on the administration of the drugs donepezil, galantamine, rivastigmine and memantine. Until disease-modifying therapies become available, further research is needed to develop new drug delivery strategies to ensure ease of administration and treatment persistence. In addition to the conventional oral formulations, a variety of drug delivery strategies applied to the treatment of AD are reviewed in this paper, with a focus on strategies leading to simplified dosage regimens and to providing new pharmacological tools. Alternatives include extended release, orally disintegrating or sublingual formulations, intranasal or short- and long-acting intramuscular or transdermal forms, and nanotechnology-based delivery systems. The advent of new research on molecular mechanisms of AD pathogenesis has outlined new strategies for therapeutic intervention; these include the stimulation of α-secretase cleavage, the inhibition of γ-secretase activity, the use of non-steroidal anti-inflammatory drugs, neuroprotection based on antioxidant therapy, the use of estrogens, NO synthetase inhibitors, and natural agents such as polyphenols. Unfortunately, these compounds might not help patients with end stage AD, but might hopefully slow or stop the disease process in its early stage. Nanotechnologies may prove to be a promising contribution in future AD drug delivery strategies, in particular drug carrier nano- or microsystems, which can limit the side effects of anti-Alzheimer drugs.

Gender differences in drug use and expenditures in a privately insured population of older adults.

PubMed

Correa-de-Araujo, Rosaly; Miller, G Edward; Banthin, Jessica S; Trinh, Yen

2005-01-01

We examine gender differences in use and expenditures for prescription drugs among Medicare and privately insured older adults aged 65 and over, using data on a nationally representative sample of prescription drug purchases collected for the Medical Expenditure Panel Survey Household Component. Overall, women spent about $1,178 for drugs, about 17% more than the $1,009 in average expenditures by men. Older women constituted 50.7% of the population and had average annual aggregate expenditures for prescribed medicines of $6.93 billion compared to $5.77 billion for men. Women were more likely than men to use drugs from a number of therapeutic classes-analgesics, hormones and psychotherapeutic agents-and therapeutic subclasses-thyroid drugs, COX-2 inhibitors and anti-depressants. Women also had higher average prescriptions per user for a number of therapeutic classes-hormones, psychotherapeutic agents and analgesics-and therapeutic subclasses-anti-diabetic drugs and beta blockers. Prescribed medications are, arguably, the most important healthcare technology in preventing illness, disability, and death in older adults. It is critical that older women and men have proper access to prescribed medicines. Given the financial vulnerability of this priority population, particularly women, the expanded drug coverage available under the Medicare Modernization Act is of particular relevance in meeting this goal.

Nanomedicine in the development of anti-HIV microbicides.

PubMed

das Neves, José; Nunes, Rute; Rodrigues, Francisca; Sarmento, Bruno

2016-08-01

Prevention plays an invaluable role in the fight against HIV/AIDS. The use of microbicides is considered an interesting potential approach for topical pre-exposure prophylaxis of HIV sexual transmission. The prospects of having an effective product available are expected to be fulfilled in the near future as driven by recent and forthcoming results of clinical trials. Different dosage forms and delivery strategies have been proposed and tested for multiple microbicide drug candidates presently at different stages of the development pipeline. One particularly interesting approach comprises the application of nanomedicine principles to the development of novel anti-HIV microbicides, but its implications to efficacy and safety are not yet fully understood. Nanotechnology-based systems, either presenting inherent anti-HIV activity or acting as drug nanocarriers, may significantly influence features such as drug solubility, stability of active payloads, drug release, interactions between active moieties and virus/cells, intracellular drug delivery, drug targeting, safety, antiviral activity, mucoadhesive behavior, drug distribution and tissue penetration, and pharmacokinetics. The present manuscript provides a comprehensive and holistic overview of these topics as relevant to the development of vaginal and rectal microbicides. In particular, recent advances pertaining inherently active microbicide nanosystems and microbicide drug nanocarriers are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Risk management in dermatology: an analysis of data available from several British-based reporting systems.

PubMed

Gawkrodger, D J

2011-03-01

The elimination or reduction of risk is a prime requirement of all healthcare workers. The matter has come to the fore in dermatological practice recently with the widespread use of effective drugs that have significant side-effects (e.g. retinoids, cytotoxic drugs, biologics), the increase in skin surgery, especially for skin cancer, and the extensive use of phototherapies. To examine the available database from different agencies to which adverse events may be reported over at least a 5-year time frame, categorize the risks, look forward to where as yet unidentified risks might exist, and draw conclusions to improve the safety of dermatological practice. This work came about through a request from the National Patient Safety Agency [to the Joint Specialty Committee of the British Association of Dermatologists (BAD) and Royal College of Physicians] for information on risks to patients receiving treatment or investigation for skin disease. Organizations in the U.K. that receive information about adverse events, whether caused by drugs or procedures in dermatological treatments, were approached for information about reported events over a 5-year (or, in one case, 10-year) time frame up to 2009. Data were received from the National Patient Safety Agency, the Medicines and Healthcare Products Regulatory Agency, the National Health Service Litigation Authority, the Medical Protection Society and the Medical Defence Union. In addition, the results of a survey conducted in 2010 by the BAD of its members concerning potential critical incident reporting were included. The received information was analysed according to category of event and conclusions drawn about how best to manage the risks that were identified. Adverse events were divided into the following categories, listed in order of the number of reports received: drug side-effects (biologics and retinoids), phototherapy dosage, drug monitoring (including initial screening), pregnancy prevention programmes, skin cancer follow-up (including acting on reports), dermatopathological reporting and conduct of dermatological surgery (including management of complications, equipment problems, use of lasers, cosmetic procedures and cryotherapy). Critical incidents reported by BAD members often concerned follow-up failures, e.g. of patients receiving systemic drugs or of those with skin cancer. Several of the reported adverse events concern systemic failures. Recommendations for risk reduction include the following points: better systems for drug monitoring (including regularity of attendance, provision of sufficient follow-up appointments, acting on results and adequacy of pregnancy prevention programmes); staff training and record keeping for phototherapy; acting on skin cancer multidisciplinary team meeting outcomes (including provision of sufficient follow-up appointments); and adequate training of staff in dermatological surgery including cryotherapy. Regular monitoring of the occurrence of such reports is needed to ensure safe practice and to identify early areas of new risk. © 2011 The Author. BJD © 2011 British Association of Dermatologists.

Killing the dead: chemotherapeutic strategies against free-living cyst-forming protists (Acanthamoeba sp. and Balamuthia mandrillaris).

PubMed

Siddiqui, Ruqaiyyah; Aqeel, Yousuf; Khan, Naveed Ahmed

2013-01-01

The opportunist free-living protists such as Acanthamoeba spp. and Balamuthia mandrillaris have become a serious threat to human life. As most available drugs target functional aspects of pathogens, the ability of free-living protists to transform into metabolically inactive cyst forms presents a challenge in treatment. It is hoped, that the development of broad spectrum antiprotist agents acting against multiple cyst-forming protists to provide target-directed inhibition will offer a viable drug strategy in the treatment of these rare infections. Here, we present a comprehensive report on upcoming drug targets, with emphasis on cyst wall biosynthesis along with the related biochemistry of encystment pathways, as we strive to bring ourselves a step closer to being able to combat these deadly diseases. © 2013 The Author(s) Journal of Eukaryotic Microbiology © 2013 International Society of Protistologists.

Dissociated learning using GABAergic drugs.

PubMed

Azarashvili, A A; Kaimachnikova, I E

2009-02-01

Experiments on Wistar rats addressed the possibility of dissociated learning using drugs acting directly on brain GABA(B) receptors. A previously suggested hypothesis was tested: that the cholinergic system of the brain plays the decisive role in the mechanisms of dissociative learning. The data obtained here provided evidence that dissociated learning an occur with compounds acting on the GABAergic transmitter system of the brain. Dissociated states arose on treatment of animals with both the GABA-mimetic baclofen and the GABA receptor antagonist 5-aminovaleric acid. Thus, these results show that dissociated learning can occur using drugs acting on both the cholinergic and the GABAergic transmitter systems of the brain.

[Veterinary Drug 'what'? Various marginal notes by an 'industrial veterinarian'].

PubMed

Hoftijzer, J

1987-04-15

A retrospective view of the history of the Veterinary Medicinal Products Act and the current situation of the trade in veterinary drugs is followed by a discussion of a number of changes which will have to be made in the fields of production, packing, distribution and the trade in these drugs. With regard to these last-named items, a connection with the Act on the Practice of Veterinary Medicine should be made. In general it can be stated that the innovating industry is not dissatisfied, but only the actual enforcement of the act will provide genuine replies to questions which are still unanswered.

Subsidising artemisinin-based combination therapy in the private retail sector.

PubMed

Opiyo, Newton; Yamey, Gavin; Garner, Paul

2016-03-09

Malaria causes ill health and death in Africa. Treating illness promptly with artemisinin-based combination therapy (ACT) is likely to cure people and avoid the disease progressing to more severe forms and death. In many countries, ACT use remains low. Part of the problem is that most people seek treatment from the retail sector where ACTs are expensive; this expense is a barrier to their use.The Global Fund and other international organisations are subsidising the cost of ACTs for private retail providers to improve access to ACTs. The subsidy was initially organised through a stand-alone initiative, called the Affordable Medicines Facility-malaria (AMFm), but has since been integrated into the Global Fund core grant management and financial processes. To assess the effect of programmes that include ACT price subsidies for private retailers on ACT use, availability, price and market share. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 1, The Cochrane Library, including the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register); MEDLINE (OvidSP), EMBASE (OvidSP), CINAHL (EbscoHost), EconLit (ProQuest), Global Health (OvidSP), Regional Indexes (Global Health Library, WHO), LILACS (Global Health Library, WHO), Science Citation Index and Social Sciences Citation Index (ISI Web of Science) and Health Management (ProQuest). All databases were searched February 2015, except for Health Management which was searched November 2013, without any date, language or publication status restrictions. We also searched the International Clinical Trials Registry Platform (ICTRP; WHO), ClinicalTrials.gov (NIH) and various grey literature sources. We also conducted a cited reference search for all included studies in ISI Web of Knowledge, checked references of identified articles and contacted authors to identify additional studies. Randomised trials, non-randomised trials, controlled before-after studies and interrupted-time-series studies that compared the effects of ACT price subsidies for private retailers to no subsidies or alternative ACT financing mechanisms were eligible for inclusion. Two authors independently screened and selected studies for inclusion. Two review authors independently extracted data, assessed study risk of bias and confidence in effect estimates (certainty of evidence) using Grading of Recommendations, Assessment, Development and Evaluation (GRADE). We included four trials (two cluster-randomised trials reported in three articles and two non-randomised cluster trials). Three trials assessed retail sector ACT subsidies combined with supportive interventions (retail outlet provider training, community awareness and mass media campaigns). One trial assessed vouchers provided to households to purchase subsidised ACTs. Price subsidies ranged from 80% to 95%. One trial enrolled children under five years of age; the other three trials studied people of all age groups. The studies were done in rural districts in East Africa (Kenya, Uganda and Tanzania).In this East Africa setting, these ACT subsidy programmes increased the percentage of children under five years of age receiving ACTs on the day, or following day, of fever onset by 25 percentage points (95% confidence interval (CI) 14.1 to 35.9 percentage points; 1 study, high certainty evidence). This suggests that in practice, among febrile children under five years of age with an ACT usage rate of 5% without a subsidy, subsidy programmes would increase usage by between 19% and 41% over a one year period.The ACT subsidy programmes increased the percentage of retail outlets stocking ACTs for children under five years of age by 31.9 percentage points (95% CI 26.3 to 37.5 percentage points; 1 study, high certainty evidence). Effects on ACT stocking for patients of any age is unknown because the certainty of evidence was very low.The ACT subsidy programmes decreased the median cost of ACTs for children under five years of age by US$ 0.84 (median cost per ACT course without subsidy: US$ 1.08 versus with subsidy: US$ 0.24; 1 study, high certainty evidence).The ACT subsidy programmes increased the market share of ACTs for children under five years of age by between 23.6 and 63.0 percentage points (1 study, high certainty evidence).The ACT subsidy programmes decreased the use of older antimalarial drugs (such as amodiaquine and sulphadoxine-pyrimethamine) among children under five years of age by 10.4 percentage points (95% CI 3.9 to 16.9 percentage points; 1 study, high certainty evidence).None of the three studies of ACT subsidies reported the number of patients treated who had confirmed malaria.Vouchers increased the likelihood that an illness is treated with an ACT by 16 to 23 percentage points; however, vouchers were associated with a high rate of over-treatment of malaria (only 56% of patients taking ACTs from the drug shop tested positive for malaria under the 92% subsidy; 1 study, high certainty evidence). Programmes that include substantive subsidies for private sector retailers combined with training of providers and social marketing improved use and availability of ACTs for children under five years of age with suspected malaria in research studies from three countries in East Africa. These programmes also reduced prices of ACTs, improved market share of ACTs and reduced the use of older antimalarial drugs among febrile children under five years of age. The research evaluates drug delivery but does not assess whether the patients had confirmed (parasite-diagnosed) malaria. None of the included studies assessed patient outcomes; it is therefore not known whether the effects seen in the studies would translate to an impact on health.

Direct Oral Anticoagulants: An Overview for the Interventional Radiologist

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, Pradesh, E-mail: pradeshkumar@doctors.org.uk; Ravi, Rajeev, E-mail: rajeev.ravi@aintree.nhs.uk; Sundar, Gaurav, E-mail: gaurav.sundar@aintree.nhs.uk

The direct oral anticoagulants (DOACs) have emerged as a good alternative for the treatment of thromboembolic diseases, and their use in clinical practice is increasing rapidly. The DOACs act by blocking the activity of one single step in the coagulation cascade. These drugs act downstream in the common pathway of the coagulation cascade by directly antagonising the action of thrombin or factor Xa. The development of DOACs represents a paradigm shift from the oral vitamin K antagonists such as warfarin. This article aims to describe the properties of the currently available DOACs including pharmacology and dosing. We also address themore » strategies for periprocedural management and reversal of anticoagulation of patients treated with these agents.« less

A pharmacy too far? Equity and spatial distribution of outcomes in the delivery of subsidized artemisinin-based combination therapies through private drug shops

PubMed Central

2010-01-01

Background Millions of individuals with malaria-like fevers purchase drugs from private retailers, but artemisinin-based combination therapies (ACTs), the only effective treatment in regions with high levels of resistance to older drugs, are rarely obtained through these outlets due to their relatively high cost. To encourage scale up of ACTs, the Affordable Medicines Facility – malaria is being launched to subsidize their price. The Government of Tanzania and the Clinton Foundation piloted this subsidized distribution model in two Tanzanian districts to examine concerns about whether the intervention will successfully reach poor, rural communities. Methods Stocking of ACTs and other antimalarial drugs in all retail shops was observed at baseline and in four subsequent surveys over 15 months. Exit interviews were conducted with antimalarial drug customers during each survey period. All shops and facilities were georeferenced, and variables related to population density and proximity to distribution hubs, roads, and other facilities were calculated. To understand the equity of impact, shops stocking ACTs and consumers buying them were compared to those that did not, according to geographic and socioeconomic variables. Patterning in ACT stocking and sales was evaluated against that of other common antimalarials to identify factors that may have impacted access. Qualitative data were used to assess motivations underlying stocking, distribution, and buying disparities. Results Results indicated that although total ACT purchases rose from negligible levels to nearly half of total antimalarial sales over the course of the pilot, considerable geographic variation in stocking and sales persisted and was related to a variety of socio-spatial factors; ACTs were stocked more often in shops located closer to district towns (p<0.01) and major roads (p<0.01) and frequented by individuals of higher socioeconomic status (p<0.01). However, other antimalarial drugs displayed similar patterning, indicating the existence of underlying disparities in access to antimalarial drugs in general in these districts. Conclusions As this subsidy model is scaled up across multiple countries, these results confirm the potential for increased ACT usage but suggest that additional efforts to increase access in remote areas will be needed for the scale-up to have equitable impact. Trial registration Current Controlled Trials ISRCTN39125414. PMID:20594372

A pharmacy too far? Equity and spatial distribution of outcomes in the delivery of subsidized artemisinin-based combination therapies through private drug shops.

PubMed

Cohen, Justin M; Sabot, Oliver; Sabot, Kate; Gordon, Megumi; Gross, Isaac; Bishop, David; Odhiambo, Moses; Ipuge, Yahya; Ward, Lorrayne; Mwita, Alex; Goodman, Catherine

2010-07-02

Millions of individuals with malaria-like fevers purchase drugs from private retailers, but artemisinin-based combination therapies (ACTs), the only effective treatment in regions with high levels of resistance to older drugs, are rarely obtained through these outlets due to their relatively high cost. To encourage scale up of ACTs, the Affordable Medicines Facility--malaria is being launched to subsidize their price. The Government of Tanzania and the Clinton Foundation piloted this subsidized distribution model in two Tanzanian districts to examine concerns about whether the intervention will successfully reach poor, rural communities. Stocking of ACTs and other antimalarial drugs in all retail shops was observed at baseline and in four subsequent surveys over 15 months. Exit interviews were conducted with antimalarial drug customers during each survey period. All shops and facilities were georeferenced, and variables related to population density and proximity to distribution hubs, roads, and other facilities were calculated. To understand the equity of impact, shops stocking ACTs and consumers buying them were compared to those that did not, according to geographic and socioeconomic variables. Patterning in ACT stocking and sales was evaluated against that of other common antimalarials to identify factors that may have impacted access. Qualitative data were used to assess motivations underlying stocking, distribution, and buying disparities. Results indicated that although total ACT purchases rose from negligible levels to nearly half of total antimalarial sales over the course of the pilot, considerable geographic variation in stocking and sales persisted and was related to a variety of socio-spatial factors; ACTs were stocked more often in shops located closer to district towns (p<0.01) and major roads (p<0.01) and frequented by individuals of higher socioeconomic status (p<0.01). However, other antimalarial drugs displayed similar patterning, indicating the existence of underlying disparities in access to antimalarial drugs in general in these districts. As this subsidy model is scaled up across multiple countries, these results confirm the potential for increased ACT usage but suggest that additional efforts to increase access in remote areas will be needed for the scale-up to have equitable impact. Current Controlled Trials ISRCTN39125414.

77 FR 45688 - Electronic Prescriptions for Controlled Substances Notice of Approved Certification Process

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-01

... Comprehensive Drug Abuse Prevention and Control Act of 1970, often referred to as the Controlled Substances Act... substances, particularly Schedule II controlled substances, which have a significant potential for abuse... Prescriptions for Controlled Substances Notice of Approved Certification Process AGENCY: Drug Enforcement...

Triple-acting lytic enzyme treatment of drug-resistant and intracellular Staphylococcus aureus

USDA-ARS?s Scientific Manuscript database

Multi-drug resistant bacteria are a persistent problem in modern health care, food safety and animal health. There is a need for new antimicrobials to replace over-used conventional antibiotics. Here we describe engineered triple-acting staphylolytic peptidoglycan hydrolases wherein three unique a...

Antibody-mediated delivery of therapeutics for cancer therapy.

PubMed

Parakh, Sagun; Parslow, Adam C; Gan, Hui K; Scott, Andrew M

2016-01-01

Antibody-conjugated therapies (ACTs) combine the specificity of monoclonal antibodies to target cancer cells directly with highly potent payloads, often resulting in superior efficacy and/or reduced toxicity. This represents a new approach to the treatment of cancer. There have been highly promising clinical trial results using this approach with improvements in linker and payload technology. The breadth of current trials examining ACTs in haematological malignancies and solid tumours indicate the potential for clinical impact. This review will provide an overview of ACTs currently in clinical development as well as the principles of antibody delivery and types of payloads used, including cytotoxic drugs, radiolabelled isotopes, nanoparticle-based siRNA particles and immunotoxins. The focus of much of the clinical activity in ACTs has, understandably, been on their use as a monotherapy or in combination with standard of care drugs. This will continue, as will the search for better targets, linkers and payloads. Increasingly, as these drugs enter routine clinical care, important questions will arise regarding how to optimise ACT treatment approaches, including investigation of resistance mechanisms, biomarker and patient selection strategies, understanding of the unique toxicities of these drugs, and combinatorial approaches with standard therapies as well as emerging therapeutic agents like immunotherapy.

Regulatory framework on bioequivalence criteria for locally acting gastrointestinal drugs: the case for oral modified release mesalamine formulations.

PubMed

Sferrazza, Gianluca; Siviero, Paolo D; Nicotera, Giuseppe; Turella, Paola; Serafino, Annalucia; Blandizzi, Corrado; Pierimarchi, Pasquale

2017-09-01

Bioequivalence testing for locally acting gastrointestinal drugs is a challenging issue for both regulatory authorities and pharmaceutical industries. The international regulatory framework has been characterized by the lack of specific bioequivalence tests that has generated a negative impact on the market competition and drug use in clinical practice. Areas covered: This review article provides an overview of the European Union and United States regulatory frameworks on bioequivalence criteria for locally acting gastrointestinal drugs, also discussing the most prominent scientific issues and advances that has been made in this field. A focus on oral modified release mesalamine formulations will be also provided, with practical examples of the regulatory pathways followed by pharmaceutical companies to determine bioequivalence. Expert commentary: The development of a scientific rationale to demonstrate bioequivalence in this field has been complex and often associated with uncertainties related to scientific and regulatory aspects. Only in recent years, thanks to advanced knowledge in this field, the criteria for bioequivalence assessment are undergoing substantial changes. This new scenario will likely result in a significant impact on pharmaceutical companies, promoting more competition through a clearer regulatory approach, conceived for streamlining the demonstration of therapeutic equivalence for locally acting gastrointestinal drugs.

Pharmaceutical expenditure on drugs for rare diseases in Canada: a historical (2007-13) and prospective (2014-18) MIDAS sales data analysis.

PubMed

Divino, Victoria; DeKoven, Mitch; Kleinrock, Michael; Wade, Rolin L; Kim, Tony; Kaura, Satyin

2016-05-21

Health Canada has defined rare diseases as life-threatening, seriously debilitating, or serious chronic conditions affecting a very small number of patients (~1 in 2,000 persons). An estimated 9 % of Canadians suffer from a rare disease. Drugs treating rare diseases (DRDs) are also known as orphan drugs. While Canada is currently developing an orphan drug framework, in the United States (US), the Orphan Drug Act (ODA) of 1983 established incentives for the development of orphan drugs. This study measured total annual expenditure of orphan drugs in Canada (2007-13) and estimated future (2014-18) orphan drug expenditure. Orphan drugs approved by the US Food and Drug Administration (FDA) in the US were used as a proxy for the orphan drug landscape in Canada. Branded, orphan drugs approved by the FDA between 1983 through 2013 were identified (N = 356 unique products). Only US orphan drugs with the same orphan indication(s) approved in Canada were included in the analysis. Adjustment via an indication factoring was applied to products with both orphan and non-orphan indications using available data sources to isolate orphan-indication sales. The IMS Health MIDAS database of audited biopharmaceutical sales was utilized to measure total orphan drug expenditure, calculated annually from 2007-2013 and evaluated as a proportion of total annual pharmaceutical drug expenditure (adjusted to 2014 CAD). Between 2007 and 2013, expenditure was measured for a final N = 147 orphan drugs. Orphan drug expenditure totaled $610.2 million (M) in 2007 and $1,100.0 M in 2013, representing 3.3- 5.6 % of total Canadian pharmaceutical drug expenditure in 2007-2013, respectively. Future trend analysis suggests orphan drug expenditure will remain under 6 % of total expenditure in 2014-18. While the number of available orphan drugs and associated expenditure increased over time, access remains an issue, and from the perspectives of society and equity, overall spending on orphan drugs is lower relative to the number of patients affected with an orphan disease in Canada. The overall budget impact of orphan drugs is small and fairly stable relative to total pharmaceutical expenditure. Concerns that growth in orphan drug expenditure may lead to unsustainable drug expenditure do not appear to be justified.

PDT in clinics: indications, results, and markets.

PubMed

Patrice, Thierry; Olivier, David; Bourre, Ludovic

2006-01-01

Photodynamic therapy (PDT) is based on the selective light activation of an exogenously given drug to patients. PDT acts mainly on cell membranes either of neovascular endothelial cells or of cancer cells leading to cancer cell death. Six drugs are now marketed based on clinical assays in various indications, which showed a clear cost efficiency as compared to other classical procedures. PDT is easy to handle and can be performed in medical installations fitting the conditions of health care in developing countries. Its cost effectiveness could represent an appropriate solution to the increasing number of cancers of various origin. However despite all the clinical results now available, PDT development remains slow. The reasons for this situation include cost of development, intellectual property, and competition between pharmaceutical companies.

45 CFR 2541.40 - Applicability.

Code of Federal Regulations, 2011 CFR

2011-10-01

... and Health Services; Alcohol, Drug Abuse, and Mental Health Services; Maternal and Child Health....) and under the Public Health Services Act (42 U.S.C. 201 et seq.), Alcohol and Drug Abuse Treatment and...) Aid to Needy Families with Dependent Children (title IV-A of the Act, not including the Work Incentive...

21 CFR 200.10 - Contract facilities (including consulting laboratories) utilized as extramural facilities by...

Code of Federal Regulations, 2014 CFR

2014-04-01

... Cosmetic Act specifically authorizes inspection of consulting laboratories as well as any factory... Federal Food, Drug, and Cosmetic Act. The Food and Drug Administration's position is that by the... Administration does not consider results of validation studies of analytical and assay methods and control...

21 CFR 200.10 - Contract facilities (including consulting laboratories) utilized as extramural facilities by...

Code of Federal Regulations, 2011 CFR

2011-04-01

... Cosmetic Act specifically authorizes inspection of consulting laboratories as well as any factory... Federal Food, Drug, and Cosmetic Act. The Food and Drug Administration's position is that by the... Administration does not consider results of validation studies of analytical and assay methods and control...

21 CFR 200.10 - Contract facilities (including consulting laboratories) utilized as extramural facilities by...

Code of Federal Regulations, 2013 CFR

2013-04-01

... Cosmetic Act specifically authorizes inspection of consulting laboratories as well as any factory... Federal Food, Drug, and Cosmetic Act. The Food and Drug Administration's position is that by the... Administration does not consider results of validation studies of analytical and assay methods and control...

21 CFR 200.10 - Contract facilities (including consulting laboratories) utilized as extramural facilities by...

Code of Federal Regulations, 2012 CFR

2012-04-01

... Cosmetic Act specifically authorizes inspection of consulting laboratories as well as any factory... Federal Food, Drug, and Cosmetic Act. The Food and Drug Administration's position is that by the... Administration does not consider results of validation studies of analytical and assay methods and control...

21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

Code of Federal Regulations, 2010 CFR

2010-04-01

... application of sections 302, 303, 310, 1007, and 1008 of the Act (21 U.S.C. 822-823, 830, and 957-958), to the... pursuant to 1310.10 affects the criminal liability for illegal possession or distribution of listed...

21 CFR 1210.17 - Authority to sample and inspect.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 1210.17 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... FEDERAL IMPORT MILK ACT Inspection and Testing § 1210.17 Authority to sample and inspect. Inspectors engaged in the enforcement of the Federal Import Milk Act are empowered to test for temperature, to take...

21 CFR 1210.17 - Authority to sample and inspect.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 1210.17 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... FEDERAL IMPORT MILK ACT Inspection and Testing § 1210.17 Authority to sample and inspect. Inspectors engaged in the enforcement of the Federal Import Milk Act are empowered to test for temperature, to take...

Hypertension Canada's 2017 Guidelines for the Diagnosis, Assessment, Prevention, and Treatment of Pediatric Hypertension.

PubMed

Dionne, Janis M; Harris, Kevin C; Benoit, Geneviève; Feber, Janusz; Poirier, Luc; Cloutier, Lyne; Nakhla, Meranda; Rabi, Doreen M; Daskalopoulou, Stella S; Fournier, Anne

2017-05-01

After the 2016 guidelines for blood pressure measurement, diagnosis, and investigation of pediatric hypertension, we now present evidence-based guidelines for the prevention and treatment of hypertension in children. These guidelines were developed by Hypertension Canada's Guideline Committee pediatric subgroup after thorough evaluation of the available literature. Included are 10 guidelines specifically addressing health behaviour management, indications for drug therapy in children with hypertension, choice of therapy for children with primary hypertension, and goals of therapy for children with hypertension. Although the pediatric literature is inherently limited by small numbers of participants, fewer trials, and a prolonged latency to the development of vascular outcomes, this report reflects the current and highest level of evidence and provides guidance for primary care practitioners on the management of pediatric hypertension. Studies of therapeutic lifestyle modifications in children are available to guide current management and more antihypertensive drugs have been studied in children since the Food and Drug Administration Modernization Act. Consistent with Hypertension Canada's guideline policy, diagnostic and therapeutic algorithm tools will be developed and the guidelines will be reviewed annually and updated according to new evidence. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Advances in the Treatment of Malaria

PubMed Central

Castelli, Francesco; Tomasoni, Lina Rachele; Matteelli, Alberto

2012-01-01

Malaria still claims a heavy toll of deaths and disabilities even at the beginning of the third millennium. The inappropriate sequential use of drug monotherapy in the past has facilitated the spread of drug-resistant P. falciparum, and to a lesser extend P. vivax, strains in most of the malaria endemic areas, rendering most anti-malarial ineffective. In the last decade, a new combination strategy based on artemisinin derivatives (ACT) has become the standard of treatment for most P. falciparum malaria infections. This strategy could prevent the selection of resistant strains by rapidly decreasing the parasitic burden (by the artemisinin derivative, mostly artesunate) and exposing the residual parasite to effective concentrations of the partner drug. The widespread use of this strategy is somehow constrained by cost and by the inappropriate use of artemisinin, with possible impact on resistance, as already sporadically observed in South East Asia. Parenteral artesunate has now become the standard of care for severe malaria, even if quinine still retains its value in case artesunate is not immediately available. The appropriateness of pre-referral use of suppository artesunate is under close monitoring, while waiting for an effective anti-malarial vaccine to be made available. PMID:23170193

The safety of istradefylline for the treatment of Parkinson's disease.

PubMed

Müller, Thomas

2015-05-01

Antagonism of the A2A receptor improves motor behavior in patients with Parkinson's disease (PD), according to results of clinical studies which confirm findings of previous experimental research. The xanthine derivative, istradefylline , has the longest half-life out of the available A2A receptor antagonists. Istradefylline easily crosses the blood-brain barrier and shows a high affinity to the human A2A receptor. This narrative review aims to discuss the safety and tolerability of istradefylline against the background of the currently available drug portfolio for the treatment of PD patients. Istradefylline was safe and well tolerated in clinical trials, which have focused on l-DOPA-treated PD patients. The future of istradefylline as a complementary drug for modulation of the dopaminergic neurotransmission also relies on its potential to act like an l-DOPA plus dopamine agonist sparing future treatment alternative and to reduce the risk of predominant l-DOPA-related onset of motor complications in addition to its direct ameliorating effect on motor symptoms. Dopamine-substituting drugs may dose-dependently produce systemic side effects, particularly onset of hypotension and nausea by peripheral dopamine receptor stimulation. Istradefylline does not interfere with these peripheral receptors and therefore shows a good safety and tolerability profile.

The Medicaid Rebate: Changes in Oncology Drug Prices After the Affordable Care Act.

PubMed

Bonakdar Tehrani, Ali; Carroll, Norman V

2017-08-01

Prescription drug spending is a significant component of Medicaid total expenditures. The Affordable Care Act (ACA) includes a provision that increases the Medicaid rebate for both brand-name and generic drugs. This study examines the extent to which oncology drug prices changed after the increase in the Medicaid rebate in 2010. A pre-post study design was used to evaluate the correlation between the Medicaid rebate increase and oncology drug prices after 2010 using 2006-2013 State Drug Utilization Data. The results show that the average annual price of top-selling cancer drugs in 2006, adjusted for inflation and secular changes in drug prices, have increased by US$154 and US$235 for branded and competitive brand drugs, respectively, following the 2010 ACA; however, generic oncology drug prices showed no significant changes. The findings from this study indicate that oncology drug prices have increased after the 2010 ACA, and suggest that pharmaceutical companies may have increased their drug prices to offset increases in Medicaid rebates.

War on Drugs Policing and Police Brutality.

PubMed

Cooper, Hannah L F

2015-01-01

War on Drugs policing has failed to reduce domestic street-level drug activity: the cost of drugs remains low and drugs remain widely available. In light of growing attention to police brutality in the United States, this paper explores interconnections between specific War on Drugs policing strategies and police-related violence against Black adolescents and adults in the United States. This paper reviews literature about (1) historical connections between race/ethnicity and policing in the United States; (2) the ways that the War on Drugs eroded specific legal protections originally designed to curtail police powers; and (3) the implications of these erosions for police brutality targeting Black communities. Policing and racism have been mutually constitutive in the United States. Erosions to the 4th Amendment to the Constitution and to the Posse Comitatus Act set the foundations for two War on Drugs policing strategies: stop and frisk and Special Weapons and Tactics (SWAT) teams. These strategies have created specific conditions conducive to police brutality targeting Black communities. Conclusions/Importance: War on Drugs policing strategies appear to increase police brutality targeting Black communities, even as they make little progress in reducing street-level drug activity. Several jurisdictions are retreating from the War on Drugs; this retreat should include restoring rights originally protected by the 4th Amendment and Posse Comitatus. While these legal changes occur, police chiefs should discontinue the use of SWAT teams to deal with low-level nonviolent drug offenses and should direct officers to cease engaging in stop and frisk.

The impact of the Orphan Drug Act on drug discovery.

PubMed

Haffner, Marlene E; Maher, Paul D

2006-11-01

For nearly a quarter of a century the FDA Office of Orphan Products Development has administered the US Orphan Drug Act, which assists in bringing a wide variety of drug and biological (drug) products to treat rare diseases to market. Enthusiasm for rare disease product development has been sustained, seen throughout a wide spectrum of product types and disease conditions, and has resulted in clinically meaningful medical advances. Development of programmes for rare disease treatment worldwide, coupled with the development of drugs for diseases affecting developing countries, attests to the strength of this legislation. The marketing of almost 300 products in the US for rare diseases also testifies to the depth and intensity of scientific endeavour in this area.

Long-acting injectable antipsychotics for prevention and management of violent behaviour in psychotic patients.

PubMed

Mohr, Pavel; Knytl, Pavel; Voráčková, Veronika; Bravermanová, Anna; Melicher, Tomáš

2017-09-01

It has been well established that long-term antipsychotic treatment prevents relapse, lowers number of rehospitalisations, and also effectively reduces violent behaviour. Although violent behaviour is not a typical manifestation of schizophrenia or other psychotic disorders, the diagnosis of psychosis increases the overall risk of violence. One of the few modifiable factors of violence risk is adherence with medication. In contrast, non-adherence with drug treatment and subsequent relapse increases risk of violent acts. Non-adherence can be addressed partially by long-acting injectable antipsychotics (LAI). The aim of our review was to examine the role of antipsychotic drugs, especially LAI, in prevention and management of violent behaviour in psychosis. This is a non-systematic, narrative review of the data from open, naturalistic, retrospective, and population studies, case series, and post hoc analyses of randomised controlled trials. Search of electronic databases (PubMed, Embase) was performed to identify relevant papers. Nine published papers (3 cross-sectional chart reviews, 4 retrospective studies, 2 prospective, randomised trials) were found. The results indicated positive clinical and antiaggressive effects of LAI in psychotic patients with high risk of violent behaviour. Reviewed evidence suggests that secured drug treatment with LAI may have clinical benefit in schizophrenia patients with high risk of violent behaviour. LAI significantly reduced the severity of hostility, aggressivity, number of violent incidents, and criminal offences. These findings are supported further by the empirical evidence from clinical practice, high rates of prescribed LAI to schizophrenia patients in high-security and forensic psychiatric facilities. Available data encourage the use of LAI in forensic psychiatry, especially during court-ordered commitment treatment. © 2017 John Wiley & Sons Ltd.

Issues with monitoring the safety of psychoactive products under a legal regulated market for new psychoactive substances ('legal highs') in New Zealand.

PubMed

Rychert, Marta; Wilkins, Chris; Witten, Karen

2017-09-01

New Zealand's Psychoactive Substances Act (2013) established the world's first regulated market for 'low risk' psychoactive products ('legal highs'). Under an interim PSA regime, 47 existing products were permitted to be continued to be sold. To explore issues with the implementation of regulatory systems to monitor the safety of products on the legal market under the interim Psychoactive Substances Act regime. Semi-structured interviews with 30 key stakeholders, including industry, government agency, health and drug service professionals were conducted, transcribed and analysed thematically. In retrospect stakeholders questioned the decision to approve strong synthetic cannabinoid smoking products, noting their health risks because of product formulation, inconsistent manufacturing practices and smoking as the means of administration. Industry actors claimed the decision to approve synthetic cannabinoid smokeable products prevented potentially safer products from gaining market share. The system for withdrawing approved products which were subsequently found to be harmful was criticised for the poor quality of data available, limited engagement with health professionals and the slowness of product withdrawal. Many of the problems with the regime were attributed to the urgency under which the legal market under the interim Psychoactive Substances Act was established and implemented. The selection of 'safer' products, implementation of the product monitoring system, and engagement with health professionals may have benefited from more time and resources. An incremental approach to establishing the new market may have made the regulatory management of the new regime more workable. [Rychert M, Wilkins C, Witten K. Issues with monitoring the safety of psychoactive products under a legal regulated market for new psychoactive substances ('legal highs') in New Zealand. Drug Alcohol Rev 2017;00:000-000]. © 2017 Australasian Professional Society on Alcohol and other Drugs.

Drug interactions between buprenorphine, methadone and hepatitis C therapeutics.

PubMed

Ogbuagu, Onyema; Friedland, Gerald; Bruce, R Douglas

2016-07-01

People who inject drugs (PWID) and other individuals with opioid use disorders have a dramatically higher prevalence of hepatitis C virus (HCV) infection than the general population. The availability of novel direct acting antivirals (DAAs) for the treatment of HCV infection with very high efficacy, improved tolerability and shortened treatment durations have led to global efforts to ramp up treatment for all HCV-infected individuals to prevent or delay complications of the disease. Individuals with opioid use disorders, including those on medication-assisted therapy such as methadone or buprenorphine, are a key demographic group that can benefit from HCV treatment given their high HCV prevalence; however, pharmacokinetic and pharmacodynamic drug interactions could blunt their utility. We performed a comprehensive literature review of published and unpublished data from PubMed database, relevant conference abstracts/proceedings and FDA approved drug package inserts, to review the pharmacokinetic (PK) profile and drug interactions between currently approved HCV DAAs and methadone and buprenorphine. The paper highlights specific drug combinations which result in altered opioid drug levels including telaprevir/methadone, daclatasvir/buprenorphine, and Abbvie 3D combination regimen (paritaprevir, ritonavir, ombitasvir and dasabuvir)/buprenorphine. However, concurrent pharmacodynamics assessments did not reveal significant signs and symptoms of opioid withdrawal or toxicity that would preclude concurrent administration.

Monitoring risk: post marketing surveillance and signal detection.

PubMed

Dart, Richard C

2009-12-01

The primary goal of postmarketing surveillance is to provide information for risk assessment of a drug. Drugs affecting the central nervous system form a unique group of products for surveillance because they are often misused, abused, and diverted. These medications include opioid analgesics, stimulants, sedative-hypnotics, muscle relaxants, anticonvulsants and other drug classes. Their adverse events are difficult to monitor because the perpetrator often attempts to conceal the misuse, abuse and diversion of the product. A postmarketing surveillance system for prescription drugs of abuse in the U.S. should include product specific information that is accurate, immediately available, geographically specific and includes all areas of the country. Most producers of branded opioid analgesic products have created systems that measure abuse from multiple vantage points: criminal justice, treatment professionals, susceptible patient populations and acute health events. In the past, the U.S. government has not established similar requirements for the same products produced by generic manufacturers. However, the Food and Drug Administration Amendments Act of 2007 includes generic opioid analgesic products by requiring that all products containing potent opioid drugs perform rigorous surveillance and risk management. While general risk management guidance has been developed by FDA, more specific analyses and guidance are needed to improve surveillance methodology for drugs which are misused, abused, diverted.

75 FR 6434 - Procedures for Monitoring Secrecy Act Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-09

... Act commonly known as the `Bank Secrecy Act' (``BSA''). The Money Laundering Control Act of 1986... Deposit Insurance Act, which applies to savings associations. Specifically, Section 1359 of the Anti-Drug... examine savings association procedures periodically to ensure their effectiveness; OTS is therefore...

Molecular Dynamics Simulations of G Protein-Coupled Receptors.

PubMed

Bruno, Agostino; Costantino, Gabriele

2012-04-01

G protein-coupled receptors (GPCRs) constitute the largest family of membrane-bound receptors with more than 800 members encoded by 351 genes in humans. It has been estimated that more than 50 % of clinically available drugs act on GPCRs, with an amount of 400, 50 and 25 druggable proteins for the class A, B and C, respectively. Furthermore, Class A GPCRs with approximately 25 % of marketed small drugs represent the most attractive pharmaceutical class. The recent availability of high-resolution 3-dimensional structures of some GPCRs supports the notion that GPCRs are dynamically versatile, and their functions can be modulated by several factors. In this scenario, molecular dynamics (MD) simulations techniques appear to be crucial when studying GPCR flexibility associated to functioning and ligand recognition. A general overview of biased and unbiased MD techniques is here presented with special emphasis on the recent results obtained in the GPCRs field. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Drug Enforcement Administration

MedlinePlus

... Cannabis Plant Counterfeit Prescription Pills Containing Fentanyls: A Global Threat Public Drug Disposal: Search for an Authorized Drug Disposal Location RESOURCE CENTER Controlled Substances Act DEA Museum and Visitors Center Doing Business with DEA Drug Disposal Employee Assistance Program For ...

Industry funding of the FDA: effects of PDUFA on approval times and withdrawal rates.

PubMed

Berndt, Ernst R; Gottschalk, Adrian H B; Philipson, Tomas J; Strobeck, Matthew W

2005-07-01

The development of new therapies is a crucial component of efforts to improve healthcare. Because drug development and FDA regulatory review have historically been lengthy and costly processes, the US Congress passed a series of legislative acts, beginning in 1992, known collectively as the Prescription Drug User Fee Acts (PDUFA), which sought to expedite the FDA drug-review process. Here, we review data on drug approvals and drug-approval times, both as a whole and by therapeutic class, which demonstrate that implementation of the PDUFAs led to substantial incremental reductions in approval times beyond what would have been observed in the absence of these legislative acts. In addition, our preliminary examination of the trends in the number of new molecular entity withdrawals, frequently used as a proxy to assess the FDA's safety record, suggests that the proportion of approvals ultimately leading to safety withdrawals prior to PDUFA and during PDUFA I and II were not statistically different.

How Might the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 Affect the Financial Viability of Rural Pharmacies? An Analysis of Preimplementation Prescription Volume and Payment Sources in Rural and Urban Areas

ERIC Educational Resources Information Center

Fraher, Erin P.; Slifkin, Rebecca T.; Smith, Laura; Randolph, Randy; Rudolf, Matthew; Holmes, George M.

2005-01-01

Passage of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA) has created interest in how the legislation will affect access to prescription drugs among rural beneficiaries. Policy attention has focused to a much lesser degree on the implications of the MMA for the financial viability of rural pharmacies. This article…

Industry invites regulation: the passage of the Pure Food and Drug Act of 1906.

PubMed Central

Barkan, I D

1985-01-01

Ending its 27-year stranglehold on proposals for federal pure food and drug legislation, Congress passed the Pure Food and Drug Act and its companion bill, the Meat Inspection Act, on June 30, 1906. An unprecedented convergence of consumer, scientific, and industrial support in 1906 prompted such action; most industries even planned for it, hoping regulation would restore the competitiveness of their products on weak foreign and domestic markets. The ways in which these interests converged, and the reasons therefore, suggest a change in their relationships to each other and with the federal government as America headed into the twentieth century. Images p21-a p21-b PMID:3881052

Evaluation of amlodipine, lisinopril, and a combination in the treatment of essential hypertension

PubMed Central

Naidu, M; Usha, P; Rao, T; Shobha, J

2000-01-01

Angiotensin converting enzyme (ACE) inhibitors and dihydropyridine calcium antagonists are well established and widely used as monotherapy in patients with mild to moderate essential hypertension. Earlier studies combining short acting drugs from these classes require multiple dosing and were associated with poor compliance. Availability of longer acting compounds allows once daily administration to avoid the inconvenience of a multiple daily dose. It was decided to perform a randomised double blind, crossover study with the long acting calcium channel blocker amlodipine and the long acting ACE inhibitor lisinopril, given either alone or in combination in essential hypertension. Twenty four patients with diastolic blood pressure (DBP) between 95 and 104 mm Hg received amlodipine 2.5 mg and 5 mg, lisinopril 5 mg and 10 mg, and their combination as per a prior randomisation schedule. Supine and standing blood pressure and heart rate were recorded at weekly intervals. Higher doses of both the drugs individually or in combination were used if the target supine DBP below 90 mm Hg was not achieved. There was a significant additional blood pressure lowering effect with the combination when compared either with amlodipine or lisinopril alone. Five mg amlodipine and 10 mg lisinopril monotherapy achieved the target blood pressure in 71% and 72% patients respectively. The combination of 2.5 mg amlodipine with 5 mg lisinopril produced a much more significant lowering of blood pressure in a higher percentage of patients than that with an individual low dose.


Keywords: amlodipine; lisinopril; hypertension; combination therapy PMID:10824049

Prevalence of reported peyote use 1985-2010 effects of the American Indian Religious Freedom Act of 1994.

PubMed

Prue, Bob

2014-01-01

Peyote was classified as a hallucinogen in the Drug Abuse Control Act of 1965, leaving American Indian (AI) religious use in legal ambiguity. In 1994, the American Indian Religious Freedom Act was amended to unambiguously protect the right of religious use of peyote for AIs. The purpose of this article is to report the prevalence rates of peyote use by AIs compared to the rest of the US population and to determine what effect the act's passage had on peyote use rates. This investigation utilized an analysis of existing archived large nationally representative surveys of the American population. Data on peyote use rates was determined for most years 1985 through 2010. A total of 886,088 completed surveys were analyzed, of which 12,749 were from AIs. Use rates were triangulated using peyote harvest data. Peyote use for AIs and the rest of the US population has remained stable between 1% and 2%. American Indian use rose dramatically in the 4 years following the AIRFA and leveled to just under 10%. The rapidity of the rise was excessive in light of the growth in the NAC and compared to the amounts of peyote stocks available. It is hypothesized that social desirability biases suppressed the Pre-AIRFA use rates due to peyote illegal status. Beyond describing peyote use rates and the effects of the AIRFA, this research adds to the body of evidence regarding the levels of under-reporting of illicit drugs. Copyright © American Academy of Addiction Psychiatry.

New rules for physicians implement sample drug bill.

PubMed

1990-06-01

Record keeping requirements for dangerous drugs, including samples, has been a source of confusion for physicians and often has lead to misinterpretation of the law. To clarify this issue and to assist in implementing Senate Bill 788 (the sample drug bill), the Texas State Board of Medical Examiners recently has adopted rules for record keeping for dangerous drugs and controlled substances. A dangerous drug is any drug or device that is not listed in the Controlled Substances Act and thus is not safe for self-medication, or bears the legend, "Caution: Federal law prohibits dispensing without a prescription." The Dangerous Drugs Act requires a physician to maintain records for 2 years after the date of the acquisition or disposal of the dangerous drug. The new TSBME rules provide a presumption of compliance by a physician for record keeping for dangerous drug samples if he or she (1) retains a copy of the signed request form required by the Prescription Drug Marketing Act of 1987 for 2 years and (2) makes appropriate entries in a patient's medical records when a dangerous drug sample is supplied to the patient. Generally, a drug company representative provides a copy of the request as a receipt at the time the physician receives the samples. For dangerous drugs that the physician acquires other than as samples, the physician needs to retain a copy of the invoice or receiving order or other form of documentation of receipt or acquisition for 2 years. Once again, the physician should make appropriate entries in patients' records.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluating Appropriateness of Prescribing of Long-Acting Risperidone for Injection in Acute Care Settings

PubMed Central

Mah, Greg T; Dumontet, Jane; Lakhani, Anisha; Corrigan, Susan

2010-01-01

Background Long-acting risperidone for injection is a second-generation antipsychotic indicated for the treatment of schizophrenia and related psychotic disorders. It is a relatively new agent with pharmacokinetic and dosing properties unlike those of conventional long-acting antipsychotic drugs administered by injection. Objective To determine the proportion of patients for whom long-acting risperidone for injection was prescribed appropriately in acute care settings in the Fraser Health Authority of British Columbia, according to the following 4 criteria: approved indication for therapy, 2-week dosing intervals, dose increases no sooner than every 4 weeks, and initial overlap supplementation with another antipsychotic for at least 3 weeks. A variety of other variables, including documented approval under special authority from the provincial drug coverage program, length of hospital stay, initial dose of risperidone, and total number of doses, were assessed as secondary outcomes. Methods A chart review was conducted for all patients for whom therapy with long-acting risperidone for injection was prescribed during stays in 8 acute care hospitals between July 1, 2007, and July 22, 2008. The appropriateness of prescribing was assessed according to the 4 prespecified criteria. Results Long-acting risperidone for injection was prescribed for 116 patients during the study period, and 82 of these started therapy and were included in the evaluation. The primary outcome could not be assessed for 27 of these 82 patients, because they were discharged early, and data for some or all of the 4 criteria were not available. For 33 (60%) of the 55 remaining patients, long-acting risperidone for injection had been prescribed appropriately. In contrast, for 22 (40%) of the patients, prescription of risperidone was deemed inappropriate because of failure to meet at least 1 of the 4 criteria. Premature escalation of the dose and inadequate overlap with antipsychotic supplementation were the most common reasons for designation of the prescription as inappropriate. Conclusions Opportunities exist to improve prescribing practices for long-acting risperidone for injection in acute care institutions in this health authority. PMID:22479015

21 CFR 807.25 - Information required for device establishment registration and device listing.

Code of Federal Regulations, 2013 CFR

2013-04-01

... other provision of the Federal Food, Drug, and Cosmetic Act. (g) Device listing information must be... establishment under the ownership and control of the owner or operator where the device is manufactured..., Drug, and Cosmetic Act, which includes devices that are not exempt from premarket notification and...

21 CFR 807.25 - Information required for device establishment registration and device listing.

Code of Federal Regulations, 2014 CFR

2014-04-01

... other provision of the Federal Food, Drug, and Cosmetic Act. (g) Device listing information must be... establishment under the ownership and control of the owner or operator where the device is manufactured..., Drug, and Cosmetic Act, which includes devices that are not exempt from premarket notification and...

21 CFR 164.150 - Peanut butter.

Code of Federal Regulations, 2011 CFR

2011-04-01

... food additives as defined in section 201(s) of the Federal Food, Drug, and Cosmetic Act (the act), or if they are food additives as so defined, they are used in conformity with regulations established... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Peanut butter. 164.150 Section 164.150 Food and...

75 FR 14510 - Implementation of Device Registration and Listing Requirements Enacted in the Public Health...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 807 [Docket No... in the Public Health Security and Bioterrorism Preparedness and Response Act of 2002, the Medical Device User Fee and Modernization Act of 2002, and Title II of the Food and Drug Administration...

76 FR 32215 - Agency Information Collection Activities; Proposed Collection; Comment Request; Substantiation...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-03

... Dietary Supplement Claims Made Under the Federal Food, Drug, and Cosmetic Act AGENCY: Food and Drug... of information technology. Substantiation for Dietary Supplement Claims Made Under the Federal Food...) of the FD&C Act (21 U.S.C. 343(r)(6)) requires that a manufacturer of a dietary supplement making a...

78 FR 46962 - Biosimilar User Fee Rates for Fiscal Year 2014

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-02

...] Biosimilar User Fee Rates for Fiscal Year 2014 AGENCY: Food and Drug Administration, HHS. ACTION: Notice... fiscal year (FY) 2014. The Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended by the... October 1, 2013, and will remain in effect through September 30, 2014. FOR FURTHER INFORMATION CONTACT...

76 FR 24960 - Sentencing Guidelines for United States Courts

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-03

... 2010, Public Law 111-220 (the ``Act''). The Act reduced the statutory penalties for cocaine base... other drugs, i.e., the base offense levels for crack cocaine are set in the Drug Quantity Table so that..., offenses involving 28 grams or more of crack cocaine are assigned a base offense level of 26, offenses...

Creating Safe Schools: Roles and Challenges, a Federal Perspective.

ERIC Educational Resources Information Center

Modzeleski, William

1996-01-01

Presents an overview of the Safe and Drug-Free Schools and Communities Act, a key federal program that provides funding directly to states and local educational agencies to facilitate drug and violence prevention programs. The Gun-Free Schools Act is also examined, and the major challenges communities face in correcting school safety problems are…

21 CFR 21.21 - Changes in systems and new systems.

Code of Federal Regulations, 2010 CFR

2010-04-01

... PROTECTION OF PRIVACY Food and Drug Administration Privacy Act Record Systems § 21.21 Changes in systems and... or establish Privacy Act Record Systems in accordance with procedures of the Department and the Office of Management and Budget. (b) The Food and Drug Administration shall issue a notice, in accordance...

Understanding the Impacts of the Medicare Modernization Act: Concerns of Congressional Staff

ERIC Educational Resources Information Center

Mueller, Keith J.; Coburn, Andrew F.; MacKinney, Clinton; McBride, Timothy D.; Slifkin, Rebecca T.; Wakefield, Mary K.

2005-01-01

Sweeping changes to the Medicare program embodied in the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA), including a new prescription drug benefit, changes in payment policies, and reform of the Medicare managed-care program, have major implications for rural health care. The most efficient mechanism for research to…

78 FR 19715 - Implementation of the FDA Food Safety Modernization Act Provision Requiring FDA To Establish...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1153] Implementation of the FDA Food Safety Modernization Act Provision Requiring FDA To Establish Pilot Projects and...: The Food and Drug Administration (FDA) is extending the comment period for the notice entitled...

75 FR 30035 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-28

... Request; Cosmetic Labeling Regulations AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY... collection of information to OMB for review and clearance. Cosmetic Labeling Regulations--(OMB Control Number 0910-0599)-- Extension The Federal Food, Drug, and Cosmetic Act (the act) and the Fair Packaging and...

[Clinical significance of drug resistance-associated mutations in treatment of hepatitis C with direct-acting antiviral agents].

PubMed

Li, Z; Chen, Z W; Ren, H; Hu, P

2017-03-20

Direct-acting antiviral agents (DAAs) achieve a high sustained virologic response rate in the treatment of chronic hepatitis C virus infection. However, drug resistance-associated mutations play an important role in treatment failure and have attracted more and more attention. This article elaborates on the clinical significance of drug resistance-associated mutations from the aspects of their definition, association with genotype, known drug resistance-associated mutations and their prevalence rates, the impact of drug resistance-associated mutations on treatment naive and treatment-experienced patients, and the role of clinical detection, in order to provide a reference for clinical regimens with DAAs and help to achieve higher sustained virologic response rates.

The malaria testing and treatment landscape in Benin.

PubMed

Zinsou, Cyprien; Cherifath, Adjibabi Bello

2017-04-26

Since 2004, artemisinin-based combination therapy (ACT) has been the first-line treatment for uncomplicated malaria in Benin. In 2016, a medicine outlet survey was implemented to investigate the availability, price, and market share of anti-malarial treatment and malaria diagnostics. Results provide a timely and important benchmark to measure future interventions aimed at increasing access to quality malaria case management services. Between July 5th to August 6th 2016, a cross sectional, nationally-representative malaria outlet survey was conducted in Benin. A census of all public and private outlets with potential to distribute malaria testing and/or treatment was implemented among 30 clusters (arrondissements). Outlets were eligible for inclusion in the study if they met at least one of three study criteria: (1) one or more anti-malarials reportedly in stock on the day of the survey; (2) one or more anti-malarials reportedly in stock within the 3 months preceding the survey; and/or (3) provided malaria blood testing. An audit was completed for all anti-malarials, malaria rapid diagnostic tests (RDT) and microscopy. 7260 outlets with the potential to sell or distribute anti-malarials were included in the census and 2966 were eligible and interviewed. A total of 17,669 anti-malarial and 494 RDT products were audited. Quality-assured ACT was available in 95.0% of all screened public health facilities and 59.4% of community health workers (CHW), and availability of malaria blood testing was 94.7 and 68.4% respectively. Sulfadoxine-pyrimethamine (SP) was available in 73.9% of public health facilities and not found among CHWs. Among private-sector outlets stocking at least one anti-malarial, non-artemisinin therapies were most commonly available (94.0% of outlets) as compared to quality-assured ACT (36.1%). 31.3% of the ACTs were marked with a "green leaf" logo, suggesting leakage of a co-paid ACT into Benin's unsubsidized ACT market from another country. 78.5% of the anti-malarials distributed were through the private sector, typically through general retailers (47.6% of all anti-malarial distribution). ACT comprised 44% of the private anti-malarial market share. Private-sector price of quality-assured ACT ($1.35) was three times more expensive than SP ($0.42) or chloroquine ($0.41). Non-artemisinin therapies were cited as the most effective treatment for uncomplicated malaria among general retailers and itinerant drug vendors. The ACTwatch data has shown the importance of the private sector in terms of access to malaria treatment for the majority of the population in Benin. These findings highlight the need for increased engagement with the private sector to improve malaria case management and an immediate need for a national ACT subsidy.

Expanding access to parasite-based malaria diagnosis through retail drug shops in Tanzania: evidence from a randomized trial and implications for treatment.

PubMed

Maloney, Kathleen; Ward, Abigail; Krenz, Bonnie; Petty, Nora; Bryson, Lindsay; Dolkart, Caitlin; Visser, Theodoor; Le Menach, Arnaud; Scott, Valerie K; Cohen, Justin M; Mtumbuka, Esther; Mkude, Sigsbert

2017-01-03

Tanzania has seen a reduction in the fraction of fevers caused by malaria, likely due in part to scale-up of control measures. While national guidelines require parasite-based diagnosis prior to treatment, it is estimated that more than half of suspected malaria treatment-seeking in Tanzania initiates in the private retail sector, where diagnosis by malaria rapid diagnostic test (RDT) or microscopy is illegal. This pilot study investigated whether the introduction of RDTs into Accredited Drug Dispensing Outlets (ADDOs) under realistic market conditions would improve case management practices. Dispensers from ADDOs in two intervention districts in Tanzania were trained to stock and perform RDTs and monitored quarterly. Each district was assigned a different recommended retail price to evaluate the need for a subsidy. Malaria RDT and artemisinin-based combination therapy (ACT) uptake and availability were measured pre-intervention and 1 year post-intervention through structured surveys of ADDO owners and exiting customers in both intervention districts and one contiguous control district. Descriptive analysis and logistic regression were used to compare the three districts and identify predictive variables for testing. A total of 310 dispensers from 262 ADDOs were trained to stock and perform RDTs. RDT availability in intervention ADDOs increased from 1% (n = 172) to 73% (n = 163) during the study; ACT medicines were available in 75% of 260 pre-intervention and 68% of 254 post-intervention ADDOs. Pre-treatment testing performed within the ADDO increased from 0 to 65% of suspected malaria patients who visited a shop (95% CI 60.8-69.6%) with no difference between intervention districts. Overall parasite-based diagnosis increased from 19 to 74% in intervention districts and from 3 to 18% in the control district. Prior knowledge of RDT availability (aOR = 1.9, p = 0.03) and RDT experience (aOR = 1.9, p = 0.01) were predictors for testing. Adherence data indicated that 75% of malaria positives received ACT, while 3% of negatives received ACT. Trained and supervised ADDO dispensers in rural Tanzania performed and sold RDTs under real market conditions to two-thirds of suspected malaria patients during this one-year pilot. These results support the hypothesis that introducing RDTs into regulated private retail sector settings can improve malaria testing and treatment practices without an RDT subsidy. Trial registration ISRCTN ISRCTN14115509.

Mind the gap: knowledge and practice of providers treating uncomplicated malaria at public and mission health facilities, pharmacies and drug stores in Cameroon and Nigeria

PubMed Central

Mangham-Jefferies, Lindsay; Hanson, Kara; Mbacham, Wilfred; Onwujekwe, Obinna; Wiseman, Virginia

2015-01-01

Background Artemisinin combination therapy (ACT) has been the first-line treatment for uncomplicated malaria in Cameroon since 2004 and Nigeria since 2005, though many febrile patients receive less effective antimalarials. Patients often rely on providers to select treatment, and interventions are needed to improve providers’ practice and encourage them to adhere to clinical guidelines. Methods Providers’ adherence to malaria treatment guidelines was examined using data collected in Cameroon and Nigeria at public and mission facilities, pharmacies and drug stores. Providers’ choice of antimalarial was investigated separately for each country. Multilevel logistic regression was used to determine whether providers were more likely to choose ACT if they knew it was the first-line antimalarial. Multiple imputation was used to impute missing data that arose when linking exit survey responses to details of the provider responsible for selecting treatment. Results There was a gap between providers’ knowledge and their practice in both countries, as providers’ decision to supply ACT was not significantly associated with knowledge of the first-line antimalarial. Providers were, however, more likely to supply ACT if it was the type of antimalarial they prefer. Other factors were country-specific, and indicated providers can be influenced by what they perceived their patients prefer or could afford, as well as information about their symptoms, previous treatment, the type of outlet and availability of ACT. Conclusions Public health interventions to improve the treatment of uncomplicated malaria should strive to change what providers prefer, rather than focus on what they know. Interventions to improve adherence to malaria treatment guidelines should emphasize that ACT is the recommended antimalarial, and it should be used for all patients with uncomplicated malaria. Interventions should also be tailored to the local setting, as there were differences between the two countries in providers’ choice of antimalarial, and who or what influenced their practice. PMID:25339637

Eating high fat chow increases the sensitivity of rats to 8-OH-DPAT-induced lower lip retraction.

PubMed

Li, Jun-Xu; Ju, Shutian; Baladi, Michelle G; Koek, Wouter; France, Charles P

2011-12-01

Eating high fat food can alter sensitivity to drugs acting on dopamine systems; this study examined whether eating high fat food alters sensitivity to a drug acting on serotonin (5-HT) systems. Sensitivity to (+)-8-hydroxy-2-(dipropylamino) tetralin hydrobromide (8-OH-DPAT; 5-HT1A receptor agonist)-induced lower lip retraction was examined in separate groups (n=8-9) of rats with free access to standard (5.7% fat) or high fat (34.3% fat) chow; sensitivity to quinpirole (dopamine D3/D2 receptor agonist)-induced yawning was also examined. Rats eating high fat chow gained more body weight than rats eating standard chow and, after 6 weeks of eating high fat chow, they were more sensitive to 8-OH-DPAT (0.01-0.1 mg/kg)-induced lower lip retraction and quinpirole (0.0032-0.32 mg/kg)-induced yawning. These changes were not reversed when rats that previously ate high fat chow were switched to eating standard chow and sensitivity to 8-OH-DPAT and quinpirole increased when rats that previously ate standard chow ate high fat chow. These data extend previous results showing changes in sensitivity to drugs acting on dopamine systems in animals eating high fat chow to a drug acting at 5-HT1A receptors and they provide support for the notion that eating certain foods impacts sensitivity to drugs acting on monoamine systems.

Eating high fat chow increases the sensitivity of rats to 8-OH-DPAT-induced lower lip retraction

PubMed Central

Li, Jun-Xu; Ju, Shutian; Baladi, Michelle G; Koek, Wouter; France, Charles P

2011-01-01

Eating high fat food can alter sensitivity to drugs acting on dopamine systems; this study examined whether eating high fat food alters sensitivity to a drug acting on serotonin (5-HT) systems. Sensitivity to (+)-8-hydroxy-2-(dipropylamino) tetralin hydrobromide (8-OH-DPAT; 5-HT1A receptor agonist)-induced lower lip retraction was examined in separate groups (n=8-9) of rats with free access to standard (5.7% fat) or high fat (34.3% fat) chow; sensitivity to quinpirole (dopamine D3/D2 receptor agonist)-induced yawning was also examined. Rats eating high fat chow gained more body weight than rats eating standard chow and, after 6 weeks of eating high fat chow, they were more sensitive to 8-OH-DPAT (0.01-0.1 mg/kg)-induced lower lip retraction and quinpirole (0.0032-0.32 mg/kg)-induced yawning. These changes were not reversed when rats that previously ate high fat chow were switched to eating standard chow and sensitivity to 8-OH-DPAT and quinpirole increased when rats that previously ate standard chow ate high fat chow. These data extend previous results showing changes in sensitivity to drugs acting on dopamine systems in animals eating high fat chow to a drug acting at 5-HT1A receptors and they provide support for the notion that eating certain foods impacts sensitivity to drugs acting on monoamine systems. PMID:21979831

Impacts analysis regarding partially hydrogenated oils

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Ellen D.; Turhollow, Jr., Anthony F.; Zimmerman, Gregory P..

The U.S. Food and Drug Administration (FDA) has the responsibility under the Federal Food, Drug, and Cosmetic Act (FD&C Act) [21 United States Code (U.S.C.) 301 et seq.] for assuring that the U.S. food supply is safe, sanitary, wholesome, and honestly labeled. Toward that end, FDA exercised approval authority over substances permitted for use as food additives. Substances that are generally recognized as safe (GRAS) are not subject to regulation as food additives under the FD&C Act.

Current challenges and problems in the field of new psychoactive substances in Germany from a law enforcement perspective.

PubMed

Duffert, Anna

2014-01-01

Over the last few years, a range of so-called new psychoactive substances (NPS) have established themselves on the German recreational drug scene, causing increased concern. At the same time, a great number of Internet shops have come into existence offering these substances for sale online, ensuring a high level of availability. A number of these substances derived from pharmaceutical research which did not result in marketing authorization, presumably due to unfavourable properties. There are hardly any reliable data on long-term health damage, addictive potential, and other aspects of these scientifically unexplored substances. A number of fatal intoxications have also become known. As a rule, the mostly young consumers do not know what substance they are taking and in what concentration, thus exposing themselves to incalculable health risks and consequences. The punishability of the handling of NPS depends on the actual content: the Narcotic Drugs Act (BtMG) is applicable if a product contains narcotic drugs. If similarly effective substances are contained, which are not classified as narcotic drugs, the (penal) provisions of the Medicinal Products Act might be applicable, if the product has a pharmaceutical effect. Experience gained so far has shown that manufacturers of these intoxicating substances react immediately to inclusions in the German BtMG and put new substances on the market which are chemically similar to the known substances thus circumventing legislation. In view of the immense variety of NPS and the enormous profits derived from their sale, an end to this development is not in sight. Copyright © 2014 John Wiley & Sons, Ltd.

Optimal designs for population pharmacokinetic studies of the partner drugs co-administered with artemisinin derivatives in patients with uncomplicated falciparum malaria.

PubMed

Jamsen, Kris M; Duffull, Stephen B; Tarning, Joel; Lindegardh, Niklas; White, Nicholas J; Simpson, Julie A

2012-07-11

Artemisinin-based combination therapy (ACT) is currently recommended as first-line treatment for uncomplicated malaria, but of concern, it has been observed that the effectiveness of the main artemisinin derivative, artesunate, has been diminished due to parasite resistance. This reduction in effect highlights the importance of the partner drugs in ACT and provides motivation to gain more knowledge of their pharmacokinetic (PK) properties via population PK studies. Optimal design methodology has been developed for population PK studies, which analytically determines a sampling schedule that is clinically feasible and yields precise estimation of model parameters. In this work, optimal design methodology was used to determine sampling designs for typical future population PK studies of the partner drugs (mefloquine, lumefantrine, piperaquine and amodiaquine) co-administered with artemisinin derivatives. The optimal designs were determined using freely available software and were based on structural PK models from the literature and the key specifications of 100 patients with five samples per patient, with one sample taken on the seventh day of treatment. The derived optimal designs were then evaluated via a simulation-estimation procedure. For all partner drugs, designs consisting of two sampling schedules (50 patients per schedule) with five samples per patient resulted in acceptable precision of the model parameter estimates. The sampling schedules proposed in this paper should be considered in future population pharmacokinetic studies where intensive sampling over many days or weeks of follow-up is not possible due to either ethical, logistic or economical reasons.

48 CFR 23.502 - Authority.

Code of Federal Regulations, 2013 CFR

2013-10-01

... ENVIRONMENT, ENERGY AND WATER EFFICIENCY, RENEWABLE ENERGY TECHNOLOGIES, OCCUPATIONAL SAFETY, AND DRUG-FREE WORKPLACE Drug-Free Workplace 23.502 Authority. Drug-Free Workplace Act of 1988 (Pub. L. 100-690). ...

48 CFR 23.502 - Authority.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ENVIRONMENT, ENERGY AND WATER EFFICIENCY, RENEWABLE ENERGY TECHNOLOGIES, OCCUPATIONAL SAFETY, AND DRUG-FREE WORKPLACE Drug-Free Workplace 23.502 Authority. Drug-Free Workplace Act of 1988 (Pub. L. 100-690). ...

48 CFR 23.502 - Authority.

Code of Federal Regulations, 2012 CFR

2012-10-01

... ENVIRONMENT, ENERGY AND WATER EFFICIENCY, RENEWABLE ENERGY TECHNOLOGIES, OCCUPATIONAL SAFETY, AND DRUG-FREE WORKPLACE Drug-Free Workplace 23.502 Authority. Drug-Free Workplace Act of 1988 (Pub. L. 100-690). ...

48 CFR 23.502 - Authority.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ENVIRONMENT, ENERGY AND WATER EFFICIENCY, RENEWABLE ENERGY TECHNOLOGIES, OCCUPATIONAL SAFETY, AND DRUG-FREE WORKPLACE Drug-Free Workplace 23.502 Authority. Drug-Free Workplace Act of 1988 (Pub. L. 100-690). ...

Predicting Global Fund grant disbursements for procurement of artemisinin-based combination therapies

PubMed Central

Cohen, Justin M; Singh, Inder; O'Brien, Megan E

2008-01-01

Background An accurate forecast of global demand is essential to stabilize the market for artemisinin-based combination therapy (ACT) and to ensure access to high-quality, life-saving medications at the lowest sustainable prices by avoiding underproduction and excessive overproduction, each of which can have negative consequences for the availability of affordable drugs. A robust forecast requires an understanding of the resources available to support procurement of these relatively expensive antimalarials, in particular from the Global Fund, at present the single largest source of ACT funding. Methods Predictive regression models estimating the timing and rate of disbursements from the Global Fund to recipient countries for each malaria grant were derived using a repeated split-sample procedure intended to avoid over-fitting. Predictions were compared against actual disbursements in a group of validation grants, and forecasts of ACT procurement extrapolated from disbursement predictions were evaluated against actual procurement in two sub-Saharan countries. Results Quarterly forecasts were correlated highly with actual smoothed disbursement rates (r = 0.987, p < 0.0001). Additionally, predicted ACT procurement, extrapolated from forecasted disbursements, was correlated strongly with actual ACT procurement supported by two grants from the Global Fund's first (r = 0.945, p < 0.0001) and fourth (r = 0.938, p < 0.0001) funding rounds. Conclusion This analysis derived predictive regression models that successfully forecasted disbursement patterning for individual Global Fund malaria grants. These results indicate the utility of this approach for demand forecasting of ACT and, potentially, for other commodities procured using funding from the Global Fund. Further validation using data from other countries in different regions and environments will be necessary to confirm its generalizability. PMID:18831742

Era of faster FDA drug approval has also seen increased black-box warnings and market withdrawals.

PubMed

Frank, Cassie; Himmelstein, David U; Woolhandler, Steffie; Bor, David H; Wolfe, Sidney M; Heymann, Orlaith; Zallman, Leah; Lasser, Karen E

2014-08-01

After approval, many prescription medications that patients rely on subsequently receive new black-box warnings or are withdrawn from the market because of safety concerns. We examined whether the frequency of these safety problems has increased since 1992, when the Prescription Drug User Fee Act, legislation designed to accelerate the drug approval process at the Food and Drug Administration, was passed. We found that drugs approved after the act's passage were more likely to receive a new black-box warning or be withdrawn than drugs approved before its passage (26.7 per 100.0 drugs versus 21.2 per 100.0 drugs at up to sixteen years of follow-up). We could not establish causality, however. Our findings suggest the need for reforms to reduce patients' exposure to unsafe drugs, such as a statement or symbol in the labeling, medication guides for patients, and marketing materials indicating that a drug was approved only recently. Project HOPE—The People-to-People Health Foundation, Inc.

Subcutaneous implants for long-acting drug therapy in laboratory animals may generate unintended drug reservoirs.

PubMed

Guarnieri, Michael; Tyler, Betty M; Detolla, Louis; Zhao, Ming; Kobrin, Barry

2014-01-01

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. Compare bioavailability of buprenorphine with the biodegradation of lipid-encapsulated subcutaneous drug pellets. Pharmacokinetic and histopathology studies were conducted in BALB/c female mice implanted with cholesterol-buprenorphine drug pellets. 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. The results demonstrate that biodegradable scaffolds can become sequestered in the subcutaneous space. Drug implants can retain significant and unintended reservoirs of drugs.

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

The Use of Physiology-Based Pharmacokinetic and Pharmacodynamic Modeling in the Discovery of the Dual Orexin Receptor Antagonist ACT-541468.

PubMed

Treiber, Alexander; de Kanter, Ruben; Roch, Catherine; Gatfield, John; Boss, Christoph; von Raumer, Markus; Schindelholz, Benno; Muehlan, Clemens; van Gerven, Joop; Jenck, Francois

2017-09-01

The identification of new sleep drugs poses particular challenges in drug discovery owing to disease-specific requirements such as rapid onset of action, sleep maintenance throughout major parts of the night, and absence of residual next-day effects. Robust tools to estimate drug levels in human brain are therefore key for a successful discovery program. Animal models constitute an appropriate choice for drugs without species differences in receptor pharmacology or pharmacokinetics. Translation to man becomes more challenging when interspecies differences are prominent. This report describes the discovery of the dual orexin receptor 1 and 2 (OX 1 and OX 2 ) antagonist ACT-541468 out of a class of structurally related compounds, by use of physiology-based pharmacokinetic and pharmacodynamic (PBPK-PD) modeling applied early in drug discovery. Although all drug candidates exhibited similar target receptor potencies and efficacy in a rat sleep model, they exhibited large interspecies differences in key factors determining their pharmacokinetic profile. Human PK models were built on the basis of in vitro metabolism and physicochemical data and were then used to predict the time course of OX 2 receptor occupancy in brain. An active ACT-541468 dose of 25 mg was estimated on the basis of OX 2 receptor occupancy thresholds of about 65% derived from clinical data for two other orexin antagonists, almorexant and suvorexant. Modeling predictions for ACT-541468 in man were largely confirmed in a single-ascending dose trial in healthy subjects. PBPK-PD modeling applied early in drug discovery, therefore, has great potential to assist in the identification of drug molecules when specific pharmacokinetic and pharmacodynamic requirements need to be met. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

The Prescription Drug User Fee Act: Cause for Concern?

PubMed

Gabay, Michael

2018-04-01

The Prescription Drug User Fee Act (PDUFA) was originally enacted into law in 1992. PDUFA provides the Food and Drug Administration (FDA) with needed revenue in the form of various fees paid by drug and biologic manufacturers. The FDA utilizes this revenue to streamline the review and approval process for medications. Since the enactment of PDUFA, the median approval time for priority new drug applications and biologics license applications has reduced significantly. The FDA views PDUFA as a successful program that provides a consistent revenue stream to the agency, improves access to medications for patients, and allows industry to have a more predictable product review timeline. However, critics of PDUFA cite concerns including the potential for a lack of FDA independence and medication safety issues involving drugs approved after the existence of PDUFA.

Use of quantitative pharmacology tools to improve malaria treatments.

PubMed

Davis, Timothy M E; Moore, Brioni R; Salman, Sam; Page-Sharp, Madhu; Batty, Kevin T; Manning, Laurens

2016-01-01

The use of pharmacokinetic (PK) and pharmacodynamic (PD) data to inform antimalarial treatment regimens has accelerated in the past few decades, due in no small part to the stimulus provided by progressive development of parasite resistance to most of the currently available drugs. An understanding of the disposition, interactions, efficacy and toxicity of the mainstay of contemporary antimalarial treatment, artemisinin combination therapy (ACT), has been facilitated by PK/PD studies which have been used to refine treatment regimens across the spectrum of disease, especially in special groups including young children and pregnant women. The present review highlights recent clinically-important examples of the ways in which these quantitative pharmacology tools have been applied to improve ACT, as well as 8-aminoquinoline use and the characterisation of novel antimalarial therapies such as the spiroindolones.

Women, violence with intimates, and substance abuse: relevant theory, empirical findings, and recommendations for future research.

PubMed

Hien, D; Hien, N M

1998-08-01

Evidence from the disparate domains of anthropology, criminology, psychology, and sociology indicates that women are involved in many of the same acts of aggression and violence as men, and that substance use may play an important role in these acts. Yet little is known of the pathways between violence and drugs for women. The aims of this paper are threefold: 1) To review and integrate existing literature addressing female violence and substance abuse, presenting available epidemiology, theories, and research applicable to the study of this problem. 2) To examine the political and methodological obstacles to conducting systematic research on female aggressiveness. 3) To offer recommendations for future epidemiological, preventive, and therapeutic research efforts in this vital yet grossly understudied area.

A Systematic Review of In vitro and In vivo Activities of Anti-Toxoplasma Drugs and Compounds (2006–2016)

PubMed Central

Montazeri, Mahbobeh; Sharif, Mehdi; Sarvi, Shahabeddin; Mehrzadi, Saeed; Ahmadpour, Ehsan; Daryani, Ahmad

2017-01-01

The currently available anti-Toxoplasma agents have serious limitations. This systematic review was performed to evaluate drugs and new compounds used for the treatment of toxoplasmosis. Data was systematically collected from published papers on the efficacy of drugs/compounds used against Toxoplasma gondii (T. gondii) globally during 2006–2016. The searched databases were PubMed, Google Scholar, Science Direct, ISI Web of Science, EBSCO, and Scopus. One hundred and eighteen papers were eligible for inclusion in this systematic review, which were both in vitro and in vivo studies. Within this review, 80 clinically available drugs and a large number of new compounds with more than 39 mechanisms of action were evaluated. Interestingly, many of the drugs/compounds evaluated against T. gondii act on the apicoplast. Therefore, the apicoplast represents as a potential drug target for new chemotherapy. Based on the current findings, 49 drugs/compounds demonstrated in vitro half-maximal inhibitory concentration (IC50) values of below 1 μM, but most of them were not evaluated further for in vivo effectiveness. However, the derivatives of the ciprofloxacin, endochin-like quinolones and 1-[4-(4-nitrophenoxy) phenyl] propane-1-one (NPPP) were significantly active against T. gondii tachyzoites both in vitro and in vivo. Thus, these compounds are promising candidates for future studies. Also, compound 32 (T. gondii calcium-dependent protein kinase 1 inhibitor), endochin-like quinolones, miltefosine, rolipram abolish, and guanabenz can be repurposed into an effective anti-parasitic with a unique ability to reduce brain tissue cysts (88.7, 88, 78, 74, and 69%, respectively). Additionally, no promising drugs are available for congenital toxoplasmosis. In conclusion, as current chemotherapy against toxoplasmosis is still not satisfactory, development of well-tolerated and safe specific immunoprophylaxis in relaxing the need of dependence on chemotherapeutics is a highly valuable goal for global disease control. However, with the increasing number of high-risk individuals, and absence of a proper vaccine, continued efforts are necessary for the development of novel treatment options against T. gondii. Some of the novel compounds reviewed here may represent good starting points for the discovery of effective new drugs. In further, bioinformatic and in silico studies are needed in order to identify new potential toxoplasmicidal drugs. PMID:28163699

21 CFR 310.201 - Exemption for certain drugs limited by new-drug applications to prescription sale.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE NEW DRUGS New Drugs Exempted From..., Drug, and Cosmetic Act are not necessary for the protection of the public health with respect to the...-cyclohexylhexahydrobenzoic acid. β-diethylaminoethyl ester hydrochloride; diethylaminocarbethoxy-bicyclohexyl hydrochloride...

21 CFR 310.201 - Exemption for certain drugs limited by new-drug applications to prescription sale.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE NEW DRUGS New Drugs Exempted From..., Drug, and Cosmetic Act are not necessary for the protection of the public health with respect to the...-cyclohexylhexahydrobenzoic acid. β-diethylaminoethyl ester hydrochloride; diethylaminocarbethoxy-bicyclohexyl hydrochloride...

21 CFR 290.5 - Drugs; statement of required warning.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Drugs; statement of required warning. 290.5... (CONTINUED) DRUGS: GENERAL CONTROLLED DRUGS General Provisions § 290.5 Drugs; statement of required warning... Controlled Substances Act shall, when dispensed to or for a patient, contain the following warning: “Caution...

21 CFR 290.5 - Drugs; statement of required warning.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Drugs; statement of required warning. 290.5... (CONTINUED) DRUGS: GENERAL CONTROLLED DRUGS General Provisions § 290.5 Drugs; statement of required warning... Controlled Substances Act shall, when dispensed to or for a patient, contain the following warning: “Caution...

21 CFR 290.5 - Drugs; statement of required warning.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Drugs; statement of required warning. 290.5... (CONTINUED) DRUGS: GENERAL CONTROLLED DRUGS General Provisions § 290.5 Drugs; statement of required warning... Controlled Substances Act shall, when dispensed to or for a patient, contain the following warning: “Caution...

21 CFR 290.5 - Drugs; statement of required warning.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Drugs; statement of required warning. 290.5... (CONTINUED) DRUGS: GENERAL CONTROLLED DRUGS General Provisions § 290.5 Drugs; statement of required warning... Controlled Substances Act shall, when dispensed to or for a patient, contain the following warning: “Caution...

21 CFR 290.5 - Drugs; statement of required warning.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Drugs; statement of required warning. 290.5... (CONTINUED) DRUGS: GENERAL CONTROLLED DRUGS General Provisions § 290.5 Drugs; statement of required warning... Controlled Substances Act shall, when dispensed to or for a patient, contain the following warning: “Caution...

21 CFR 201.10 - Drugs; statement of ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Drugs; statement of ingredients. 201.10 Section 201.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... ingredient information required by section 502(e) of the Federal Food, Drug, and Cosmetic Act shall appear...

Detection of phenazepam in impaired driving.

PubMed

Kerrigan, Sarah; Mellon, Monica Brady; Hinners, Paige

2013-10-01

Phenazepam is a potent 1,4-benzodiazepine that has gained notoriety among recreational drug users. First synthesized in Ukraine in the 1970s, it is one of the most commonly prescribed benzodiazepines in Russia and other commonwealth of independent state nations, where it is used therapeutically as a prescription drug. Reports of abuse are widespread and several European countries have taken steps to control its use. However, in the USA, phenazepam is not approved for use by the Food and Drug Administration, nor scheduled under the Federal Controlled Substances Act. Phenazepam is widely available on the Internet, and recreational drug users report a potency 10-fold greater than that of nordiazepam. We report a case of a 24-year-old male driver who was apprehended for impaired driving following a two-vehicle crash. The subject exhibited slurred speech and profound psychomotor impairment. Toxicology testing revealed phenazepam at a concentration of 76 ng/mL in blood, with no other drugs detected. This case report not only demonstrates the potential for adverse traffic safety consequences following the misuse of phenazepam, but also highlights the importance of analytical factors such as immunoassay cutoff concentration, cross-reactivity and comprehensive screening using chromatographic-based techniques for impaired driving investigations.

Polymer excipients enable sustained drug release in low pH from mechanically strong inorganic geopolymers.

PubMed

Jämstorp, Erik; Yarra, Tejaswi; Cai, Bing; Engqvist, Håkan; Bredenberg, Susanne; Strømme, Maria

2012-01-01

Improving acid resistance, while maintaining the excellent mechanical stability is crucial in the development of a sustained and safe oral geopolymer dosage form for highly potent opioids. In the present work, commercially available Methacrylic acid-ethyl acrylate copolymer, Polyethylene-glycol (PEG) and Alginate polymer excipients were included in dissolved or powder form in geopolymer pellets to improve the release properties of Zolpidem, herein acting as a model drug for the highly potent opioid Fentanyl. Scanning electron microscopy, compression strength tests and drug release experiments, in gastric pH 1 and intestinal pH 6.8 conditions, were performed. The polymer excipients, with an exception for PEG, reduced the drug release rate in pH 1 due to their ability to keep the pellets in shape, in combination with the introduction of an insoluble excipient, and thereby maintain a barrier towards drug diffusion and release. Neither geopolymer compression strength nor the release in pH 6.8 was considerably impaired by the incorporation of the polymer excipients. The geopolymer/polymer composites combine high mechanical strength and good release properties under both gastric and intestinal pH conditions, and are therefore promising oral dosage forms for sustained release of highly potent opioids.

Bovine milk-derived exosomes for drug delivery

PubMed Central

Gupta, Ramesh C.

2015-01-01

Exosomes are biological nanovesicles that are involved in cell-cell communication via the functionally-active cargo (such as miRNA, mRNA, DNA and proteins). Because of their nanosize, exosomes are explored as nanodevices for the development of new therapeutic applications. However, bulk, safe and cost-effective production of exosomes is not available. Here, we show that bovine milk can serve as a scalable source of exosomes that can act as a carrier for chemotherapeutic/chemopreventive agents. Drug-loaded exosomes showed significantly higher efficacy compared to free drug in cell culture studies and against lung tumor xenografts in vivo. Moreover, tumor targeting ligands such as folate increased cancer-cell targeting of the exosomes resulting in enhanced tumor reduction. Milk exosomes exhibited cross-species tolerance with no adverse immune and inflammatory response. Thus, we show the versatility of milk exosomes with respect to the cargo it can carry and ability to achieve tumor targetability. This is the first report to identify a biocompatible and cost-effective means of exosomes to enhance oral bioavailability, improve efficacy and safety of drugs. PMID:26604130

[Irritable bowel syndrome: current treatment options].

PubMed

Ducrotté, Philippe

2007-11-01

Relieving abdominal pain is the principal treatment objective for patients with irritable bowel syndrome. No single drug stands out in the treatment strategy for this illness. Antispasmodics, magnesium aluminum silicates, and alverine citrate drugs all remain initial options for treatment, although their prescription is impeded by the fact that an increasing number are no longer approved for reimbursement. Increased dietary fibers often have a harmful effect on symptoms. Some patients are probably intolerant to some foods but there is no satisfactory proof on which to base a restrictive diet. Improved knowledge of the pathophysiology of irritable bowel syndrome has made it possible to diversify treatments that act first on one of the key pathophysiologic elements, visceral hypersensitivity. Antidepressants (especially tricyclics) can be used at low doses. Among the serotonergic drugs, serotonin 5-HT4 receptors agonists (tegaserod) may be available soon, but the development of 5-HT3 antagonists (alosetron, cilansetron) has been stopped for safety reasons (ischemic colitis and severe constipation). Non-drug options such as hypnosis, psychotherapy, relaxation, or yoga, may also be proposed to some patients. Probiotics are a possible treatment in the future.

76 FR 58277 - Animal Generic Drug User Fee Act; Public Meeting; Request for Comments

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-20

... including specific suggestions for changes to the goals referred to in section 740A(a) of FD&C Act; (3... performance goals for certain submissions over 5 years from fiscal year (FY) 2009 through FY 2013. These review performance goals strive to expedite the review of abbreviated new animal drug applications...

21 CFR 1.101 - Notification and recordkeeping.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., animal drug, food, and cosmetic exports under sections 801 or 802 of the Federal Food, Drug, and Cosmetic..., foods, and cosmetics exported under or subject to section 801(e)(1) of the act. Persons exporting an... foods and cosmetics under section 801(e)(1) of the act shall be kept for 3 years after the date of...

75 FR 69093 - Prescription Drug User Fee Act; Reopening of the Comment Period

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-10

... review program after negotiations with the regulated industry conclude. FDA expects that this additional...)(2) (21 U.S.C. 379h-2(d)(2)) of the FD&C Act requires that before FDA begins negotiations with the... requires public review of the recommendations for the human drug review program after negotiations with the...

75 FR 45641 - Medical Device User Fee Rates for Fiscal Year 2011

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-03

...] Medical Device User Fee Rates for Fiscal Year 2011 AGENCY: Food and Drug Administration, HHS. ACTION... payment procedures for medical device user fees for fiscal year (FY) 2011. The Federal Food, Drug, and Cosmetic Act (the act), as amended by the Medical Device User Fee Amendments of 2007 (title II of the Food...

78 FR 41803 - Establishment of a Public Docket for Comment on the Report Prepared Under the Food and Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-11

... Safety and Innovation Act Section 1138 AGENCY: Food and Drug Administration, HHS. ACTION: Establishment... Administration Safety and Innovation Act (FDASIA) Section 1138, enacted July 9, 2012, and posted on the FDA Web... comments to http://www.regulations.gov . Submit written comments to the Division of Dockets Management (HFA...

75 FR 27672 - Request for Comment on Implementation of the Family Smoking Prevention and Tobacco Control Act...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-18

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 1140 [Docket No. FDA-2010-N-0136] RIN 0910-AG33 Request for Comment on Implementation of the Family Smoking Prevention and Tobacco Control Act; Extension of Comment Period AGENCY: Food and Drug Administration, HHS. ACTION...

28 CFR Appendix B to Part 61 - Drug Enforcement Administration Procedures Relating to the Implementation of the National...

Code of Federal Regulations, 2013 CFR

2013-07-01

... appropriate. 3. Environmental Information Interested persons may contact the Office of Science and Technology... Procedures Relating to the Implementation of the National Environmental Policy Act B Appendix B to Part 61... ENVIRONMENTAL POLICY ACT Pt. 61, App. B Appendix B to Part 61—Drug Enforcement Administration Procedures...

28 CFR Appendix B to Part 61 - Drug Enforcement Administration Procedures Relating to the Implementation of the National...

Code of Federal Regulations, 2012 CFR

2012-07-01

... appropriate. 3. Environmental Information Interested persons may contact the Office of Science and Technology... Procedures Relating to the Implementation of the National Environmental Policy Act B Appendix B to Part 61... ENVIRONMENTAL POLICY ACT Pt. 61, App. B Appendix B to Part 61—Drug Enforcement Administration Procedures...

28 CFR Appendix B to Part 61 - Drug Enforcement Administration Procedures Relating to the Implementation of the National...

Code of Federal Regulations, 2014 CFR

2014-07-01

... appropriate. 3. Environmental Information Interested persons may contact the Office of Science and Technology... Procedures Relating to the Implementation of the National Environmental Policy Act B Appendix B to Part 61... ENVIRONMENTAL POLICY ACT Pt. 61, App. B Appendix B to Part 61—Drug Enforcement Administration Procedures...

77 FR 52036 - Privacy Act of 1974; Report of a New System of Records; FDA Records Related to Research...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0253] Privacy Act of 1974; Report of a New System of Records; FDA Records Related to Research Misconduct... Drug Administration's (FDA's) regulations for the protection of privacy, FDA is publishing notice of a...

78 FR 14309 - Implementation of the FDA Food Safety Modernization Act Provision Requiring FDA To Establish...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-05

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1153] Implementation of the FDA Food Safety Modernization Act Provision Requiring FDA To Establish Pilot Projects and... information. SUMMARY: In September 2011, the Food and Drug Administration (FDA or the Agency) asked the...

21 CFR 60.3 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-04-01

... means the Federal Food, Drug, and Cosmetic Act (secs. 201-901, 52 Stat. 1040 et seq. as amended (21 U.S... held for inspection by, FDA as part of an application for a research or marketing permit. The term does... new drug or human biologic product (as those terms are used in the Act and the Public Health Service...

21 CFR 60.3 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... means the Federal Food, Drug, and Cosmetic Act (secs. 201-901, 52 Stat. 1040 et seq. as amended (21 U.S... held for inspection by, FDA as part of an application for a research or marketing permit. The term does... new drug or human biologic product (as those terms are used in the Act and the Public Health Service...

21 CFR 60.3 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... means the Federal Food, Drug, and Cosmetic Act (secs. 201-901, 52 Stat. 1040 et seq. as amended (21 U.S... held for inspection by, FDA as part of an application for a research or marketing permit. The term does... new drug or human biologic product (as those terms are used in the Act and the Public Health Service...

21 CFR 60.3 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-04-01

... means the Federal Food, Drug, and Cosmetic Act (secs. 201-901, 52 Stat. 1040 et seq. as amended (21 U.S... held for inspection by, FDA as part of an application for a research or marketing permit. The term does... new drug or human biologic product (as those terms are used in the Act and the Public Health Service...

21 CFR 60.3 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... means the Federal Food, Drug, and Cosmetic Act (secs. 201-901, 52 Stat. 1040 et seq. as amended (21 U.S... held for inspection by, FDA as part of an application for a research or marketing permit. The term does... new drug or human biologic product (as those terms are used in the Act and the Public Health Service...

Mechanism of tissue-selective drug action in the cardiovascular system.

PubMed

Barrett, Terrance D; Triggle, David J; Walker, Michael J A; Maurice, Donald H

2005-04-01

Analysis of the human genome project tells us that there may be as few as 3000 genes that are likely to be good drug targets. Although the number of targets is still very large, these data have been interpreted by some to mean that the pharmaceutical industry may someday run out of novel drug targets. Despite the doom and gloom of such analysis, there is considerable reason for optimism. Drugs may exhibit selectivity of action beyond that predicted by target expression alone. Drugs that act at a single molecular target may have very different pharmacology and, as a result, different therapeutic uses. Three well-characterized model systems are highlighted to illustrate this point. The first model system is exemplified by nifedipine and verapamil, both of which act on L-type calcium channels. Both drugs are used to treat hypertension, but only verapamil can be used to produce atrioventricular block in patients with atrial fibrillation. The second model system describes the therapeutic exploitation of unusual conditions that occur in the ischemic myocardium to produce drugs that are more effective for suppressing ischemia-induced arrhythmias. The third model system discusses the mechanisms through which phosphodiesterase-5 (PDE5) inhibitors act selectively to facilitate penile erection while having little effect in the non-penile vasculature that also expresses PDE5.

Saquinavir Loaded Acetalated Dextran Microconfetti – a Long Acting Protease Inhibitor Injectable

PubMed Central

Collier, Michael A.; Gallovic, Matthew D.; Bachelder, Eric M.; Sykes, Craig D.; Kashuba, Angela; Ainslie, Kristy M.

2018-01-01

Purpose Since the adoption of highly active antiretroviral therapy, HIV disease progression has slowed across the world; however, patients are often required to take multiple medications daily of poorly bioavailable drugs via the oral route, leading to gastrointestinal irritation. Recently, long acting antiretroviral injectables that deliver drug for months at a time have moved into late phase clinical trials. Unfortunately, these solid phase crystal formulations have inherent drawbacks in potential dose dumping and a greater likelihood for burst release of drug compared to polymeric formulations. Methods Using electrospinning, acetalated dextran scaffolds containing the protease inhibitor saquinavir were created. Grinding techniques were then used to process these scaffolds into injectables which are termed saquinavir microconfetti. Microconfetti was analyzed for in vitro and in vivo release kinetics. Results Highly saquinavir loaded acetalated dextran electrospun fibers were able to be formed and processed into saquinavir microconfetti while other polymers such as poly lactic-co-glycolic acid and polycaprolactone were unable to do so. Saquinavir microconfetti release kinetics were able to be tuned via drug loading and polymer degradation rates. In vivo, a single subcutaneous injection of saquinavir microconfetti released drug for greater than a week with large tissue retention. Conclusions Microconfetti is a uniquely tunable long acting injectable that would reduce the formation of adherence related HIV resistance. Our findings suggest that the injectable microconfetti delivery system could be used for long acting controlled release of saquinavir and other hydrophobic small molecule drugs. PMID:27154460

Statins, the renin-angiotensin-aldosterone system and hypertension - a tale of another beneficial effect of statins.

PubMed

Drapala, Adrian; Sikora, Mariusz; Ufnal, Marcin

2014-09-01

Statins, a class of lipid lowering drugs, decrease mortality associated with cardiovascular events. As hypercholesterolemia is often accompanied by hypertension, a large number of patients receive therapy with statins and antihypertensive drugs which act via the renin-angiotensin-aldosterone system (RAAS). New guidelines published by the American Heart Association and American College of Cardiology on the treatment of dyslipidaemia and the reduction of atherosclerotic cardiovascular risk, which use a risk prediction algorithm based on risk factors such as hypertension but not low-density lipoprotein (LDL) level, may even further increase the number of patients receiving such concomitant therapy. In this paper we review studies on an interaction between statins, the RAAS and antihypertensive drugs acting via the RAAS. Accumulating evidence suggests that the combination of statins and drugs affecting the RAAS exerts a synergistic effect on the circulatory system. For example, statins may lower arterial blood pressure and augment the effect of antihypertensive drugs acting via the RAAS. Statins may interact with the RAAS in a number of ways i.e. to decrease the expression of receptors for angiotensin II (Ang II), inhibit the Ang II-dependent intracellular signalling, reduce the RAAS-dependent oxidative stress and inflammation as well as inhibit the synthesis of Ang II and aldosterone. Although statins given either alone or together with antihypertensive drugs acting via the RAAS may lower arterial blood pressure, further research is needed to evaluate the mechanisms and their therapeutic significance. © The Author(s) 2014.

[Pharmacological, toxicological, deontologic, and medico-legal aspects of the use of appetite suppressant agents in "weight-loss cures"].

PubMed

Carolei, L; Ermio, G; Accorinti, N; Meo, G; Lamberti, V; De Sarro, G

1997-01-01

The pharmacological, deontologic and medico-legal aspects in the use of appetite suppressant drugs have been evaluated. Appetite suppressant drugs used in the treatment of obesity are divided into 2 broad pharmacological categories: those acting via brain catecholamine pathways and those acting via serotonin pathways. Of the former group, amphetamines and phenimetrazines are no longer used because of their stimulant properties and addictive potential. The remaining drugs of this group have some sympathomimetic and stimulant properties. Anorectic drugs which promote serotonin neurotransmission have no such stimulant or sympathomimetic properties. They reduce appetite and food intake and are effective in the treatment of obesity. If they are not used appropriately, appetite suppressants can be of no therapeutic benefit and cause marked health risks. As regards to anorectic drugs, the 13/4/1995 act "Rules and limits in preparing drugs containing anorectic substances", precisely defines rules about selling and use of those substances. Behavior of health care personnel neglecting observance of the rule, could be interpreted as "imprudence", "negligence" and "inexpertness" in designing and managing a fat-reducing diet, that may imply, in case of damage to the patient, a professional fault.

21 CFR 203.1 - Scope.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Scope. 203.1 Section 203.1 Food and Drugs FOOD AND... DRUG MARKETING General Provisions § 203.1 Scope. This part sets forth procedures and requirements... requirements of the Prescription Drug Marketing Act of 1987 and the Prescription Drug Amendments of 1992. ...

21 CFR 209.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Definitions. 209.2 Section 209.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL... Federal Food, Drug, and Cosmetic Act (sections 201-907 (21 U.S.C. 301-397)). Authorized dispenser means an...

Development and characterization of a long-acting nanoformulated abacavir prodrug.

PubMed

Singh, Dhirender; McMillan, JoEllyn; Hilaire, James; Gautam, Nagsen; Palandri, Diana; Alnouti, Yazen; Gendelman, Howard E; Edagwa, Benson

2016-08-01

A myristoylated abacavir (ABC) prodrug was synthesized to extend drug half-life and bioavailability. Myristoylated ABC (MABC) was made by esterifying myristic acid to the drug's 5-hydroxy-cyclopentene group. Chemical composition, antiretroviral activity, cell uptake and retention and cellular trafficking of free MABC and poloxamer nanoformulations of MABC were assessed by proton nuclear magnetic resonance and tested in human monocyte-derived macrophages. Pharmacokinetics of ABC and nanoformulated MABC were evaluated after intramuscular injection into mice. MABC antiretroviral activity in monocyte-derived macrophages was comparable to native drug. Encasement of MABC into poloxamer nanoparticles extended drug bioavailability for 2 weeks. MABC synthesis and encasement in polymeric nanoformulations improved intracellular drug accumulation and demonstrate translational potential as part of a long-acting antiretroviral regimen.

The Drug Facts Box: Improving the communication of prescription drug information.

PubMed

Schwartz, Lisa M; Woloshin, Steven

2013-08-20

Communication about prescription drugs ought to be a paragon of public science communication. Unfortunately, it is not. Consumers see $4 billion of direct-to-consumer advertising annually, which typically fails to present data about how well drugs work. The professional label--the Food and Drug Administration's (FDA) mechanism to get physicians information needed for appropriate prescribing--may also fail to present benefit data. FDA labeling guidance, in fact, suggests that industry omit benefit data for new drugs in an existing class and for drugs approved on the basis of unfamiliar outcomes (such as depression rating scales). The medical literature is also problematic: there is selective reporting of favorable trials, favorable outcomes within trials, and "spinning" unfavorable results to maximize benefit and minimize harm. In contrast, publicly available FDA reviews always include the phase 3 trial data on benefit and harm, which are the basis of drug approval. However, these reviews are practically inaccessible: lengthy, poorly organized, and weakly summarized. To improve accessibility, we developed the Drug Facts Box: a one-page summary of benefit and harm data for each indication of a drug. A series of studies--including national randomized trials--demonstrates that most consumers understand the Drug Facts Box and that it improves decision-making. Despite calls from their own Risk Communication Advisory Committee and Congress (in the Affordable Care Act) to consider implementing boxes, the FDA announced it needs at least 3-5 y more to make a decision. Given its potential public health impact, physicians and the public should not have to wait that long for better drug information.

The Drug Facts Box: Improving the communication of prescription drug information

PubMed Central

Schwartz, Lisa M.; Woloshin, Steven

2013-01-01

Communication about prescription drugs ought to be a paragon of public science communication. Unfortunately, it is not. Consumers see $4 billion of direct-to-consumer advertising annually, which typically fails to present data about how well drugs work. The professional label—the Food and Drug Administration's (FDA) mechanism to get physicians information needed for appropriate prescribing—may also fail to present benefit data. FDA labeling guidance, in fact, suggests that industry omit benefit data for new drugs in an existing class and for drugs approved on the basis of unfamiliar outcomes (such as depression rating scales). The medical literature is also problematic: there is selective reporting of favorable trials, favorable outcomes within trials, and “spinning” unfavorable results to maximize benefit and minimize harm. In contrast, publicly available FDA reviews always include the phase 3 trial data on benefit and harm, which are the basis of drug approval. However, these reviews are practically inaccessible: lengthy, poorly organized, and weakly summarized. To improve accessibility, we developed the Drug Facts Box: a one-page summary of benefit and harm data for each indication of a drug. A series of studies—including national randomized trials—demonstrates that most consumers understand the Drug Facts Box and that it improves decision-making. Despite calls from their own Risk Communication Advisory Committee and Congress (in the Affordable Care Act) to consider implementing boxes, the FDA announced it needs at least 3–5 y more to make a decision. Given its potential public health impact, physicians and the public should not have to wait that long for better drug information. PMID:23942130

Treatment-seeking patterns for malaria in pharmacies in five sub-Saharan African countries.

PubMed

Ladner, Joël; Davis, Ben; Audureau, Etienne; Saba, Joseph

2017-08-29

Artemisinin-based combination therapy (ACT) is recommended as the first-line anti-malarial treatment strategy in sub-Saharan African countries. WHO policy recommends parasitological confirmation by microscopy or rapid diagnostic test (RDT) in all cases of suspected malaria prior to treatment. Gaps remain in understanding the factors that influence patient treatment-seeking behaviour and anti-malarial drug purchase decisions in the private sector. The objective of this study was to identify patient treatment-seeking behaviour in Ghana, Kenya, Nigeria, Tanzania, and Uganda. Face-to-face patient interviews were conducted at a total of 208 randomly selected retail outlets in five countries. At each outlet, exit interviews were conducted with five patients who indicated they had come seeking anti-malarial treatment. The questionnaire was anonymous and standardized in the five countries and collected data on different factors, including socio-demographic characteristics, history of illness, diagnostic practices (i.e. microscopy or RDT), prescription practices and treatment purchase. The price paid for the treatment was also collected from the outlet vendor. A total of 994 patients were included from the five countries. Location of malaria diagnosis was significantly different in the five countries. A total of 484 blood diagnostic tests were performed, (72.3% with microscopy and 27.7% with RDT). ACTs were purchased by 72.5% of patients who had undergone blood testing and 86.5% of patients without a blood test, regardless of whether the test result was positive or negative (p < 10 -4 ). A total of 531 patients (53.4%) had an anti-malarial drug prescription, of which 82.9% were prescriptions for an ACT. There were significant differences in prescriptions by country. A total of 923 patients (92.9%) purchased anti-malarial drugs in an outlet, including 79.1% of patients purchasing an ACT drug: 98.0% in Ghana, 90.5% in Kenya, 80.4% in Nigeria, 69.2% in Tanzania, and 57.7% in Uganda (p < 10 -4 ). Having a drug prescription was not a significant predictive factor associated with an ACT drug purchase (except in Kenya). The number of ACT drugs purchased with a prescription was greater than the number purchased without a prescription in Kenya, Nigeria and Tanzania. This study highlights differences in drug prescription and purchase patterns in five sub-Saharan African countries. The private sector is playing an increasingly important role in fever case management in sub-Saharan Africa. Understanding the characteristics of private retail outlets and the role they play in providing anti-malaria drugs may support the design of effective malaria interventions.

US Food and Drug Administration's Risk Evaluation and Mitigation Strategy for extended-release and long-acting opioids: pros and cons, and a European perspective.

PubMed

Mercadante, Sebastiano; Craig, David; Giarratano, Antonello

2012-12-24

Prescriptions for opioid analgesics to manage moderate-to-severe chronic non-cancer pain have increased markedly over the last decade. An unintentional consequence of greater prescription opioid utilization has been the parallel increase in misuse, abuse and overdose, which are serious risks associated with all opioid analgesics. In response to disturbing rises in prescription opioid abuse, the US Food and Drug Administration (FDA) has proposed the implementation of aggressive Risk Evaluation and Mitigation Strategies (REMS). While REMS could dramatically change the development, release, marketing and prescription of extended-release opioids, questions remain on how these programmes may influence prescribing practices, patient safety and ultimately patient access to these agents. The extent of the availability and misuse of prescription opioids in Europe is difficult to assess from the data currently available, due in large part to the considerable differences in prescribing patterns and regulations between countries. Balancing the availability of prescription opioids for those patients who have pain, while discouraging illicit use, is a complex challenge and requires effective efforts on many levels, particularly in Europe where policies are quite different between countries.

Antimicrobial drug use in food-producing animals and associated human health risks: what, and how strong, is the evidence?

PubMed

Hoelzer, Karin; Wong, Nora; Thomas, Joe; Talkington, Kathy; Jungman, Elizabeth; Coukell, Allan

2017-07-04

Antimicrobial resistance is a public health threat. Because antimicrobial consumption in food-producing animals contributes to the problem, policies restricting the inappropriate or unnecessary agricultural use of antimicrobial drugs are important. However, this link between agricultural antibiotic use and antibiotic resistance has remained contested by some, with potentially disruptive effects on efforts to move towards the judicious or prudent use of these drugs. The goal of this review is to systematically evaluate the types of evidence available for each step in the causal pathway from antimicrobial use on farms to human public health risk, and to evaluate the strength of evidence within a 'Grades of Recommendations Assessment, Development and Evaluation'(GRADE) framework. The review clearly demonstrates that there is compelling scientific evidence available to support each step in the causal pathway, from antimicrobial use on farms to a public health burden caused by infections with resistant pathogens. Importantly, the pathogen, antimicrobial drug and treatment regimen, and general setting (e.g., feed type) can have significant impacts on how quickly resistance emerges or spreads, for how long resistance may persist after antimicrobial exposures cease, and what public health impacts may be associated with antimicrobial use on farms. Therefore an exact quantification of the public health burden attributable to antimicrobial drug use in animal agriculture compared to other sources remains challenging. Even though more research is needed to close existing data gaps, obtain a better understanding of how antimicrobial drugs are actually used on farms or feedlots, and quantify the risk associated with antimicrobial use in animal agriculture, these findings reinforce the need to act now and restrict antibiotic use in animal agriculture to those instances necessary to ensure the health and well-being of the animals.

New Milestones Ahead in Complement-Targeted Therapy

PubMed Central

Ricklin, Daniel; Lambris, John D.

2017-01-01

The complement system is a powerful effector arm of innate immunity that typically confers protection from microbial intruders and accumulating debris. In many clinical situations, however, the defensive functions of complement can turn against host cells and induce or exacerbate immune, inflammatory, and degenerative conditions. Although the value of inhibiting complement in a therapeutic context has long been recognized, bringing complement-targeted drugs into clinical use has proved challenging. This important milestone was finally reached a decade ago, yet the clinical availability of complement inhibitors has remained limited. Still, the positive long-term experience with complement drugs and their proven effectiveness in various diseases has reinvigorated interest and confidence in this approach. Indeed, a broad variety of clinical candidates that act at almost any level of the complement activation cascade are currently in clinical development, with several of them being evaluated in phase 2 and phase 3 trials. With antibody-related drugs dominating the panel of clinical candidates, the emergence of novel small-molecule, peptide, protein, and oligonucleotide-based inhibitors offers new options for drug targeting and administration. Whereas all the currently approved and many of the proposed indications for complement-targeted inhibitors belong to the rare disease spectrum, these drugs are increasingly being evaluated for more prevalent conditions. Fortunately, the growing experience from preclinical and clinical use of therapeutic complement inhibitors has enabled a more evidence-based assessment of suitable targets and rewarding indications as well as related technical and safety considerations. This review highlights recent concepts and developments in complement-targeted drug discovery, provides an overview of current and emerging treatment options, and discusses the new milestones ahead on the way to the next generation of clinically available complement therapeutics. PMID:27321574

Deeming Tobacco Products To Be Subject to the Federal Food, Drug, and Cosmetic Act, as Amended by the Family Smoking Prevention and Tobacco Control Act; Restrictions on the Sale and Distribution of Tobacco Products and Required Warning Statements for Tobacco Products. Final rule.

PubMed

2016-05-10

The Food and Drug Administration (FDA) is issuing this final rule to deem products meeting the statutory definition of "tobacco product,'' except accessories of the newly deemed tobacco products, to be subject to the Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended by the Family Smoking Prevention and Tobacco Control Act (Tobacco Control Act). The Tobacco Control Act provides FDA authority to regulate cigarettes, cigarette tobacco, roll-your-own tobacco, smokeless tobacco, and any other tobacco products that the Agency by regulation deems to be subject to the law. With this final rule, FDA is extending the Agency's "tobacco product'' authorities in the FD&C Act to all other categories of products that meet the statutory definition of "tobacco product" in the FD&C Act, except accessories of such newly deemed tobacco products. This final rule also prohibits the sale of "covered tobacco products" to individuals under the age of 18 and requires the display of health warnings on cigarette tobacco, roll-your own tobacco, and covered tobacco product packages and in advertisements. FDA is taking this action to reduce the death and disease from tobacco products. In accordance with the Tobacco Control Act, we consider and intend the extension of our authorities over tobacco products and the various requirements and prohibitions established by this rule to be severable.