21 CFR 341.74 - Labeling of antitussive drug products.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) (certain drugs for depression, psychiatric, or emotional conditions, or Parkinson's disease), or for 2... oxidase inhibitor (MAOI) (certain drugs for depression, psychiatric, or emotional conditions, or Parkinson...

Antitussive activity of Althaea officinalis L. polysaccharide rhamnogalacturonan and its changes in guinea pigs with ovalbumine-induced airways inflammation.

PubMed

Sutovska, M; Capek, P; Franova, S; Joskova, M; Sutovsky, J; Marcinek, J; Kalman, M

2011-01-01

The presented studies were aimed on experimental confirmation of Althaea officinalis polysaccharide rhamnogalacturonan antitussive effect and its changes in conditions of allergic inflammation. We have tested whether rhamnogalacturonan inhibits cough reflex and modulates airways reactivity of guinea pigs in vivo. The cough in guinea pigs was induced by 0.3 M citric acid (CA) aerosol for 3 min interval, in which total number of cough efforts (sudden enhancement of expiratory flow accompanied by cough movement and sound) was counted. Specific airway resistance and its changes induced by citric acid aerosol were considered as an indicator of the in vivo reactivity changes. 1) Althaea officinalis polysaccharide rhamnogalacturonan dose- dependently inhibits cough reflex in unsensitized guinea pigs. Simultaneously, plant polysaccharide shortened the duration of antitussive effect when it was been tested in inflammatory conditions. 2) Rhamnogalacturonan did not influence airways reactivity in vivo conditions expressed as specific resistance values neither sensitized nor unsensitized groups of animals. 3) The antitussive activity of codeine (dose 10 mg.kg(-1) b.w. orally) tested under the same condition was comparable to higher dose of rhamnogalacturonan in unsensitized animals. 4) The characteristic cellular pattern of allergic airways inflammation was confirmed by histopathological investigations. Rhamnogalacturonan isolated from Althaea officinalis mucilage possesses very high cough suppressive effect in guinea pigs test system, which is shortened in conditions of experimentally induced airways allergic inflammation (Tab. 1, Fig. 4, Ref. 25). Full Text in free PDF www.bmj.sk.

Dextromethorphan Analogs: Receptor Binding and Pharmacological Profile of Novel Anticonvulsant/Neuroprotectant Drugs

DTIC Science & Technology

1993-05-13

AD-POO8 801 Dextromethorphan Analogs: Receptor Binding and Pharmacological Profile of Novel Anticonvulsant/Neuroprotective Drugs F.C. Tortella, L...Baltimore, MD 21224 CD ABSTRACT A series of 3-substituted 17-methylmorphinan analogs of dextromethorphan (DM) have open developed which are...nTTrTTn) INTRODUCTION The antitussives dextromethorphan (DM), caramiphen and carbetapentane have distinguished themselves as anticonvulsant drugs (1

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...

Analysis of the impact of removing mucolytics and expectorants from the list of reimbursable drugs on prescription rates: a time-series analysis for France 1998-2010.

PubMed

Pichetti, Sylvain; Sorasith, Christine; Sermet, Catherine

2011-10-01

After a comprehensive review of the therapeutic advantage of all drugs reimbursed by the French Public Health Insurance, a large number of drugs were removed from the list of reimbursable drugs, among them mucolytics and expectorants (ATC Class R05C) in March 2006. The aim of this study is to evaluate the impact of this measure on the mucolytic and expectorant class, on the prescription of possible substitute drugs (other bronchodilators, antitussives and antibacterials) and on the costs for Public Health Insurance. Prescription data were taken from a 850 French physicians sample surveyed by the IMS-Health Permanent Survey on Medical Prescription from 1998 to 2010. We performed linear segmented regression to determine changes in the level and slope of the prescription rates and to estimate the budget impact. Following their removal from the list of reimbursable drugs, the prescription rate for mucolytics declined significantly and we recorded an increase in the prescription rates for antitussives and bronchodilators. The medically unexpected increase in antitussives can be viewed as a negative side-effect of the policy. Four years after the reform, total savings for Public Health Insurance were estimated at EUR 32.1 million. Further removals from the list of reimbursable drugs should take into account the possibility of negative impact on public health and potential savings. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

21 CFR 341.70 - Labeling of OTC drug products containing ingredients that are used for treating concurrent...

Code of Federal Regulations, 2011 CFR

2011-04-01

... name of the drug, if any, and identifies the product as a “cough suppressant/oral anesthetic” or “antitussive (cough suppressant)/oral anesthetic.” The indications shall be combined from § 341.74(b) and part...

21 CFR 341.70 - Labeling of OTC drug products containing ingredients that are used for treating concurrent...

Code of Federal Regulations, 2010 CFR

2010-04-01

... name of the drug, if any, and identifies the product as a “cough suppressant/oral anesthetic” or “antitussive (cough suppressant)/oral anesthetic.” The indications shall be combined from § 341.74(b) and part...

21 CFR 341.70 - Labeling of OTC drug products containing ingredients that are used for treating concurrent...

Code of Federal Regulations, 2014 CFR

2014-04-01

... name of the drug, if any, and identifies the product as a “cough suppressant/oral anesthetic” or “antitussive (cough suppressant)/oral anesthetic.” The indications shall be combined from § 341.74(b) and part...

21 CFR 341.70 - Labeling of OTC drug products containing ingredients that are used for treating concurrent...

Code of Federal Regulations, 2012 CFR

2012-04-01

... name of the drug, if any, and identifies the product as a “cough suppressant/oral anesthetic” or “antitussive (cough suppressant)/oral anesthetic.” The indications shall be combined from § 341.74(b) and part...

21 CFR 341.70 - Labeling of OTC drug products containing ingredients that are used for treating concurrent...

Code of Federal Regulations, 2013 CFR

2013-04-01

... name of the drug, if any, and identifies the product as a “cough suppressant/oral anesthetic” or “antitussive (cough suppressant)/oral anesthetic.” The indications shall be combined from § 341.74(b) and part...

Identifying mechanism-of-action targets for drugs and probes

PubMed Central

Gregori-Puigjané, Elisabet; Setola, Vincent; Hert, Jérôme; Crews, Brenda A.; Irwin, John J.; Lounkine, Eugen; Marnett, Lawrence; Roth, Bryan L.; Shoichet, Brian K.

2012-01-01

Notwithstanding their key roles in therapy and as biological probes, 7% of approved drugs are purported to have no known primary target, and up to 18% lack a well-defined mechanism of action. Using a chemoinformatics approach, we sought to “de-orphanize” drugs that lack primary targets. Surprisingly, targets could be easily predicted for many: Whereas these targets were not known to us nor to the common databases, most could be confirmed by literature search, leaving only 13 Food and Drug Administration—approved drugs with unknown targets; the number of drugs without molecular targets likely is far fewer than reported. The number of worldwide drugs without reasonable molecular targets similarly dropped, from 352 (25%) to 44 (4%). Nevertheless, there remained at least seven drugs for which reasonable mechanism-of-action targets were unknown but could be predicted, including the antitussives clemastine, cloperastine, and nepinalone; the antiemetic benzquinamide; the muscle relaxant cyclobenzaprine; the analgesic nefopam; and the immunomodulator lobenzarit. For each, predicted targets were confirmed experimentally, with affinities within their physiological concentration ranges. Turning this question on its head, we next asked which drugs were specific enough to act as chemical probes. Over 100 drugs met the standard criteria for probes, and 40 did so by more stringent criteria. A chemical information approach to drug-target association can guide therapeutic development and reveal applications to probe biology, a focus of much current interest. PMID:22711801

Antitussive and antibronchoconstriction actions of fenspiride in guinea-pigs.

PubMed

Laude, E A; Bee, D; Crambes, O; Howard, P

1995-10-01

Fenspiride is a nonsteroidal anti-inflammatory agent, which we have previously shown to have an in vivo antibronchoconstrictor action in guinea pigs. We have currently studied this action using the constrictors Substance P, neurokinin A, citric acid and capsaicin in anaesthetized guinea-pigs. Fenspiride has also been reported to produce a subjective improvement in cough in patients. We have used a conscious guinea-pig model of cough as a more definitive method to study the effect of fenspiride on capsaicin- and citric acid-induced cough. Aerosolized fenspiride (1 mg.mL-1) caused a 58% reversal of capsaicin-induced bronchoconstriction; and i.v. fenspiride (1mg.kg-1) a 45% reversal of citric acid induced bronchoconstriction. Substance P- and neurokinin A-induced bronchoconstriction were unaffected by 1 mg.kg-1 i.v. fenspiride. Aerosolized fenspiride (1, 3 and 10 mg.mL-1) administered for 4 min reduced citric acid (300 mM) induced cough, but 0.1 mg.mL-1 was without effect. Pretreatment with aerosolized fenspiride (10 mg.mL-1) caused a shift in the citric acid dose response curve to the right. For citric acid-induced cough, the duration of action of aerosolized fenspiride (10 mg.mL-1) was found to be 5 and 15 min post-treatment. Aerosolized capsaicin (30 microM) induced cough was also reduced by 3 and 10 mg.mL-1 aerosolized fenspiride, but no significant effect was found with 1 mg.mL-1. We conclude that aerosolized fenspiride reduces capsaicin- and citric acid-induced bronchoconstriction as well as induced cough in guinea-pigs in vivo. Whether a pathway common to both cough and bronchoconstriction is the site of action of fenspiride remains to be established. We postulate that fenspiride, acting as an antitussive and antibronchoconstrictor agent, would be beneficial in the clinical situation for those patients with hyperresponsive airways.

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 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...

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.

[Prescription of systemic cold and cough drugs to children 0-13 years old. An unresolved problem].

PubMed

Cano Garcinuño, A; Casares Alonso, I; Rodríguez Barbero, J; Pérez García, I; Blanco Quirós, A

2013-01-01

Upper respiratory tract infections are the most common cause of paediatric consultation, generating a high volume of prescriptions of drugs with unfavourable risk-benefit ratio. The aim of this study is to describe the prescription of systemic cough and cold medicines to children under 14 years of age in Castilla y León and analyse its variability. A count was made of the prescriptions for the R05 therapeutic subgroup (antitussives and mucolytics) and the R01B pharmacological therapeutic subgroup (nasal decongestants for systemic use), prescribed for children under the age of 14 in the Public Health System between 2005-2010. The number of prescriptions was analysed as crude and age-adjusted rates, as well as a a multivariate analysis (Poisson regression) of the variability associated with health area, the urban/rural environment, age, and year of prescription. There were 806,785 prescriptions for systemic cough and cold drugs given to an exposed population of 1,580,229 person-years. Prescription rates (per 100 person-years) were 20.7 (antitussives), 7.0 (sympathomimetic) and 23.4 (mucolytics). These drugs were employed more often in children <4 years. The prescription of mucolytics and sympathomimetics was highest at age of 1 year (rates=41.9 and 18.7, respectively) and of antitussives at 3 years (35.7). Multivariate analysis showed that in rural areas the prescription was higher than in urban areas, and that there were also significant differences between health areas. Between 2005 and 2010 there was a high prescription of systemic cough and cold medicines, especially in children under 2 years old, and often outside the recommended conditions of use, and there was a high geographic variabilty. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier España. All rights reserved.

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,…

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.

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...

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...

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.

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

Prevalence of Malaria Parasitemia and Purchase of Artemisinin-Based Combination Therapies (ACTs) among Drug Shop Clients in Two Regions in Tanzania with ACT Subsidies

PubMed Central

Briggs, Melissa A.; Kalolella, Admirabilis; Bruxvoort, Katia; Wiegand, Ryan; Lopez, Gerard; Festo, Charles; Lyaruu, Pierre; Kenani, Mitya; Abdulla, Salim; Goodman, Catherine; Kachur, S. Patrick

2014-01-01

Background Throughout Africa, many people seek care for malaria in private-sector drug shops where diagnostic testing is often unavailable. Recently, subsidized artemisinin-based combination therapies (ACTs), a first-line medication for uncomplicated malaria, were made available in these drug shops in Tanzania. This study assessed the prevalence of malaria among and purchase of ACTs by drug shop clients in the setting of a national ACT subsidy program and sub-national drug shop accreditation program. Method and Findings A cross-sectional survey of drug shop clients was performed in two regions in Tanzania, one with a government drug shop accreditation program and one without, from March-May, 2012. Drug shops were randomly sampled from non-urban districts. Shop attendants were interviewed about their education, training, and accreditation status. Clients were interviewed about their symptoms and medication purchases, then underwent a limited physical examination and laboratory testing for malaria. Malaria prevalence and predictors of ACT purchase were assessed using univariate analysis and multiple logistic regression. Amongst 777 clients from 73 drug shops, the prevalence of laboratory-confirmed malaria was 12% (95% CI: 6–18%). Less than a third of clients with malaria had purchased ACTs, and less than a quarter of clients who purchased ACTs tested positive for malaria. Clients were more likely to have purchased ACTs if the participant was <5 years old (aOR: 6.6; 95% CI: 3.9–11.0) or the shop attendant had >5 years, experience (aOR: 2.8; 95% CI: 1.2–6.3). Having malaria was only a predictor of ACT purchase in the region with a drug shop accreditation program (aOR: 3.4; 95% CI: 1.5–7.4). Conclusion Malaria is common amongst persons presenting to drug shops with a complaint of fever. The low proportion of persons with malaria purchasing ACTs, and the high proportion of ACTs going to persons without malaria demonstrates a need to better target who receives

Prevalence of malaria parasitemia and purchase of artemisinin-based combination therapies (ACTs) among drug shop clients in two regions in Tanzania with ACT subsidies.

PubMed

Briggs, Melissa A; Kalolella, Admirabilis; Bruxvoort, Katia; Wiegand, Ryan; Lopez, Gerard; Festo, Charles; Lyaruu, Pierre; Kenani, Mitya; Abdulla, Salim; Goodman, Catherine; Kachur, S Patrick

2014-01-01

Throughout Africa, many people seek care for malaria in private-sector drug shops where diagnostic testing is often unavailable. Recently, subsidized artemisinin-based combination therapies (ACTs), a first-line medication for uncomplicated malaria, were made available in these drug shops in Tanzania. This study assessed the prevalence of malaria among and purchase of ACTs by drug shop clients in the setting of a national ACT subsidy program and sub-national drug shop accreditation program. A cross-sectional survey of drug shop clients was performed in two regions in Tanzania, one with a government drug shop accreditation program and one without, from March-May, 2012. Drug shops were randomly sampled from non-urban districts. Shop attendants were interviewed about their education, training, and accreditation status. Clients were interviewed about their symptoms and medication purchases, then underwent a limited physical examination and laboratory testing for malaria. Malaria prevalence and predictors of ACT purchase were assessed using univariate analysis and multiple logistic regression. Amongst 777 clients from 73 drug shops, the prevalence of laboratory-confirmed malaria was 12% (95% CI: 6-18%). Less than a third of clients with malaria had purchased ACTs, and less than a quarter of clients who purchased ACTs tested positive for malaria. Clients were more likely to have purchased ACTs if the participant was <5 years old (aOR: 6.6; 95% CI: 3.9-11.0) or the shop attendant had >5 years, experience (aOR: 2.8; 95% CI: 1.2-6.3). Having malaria was only a predictor of ACT purchase in the region with a drug shop accreditation program (aOR: 3.4; 95% CI: 1.5-7.4). Malaria is common amongst persons presenting to drug shops with a complaint of fever. The low proportion of persons with malaria purchasing ACTs, and the high proportion of ACTs going to persons without malaria demonstrates a need to better target who receives ACTs in these drug shops.

Codeine and its alternates for pain and cough relief*

PubMed Central

Eddy, Nathan B.; Friebel, Hans; Hahn, Klaus-Jürgen; Halbach, Hans

1969-01-01

This report—the third of a series on codeine and its alternates for pain and cough relief—presents a detailed review of the physiology and pathophysiology of cough, the methods for the experimental and clinical measurement of the antitussive action of drugs, possible mechanisms of action of antitussive agents, and includes a compilation of experimental results and clinical experience with codeine as an antitussive. PMID:4896168

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 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...

DANGEROUS AND HYPNOTIC DRUG ACT

PubMed Central

Whelan, William M.

1961-01-01

It is unprofessional conduct within the meaning of the Medical Practice Act to prescribe a dangerous drug without either a medical examination by a physician or other medical indications. Dangerous and hypnotic drugs are specifically defined by both state and federal law and distribution is strictly regulated. A physician may administer to his own patients such amounts of dangerous drugs as are necessary for the immediate needs of the patient. The physician may obtain such needed amounts of these drugs by an order placed with a pharmacist marked “for administration to immediate needs of patients.” A licensed physician may also prescribe dangerous and hypnotic drugs for patients and such prescriptions may be refilled on the specific authorization of the physician. A physician who dispenses dangerous and hypnotic drugs to patients must obtain a hypnotic drug license; he must use specific purchase orders when purchasing; the drugs must be labeled in the manner provided by law; and all records of sale shall be open to inspection by authorized officers of the law and kept for three years. By the Principles of Medical Ethics physicians are bound to limit the source of their professional income to medical services actually rendered. Recent decisions of the Judicial Council answer questions concerning a physician's interest in a corporation which purchases, packages and sells medicines under a corporate name. Also answered are questions as to the measures that exist to prevent physicians from abusing the privilege of owning a pharmacy, and whether a physician can ethically rent space in a building owned by him to a pharmacist with a percentage of the income of the pharmacy as rental. The public welfare of California and the nation as determined by legislation strictly regulates the distribution of dangerous drugs. It is in the best interest of the medical profession and its patients that these laws be understood and carefully observed. PMID:13784776

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...

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...

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...

Erosive and cariogenicity potential of pediatric drugs: study of physicochemical parameters

PubMed Central

2013-01-01

Background Pediatric medications may possess a high erosive potential to dental tissues due to the existence of acid components in their formulations. The purpose was to determine the erosive and cariogenic potential of pediatric oral liquid medications through the analysis of their physicochemical properties in vitro. Methods A total of 59 substances were selected from the drug reference list of the National Health Surveillance Agency (ANVISA), which belong to 11 therapeutic classes, as follows: analgesics, non-steroidal anti-inflammatory, corticosteroids, antihistamines, antitussives, bronchodilators, antibacterials, antiparasitics, antiemetics, anticonvulsants and antipsychotics. Measurement of pH was performed by potentiometry, using a digital pH meter. For the Total Titratable Acidity (TTA) chemical assay, a 0.1 N NaOH standard solution was used, which was titrated until drug pH was neutralized. The Total Soluble Solids Contents (TSSC) quantification was carried out by refractometry using Brix scale and the analysis of Total Sugar Content was performed according to Fehling’s method. In addition, it was analyzed the information contained in the drug inserts with regard to the presence of sucrose and type of acid and sweetener added to the formulations. Results All drug classes showed acidic pH, and the lowest mean was found for antipsychotics (2.61 ± 0.08). There was a large variation in the TTA (0.1% - 1.18%) and SST (10.44% - 57.08%) values. High total sugar contents were identified in the antitussives (53.25%) and anticonvulsants (51.75%). As described in the drug inserts, sucrose was added in 47.5% of the formulations, as well as citric acid (39.0%), sodium saccharin (36.4%) and sorbitol (34.8%). Conclusion The drugs analyzed herein showed physicochemical characteristics indicative of a cariogenic and erosive potential on dental tissues. Competent bodies’ strategies should be implemented in order to broaden the knowledge of health professionals

Erosive and cariogenicity potential of pediatric drugs: study of physicochemical parameters.

PubMed

Xavier, Alidianne Fábia C; Moura, Eline F F; Azevedo, Waldeneide F; Vieira, Fernando F; Abreu, Mauro H N G; Cavalcanti, Alessandro L

2013-12-10

Pediatric medications may possess a high erosive potential to dental tissues due to the existence of acid components in their formulations. The purpose was to determine the erosive and cariogenic potential of pediatric oral liquid medications through the analysis of their physicochemical properties in vitro. A total of 59 substances were selected from the drug reference list of the National Health Surveillance Agency (ANVISA), which belong to 11 therapeutic classes, as follows: analgesics, non-steroidal anti-inflammatory, corticosteroids, antihistamines, antitussives, bronchodilators, antibacterials, antiparasitics, antiemetics, anticonvulsants and antipsychotics. Measurement of pH was performed by potentiometry, using a digital pH meter. For the Total Titratable Acidity (TTA) chemical assay, a 0.1 N NaOH standard solution was used, which was titrated until drug pH was neutralized. The Total Soluble Solids Contents (TSSC) quantification was carried out by refractometry using Brix scale and the analysis of Total Sugar Content was performed according to Fehling's method. In addition, it was analyzed the information contained in the drug inserts with regard to the presence of sucrose and type of acid and sweetener added to the formulations. All drug classes showed acidic pH, and the lowest mean was found for antipsychotics (2.61 ± 0.08). There was a large variation in the TTA (0.1% - 1.18%) and SST (10.44% - 57.08%) values. High total sugar contents were identified in the antitussives (53.25%) and anticonvulsants (51.75%). As described in the drug inserts, sucrose was added in 47.5% of the formulations, as well as citric acid (39.0%), sodium saccharin (36.4%) and sorbitol (34.8%). The drugs analyzed herein showed physicochemical characteristics indicative of a cariogenic and erosive potential on dental tissues. Competent bodies' strategies should be implemented in order to broaden the knowledge of health professionals, drug manufacturers and general consuming public

Drug Interactions of Direct-Acting Oral Anticoagulants.

PubMed

Fitzgerald, John Leonard; Howes, Laurence Guy

2016-09-01

In recent years, new direct-acting oral anticoagulants (DOACs) have been introduced into clinical practice that specifically inhibit either factor Ia or Xa. These drugs have, to a large extent, replaced warfarin for the treatment of venous thrombosis, pulmonary embolism, and non-valvular atrial fibrillation. They have potential advantages over warfarin in providing more stable anticoagulation and the lack of a need for regular venesection to monitor activity. They also have the promise of less drug and food interactions. All of these drugs are substrates for the permeability glycoprotein (P-gp) excretion system, and several are metabolised, in part, by cytochrome P450 (CYP) 3A4. This current article assesses the interactions that do or may occur with the DOACs, particularly with respect to the P-gp and CYP3A4 systems.

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,…

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.

Assessment of antitussive efficacy of dextromethorphan in smoking related cough: objective vs. subjective measures

PubMed Central

Ramsay, James; Wright, Caroline; Thompson, Rachel; Hull, David; Morice, Alyn H

2008-01-01

AIMS Using an established model of smokers cough we measured the antitussive effects of dextromethorphan compared with placebo. METHODS The study was a randomized, double-blind placebo controlled, crossover comparison of 22 mg 0.8 ml−1 dextromethorphan delivered pregastrically with matched placebo. Objective and subjective measurements of cough were recorded. Subjective measures included a daily diary record of cough symptoms and the Leicester quality of life questionnaire. Cough frequency was recorded using a manual cough counter. The objective measure of cough reflex sensitivity was the citric acid, dose–response cough challenge. RESULTS Dextromethorphan was significantly associated with an increase in the concentration of citric acid eliciting an average of two coughs/inhalation (C2) when compared with placebo, 1 h post dose by 0.49 mM (95% CI 0.05, 0.45, geometric mean 3.09) compared with placebo 0.24 mM (geometric mean 1.74) P < 0.05 and at 2 h 0.57 mM (95% CI 0.01, 0.43, geometric mean 3.75) compared with placebo 0.34 mM (geometric mean 2.19) P < 0.05). There was a highly significant improvement in the subjective data when compared with baseline. However, there was no significant difference between placebo and active treatment. No correlation was seen between cough sensitivity to citric acid and recorded cough counts or symptoms. When both subjective and objective data were compared with screening data there was evidence of a marked ‘placebo’ effect. CONCLUSIONS The objective measure of cough sensitivity demonstrates dextromethorphan effectively diminishes the cough reflex sensitivity. However, subjective measures do not support this. Other studies support these findings, which may represent a profound sensitivity of the cough reflex to higher influences. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Dextromethorphan is widely used as a cough suppressant in over the counter medications. Its efficacy in altering cough reflex sensitivity has been shown in

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.

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...

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

Venetoclax (ABT-199) Might Act as a Perpetrator in Pharmacokinetic Drug-Drug Interactions.

PubMed

Weiss, Johanna; Gajek, Thomas; Köhler, Bruno Christian; Haefeli, Walter Emil

2016-02-24

Venetoclax (ABT-199) represents a specific B-cell lymphoma 2 (Bcl-2) inhibitor that is currently under development for the treatment of lymphoid malignancies. So far, there is no published information on its interaction potential with important drug metabolizing enzymes and drug transporters, or its efficacy in multidrug resistant (MDR) cells. We therefore scrutinized its drug-drug interaction potential in vitro. Inhibition of cytochrome P450 enzymes (CYPs) was quantified by commercial kits. Inhibition of drug transporters (P-glycoprotein (P-gp, ABCB1), breast cancer resistance protein (BCRP), and organic anion transporting polypeptides (OATPs)) was evaluated by the use of fluorescent probe substrates. Induction of drug transporters and drug metabolizing enzymes was quantified by real-time RT-PCR. The efficacy of venetoclax in MDR cells lines was evaluated with proliferation assays. Venetoclax moderately inhibited P-gp, BCRP, OATP1B1, OATP1B3, CYP3A4, and CYP2C19, whereas CYP2B6 activity was increased. Venetoclax induced the mRNA expression of CYP1A1, CYP1A2, UGT1A3, and UGT1A9. In contrast, expression of ABCB1 was suppressed, which might revert tumor resistance towards antineoplastic P-gp substrates. P-gp over-expression led to reduced antiproliferative effects of venetoclax. Effective concentrations for inhibition and induction lay in the range of maximum plasma concentrations of venetoclax, indicating that it might act as a perpetrator drug in pharmacokinetic drug-drug interactions.

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.

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...

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...

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...

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…

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...

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

[Acting out and psychoactive substances: alcohol, drugs, illicit substances].

PubMed

Gillet, C; Polard, E; Mauduit, N; Allain, H

2001-01-01

In humans, some psychotropic agents (alcohol, drugs, illicit substances) have been suggested to play a role in the occurrence of major behavioural disorders, mainly due to the suppression of psychomotor inhibition. Behavioural disinhibition is a physiological mechanism which allows humans to behave appropriately according to a given environmental situation. The behavioural disinhibition induced by either therapeutic dosage or misuse involves the loss of restraint over certain types of social behaviour and may increase the risk of auto or hetero-aggression and acting out. The increased use of psychotropic agents in recent years and the occurrence of unwanted effects are worrying and must be detected and evaluated. The objective of the present study was to establish a causal relationship between psychoactive substance use and occurrence of major behavioural disorders, such as paradoxical rage reactions and suicidal behaviour, based on a literature analysis. It consisted of reviewing reports of drug-induced violent reactions in healthy volunteers and demonstrating, where possible, a cause-effect relationship. Patients with schizophrenia and psychopathic personalities were not included in our study since psychiatric comorbidity could influence behavioural responses. Psychotropic agents included drugs, licit and illicit substances already associated with violence in the past. Many reports used the "Go/No Go test" to evaluate the disinhibiting effect of psychotropic substances; this allows the "cognitive mapping" of drugs. The results suggest that only alcohol, antidepressants, benzodiazepines and cocaïne are related to aggressive behaviour. The best known precipitant of behavioural disinhibition is alcohol, which induces aggressive behaviour. However, there are large differences between individuals, and attentional mechanisms are now recognised as being important in mediating the effects of alcohol. Suicidal tendency as an adverse antidepressant reaction is rare

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...

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.

Therapies for inborn errors of metabolism: what has the orphan drug act delivered?

PubMed

Talele, Sonali S; Xu, Kui; Pariser, Anne R; Braun, M Miles; Farag-El-Massah, Sheiren; Phillips, M Ian; Thompson, Barry H; Coté, Timothy R

2010-07-01

The 1983 US Orphan Drug Act established a process through which promising therapies are designated as orphan products and, later, with satisfactory safety and efficacy data, receive marketing approval and fiscal incentives. We examined accomplishments in drug development for inborn errors of metabolism (IEMs). Food and Drug Administration data were used to identify orphan product designations and approvals for IEMs, and the trends for the past 26 years were summarized. Individual clinical development times (CDTs) from filing investigational new drug application to marketing approval were determined. We examined 1956 orphan product designations from 1983 through 2008 and found 93 (4.8%) for IEMs. Of those, 24 (25.8%) received marketing approval. This proportion of approval was significantly (P = .036) higher than that for non-IEM orphan products (17%). Among the IEM products, disorders of complex molecules received the most designations and approvals (61 and 11, respectively). Among the subgroups, lysosomal storage diseases received the most designations and approvals (43 and 9, respectively), whereas mitochondrial diseases (other than fatty acid oxidation disorders) received 7 designations with no approvals. We then examined the CDTs for the approved IEM products and found a median of 6.4 years (range: 2.6-25.1 years). Biological products had significantly shorter CDTs than drugs (mean: 4.6 vs 11.0 years; P = .003). For 26 years, the Orphan Drug Act has generated new therapies for IEMs. Why some IEMs have motivated successful drug development and others have not remains enigmatic; yet the needs of IEM patients without treatment are a certainty.

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

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...

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...

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.

Antitussive, antispasmodic, bronchodilating and cardiac inotropic effects of the essential oil from Blepharocalyx salicifolius leaves.

PubMed

Hernández, Jehison Jiménez; Ragone, María Inés; Bonazzola, Patricia; Bandoni, Arnaldo L; Consolini, Alicia E

2018-01-10

Blepharocalyx salicifolius (Kunth) O. Berg (Myrtaceae) is a tree native to Argentina and Uruguay that grows and is cultivated along the riverside of the Rio de la Plata. The leaves of this plant species, locally known as "anacahuita" are used in South America to prepare infusions for the empiric treatment of cough and bronchospasm, as well as diarrhoea and other intestinal disorders. Although previous phytochemical studies have been performed with the essential oil extracted from Blepharocalyx salicifolius, pharmacological evidence supporting its traditional use is still lacking. To experimentally evaluate the pharmacological properties of Blepharocalyx salicifolius based on its traditional use. The studies were performed with tincture (T-Bs) and essential oil (EO-Bs) prepared from its leaves, in isolated rat trachea, intestine and heart preparations. The ex-vivo effects of T-Bs and EO-Bs were evaluated with the agonists carbachol (CCh) and calcium chloride (Ca 2+ ) in the contractile concentration-response curves (CRC) of the isolated intestine. The muscle relaxant effect of EO-Bs was evaluated in the isolated trachea and compared with the effect achieved with papaverine as a positive control. The T-Bs and EO-Bs cardiac effects were analysed by perfusion of an isolated rat heart before a period of ischemia/reperfusion (stunning model). The antitussive effect of both T-Bs and EO-Bs was evaluated in mice exposed to ammonia using codeine as a positive control. Both T-Bs and EO-Bs induced a non-competitive inhibition of the CCh-CRC in the rat intestine, with IC 50 values of 170.3 ± 48.5µg T-Bs/mL (n = 6) and 5.9 ± 1.6µg EO-Bs/mL (n = 6), respectively. EO-Bs also inhibited non-competitively the Ca 2+ -CRC, with IC 50 value of 1.8 ± 0.3µg EO-Bs/mL (n = 8). A similar effect was obtained with the main active component of the EO-Bs 1,8-cineole. In isolated trachea, EO-Bs induced the relaxation of the CCh-contracted tissue (1.7 ± 0.2µg EO-Bs/mL, n = 11) up to a

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...

Direct Acting Anti-hepatitis C Virus Drugs: Clinical Pharmacology and Future Direction

PubMed Central

Geddawy, Ayman; Ibrahim, Yasmine F.; Elbahie, Nabil M.; Ibrahim, Mohammad A.

2017-01-01

Abstract Chronic hepatitis C virus (HCV) infection is a leading cause of chronic liver disease. The introduction of direct acting antiviral agents (DAAs) for its treatment represents a major advance in terms of sustained virologic response (SVR) rates and adverse effect profiles. Mechanistically, DAAs inhibit specific HCV non-structural proteins (NS) that are vital for its replication. Boceprevir, telaprevir, simeprevir, asunaprevir, grazoprevir and paritaprevir are NS3/4A inhibitors. Ombitasvir, ledipasvir, daclatasvir, elbasvir and velpatasvir are NS5A inhibitors. Sofosbuvir and dasabuvir are NS5B inhibitors. Currently, a combination of two or more DAAs is the corner stone for the treatment of HCV infection. However, the success of DAA therapy is facing several challenges, including the potential of drug-drug interactions and resistant variance. Moreover, the shortage of relevant clinical pharmacological data and drug interaction regarding DAA is a clinical concern. The present review discusses the clinical pharmacology of DAAs with special emphasis on drug-drug interaction. PMID:28680834

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…

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.

The role of trigeminal nasal TRPM8-expressing afferent neurons in the antitussive effects of menthol.

PubMed

Plevkova, J; Kollarik, M; Poliacek, I; Brozmanova, M; Surdenikova, L; Tatar, M; Mori, N; Canning, B J

2013-07-15

The cold-sensitive cation channel TRPM8 is a target for menthol, which is used routinely as a cough suppressant and as an additive to tobacco and food products. Given that cold temperatures and menthol activate neurons through gating of TRPM8, it is unclear how menthol actively suppresses cough. In this study we describe the antitussive effects of (-)-menthol in conscious and anesthetized guinea pigs. In anesthetized guinea pigs, cough evoked by citric acid applied topically to the tracheal mucosa was suppressed by menthol only when it was selectively administered as vapors to the upper airways. Menthol applied topically to the tracheal mucosa prior to and during citric acid application or administered continuously as vapors or as an aerosol to the lower airways was without effect on cough. These actions of upper airway menthol treatment were mimicked by cold air delivered to the upper airways but not by (+)-menthol, the inactive isomer of menthol, or by the TRPM8/TRPA1 agonist icilin administered directly to the trachea. Subsequent molecular analyses confirmed the expression of TRPM8 in a subset of nasal trigeminal afferent neurons that do not coincidently express TRPA1 or TRPV1. We conclude that menthol suppresses cough evoked in the lower airways primarily through a reflex initiated from the nose.

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.

Impact of the Pharma Economic Act on Diffusion of Innovation and Reduction of Costs in the Hungarian Prescription Drug Market (2007-2010).

PubMed

Hren, Rok

In this study, we examined the impact of the Pharma Economic Act, which was introduced in Hungary in 2007. We used detailed data on the Hungarian prescription drug market, which had been made publicly available by the authorities. We evaluated the effect of the Pharma Economic Act on both dynamic and static efficiencies and also on equity, which has been historically a controversial issue in Hungary. We analyzed the overall prescription drug market and statin and atorvastatin markets; as a proxy for determining dynamic efficiency, we examined the oncology drug market for some specific products (e.g., bortezomib) and the long-acting atypical antipsychotic drugs market. There is no denying that the authorities managed to control the overall prescription drug costs; however, they were still paying excessive rents for off-patent drugs. Examples of oncology and long-acting atypical antipsychotic drugs showed that the diffusion of innovation was on per-capita basis at least comparable to G-5 countries. While the share of out-of-pocket co-payments markedly increased and the reimbursement was lowered, the concurrent price decreases often meant that the co-payment per milligram of a given dispensed drug was actually lower than that before the Act, thereby benefiting the patient. It appears that strong mechanisms to control volume rather than price on the supply side (marketing authorization holders) contained the drug expenditure, while offering enough room to strive for innovation. Making data on prescription drug expenditures and associated co-payments publicly available is an item that should be definitely followed by the surrounding jurisdictions. Copyright © 2013, International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc.

Adverse drug events and the Freedom of Information Act: an apple in Eden.

PubMed

Stang, P E; Fox, J L

1992-02-01

To review some of the abuses and proper uses of the Food and Drug Administration's (FDA's) spontaneous adverse-reaction reporting system, as a way of educating the reader to its strengths and limitations. Published literature and reports based on information obtained from the FDA's database of spontaneous adverse drug-event reports. The Freedom of Information Act has increased public access to the FDA's database of spontaneous adverse drug reaction reports. As these reports are voluntarily received and reported to the FDA, their use for comparisons of drug safety is severely limited. Despite these limitations and the FDA's caveats for use of these data, consumer advocacy groups, researchers, and various pharmaceutical marketing groups have used this source to project the incidence of adverse drug reactions. The FDA's spontaneous adverse-event reporting system is designed to generate signals of unexpected adverse drug events. Use of the data gathered by this system to make drug safety comparisons is beyond their credible scope because many factors influence the reporting of adverse events. Researchers and peer reviewers should place these data in the proper perspective and support sound research into questions of drug safety.

Estimating antimalarial drugs consumption in Africa before the switch to artemisinin-based combination therapies (ACTs).

PubMed

Kindermans, Jean-Marie; Vandenbergh, Daniel; Vreeke, Ed; Olliaro, Piero; D'Altilia, Jean-Pierre

2007-07-10

Having reliable forecasts is critical now for producers, malaria-endemic countries and agencies in order to adapt production and procurement of the artemisinin-based combination treatments (ACTs), the new first-line treatments of malaria. There is no ideal method to quantify drug requirements for malaria. Morbidity data give uncertain estimations. This study uses drug consumption to provide elements to help estimate quantities and financial requirements of ACTs. The consumption of chloroquine, sulphadoxine/pyrimethamine and quinine both through the private and public sector was assessed in five sub-Saharan Africa countries with different epidemiological patterns (Senegal, Rwanda, Tanzania, Malawi, Zimbabwe). From these data the number of adult treatments per capita was calculated and the volumes and financial implications derived for the whole of Africa. Identifying and obtaining data from the private sector was difficult. The quality of information on drug supply and distribution in countries must be improved. The number of adult treatments per capita and per year in the five countries ranged from 0.18 to 0.50. Current adult treatment prices for ACTs range US$ 1-1.8. Taking the upper range for both volumes and costs, the highest number of adult treatments consumed for Africa was estimated at 314.5 million, corresponding to an overall maximum annual need for financing ACT procurement of US$ 566.1 million. In reality, both the number of cases treated and the cost of treatment are likely to be lower (projections for the lowest consumption estimate with the least expensive ACT would require US $ 113 million per annum). There were substantial variations in the market share between public and private sources among these countries (the public sector share ranging from 98% in Rwanda to 33% in Tanzania). Additional studies are required to build a more robust methodology, and to assess current consumptions more accurately in order to better quantify volumes and finances for

78 FR 26374 - An Evaluation of the Prescription Drug User Fee Act Workload Adjuster; Request for Comments

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-06

... XV, ``Improving FDA Performance Management,'' subsection B, which was reauthorized by the Food and Drug Administration Safety and Innovation Act (FDASIA) of 2012. The assessment will be conducted by an... Division of Dockets Management (HFA- 305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061...

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).

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.

In Vivo Evaluation of the Antiasthmatic, Antitussive, and Expectorant Activities and Chemical Components of Three Elaeagnus Leaves

PubMed Central

Ge, Yuebin; Zhang, Fei; Qin, Qin; Shang, Yingying; Wan, Dingrong

2015-01-01

The leaf of Elaeagnus lanceolata and Elaeagnus henryi as well as Elaeagnus pungens has been documented as an effective herb for the treatment of asthma and chronic bronchitis in traditional clinical medicine. This study was aimed at evaluating the antiasthmatic, antitussive, and expectorant activities of the water extracts from the three plants in vivo and analyzing their chemical components by HPLC-DAD. At the medium and high doses, the water extracts of three Elaeagnus leaves significantly prolonged the preconvulsive time (P < 0.01) in guinea pigs, lengthened the latent period of cough (P < 0.01) and decreased the cough frequency caused by aqueous ammonia in mice (P < 0.01), and enhanced tracheal phenol red output in mice (P < 0.01). There were no significant differences in the pharmacological actions between the three Elaeagnus leaves. Moreover, there was more similarity on overlap peaks in the range of retention time from 10 to 40 min by HPLC and many peaks that belonged to flavonoids compounds. It suggested that the main constituents of the three Elaeagnus leaves were flavonoid for the pharmacological activities. These effects were the important evidence for the traditional use of E. henryi leaf and E. lanceolata leaf as well as E. pungens to treat asthma and chronic bronchitis. PMID:26576193

In Vivo Evaluation of the Antiasthmatic, Antitussive, and Expectorant Activities and Chemical Components of Three Elaeagnus Leaves.

PubMed

Ge, Yuebin; Zhang, Fei; Qin, Qin; Shang, Yingying; Wan, Dingrong

2015-01-01

The leaf of Elaeagnus lanceolata and Elaeagnus henryi as well as Elaeagnus pungens has been documented as an effective herb for the treatment of asthma and chronic bronchitis in traditional clinical medicine. This study was aimed at evaluating the antiasthmatic, antitussive, and expectorant activities of the water extracts from the three plants in vivo and analyzing their chemical components by HPLC-DAD. At the medium and high doses, the water extracts of three Elaeagnus leaves significantly prolonged the preconvulsive time (P < 0.01) in guinea pigs, lengthened the latent period of cough (P < 0.01) and decreased the cough frequency caused by aqueous ammonia in mice (P < 0.01), and enhanced tracheal phenol red output in mice (P < 0.01). There were no significant differences in the pharmacological actions between the three Elaeagnus leaves. Moreover, there was more similarity on overlap peaks in the range of retention time from 10 to 40 min by HPLC and many peaks that belonged to flavonoids compounds. It suggested that the main constituents of the three Elaeagnus leaves were flavonoid for the pharmacological activities. These effects were the important evidence for the traditional use of E. henryi leaf and E. lanceolata leaf as well as E. pungens to treat asthma and chronic bronchitis.

The role of trigeminal nasal TRPM8-expressing afferent neurons in the antitussive effects of menthol

PubMed Central

Plevkova, J.; Kollarik, M.; Poliacek, I.; Brozmanova, M.; Surdenikova, L.; Tatar, M.; Mori, N.

2013-01-01

The cold-sensitive cation channel TRPM8 is a target for menthol, which is used routinely as a cough suppressant and as an additive to tobacco and food products. Given that cold temperatures and menthol activate neurons through gating of TRPM8, it is unclear how menthol actively suppresses cough. In this study we describe the antitussive effects of (−)-menthol in conscious and anesthetized guinea pigs. In anesthetized guinea pigs, cough evoked by citric acid applied topically to the tracheal mucosa was suppressed by menthol only when it was selectively administered as vapors to the upper airways. Menthol applied topically to the tracheal mucosa prior to and during citric acid application or administered continuously as vapors or as an aerosol to the lower airways was without effect on cough. These actions of upper airway menthol treatment were mimicked by cold air delivered to the upper airways but not by (+)-menthol, the inactive isomer of menthol, or by the TRPM8/TRPA1 agonist icilin administered directly to the trachea. Subsequent molecular analyses confirmed the expression of TRPM8 in a subset of nasal trigeminal afferent neurons that do not coincidently express TRPA1 or TRPV1. We conclude that menthol suppresses cough evoked in the lower airways primarily through a reflex initiated from the nose. PMID:23640596

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...

Are We Using Slow-Acting Symptomatic Chondroprotective Drugs Conscious Enough?

PubMed

Gumustas, Seyit Ali; Oznam, Kadir; Mutlu, Cagri Ata; Kaya, Yasin Emre; Yilmaz, Ibrahim; Isyar, Mehmet; Guzelant, Aliye Yıldırım; Guler, Olcay; Akkaya, Semih; Mahirogullari, Mahir

2017-01-01

Osteochondral injuries constitute an entity that is widespread and can be seen in patients of all ages. Actual treatment modalities aim to relieve pain, obtain full range of movement of the joint, and improve the quality of life. There are many slow-acting chondroprotective agents prevalently used in the United States that are classified as nutritional support but not as medicines . This study presents the importance of clinical adverse effect profiles as well as the pharmacological mechanism of action and application of combinations of drugs that are widely prescribed and not subjected to control. Electronic databases were searched with keywords about the chondroprotective drugs without any language restriction. Evaluations of the descriptive statistics were represented via Microsoft Office Excel 2010 lists in the form of a mean±standard deviation or frequency (%). The first evaluation showed that 1502 studies were potentially relevant. Following exclusion of the 1277 studies which were not clinical, full versions of the remaining 225 studies were subjected to further evaluation. No controlled, blinded, randomized and/or comparative studies met the inclusion criteria of the study, and no studies evaluated the comparative clinical results of the hyaluronan of different molecular weights. The findings of this study concluded that especially when prescribing drugs with ingredients like GS and CS, many patients' pre-existing conditions must be considered, such as whether the patient has a glucose intolerance or not. Additionally, mineral toxication should be considered since the drugs contain minerals, and after the application of injected hyaluronan, complications should be considered. Clinical, controlled and comparative studies about the use of chondroprotective drugs must be performed to define the benefits of these drugs, if any, in order to determine the most suitable time for operative intervention.

The US Food and Drug Administration Modernization Act of 1997: impact on consumers.

PubMed

Golodner, L F

1998-01-01

This paper provides a consumer's perspective on an important issue that has a profound impact on all of us: the US Food and Drug Administration (FDA) Modernization Act of 1997. In addition, it provides some background information on the National Consumers League, an organization that promotes consumer safety and protection with the FDA and its predecessors.

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.

Pressure for drug development in lysosomal storage disorders - a quantitative analysis thirty years beyond the US orphan drug act.

PubMed

Mechler, Konstantin; Mountford, William K; Hoffmann, Georg F; Ries, Markus

2015-04-18

Lysosomal storage disorders are a heterogeneous group of approximately 50 monogenically inherited orphan conditions. A defect leads to the storage of complex molecules in the lysosome, and patients develop a complex multisystemic phenotype of high morbidity often associated with premature death. More than 30 years ago the Orphan Drug Act of 1983 passed the United States legislation intended to facilitate the development of drugs for rare disorders. We directed our efforts in assessing which lysosomal diseases had drug development pressure and what distinguished those with successful development and approvals from diseases not treated or without orphan drug designation. Analysis of the FDA database for orphan drug designations through descriptive and comparative statistics. Between 1983 and 2013, fourteen drugs for seven conditions received FDA approval. Overall, orphan drug status was designated 70 times for 20 conditions. Approved therapies were enzyme replacement therapies (N = 10), substrate reduction therapies (N = 1), small molecules facilitating lysosomal substrate transportation (N = 3). FDA approval was significantly associated with a disease prevalence higher than 0.5/100,000 (p = 0.00742) and clinical development programs that did not require a primary neurological endpoint (p = 0.00059). Orphan drug status was designated for enzymes, modified enzymes, fusion proteins, chemical chaperones, small molecules leading to substrate reduction, or facilitating subcellular substrate transport, stem cells as well as gene therapies. Drug development focused on more common diseases. Primarily neurological diseases were neglected. Small clinical trials with either somatic or biomarker endpoints were successful. Enzyme replacement therapy was the most successful technology. Four factors played a key role in successful orphan drug development or orphan drug designations: 1) prevalence of disease 2) endpoints 3) regulatory precedent, and 4) technology platform

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...

Drug discovery and the impact of the safe harbor provision of the Hatch- Waxman Act.

PubMed

Goodson, Susanne H

2010-01-01

Many facets of drug discovery involve the use of patented materials and methods, subjecting the researcher to potential liability from infringement of the underlying patents. Enacted in 1984, the Hatch-Waxman Act established a “safe harbor” for activities that would otherwise constitute infringement of a patented invention, if those activities were “solely for uses reasonably related to the development and submission of information under a Federal law which regulates the manufacture, use, or sale of drugs or veterinary biological products”. This article examines the major court decisions interpreting the scope of the safe harbor and their application to various activities in drug development.

78 FR 78366 - Draft Generic Drug User Fee Act Information Technology Plan; Availability for Comment

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-26

...] Draft Generic Drug User Fee Act Information Technology Plan; Availability for Comment AGENCY: Food and... the availability for public comment of the draft information technology (IT) plan entitled ``GDUFA Information Technology Plan.'' This plan is intended to provide FDA's approach for enhancing business...

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…

Venetoclax (ABT-199) Might Act as a Perpetrator in Pharmacokinetic Drug–Drug Interactions

PubMed Central

Weiss, Johanna; Gajek, Thomas; Köhler, Bruno Christian; Haefeli, Walter Emil

2016-01-01

Venetoclax (ABT-199) represents a specific B-cell lymphoma 2 (Bcl-2) inhibitor that is currently under development for the treatment of lymphoid malignancies. So far, there is no published information on its interaction potential with important drug metabolizing enzymes and drug transporters, or its efficacy in multidrug resistant (MDR) cells. We therefore scrutinized its drug–drug interaction potential in vitro. Inhibition of cytochrome P450 enzymes (CYPs) was quantified by commercial kits. Inhibition of drug transporters (P-glycoprotein (P-gp, ABCB1), breast cancer resistance protein (BCRP), and organic anion transporting polypeptides (OATPs)) was evaluated by the use of fluorescent probe substrates. Induction of drug transporters and drug metabolizing enzymes was quantified by real-time RT-PCR. The efficacy of venetoclax in MDR cells lines was evaluated with proliferation assays. Venetoclax moderately inhibited P-gp, BCRP, OATP1B1, OATP1B3, CYP3A4, and CYP2C19, whereas CYP2B6 activity was increased. Venetoclax induced the mRNA expression of CYP1A1, CYP1A2, UGT1A3, and UGT1A9. In contrast, expression of ABCB1 was suppressed, which might revert tumor resistance towards antineoplastic P-gp substrates. P-gp over-expression led to reduced antiproliferative effects of venetoclax. Effective concentrations for inhibition and induction lay in the range of maximum plasma concentrations of venetoclax, indicating that it might act as a perpetrator drug in pharmacokinetic drug–drug interactions. PMID:26927160

[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.

Drug-Free Platelets Can Act as Seeds for Aggregate Formation During Antiplatelet Therapy

PubMed Central

Hoefer, Thomas; Armstrong, Paul C.; Finsterbusch, Michaela; Chan, Melissa V.; Kirkby, Nicholas S.

2015-01-01

Objective— Reduced antiplatelet drug efficacy occurs in conditions of increased platelet turnover, associated with increased proportions of drug-free, that is, uninhibited, platelets. Here, we detail mechanisms by which drug-free platelets promote platelet aggregation in the face of standard antiplatelet therapy. Approach and Results— To model standard antiplatelet therapy, platelets were treated in vitro with aspirin, the P2Y12 receptor blocker prasugrel active metabolite, or aspirin plus prasugrel active metabolite. Different proportions of uninhibited platelets were then introduced. Light transmission aggregometry analysis demonstrated clear positive associations between proportions of drug-free platelets and percentage platelet aggregation in response to a range of platelet agonists. Using differential platelet labeling coupled with advanced flow cytometry and confocal imaging we found aggregates formed in mixtures of aspirin-inhibited platelets together with drug-free platelets were characterized by intermingled platelet populations. This distribution is in accordance with the ability of drug-free platelets to generate thromboxane A2 and so drive secondary platelet activation. Conversely, aggregates formed in mixtures of prasugrel active metabolite–inhibited or aspirin plus prasugrel active metabolite–inhibited platelets together with drug-free platelets were characterized by distinct cores of drug-free platelets. This distribution is consistent with the ability of drug-free platelets to respond to the secondary activator ADP. Conclusions— These experiments are the first to image the interactions of inhibited and uninhibited platelets in the formation of platelet aggregates. They demonstrate that a general population of platelets can contain subpopulations that respond strikingly differently to overall stimulation of the population and so act as the seed for platelet aggregation. PMID:26272940

The clinical significance of drug-drug interactions in the era of direct-acting anti-viral agents against chronic hepatitis C.

PubMed

Maasoumy, B; Port, K; Calle Serrano, B; Markova, A A; Sollik, L; Manns, M P; Cornberg, M; Wedemeyer, H

2013-12-01

Drug-drug interactions (DDIs) in the treatment of chronic hepatitis C infection became a potential challenge with the introduction of direct-acting anti-virals (DAAs). Both currently approved DAAs, the protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC), are substrates and inhibitors of P-glycoprotein and the cytochrome P450 3A4, which are regularly involved in DDIs. To analyse the risk for DDIs in patients with chronic HCV genotype 1 infection considered for PI treatment at a tertiary referral centre. The first 115 consecutive patients selected for a PI therapy at Hannover Medical School were included. All changes to co-medication before and during PI treatment were documented. Drugs were checked for DDIs with TVR and BOC using DDI websites and the respective prescribing information. Out-patient medication contained 116 different drugs. Median number of drugs/patient was 2 (range 0-11). The risk for DDIs was substantial for 38% of the drugs affecting 49% of patients. Only 4% of the drugs were strictly contraindicated. DDIs between a PI and drugs newly prescribed during anti-viral therapy were considerable in 42% of the patients. Suspected DDIs were managed by dose adjustments and discontinuation of co-medication in 7% and 21% of the patients respectively. Many patients with chronic HCV genotype 1 infection are affected by potential DDIs if treated with a protease inhibitor, but only in a minority of cases co-medication is strictly incompatible. Overall, the challenge of DDIs is time-consuming, but well manageable by a careful review of the patient's drug chart and monitoring during treatment. © 2013 John Wiley & Sons Ltd.

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...

78 FR 78367 - Draft Prescription Drug User Fee Act V Information Technology Plan; Availability for Comment

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-26

...] Draft Prescription Drug User Fee Act V Information Technology Plan; Availability for Comment AGENCY... announcing the availability for public comment of the draft information technology (IT) plan entitled ``PDUFA V Information Technology Plan.'' This plan is intended to provide FDA's approach for enhancing...

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.

Moving Synergistically Acting Drug Combinations to the Clinic by Comparing Sequential versus Simultaneous Drug Administrations.

PubMed

Dinavahi, Saketh S; Noory, Mohammad A; Gowda, Raghavendra; Drabick, Joseph J; Berg, Arthur; Neves, Rogerio I; Robertson, Gavin P

2018-03-01

Drug combinations acting synergistically to kill cancer cells have become increasingly important in melanoma as an approach to manage the recurrent resistant disease. Protein kinase B (AKT) is a major target in this disease but its inhibitors are not effective clinically, which is a major concern. Targeting AKT in combination with WEE1 (mitotic inhibitor kinase) seems to have potential to make AKT-based therapeutics effective clinically. Since agents targeting AKT and WEE1 have been tested individually in the clinic, the quickest way to move the drug combination to patients would be to combine these agents sequentially, enabling the use of existing phase I clinical trial toxicity data. Therefore, a rapid preclinical approach is needed to evaluate whether simultaneous or sequential drug treatment has maximal therapeutic efficacy, which is based on a mechanistic rationale. To develop this approach, melanoma cell lines were treated with AKT inhibitor AZD5363 [4-amino- N -[(1 S )-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7 H -pyrrolo[2,3- d ]pyrimidin-4-yl)piperidine-4-carboxamide] and WEE1 inhibitor AZD1775 [2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1 H -pyrazolo[3,4- d ]pyrimidin-3(2 H )-one] using simultaneous and sequential dosing schedules. Simultaneous treatment synergistically reduced melanoma cell survival and tumor growth. In contrast, sequential treatment was antagonistic and had a minimal tumor inhibitory effect compared with individual agents. Mechanistically, simultaneous targeting of AKT and WEE1 enhanced deregulation of the cell cycle and DNA damage repair pathways by modulating transcription factors p53 and forkhead box M1, which was not observed with sequential treatment. Thus, this study identifies a rapid approach to assess the drug combinations with a mechanistic basis for selection, which suggests that combining AKT and WEE1 inhibitors is needed for maximal efficacy. Copyright © 2018 by The American

Differential profile and treatment development of drug-addicted patients depending on violent behaviours and/or criminal acts.

PubMed

López-Goñi, José J; Fernández-Montalvo, Javier; Arteaga, Alfonso; Cacho, Raúl

2015-01-01

This study explored the prevalence of violent and/or criminal behaviors in drug-addicted patients. A sample of 252 drug-addicted patients who sought treatment was assessed. Information was collected on violent behaviors, criminal acts, socio-demographic factors, consumption factors, psychopathological factors, and personality variables. The sample was divided into 4 groups according to the presence of violence and/or criminal behaviors. There were significant differences between the groups on some variables. In general, patients associated with both violence and criminal behaviors showed a greater severity in drug consumption and maladjustment variables, as well as a higher rate of treatment dropout and re-entry.

Effect of the Medicare Prescription Drug Improvement and Modernization Act on the bottom line.

PubMed

Jarrett, Anne T

2006-11-01

An historical perspective on the impact of the Medicare Prescription Drug Improvement and Modernization Act (MMA) on pharmaceutical reimbursement, and the financial bottom line at health systems and various strategies to use in the inpatient and outpatient setting to improve the bottom line are described. Implementation of MMA has affected the entire healthcare continuum by reducing pharmaceutical reimbursement rates and health system revenues and increasing prescription drug copayments, emergency department visits, and hospital admissions. Physician-owned clinics are less profitable than in the past because of MMA, which may prompt clinic closures and shift the patient care burden to clinics at public hospitals. Negotiating carve-outs for costly drugs and evaluating the feasibility of obtaining outlier payments can improve the bottom line in the hospital inpatient setting. Ensuring that billing codes are accurate and verifying that reimbursement was received can help minimize the impact of MMA on the financial bottom line in the outpatient setting. Negotiating favorable purchasing contracts and ensuring that drugs are used appropriately by following evidence-based guidelines can improve the financial bottom line in both the inpatient and outpatient settings. Strategies to decrease drug acquisition costs and increase reimbursement rates can help minimize the adverse impact of MMA on the financial bottom line at health systems.

Therapeutic options for acute cough due to upper respiratory infections in children.

PubMed

Paul, Ian M

2012-02-01

Cough due to upper respiratory tract infections (URIs) is one of the most frequent complaints encountered by pediatric health-care providers, and one of the most disruptive symptoms for children and families. Despite the frequency of URIs, there is limited evidence to support the few therapeutic agents currently available in the United States (US) to treat acute cough due to URI. Published, well-designed, contemporary research supporting the efficacy of narcotics (codeine, hydrocodone) and US Food and Drug Administration (FDA)-approved over-the-counter (OTC) oral antitussives and expectorants (dextromethorphan, diphenhydramine, chlophedianol, and guaifenesin) is absent for URI-associated pediatric cough. Alternatively, honey and topically applied vapor rubs may be effective antitussives.

Dual-acting of Hybrid Compounds - A New Dawn in the Discovery of Multi-target Drugs: Lead Generation Approaches.

PubMed

Abdolmaleki, Azizeh; Ghasemi, Jahan B

2017-01-01

Finding high quality beginning compounds is a critical job at the start of the lead generation stage for multi-target drug discovery (MTDD). Designing hybrid compounds as selective multitarget chemical entity is a challenge, opportunity, and new idea to better act against specific multiple targets. One hybrid molecule is formed by two (or more) pharmacophore group's participation. So, these new compounds often exhibit two or more activities going about as multi-target drugs (mtdrugs) and may have superior safety or efficacy. Application of integrating a range of information and sophisticated new in silico, bioinformatics, structural biology, pharmacogenomics methods may be useful to discover/design, and synthesis of the new hybrid molecules. In this regard, many rational and screening approaches have followed by medicinal chemists for the lead generation in MTDD. Here, we review some popular lead generation approaches that have been used for designing multiple ligands (DMLs). This paper focuses on dual- acting chemical entities that incorporate a part of two drugs or bioactive compounds to compose hybrid molecules. Also, it presents some of key concepts and limitations/strengths of lead generation methods by comparing combination framework method with screening approaches. Besides, a number of examples to represent applications of hybrid molecules in the drug discovery are included. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Comments on the discordant recommendations for the use of symptomatic slow-acting drugs in knee osteoarthritis.

PubMed

Reginster, Jean-Yves; Cooper, Cyrus; Hochberg, Marc; Pelletier, Jean-Pierre; Rizzoli, René; Kanis, John; Abadie, Eric; Maheu, Emmanuel; Brandi, Maria Luisa; Devogelaer, Jean-Pierre; Branco, Jaime; Herrero-Beaumont, Gabriel; D'Hooghe, Pieter; Bruyère, Olivier

2015-05-01

Despite the near concurrent publication by influential scientific organizations, there are important differences in interpretation of the evidence base and the conclusions derived from the recent Osteoarthritis Research Society International (OARSI) guidelines for the management of knee osteoarthritis, the American College of Rheumatology (ACR) guidelines (concerning also hip and hand osteoarthritis) and the algorithm recommendations by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). This is particularly evident for the drug class of symptomatic slow-acting drugs in osteoarthritis. In this paper, we highlight these differences and try to understand where they derive from, proposing an evidence-based interpretation.

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 - ...

Seventeen-Year Nationwide Trends in Use of Long-acting Bronchodilators and Inhaled Corticosteroids among Adults - A Danish Drug Utilization Study.

PubMed

Reilev, Mette; Pottegård, Anton; Davidsen, Jesper Rømhild; Rasmussen, Lotte; Søndergaard, Jens; Laursen, Christian B; Henriksen, Daniel Pilsgaard

2018-02-08

Long-acting bronchodilators and inhaled corticosteroids (ICS) are the cornerstones in treatment of chronic obstructive and inflammatory pulmonary diseases. However, non-adherence to guidelines is widespread. Detailed information on real-life treatment patterns is needed to promote rational use. We aimed to investigate nationwide time trends in individual-level treatment patterns of long-acting bronchodilators and ICS. Using nationwide Danish health registries, we identified all Danish adults with a prescription for long-acting bronchodilators and/or ICS from 2000 to 2016. We investigated the total use of long-acting bronchodilators and ICS, the proportion of current users and the rate of new users over time. Finally, we assessed treatment persistence. We included 23,061,681 prescriptions for long-acting bronchodilators and ICS issued to 805,860 individuals from 2000 to 2016. Over this period, the total annual amount of prescribed long-acting bronchodilators and ICS increased by 39%. Similarly, the proportion of adult users increased from 2.6% to 4.5%, mainly driven by the introduction of combination therapy and long-acting muscarinic antagonist (LAMA). Although the rate of new users of fixed-dose combination drugs increased substantially over time, the overall rate of new users was stable. In general, the proportion of patients on therapy after 1 year was low (25-53%), especially among young individuals and users of ICS. We document a pronounced increase in the total use of long-acting bronchodilators and ICS over time, mainly driven by the introduction of combination drugs and LAMA. Special attention should be paid to the low level of persistence, especially among young individuals and users of ICS. © 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

What is the prognosis for new centrally-acting anti-obesity drugs?

PubMed

Heal, David J; Gosden, Jane; Smith, Sharon L

2012-07-01

Obesity is a global problem that is predominantly caused by the increasing adoption of a low-cost, Westernised diet that is rich in fat and sugar and a more sedentary lifestyle. The costs of this epidemic are substantial increases in Type 2 diabetes, cardiovascular disease and some types of cancer that are certain to place a huge burden on individuals, healthcare providers and society. In this review, we provide an overview of the chequered history of pharmacotherapy for the treatment of obesity and an analysis of the regulatory and commercial challenges for developing new centrally-acting drugs in this metabolic indication. The efficacy and safety of the drug candidates that are currently at the pre-registration phase, i.e., lorcaserin, Qnexa and Contrave, are critically assessed. The main focus, however, is to provide a comprehensive review of the wide range of novel CNS compounds that are in the discovery phase or early clinical development. The profiles of various clinical candidates in animal models of obesity predict that several new CNS approaches in the clinic have the potential to deliver greater weight-loss than existing agents. This article is part of a Special Issue entitled 'Central Control of Food Intake'. Copyright © 2012 Elsevier Ltd. All rights reserved.

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.

Effects of four antitussives on airway neurogenic inflammation in a guinea pig model of chronic cough induced by cigarette smoke exposure.

PubMed

Luo, Yu-long; Li, Pei-bo; Zhang, Chen-chen; Zheng, Yan-fang; Wang, Sheng; Nie, Yi-chu; Zhang, Ke-jian; Su, Wei-wei

2013-12-01

The effects of four antitussives, including codeine phosphate (CP), moguisteine, levodropropizine (LVDP) and naringin, on airway neurogenic inflammation and enhanced cough were investigated in guinea pig model of chronic cough. Guinea pigs were exposed to CS for 8 weeks. At the 7th and 8th week, the animals were treated with vehicle, CP (4.8 mg/kg), moguisteine (24 mg/kg), LVDP (14 mg/kg) and naringin (18.4 mg/kg) respectively. Then the cough and the time-enhanced pause area under the curve (Penh-AUC) during capsaicin challenge were recorded. The substance P (SP) content, NK-1 receptor expression and neutral endopeptidase (NEP) activity in lung were determined. Chronic CS exposure induced a bi-phase time course of cough responsiveness to capsaicin. Eight weeks of CS exposure significantly enhanced the airway neurogenic inflammation and cough response in guinea pigs. Two weeks of treatment with CP, moguisteine, LVDP or naringin effectively attenuated the chronic CS-exposure enhanced cough. Only naringin exerted significant effect on inhibiting Penh-AUC, SP content and NK-1 receptor expression, as well as preventing the declining of NEP activity in lung. Chronic CS-exposed guinea pig is suitable for studying chronic pathological cough, in which naringin is effective on inhibiting both airway neurogenic inflammation and enhanced cough.

77 FR 31039 - Andean Trade Preference Act: Impact on the U.S. Economy and on Andean Drug Crop Eradication

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-24

...The Commission's notice published in the Federal Register on May 15, 2012 (77 FR 28620) contained an error that incorrectly identified ``September 30, 2010'' as the date for transmittal to Congress of the Commission report under investigation No. 332-352, Andean Trade Preference Act: Impact on the U.S. Economy and on Andean Drug Crop Eradication, under section 206 of the Andean Trade Preference Act (19 U.S.C. 3204). The correct date for transmittal of the Commission report to Congress is September 28, 2012.

A fatal case of potential chronic overdoses of prescribed and proprietary remedies.

PubMed

Takase, Izumi; Yamamoto, Yoshio; Nakagawa, Tokiko; Nishi, Katsuji

2010-08-01

A 33-year-old man was found in a state of cardiopulmonary arrest. He was transported to an emergency hospital but was pronounced dead. He had suffered from depression for about 8 years and had attempted suicide repeatedly. A search by the police found 645 empty Press Through Package (PTP) sheets. They had included neuroleptics, antidepressants, hypnotics, proprietary antitussives containing caffeine, proprietary cold remedies containing caffeine, and other unidentified drugs. An autopsy showed higher rectal temperature (38 degrees C), severe pulmonary edema (left: 681 g, right: 821 g), and a large amount of urine in the bladder (about 760 mL). Toxicological analyses using gas chromatography-mass spectrometry (GC/MS) and high performance liquid chromatography (HPLC) demonstrated that doses of clomipramine hydrochloride (a tricyclic antidepressant), chlorpromazine (a phenothiazine), and caffeine (a methylxanthine derivative) were within the toxic range (0.68, 0.64, and 34.24 [microg/mL], respectively). Histological examination showed centrilobular necrosis of the liver with small fat droplets. We concluded that he had died of pulmonary edema due to combined drug intoxication including proprietary antitussives and cold remedies. Furthermore, there was a strong possibility that he had habitually taken overdoses of those drugs. Herein, the risk of misuse of prescribed and proprietary drugs, especially for people with psychological problems, should be reemphasized.

Did changes in drug reimbursement after the medicare modernization act affect chemotherapy prescribing?

PubMed

Hornbrook, Mark C; Malin, Jennifer; Weeks, Jane C; Makgoeng, Solomon B; Keating, Nancy L; Potosky, Arnold L

2014-12-20

The Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA) decreased fee-for-service (FFS) payments for outpatient chemotherapy. We assessed how this policy affected chemotherapy in FFS settings versus in integrated health networks (IHNs). We examined 5,831 chemotherapy regimens for 3,613 patients from 2003 to 2006 with colorectal cancer (CRC) or lung cancers in the Cancer Care Outcomes Research Surveillance Consortium. Patients were from four geographically defined regions, seven large health maintenance organizations, and 15 Veterans Affairs Medical Centers. The outcome of interest was receipt of chemotherapy that included at least one drug for which reimbursement declined after the MMA. The odds of receiving an MMA-affected drug were lower in the post-MMA era: the odds ratio (OR) was 0.73 (95% CI, 0.59 to 0.89). Important differences across cancers were detected: for CRC, the OR was 0.65 (95% CI, 0.46 to 0.92); for non-small-cell lung cancer (NSCLC), the OR was 1.60 (95% CI, 1.09 to 2.35); and for small-cell lung cancer, the OR was 0.63 (95% CI, 0.34 to 1.16). After the MMA, FFS patients were less likely to receive MMA-affected drugs: OR, 0.73 (95% CI, 0.59 to 0.89). No pre- versus post-MMA difference in the use of MMA-affected drugs was detected among IHN patients: OR, 1.01 (95% CI, 0.66 to 1.56). Patients with CRC were less likely to receive an MMA-affected drug in both FFS and IHN settings in the post- versus pre-MMA era, whereas patients with NSCLC were the opposite: OR, 1.60 (95% CI, 1.09 to 2.35) for FFS and 6.33 (95% CI, 2.09 to 19.11) for IHNs post- versus pre-MMA. Changes in reimbursement after the passage of MMA appear to have had less of an impact on prescribing patterns in FFS settings than the introduction of new drugs and clinical evidence as well as other factors driving adoption of new practice patterns. © 2014 by American Society of Clinical Oncology.

Did Changes in Drug Reimbursement After the Medicare Modernization Act Affect Chemotherapy Prescribing?

PubMed Central

Hornbrook, Mark C.; Malin, Jennifer; Weeks, Jane C.; Makgoeng, Solomon B.; Keating, Nancy L.; Potosky, Arnold L.

2014-01-01

Purpose The Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA) decreased fee-for-service (FFS) payments for outpatient chemotherapy. We assessed how this policy affected chemotherapy in FFS settings versus in integrated health networks (IHNs). Patients and Methods We examined 5,831 chemotherapy regimens for 3,613 patients from 2003 to 2006 with colorectal cancer (CRC) or lung cancers in the Cancer Care Outcomes Research Surveillance Consortium. Patients were from four geographically defined regions, seven large health maintenance organizations, and 15 Veterans Affairs Medical Centers. The outcome of interest was receipt of chemotherapy that included at least one drug for which reimbursement declined after the MMA. Results The odds of receiving an MMA-affected drug were lower in the post-MMA era: the odds ratio (OR) was 0.73 (95% CI, 0.59 to 0.89). Important differences across cancers were detected: for CRC, the OR was 0.65 (95% CI, 0.46 to 0.92); for non–small-cell lung cancer (NSCLC), the OR was 1.60 (95% CI, 1.09 to 2.35); and for small-cell lung cancer, the OR was 0.63 (95% CI, 0.34 to 1.16). After the MMA, FFS patients were less likely to receive MMA-affected drugs: OR, 0.73 (95% CI, 0.59 to 0.89). No pre- versus post-MMA difference in the use of MMA-affected drugs was detected among IHN patients: OR, 1.01 (95% CI, 0.66 to 1.56). Patients with CRC were less likely to receive an MMA-affected drug in both FFS and IHN settings in the post- versus pre-MMA era, whereas patients with NSCLC were the opposite: OR, 1.60 (95% CI, 1.09 to 2.35) for FFS and 6.33 (95% CI, 2.09 to 19.11) for IHNs post- versus pre-MMA. Conclusion Changes in reimbursement after the passage of MMA appear to have had less of an impact on prescribing patterns in FFS settings than the introduction of new drugs and clinical evidence as well as other factors driving adoption of new practice patterns. PMID:25267762

Olodaterol Attenuates Citric Acid-Induced Cough in Naïve and Ovalbumin-Sensitized and Challenged Guinea Pigs

PubMed Central

Wex, Eva; Bouyssou, Thierry

2015-01-01

Excessive coughing is a common feature of airway diseases. Different G-protein coupled receptors, including β2-adrenergic receptors (β2-AR), have been implicated in the molecular mechanisms underlying the cough reflex. However, the potential antitussive property of β2-AR agonists in patients with respiratory disease is a matter of ongoing debate. The aim of our study was to test the efficacy of the long-acting β2-AR agonist olodaterol with regard to its antitussive property in a pre-clinical model of citric acid-induced cough in guinea pigs and to compare the results to different clinically relevant β2-AR agonists. In our study β2-AR agonists were intratracheally administered, as dry powder, into the lungs of naïve or ovalbumin-sensitized guinea pigs 15 minutes prior to induction of cough by exposure to citric acid. Cough events were counted over 15 minutes during the citric acid exposure. Olodaterol dose-dependently inhibited the number of cough events in naïve and even more potently and with a greater maximal efficacy in ovalbumin-sensitized guinea pigs (p < 0.01). Formoterol and salmeterol showed a trend towards reducing cough. On the contrary, indacaterol demonstrated pro-tussive properties as it significantly increased the number of coughs, both in naïve and ovalbumin-sensitized animals (p < 0.001). In conclusion, olodaterol, at doses eliciting bronchodilation, showed antitussive properties in a model of citric acid-induced cough in naïve and ovalbumin-sensitized guinea pigs. This is in agreement with pre-clinical and clinical studies showing antitussive efficacy of β2-AR agonists. Indacaterol increased the number of coughs in this model, which concurs with clinical data where a transient cough has been observed after indacaterol inhalation. While the antitussive properties of β2-AR agonists can be explained by their ability to lead to the cAMP-induced hyperpolarization of the neuron membrane thereby inhibiting sensory nerve activation and the

Interesting asian plants: their compounds and effects on electrophysiology and behaviour.

PubMed

Abdullah, Jafri Malin

2011-10-01

There have been numerous non-scientific reports on the behavioural effects of Asian plants in humans who consumed these plants wholly or part thereof. Knowledge passed from generation to generation informs us of plants that increase effort and stamina, such as during paddy planting after the ingestion of Mitragyna speciosa Korth (ketum) as a tea supplement. Centella asiatica and Myristica fragrans are used as herbs to improve memory and to treat epilepsy, respectively. Zizyphus mauritiana is used to treat headache and burn pain, acts as an antitussive, and reduces rigor mortis immediately after death. These plants, which have been identified to exhibit analgaesic, muscle-relaxing, and nootropic effects, may contain important bio-compounds for medicinal chemistry and pharmaceutical research in Malaysia. The electrophysiology properties of these plants and their effects on epilepsy, behaviour, and pain will lead Malaysia to future new drug discoveries.

Dual- and triple-acting agents for treating core and co-morbid symptoms of major depression: novel concepts, new drugs.

PubMed

Millan, Mark J

2009-01-01

The past decade of efforts to find improved treatment for major depression has been dominated by genome-driven programs of rational drug discovery directed toward highly selective ligands for nonmonoaminergic agents. Selective drugs may prove beneficial for specific symptoms, for certain patient subpopulations, or both. However, network analyses of the brain and its dysfunction suggest that agents with multiple and complementary modes of action are more likely to show broad-based efficacy against core and comorbid symptoms of depression. Strategies for improved multitarget exploitation of monoaminergic mechanisms include triple inhibitors of dopamine, serotonin (5-HT) and noradrenaline reuptake, and drugs interfering with feedback actions of monoamines at inhibitory 5-HT(1A), 5-HT(1B) and possibly 5-HT(5A) and 5-HT(7) receptors. Specific subsets of postsynaptic 5-HT receptors mediating antidepressant actions are under study (e.g., 5-HT(4) and 5-HT(6)). Association of a clinically characterized antidepressant mechanism with a nonmonoaminergic component of activity is an attractive strategy. For example, agomelatine (a melatonin agonist/5-HT(2C) antagonist) has clinically proven activity in major depression. Dual neurokinin(1) antagonists/5-HT reuptake inhibitors (SRIs) and melanocortin(4) antagonists/SRIs should display advantages over their selective counterparts, and histamine H(3) antagonists/SRIs, GABA(B) antagonists/SRIs, glutamatergic/SRIs, and cholinergic agents/SRIs may counter the compromised cognitive function of depression. Finally, drugs that suppress 5-HT reuptake and blunt hypothalamo-pituitary-adrenocorticotrophic axis overdrive, or that act at intracellular proteins such as GSK-3beta, may abrogate the negative effects of chronic stress on mood and neuronal integrity. This review discusses the discovery and development of dual- and triple-acting antidepressants, focusing on novel concepts and new drugs disclosed over the last 2 to 3 years.

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)

The Drug Abuse Prevention and Control Act of 1970: Retrospective Assessments of Disparate Treatment and Consequential Impact.

PubMed

Yamatani, Hide; Feit, Marvin; Mann, Aaron

2017-01-01

Although the basic paradigm of the U.S. federal drug policy targeting the supply and demand reduction has not changed since its enactment in 1970, there have been seriously undesirable disparate treatments and impacts among various population groups. Although U.S. Congress could not define what is discrimination, it did provide two major criteria for the assessment of discriminatory practices as follows: (a) disparate treatment-basing a key decision on association with any of the five prohibited individual's demographic classifications (race, color, religion, sex, or national origin); and (b) disparate impact-correlation between any of the five prohibited demographic classifications and the key outcomes. In reference to those criteria, this article describes evidence-based indicators of national failure of the Comprehensive Drug Abuse Prevention and Control Act.

Analgesic and Antineuropathic Drugs Acting Through Central Cholinergic Mechanisms

PubMed Central

Bartolini, Alessandro; Cesare Mannelli, Lorenzo Di; Ghelardini, Carla

2011-01-01

The role of muscarinic and nicotinic cholinergic receptors in analgesia and neuropathic pain relief is relatively unknown. This review describes how such drugs induce analgesia or alleviate neuropathic pain by acting on the central cholinergic system. Several pharmacological strategies are discussed which increase synthesis and release of acetylcholine (ACh) from cholinergic neurons. The effects of their acute and chronic administration are described. The pharmacological strategies which facilitate the physiological functions of the cholinergic system without altering the normal modulation of cholinergic signals are highlighted. It is proposed that full agonists of muscarinic or nicotinic receptors should be avoided. Their activation is too intense and un-physiological because neuronal signals are distorted when these receptors are constantly activated. Good results can be achieved by using agents that are able to a) increase ACh synthesis, b) partially inhibit cholinesterase activity c) selectively block the autoreceptor or heteroreceptor feedback mechanisms. Activation of M1 subtype muscarinic receptors induces analgesia. Chronic stimulation of nicotinic (N1) receptors has neuronal protective effects. Recent experimental results indicate a relationship between repeated cholinergic stimulation and neurotrophic activation of the glial derived neurotrophic factor (GDNF) family. At least 9 patents covering novel chemicals for cholinergic system modulation and pain control are discussed. PMID:21585331

Characterization and pharmacodynamic properties of Arnica montana complex.

PubMed

Šutovská, M; Capek, P; Kočmalová, M; Pawlaczyk, I; Zaczyńska, E; Czarny, A; Uhliariková, I; Gancarz, R; Fraňová, S

2014-08-01

A dark brown polymeric complex was isolated from flowering parts of medicinal plant Arnica montana L. by hot alkaline extraction followed by neutralization and multi-step extractions with organic solvents. It was recovered in 5.7% yield, on GPC showed two peaks of molecular mass of 9 and 3.5kDa. The compositional analyses of Arnica complex revealed the presence of carbohydrates (26%), uronic acids (12%), phenolics (1.25mM or 213mg of GAE/1g), and low protein content (∼1%). The carbohydrate moiety was rich mainly in rhamnogalacturonan and arabinogalactan. The antitussive tests showed the reduction of the cough efforts by Arnica complex, however, its total antitussive effect was lower compared with that of codeine, the strongest antitussive agent. The bronchodilatory activity of Arnica complex was similar to salbutamol, a classic antiasthmatic drug, and was confirmed by significantly decreased values of specific airways resistance in vivo and by considerably attenuated the amplitude of acetylcholine and histamine-induced contractions in vitro. Arnica complex did not show any cytotoxic effect on mouse fibroblast cultures and human lung cells, up to the dose of 500μg/mL. Copyright © 2014 Elsevier B.V. All rights reserved.

Synthetic substances with morphine-like effect

PubMed Central

Eddy, Nathan B.; Halbach, H.; Braenden, Olav J.

1957-01-01

A review of effects in man of morphine-like drugs which have been brought under international narcotics control is presented in the form of individual monographs. These are based on controlled observations with quantitative data and significant reports of results obtained in medical practice. In a summarizing section, the drugs are compared with respect to effectiveness, side-effects and addiction liability. Morphine-like drugs of natural and synthetic origin now cover a wide range of potency (analgesic, antitussive), not necessarily paralleled by incidence of side-effects or addiction liability. PMID:13511135

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 ...

Discovery and Characterization of ACT-451840: an Antimalarial Drug with a Novel Mechanism of Action.

PubMed

Boss, Christoph; Aissaoui, Hamed; Amaral, Nathalie; Bauer, Aude; Bazire, Stephanie; Binkert, Christoph; Brun, Reto; Bürki, Cédric; Ciana, Claire-Lise; Corminboeuf, Olivier; Delahaye, Stephane; Dollinger, Claire; Fischli, Christoph; Fischli, Walter; Flock, Alexandre; Frantz, Marie-Céline; Girault, Malory; Grisostomi, Corinna; Friedli, Astrid; Heidmann, Bibia; Hinder, Claire; Jacob, Gael; Le Bihan, Amelie; Malrieu, Sophie; Mamzed, Saskia; Merot, Aurelien; Meyer, Solange; Peixoto, Sabrina; Petit, Nolwenn; Siegrist, Romain; Trollux, Julien; Weller, Thomas; Wittlin, Sergio

2016-09-20

More than 40 % of the world's population is at risk of being infected with malaria. Most malaria cases occur in the countries of sub-Saharan Africa, Central and South America, and Asia. Resistance to standard therapy, including artemisinin combinations, is increasing. There is an urgent need for novel antimalarials with new mechanisms of action. In a phenotypic screen, we identified a series of phenylalanine-based compounds that exhibit antimalarial activity via a new and yet unknown mechanism of action. Our optimization efforts culminated in the selection of ACT-451840 [(S,E)-N-(4-(4-acetylpiperazin-1-yl)benzyl)-3-(4-(tert-butyl)phenyl)-N-(1-(4-(4-cyanobenzyl)piperazin-1-yl)-1-oxo-3-phenylpropan-2-yl)acrylamide] for clinical development. Herein we describe our optimization efforts from the screening hit to the potential drug candidate with respect to antiparasitic activity, drug metabolism and pharmacokinetics (DMPK) properties, and in vivo pharmacological efficacy. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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 Policy Governance in the UK: lessons from changes to and debates concerning the classification of cannabis under the 1971 Misuse of Drugs Act.

PubMed

Monaghan, Mark

2014-09-01

Drugs policy is made in a politically charged atmosphere. This is often not seen to be conducive to the ideals of evidence-based policymaking. In the UK over recent years the efficacy of the 1971 Misuse of Drugs Act (MDA) has been one of the most widely discussed and debated areas of UK drug policy. Since inception, the MDA 1971 has remained relatively stable with very few drugs moving up or down the scale and until recently, and with very few exceptions, there has been little public debate on the nature of the system. This changed in the run up to the cannabis reclassification in 2004 from class B to class C, through the reverse of this decision in 2009 and the fallout between the Government of the time and leading members of the Advisory Council on the Misuse of Drugs. Based on wide-ranging survey of the literature and secondary analysis of various official publications and academic commentaries, this paper considers what the cannabis episode can tell us about the current state of UK drug policy governance. Previous research on drug policy governance has suggested that policy goals should be clearly articulated so as to avoid confusion over what constitutes evidence, decision-makers should be 'evidence-imbued' and there should be widespread consultation with, and transparency of, stakeholder engagement. The interpretation here is that recent changes to cannabis legislation reveal that these aspects of good governance were called into question although there were fleeting moments of good practice. The use of evidence in drug policy formulation continues to be bedevilled by political stalemate and reluctance to countenance radical reform. Where evidence does play a role it tends to be at the margins. There are, however, potential lessons to be learned from other policy areas but this requires a more pragmatic attitude on behalf of decision-makers. Copyright © 2014 Elsevier B.V. All rights reserved.

Does Drug Testing Deter Drug Court Participants from Using Drugs or Alcohol?

ERIC Educational Resources Information Center

Kleinpeter, Christine B.; Brocato, Jo; Koob, Jeffrey J.

2010-01-01

This study evaluates 3 drug-testing strategies implemented in 5 different jurisdictions with drug courts in Orange County, California. The purpose of the study was to determine whether the sweat patch acts as a deterrent and under what conditions it can be used to improve outcomes. Results indicated that although the use of the sweat patch did not…

Cough: impact, beliefs, and expectations from a national survey.

PubMed

Dal Negro, Roberto W; Mazzolini, Massimiliano; Turco, Paola; Zanasi, Alessandro

2016-01-01

standard for treating persistent cough (61.2 and 58.2 %, respectively), while anti-tussive drugs and aerosols in general are regarded as the most effective strategies (69.1 and 74.1 %, respectively). Moreover, 33.8 % of the sample is in favour of homeopathic drugs, while 23.2 % had already used an homeopathic anti-tussive syrup, and 27.6 % of subjects are really interested in using the homeopathic approach. The willingness to pay for an effective anti-tussive remedy was: 46.3 % up to 10 €; 27.8 % up to 20 €, and 13.3 % more than 20 €. Cough confirms its high impact in Italy, and a substantial proportion of individuals regards cough as "a disease". Only one out of three Italians refers to their doctor, but when cough is already persistent. Cough in children is much more feared than in adults. The majority of Italians have a proper and conservative position versus both antibiotic and the systemic steroid uses against cough. The Italian attitude to aerosol therapy confirms very high. Differently from the cough guidelines, anti-tussive drugs are highly valued among Italian people. The attitude and the interest to homeopathic anti-tussive remedies proves high. Finally, the willingness to pay for an effective anti-tussive remedy is quite high in Italy.

Effects of the Affordable Care Act's young adult insurance expansion on prescription drug insurance coverage, utilization, and expenditures.

PubMed

Look, Kevin A; Arora, Prachi

2016-01-01

The US Affordable Care Act (ACA) extended the age of eligibility for young adults to remain on their parents' health insurance plans in order to address the disproportionate number of uninsured young adults in the United States. Effective September 23, 2010, the ACA has required all private health insurance plans to cover dependents until the age of 26. However, it is unknown whether the ACA dependent coverage expansion had an impact on prescription drug insurance or the use of prescription drugs. To evaluate short-term changes in prescription health insurance coverage, prescription drug insurance coverage, prescription drug use, and prescription drug expenditures following implementation of the ACA young adult insurance expansion using national data from 2009 and 2011. Full-year health insurance coverage increased 4.9 percentage points during the study period, which was mainly due to increases in private health insurance among middle- and high-income young adults. In contrast, full-year prescription drug insurance coverage increased 5.5 percentage points and was primarily concentrated among high-income young adults. Although no significant short-term changes in overall prescription drug use were observed, a 30% decrease in out-of-pocket expenditures was seen among young adults. While the main goal of the ACA's young adult insurance expansion was to increase health insurance coverage among young adults, it also had the unintended positive effect of increasing coverage for prescription drug insurance. Additionally, young adults experienced substantial decreases in out-of-pocket spending for prescription drugs. It is important for evaluations of health care policies to assess both intended and unintended outcomes to better understand the implications for the broader health system. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

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...

A Review of US Drug Costs Relevant to Medicare, Medicaid, and Commercial Insurers Post-Affordable Care Act Enactment, 2010-2016.

PubMed

McRae, Jacquelyn; Vogenberg, F Randy; Beaty, Silky Webb; Mearns, Elizabeth; Varga, Stefan; Pizzi, Laura

2017-02-01

Since passage of the Affordable Care Act (ACA) in 2010, US stakeholders are increasingly being held accountable for the value of healthcare services and drugs administered to patients. Pharmacoeconomic analyses offer one method of demonstrating a product's value, yet there is a lack of resources specific to US drug costs relevant to each stakeholder. The aim of this study was to review current US drug costs (post-ACA). A literature review aimed at finding evidence on outpatient prescription drug costs was performed using the following sources: PubMed, governmental agencies, news websites, the Academy of Managed Care Pharmacy (AMCP) website, and Google Scholar. Articles were limited to those published in the years "2010-2016" and the "English" language, and those that described drug acquisition costs, reimbursement costs, and rebates or discounting for Medicare, Medicaid, and commercial payors. The Drug Cost Focus Group (DCFG) was convened to supplement the literature review; the DCFG provided their expertise on US drug costs and emerging issues affecting drug costs. ACA legislation increased drug rebates for manufacturers participating in the Medicaid Drug Rebate Program. Acquisition costs commonly referred to in the literature include the wholesale acquisition cost and average manufacture price. Drugs reimbursed by Medicaid are currently based on the actual acquisition cost and ACA-Federal Upper Limit. Evidence suggests that reimbursement methods in the public market are varied. Current gaps in the literature regarding commercial insurers' drug costs (post-ACA) present barriers to the application of relevant drug costs to pharmacoeconomic analyses.

Opioid tolerance and urine drug testing among initiates of extended-release or long-acting opioids in Food and Drug Administration's Sentinel System.

PubMed

Larochelle, Marc R; Cocoros, Noelle M; Popovic, Jennifer; Dee, Elizabeth C; Kornegay, Cynthia; Ju, Jing; Racoosin, Judith A

A risk evaluation and mitigation strategy for extended-release and long-acting (ER/LA) opioid analgesics was approved by the Food and Drug Administration in 2012. Our objective was to assess frequency of opioid tolerance and urine drug testing for individuals initiating ER/LA opioid analgesics. Retrospective cohort study. Sentinel, a distributed database with electronic healthcare data on >190 million predominantly commercially insured members. Members under age 65 initiating ER/LA opioid analgesics between January 2009 and December 2013. We examined the proportion of opioid-tolerant-only ER/LA opioid analgesic initiates meeting tolerance criteria: receipt of ≥30 mg oxycodone equivalents per day in 7 days prior to the first opioid-tolerant-only dispensing. We separately examined the proportion of new users of extended-release oxycodone (ERO) and other ER/LA opioid analgesics with a claim for a urine drug test in the 30 days prior to, and separately for the 183 days after, dispensing. We identified 79,824 ERO, 7,343 extended-release hydromorphone, and 91,778 transdermal fentanyl opi-oid-tolerant-only episodes. Tolerance criteria were met in 64 percent of ERO, 64 percent of extended-release hydromorphone and 40 percent of transdermal fentanyl episodes. We identified 210,581 incident ERO and 311,660 other ER/LA opioid analgesic episodes. Use of urine drug testing for ERO compared with other ER/LA opioid analgesics was: 4 percent vs 14 percent respectively in the 30 days prior to initiation and 9 percent vs 23 percent respectively in the 183 days following initiation. These results suggest potential areas for improving appropriate ER/LA opioid analgesic prescribing practices.

78 FR 46977 - Generic Drug User Fee-Abbreviated New Drug Application, Prior Approval Supplement, Drug Master...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-02

... costs to total FDA costs of the review of human generic drug activities for the first 3 of the preceding... review of human generic drug activities. Since the first year of the Generic Drug User Fee Program has... activities other than PC&B (see section 744B(c)(1)(C) of the FD&C Act). Table 3 of this document provides the...

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

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

Brand-name drug, generic drug, orphan drug. Pharmacological therapy with biosimilar drugs - provision of due diligence in the treatment process.

PubMed

Zajdel, Justyna; Zajdel, Radosław

2013-01-01

Due diligence in the process of provision of healthcare services refers, among other elements, to the application of pharmacological therapy at a time which offers the greatest chance for a successful outcome of treatment, i.e. for achieving the optimum expected effect understood as an improvement in the patient's health, reduction of health risks or elimination of the disease. However, due diligence may also refer to actions aimed at ensuring that neither the patient nor the healthcare payer is required to incur unreasonable costs in the process of treatment. The validity of that statement stems not only from normative acts but also from ethical standards laid down in the Medical Code of Ethics (Article 57 section 2). It often happens that the provision of optimal treatment calls for deviations from the formal provisions included in Summary Product Characteristics (SPCs), and the application of drugs that are bioequivalent to reference drugs, which translates into a significant reduction of costs. The present study addresses the problem of acceptability of a specific form of drug substitution consisting in the replacement of a reference drug with a generic drug. Also explored are legal aspects associated with the possibility of therapy based on "off-label use". The study reviews normative acts existing in the Polish and EU legislation. It also provides a clear definition of orphan drug, which has made it possible to make a distinction and investigate mutual relations between the concepts of brand-name (reference) drug, orphan drug and generic drug.

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.

Progesterone for Prevention of Preterm Birth: Shortcomings and Unintended Consequences of the Orphan Drug Act.

PubMed

Gee, Rebekah E; Kuy, SreyRam; Karas, Laura O

2017-12-01

Preterm birth is a problem of major public health significance that continues to plague our country despite the existence of a therapy, 17α-hydroxyprogesterone caproate, with known efficacy in reducing the risk of spontaneous preterm birth among high-risk women. Over the past several years, the Louisiana Department of Health has undertaken a robust, multifaceted initiative to improve access to 17α-hydroxyprogesterone caproate, which resulted in a 3.5-fold increase in the percentage of eligible high-risk pregnant women in the Medicaid program who received the therapy between 2013 and 2016. Yet despite Louisiana's progress, the vast majority of the eligible population still fails to receive 17α-hydroxyprogesterone caproate. In this Current Commentary, we argue that the high price of progesterone since U.S. Food and Drug Administration approval has unnecessarily complicated access, and our nation has potentially suffered nearly 60,000 avoidable premature births as a consequence. We present the history of the orphan drug approval and manufacturer-imposed price increase for injectable progesterone, the interplay between the drug's high price and the persistence of racial and ethnic disparities in preterm birth, which are particularly germane in Louisiana, and Louisiana's broad-reaching efforts to improve progesterone coverage. The story of 17α-hydroxyprogesterone caproate highlights the durable barriers that high prices place in the way of access and helps illuminate the shortcomings and unintended consequences of the Orphan Drug Act. This case, however, is not an outlier; it is the far-too-common product of monopoly pricing in the U.S. pharmaceutical market, inadvertently bolstered by existing law, at the expense of affordability and patient access.

Implementation of the Provision of the Comprehensive Addiction and Recovery Act of 2016 Relating to the Dispensing of Narcotic Drugs for Opioid Use Disorder. Final rule.

PubMed

2018-01-23

The Comprehensive Addiction and Recovery Act (CARA) of 2016, which became law on July 22, 2016, amended the Controlled Substances Act (CSA) to expand the categories of practitioners who may, under certain conditions on a temporary basis, dispense a narcotic drug in Schedule III, IV, or V for the purpose of maintenance treatment or detoxification treatment. Separately, the Department of Health and Human Services, by final rule effective August 8, 2016, increased to 275 the maximum number of patients that a practitioner may treat for opioid use disorder without being separately registered under the CSA for that purpose. The Drug Enforcement Administration (DEA) is hereby amending its regulations to incorporate these statutory and regulatory changes.

Brand-name drug, generic drug, orphan drug. Pharmacological therapy with biosimilar drugs – provision of due diligence in the treatment process

PubMed Central

Zajdel, Justyna

2013-01-01

Due diligence in the process of provision of healthcare services refers, among other elements, to the application of pharmacological therapy at a time which offers the greatest chance for a successful outcome of treatment, i.e. for achieving the optimum expected effect understood as an improvement in the patient's health, reduction of health risks or elimination of the disease. However, due diligence may also refer to actions aimed at ensuring that neither the patient nor the healthcare payer is required to incur unreasonable costs in the process of treatment. The validity of that statement stems not only from normative acts but also from ethical standards laid down in the Medical Code of Ethics (Article 57 section 2). It often happens that the provision of optimal treatment calls for deviations from the formal provisions included in Summary Product Characteristics (SPCs), and the application of drugs that are bioequivalent to reference drugs, which translates into a significant reduction of costs. The present study addresses the problem of acceptability of a specific form of drug substitution consisting in the replacement of a reference drug with a generic drug. Also explored are legal aspects associated with the possibility of therapy based on “off-label use”. The study reviews normative acts existing in the Polish and EU legislation. It also provides a clear definition of orphan drug, which has made it possible to make a distinction and investigate mutual relations between the concepts of brand-name (reference) drug, orphan drug and generic drug. PMID:24592133

7 CFR 29.41 - The Appropriations Act.

Code of Federal Regulations, 2014 CFR

2014-01-01

... REGULATIONS TOBACCO INSPECTION Regulations Definitions § 29.41 The Appropriations Act. The Agriculture, Rural Development, Food and Drug Administration, and Related Agencies Appropriations Act for 2002 (Pub. L. 107-76... 7 Agriculture 2 2014-01-01 2014-01-01 false The Appropriations Act. 29.41 Section 29.41...

7 CFR 29.41 - The Appropriations Act.

Code of Federal Regulations, 2011 CFR

2011-01-01

... REGULATIONS TOBACCO INSPECTION Regulations Definitions § 29.41 The Appropriations Act. The Agriculture, Rural Development, Food and Drug Administration, and Related Agencies Appropriations Act for 2002 (Pub. L. 107-76... 7 Agriculture 2 2011-01-01 2011-01-01 false The Appropriations Act. 29.41 Section 29.41...

7 CFR 29.41 - The Appropriations Act.

Code of Federal Regulations, 2010 CFR

2010-01-01

... REGULATIONS TOBACCO INSPECTION Regulations Definitions § 29.41 The Appropriations Act. The Agriculture, Rural Development, Food and Drug Administration, and Related Agencies Appropriations Act for 2002 (Pub. L. 107-76... 7 Agriculture 2 2010-01-01 2010-01-01 false The Appropriations Act. 29.41 Section 29.41...

7 CFR 29.41 - The Appropriations Act.

Code of Federal Regulations, 2013 CFR

2013-01-01

... REGULATIONS TOBACCO INSPECTION Regulations Definitions § 29.41 The Appropriations Act. The Agriculture, Rural Development, Food and Drug Administration, and Related Agencies Appropriations Act for 2002 (Pub. L. 107-76... 7 Agriculture 2 2013-01-01 2013-01-01 false The Appropriations Act. 29.41 Section 29.41...

7 CFR 29.41 - The Appropriations Act.

Code of Federal Regulations, 2012 CFR

2012-01-01

... REGULATIONS TOBACCO INSPECTION Regulations Definitions § 29.41 The Appropriations Act. The Agriculture, Rural Development, Food and Drug Administration, and Related Agencies Appropriations Act for 2002 (Pub. L. 107-76... 7 Agriculture 2 2012-01-01 2012-01-01 false The Appropriations Act. 29.41 Section 29.41...

The Regulation of Medical Computer Software as a “Device” under the Food, Drug, and Cosmetic Act

PubMed Central

Brannigan, Vincent

1986-01-01

Recent developments in computer software have raised the possibility that federal regulators may claim to control medical computer software as a “device” under the Food, Drug and Cosmetic Act. The purpose of this paper is to analyze the FDCA to determine whether computer software is included in the statutory scheme, examine constitutional arguments relating to computer software, and discuss regulatory principles that should be taken into account when deciding appropriate regulation. This paper is limited to computer program output used by humans in deciding appropriate medical therapy for a patient.

The effect of bariatric surgery on direct-acting oral anticoagulant drug levels.

PubMed

Rottenstreich, Amihai; Barkai, Aviv; Arad, Ariela; Raccah, Bruria Hirsh; Kalish, Yosef

2018-03-01

To determine direct-acting oral anticoagulant (DOAC) blood levels in post-bariatric surgery (BS) patients treated with long-term anticoagulation therapy. We identified from medical records patients who underwent BS during 2005-2016 and who were treated with DOACs. We offered testing DOAC blood levels to these patients and to age, sex, body mass index, and serum creatinine-matched individuals treated by DOACs who did not undergo BS. Overall, 36 individuals were enrolled, 18 post-BS patients and 18 control subjects. Of the post-BS patients, 12 underwent laparoscopic sleeve gastrectomy, 4 laparoscopic adjustable gastric banding and 2 laparoscopic Roux-en-Y gastric bypass surgery. Median time lapsed from surgery until study inclusion was 4.9years. Five post-BS patients had peak drug levels below expected levels compared to none of the control subjects (P=0.05). For patients who used apixaban (n=9) and dabigatran (n=2), peak drug levels were within the expected range. In contrast, for the 7 patients who used rivaroxaban, levels were below the expected range in 5, including all four who underwent sleeve gastrectomy and one following adjustable gastric banding. Peak rivaroxaban levels were significantly lower in the post-BS than the control group (P=0.02). This preliminary study suggests that all DOACs, particularly rivaroxaban, be cautiously used following BS, if used at all. Given that vitamin-K antagonists can be easily monitored, they may be a better choice, until more data on DOAC use in this patient population are available. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pharmacokinetics of rectal drug administration, Part I. General considerations and clinical applications of centrally acting drugs.

PubMed

van Hoogdalem, E; de Boer, A G; Breimer, D D

1991-07-01

Generally, oral administration is the route of choice in the daily practice of pharmacotherapy. However, in some circumstances this is impractical or even impossible (during nausea and vomiting or convulsions, in uncooperative patients and before surgery). In these cases, the rectal route may represent a practical alternative and rectal administration is now well accepted for delivering, for example, anticonvulsants, non-narcotic and narcotic analgesics, theophylline, antiemetics and antibacterial agents, and for inducing anaesthesia in children. It may also represent an interesting alternative to intravenous or other injection routes of drug administration. The rate and extent of rectal drug absorption are often lower than with oral absorption, possibly an inherent factor owing to the relatively small surface area available for drug uptake. In addition, the composition of the rectal formulation (solid vs liquid, nature of the suppository base) appears to be an important factor in the absorption process by determining the pattern of drug release. This relation between formulation and drug uptake has been clearly demonstrated for drugs like diazepam, paracetamol (acetaminophen), indomethacin, methadone and diflunisal. Coadministration of absorption-promoting agents (surfactants, sodium salicylate, enamines) represents another approach towards manipulating rectal drug absorption, although this concept requires further research concerning both efficacy and safety. For a number of drugs the extent of rectal absorption has been reported to exceed oral values, which may reflect partial avoidance of hepatic first-pass metabolism after rectal delivery. This phenomenon has been reported for morphine, metoclopramide, ergotamine, lidocaine (lignocaine) and propranolol. Rectal drug delivery in a site- and rate-controlled manner using osmotic pumps or hydrogel formulations may provide opportunities for manipulating systemic drug concentrations and drug effects. The extent of

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...

[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.

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...

High HCV cure rates for people who use drugs treated with direct acting antiviral therapy at an urban primary care clinic.

PubMed

Norton, Brianna L; Fleming, Julia; Bachhuber, Marcus A; Steinman, Meredith; DeLuca, Joseph; Cunningham, Chinazo O; Johnson, Nirah; Laraque, Fabienne; Litwin, Alain H

2017-09-01

Though direct acting antivirals (DAAs) promise high cure rates, many providers and payers remain concerned about successful treatment for people who use drugs (PWUD), even among those engaged in opioid agonist treatment (OAT). The efficacy of DAAs among PWUD in real-world settings is unclear. We conducted a cohort study of patients initiating HCV treatment between January 2014 and August 2015 (n=89) at a primary care clinic in the Bronx, NY. Onsite HCV treatment with DAAs was performed by an HCV specialist, with support from a care coordinator funded by the NYC Department of Health. We identified four categories of drug use and drug treatment: (1) no active drug use/not receiving OAT (defined as non-PWUD); (2) no active drug use/receiving OAT; (3) active drug use/not receiving OAT; and (4) active drug use/receiving OAT. The primary outcome was SVR at 12 weeks post-treatment. Overall SVR rates were 95% (n=41/43) for non-PWUD and 96% (n=44/46) for patients actively using drugs and/or receiving OAT [p=0.95]. There were no differences in SVR rates by drug use or drug treatment category. Compared to non-PWUD, those with no active drug use/receiving OAT had 100% SVR (n=15/15; p=1.0), those actively using drugs/not receiving OAT had 90% SVR (n=9/10; p=0.47), and those actively using drugs/receiving OAT had 95% SVR (20/21; p=1.0). Regardless of active drug use or OAT, patients who received DAA therapy at an urban primary care clinic achieved high HCV cure rates. We found no clinical evidence to justify restricting access to HCV treatment for patients actively using drugs and/or receiving OAT. Copyright © 2017 Elsevier B.V. All rights reserved.

High HCV cure rates for people who use drugs treated with direct acting antiviral therapy at an urban primary care clinic

PubMed Central

Norton, Brianna L.; Fleming, Julia; Bachhuber, Marcus A.; Steinman, Meredith; DeLuca, Joseph; Cunningham, Chinazo O.; Johnson, Nirah; Laraque, Fabienne; Litwin, Alain H.

2018-01-01

Background Though direct acting antivirals (DAAs) promise high cure rates, many providers and payers remain concerned about successful treatment for people who use drugs (PWUD), even among those engaged in opioid agonist treatment (OAT). The efficacy of DAAs among PWUD in real-world settings is unclear. Methods We conducted a cohort study of patients initiating HCV treatment between January 2014 and August 2015 (n = 89) at a primary care clinic in the Bronx, NY. Onsite HCV treatment with DAAs was performed by an HCV specialist, with support from a care coordinator funded by the NYC Department of Health. We identified four categories of drug use and drug treatment: (1) no active drug use/not receiving OAT (defined as non-PWUD); (2) no active drug use/receiving OAT; (3) active drug use/not receiving OAT; and (4) active drug use/receiving OAT. The primary outcome was SVR at 12 weeks post-treatment. Results Overall SVR rates were 95% (n = 41/43) for non-PWUD and 96% (n = 44/46) for patients actively using drugs and/or receiving OAT [p = 0.95]. There were no differences in SVR rates by drug use or drug treatment category. Compared to non-PWUD, those with no active drug use/receiving OAT had 100% SVR (n = 15/15; p = 1.0), those actively using drugs/not receiving OAT had 90% SVR (n = 9/10; p = 0.47), and those actively using drugs/receiving OAT had 95% SVR (20/21; p = 1.0). Conclusion Regardless of active drug use or OAT, patients who received DAA therapy at an urban primary care clinic achieved high HCV cure rates. We found no clinical evidence to justify restricting access to HCV treatment for patients actively using drugs and/or receiving OAT. PMID:28811158

Drugs acting on amino acid neurotransmitters.

PubMed

Meldrum, B S

1986-01-01

The most potent agents currently available for suppressing myoclonic activity in animals and humans act to enhance GABA-mediated inhibition and/or to diminish amino acid-induced excitation. Postsynaptic GABA-mediated inhibition plays an important role at the cortical level, diminishing the effect of augmented afferent activity and preventing pathologically enhanced output. Enhancement of GABAergic inhibition, principally at the cortical level but also at lower levels, by clonazepam and by valproate appears to be a predominant element in their antimyoclonic action. Studies in various animal models, including photically induced myoclonus in the baboon, P papio, indicate the value of other approaches to enhancing GABA-mediated inhibition. Among such approaches meriting evaluation in humans are inhibition of GABA-transaminase activity by gamma-vinyl GABA and action at some of the benzodiazepine receptors to enhance the action of GABA, as by the novel anticonvulsant beta-carbolines. Excitatory transmission mediated by dicarboxylic amino acids appears to play a role in myoclonus, especially at the spinal level, but also in the brainstem, cerebellum, basal ganglia, and cortex. Among various novel agents that act at the postsynaptic receptor site to antagonize such excitation, those specifically blocking excitation induced by aspartate and/or NMDA prevent myoclonic activity in a wide range of animal models. Further research is required before such agents can be evaluated in humans.

Using long-acting beta2-agonists safely: What will be the impact of the US Food and Drug Administration's panel recommendations?

PubMed

Smart, Brian A

2009-01-01

The US Food and Drug Administration (FDA) has launched an investigation into the safety of long-acting beta(2)-agonists (LABAs). While the impact of this investigation is yet to be seen, clinicians should be circumspect in the use of these agents and prescribe them according to the recommendations of current asthma guidelines, informing patients and their caretakers about potential risks. As clinical trials attempt to address the question of whether LABAs are safe for use in pediatric and adult populations, current data provide no clear answers. A special hearing of the FDA's Pulmonary-Allergy Drugs Advisory Committee, Drug Safety and Risk Management Advisory Committee, and Pediatric Advisory Committee attempted to seek consensus on the matter as it reviewed the results of controlled clinical trials and conducted a benefit:risk assessment of LABAs to make recommendations on their safety.

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...

Dextromethorphan abuse leading to assault, suicide, or homicide.

PubMed

Logan, Barry K; Yeakel, Jillian K; Goldfogel, Gary; Frost, Michael P; Sandstrom, Greg; Wickham, Dennis J

2012-09-01

Dextromethorphan is a commonly encountered antitussive medication which has found additional therapeutic use in the treatment of pseudobulbar disorder and as an adjunct to opiate use in pain management. Dextromethorphan at high doses has phencyclidine-like effects on the NMDA receptor system; recreational use of high doses has been found to cause mania and hallucinations. The toxicology and pharmacology of the drug in abuse are reviewed, and the historical literature of adverse psychiatric outcomes is assessed. Five new cases of dextromethorphan intoxication that resulted in assault, suicide, and homicide are reported, together with the corresponding toxicology results. Blood concentrations ranged from 300 to 19,000 μg/L. These results are compared with typical concentrations reported in therapeutic use and impaired driving cases. Based on these findings, dextromethorphan should be considered as a potential causative agent in subjects presenting with mania, psychosis, or hallucinations, and abusers are at risk for violent and self-destructive acts. © 2012 American Academy of Forensic Sciences.

[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

Effect of generic drug competition on the price of prescription drugs in Ontario.

PubMed Central

Lexchin, J

1993-01-01

OBJECTIVE: To analyse the potential effect of generic drug competition on prices in Ontario to assess the costs and benefits associated with Bill C-22 (An Act to amend the Patent Act). DESIGN: Comparison of the cost of the least and most expensive versions of all products sold by more than one manufacturer in 1991. The number of brand-name and generic drug companies marketing each of the products was recorded. RESULTS: Of 1599 products 437 (27.3%) were made by more than one company. Almost half (44.6%) of the 437 were sold by two companies. The more companies that sold a drug the greater the difference in price between the least and most expensive versions. Similarly, as the proportion of generic drug companies in competition increased, the greater the price difference. When competition was between generic drug companies only, the price spread was smaller than when it was between brand-name drug companies only. CONCLUSIONS: Generic drug competition can result in savings to the Ontario Drug Benefit Plan. A more in-depth analysis of the potential savings is necessary to fully assess the costs and benefits associated with Bill C-22. PMID:8439888

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...

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.

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.

Neurocircuitry of drug reward

PubMed Central

Ikemoto, Satoshi; Bonci, Antonello

2013-01-01

In recent years, neuroscientists have produced profound conceptual and mechanistic advances on the neurocircuitry of reward and substance use disorders. Here, we will provide a brief review of intracranial drug self-administration and optogenetic self-stimulation studies that identified brain regions and neurotransmitter systems involved in drug- and reward-related behaviors. Also discussed is a theoretical framework that helps to understand the functional properties of the circuitry involved in these behaviors. The circuitry appears to be homeostatically regulated and mediate anticipatory processes that regulate behavioral interaction with the environment in response to salient stimuli. That is, abused drugs or, at least, some may act on basic motivation and mood processes, regulating behavior-environment interaction. Optogenetics and related technologies have begun to uncover detailed circuit mechanisms linking key brain regions in which abused drugs act for rewarding effects. PMID:23664810

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.

Orphan drug development in the United States.

PubMed

Groft, S C

1985-05-01

Drug research and development in the U.S. tends to focus on drugs to treat common diseases because of the anticipated return on investment. To stimulate pharmaceutical manufacturers to pursue the development of drugs for rare conditions, the Orphan Drug Act was enacted by Congress on January 4, 1983. Under the provisions of this Act, the FDA can make recommendations on the investigations necessary for marketing approval; exclusive marketing privileges can be obtained; tax credits for expenses incurred are allowed; availability of orphan drugs on an investigational basis is encouraged; and the Orphan Product Board is established for the coordination of research efforts and their reimbursement. The effects of this legislation are evident in the continuing increase in orphan drug designations.

[Designer drugs in Finland].

PubMed

Tacke, Ulrich; den Hollander, Bjørnar; Simojoki, Kaarlo; Korpi, Esa R; Pihlainen, Katja; Alho, Hannu

2011-01-01

Designer drugs are synthetic psychotropic drugs which are marketed as "legal drugs". Their emergence, rapid spreading and unpredictable effects have challenged the health and substance abuse care. The slow process of classification of an abusable drug has provided too many possibilities for spreading the designer drugs. Once a certain substance receives an illegal drugs classification, dealers and users usually move to another, slightly different molecule that is still legal. In Finland, the Narcotics Act has been amended to the effect that the addition of a new substance to the illegal drug list does not require an amendment to the law.

Effects of landiolol, an ultra-short-acting beta1-selective blocker, on electrical storm refractory to class III antiarrhythmic drugs.

PubMed

Miwa, Yosuke; Ikeda, Takanori; Mera, Hisaaki; Miyakoshi, Mutsumi; Hoshida, Kyoko; Yanagisawa, Ryoji; Ishiguro, Haruhisa; Tsukada, Takehiro; Abe, Atsuko; Yusu, Satoru; Yoshino, Hideaki

2010-05-01

Occasionally it is difficult to inhibit electrical storm (ES) with standard pharmacological treatment. In the present study the effect of landiolol, an ultra-short-acting beta(1)-selective blocker, on ES refractory to class III antiarrhythmic drugs was evaluated. The study group comprised 42 consecutive patients who developed ES for which intravenous class III antiarrhythmic drugs, such as amiodarone and nifekalant, were ineffective. Landiolol was administered intravenously with an initial dose of 2.5 microg x kg(-1) x min(-1), which was doubled if it was ineffective, up to a maximum dose of 80 microg x kg(-1) x min(-1). Landiolol inhibited ES in 33 patients (79%) at a mean dose of 7.5+/-12.2 microg x kg(-1) x min(-1). All patients in whom landiolol was ineffective died of arrhythmia. Of the 33 patients in whom landiolol was effective, 25 survived and were discharged (60% of all patients). Landiolol significantly decreased heart rate (P<0.0001), but did not affect blood pressure. Landiolol was not discontinued for adverse effects in any of the responders. Age, APACHE II score, and pH of arterial blood gas differed significantly between the responders and nonresponders. Landiolol is useful as a life-saving drug for class III antiarrhythmic drug-resistant ES. The main mechanism of ES refractory to class III antiarrhythmic drugs could be abnormal automaticity but not reentry.

Physiologically-Based Pharmacokinetic Modeling of Macitentan: Prediction of Drug-Drug Interactions.

PubMed

de Kanter, Ruben; Sidharta, Patricia N; Delahaye, Stéphane; Gnerre, Carmela; Segrestaa, Jerome; Buchmann, Stephan; Kohl, Christopher; Treiber, Alexander

2016-03-01

Macitentan is a novel dual endothelin receptor antagonist for the treatment of pulmonary arterial hypertension (PAH). It is metabolized by cytochrome P450 (CYP) enzymes, mainly CYP3A4, to its active metabolite ACT-132577. A physiological-based pharmacokinetic (PBPK) model was developed by combining observations from clinical studies and physicochemical parameters as well as absorption, distribution, metabolism and excretion parameters determined in vitro. The model predicted the observed pharmacokinetics of macitentan and its active metabolite ACT-132577 after single and multiple dosing. It performed well in recovering the observed effect of the CYP3A4 inhibitors ketoconazole and cyclosporine, and the CYP3A4 inducer rifampicin, as well as in predicting interactions with S-warfarin and sildenafil. The model was robust enough to allow prospective predictions of macitentan-drug combinations not studied, including an alternative dosing regimen of ketoconazole and nine other CYP3A4-interacting drugs. Among these were the HIV drugs ritonavir and saquinavir, which were included because HIV infection is a known risk factor for the development of PAH. This example of the application of PBPK modeling to predict drug-drug interactions was used to support the labeling of macitentan (Opsumit).

Ozone-Induced Hypertussive Responses in Rabbits and Guinea Pigs

PubMed Central

Clay, Emlyn; Patacchini, Riccardo; Trevisani, Marcello; Preti, Delia; Branà, Maria Pia; Spina, Domenico

2016-01-01

Cough remains a major unmet clinical need, and preclinical animal models are not predictive for new antitussive agents. We have investigated the mechanisms and pharmacological sensitivity of ozone-induced hypertussive responses in rabbits and guinea pigs. Ozone induced a significant increase in cough frequency and a decrease in time to first cough to inhaled citric acid in both conscious guinea pigs and rabbits. This response was inhibited by the established antitussive drugs codeine and levodropropizine. In contrast to the guinea pig, hypertussive responses in the rabbit were not inhibited by bronchodilator drugs (β2 agonists or muscarinic receptor antagonists), suggesting that the observed hypertussive state was not secondary to bronchoconstriction in this species. The ozone-induced hypertussive response in the rabbit was inhibited by chronic pretreatment with capsaicin, suggestive of a sensitization of airway sensory nerve fibers. However, we could find no evidence for a role of TRPA1 in this response, suggesting that ozone was not sensitizing airway sensory nerves via activation of this receptor. Whereas the ozone-induced hypertussive response was accompanied by a significant influx of neutrophils into the airway, the hypertussive response was not inhibited by the anti-inflammatory phosphodiesterase 4 inhibitor roflumilast at a dose that clearly exhibited anti-inflammatory activity. In summary, our results suggest that ozone-induced hypertussive responses to citric acid may provide a useful model for the investigation of novel drugs for the treatment of cough, but some important differences were noted between the two species with respect to sensitivity to bronchodilator drugs. PMID:26837703

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...

[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.

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...

Drugs and Crime: The Relationship of Drug Use and Concomitant Criminal Behavior. Research Issues 17.

ERIC Educational Resources Information Center

Austin, Gregory A., Ed.; Lettieri, Dan J., Ed.

This volume of abstracts of major research and theoretical studies dealing with the relationship between drug use, criminal behavior and the law is concerned with criminal acts other than the possession of, or trafficking in, illicit drugs. Included are 107 selected studies categorized into seven major topic areas: Reviews and Theories, Drug Use…

The common antitussive agent dextromethorphan protects against hyperoxia-induced cell death in established in vivo and in vitro models of neonatal brain injury.

PubMed

Posod, A; Pinzer, K; Urbanek, M; Wegleiter, K; Keller, M; Kiechl-Kohlendorfer, U; Griesmaier, E

2014-08-22

Preterm infants are prematurely subjected to relatively high oxygen concentrations, even when supplemental oxygen is not administered. There is increasing evidence to show that an excess of oxygen is toxic to the developing brain. Dextromethorphan (DM), a frequently used antitussive agent with pleiotropic mechanisms of action, has been shown to be neuroprotective in various models of central nervous system pathology. Due to its numerous beneficial properties, it might also be able to counteract detrimental effects of a neonatal oxygen insult. The aim of the current study was to evaluate its therapeutic potential in established cell culture and rodent models of hyperoxia-induced neonatal brain injury. For in vitro studies pre- and immature oligodendroglial (OLN-93) cells were subjected to hyperoxic conditions for 48 h after pre-treatment with increasing doses of DM. For in vivo studies 6-day-old Wistar rat pups received a single intraperitoneal injection of DM in two different dosages prior to being exposed to hyperoxia for 24h. Cell viability and caspase-3 activation were assessed as outcome parameters at the end of exposure. DM significantly increased cell viability in immature oligodendroglial cells subjected to hyperoxia. In pre-oligodendroglial cells cell viability was not significantly affected by DM treatment. In vivo caspase-3 activation induced by hyperoxic exposure was significantly lower after administration of DM in gray and white matter areas. In control animals kept under normoxic conditions DM did not significantly influence caspase-3-dependent apoptosis. The present results indicate that DM is a promising and safe treatment strategy for neonatal hyperoxia-induced brain injury that merits further investigation. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

DrugPath: a database for academic investigators to match oncology molecular targets with drugs in development.

PubMed

Shah, Eric D; Fisch, Brandon M A; Arceci, Robert J; Buckley, Jonathan D; Reaman, Gregory H; Sorensen, Poul H; Triche, Timothy J; Reynolds, C Patrick

2014-05-01

Academic laboratories are developing increasingly large amounts of data that describe the genomic landscape and gene expression patterns of various types of cancers. Such data can potentially identify novel oncology molecular targets in cancer types that may not be the primary focus of a drug sponsor's initial research for an investigational new drug. Obtaining preclinical data that point toward the potential for a given molecularly targeted agent, or a novel combination of agents requires knowledge of drugs currently in development in both the academic and commercial sectors. We have developed the DrugPath database ( http://www.drugpath.org ) as a comprehensive, free-of-charge resource for academic investigators to identify agents being developed in academics or industry that may act against molecular targets of interest. DrugPath data on molecular targets overlay the Michigan Molecular Interactions ( http://mimi.ncibi.org ) gene-gene interaction map to facilitate identification of related agents in the same pathway. The database catalogs 2,081 drug development programs representing 751 drug sponsors and 722 molecular and genetic targets. DrugPath should assist investigators in identifying and obtaining drugs acting on specific molecular targets for biological and preclinical therapeutic studies.

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

[Caffeine: a nutrient, a drug or a drug of abuse].

PubMed

Pardo Lozano, Ricardo; Alvarez García, Yolanda; Barral Tafalla, Diego; Farré Albaladejo, Magí

2007-01-01

Coffee, tea, chocolate and caffeinated drinks are the main sources of caffeine, which is consumed in almost all ages and socioeconomic levels. Caffeine acts as a non-selective adenosine receptor antagonist in the central nervous system. Its main effects are as psychostimulant, acting in addition on the respiratory, muscular and cardiovascular systems. Basically, caffeine is metabolized by the hepatic cytochrome P-450 1A2 enzymes (CYP1A2). Several drugs can interact with its metabolism. The observed interindividual differences of its effects can be explained by variations in its metabolism. The main therapeutic use of caffeine is bronchodilator in respiratory diseases. Other possible uses are under investigation. Acute or chronic consumption of caffeine can induce several adverse effects, including intoxication that can be lethal. Finally, caffeine can be considered a drug of abuse. It has positive reinforcing actions, produces tolerance, and a withdrawal syndrome after stopping its consumption. Caffeine can cause different mental disorders such as dependence, which is not included in the DSM-IV-R, withdrawal syndrome and intoxication. Depending on its use, caffeine can be considered a nutrient, a drug or a drug of abuse.

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.

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.

78 FR 35117 - Orphan Drug Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-12

...The Food and Drug Administration (FDA) is issuing final regulations amending the 1992 Orphan Drug Regulations issued to implement the Orphan Drug Act. These amendments are intended to clarify regulatory provisions and make minor improvements to address issues that have arisen since those regulations were issued.

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.

Indolealkylamines: biotransformations and potential drug-drug interactions.

PubMed

Yu, Ai-Ming

2008-06-01

Indolealkylamine (IAA) drugs are 5-hydroxytryptamine (5-HT or serotonin) analogs that mainly act on the serotonin system. Some IAAs are clinically utilized for antimigraine therapy, whereas other substances are notable as drugs of abuse. In the clinical evaluation of antimigraine triptan drugs, studies on their biotransformations and pharmacokinetics would facilitate the understanding and prevention of unwanted drug-drug interactions (DDIs). A stable, principal metabolite of an IAA drug of abuse could serve as a useful biomarker in assessing intoxication of the IAA substance. Studies on the metabolism of IAA drugs of abuse including lysergic acid amides, tryptamine derivatives and beta-carbolines are therefore emerging. An important role for polymorphic cytochrome P450 2D6 (CYP2D6) in the metabolism of IAA drugs of abuse has been revealed by recent studies, suggesting that variations in IAA metabolism, pharmaco- or toxicokinetics and dynamics can arise from distinct CYP2D6 status, and CYP2D6 polymorphism may represent an additional risk factor in the use of these IAA drugs. Furthermore, DDIs with IAA agents could occur additively at the pharmaco/toxicokinetic and dynamic levels, leading to severe or even fatal serotonin toxicity. In this review, the metabolism and potential DDIs of these therapeutic and abused IAA drugs are described.

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...

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.

75 FR 19463 - Procedures for Monitoring Bank Secrecy Act Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-14

... `Bank Secrecy Act' (``BSA''). The Money Laundering Control Act of 1986 further augmented the BSA's... savings associations. Specifically, Section 1359 of the Anti-Drug Abuse Act of 1986, Public Law 99-570... of Thrift Supervision (``OTS'') is charged with the responsibility to examine savings association...

Involvement of AMPA receptors in the antidepressant-like effects of dextromethorphan in mice.

PubMed

Nguyen, Linda; Matsumoto, Rae R

2015-12-15

Dextromethorphan (DM) is an antitussive with rapid acting antidepressant potential based on pharmacodynamic similarities to ketamine. Building upon our previous finding that DM produces antidepressant-like effects in the mouse forced swim test (FST), the present study aimed to establish the antidepressant-like actions of DM in the tail suspension test (TST), another well-established model predictive of antidepressant efficacy. Additionally, using the TST and FST, we investigated the role of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors in the antidepressant-like properties of DM because accumulating evidence suggests that AMPA receptors play an important role in the pathophysiology of depression and may contribute to the efficacy of antidepressant medications, including that of ketamine. We found that DM displays antidepressant-like effects in the TST similar to the conventional and fast acting antidepressants characterized by imipramine and ketamine, respectively. Moreover, decreasing the first-pass metabolism of DM by concomitant administration of quinidine (CYP2D6 inhibitor) potentiated antidepressant-like actions, implying DM itself has antidepressant efficacy. Finally, in both the TST and FST, pretreatment with the AMPA receptor antagonist NBQX (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide) significantly attenuated the antidepressant-like behavior elicited by DM. Together, the data show that DM exerts antidepressant-like actions through AMPA receptors, further suggesting DM may act as a safe and effective fast acting antidepressant drug. Copyright © 2015 Elsevier B.V. All rights reserved.

Economic Impacts of the Generic Drug User Fee Act Fee Structure.

PubMed

Dong, Ke; Boehm, Garth; Zheng, Qiang

2017-06-01

A Food and Drug Administration (FDA) Generic Drug User system, Generic Drug User Fee Amendment of 2012 (GDUFA), started October 1, 2012, and has been in place for over 3 years. There is controversy about the GDUFA fee structure but no analysis of GDUFA data that we could find. To look at the economic impact of the GDUFA fee structure. We compared the structure of GDUFA with that of other FDA Human Drug User fees. We then, using FDA-published information, analyzed where GDUFA facility and Drug Master File fees are coming from. We used the Orange Book to identify the sponsors of all approved Abbreviated New Drug Applications (ANDAs) and the S&P Capital IQ database to find the ultimate parent companies of sponsors of approved ANDAs. The key differences between the previous structure for Human Drug User fees and the GDUFA are as follows: GDUFA has no approved product fee and no first-time or small business fee exemptions and GDUFA charges facility fees from the time of filing and charges a foreign facility levy. Most GDUFA fees are paid by or on behalf of foreign entities. The top 10 companies hold nearly 50% of all approved ANDAs but pay about 14% of GDUFA facility fees. We conclude that the regressive nature of the GDUFA fee structure penalizes small, new, and foreign firms while benefiting the large established firms. A progressive fee structure in line with other human drug user fees is needed to ensure a healthy generic drug industry. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

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

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.

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...

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)

Cough Suppressant and Pharmacologic Protussive Therapy

PubMed Central

Bolser, Donald C.

2011-01-01

Background Cough-suppressant therapy, previously termed nonspecific antitussive therapy, incorporates the use of pharmacologic agents with mucolytic effects and/or inhibitory effects on the cough reflex itself. The intent of this type of therapy is to reduce the frequency and/or intensity of coughing on a short-term basis. Methods Data for this review were obtained from several National Library of Medicine (PubMed) searches (from 1960 to 2004), which were performed between May and September 2004, of the literature published in the English language, limited to human studies, using combinations of the search terms “cough,” “double-blind placebo-controlled,” “antitussive,” “mucolytic,” “cough clearance,” “common cold,” “protussive,” “guaifenesin,” “glycerol,” and “zinc.” Results Mucolytic agents are not consistently effective in ameliorating cough in patients with bronchitis, although they may be of benefit to this population in other ways. Peripheral and central antitussive agents can be useful in patients with chronic bronchitis, but can have little efficacy in patients with cough due to upper respiratory infection. Some protussive agents are effective in increasing cough clearance, but their long-term effectiveness has not been established. DNase is not effective as a protussive agent in patients with cystic fibrosis. Inhaled mannitol is acutely effective in this patient population, but its therapeutic potential must be investigated further. Conclusions These findings suggest that suppressant therapy is most effective when used for the short-term reduction of coughing. Relatively few drugs are effective as cough suppressants. PMID:16428717

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 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...

76 FR 51310 - Branded Prescription Drug Fee

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-18

... Branded Prescription Drug Fee AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of proposed... prescription drug fee imposed by the Affordable Care Act (ACA). The regulations affect persons engaged in the business of manufacturing or importing certain branded prescription drugs. The text of the temporary...

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.

Impact of Federal Regulatory Changes on Clinical Pharmacology and Drug Development: the Common Rule and the 21st Century Cures Act.

PubMed

Burris, James F; Puglisi, J Thomas

2017-10-05

the Food and Drug Administration (FDA), although it is not a signatory to the Common Rule. The 21st Century Cures Act, which became law in December 2016, enables faster drug approvals by expanding the kinds of evidence, beyond traditional clinical trials, that the FDA can consider when reviewing new drug applications. For example, the law allows greater use of surrogate markers and data from "real-world experience" to evaluate a drug's efficacy. The Cures Act requires HHS and the FDA to harmonize differences between the Common Rule and FDA regulations for protection of human subjects in research. © 2017, The American College of Clinical Pharmacology.

"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.

The effect of administering long-acting oxytetracycline and tilmicosin either by dart gun or by hand on injection site lesions and drug residues in beef cattle.

PubMed Central

Van Donkersgoed, J; VanderKop, M; Salisbury, C; Sears, L; Holowath, J

1999-01-01

Forty yearling cattle were injected intramuscularly with long-acting oxytetracycline and subcutaneously with tilmicosin by dart gun or by hand in a chute 28 days prior to slaughter. The drugs caused injection site lesions and antibiotic residues in the neck and thigh that varied by technique, dose, and site. PMID:12001341

78 FR 36711 - Food and Drug Administration Safety and Innovation Act Title VII-Drug Supply Chain; Standards for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-19

...: Food and Drug Administration, HHS. ACTION: Notification of public meeting; request for comments. SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing a public meeting regarding FDA's... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Chapter I [Docket Nos...

Orphan drugs: trends and issues in drug development.

PubMed

Rana, Proteesh; Chawla, Shalini

2018-04-12

Research in rare diseases has contributed substantially toward the current understanding in the pathophysiology of the common diseases. However, medical needs of patients with rare diseases have always been neglected by the society and pharmaceutical industries based on their small numbers and unprofitability. The Orphan Drug Act (1983) was the first serious attempt to address the unmet medical needs for patients with rare diseases and to provide impetus for the pharmaceutical industry to promote orphan drug development. The process of drug development for rare diseases is no different from common diseases but involves significant cost and infrastructure. Further, certain aspect of drug research may not be feasible for the rare diseases. The drug-approving authority must exercise their scientific judgment and ensure due flexibility while evaluating data at various stages of orphan drug development. The emergence of patent cliff combined with the government incentives led the pharmaceutical industry to realize the good commercial prospects in developing an orphan drug despite the small market size. Indeed, many drugs that were given orphan designation ended up being blockbusters. The orphan drug market is projected to reach $178 billion by 2020, and the prospects of research and development in rare diseases appears to be quite promising and rewarding.

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…

Managing drugs safely.

PubMed

van den Anker, John N

2005-02-01

There is hard data to show that newborn infants are more likely than adults to experience adverse reactions to drugs. Paradoxically, drug-related legislation to ensure safe and effective drug use in humans neglected neonates until 2002, when the Best Pharmaceuticals Act for Children was signed into law in the USA. The situation for neonates should now catch up with that for adults and neonates will be prescribed more licensed drugs in the near future. If we are to be able to analyze the underlying system errors to improve the safe use of drugs in the studied patient population, reporting of adverse drug events and reactions needs to happen in a blame free environment. In addition, computerized physician order entry will certainly further improve the current situation by preventing errors in ordering, transcribing, verifying, and transmitting medication orders.

Unclear loss of consciousness after clobutinol intake.

PubMed

Kirschbaum, Katrin M; Musshoff, Frank; Madea, Burkhard

2009-08-10

The case of a 13-month-old boy with a diagnosis of unclear unconsciousness is reported on. As the physical examination did not lead to any explanation of his condition, the administration of drugs in the context of Munchausen syndrome by proxy was suspected. Complex forensic-toxicological analyses using HPLC/UV, LC/MS/MS, and GC/MS identified ambroxol and clobutinol, two drugs that are indicated for acute respiratory diseases. No other central active compounds were detected. The accusation of intentional bodily injury raised against the parents could be rebutted, since the boy's unconsciousness could be explained with a rare but harmful side effect of the antitussive clobutinol.

Glutamatergic transmission in drug reward: implications for drug addiction.

PubMed

D'Souza, Manoranjan S

2015-01-01

Individuals addicted to drugs of abuse such as alcohol, nicotine, cocaine, and heroin are a significant burden on healthcare systems all over the world. The positive reinforcing (rewarding) effects of the above mentioned drugs play a major role in the initiation and maintenance of the drug-taking habit. Thus, understanding the neurochemical mechanisms underlying the reinforcing effects of drugs of abuse is critical to reducing the burden of drug addiction in society. Over the last two decades, there has been an increasing focus on the role of the excitatory neurotransmitter glutamate in drug addiction. In this review, pharmacological and genetic evidence supporting the role of glutamate in mediating the rewarding effects of the above described drugs of abuse will be discussed. Further, the review will discuss the role of glutamate transmission in two complex heterogeneous brain regions, namely the nucleus accumbens (NAcc) and the ventral tegmental area (VTA), which mediate the rewarding effects of drugs of abuse. In addition, several medications approved by the Food and Drug Administration that act by blocking glutamate transmission will be discussed in the context of drug reward. Finally, this review will discuss future studies needed to address currently unanswered gaps in knowledge, which will further elucidate the role of glutamate in the rewarding effects of drugs of abuse.

[Rational estimation of drug dosage through pharmacometric modeling: The case of a long-acting depot antipsychotic].

PubMed

Simon, N; Azorin, J-M

2015-04-01

Drug manufacturer seeking authorization to bring a newly medicinal compound to the market (Market Authorization Application) have to undertake various studies, each of them providing a specific report. It is however essential to know how to pool results in order to understand the behavior of the drug in all the situations likely to be encountered in clinical practice. The exploitation of these data is now carried out through pharmacometric analyzes which aim at quantifying the exposure and the response of a drug over time. These methods (named "population approach") are based on non-linear mixed effects model and therefore, on the identification of a mathematical model. A first step is to model the variations in concentrations over time by integrating the physio-pathological characteristics of the patients. At this stage, the Bayesian analysis is essential to identify and select the factors of interindividual variability. This pharmacokinetic (PK) modeling allows us to obtain the prescribed dose for each patient, but also their exposure. The second step consists in defining the relationship between exposure and effect: pharmacodynamic (PD) modeling. In psychiatry, the response can be the receptors' occupancy rate or the evolution of a clinical score (BPRS, PANSS…) over time. The final PK-PD model defines the target exposure, that is to say, the concentration values required to achieve maximum effect on the score studied without risking over-exposure. Ultimately, a Monte Carlo simulation will be conducted which will test the expected response for different doses and will facilitate a rational choice in dosage. Assessing the process behind the transition from an oral to a long-acting injectable form of an active ingredient such as aripiprazole can be done by following the same protocol. A 10- to 30-mg per day therapeutic range has thus been identified. The model incorporates all the identified factors of variability of aripiprazole (drug interactions and genetic

Medicare prescription drug discount cards.

PubMed

Bryant, Natasha

2004-01-01

With the passage of the Medicare Prescription Drug Improvement and Modernization Act of 2003 came the creation of a Part D drug benefit through Medicare. Until that benefit is implemented, Medicare has established a drug discount card program to help your clients save money on their outpatient prescription drug expenses. In this brief, we discuss the Medicare-approved discount cards--who is eligible, how they work, how your clients can best make important decisions about them, and what help is out there for people with low incomes.

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...

Once Upon a Synapse: A Drug Education Simulation in Three Acts.

ERIC Educational Resources Information Center

London, William M.

1989-01-01

An instructional activity designed to clarify pharmacological concepts related to drug use is described. The focus of the activity is a simulation, with student actors, of the effect of drugs and alcohol on the nervous system. (IAH)

Long-acting antiviral agents for HIV treatment

PubMed Central

Margolis, David A.; Boffito, Marta

2015-01-01

Purpose of review Long-acting antiretroviral (ARV) agents are currently under development for the treatment of chronic HIV infection. This review focuses on data recently produced on injectable ARVs for patients living with HIV/AIDS and on the patients’ perspectives on the use of these agents. Recent findings Crystalline nanoparticle formulations of the nonnucleoside reverse transcriptase inhibitor rilpivirine (TMC278) and of the HIV-1 integrase strand transfer inhibitor cabotegravir (GSK1265744) have progressed into phase II clinical trials as injectable maintenance therapy for patients living with HIV/AIDS with an undetectable viral load. Summary Phase II studies evaluating the coadministration of rilpivirine and cabotegravir intramuscularly to HIV-infected individuals with an undetectable viral load are currently underway. Rilpivirine and cabotegravir are characterized by different mechanisms of action against HIV and a favorable drug interaction profile, providing a rationale for coadministration. The high potency and low daily dosing requirements of oral cabotegravir and rilpivirine facilitate long-acting formulation development. Intramuscular dosing is preceded by an oral lead-in phase to assess safety and tolerability in individual participants. In addition to assessing the safety of injectable therapies in ongoing studies, it will be important to evaluate whether differences in drug adherence between injectable and oral therapies lead to different virologic outcomes, including rates of virologic failure and the emergence of resistance. Long-acting formulations may be associated with challenges, such as the management of adverse effects with persistent drug concentrations and the risk of virologic resistance, as drug concentrations decline following discontinuation. PMID:26049949

76 FR 59898 - Branded Prescription Drug Fee; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-28

... Branded Prescription Drug Fee; Correction AGENCY: Internal Revenue Service (IRS), Treasury. ACTION... prescription drug fee imposed by the Affordable Care Act. FOR FURTHER INFORMATION CONTACT: Celia Gabrysh, (202... as follows: 1. On Page 51311, column 2, under the part heading PART 51--BRANDED PRESCRIPTION DRUGS...

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

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...

Debating the Controlled Substances Act.

PubMed

Spillane, Joseph F

2004-10-05

In the United States, the basis of modern drug regulation is the Controlled Substances Act (CSA) of 1970. The CSA laid out the authority of the federal government and provided a framework within which all existing and new substances could be regulated on their abuse potential, safety, and medical utility. The debates over the CSA centered on several critical issues: where to place the authority to make scheduling designations, the impact of scheduling on drug research, and defining what constituted drug "abuse" for purposes of scheduling. Passage of the CSA was aided by broad language that provided a kind of "big tent" which could accommodate diverse points of view. A retrospective assessment of the CSA shows it to have greatly expanded federal administrative authority over the nation's drug supply, much as its authors intended. Other impacts of the CSA, however, are much less certain. This article concludes by highlighting the issues and questions that should guide future retrospective research on the efficacy of drug control regimes.

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.

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...

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

Code of Federal Regulations, 2013 CFR

2013-01-01

... 16 Commercial Practices 2 2013-01-01 2013-01-01 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...

Drug Testing Park Law Enforcement Officers.

ERIC Educational Resources Information Center

Murrell, Dan S.; And Others

1991-01-01

Discusses drug testing for park law enforcement officers, presenting drug screening guidelines for park managers. The article examines how to establish programs, whether to screen, legal aspects, and implications of the Handicap Act (which makes it difficult to dismiss employees claiming the handicap of substance abuse without providing…

Regulatory challenges in developing long-acting antiretrovirals for treatment and prevention of HIV infection.

PubMed

Arya, Vikram; Au, Stanley; Belew, Yodit; Miele, Peter; Struble, Kimberly

2015-07-01

To outline some of the regulatory challenges inherent to the development of long-acting antiretrovirals (ARVs) for the treatment or prevention of HIV infection. Despite advances in drug development that have reduced ARV dosing to once daily, suboptimal drug adherence remains an obstacle to successful HIV treatment. Further, large randomized trials of once daily oral ARVs for preexposure prophylaxis (PrEP) have shown that drug adherence correlates strongly with prophylactic effect and study outcomes. Thus, the prospect of developing long-acting ARVs, which may mitigate drug adherence issues, has attracted considerable attention lately. Because of their pharmacokinetic properties, the development of long-acting ARVs can present novel regulatory challenges. Chief among them is determining the appropriate dosing regimen, the need for an oral lead-in, and whether existing data with an approved oral agent, if available, can be leveraged for a treatment or prevention indication. For PrEP, because validated biomarkers are lacking, additional nonclinical studies and evaluation of tissue concentrations in multiple compartments may be necessary to identify optimal dosages. Study design and choice of controls for registrational trials of new long-acting PrEP agents might also prove challenging following the availability of an oral PrEP drug.

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.

Exercise acts as a drug; the pharmacological benefits of exercise

PubMed Central

Vina, J; Sanchis-Gomar, F; Martinez-Bello, V; Gomez-Cabrera, MC

2012-01-01

The beneficial effects of regular exercise for the promotion of health and cure of diseases have been clearly shown. In this review, we would like to postulate the idea that exercise can be considered as a drug. Exercise causes a myriad of beneficial effects for health, including the promotion of health and lifespan, and these are reviewed in the first section of this paper. Then we deal with the dosing of exercise. As with many drugs, dosing is extremely important to get the beneficial effects of exercise. To this end, the organism adapts to exercise. We review the molecular signalling pathways involved in these adaptations because understanding them is of great importance to be able to prescribe exercise in an appropriate manner. Special attention must be paid to the psychological effects of exercise. These are so powerful that we would like to propose that exercise may be considered as a psychoactive drug. In moderate doses, it causes very pronounced relaxing effects on the majority of the population, but some persons may even become addicted to exercise. Finally, there may be some contraindications to exercise that arise when people are severely ill, and these are described in the final section of the review. Our general conclusion is that exercise is so effective that it should be considered as a drug, but that more attention should be paid to the dosing and to individual variations between patients. PMID:22486393

20 CFR 638.511 - Drug use and abuse.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Drug use and abuse. 638.511 Section 638.511... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.511 Drug use and abuse. The Job... and education programs related to drug and alcohol use and abuse. ...

20 CFR 638.511 - Drug use and abuse.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Drug use and abuse. 638.511 Section 638.511... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.511 Drug use and abuse. The Job... and education programs related to drug and alcohol use and abuse. ...

76 FR 40306 - Harmonizing Schedule I Drug Requirements

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-08

... [Docket No. FMCSA-2011-0073] RIN 2126-AB35 Harmonizing Schedule I Drug Requirements AGENCY: Federal Motor... instructions for the medical examination report to clarify that drivers may not use Schedule I drugs and be.... Abbreviations CAA Clean Air Act. CFR Code of Federal Regulations. CMV Commercial Motor Vehicle. DEA Drug...

20 CFR 638.511 - Drug use and abuse.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Drug use and abuse. 638.511 Section 638.511... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.511 Drug use and abuse. The Job... and education programs related to drug and alcohol use and abuse. ...

Analysis of U.S. Food and Drug Administration food allergen recalls after implementation of the food allergen labeling and consumer protection act.

PubMed

Gendel, Steven M; Zhu, Jianmei

2013-11-01

To avoid potentially life-threatening reactions, food allergic consumers rely on information on food labels to help them avoid exposure to a food or ingredient that could trigger a reaction. To help consumers in the United States obtain the information that they need, the Food Allergen Labeling and Consumer Protection Act of 2004 defined a major food allergen as being one of eight foods or food groups and any ingredient that contains protein from one of these foods or food groups. A food that contains an undeclared major food allergen is misbranded under the U.S. Food, Drug, and Cosmetic Act and is subject to recall. Food allergen labeling problems are the most common cause of recalls for U.S. Food and Drug Administration (FDA)-regulated food products. To help understand why food allergen recalls continue to occur at a high rate, information on each food allergen recall that occurred in fiscal years 2007 through 2012 was obtained from the FDA recall database. This information was analyzed to identify the food, allergen, root cause, and mode of discovery for each food allergen recall. Bakery products were the most frequently recalled food type, and milk was the most frequently undeclared major food allergen. Use of the wrong package or label was the most frequent problem leading to food allergen recalls. These data are the first reported that indicate the importance of label and package controls as public health measures.

[Resistance to the antimalarial drugs].

PubMed

Venanzi, E; López-Vélez, R

2016-09-01

Malaria is one of the most widespread infectious diseases around the world with 214 million cases and 438,000 deaths in 2015. In the early twentieth century it was described for the first time the resistance to quinine and, since then, drug resistance to antimalarial drugs has spread up to represent a global challenge in the fight and control of malaria. Understanding the mechanisms, geography and monitoring tools that we can act against resistance to antimalarial drugs is critical to prevent its expansion.

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.

Code of Federal Regulations, 2013 CFR

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.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 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, 2012 CFR

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...

Federal Strategy for Prevention of Drug Abuse and Drug Trafficking, 1982. Prepared for the President Pursuant to the Drug Abuse Office and Treatment Act of 1972.

ERIC Educational Resources Information Center

Office of Policy Development, Washington, DC.

This document describes the Federal response to drug abuse and drug trafficking. The actions of President Reagan, in Executive Order 12368, establishing an official advisor on drug abuse policy matters, and the priorities, issues, and objectives (international cooperation, drug law enforcement, education and prevention, detoxification and…

[Mechanism of action of antiepileptic drugs].

PubMed

Saidón, Patricia

2003-01-01

Antiepileptic drugs (DAEs) act through different mechanisms of action: increase in central inhibition, inhibition of excitatorios mechanisms and modification of the excitability through their action on the ionic channels. Epilepsy is characterized by an abnormal and hypersynchronic unloading of a neuronal population. The activity of numerous drugs is associated to increase in gabaergic activity. Another group of drugs decreases excitatory mechanisms, through the inhibition of ionic channels, or through a decrease in the activity of the excitatory neurotransmitters. There are some of antiepileptic drugs, especially within the group of drugs of recent appearance, for wich the mechanism of action remains unknown.

[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.

75 FR 12555 - Prescription Drug User Fee Act; Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-16

... negotiations with the regulated industry on PDUFA reauthorization, we publish a notice in the Federal Register...)(2)) of the FD&C Act requires that before FDA begins negotiations with the regulated industry on...

Exploring drug-target interaction networks of illicit drugs.

PubMed

Atreya, Ravi V; Sun, Jingchun; Zhao, Zhongming

2013-01-01

Drug addiction is a complex and chronic mental disease, which places a large burden on the American healthcare system due to its negative effects on patients and their families. Recently, network pharmacology is emerging as a promising approach to drug discovery by integrating network biology and polypharmacology, allowing for a deeper understanding of molecular mechanisms of drug actions at the systems level. This study seeks to apply this approach for investigation of illicit drugs and their targets in order to elucidate their interaction patterns and potential secondary drugs that can aid future research and clinical care. In this study, we extracted 188 illicit substances and their related information from the DrugBank database. The data process revealed 86 illicit drugs targeting a total of 73 unique human genes, which forms an illicit drug-target network. Compared to the full drug-target network from DrugBank, illicit drugs and their target genes tend to cluster together and form four subnetworks, corresponding to four major medication categories: depressants, stimulants, analgesics, and steroids. External analysis of Anatomical Therapeutic Chemical (ATC) second sublevel classifications confirmed that the illicit drugs have neurological functions or act via mechanisms of stimulants, opioids, and steroids. To further explore other drugs potentially having associations with illicit drugs, we constructed an illicit-extended drug-target network by adding the drugs that have the same target(s) as illicit drugs to the illicit drug-target network. After analyzing the degree and betweenness of the network, we identified hubs and bridge nodes, which might play important roles in the development and treatment of drug addiction. Among them, 49 non-illicit drugs might have potential to be used to treat addiction or have addictive effects, including some results that are supported by previous studies. This study presents the first systematic review of the network

Exploring drug-target interaction networks of illicit drugs

PubMed Central

2013-01-01

Background Drug addiction is a complex and chronic mental disease, which places a large burden on the American healthcare system due to its negative effects on patients and their families. Recently, network pharmacology is emerging as a promising approach to drug discovery by integrating network biology and polypharmacology, allowing for a deeper understanding of molecular mechanisms of drug actions at the systems level. This study seeks to apply this approach for investigation of illicit drugs and their targets in order to elucidate their interaction patterns and potential secondary drugs that can aid future research and clinical care. Results In this study, we extracted 188 illicit substances and their related information from the DrugBank database. The data process revealed 86 illicit drugs targeting a total of 73 unique human genes, which forms an illicit drug-target network. Compared to the full drug-target network from DrugBank, illicit drugs and their target genes tend to cluster together and form four subnetworks, corresponding to four major medication categories: depressants, stimulants, analgesics, and steroids. External analysis of Anatomical Therapeutic Chemical (ATC) second sublevel classifications confirmed that the illicit drugs have neurological functions or act via mechanisms of stimulants, opioids, and steroids. To further explore other drugs potentially having associations with illicit drugs, we constructed an illicit-extended drug-target network by adding the drugs that have the same target(s) as illicit drugs to the illicit drug-target network. After analyzing the degree and betweenness of the network, we identified hubs and bridge nodes, which might play important roles in the development and treatment of drug addiction. Among them, 49 non-illicit drugs might have potential to be used to treat addiction or have addictive effects, including some results that are supported by previous studies. Conclusions This study presents the first systematic

75 FR 49502 - Medical Device User Fee Act; Public Meeting; Request for Comments

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-13

... Federal Food, Drug, and Cosmetic Act (FD&C Act) requires that before FDA begins negotiations with the...)) requires that, before FDA begins negotiations with the regulated industry on user fee reauthorization, we...

Pharmacosomes: An Emerging Novel Vesicular Drug Delivery System for Poorly Soluble Synthetic and Herbal Drugs

PubMed Central

2013-01-01

In the arena of solubility enhancement, several problems are encountered. A novel approach based on lipid drug delivery system has evolved, pharmacosomes. Pharmacosomes are colloidal, nanometric size micelles, vesicles or may be in the form of hexagonal assembly of colloidal drug dispersions attached covalently to the phospholipid. They act as befitting carrier for delivery of drugs quite precisely owing to their unique properties like small size, amphiphilicity, active drug loading, high entrapment efficiency, and stability. They help in controlled release of drug at the site of action as well as in reduction in cost of therapy, drug leakage and toxicity, increased bioavailability of poorly soluble drugs, and restorative effects. There has been advancement in the scope of this delivery system for a number of drugs used for inflammation, heart diseases, cancer, and protein delivery along with a large number of herbal drugs. Hence, pharmacosomes open new challenges and opportunities for improved novel vesicular drug delivery system. PMID:24106615

Crime Control Act of 1990 [29 November 1990]. [Summary].

PubMed

1990-01-01

In the US, the Crime Control Act of 1990 was approved on November 29, 1990. This various titles of this Act include provisions relating to the following: 1) international money laundering; 2) child abuse; 3) child pornography; 4) kidnapping, abducting, or unlawfully restraining a child; 5) the protection of crime victims; 6) funding for local law enforcement agencies; 7) funding for federal law enforcement; 8) rural drug enforcement assistance; 9) mandatory detention for certain criminals; 10) juvenile justice; 11) penalties for use of certain firearms; 12) improvements in miscellaneous criminal law; 13) disability benefits for public safety officers; 14) money laundering; 15) drug-free school zones; 16) miscellaneous amendments to the federal judicial and criminal codes; 17) general provisions; 18) grants for correctional options; 19) control of anabolic steroids; 20) asset forfeiture; 21) student loan cancellation for law enforcement officers; 22) firearms provisions; 23) chemical diversion and trafficking; 24) drug paraphernalia; 25) banking law enforcement; 26) licit opium imports; 27) sentencing for methamphetamine offenses; 28) drug enforcement grants; 29) prisons; 30) shock incarceration (prison boot camps); 31) bankruptcy and restitution; 32) appropriations for law and drug enforcement agencies; 33) anti-drug programs; 34) support of law enforcement; 35) technical and minor substantive amendments to the federal criminal code; 36) federal debt collection; and 37) national child search assistance (for missing children).

[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.

The Employee Polygraph Protection Act of 1988.

ERIC Educational Resources Information Center

Duffy, Patrick J.

1989-01-01

Aspects of the new Employee Polygraph Protection Act are discussed, including exemptions, prohibited devices, limitations, exceptions, injury and access requirements, reasonable suspicion, drug industry investigations, procedural requirements, disclosure, basis for discharge, enforcement and remedies, and preemption and existing state laws. (MSE)

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

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

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...

21 CFR 500.26 - Timed-release dosage form drugs.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 201(v) of the Federal Food, Drug, and Cosmetic Act. (b) Timed-release dosage form animal drugs that... using procedures and controls to ensure release of the total dosage at a safe and effective rate. Data...

21 CFR 500.26 - Timed-release dosage form drugs.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 201(v) of the Federal Food, Drug, and Cosmetic Act. (b) Timed-release dosage form animal drugs that... using procedures and controls to ensure release of the total dosage at a safe and effective rate. Data...

21 CFR 500.26 - Timed-release dosage form drugs.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 201(v) of the Federal Food, Drug, and Cosmetic Act. (b) Timed-release dosage form animal drugs that... using procedures and controls to ensure release of the total dosage at a safe and effective rate. Data...

21 CFR 500.26 - Timed-release dosage form drugs.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 201(v) of the Federal Food, Drug, and Cosmetic Act. (b) Timed-release dosage form animal drugs that... using procedures and controls to ensure release of the total dosage at a safe and effective rate. Data...

21 CFR 500.26 - Timed-release dosage form drugs.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 201(v) of the Federal Food, Drug, and Cosmetic Act. (b) Timed-release dosage form animal drugs that... using procedures and controls to ensure release of the total dosage at a safe and effective rate. Data...

A comparison of complex sleep behaviors with two short-acting Z-hypnosedative drugs in nonpsychotic patients

PubMed Central

Chen, Li-Fen; Lin, Ching-En; Chou, Yu-Ching; Mao, Wei-Chung; Chen, Yi-Chyan; Tzeng, Nian-Sheng

2013-01-01

Objective Complex sleep behaviors (CSBs) are classified as “parasomnias” in the International Classifcation of Sleep Disorders, Second Edition (ICSD-2). To realize the potential danger after taking two short-acting Z-hypnosedative drugs, we estimated the incidence of CSBs in nonpsychotic patients in Taiwan. Methods Subjects (N = 1,220) using zolpidem or zopiclone were enrolled from the psychiatric outpatient clinics of a medical center in Taiwan over a 16-month period in 2006–2007. Subjects with zolpidem (N = 1,132) and subjects with zopiclone (N = 88) were analyzed. All subjects completed a questionnaire that included demographic data and complex sleep behaviors after taking hypnotics. Results Among zolpidem and zopiclone users, 3.28% of patients reported incidents of somnambulism or amnesic sleep-related behavior problems. The incidence of CSBs with zolpidem and zopiclone were 3.27%, and 3.41%, respectively, which was signifcantly lower than other studies in Taiwan. Conclusion These results serve as a reminder for clinicians to make inquiries regarding any unusual performance of parasomnic activities when prescribing zolpidem or zopiclone. PMID:23976857

Key Issues in Education: Drug-Free Schools. 1990-91 Program Evaluation of Federally Funded Drug-Free Schools Programs.

ERIC Educational Resources Information Center

Smyer, Roxane

The Austin (Texas) Independent School District (AISD) received monies to combat drug and alcohol abuse on its campuses through the Drug-Free Schools and Communities (DFSC) Act of 1986. Each year, programs funded and services purchased with these funds have changed. In 1990-91 most of the DFSC monies were used for these projects: the Secondary…

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.

75 FR 13702 - Implementation of the Methamphetamine Production Prevention Act of 2008

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-23

... 1117-AB25 Implementation of the Methamphetamine Production Prevention Act of 2008 AGENCY: Drug..., the President signed the Methamphetamine Production Prevention Act of 2008, which clarifies the... Title 21 of the Code of Federal Regulations (CFR), Parts 1300 to 1399. These regulations are designed to...

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.

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.

[Orphan drugs].

PubMed

Golocorbin Kon, Svetlana; Vojinović, Aleksandra; Lalić-Popović, Mladena; Pavlović, Nebojsa; Mikov, Momir

2013-01-01

Drugs used for treatment of rare diseases are known worldwide under the term of orphan drugs because pharmaceutical companies have not been interested in "adopting" them, that is in investing in research, developing and producing these drugs. This kind of policy has been justified by the fact that these drugs are targeted for small markets, that only a small number of patients is available for clinical trials, and that large investments are required for the development of drugs meant to treat diseases whose pathogenesis has not yet been clarified in majority of cases. The aim of this paper is to present previous and present status of orphan drugs in Serbia and other countries. THE BEGINNING OF ORPHAN DRUGS DEVELOPMENT: This problem was first recognized by Congress of the United States of America in January 1983, and when the "Orphan Drug Act" was passed, it was a turning point in the development of orphan drugs. This law provides pharmaceutical companies with a series of reliefs, both financial ones that allow them to regain funds invested into the research and development and regulatory ones. Seven years of marketing exclusivity, as a type of patent monopoly, is the most important relief that enables companies to make large profits. There are no sufficient funds and institutions to give financial support to the patients. It is therefore necessary to make health professionals much more aware of rare diseases in order to avoid time loss in making the right diagnosis and thus to gain more time to treat rare diseases. The importance of discovery, development and production of orphan drugs lies in the number of patients whose life quality can be improved significantly by administration of these drugs as well as in the number of potential survivals resulting from the treatment with these drugs.

Computer-Aided Drug Design Applied to Marine Drug Discovery: Meridianins as Alzheimer's Disease Therapeutic Agents.

PubMed

Llorach-Pares, Laura; Nonell-Canals, Alfons; Sanchez-Martinez, Melchor; Avila, Conxita

2017-11-27

Computer-aided drug discovery/design (CADD) techniques allow the identification of natural products that are capable of modulating protein functions in pathogenesis-related pathways, constituting one of the most promising lines followed in drug discovery. In this paper, we computationally evaluated and reported the inhibitory activity found in meridianins A-G, a group of marine indole alkaloids isolated from the marine tunicate Aplidium , against various protein kinases involved in Alzheimer's disease (AD), a neurodegenerative pathology characterized by the presence of neurofibrillary tangles (NFT). Balance splitting between tau kinase and phosphate activities caused tau hyperphosphorylation and, thereby, its aggregation and NTF formation. Inhibition of specific kinases involved in its phosphorylation pathway could be one of the key strategies to reverse tau hyperphosphorylation and would represent an approach to develop drugs to palliate AD symptoms. Meridianins bind to the adenosine triphosphate (ATP) binding site of certain protein kinases, acting as ATP competitive inhibitors. These compounds show very promising scaffolds to design new drugs against AD, which could act over tau protein kinases Glycogen synthetase kinase-3 Beta (GSK3β) and Casein kinase 1 delta (CK1δ, CK1D or KC1D), and dual specificity kinases as dual specificity tyrosine phosphorylation regulated kinase 1 (DYRK1A) and cdc2-like kinases (CLK1). This work is aimed to highlight the role of CADD techniques in marine drug discovery and to provide precise information regarding the binding mode and strength of meridianins against several protein kinases that could help in the future development of anti-AD drugs.

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…

DrugBank 3.0: a comprehensive resource for ‘Omics’ research on drugs

PubMed Central

Knox, Craig; Law, Vivian; Jewison, Timothy; Liu, Philip; Ly, Son; Frolkis, Alex; Pon, Allison; Banco, Kelly; Mak, Christine; Neveu, Vanessa; Djoumbou, Yannick; Eisner, Roman; Guo, An Chi; Wishart, David S.

2011-01-01

DrugBank (http://www.drugbank.ca) is a richly annotated database of drug and drug target information. It contains extensive data on the nomenclature, ontology, chemistry, structure, function, action, pharmacology, pharmacokinetics, metabolism and pharmaceutical properties of both small molecule and large molecule (biotech) drugs. It also contains comprehensive information on the target diseases, proteins, genes and organisms on which these drugs act. First released in 2006, DrugBank has become widely used by pharmacists, medicinal chemists, pharmaceutical researchers, clinicians, educators and the general public. Since its last update in 2008, DrugBank has been greatly expanded through the addition of new drugs, new targets and the inclusion of more than 40 new data fields per drug entry (a 40% increase in data ‘depth’). These data field additions include illustrated drug-action pathways, drug transporter data, drug metabolite data, pharmacogenomic data, adverse drug response data, ADMET data, pharmacokinetic data, computed property data and chemical classification data. DrugBank 3.0 also offers expanded database links, improved search tools for drug–drug and food–drug interaction, new resources for querying and viewing drug pathways and hundreds of new drug entries with detailed patent, pricing and manufacturer data. These additions have been complemented by enhancements to the quality and quantity of existing data, particularly with regard to drug target, drug description and drug action data. DrugBank 3.0 represents the result of 2 years of manual annotation work aimed at making the database much more useful for a wide range of ‘omics’ (i.e. pharmacogenomic, pharmacoproteomic, pharmacometabolomic and even pharmacoeconomic) applications. PMID:21059682

The success of the citizen suit: protecting consumers from inaccurate food labeling by amending the Federal Food, Drug, and Cosmetic Act.

PubMed

Springer, James

2013-01-01

The Federal Food, Drug, and Cosmetic Act ("FDCA"), amended in 1990 by the Nutrition Education and Labeling Act ("NLEA"), established a national framework for the administration and promulgation of uniform food labeling standards. Specifically, the NLEA created affirmative obligations for the food--requiring detailed disclosure of food content and strict adherence to regulations governing the use of health and nutritional claims on food packaging. To accomplish these goals, Congress tasked the Food and Drug Administration ("FDA") with the sole responsibility of the enforcement of these new requirements. Under the statutory framework of the FDCA, the United States Supreme Court ("Court") has held that there is no private right of action, of which extended to the enforcement of NLEA standards. This interpretation has left individuals with no federal outlet for relief in the enforcement of federal food labeling standards. Adherence to this interpretation is especially concerning when the FDA currently faces exponential growth in administrative responsibilities while simultaneously experiencing employment reduction, a $206 million "Sequester," and a recent government-wide shutdown. As a result, the American people are left to depend on an Agency that is struggling with drastic resource reduction while being accountable for ever increasing enforcement responsibilities. To ensure consumer protection, this Article argues that Congress should amend the FDCA to include a citizen suit provision in order to provide individuals with a right of private action for the enforcement of NLEA standards. Borrowing from the successes realized under similar citizen suit provisions found in environmental legislation, this Article argues that a citizen suit provision is amendable to the FDCA and would relieve fiscal pressures, strengthen the current enforcement framework of the FDCA, encourage more robust enforcement by the FDA and states, and ensure uniform interpretation of NLEA

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.

[Acceptance and commitment therapy (ACT) and addiction: a literature review].

PubMed

De Groot, F; Morrens, M; Dom, G

2014-01-01

Acceptance and commitment therapy (ACT) is a recent form of cognitive behavioural therapy, based on the relational frame theory (RFT). act is being used to treat a wide range of problems, including addiction. To review the literature on the use of act to treat addiction. We searched the literature systematically using PubMed en Psycinfo. We found 16 studies, 10 of which were rct's. Eight studies dealt with drug problems or mixed substance problems, 7 studies focused on cigarette smoking, and only 1 publication concerned alcohol treatment. The majority of studies reported positive results for act following treatment and at follow-up. Although more research is needed, act is shown itself to be a promising treatment for addiction.

The Dangerous Drugs Act Amendment in Jamaica: Reviewing goals, implementation, and challenges.

PubMed

Davenport, Steven; Pardo, Bryce

2016-11-01

After decades of internal discussion, the Government of Jamaica recently amended its laws to create a regulated and licensed cannabis industry for medical and scientific purposes. The new law also decriminalizes personal possession and use of cannabis; allows cannabis to be used by individuals for religious, medical, scientific and therapeutic purposes; and permits home cultivation of up to five plants. We first describe the statutory changes under the Dangerous Drugs (Amendment) Act of 2015 and compare it with other jurisdictions. We provide an analytical framework for understanding how the DDA Amendment affects key populations and achieves its stated goals, drawing on publicly available information and unstructured interviews with non-governmental stakeholders in Jamaica. The Amendment's primary goals are to deliver economic impact and reduce criminal justice costs. A relaxed policy of enforcement toward possession and use seems to have occurred even before the law's passage; after the law's passage, enforcement remains limited. To access medical cannabis under the DDA residents must receive authorization from a certified health professional in Jamaica; tourists may self-declare their medical need; and Rastafarians may grow and exchange non-commercially for religious purposes. Internally, many see "ganja" as an industry sorely needed to drive economic growth in Jamaica. Indeed, the potential impacts could be large, especially if Jamaica draws additional tourism or creates a viable export industry. A growing cannabis-related tourism industry seems more realistic. We maintain that policymakers and observers should proceed in an orderly fashion, continuing to identify and resolve remaining uncertainties, initiate new types of data collection, and make decisions based on realistic assessments of potentials for economic impact. Copyright © 2016 Elsevier B.V. All rights reserved.

Modeling of signaling crosstalk-mediated drug resistance and its implications on drug combination.

PubMed

Sun, Xiaoqiang; Bao, Jiguang; You, Zhuhong; Chen, Xing; Cui, Jun

2016-09-27

The efficacy of pharmacological perturbation to the signaling transduction network depends on the network topology. However, whether and how signaling dynamics mediated by crosstalk contributes to the drug resistance are not fully understood and remain to be systematically explored. In this study, motivated by a realistic signaling network linked by crosstalk between EGF/EGFR/Ras/MEK/ERK pathway and HGF/HGFR/PI3K/AKT pathway, we develop kinetic models for several small networks with typical crosstalk modules to investigate the role of the architecture of crosstalk in inducing drug resistance. Our results demonstrate that crosstalk inhibition diminishes the response of signaling output to the external stimuli. Moreover, we show that signaling crosstalk affects the relative sensitivity of drugs, and some types of crosstalk modules that could yield resistance to the targeted drugs were identified. Furthermore, we quantitatively evaluate the relative efficacy and synergism of drug combinations. For the modules that are resistant to the targeted drug, we identify drug targets that can not only increase the relative drug efficacy but also act synergistically. In addition, we analyze the role of the strength of crosstalk in switching a module between drug-sensitive and drug-resistant. Our study provides mechanistic insights into the signaling crosstalk-mediated mechanisms of drug resistance and provides implications for the design of synergistic drug combinations to reduce drug resistance.

77 FR 46653 - Branded Prescription Drug Fee; Hearing

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-06

... DEPARTMENT OF THE TREASURY Internal Revenue Service 26 CFR Part 51 [REG-112805-10] RIN 1545-BJ39 Branded Prescription Drug Fee; Hearing AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of... drug fee imposed by the Affordable Care Act. DATES: The public hearing is being held on Friday...

32 CFR 147.10 - Guideline H-Drug involvement.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Controlled Substances Act of 1970, as amended (e.g., marijuana or cannabis, depressants, narcotics... use of a drug or use of a legal drug in a manner that deviates from approved medical direction. (b..., sale, or distribution; (3) Diagnosis by a credentialed medical professional (e.g., physician, clinical...

Paid protection? Ethics of incentivised long-acting reversible contraception in adolescents with alcohol and other drug use.

PubMed

Won, Tiana; Blumenthal-Barby, Jennifer; Chacko, Mariam

2017-03-01

Pregnant adolescents have a higher risk of poor maternal and fetal outcomes, particularly in the setting of concomitant maternal alcohol and other drug (AOD) use. Despite numerous programmes aimed at reducing overall teen pregnancy rates and the recognition of AOD use as a risk factor for unintended pregnancy in adolescents, interventions targeting this specific group have been sparse. In adult drug-using women, financial incentives for contraception have been provided but are ethically controversial. This article explores whether a trial could ethically employ monetary incentives in adolescents with AOD use to promote the use of long-acting reversible contraception (LARC), with special attention to the relevant distinctions between adults and adolescents. We conclude that a trial of incentives to promote LARC in this patient population is ethically permissible if the incentives are small, are tied to completion of an educational activity to minimise the quick fix temptation and potential for non-attendance to the risks and benefits of LARC and are provided only to the adolescent after an assessment of her reasoning to rule out coercion (eg, by guardians) as motivation. Information about treatment for AOD use and follow-up care in case of problems with the contraceptive or desire for removal should also be provided. Before implementing such a trial, qualitative research with input from providers, potential patients and their parents should be conducted to inform the programme's specific structure. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Neonatal Safety Information Reported to the FDA During Drug Development Studies

PubMed Central

Avant, Debbie; Baer, Gerri; Moore, Jason; Zheng, Panli; Sorbello, Alfred; Ariagno, Ron; Yao, Lynne; Burckart, Gilbert J.; Wang, Jian

2017-01-01

Background Relatively few neonatal drug development studies have been conducted, but an increase is expected with the enactment of the Food and Drug Administration Safety and Innovation Act (FDASIA). Understanding the safety of drugs studied in neonates is complicated by the unique nature of the population and the level of illness. The objective of this study was to examine neonatal safety data submitted to the FDA in studies pursuant to the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA) between 1998 and 2015. Methods FDA databases were searched for BPCA and/or PREA studies that enrolled neonates. Studies that enrolled a minimum of 3 neonates were analyzed for the presence and content of neonatal safety data. Results The analysis identified 40 drugs that were studied in 3 or more neonates. Of the 40 drugs, 36 drugs received a pediatric labeling change as a result of studies between 1998 and 2015, that included information from studies including neonates. Fourteen drugs were approved for use in neonates. Clinical trials for 20 of the drugs reported serious adverse events (SAEs) in neonates. The SAEs primarily involved cardiovascular events such as bradycardia and/or hypotension or laboratory abnormalities such as anemia, neutropenia, and electrolyte disturbances. Deaths were reported during studies of 9 drugs. Conclusions Our analysis revealed that SAEs were reported in studies involving 20 of the 40 drugs evaluated in neonates, with deaths identified in 9 of those studies. Patients enrolled in studies were often critically ill, which complicated determination of whether an adverse event was drug-related. We conclude that the traditional means for collecting safety information in drug development trials needs to be adjusted for neonates and will require the collaboration of regulators, industry, and the clinical and research communities to establish appropriate definitions and reporting strategies for the neonatal

The effects and consequences of selected club drugs.

PubMed

Freese, Thomas E; Miotto, Karen; Reback, Cathy J

2002-09-01

Ecstasy (MDMA), gamma-hydroxybutyrate (GHB), ketamine, and methamphetamine are 4 examples of club drugs that are increasing in popularity. Although the pharmacological classifications of these drugs vary, MDMA has structural similarities to both amphetamine and the hallucinogen mescaline. Ketamine and GHB are anesthetic agents and methamphetamine is a long-acting psychostimulant. Medical visits for club drug-related toxicity have sharply increased across the country. This article provides a brief review of the literature on club drugs. Copyright 2002 Elsevier Science Inc.

Prescription drug coverage and effects on drug expenditures among elderly Medicare beneficiaries.

PubMed

Huh, Soonim; Rice, Thomas; Ettner, Susan L

2008-06-01

To identify determinants of drug coverage among elderly Medicare beneficiaries and to investigate the impact of drug coverage on drug expenditures with and without taking selection bias into account. The primary data were from the 2000 Medicare Current Beneficiary Survey (MCBS) Cost and Use file, linked to other data sources at the county or state-level that provided instrumental variables. Community-dwelling elderly Medicare beneficiaries who completed the survey were included in the study (N=7,525). A probit regression to predict the probability of having drug coverage and the effects of drug coverage on drug expenditures was estimated by a two-part model, assuming no correlation across equations. In addition, the discrete factor model estimated choice of drug coverage and expenditures for prescription drugs simultaneously to control for self-selection into drug coverage, allowing for correlation of error terms across equations. Findings indicated that unobservable characteristics leading elderly Medicare beneficiaries to purchase drug coverage also lead them to have higher drug expenditures on conditional use (i.e., adverse selection), while the same unobservable factors do not influence their decisions whether to use any drugs. After controlling for potential selection bias, the probability of any drug use among persons with drug coverage use was 4.5 percent higher than among those without, and drug coverage led to an increase in drug expenditures of $308 among those who used prescription drugs. Given significant adverse selection into drug coverage before the implementation of the Medicare Prescription Drug Improvement and Modernization Act, it is essential that selection effects be monitored as beneficiaries choose whether or not to enroll in this voluntary program.

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.

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.

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.

Fetal effects of psychoactive drugs.

PubMed

Salisbury, Amy L; Ponder, Kathryn L; Padbury, James F; Lester, Barry M

2009-09-01

Psychoactive drug use by pregnant women has the potential to effect fetal development; the effects are often thought to be drug-specific and gestational age dependent. This article describes the effects of three drugs with similar molecular targets that involve monoaminergic transmitter systems: cocaine, methamphetamine, and selective serotonin re-uptake inhibitors (SSRIs) used to treat maternal depression during pregnancy. We propose a possible common epigenetic mechanism for their potential effects on the developing child. We suggest that exposure to these substances acts as a stressor that affects fetal programming, disrupts fetal placental monoamine transporter expression and alters neuroendocrine and neurotransmitter system development. We also discuss neurobehavioral techniques that may be useful in the early detection of the effects of in utero drug exposure.

[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.

Long-Acting Beta Agonists Enhance Allergic Airway Disease.

PubMed

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

2015-01-01

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

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 balance between innovation and competition: the Hatch-Waxman Act, the 2003 Amendments, and beyond.

PubMed

Kelly, Colleen

2011-01-01

In 1984, Congress passed the Hatch-Waxman Act, a landmark statute designed both to encourage innovation by pioneer drug companies and to increase competition by generic drug companies. After its enactment, drug companies attempted to "ga the regulatory regime to their respective economic advantage. In 2003, in an effort to address these issues, FDA promulgated a final rule and Congress passed the Medicare Modernization Act, amending the Hatch-Waxman Act. This article provides a comprehensive look at the 2003 statutory and regulatory changes. First, the article analyzes the history and provisions of the original Hatch-Waxman Act and the issues that arose after its enactment. Second, the article discusses the passage of the 2003 FDA rule and the 2003 Medicare Modernization Act. Next, the article demonstrates that, although the 2003 amendments may have definitively resolved some issues, the amendments did not resolve all interpretive issues and have even led to unintended consequences. In particular, the article discusses several areas of current controversy, including the effect of patent delisting and patent expiration on 180-day exclusivity, the patent delisting counterclaim provision, the declaratory judgment action provision, patent settlement agreements, and authorized generics. Finally, the article assesses the potential for future reform of the Hatch-Waxman Act. The article concludes that maintaining the balance between innovation and competition will likely remain a daunting task for legislators and regulators in the future.

21 CFR 314.410 - Imports and exports of new drugs.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., and is shipped with a copy of the labeling required for, the approved drug product. (3) Insulin or an antibiotic drug may be exported without regard to the requirements in section 802 of the act if the insulin...

21 CFR 314.410 - Imports and exports of new drugs.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., and is shipped with a copy of the labeling required for, the approved drug product. (3) Insulin or an antibiotic drug may be exported without regard to the requirements in section 802 of the act if the insulin...

21 CFR 314.410 - Imports and exports of new drugs.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., and is shipped with a copy of the labeling required for, the approved drug product. (3) Insulin or an antibiotic drug may be exported without regard to the requirements in section 802 of the act if the insulin...

21 CFR 314.410 - Imports and exports of new drugs.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., and is shipped with a copy of the labeling required for, the approved drug product. (3) Insulin or an antibiotic drug may be exported without regard to the requirements in section 802 of the act if the insulin...

Emerging drugs for the treatment of erectile dysfunction.

PubMed

Peak, Taylor C; Yafi, Faysal A; Sangkum, Premsant; Hellstrom, Wayne J G

2015-06-01

Erectile dysfunction adversely affects the lives of millions of men, and is the most commonly treated sexual disorder today. The erectile process has been extensively investigated, with major advances made in elucidating many of the complex molecular pathways involved. These advances have allowed researchers to design and study drug formulations that target various aspects of this complex process. The initial culmination of this research was the introduction of phosphodiesterase 5-inhibitors. While effective in many patients, they are not satisfactory for all afflicted men. As a result, researchers are developing novel drugs that target different molecular pathways. The paper will review these pathways, and the potential agents that target them. More specifically, first dopaminergic and melanocortin receptor agonists that act centrally will be covered. Then, the paper will examine the "second-generation" phosphodiesterase 5-inhibitors, soluble guanylate cyclases, rho-kinase inhibitors, and maxi-k channel activators that act peripherally. Most of these novel drugs have yet to reach Phase III studies. However, it is likely that in years to come, patients will be selectively treated with these novel agents as a monotherapy or in combination with others acting in a synergistic manner.

New Initiation of Long-Acting Opioids in Long-Stay Nursing Home Residents

PubMed Central

Pimentel, Camilla B.; Gurwitz, Jerry H.; Tjia, Jennifer; Hume, Anne L.; Lapane, Kate L.

2016-01-01

BACKGROUND Despite known risks of overdose and respiratory depression when treating opioid-naïve individuals with long-acting opioids, use of these potent agents may be common in nursing homes. OBJECTIVES To estimate prevalence of new initiation of long-acting opioids since national efforts to increase prescriber and public awareness on safe use of transdermal fentanyl patches. DESIGN Cross-sectional. SETTING US nursing homes. PARTICIPANTS 22,253 Medicare-enrolled long-stay nursing home residents. MEASUREMENTS The Minimum Data Set 3.0 linked with Medicare enrollment, hospital claims, and prescription drug transaction data (January–December 2011) were used to determine the prevalence of new initiation among nursing home residents who were prescribed a long-acting opioid in the nursing home. RESULTS Of nursing home residents who were prescribed a long-acting opioid within 30 days of a nursing home admission (n = 12,278), 9.4% (95% confidence interval [CI]: 8.9–9.9%) lacked a prescription drug claim for a short-acting opioid in the previous 60 days. The most common initial prescriptions of long-acting opioids were fentanyl patch (51.9% of opioid-naïve nursing home residents), morphine sulfate (28.1%), and oxycodone (17.2%). CONCLUSION New initiation of long-acting opioids—especially fentanyl patches that have been the subject of safety communications—persists in nursing homes. PMID:27487158

Administrator's Handbook for Crime Prevention and Drug Education.

ERIC Educational Resources Information Center

Texas Education Agency, Austin. Div. of Crime Prevention and Drug Education.

Acts of three Texas Legislatures have mandated that the schools of Texas provide a program for all public school students, grades K-12, in crime prevention and drug education. To assist schools in formulating a philosophy about and in developing appropriate programs and techniques for drug education and crime prevention programs, the Texas…

Decriminalization of drug use.

PubMed

Vicknasingam, Balasingam; Narayanan, Suresh; Singh, Darshan; Chawarski, Marek

2018-05-08

To review the literature on decriminalization of drug use from 2016 to 2017 and suggest the way forward. The systematic review of the literature on decriminalization resulted in seven articles that discuss decriminalization as compared with 57 published articles on legalization. Decriminalization of drug use did not have an effect on the age of onset of drug use and the prices of drugs did not decrease after the implementation of drug decriminalization. Policy-based studies on decriminalization suggest shifting from criminal sanctions to a public health approach, which was endorsed by the United Nations (UN) that viewed drug addiction as a preventable and treatable health disorder. One study preferred decriminalization only for cannabis and cautioned against regulating cannabis like alcohol. Another study indicated that general medical practitioners in Ireland did not favour the decriminalization of cannabis. Scientific evidence supporting drug addiction as a health disorder and the endorsement by the UN strengthen the case for decriminalization. However, studies reporting on the positive outcomes of decriminalization remain scarce. The evidence needs to be more widespread in order to support the case for decriminalization. Furthermore, the endorsement by the UN needs to be acted upon by individual member states.

Downregulation of the cough reflex by aclidinium and tiotropium in awake and anesthetized rabbits.

PubMed

Mutolo, Donatella; Cinelli, Elenia; Iovino, Ludovica; Pantaleo, Tito; Bongianni, Fulvia

2016-06-01

Long-acting muscarinic receptor antagonists (LAMAs) have been reported to attenuate cough in preclinical and clinical studies. The present study was performed on rabbits to compare aclidinium and tiotropium efficacy in the downregulation of the cough reflex. This reflex was evoked by citric acid inhalation in unanesthetized animals and by both citric acid inhalation and mechanical stimulation of the tracheobronchial tree in anesthetized animals 90 min following the inhalation of each drug (nebulizer output always at 1 mL/min). Aclidinium 4 mg/mL and tiotropium 200 μg/mL inhaled in 1 min proved to have similar protective effect on methacholine-induced bronchoconstriction in anesthetized animals. The total dosage employed for aclidinium and tiotropium was 4 mg and 200 μg, respectively. In awake animals, similar reductions in the cough number were observed following 10-min inhalation of each drug with a slight, not significant tendency to higher antitussive effects for aclidinium. In anesthetized animals, 1-min inhalation of each drug caused similar depressant effects on cough responses induced by both mechanical and chemical stimulation. A complete suppression of cough responses to mechanical stimuli was seen in some preparations. The results strongly suggest that the LAMA-induced downregulation of cough may be mediated not only by transient receptor potential vanilloid type 1 channels, as already reported, but also by acid-sensing ion channels and mechanoreceptors. The route of administration along with the more rapid hydrolysis of aclidinium into inactive metabolites minimize potential systemic side effects and give to this drug a very favorable safety profile. Copyright © 2016 Elsevier Ltd. All rights reserved.

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…

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

75 FR 53702 - Medical Device User Fee Act; Public Meeting; Request for Comments; Amendment of Notice

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. 2010-N-0389] Medical Device User Fee Act; Public Meeting; Request for Comments; Amendment of Notice AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing...

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.

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...

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...

Privacy Act of 1974; altered system of records--PHS. Notification of altered system of records: 09-30-0036, "Alcohol, Drug Abuse, and Mental Health Epidemiologic and Biometric Research Data, HHS/ADAMHA/OA".

PubMed

1984-10-23

In accordance with the requirements of the Privacy Act, the Public Health Service (OHS) is publishing a notice of proposal to alter the system of records in the Alcohol, Drug Abuse, and Mental Health Administration (ADAMHA), National Institute of Mental Health (NIMH), entitled, "Mental Health Epidemiologic and Biometric Research Data, HHS/ADAMHA/NIMH," to create an umbrella system of records to include epidemiologic and biometric research data in the areas of alcohol and drug abuse in addition to data already collected and maintained for mental health research. The system is to be retitled, "Alcohol, Drug Abuse, and Mental Health Epidemiologic and Biometric Research Data, HHS/ADAMHA/OA." PHS invites interested persons to submit comments on the proposed alteration on or before November 23, 1984.

21 CFR 314.170 - Adulteration and misbranding of an approved drug.

Code of Federal Regulations, 2013 CFR

2013-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on... subject to the adulteration and misbranding provisions in sections 501, 502, and 503 of the act. FDA is...

21 CFR 314.170 - Adulteration and misbranding of an approved drug.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on... subject to the adulteration and misbranding provisions in sections 501, 502, and 503 of the act. FDA is...

21 CFR 314.170 - Adulteration and misbranding of an approved drug.

Code of Federal Regulations, 2011 CFR

2011-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on... subject to the adulteration and misbranding provisions in sections 501, 502, and 503 of the act. FDA is...

21 CFR 314.170 - Adulteration and misbranding of an approved drug.

Code of Federal Regulations, 2014 CFR

2014-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on... subject to the adulteration and misbranding provisions in sections 501, 502, and 503 of the act. FDA is...

21 CFR 314.170 - Adulteration and misbranding of an approved drug.

Code of Federal Regulations, 2012 CFR

2012-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on... subject to the adulteration and misbranding provisions in sections 501, 502, and 503 of the act. FDA is...

Effects of Motivation and Problem Severity on Court-Based Drug Treatment

ERIC Educational Resources Information Center

Cosden, Merith; Basch, Janice E.; Campos, Emily; Greenwell, Ashley; Barazani, Sivan; Walker, Sara

2006-01-01

This study addresses the effects of motivation and problem severity on outcomes in two court-based drug treatment programs. Data were examined for 578 offenders served by a drug court and 223 served by a drug treatment court mandated through California's Substance Abuse Crime Prevention Act (SACPA). It was hypothesized that client-reported…

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.

Hematology and pathology devices; reclassification; restricted devices; OTC test sample collection systems for drugs of abuse testing. Food and Drug Administration, HHS. Final rule.

PubMed

2000-04-07

The Food and Drug Administration (FDA) is reclassifying over-the-counter (OTC) test sample collection systems for drugs of abuse testing from class III (premarket approval) into class I (general controls) and exempting them from premarket notification (510(k)) and current good manufacturing practice (CGMP) requirements. FDA is also designating OTC test sample collection systems for drugs of abuse testing as restricted devices under the Federal Food, Drug, and Cosmetic Act (the act) and establishing restrictions intended to assure consumers that: The underlying laboratory test(s) are accurate and reliable; the laboratory performing the test(s) has adequate expertise and competency; and the product has adequate labeling and methods of communicating test results to consumers. Finally, FDA is adding a conforming amendment to the existing classification regulation for specimen transport and storage containers to clarify that it does not apply to specimen transport and storage containers that are part of an OTC test sample collection system for the purpose of testing for the presence of drugs of abuse or their metabolites in a laboratory.

In vivo cough suppressive activity of pectic polysaccharide with arabinogalactan type II side chains of Piper nigrum fruits and its synergistic effect with piperine.

PubMed

Khawas, Sadhana; Nosáľová, Gabriela; Majee, Sujay Kumar; Ghosh, Kanika; Raja, Washim; Sivová, Veronika; Ray, Bimalendu

2017-06-01

Piper nigrum L. fruits are not only a prized spice, but also highly valued therapeutic agent that heals many ailments including asthma, cold and respiratory problems. Herein, we have investigated structural features and in vivo antitussive activity of three fractions isolated from Piper nigrum fruits. The water extract (PN-WE) upon fractionation with EtOH yielded two fractions: a soluble fraction (PN-eSf) and a precipitated (PN-ePf) one. The existence of a pectic polysaccharide with arabinogalactan type II side chains (147kDa) in PN-ePf and piperine in PN-eSf were revealed. Moreover, oligosaccharides providing fine structural details of side chains were generated from PN-ePf and then characterized. The parental water extract (PN-WE) that contained both pectic polysaccharide and piperine, after oral administration (50mgkg -1 body weight) to guinea pigs, showed antitussive activity comparable to codeine phosphate (10mgkg -1 body weight). The EtOH precipitated fraction (PN-ePf) containing pectic polysaccharide showed comparatively higher antitussive activity than EtOH soluble fraction (PN-eSf) that contained piperine, but their potencies are lower than the parental water extract. Significantly, the specific airway smooth muscle reactivity of all three fractions remained unchanged. Finally, pectic polysaccharide-piperine combination in parental extract synergistically enhances antitussive effect in guinea pigs. Copyright © 2017 Elsevier B.V. All rights reserved.

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...

Drugs and Disparity: The Racial Impact of Illinois' Practice of Transferring Young Drug Offenders to Adult Court. Building Blocks for Youth.

ERIC Educational Resources Information Center

Ziedenberg, Jason

This report describes the racial impact of Illinois' practice of transferring young drug offenders to adult court. The state's Safe School Zone Act of 1986 and subsequent bills enacted by the legislature provide that youth age 15-16 years charged with drug sales within 1,000 feet of a school or public housing development are automatically…

Drug-nutrient interaction.

PubMed

Matsui, M S; Rozovski, S J

1982-01-01

The effect of certain drugs on nutrient metabolism is discussed. Antituberculotic drugs such as INH and cycloserine interfere with vitamin B6 metabolism and may produce a secondary niacin deficiency. Oral contraceptives interfere with the metabolism of folic acid and ascorbic acid, and in cases of deficient nutrition, they also seem to interfere with riboflavin. Anticonvulsants can act as folate antagonists and precipitate folic acid deficiency. Therefore, in some cases, supplementation with folate has been recommended simultaneously with anticonvulsant therapy. Cholestyramine therapy has been associated with malabsorption of vitamins; several reports suggest that cholestyramine affects absorption of the fat-soluble vitamins K and D and, in addition, may alter water-soluble vitamins, including folic acid. The study of the interaction of drugs and nutrients is an area that deserves a greater attention in the future, especially in groups where nutrient deficiencies may be prevalent.

Drug therapy in spinal tuberculosis.

PubMed

Rajasekaran, S; Khandelwal, Gaurav

2013-06-01

Although the discovery of effective anti-tuberculosis drugs has made uncomplicated spinal tuberculosis a medical disease, the advent of multi-drug-resistant Mycobacterium tuberculosis and the co-infection of HIV with tuberculosis have led to a resurgence of the disease recently. The principles of drug treatment of spinal tuberculosis are derived from our experience in treating pulmonary tuberculosis. Spinal tuberculosis is classified to be a severe form of extrapulmonary tuberculosis and hence is included in Category I of the WHO classification. The tuberculosis bacilli isolated from patients are of four different types with different growth kinetics and metabolic characteristics. Hence multiple drugs, which act on the different groups of the mycobacteria, are included in each anti-tuberculosis drug regimen. Prolonged and uninterrupted chemotherapy (which may be 'short course' and 'intermittent' but preferably 'directly observed') is effective in controlling the infection. Spinal Multi-drug-resistant TB and spinal TB in HIV-positive patients present unique problems in management and have much poorer prognosis. Failure of chemotherapy and emergence of drug resistance are frequent due to the failure of compliance hence all efforts must be made to improve patient compliance to the prescribed drug regimen.

Time Since First Acting on Same-Sex Attraction and Recreational Drug Use among Men Who Have Sex With Men (MSM): Is There an Effect of "Gay Age"?

PubMed

Rice, Cara E; Vasilenko, Sara A; Lanza, Stephanie T; Davis, John A; Fields, Karen S; Ervin, Melissa; Norris Turner, Abigail

2018-04-16

Men who have sex with men (MSM) have higher rates of substance use compared to men who have sex with women. Among MSM, drug use is linked to higher-risk sexual behavior and acquisition of HIV and other sexually transmitted infections. We hypothesize that time since first acting on one's same sex attraction, or one's "gay age", could be predictive of drug using behavior. We examined this question among 176 MSM, aged 18-35, presenting at a public sexual health clinic. Behavioral data were captured using interviewer- and self-administered surveys and clinical data were extracted from medical records. We used modified Poisson regression to examine associations between gay age and recent recreational drug use, and separately, between gay age and recent marijuana use. In total, 43% of participants reported recent marijuana use and 26% of participants reported recent use of other drugs. The associations between gay age and marijuana use and other drug use varied by HIV status. After adjustment for biological age, race, and education, a one-year increase in gay age was associated with significantly increased drug use among HIV-negative men (adjusted prevalence ratio (aPR): 1.08; 95% confidence interval (CI): 1.03-1.14), but we observed no association between gay age and drug use among HIV-positive men (aPR: 0.96, 95% CI: 0.86-1.07). Gay age was not associated with marijuana use in HIV-negative (aPR: 1.00, 95% CI: 0.95-1.04) or HIV-positive (aPR: 1.06, 95% CI: 0.98-1.14) men. In summary, HIV-negative MSM who had experienced more time since first same-sex experience had significantly increased prevalence of recent drug use.

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...

Calcium silicate-based drug delivery systems.

PubMed

Zhu, Ying-Jie; Guo, Xiao-Xuan; Sham, Tsun-Kong

2017-02-01

Compared with other inorganic materials such as silica, metal oxides, noble metals and carbon, calcium silicate-based materials, especially nanostructured calcium silicate materials, have high biocompatibility, bioactivity and biodegradability, high specific surface area, nanoporous/hollow structure, high drug-loading capacity, pH-responsive drug release behavior and desirable drug release properties, and thus they are promising for the application in drug delivery. Calcium silicate-based drug delivery systems have a long drug-release time, which can significantly prolong the therapeutic effect of drugs. Another advantage of calcium silicate-based drug delivery systems is their pH-responsive drug release property, which can act as an ideal platform for targeted drug delivery. Areas covered: In recent years, studies have been carried out on calcium silicate-based drug delivery systems, and important results and insights have been documented. This article is not intended to offer a comprehensive review on the research on calcium silicate-based drug delivery systems, but presents some examples reported in the literature, and includes new insights obtained by tracking the interactions between drug molecules and calcium silicate carriers on the molecular level using the synchrotron-based X-ray spectroscopy. Expert opinion: Finally, our opinions on calcium silicate-based drug delivery systems are provided, and several research directions for the future studies are proposed.

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...

Membrane Transporters: Structure, Function and Targets for Drug Design

NASA Astrophysics Data System (ADS)

Ravna, Aina W.; Sager, Georg; Dahl, Svein G.; Sylte, Ingebrigt

Current therapeutic drugs act on four main types of molecular targets: enzymes, receptors, ion channels and transporters, among which a major part (60-70%) are membrane proteins. This review discusses the molecular structures and potential impact of membrane transporter proteins on new drug discovery. The three-dimensional (3D) molecular structure of a protein contains information about the active site and possible ligand binding, and about evolutionary relationships within the protein family. Transporters have a recognition site for a particular substrate, which may be used as a target for drugs inhibiting the transporter or acting as a false substrate. Three groups of transporters have particular interest as drug targets: the major facilitator superfamily, which includes almost 4000 different proteins transporting sugars, polyols, drugs, neurotransmitters, metabolites, amino acids, peptides, organic and inorganic anions and many other substrates; the ATP-binding cassette superfamily, which plays an important role in multidrug resistance in cancer chemotherapy; and the neurotransmitter:sodium symporter family, which includes the molecular targets for some of the most widely used psychotropic drugs. Recent technical advances have increased the number of known 3D structures of membrane transporters, and demonstrated that they form a divergent group of proteins with large conformational flexibility which facilitates transport of the substrate.

The effect of drugs acting on cholinoceptors and mucosal chloride on luminal bicarbonate transport by rat caecum under in vitro conditions.

PubMed Central

Canfield, P.; Abdul-Ghaffar, T.

1991-01-01

1. The transport of HCO3- (Jsm) from a HCO3(-)-buffered serosal to an unbuffered mucosal saline solution has been studied in rat caecum in vitro. 2. Carbachol, bethanechol and acetylcholine (ACh) caused a concentration-dependent fall in Jsm with similar maximum effects. 1,1-Dimethyl-4-phenyl-piperazinium iodide (DMPP) also inhibited Jsm but the effect was less than with the other drugs. Maximum cholinoceptor inhibition was less than that obtained with anoxia. 3. Responses were blocked by atropine (10(-5) M) but hexamethonium (2 x 10(-4) M) significantly altered the response only to DMPP. 4. Physostigmine (10(-5) M) shifted the ACh response curve to the left but physostigmine itself caused inhibition of Jsm which was blocked by atropine. 5. Substitution of mucosal Cl- by NO3- reduced Jsm to a similar extent to maximum cholinoceptor effect and abolished responses to bethanecol. Anoxia further reduced Jsm in the presence of NO3-. 6. Mucosal SITS and DIDS (1 mM) reduced Jsm but this was less than the maximum inhibition seen with drugs acting on cholinoceptors or mucosal Cl- removal. Serosal DIDS caused a similar inhibition. 7. We conclude that cholinoceptor agonists inhibit but do not abolish luminal bicarbonate transport by an action on muscarinic receptors. PMID:1884114

Affective and Neuroendocrine Effects of Withdrawal from Chronic, Long-Acting Opiate Administration

PubMed Central

Hamilton, Kathryn L.; Harris, Andrew C.; Gewirtz, Jonathan C.

2013-01-01

Although the long-acting opiate methadone is commonly used to treat drug addiction, relatively little is known about effects of withdrawal from this drug in preclinical models. The current study examined affective, neuroendocrine, and somatic signs of withdrawal from the longer-acting methadone derivative l-alpha-acetylmethydol (LAAM) in rats. Anxiety-like behavior during both spontaneous and antagonist-precipitated withdrawal was measured by potentiation of the startle reflex. Withdrawal elevated corticosterone and somatic signs and blunted circadian variations in baseline startle responding. In addition, fear to an explicit, Pavlovian conditioned stimulus (fear-potentiated startle) was enhanced. These data suggest that anxiety-like behavior as measured using potentiated startle responding does not emerge spontaneously during withdrawal from chronic opiate exposure – in contrast to withdrawal from acute drug exposure – but rather is manifested as exaggerated fear in response to explicit threat cues. PMID:24076207

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.

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

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

Drug Trafficking and North Korea: Issues for U.S. Policy

DTIC Science & Technology

2007-01-25

Government is involved in manufacturing and trafficking in illegal drugs.”3 The provisions of the Foreign Assistance Act of 1961 referred to above require...probably manufacture methamphetamine drugs.13 The Department of State’s March 2006 International Narcotics Control Strategy Report (INCSR) notes...government cultivates opium illicitly, refines opium into heroin, and manufactures methamphetamine drugs in North Korea as a state-organized and

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.

21 CFR 20.30 - Food and Drug Administration Freedom of Information Staff.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Food and Drug Administration Freedom of... HUMAN SERVICES GENERAL PUBLIC INFORMATION General Policy § 20.30 Food and Drug Administration Freedom of Information Staff. (a) The Office responsible for agency compliance with the Freedom of Information Act and...

Oral Drug Delivery Systems Comprising Altered Geometric Configurations for Controlled Drug Delivery

PubMed Central

Moodley, Kovanya; Pillay, Viness; Choonara, Yahya E.; du Toit, Lisa C.; Ndesendo, Valence M. K.; Kumar, Pradeep; Cooppan, Shivaan; Bawa, Priya

2012-01-01

Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix® multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise®, which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix® as well as “release modules assemblage”, which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments. PMID:22312236

Quantifying the effects of antiangiogenic and chemotherapy drug combinations on drug delivery and treatment efficacy

PubMed Central

Yιlmaz, Defne; Phipps, Colin; Kohandel, Mohammad

2017-01-01

Tumor-induced angiogenesis leads to the development of leaky tumor vessels devoid of structural and morphological integrity. Due to angiogenesis, elevated interstitial fluid pressure (IFP) and low blood perfusion emerge as common properties of the tumor microenvironment that act as barriers for drug delivery. In order to overcome these barriers, normalization of vasculature is considered to be a viable option. However, insight is needed into the phenomenon of normalization and in which conditions it can realize its promise. In order to explore the effect of microenvironmental conditions and drug scheduling on normalization benefit, we build a mathematical model that incorporates tumor growth, angiogenesis and IFP. We administer various theoretical combinations of antiangiogenic agents and cytotoxic nanoparticles through heterogeneous vasculature that displays a similar morphology to tumor vasculature. We observe differences in drug extravasation that depend on the scheduling of combined therapy; for concurrent therapy, total drug extravasation is increased but in adjuvant therapy, drugs can penetrate into deeper regions of tumor. PMID:28922358

Quantifying the effects of antiangiogenic and chemotherapy drug combinations on drug delivery and treatment efficacy.

PubMed

Yonucu, Sirin; Yιlmaz, Defne; Phipps, Colin; Unlu, Mehmet Burcin; Kohandel, Mohammad

2017-09-01

Tumor-induced angiogenesis leads to the development of leaky tumor vessels devoid of structural and morphological integrity. Due to angiogenesis, elevated interstitial fluid pressure (IFP) and low blood perfusion emerge as common properties of the tumor microenvironment that act as barriers for drug delivery. In order to overcome these barriers, normalization of vasculature is considered to be a viable option. However, insight is needed into the phenomenon of normalization and in which conditions it can realize its promise. In order to explore the effect of microenvironmental conditions and drug scheduling on normalization benefit, we build a mathematical model that incorporates tumor growth, angiogenesis and IFP. We administer various theoretical combinations of antiangiogenic agents and cytotoxic nanoparticles through heterogeneous vasculature that displays a similar morphology to tumor vasculature. We observe differences in drug extravasation that depend on the scheduling of combined therapy; for concurrent therapy, total drug extravasation is increased but in adjuvant therapy, drugs can penetrate into deeper regions of tumor.

Non-Systemic Drugs: A Critical Review

PubMed Central

Charmot, Dominique

2012-01-01

Non-systemic drugs act within the intestinal lumen without reaching the systemic circulation. The first generation included polymeric resins that sequester phosphate ions, potassium ions, or bile acids for the treatment of electrolyte imbalances or hypercholesteremia. The field has evolved towards non-absorbable small molecules or peptides targeting luminal enzymes or transporters for the treatment of mineral metabolism disorders, diabetes, gastrointestinal (GI) disorders, and enteric infections. From a drug design and development perspective, non-systemic agents offer novel opportunities to address unmet medical needs while minimizing toxicity risks, but also present new challenges, including developing a better understanding and control of non-transcellular leakage pathways into the systemic circulation. The pharmacokinetic-pharmacodynamic relationship of drugs acting in the GI tract can be complex due to the variability of intestinal transit, interaction with chyme, and the complex environment of the surface epithelia. We review the main classes of non-absorbable agents at various stages of development, and their therapeutic potential and limitations. The rapid progress in the identification of intestinal receptors and transporters, their functional characterization and role in metabolic and inflammatory disorders, will undoubtedly renew interest in the development of novel, safe, non-systemic therapeutics. PMID:22300258

Development and characterization of a long-acting nanoformulated abacavir prodrug

PubMed Central

Singh, Dhirender; McMillan, JoEllyn; Hilaire, James; Gautam, Nagsen; Palandri, Diana; Alnouti, Yazen; Gendelman, Howard E; Edagwa, Benson

2016-01-01

Aim: A myristoylated abacavir (ABC) prodrug was synthesized to extend drug half-life and bioavailability. Methods: 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. Results: MABC antiretroviral activity in monocyte-derived macrophages was comparable to native drug. Encasement of MABC into poloxamer nanoparticles extended drug bioavailability for 2 weeks. Conclusion: MABC synthesis and encasement in polymeric nanoformulations improved intracellular drug accumulation and demonstrate translational potential as part of a long-acting antiretroviral regimen. PMID:27456759

77 FR 51949 - Privacy Act, Exempt Record System

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-28

.... FDA-2011-N-0252] Office of the Secretary 45 CFR Part 5b Privacy Act, Exempt Record System AGENCY... Drug Administration (FDA) of the Department of Health and Human Services (HHS) will be implementing a new system of records, 09-10-0020, ``FDA Records Related to Research Misconduct Proceedings, HHS/FDA...

77 FR 51910 - Privacy Act, Exempt Record System

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-28

.... FDA-2011-N-0252] Office of the Secretary 45 CFR Part 5b Privacy Act, Exempt Record System AGENCY... and Drug Administration (FDA) of the Department of Health and Human Services (HHS) will be implementing a new system of records, 09-10-0020, ``FDA Records Related to Research Misconduct Proceedings, HHS...

Development of a capillary electrophoresis method for the determination of the chiral purity of dextromethorphan by a dual selector system using quality by design methodology.

PubMed

Krait, Sulaiman; Heuermann, Matthias; Scriba, Gerhard K E

2018-03-01

Dextromethorphan is a centrally acting antitussive drug, while its enantiomer levomethorphan is an illicit drug with opioid analgesic effects. As capillary electrophoresis has been proven as an ideal technique for enantiomer analysis, the present study was conducted in order to develop a capillary electrophoresis-based limit test for levomethorphan. The analytical target profile was defined as a method that should be able to determine levomethorphan with acceptable precision and accuracy at the 0.1 % level. From initial scouting experiments, a dual selector system consisting of sulfated β-cyclodextrin and methyl-α-cyclodextrin was identified. The critical process parameters were evaluated in a fractional factorial resolution IV design followed by a central composite face-centered design and Monte Carlo simulations for defining the design space of the method. The selected working conditions consisted of a 30/40.2 cm, 50 μm id fused-silica capillary, 30 mM sodium phosphate buffer, pH 6.5, 16 mg/mL sulfated β-cyclodextrin, and 14 mg/mL methyl-α-cyclodextrin at 20°C and 20 kV. The method was validated according to ICH guideline Q2(R1) and applied to the analysis of a capsule formulation. Furthermore, the apparent binding constants between the enantiomers and the cyclodextrins as well as complex mobilities were determined to understand the migration behavior of the analytes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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...

Oral, ultra–long-lasting drug delivery: Application toward malaria elimination goals

PubMed Central

Bellinger, Andrew M.; Jafari, Mousa; Grant, Tyler M.; Zhang, Shiyi; Slater, Hannah C.; Wenger, Edward A.; Mo, Stacy; Lee, Young-Ah Lucy; Mazdiyasni, Hormoz; Kogan, Lawrence; Barman, Ross; Cleveland, Cody; Booth, Lucas; Bensel, Taylor; Minahan, Daniel; Hurowitz, Haley M.; Tai, Tammy; Daily, Johanna; Nikolic, Boris; Wood, Lowell; Eckhoff, Philip A.; Langer, Robert; Traverso, Giovanni

2017-01-01

Efforts at elimination of scourges, such as malaria, are limited by the logistic challenges of reaching large rural populations and ensuring patient adherence to adequate pharmacologic treatment. We have developed an oral, ultra–long-acting capsule that dissolves in the stomach and deploys a star-shaped dosage form that releases drug while assuming a geometry that prevents passage through the pylorus yet allows passage of food, enabling prolonged gastric residence. This gastric-resident, drug delivery dosage form releases small-molecule drugs for days to weeks and potentially longer. Upon dissolution of the macrostructure, the components can safely pass through the gastrointestinal tract. Clinical, radiographic, and endoscopic evaluation of a swine large-animal model that received these dosage forms showed no evidence of gastrointestinal obstruction or mucosal injury. We generated long-acting formulations for controlled release of ivermectin, a drug that targets malaria-transmitting mosquitoes, in the gastric environment and incorporated these into our dosage form, which then delivered a sustained therapeutic dose of ivermectin for up to 14 days in our swine model. Further, by using mathematical models of malaria transmission that incorporate the lethal effect of ivermectin against malaria-transmitting mosquitoes, we demonstrated that this system will boost the efficacy of mass drug administration toward malaria elimination goals. Encapsulated, gastric-resident dosage forms for ultra–long-acting drug delivery have the potential to revolutionize treatment options for malaria and other diseases that affect large populations around the globe for which treatment adherence is essential for efficacy. PMID:27856796

Addictive drugs and brain stimulation reward.

PubMed

Wise, R A

1996-01-01

Direct electrical or chemical stimulation of specific brain regions can establish response habits similar to those established by natural rewards such as food or sexual contact. Cocaine, mu and delta opiates, nicotine, phencyclidine, and cannabis each have actions that summate with rewarding electrical stimulation of the medial forebrain bundle (MFB). The reward-potentiating effects of amphetamine and opiates are associated with central sites of action where these drugs also have their direct rewarding effects, suggesting common mechanisms for drug reward per se and for drug potentiation of brain stimulation reward. The central sites at which these and perhaps other drugs of abuse potentiate brain stimulation reward and are rewarding in their own right are consistent with the hypothesis that the laboratory reward of brain stimulation and the pharmacological rewards of addictive drugs are habit forming because they act in the brain circuits that subserve more natural and biologically significant rewards.

Long-acting combination anti-HIV drug suspension enhances and sustains higher drug levels in lymph node cells than in blood cells and plasma.

PubMed

Kraft, John C; McConnachie, Lisa A; Koehn, Josefin; Kinman, Loren; Collins, Carol; Shen, Danny D; Collier, Ann C; Ho, Rodney J Y

2017-03-27

The aim of the present study was to determine whether a combination of anti-HIV drugs - tenofovir (TFV), lopinavir (LPV) and ritonavir (RTV) - in a lipid-stabilized nanosuspension (called TLC-ART101) could enhance and sustain intracellular drug levels and exposures in lymph node and blood cells above those in plasma. Four macaques were given a single dose of TLC-ART101 subcutaneously. Drug concentrations in plasma and mononuclear cells of the blood (PBMCs) and lymph nodes (LNMCs) were analysed using a validated combination LC-MS/MS assay. For the two active drugs (TFV, LPV), plasma and PBMC intracellular drug levels persisted for over 2 weeks; PBMC drug exposures were three- to four-fold higher than those in plasma. Apparent terminal half-lives (t1/2) of TFV and LPV were 65.3 and 476.9 h in plasma, and 169.1 and 151.2 h in PBMCs. At 24 and 192 h, TFV and LPV drug levels in LNMCs were up to 79-fold higher than those in PBMCs. Analysis of PBMC intracellular TFV and its active metabolite TFV-diphosphate (TFV-DP) indicated that intracellular exposures of total TFV and TFV-DP were markedly higher and persisted longer than in humans and macaques dosed with oral TFV prodrugs, tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF). A simple, scalable three-drug combination, lipid-stabilized nanosuspension exhibited persistent drug levels in cells of lymph nodes and the blood (HIV host cells) and in plasma. With appropriate dose adjustment, TLC-ART101 may be a useful HIV treatment with a potential to impact residual virus in lymph nodes.

SQ109, a New Drug Lead for Chagas Disease

PubMed Central

Veiga-Santos, Phercyles; Li, Kai; Lameira, Lilianne; de Carvalho, Tecia Maria Ulisses; Huang, Guozhong; Galizzi, Melina; Shang, Na; Li, Qian; Gonzalez-Pacanowska, Dolores; Hernandez-Rodriguez, Vanessa; Benaim, Gustavo; Guo, Rey-Ting; Urbina, Julio A.; Docampo, Roberto; de Souza, Wanderley

2015-01-01

We tested the antituberculosis drug SQ109, which is currently in advanced clinical trials for the treatment of drug-susceptible and drug-resistant tuberculosis, for its in vitro activity against the trypanosomatid parasite Trypanosoma cruzi, the causative agent of Chagas disease. SQ109 was found to be a potent inhibitor of the trypomastigote form of the parasite, with a 50% inhibitory concentration (IC50) for cell killing of 50 ± 8 nM, but it had little effect (50% effective concentration [EC50], ∼80 μM) in a red blood cell hemolysis assay. It also inhibited extracellular epimastigotes (IC50, 4.6 ± 1 μM) and the clinically relevant intracellular amastigotes (IC50, ∼0.5 to 1 μM), with a selectivity index of ∼10 to 20. SQ109 caused major ultrastructural changes in all three life cycle forms, as observed by light microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). It rapidly collapsed the inner mitochondrial membrane potential (Δψm) in succinate-energized mitochondria, acting in the same manner as the uncoupler FCCP [carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone], and it caused the alkalinization of internal acidic compartments, effects that are likely to make major contributions to its mechanism of action. The compound also had activity against squalene synthase, binding to its active site; it inhibited sterol side-chain reduction and, in the amastigote assay, acted synergistically with the antifungal drug posaconazole, with a fractional inhibitory concentration index (FICI) of 0.48, but these effects are unlikely to account for the rapid effects seen on cell morphology and cell killing. SQ109 thus most likely acts, at least in part, by collapsing Δψ/ΔpH, one of the major mechanisms demonstrated previously for its action against Mycobacterium tuberculosis. Overall, the results suggest that SQ109, which is currently in advanced clinical trials for the treatment of drug-susceptible and drug

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.

Narcotic Drug and Marihuana Controls.

ERIC Educational Resources Information Center

Miller, Donald E.

As a background paper for the National Association of Student Personnel Administrators Drug Education Conference held in November, 1966, this paper focuses first on narcotic control in general, and second, on the reasons for insisting on marijuana control. Brief descriptions are given of the currently existing narcotics acts at federal and state…

Drug-induced apnea.

PubMed

Boutroy, M J

1994-01-01

Drugs have been in the past and will in the future still be liable to induce apnea in neonates, infants and older children. At these different stages of development, the child may be abnormally vulnerable to respiratory disorders and apnea, and doses of drugs, without any abnormal side effects in adult patients, can be harmful in younger subjects. Drugs responsible for apnea during development are numerous, but more than half of the problems are induced by sedatives and hypnotics, among which phenothiazines, barbiturates, benzodiazepines (included transplacentally acquired) and general anesthetics are a few. Other pharmacological families are apnea inducers in the neonatal period and childhood: analgesics and opioid narcotics, agents acting at the levels of neuromuscular function and autonomic ganglia, and cardiovascular agents. The pathogenesis of these apneas depends on the disturbance of any mechanism responsible for the respiratory activity: medullary centers and brain stem structures, afferent influx to CNS, sleep stages, upper airways, lungs and respiratory muscles. At key stages such as birth and infancy, drugs may emphasize the particular sensitivity of the mechanisms responsible for inducing apnea. This might explain unexpected respiratory disorders during development.

Keeping the lid on: a century of drug regulation and control.

PubMed

Spillane, Joseph; McAllister, William B

2003-06-05

Since the early 1900s, national and international drug control legislation has acted as a key site of contention between important societal actors. Physicians and pharmacists, regulators and drug companies, patients and addicts, and researchers and pharmacologists all attempted to influence formulation and interpretation of the rules that regulate access to addicting but medically useful substances. The 1970 Controlled Substances Act (CSA) consolidated and rationalized previous US domestic legislation and paid careful attention to the international aspects of the issue. Yet the CSA also incorporated long-standing fundamental disputes about who would act as gatekeepers, what criteria would be employed in regulatory decisions, and the basic goals of drug control legislation. Rather than view the CSA as a beginning or an end, it is better conceived as a major milepost in a century-long odyssey of maneuvering among interested parties for advantage in a complex regulatory environment. Instead of providing a definitive authoritative structure to which all parties must adhere, the CSA has served as a vehicle for discernment and continuous renegotiation of essential concepts such as "abuse liability".

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

Anti-inflammatory properties of drugs from saffron crocus.

PubMed

Poma, Anna; Fontecchio, Gabriella; Carlucci, Giuseppe; Chichiriccò, Giuseppe

2012-01-01

The medicinal uses of saffron (Crocus sativus Linnaeus) have a long history beginning in Asian countries since the Late Bronze Age. Recent studies have validated its potential to lower the risk of several diseases. Some metabolites derived from saffron stigmas exert numerous therapeutic effects due to hypolipidemic, antitussive, antioxidant, antidiabetic activities and many others. Water and ethanol extracts of Crocus sativus L. are cardioprotective and counteract neurodegenerative disorders. Many of these medicinal properties of saffron can be attributed to a number of its compounds such as crocetin, crocins and other substances having strong antioxidant and radical scavenger properties against a variety of radical oxygen species and pro-inflammatory cytokines. Botany, worldwide spreading of cultivars, biochemical pathways, active constituents and chemical detection methods are reviewed. Therapeutic uses of saffron principles with particular regard to those exhibiting antioxidant and thus anti-inflammatory features are discussed. To date, very few adverse health effects of saffron have been demonstrated. At high doses (more than 5 g/die day), it should be avoided in pregnancy owing to its uterine stimulation activity.

Mood effects of antiepileptic drugs.

PubMed

Reijs, Rianne; Aldenkamp, Albert P; De Krom, Marc

2004-02-01

This article reviews our knowledge about a specific subgroup of chronic CNS-related side effects of antiepileptic drugs (AED) treatment, i.e., the effects of AEDs on mood. In line with a recent hypothesis, using the experience of AED treatment in psychiatry, we examined whether mood effects are related to the known anticonvulsant mechanisms of action of the AEDs. Specifically we examined whether AEDs, acting through potentiation of GABAergic neurotransmitter release, have "sedating" effects on mood, whereas AEDs that act through the reduction of excitatory glutamate neurotransmitter release have "activating" effects on mood. The results of this review yield evidence that there are relationships between the known anticonvulsant mechanisms of action of the AEDs and mood effects. Mood effects occur especially when the drugs have a sustained effect on neuronal mechanisms, in particular when the inhibitory or excitatory neurotransmitter release is altered. Drugs with "use-dependent" impact on sodium or calcium channels probably have a more transient impact and do not lead to interictal stable mood effects. Drugs with multiple mechanisms of action seem to combine a favorable efficacy profile with an increased risk of severe mood problems. The quality of the evidence, however, is not conclusive and there are many paradoxical results. One reason for this lack of "fit" may be the use in this review of a simplified classification, based only on the predominant mechanism of action to classify a drug. Only a limited number of AEDs (ethosuximide, tiagabine) are characterized by a single anticonvulsant mechanism of action. Probably more detailed coupling of mechanisms of action (e.g., inspecting the type and route of impact on GABA release) and mood effects may give less confusing results. The use of magnetic resonance imaging techniques such as spectroscopy may provide interesting results.

Drug driving and the management of risk: the perspectives and practices of a sample of problem drug users.

PubMed

McIntosh, James; O'Brien, Tommy; McKeganey, Neil

2008-06-01

This paper reports on a qualitative study of the attitudes and risk management strategies of a sample of problem drug users in relation to driving while under the influence of drugs. Interviews were conducted with 26 individuals (21 men and 5 women) all of whom had been addicted to heroin and had admitted to driving while under the influence of illegal drugs. The drug users reported four main strategies for managing the risks associated with drug driving: attempting to limit their drug intake to their tolerance level; delaying driving after taking a drug until they felt safe; stopping driving if they felt unsafe while behind the wheel; and avoiding driving altogether under the influence of certain drugs. However, the interviewees' accounts of their drug driving behaviour suggest that these strategies are not only far from reliable, they may also act to encourage drug driving by creating a false sense of security. The reassurance they provide may also undermine any educational messages targeting drug driving. There was little in the problem users' accounts to suggest that media campaigns or a more effective method of detection would have much influence upon their behaviour. The paper concludes that the most realistic approach to the problem may be to incorporate drug driving interventions within drug treatment programmes.

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.

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.

Revisiting "the origins of compulsory drug prescriptions".

PubMed Central

Marks, H M

1995-01-01

It has been argued that today's prescription drug market originated in the arbitrary acts of the US Food and Drug Administration (FDA), which in 1938 issued regulations creating a class of drugs that could be sold by prescription only. On the basis of the FDA's administrative records, I argue that the 1938 regulations on prescription drug labeling were initiated by industry and then agreed to by the FDA; that contemporaries understood and accepted the reasons for restricting the use of certain drugs; and that the subsequent evolution of these regulations is best understood as an FDA effort to limit industry abuses of the prescription labeling system. This decade-long war of position ended when drug manufacturers persuaded the US Congress to enshrine their version of prescription labeling in law in a highly politicized struggle over government's role in the economy. Images FIGURE 1 PMID:7832245

[Parental representations of children's cough and expectations on its management].

PubMed

Ventaja, G; Steyer, E; Machu, J-L; Boivin, J-M

2016-04-01

Providing medications for the management of acute cough in infants less than 24 months, a frequent reason for medical consultation, has recently been reduced by the contraindication of various antitussive specialties in France. The objective of this study was to assess the expectations and fears of coughing infants' parents, to determine their representations of coughing, and to quantify the use of self-medication and the risk of a deferral requests to prescribe other drug classes. An opinion and cross-survey was carried out with parents of infants under 24 months of age. A multiple-choice questionnaire was proposed to them in day care centers and Mother and Infant Welfare centers. The data collected were analyzed descriptively and using the Chi(2) test. Logistic regression enabled us to interpret some of the results. Sixty-four percent of parents expect an antitussive treatment from the doctor. For most parents, lifestyle modifications are well integrated (nasal irrigation, considered effective cough relief, hydration, smoking cessation). For 33 % of parents, corticosteroids are an alternative therapy to stop cough. Nearly half (43 %) of parents have sought treatment from their doctor, usually nasal suspensions, corticosteroids, and saline irrigation. Regarding self-medication, 30 % of parents have already given cough syrup or an antitussive suppository without a prescription, in order to stop the cough rapidly for 66 % of them. These parents seem more worried by coughing than other parents (P=0.0110, CI: 0.217; 1.751) as did those who had only one child (P=0.0029, CI: 0.120; 0.582). This study suggests that a large majority of parents understand and accept the new recommendations. But one-third of parents are still worried, not knowing what to do without prescribed medications, which led them to give nonprescription cough syrups and ask for inappropriate treatments. It seems essential to inform parents about the natural history of infant coughing and educate them

Effects of the Antipsychotic Drug, Haloperidol, on Reproduction in the Fathead Minnow

EPA Science Inventory

Haloperidol is a butyrophenone antipsychotic drug used for the treatment of human hyperactive and manic disorders, agitation, and schizophrenia. The drug is thought to act through antagonism of dopaminergic receptors. We have studied a variety of endocrine-disrupting chemicals wi...

Strategic Analysis of the War on Drugs

DTIC Science & Technology

1991-04-09

of the 1960s the drug culture had expanded considerably in the arts and entertainment industries, to college campuses, and to the young in general...At that time, the principal drug of choice was marihuana and to a lesser degree cocaine. 3 Debate over the benign nature of cocaine again surfaced in...widespread use. At least as strong a case could be made for legalizing it as for legalizing marihuana . Short acting--about 15 minutes--not physically

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

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

21 CFR 207.31 - Additional drug listing information.

Code of Federal Regulations, 2010 CFR

2010-04-01

... carry out the purposes of the act, a quantitative listing of all ingredients. (3) For a particular drug... Product Listing). (c) It is requested but not required that a quantitative listing of the active...

Triple-acting antimicrobial treatment for 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. Staphylococcus aureus (S. aureus) is a notorious pathogen for both animal and human health with multi-d...

Triple-acting antimicrobial treatment for 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. Staphylococcus aureus (S. aureus) is a notorious pathogen for both animal and human health with multi-d...

Role of Dopamine Signaling in Drug Addiction.

PubMed

Chen, Wan; Nong, Zhihuan; Li, Yaoxuan; Huang, Jianping; Chen, Chunxia; Huang, Luying

2017-01-01

Addiction is a chronic, relapsing disease of the brain that includes drug-induced compulsive seeking behavior and consumption of drugs. Dopamine (DA) is considered to be critical in drug addiction due to reward mechanisms in the midbrain. In this article, we review the major animal models in addictive drug experiments in vivo and in vitro. We discuss the relevance of the structure and pharmacological function of DA receptors. To improve the understanding of the role of DA receptors in reward pathways, specific brain regions, including the Ventral tegmental area, Nucleus accumbens, Prefrontal cortex, and Habenula, are highlighted. These factors contribute to the development of novel therapeutic targets that act at DA receptors. In addiction, the development of neuroimaging method will increase our understanding of the mechanisms underlying drug addiction. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Continued Steps towards Drug-Free Schools in AISD: 1989-90.

ERIC Educational Resources Information Center

Smyer, Roxane; Wilkinson, David

The Austin (Texas) Independent School District (AISD) has received federal funds through the Drug-Free Schools and Communities Act of 1986. The AISD has established a four-fold approach to educate students in kindergarten through grade 12 about the dangers of drugs and alcohol. The four components of the program include: (1) a core committee…

2-Aryl-5-carboxytetrazole as a New Photoaffinity Label for Drug Target Identification

PubMed Central

2016-01-01

Photoaffinity labels are powerful tools for dissecting ligand–protein interactions, and they have a broad utility in medicinal chemistry and drug discovery. Traditional photoaffinity labels work through nonspecific C–H/X–H bond insertion reactions with the protein of interest by the highly reactive photogenerated intermediate. Herein, we report a new photoaffinity label, 2-aryl-5-carboxytetrazole (ACT), that interacts with the target protein via a unique mechanism in which the photogenerated carboxynitrile imine reacts with a proximal nucleophile near the target active site. In two distinct case studies, we demonstrate that the attachment of ACT to a ligand does not significantly alter the binding affinity and specificity of the parent drug. Compared with diazirine and benzophenone, two commonly used photoaffinity labels, in two case studies ACT showed higher photo-cross-linking yields toward their protein targets in vitro based on mass spectrometry analysis. In the in situ target identification studies, ACT successfully captured the desired targets with an efficiency comparable to the diazirine. We expect that further development of this class of photoaffinity labels will lead to a broad range of applications across target identification, and validation and elucidation of the binding site in drug discovery. PMID:27740749

2-Aryl-5-carboxytetrazole as a New Photoaffinity Label for Drug Target Identification.

PubMed

Herner, András; Marjanovic, Jasmina; Lewandowski, Tracey M; Marin, Violeta; Patterson, Melanie; Miesbauer, Laura; Ready, Damien; Williams, Jon; Vasudevan, Anil; Lin, Qing

2016-11-09

Photoaffinity labels are powerful tools for dissecting ligand-protein interactions, and they have a broad utility in medicinal chemistry and drug discovery. Traditional photoaffinity labels work through nonspecific C-H/X-H bond insertion reactions with the protein of interest by the highly reactive photogenerated intermediate. Herein, we report a new photoaffinity label, 2-aryl-5-carboxytetrazole (ACT), that interacts with the target protein via a unique mechanism in which the photogenerated carboxynitrile imine reacts with a proximal nucleophile near the target active site. In two distinct case studies, we demonstrate that the attachment of ACT to a ligand does not significantly alter the binding affinity and specificity of the parent drug. Compared with diazirine and benzophenone, two commonly used photoaffinity labels, in two case studies ACT showed higher photo-cross-linking yields toward their protein targets in vitro based on mass spectrometry analysis. In the in situ target identification studies, ACT successfully captured the desired targets with an efficiency comparable to the diazirine. We expect that further development of this class of photoaffinity labels will lead to a broad range of applications across target identification, and validation and elucidation of the binding site in drug discovery.

Drug-DNA interactions at single molecule level: A view with optical tweezers

NASA Astrophysics Data System (ADS)

Paramanathan, Thayaparan

Studies of small molecule--DNA interactions are essential for developing new drugs for challenging diseases like cancer and HIV. The main idea behind developing these molecules is to target and inhibit the reproduction of the tumor cells and infected cells. We mechanically manipulate single DNA molecule using optical tweezers to investigate two molecules that have complex and multiple binding modes. Mononuclear ruthenium complexes have been extensively studied as a test for rational drug design. Potential drug candidates should have high affinity to DNA and slow dissociation kinetics. To achieve this, motifs of the ruthenium complexes are altered. Our collaborators designed a dumb-bell shaped binuclear ruthenium complex that can only intercalate DNA by threading through its bases. Studying the binding properties of this complex in bulk studies took hours. By mechanically manipulating a single DNA molecule held with optical tweezers, we lower the barrier to thread and make it fast compared to the bulk experiments. Stretching single DNA molecules with different concentration of drug molecules and holding it at a constant force allows the binding to reach equilibrium. By this we can obtain the equilibrium fractional ligand binding and length of DNA at saturated binding. Fitting these results yields quantitative measurements of the binding thermodynamics and kinetics of this complex process. The second complex discussed in this study is Actinomycin D (ActD), a well studied anti-cancer agent that is used as a prototype for developing new generations of drugs. However, the biophysical basis of its activity is still unclear. Because ActD is known to intercalate double stranded DNA (dsDNA), it was assumed to block replication by stabilizing dsDNA in front of the replication fork. However, recent studies have shown that ActD binds with even higher affinity to imperfect duplexes and some sequences of single stranded DNA (ssDNA). We directly measure the on and off rates by

Arylamine N-acetyltransferases: from drug metabolism and pharmacogenetics to drug discovery

PubMed Central

Sim, E; Abuhammad, A; Ryan, A

2014-01-01

Arylamine N-acetyltransferases (NATs) are polymorphic drug-metabolizing enzymes, acetylating arylamine carcinogens and drugs including hydralazine and sulphonamides. The slow NAT phenotype increases susceptibility to hydralazine and isoniazid toxicity and to occupational bladder cancer. The two polymorphic human NAT loci show linkage disequilibrium. All mammalian Nat genes have an intronless open reading frame and non-coding exons. The human gene products NAT1 and NAT2 have distinct substrate specificities: NAT2 acetylates hydralazine and human NAT1 acetylates p-aminosalicylate (p-AS) and the folate catabolite para-aminobenzoylglutamate (p-abaglu). Human NAT2 is mainly in liver and gut. Human NAT1 and its murine homologue are in many adult tissues and in early embryos. Human NAT1 is strongly expressed in oestrogen receptor-positive breast cancer and may contribute to folate and acetyl CoA homeostasis. NAT enzymes act through a catalytic triad of Cys, His and Asp with the architecture of the active site-modulating specificity. Polymorphisms may cause unfolded protein. The C-terminus helps bind acetyl CoA and differs among NATs including prokaryotic homologues. NAT in Salmonella typhimurium supports carcinogen activation and NAT in mycobacteria metabolizes isoniazid with polymorphism a minor factor in isoniazid resistance. Importantly, nat is in a gene cluster essential for Mycobacterium tuberculosis survival inside macrophages. NAT inhibitors are a starting point for novel anti-tuberculosis drugs. Human NAT1-specific inhibitors may act in biomarker detection in breast cancer and in cancer therapy. NAT inhibitors for co-administration with 5-aminosalicylate (5-AS) in inflammatory bowel disease has prompted ongoing investigations of azoreductases in gut bacteria which release 5-AS from prodrugs including balsalazide. PMID:24467436

Monoclonal antibody form and function: manufacturing the right antibodies for treating drug abuse.

PubMed

Peterson, Eric; Owens, S Michael; Henry, Ralph L

2006-05-26

Drug abuse continues to be a major national and worldwide problem, and effective treatment strategies are badly needed. Antibodies are promising therapies for the treatment of medical problems caused by drug abuse, with several candidates in preclinical and early clinical trials. Monoclonal antibodies can be designed that have customized affinity and specificity against drugs of abuse, and because antibodies can be designed in various forms, in vivo pharmacokinetic characteristics can be tailored to suit specific clinical applications (eg, long-acting for relapse prevention, or short-acting for overdose). Passive immunization with antibodies against drugs of abuse has several advantages over active immunization, but because large doses of monoclonal antibodies may be needed for each patient, efficient antibody production technology is essential. In this minireview we discuss some of the antibody forms that may be effective clinical treatments for drug abuse, as well as several current and emerging production systems that could bridge the gap from discovery to patient use.

Preparing for the physician payment sunshine act.

PubMed

Dickerson, David M; Naidu, Ramana K

2014-01-01

In March of 2010, President Barack Obama signed into law the Patient Protection and Affordable Care Act, ushering in an era of health care reform. Section 6002 of the bill, the Physician Payment Sunshine Act, requires manufacturers of drugs, devices, biological therapeutics, and medical supplies to disclose to the Centers for Medicare and Medicaid Services any payments or transfers of value to physicians. These reports are not meant to prohibit relationships between physicians and industry, but rather to generate a searchable public database illustrating the purpose of the payment, the entities involved, and the timing of each occurrence. Although the bill is meant to reveal physician-industry relationships, the question of how society at large and the medical field will interpret these data are unknown. The purpose of this article is to inform physicians of the components of the Physician Payment Sunshine Act. We discuss several resultant challenges and suggest a framework for preparing for transparency reporting and its potential effects.

Employment Outcomes of Chemical Dependency Treatment and Additional Vocational Services Publicly Funded by Washington State. A Four-and-a-Half Year Follow-up Study of Indigent Persons served by Washington State's Alcoholism and Drug Addiction Treatment and Support Act (ADATSA). Key Findings. Briefing Paper.

ERIC Educational Resources Information Center

Brown, Marsha; Longhi, Dario; Luchansky, Bill

In 1987, the state of Washington created a program--the Alcohol and Drug Addiction Treatment and Support Act (ADATSA)--to treat adults addicted to alcohol or other drugs. This paper sows the results of a four-and-a-half year follow-up study of clients receiving treatment and reviews the effectiveness of ADATSA. Whereas the immediate goal of the…

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