side-effects

Off-label Drug Use: Fact vs. Fiction

Posted by cdavenport on Friday Aug 17, 2012 Under Drug Promotion, Drug Safety, FDA

The authors – CM Wittich, CM Burkle, and WL Lanier – offer a concise review of the topic of off-label drug use including its definition, prevalence, and implications for drug safety.   The article format addresses 10 common questions and their answers about off-label drug use.  The breadth of application, its acceptance, and the liabilities of off-label use are explored.  A history of FDA regulations surrounding the practice is presented, which helps to put its evolution into proper perspective.  Off-label use, which occurs in every medical specialty, is more common in patient populations not likely to be included in clinical trials (e.g., pediatric, pregnant, or psychiatric patients).  Once a medication is marketed, the FDA does not limit or control how the medication is prescribed by physicians. The pros and cons of the distribution of information regarding the off-label use of medications by pharmaceutical companies, the use of informed consent, and the liability of prescribing physicians are discussed.

SourceMayo Clinic Proceedings  – pdf of full article.

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Linguamatics, the leader in natural language processing (NLP)-based text mining, announced that the Federal Drug Administration’s (FDA) Center for Drug Evaluation and Research (CDER) has licensed its 12E text mining platform as a discovery and decision support tool to supplement laboratory research efforts on drug safety.  The FDA will use the platform to review published literature and drug product labels to address key biomedical issues, including mechanisms of drug toxicity and disease processes.  In addition to document retrieval, the 12E platform can identify, extract, synthesize, and analyze relevant facts and relationships (e.g., between genes and diseases, drugs and side effects).  Customers include top tier commercial, academic, and governmental organizations, including 9 of the top 10 global pharmaceutical companies.  The 12E platform is available both as an in-house or cloud-based system.

Typical applications in pharmaceutical, biotechnology, and healthcare include:
•    Mapping gene-disease relationships and identifying potentially novel therapeutic targets
•    Biomarker discovery
•    Drug repurposing
•    Drug safety
•    Patent analysis
•    Clinical trial site selection and study design
•    Mining electronic medical records to improve prediction of health outcomes
•    Translational medicine
•    Competitive intelligence
•    Social media mining
•    Subjective data mining (sentiment analysis, key opinion mining)

SourcesBioSpace and Business Weekly

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PDUFA V: Risk – Benefit Emphasis New

Posted by cdavenport on Friday Jun 29, 2012 Under Drug Safety, FDA, Risk Management

What is new about PDUFA V?   Congress, the media, and the public have a history of boiling down the issue to whether drugs are safe or not safe.  In reality the issue is benefit versus risk.   In addition, this judgement needs to be aligned with that of the patients who take the medication.  Emphasis on this risk-benefit framework is a landmark difference in the pending PDUFA V legislation.

Source:  Nature

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Drug Safety: Tip of the Iceberg

Posted by cdavenport on Thursday Jun 7, 2012 Under Drug Safety, FDA, Post-market Surveillance, Risk Management, toxicity

The 10 drugs with the largest numbers of reports sent directly to the FDA by healthcare practitioners and consumers in 2011 in order of frequency are Pradaxa, Coumadin, Levaquin, Carboplatin, Zestril, Cisplatin, Zocor, Cymbalta, Cipro and Bactrim.  It is interesting to note that just two of these drugs were first introduced in the last decade (Pradaxa and Cymbalta), and only one in the previous year (Pradaxa), suggesting that major drug safety issues are not confined to recently approved drugs.  On one hand, this shows that FDA and manufacturer safety surveillance programs have identified these significant safety risks. On the other, it illustrates that placing warnings in product information only begins the process of managing drug safety risks.   Relative rates vs. report expectations are detailed.

These data come from QuarterWatch™ an Institute for Safe Medication Practices surveillance program that monitors all serious and fatal adverse drug events (ADEs) reported to the Food and Drug Administration through MedWatch, its adverse event reporting system.  The goal is to identify signals that may represent important new drug safety issues.

Source:  Philly.com/Health

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Drug Labels: Toxicity or Information Overload?

Posted by cdavenport on Saturday May 28, 2011 Under Drug Safety, Risk Management, toxicity

Side effect overload on drug labels has less to do with true toxicity and drug safety than with manufacturer liability.  Examination of more than 5600 drug labels yielded over half a million side effects.  An average drug label and the more commonly prescribed drugs averaged 70 and 100 side effects, respectively.  The upper range in a single label was 525 reactions.  Information overload can overwhelm physicians, who must weigh the risks and benefits when prescribing a medication.  The Food and Drug Administration discourages such ‘over warning,’ but information overload is presently the rule rather than the exception.  Not surprisingly, medications typically used by psychiatrists and neurologists had the most complex labels, while drugs used by dermatologists and ophthalmologists had the least.  Although providing drug safety information more efficiently to both health care providers and the public is warranted, drug manufacturer liability concerns must also be addressed.

Source: Drug Discovery and Development

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Turbulent Blood Flow may Increase Cardiovascular Risk

Posted by cdavenport on Wednesday Feb 23, 2011 Under Cardiovascular, Drug Safety, toxicity

By utilizing the basic principles of hemodynamics and hydraulics, research suggests that fluid retention is detrimental for the cardiovascular system because it increases the likelihood of turbulent blood flow, regardless of whether or not blood pressure is raised.  Increased turbulence promotes endothelial dysfunction, thereby contributing to the development of atherosclerotic cardiovascular disease.  Fluid retention induces hypertension in some individuals, increases stroke volume (the amount of blood that is ejected by the heart with each contraction) in others, and causes edema.  Some blood pressure lowering medications also increase stroke volume and cause edema but prevent heart attacks and strokes when used to treat hypertension.  For drugs that increase the risk of adverse cardiovascular events, it may be possible to reduce or neutralize the increased risk by simultaneous diuretic administration.

Source: ScienceBlog

Original Article: Clinical Hemorheology and Microcirculation (free pdf)

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As of 15 June 2010, the new Food and Drug Administration (FDA) Postmarketing Drug Safety Evaluation website was launched.   The FDA posted postmarket safety evaluations for 26 drugs approved between September 2007 and January 2008 and is reviewing an additional 20 or 30 others. To date, no label changes have been recommended.

In accordance with the Food and Drug Administration Amendments Act of 2007 (FDAAA), the FDA now summarizes information about ongoing and completed postmarketing safety evaluations of serious adverse events (SAE) submitted to the FDA for New Drug Applications (NDAs) and Biologic License Applications (BLAs) that have been approved since 27 September 2007.   These evaluations are completed to determine if there are any new SAE not previously identified during product development, known side effects reported in unusual number, or potential new safety concerns identified post approval.  These postmarketing evaluations will be performed no later than 18 months following approval (i.e., early in the product’s marketed life cycle) or after its use by 10,000 individuals, whichever is later.

To develop these postmarketing safety evaluations the FDA assesses several data sources including:
• The product’s pre-approval safety profile
• The product’s current FDA-approved label
• Reports made to FDA’s Adverse Event Reporting System (AERS)
• Reports made to the Vaccine Adverse Event Reporting System (VAERS)
• Manufacturer-submitted periodic safety reports
• Medical literature
• Drug utilization databases
• Data from post-approval clinical trials and other studies, when applicable

FDA analyses for the safety evaluations include:
• Data mining analysis of all adverse event reports in the AERS or VAERS databases
• Review serious adverse event reports
• Medication error analysis
• Product utilization analysis
• Risk management review
• Analysis of post-approval safety data from clinical trials and other studies, when applicable

Summaries of FDA safety analyses on recently approved products will now be prepared quarterly and posted on FDA’s website along with a brief discussion of the steps FDA is taking to address any identified safety issues.

Related posts:

New On-line Quarterly Drug Safety Summary and REMS are Complimentary Efforts
Postmarket Drug Safety: Institute of Medicine Recommendations to FDA

Sources:

FDA-1,   FDA-2,   Resource Shelf,   USA Today,   World Pharma News

To share this post easily, cut and paste:  New FDA Postmarketing Drug Safety Evaluation Website   http://bit.ly/b79Fqs

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Although drugs are usually targeted to be selective for a single protein, it is recognized that other proteins may also be affected, a phenomenon called polypharmacology.  While off-target interactions can cause potentially harmful side-effects, in some cases, an effect on an unintended target might suggest new disease indications for established drugs. 

Chemoinformatics, statistical programs, and experimental techniques are being utilized by Brian Shoichet of the University of California San Francisco to predict off-target interactions.  Similarities between 3665 (existing and experimental) drugs and a set of over 65,000 known ligands to protein receptors in the body were examined.  In addition, the ligands were arranged into around 250 classes depending on the type of receptor to which they bind.  This exhaustive survey yielded hundreds of previously unrecognised potential interactions between drugs and protein receptors in the body.   A number of these potential interactions were confirmed by laboratory experiments, including identification of the key receptor that binds the hallucinatory drug dimethyltryptamine.

These new computational techniques should not only prove valuable to pharmaceutical companies to both expand existing pipelines and to reap additional benefits from current compounds, they should also aid researchers to anticipate and avoid unanticipated adverse events.

Source: Chemistry World

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