Expert opinion on drug safety
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Expert Opin Drug Saf · Jun 2014
Aspirin and age-related macular degeneration: positives versus negatives.
The anti-inflammatory, analgesic, antipyretic and antithrombotic activities of aspirin confer its wide therapeutic application. The three former activities require higher doses of aspirin, whereas the latter can be achieved through a lower, thus safer dose of the drug. Low-dose, long-term aspirin is used as an antithrombotic therapy to prevent cardiovascular disease. ⋯ This editorial addresses the important issue of possible beneficial and adverse effects of long-term, low-dose aspirin treatment of AMD patients. Special emphasis is given to the ability of aspirin to acetylate cyclooxygenases (especially COX-2) and thus to initiate a biochemical pathway leading to the generation of anti-inflammatory pro-resolving mediators synthesized from both ω-3 and ω-6 long-chain polyunsaturated fatty acids. Such mediators (e.g., resolvins, lipoxins) may be of therapeutic value in retarding the development of dry form AMD.
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Expert Opin Drug Saf · May 2014
ReviewDabigatran etexilate for venous thromboembolism: a safety evaluation.
Recently, new oral anticoagulants (NOACs) have become available to treat thromboembolic disorders. The efficacy and safety of these agents have been thoroughly tested in various clinical trials. In this article, we discuss the evidence for the safety and efficacy of dabigatran in the prevention and treatment of venous thromboembolism (VTE). ⋯ For most patients the overall net clinical benefit would seem to be in favour of dabigatran. Both efficacy and safety have been proven in the setting of robust randomised controlled trials. 'Real world' registry data as well as long-term trial follow-up will add further critical information. Long-term experience might be one of the few advantages warfarin still has over dabigatran in patients who are eligible for both.
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In 2008, the US FDA required all new glucose-lowering therapies to show cardiovascular safety, and this applies to the dipeptidyl peptidase-4 inhibitors ('gliptins'). ⋯ The Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus - Thrombolysis in Myocardial Infarction 53 trial and Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care were both multicentre, randomised, double-blind, placebo-controlled, Phase IV clinical trials. These trials showed that saxagliptin and alogliptin did not increase the primary end point, which was a composite of cardiovascular outcomes that did not include hospitalisations for heart failure. However, saxagliptin significantly increased hospitalisation for heart failure, which was a component of the secondary end point. The effect of alogliptin on hospitalisations for heart failure has not been reported. Neither agent improved cardiovascular outcomes. As there is no published evidence of improved outcomes with gliptins, it is unclear to us why these agents are so widely available for use. We suggest that the use of gliptins be restricted to Phase IV clinical trials until such time as cardiovascular safety and benefits/superiority are clearly established.
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Expert Opin Drug Saf · May 2014
Review Meta AnalysisAn evidence based systematic review of remifentanil associated opioid-induced hyperalgesia.
Therapeutic opioid use continues to grow, with greater than a fivefold increase in usage of fentanyl-based products over a 10-year period. Opioids are known for their side-effect profile, including bradycardia and respiratory depression; questions remain, however, regarding lesser known side effects such as opioid-induced hyperalgesia (OIH). ⋯ There is conflicting evidence regarding the existence of remifentanil OIH. Outcomes evaluating measures of hyperalgesia frequently conclude that remifentanil OIH exists, while those evaluating opioid consumption do not. Therefore, remifentanil does induce a degree of hyperalgesia, but we do not believe that it reaches a level of clinical significance that requires prevention. If a significant concern for the development of remifentanil OIH is suspected, we suggest using the least possible effective dose of remifentanil as the primary prevention strategy.
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Expert Opin Drug Saf · Feb 2014
ReviewSequestered naltrexone in sustained release morphine or oxycodone - a way to inhibit illicit use?
Under the growing concern about prescription opioid misuse, abuse, addiction, tampering and diversion, stakeholders (e.g, governments, pharmaceutical companies and health care providers) are developing opioid formulations that they hope are less attractive to those seeking to misuse or abuse pain medications. However, these products must maintain their therapeutic effectiveness and safety. Many abusers tamper with formulations in an effort to convert the active ingredient into a form suitable for alternative and more abuse-desirable routes of administration, such as snorting, inhaling or injecting. ⋯ The clinical impact of such combined formulations on tampering for abuse/misuse potential has not yet been determined, but long-term epidemiological studies are currently being conducted in order to answer these questions. Until these studies are complete, it seems prudent to remain cautious and assume that all formulations of prescription opioids might be abusable and that, similar to other opioids, the best current practice is to adhere to the principles of opioid risk management.