Expert opinion on drug safety
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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.