Expert opinion on drug safety
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Outcomes of two large double-blind placebo-controlled studies of oral dimethyl fumarate (DMF) in multiple sclerosis (MS) provided the basis for its marketing approval as Tecfidera® by the US FDA in early 2013 and the European Medicines Agency in February 2014. The safety of DMF is complemented by experience in the use of an oral mixture of fumaric acid esters, including DMF for psoriasis (Fumaderm®; DMF and monoethyl fumarate [DMF-MEF]) licensed in Germany in 1994. ⋯ DMF is generally safe and well tolerated. Flushing and gastrointestinal side effects are relatively common for the approved DMF dose but are ordinarily mild and self-limited. No increase in malignancies has been reported despite theoretical concerns. Although progressive multifocal encephalopathy has been reported anecdotally in 5 of > 196,000 patient-years of experience with fumaric acid esters, none of the 65,000 DMF MS patients treated in the first year has been affected. Appendix to the abstract: Subsequent to the acceptance of this article for publication, the manufacturer has notified physicians of the death of one patient from PML complicating use of DMF in the DEFINE study extension (ENDORSE). This does not alter the expert opinion rendered regarding the safety of DMF. We await the outcomes and recommendations from the ongoing investigation into this case.
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Expert Opin Drug Saf · Jan 2015
Review Comparative StudyWarfarin versus dabigatran etexilate: an assessment of efficacy and safety in patients with atrial fibrillation.
Oral anticoagulation is the mainstay for stroke and thromboembolic event prevention in patients with atrial fibrillation (AF). Given limitations of warfarin therapy, non-vitamin K oral anticoagulants have been developed including direct thrombin inhibitors (i.e., dabigatran etexilate). Dabigatran etexilate has been tested thoroughly in terms of efficacy and safety in clinical trials and studies, involving 'real-world' cohorts. In this review, currently available evidence in patients with non-valvular AF is discussed. ⋯ Dabigatran etexilate appeared to have several pharmacokinetic and pharmacodynamic advantages over warfarin, as well as a favorable efficacy and safety profile being at least noninferior and often superior to warfarin in patients with non-valvular AF. The latter was shown in the clinical trials, meta-analyses and studies with 'real-world' data. Currently ongoing trials will expand the body of evidence on warfarin and will aid decision making in currently controversial areas. Important limitations of dabigatran etexilate include contraindications for its use in patients with prosthetic heart valves and end-stage chronic kidney disease.
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Expert Opin Drug Saf · Jan 2015
EditorialThe safety of liposome bupivacaine 2 years post-launch: a look back and a look forward.
The need for better post-surgical pain management continues to be unmet, despite clinicians' awareness and concern for many years. Opioids remain the standard of care because of their analgesic efficacy; however, opioid use is often associated with adverse effects and poor patient outcomes. Multimodal analgesic regimens have recently been endorsed as a way to provide adequate post-surgical pain control while reducing opioid consumption. ⋯ Based on the available clinical trial data compiled to date, as well as the author's review of publicly available post-marketing safety information, liposome bupivacaine may be a viable addition to currently available therapeutic options for post-surgical analgesia while reducing potential risks associated with use of opioid analgesics, and may represent a useful addition to the multimodal analgesic modalities currently used for post-operative pain management. The potential for its use in other areas is also being investigated. The purpose of this review is to examine the currently available post-marketing safety information on liposome bupivacaine.