Highest simvastatin dose linked to increased risk of muscle injury, FDA warns

Mar 19, 2010

Emma Hitt, PhDFrom

Medscape Medical News—a professional news service of WebMD

Rockville, MD - Simvastatin (Zocor, Merck/Schering-Plough), used at the highest approved dose of 80 mg, is associated with an increased risk of myopathy, including rhabdomyolysis, according to the US Food and Drug Administration (FDA) [1].The alert sent today from MedWatch, the FDA's safety information and adverse-event reporting program, was based on a review of data from the large clinical Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH). Other sources, including data from clinical trials, observational studies, and adverse-event reports, as well as data on prescription use of simvastatin, are under review.The SEARCH trial evaluated the number of major cardiovascular events (heart attack, revascularization, and cardiovascular death) in 6031 patients with a history of MI taking 80 mg of simvastatin and compared that number with 6033 patients taking 20 mg of simvastatin. The study included 6.7 years of follow-up.According to preliminary results, more patients in the simvastatin-80-mg group developed myopathy than patients in the simvastatin-20-mg group (52 [0.9%] cases vs one case [0.02%]). In addition, 11 (0.02%) of the patients in the simvastatin-80-mg group developed rhabdomyolysis compared with no patients in the simvastatin-20-mg group."Review of simvastatin is part of an ongoing FDA effort to evaluate the risk of statin-associated muscle injury and to provide that information to the public as it becomes available," noted Dr Eric Colman, deputy director of the FDA's Division of Metabolism and Endocrinology Products, in a written release [2]. According to the FDA safety announcement, healthcare professionals should consider the following when prescribing simvastatin:That rhabdomyolysis is a rare class effect associated with statins. The increased risk of muscle injury with the 80-mg dose of simvastatin compared with the use of lower doses of simvastatin and possibly other statin drugs. Whether simvastatin is clinically appropriate. Discussing with patients the benefits and risks of simvastatin. Potential drug-drug interactions can occur with simvastatin. In February 2010, simvastatin was one of 27 drugs or drug categories included on a watch list of the FDA, based on potential signs of serious risks or new safety information identified in the agency's adverse-event reporting system last year. Risk of myopathy may be linked to genetic heterogeneity in statin users. A study published in October 2009, reported by heartwire, found that carriers of the reduced-function single nucleotide polymorphism of the SLCO1B1 gene were found to be at an increased risk of developing mild statin-induced side effects, including myopathy and myalgia [3]. The risk of adverse events was greatest among those treated with simvastatin but minimal in those receiving pravastatin. More information about simvastatin and myopathy risk is available on the FDA's MedWatch website. Previous FDA safety communications on the increased risk of muscle injury with simvastatin in patients who concurrently take other medications are also available. Simvastatin is sold as a single agent and also in combination with ezetimibe (Vytorin, Merck/Schering-Plough) and in combination with niacin (Simcor, Abbott Laboratories).Rhabdomyolysis is the most serious form of myopathy and is associated with severe renal toxicity and failure and occasional fatalities. Adverse events related to simvastatin should be communicated to MedWatch by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online, or by mail to 5600 Fishers Lane, Rockville, MD 20852-9787.The complete contents of Medscape Medical News, a professional news service of WebMD, can be found at www.medscape.com, a website for medical professionals.