March 19, 2010 — Simvastatin (Zocor, Merck/Schering-Plough Pharmaceuticals), used at the highest approved dose of 80 mg, is associated with an increased risk for myopathy, including rhabdomyolysis, according to the US Food and Drug Administration (FDA).
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) trial. 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 myocardial infarction taking 80 mg of simvastatin and compared that number with that from 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 compared with patients in the simvastatin 20-mg group (52 cases [0.9%] vs 1 case [0.02%]). In addition, 11 patients in the simvastatin 80-mg group (0.02%) 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 Eric Colman, MD, deputy director of the FDA's Division of Metabolism and Endocrinology Products, in a news release.
According to the FDA, healthcare professionals should consider the following when prescribing simvastatin:
Rhabdomyolysis is a rare class effect associated with statins
The increased risk for muscle injury with the 80-mg dose of simvastatin is compared with the use of lower doses of simvastatin and possibly other statin drugs
Whether simvastatin is clinically appropriate
Discuss with patients the benefits and risks of simvastatin
Potential drug–drug interactions can occur with simvastatin
Last month, simvastatin was one of 27 drugs or drug categories that was included on an FDA watch list, based on potential signs of serious risks or new safety information identified in the agency's Adverse Event Reporting System last year.
Risk for myopathy may be linked to genetic heterogeneity in statin users. A study published in the October 20, 2009, issue of the Journal of American College of Cardiology found that carriers of the reduced-function single nucleotide polymorphism of the SLCO1B1 gene were at increased risk of developing mild statin-induced adverse effects, including myopathy and myalgia. The risk for 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 Web site.
Previous FDA safety communications on the increased risk for muscle injury with simvastatin in patients who concurrently take other medications is also available on the FDA's Web site.
Simvastatin is sold as a single agent and also in combination with ezetimibe (Vytorin, Merck/Schering-Plough Pharmaceuticals) 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 at http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, Maryland 20852-9787.
