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Cardiology: FDA Recommends Limits on Highest Dose of Simvastatin

by Robert Fay

The U.S. Food and Drug Administration (FDA) is recommending limiting the use of the highest approved dose of the popular statin simvastatin (Zocor) because of an increased risk of myopathy. The agency stated that the highest dose, 80 milligrams (mg), should be used only for patients who have taken it for at least 12 months without evidence of myopathy. It should not be given to new patients or to patients taking a lower dose of the medication who do not meet their LDL-C goal.

The recommendation is the result of a safety review the FDA launched in March 2010. In addition to reviewing its Adverse Event Reporting System, the agency evaluated the data from the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) clinical trial. SEARCH concluded that the 80-mg dose of simvastatin was associated with a higher rate of myopathy than the 20-mg dose (0.09 percent compared to 0.02 percent). In addition, the FDA found that the risk of muscle injury is highest in the first year of treatment with the 80-mg dose, often results from interactions with other medications, and is frequently associated with a genetic predisposition for simvastatin-related muscle injury.

The FDA is revising the drug labels for simvastatin and the simvastatin-ezetimibe combination (Vytorin) to add new contraindications and dose limitations when using the drug with other medications. Posaconazole is now contraindicated with 80 mg of simvastatin. Gemfibrozil, cyclosporine, and danazol, are contraindicated on the new label. Previously, the daily simvastatin dose was limited to 10 mg with those medications. Now, the daily dose of simvastatin should not exceed 10 mg when taken in conjunction with amiodarone, verapamil, and diltiazem. These medications are contraindicated with the combination of simvastatin and niacin (Simcor), which is unavailable at the highest dose of the statin. Simvastatin should be limited to 20 mg daily when taken with amlodipine and ranolazine.

Source: U.S. Food and Drug Administration. 2011. FDA Drug Safety Communication: New restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury. Published on June 8, 2011 on the FDA website.