Avoid high-dose simvastatin
The FDA is advising physicians to avoid high-dose simvastatin (Zocor) because of the risk of myopathy and rhabdomyolysis. The agency is advising that patients should not be started on the 80 mg dose and patients who already are on 80 mg should be continued only if they have been on that dose for 1 year or longer. The recommendations are based on results of the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocystine (SEARCH) trial a 7-year randomized, controlled trial comparing the efficacy and safety of simvastatin 80 mg vs simvastatin 20 mg with or without vitamin B12 and folate in survivors of myocardial infarction. There was no significant difference in the incidence of major vascular events between the two doses; however, 52 patients (0.9%) in the 80-mg group developed myopathy vs one patient (0.02%) in the 20-mg group. Of the high-dose group, 22 patients (0.4%) developed rhabdomyolysis vs no patients in the 20-mg group. The risk for myopathy and rhabdomyolysis with simvastatin 80 mg was highest in the first 12 months of treatment. Of concern, the risk of myopathy was approximately doubled in patients taking a calcium channel blocker, particularly diltiazem. The majority of patients who developed myopathy also had a genetic variant that affects coding of the transporter responsible for simvastatin uptake in the liver, resulting in higher serum simvastatin levels. The FDA not only recommends against using simvastatin 80 mg, but also suggests that the drug is contraindicated for use in patients taking itraconazole, ketoconazole, posaconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone, gemfibrozil, cyclosporine, and danazol. The maximum dose of simvastatin should be only 10 mg in patients taking amiodarone, verapamil, and diltiazem while the maximum dose is 20 mg in patients taking amlodipine and ranolazine. The new guidance recommends using a different statin if the patient's LDL targets aren't met with the 40-mg simvastatin dose. The loss of high-dose simvastatin comes as a blow to cost-concious consumers who now likely will be prescribed brand name atorvastatin (Lipitor) or rosuvastatin (Crestor). Generic atorvastatin is likely to be available in late 2011.