Results of a Safety Initiative for Patients on Concomitant Amiodarone and Simvastatin Therapy in a Veterans Affairs Medical Center

BACKGROUND: The FDA revised the labels of amiodarone and simvastatin in 2002 to warn of increased risk of rhabdomyolysis, the most severe form of myopathy, when the 2 drugs are taken concomitantly in doses greater than 20 milligrams (mg) per day of simvastatin. The FDA reissued the warning in 2008 after receiving reports of 52 cases of rhabdomyolysis in the Adverse Event Reporting System (AERS) after the label changes in 2002 and suggested use of an alternative statin for patients receiving amiodarone who require more than 20 mg simvastatin to attain lipid goals. OBJECTIVES: To (a) assess the prevalence of concomitant amiodarone and simvastatin in doses greater than 20 mg per day and the frequency of additional risk factors for myopathy in these patients, and (b) implement and evaluate a protocol to convert patients receiving this combination to alternative statins. METHODS: A review was conducted of all patients with active prescriptions for both simvastatin at doses greater than 20 mg per day and amiodarone from a Veterans Affairs (VA) medical center as of November 1, 2008. Data collected included demographics, duration of therapy, baseline lipid and aminotransferase values, and risk factors for myopathy (i.e., aged 80 years or older; female sex; small body frame; hypothyroidism; hepatic or renal insufficiency; diabetes; alcohol abuse; and use of medications, such as gemfibrozil and nicotinic acid, that may increase the risk of myopathy). Patients were converted to either pravastatin or rosuvastatin based on baseline simvastatin dose, low-density lipoprotein cholesterol (LDL-C) level, and renal function. The conversion protocol was developed to maintain LDL-C lowering with potentially safer statins. Follow-up lipid and aminotransferase values were collected as customary clinical markers of efficacy and safety, respectively, for patients converted per the protocol. Because creatine kinase values are not routinely assessed in clinical practice, they were not available as part of the current protocol. RESULTS: Of the 48,612 patients who accessed the pharmacy in this VA medical center, 17,760 (36.5%) had an active order for simvastatin 40 mg or 80 mg per day, and 92 of these patients (0.52%) also had an active order for amiodarone. These patients were prescribed simvastatin primarily for secondary prevention (88 [95.7%] with coronary artery disease [CAD] as the indication for statin therapy), and were highly controlled with mean (SD) baseline LDL-C of 71 (21) mg per deciliter. The mean (median) duration of therapy on the combination of amiodarone plus simvastatin 40 mg or more per day was 43 (37) months. Of the 92 patients, 26 (28.3%), 35 (38.0%), and 18 (19.6%) patients had 1, 2, or 3 or more additional risk factors for myopathy, respectively. 16 patients were not converted per protocol to an alternate statin (4 were taken off amiodarone, 2 were taken off statin therapy, 6 had the simvastatin dose reduced to 20 mg per day or less, and 4 were converted to an alternate statin off-protocol), and 14 patients did not have follow-up laboratory values. For the 62 patients converted per protocol and with follow-up laboratory values, there were no statistically significant changes in mean lipid or aminotransferase values after conversion. One patient reported symptoms of myalgia after conversion to rosuvastatin; however, the conversion protocol did not require obtaining creatine kinase values. CONCLUSIONS: 0.19% of patients (n=92) with pharmacy dispensing records in this VA facility in 2008 received amiodarone in combination with simvastatin in doses greater than 20 mg per day, and the majority of patients had additional risk factors for myopathy. There were no significant changes in mean laboratory values for lipids or aminotransferase for the 62 patients (67%) who were converted and who had baseline and follow-up values; there was 1 case of self-reported myalgia in a patient converted to rosuvastatin.