A comparison of adverse effects of simvastatin plus gemfibrozil and atorvastatin plus gemfibrozil

Background: The manufacturer of simvastatin recommends a dose limitation of 10 mg daily when used in combination with gemfibrozil, due to increased risk of myopathy and rhabdomyolysis. Little information is available regarding the risk of adverse effects of atorvastatin when used in combination with gemfibrozil. Purpose: To compare the rate of discontinuation or dose reduction due to adverse effects with simvastatin and gemfibrozil versus atorvastatin and gemfibrozil. Methods: Retrospective review of patients taking gemfibrozil in combination with simvastatin 10 mg, simvastatin 80 mg, or atorvastatin 40 mg for at least 6 months. Results: A total of 166 patients were included; 59 were taking simvastatin 10 mg (S10), 47 were taking simvastatin 80 mg (S80), and 60 were taking atorvastatin 40 mg (A40). There was no significant difference in the rate of discontinuation or dose reduction due to adverse effects among the groups (10.2% for S10, 21.2% for S80, and 10% for A40, P = 0.159). A paired comparison of discontinuation or dose reduction due to adverse effects between the simvastatin 80 mg and atorvastatin 40 mg groups approached a trend toward a difference (P = 0.104). Severe adverse effects occurred in the simvastatin 80 mg and atorvastatin 40 mg groups. Conclusion: Our results did not show a significant difference in discontinuation or dose reduction due to adverse effects between patient groups taking gemfibrozil in combination with simvastatin 10 mg, simvastatin 80 mg, or atorvastatin 40 mg. However, the rate of this outcome in the S80 group was approximately double that for the S10 and A40 groups. Further studies are needed to compare the safety of these statin-gemfibrozil combinations.