Simvastatin, Fenofibrate, and Rhabdomyolysis
- Sindhu S. Jacob, MD1,
- Sony Jacob, MD1,
- Craig Williams, PHARMD2 and
- Mark A. Deeg, MD, PHD1
- 1Department of Medicine, Indiana University, Indianapolis, Indiana
- 2Department of Pharmacy Practice, Purdue University, Indianapolis, Indiana
- Address correspondence to Sindhu S. Jacob, MD, Indiana University School of Medicine, Endocrinology 111E, 1481 W. 10th St., Indianapolis, IN 46202. E-mail: sijacob{at}iupui.edu
The National Cholesterol Education Program (NCEP) guidelines recommend use of statin-fibrate combinations to treat combined dyslipidemia. Myopathy and rhabdomyolysis are reported side effects, especially with gemfibrozil-statin combinations (1). This risk is recognized to result from both pharmacodynamic and pharmacokinetic interactions. In vitro studies in human hepatocytes have shown that unlike gemfibrozil, fenofibrate has no pharmacokinetic interaction with simvastatin at concentrations achieved with clinical dosing (2). The acid form of simvastatin is partly eliminated by glucuronidation and lactonization, both of which are inhibited by gemfibrozil but not fenofibrate (2). This lack of a pharmacokinetic interaction between simvastatin and fenofibrate relaxed the recommendation in the package insert for simvastatin, …
