Myositis and Rhabdomyolysis Associated With Concurrent Use of Simvastatin and Nefazodone

Roy H. Jacobson, MD, PhD; Ping Wang, PhD; C. J. Glueck, MD
JAMA. 1997;277(4):296. doi:10.1001/jama.1997.03540280034021.
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To the Editor.  —Simvastatin, like many drugs, is metabolized in the liver by the microsomal P-450 system.1 While definitive studies have not been done, it seems likely that simvastatin is metabolized primarily or exclusively by the 3A isoenzyme.2 Drugs that inhibit this enzyme represent a potential drug interaction, and that list of drugs includes many common agents such as grapefruit juice, ketoconazole, itraconazole, macrolide antibiotics, including erythromycin, and nefazodone. We report a case of myositis and rhabdomyolysis that followed the addition of nefazodone to the regimen of a patient previously taking simvastatin.

Report of a Case.  —A 44-year-old white man had been asymptomatic while taking simvastatin (40 mg/d) for 19 weeks with good control of his low-density lipoprotein (LDL) cholesterol level and with normal creatine kinase (CK) and liver function tests. Prior to the initiation of the new antidepressant, nefazodone, the following normal laboratory values were noted: aspartate


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