Myositis and rhabdomyolysis associated with concurrent use of simvastatin and nefazodone

In Reply. —To our knowledge, this is the first report of these adverse events associated with concomitant use of simvastatin and nefazodone. Since simvastatin is thought to be metabolized by cytochrome P-450 3A4 (CYP3A4),¹an increased likelihood of these adverse events might be expected if simvastatin is coadministered with any agent that inhibits the activity of the CYP3A4 isoenzyme (eg, nefazodone, fluvoxamine, fluoxetine, sertraline, grapefruit juice, erythromycin, ketoconazole, or itraconazole).²In addition, myositis and rhabdomyolysis are adverse events associated with simvastatin monotherapy.