Simvastatin-diltiazem drug interaction resulting in rhabdomyolysis and hepatitis

Simvastatin, a hydroxymethyl glutarate coenzyme A (HMG-CoA) reductase inhibitor, is a commonly used cholesterol lowering agent. The long-term safety profile of simvastatin, established over ten-years of clinical use, is excellent. Both rhabdomyolysis and hepatitis, however, are recognized toxic effects of this medication, and generally occur when the patients are taking more than 40 mg of simvastatin a day. Potent inhibitors of the cytochrome P450 3A4 (CYP3A4) enzyme increase the incidence of simvastatin toxicity. Calcium channel blockers are weak inhibitors of the CYP3A4 enzyme. Diltiazem is known to increase the serum concentration of simvastatin. Many patients who take both simvastatin and diltiazem require lower doses of simvastatin to achieve the recommended reduction in cholesterol. Since diltiazem is known to increase plasma levels of lovastatin, a similar phenomenon may occur with simvastatin. Our patient had been stable for three years on simvastatin therapy. His rhabdomyolysis and hepatitis coincided with the addition of diltiazem. This is the first report of the combined toxicities of rhabdomyolysis and hepatitis being induced by the addition of diltiazem to simvastatin therapy. This patient serves as a reminder to the clinician of the potential interaction of these two commonly used drugs.