High-Dose Simvastatin and Rhabdomyolysis
Simvastatin is a member of the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, or statins, which are used in the management of dyslipidemia. FDA approved its marketing in 1991. These drugs competitively inhibit the early and rate-limiting step in the conversion of HMG-CoA to mevalonate and thereby reduce the biosynthesis of cholesterol. Statins are considered the most potent agents available for lowering cholesterol; some statins (including simvastatin) have been associated with a reduced risk of mortality and nonfatal myocardial infarction in persons with coronary heart disease. A rare but serious problem with statins is rhabdomyolysis with or without acute renal failure. In most cases, rhabdomyolysis or other myopathies have been caused by drug interactions, specifically with drugs that inhibit the cytochrome P-450 (CYP) 3A4 metabolic pathway (e.g., macrolides, certain antifungals, and cyclosporine). Simvastatin, atorvastatin, and lovastatin are most prone to these interactions.
The following report describes a patient who experienced rhabdomyolysis while taking simvastatin. His myopathy was caused by an increase in the dosage of simvastatin and not by an interaction with another medication.
Simvastatin is a member of the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, or statins, which are used in the management of dyslipidemia. FDA approved its marketing in 1991. These drugs competitively inhibit the early and rate-limiting step in the conversion of HMG-CoA to mevalonate and thereby reduce the biosynthesis of cholesterol. Statins are considered the most potent agents available for lowering cholesterol; some statins (including simvastatin) have been associated with a reduced risk of mortality and nonfatal myocardial infarction in persons with coronary heart disease. A rare but serious problem with statins is rhabdomyolysis with or without acute renal failure. In most cases, rhabdomyolysis or other myopathies have been caused by drug interactions, specifically with drugs that inhibit the cytochrome P-450 (CYP) 3A4 metabolic pathway (e.g., macrolides, certain antifungals, and cyclosporine). Simvastatin, atorvastatin, and lovastatin are most prone to these interactions.
The following report describes a patient who experienced rhabdomyolysis while taking simvastatin. His myopathy was caused by an increase in the dosage of simvastatin and not by an interaction with another medication.