Rhabdomyolysis and HMG-CoA reductase inhibitors

OBJECTIVE: To review rhabdomyolysis and discuss the role of hydroxymethylgl utaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) and their intera ctions with other agents in precipitating this condition, and to present ca se reports of statin-induced rhabdomyolysis. DATA SOURCE: Relevant clinical literature was accessed using MEDLINE (Janua ry 1985-October 2000). The following search terms were used: rhabdomyolysis , adverse events, drug interactions, statins, and HMG-CoA reductase inhibit ors. DISCUSSION: Rhabdomyolysis occurs when extensive muscle damage results in t he release of cellular contents into systemic circulation. Major complicati ons include acute renal failure, cardiac abnormalities, and compartment syn drome. Treatment of rhabdomyolysis is supportive, with the primary aim of p reventing renal and cardiac complications. Statin monotherapy or combinatio n therapy may result in myopathy, which rarely progresses to rhabdomyolysis . The mechanism for drug interactions with the statins involves their prope rty of lipid or water solubility. This characteristic determines the degree of hepatoenteric or renal metabolism of the statins. All statins except pr avastatin undergo metabolism via the cytochrome P450 enzyme system. Other p harmacologic agents that are also metabolized via this pathway may interact with the statins and cause rhabdomyolysis. The risk of statin-induced rhab domyolysis is increased significantly when statins are used concomitantly w ith such drugs as fibrates, cyclosporine, macrolide antibiotics, and azole antifungals. CONCLUSIONS: Rhabdomyolysis is a rare but clinically important adverse even t of statin monotherapy or combination therapy. Thorough understanding of t his condition may help prevent or minimize adverse health outcomes in patie nts receiving statin therapy.