Rhabdomyolysis and HMG-CoA reductase inhibitors

To review rhabdomyolysis and discuss the role of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) and their interactions with other agents in precipitating this condition, and to present case reports of statin-induced rhabdomyolysis.

Relevant clinical literature was accessed using MEDLINE (January 1985-October 2000). The following search terms were used: rhabdomyolysis, adverse events, drug interactions, statins, and HMG-CoA reductase inhibitors.

Rhabdomyolysis occurs when extensive muscle damage results in the release of cellular contents into systemic circulation. Major complications include acute renal failure, cardiac abnormalities, and compartment syndrome. Treatment of rhabdomyolysis is supportive, with the primary aim of preventing renal and cardiac complications. Statin monotherapy or combination therapy may result in myopathy, which rarely progresses to rhabdomyolysis. The mechanism for drug interactions with the statins involves their property of lipid or water solubility. This characteristic determines the degree of hepatoenteric or renal metabolism of the statins. All statins except pravastatin undergo metabolism via the cytochrome P450 enzyme system. Other pharmacologic agents that are also metabolized via this pathway may interact with the statins and cause rhabdomyolysis. The risk of statin-induced rhabdomyolysis is increased significantly when statins are used concomitantly with such drugs as fibrates, cyclosporine, macrolide antibiotics, and azole antifungals.

Rhabdomyolysis is a rare but clinically important adverse event of statin monotherapy or combination therapy. Thorough understanding of this condition may help prevent or minimize adverse health outcomes in patents receiving statin therapy.