INTERACTIONS WITH HYDROXYMETHYLGLUTARYL-COENZYME-A REDUCTASE INHIBITORS

Drug-drug, drug-food, and drug-disease interactions involving hydroxym ethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are reviewed. The four available HMG-CoA reductase inhibitols- lovastatin, simvastat in, pravastatin, and fluvastatin- have different potentials for drug i nteractions, probably because of their different pharmacokinetic chara cteristics. Interactions of some of these cholesterol-lowering agents with cyclosporine, erythromycin, high-dose niacin, or gemfibrozil may produce myopathy with or without rhabdomyolysis. Interactions with oth er commonly prescribed agents, such as bile acid sequestrants, coumari n anticoagulants, and cardiovascular drugs, may alter the pharmacokine tics of either drug, but the clinical significance is generally minor. Food may affect plasma lovastatin concentrations, systemic pravastati n bioavailability, and the maximum serum concentration (C-max) and tim e to achieve C-max for fluvastatin. Hepatic dysfunction may influence the pharmacokinetics of pravastatin; all HMG-CoA reductase inhibitors are contraindicated in patients with liver disease or unexplained elev ations in serum aminotransferases. Severe renal insufficiency may nece ssitate dosage modification in lovastatin recipients. Renal dysfunctio n seems to affect the pharmacokinetics of pravastatin, simvastatin, an d fluvastatin only minimally, but caution is still warranted. Although the HMG-CoA reductase inhibitors rarely have severe adverse effects, they may interact, in some cases dangerously, with other drugs, with f ood, and with disease states.