OBJECT DRUGS

HMG-CoA Reductase Inhibitors:

• Atorvastatin (Lipitor)
• Lovastatin (Mevacor, etc.)
• Pitavastatin (Livalo)
• Rosuvastatin (Crestor)
• Simvastatin (Zocor)

PRECIPITANT DRUGS

Fibrates:

• Gemfibrozil (Lopid)

Comment:

Combined use of HMG-CoA reductase inhibitors and gemfibrozil may increase the risk of myopathy, which may lead to rhabdomyolysis and acute renal failure. There appear to be differences in the relative risk, depending upon which HMG-CoA is used. Only rare cases of myopathy have been reported with atorvastatin and gemfibrozil, but the risk appears somewhat higher when lovastatin or simvastatin are coadministered with gemfibrozil. Gemfibrozil has been shown to substantially increase the serum concentrations of simvastatin acid and lovastatin acid, while gemfibrozil tends to produce moderate elevations of rosuvastatin and pitavastatin plasma concentrations. The product information for some statins (eg, lovastatin and simvastatin) states that concurrent use of gemfibrozil is contraindicated.

Class 2: Use Only if Benefit Felt to Outweigh Risk

• Use Alternative:
• HMG-CoA Reductase Inhibitors: Although definitive incidence data are not available, the risk of myopathy during concurrent pravastatin (Pravachol) or fluvastatin (Lescol) with gemfibrozil or fenofibrate appears to be minimal.
• Gemfibrozil: The risk of myopathy with combined use of statins and fenofibrate appears to be less than with gemfibrozil. For example, fenofibrate does not appear to have a pharmacokinetic interaction with simvastatin, and fenofibrate has little effect on pitavastatin or rosuvastatin plasma concentrations.
• Circumvent/Minimize: If the combination is used, consider reducing statin dose based on current statin product information.
• Monitor: If any HMG-CoA reductase inhibitor is used with gemfibrozil or another fibrate, the patient should be monitored for evidence of myopathy (muscle pain or weakness) and myoglobinuria (dark urine). Myopathy is usually associated with increased serum CK concentrations.