OBJECT DRUGS

HMG-CoA Reductase Inhibitors:

• Atorvastatin (Lipitor)
• Lovastatin (Mevacor, etc.)
• Simvastatin (Zocor)

PRECIPITANT DRUGS

Calcium Channel Blockers:

• Diltiazem (Cardizem, etc.)
• Verapamil (Isoptin, etc.)

Comment:

Lovastatin and simvastatin undergo extensive first-pass metabolism by CYP3A4; calcium channel blockers that inhibit CYP3A4 (diltiazem and verapamil) increase the statin serum concentrations, increasing the risk of myopathy, rhabdomyolysis and acute renal failure. Consider the increased risk of myopathy against the specific need for one of the calcium channel blockers that inhibits CYP3A4. Atorvastatin (Lipitor) undergoes less first-pass metabolism by CYP3A4 than lovastatin or simvastatin, so the risk of myopathy when combined with CYP3A4 inhibitors appears to be less. Nonetheless, some cases have been reported.

Class 3: Assess Risk & Take Action if Necessary

• Consider Alternative:
• HMG-CoA Reductase Inhibitors: Pravastatin (Pravachol) is not metabolized by cytochrome P450 isozymes, while fluvastatin (Lescol) and rosuvastatin (Crestor) are metabolized by CYP2C9—thus, they are not affected by CYP3A4 inhibition.
• Calcium channel blockers: Calcium channel blockers other than diltiazem and verapamil are unlikely to inhibit the metabolism of HMG-CoA reductase inhibitors. However, the 2013 product information for simvastatin states that amlodipine (Norvasc) may increase the risk of myopathy, and the simvastatin dose should not exceed 20 mg/day.
• Circumvent/Minimize: If the combination is used, consider reducing statin dose based on current statin product information.
• Monitor: If either diltiazem or verapamil is used with the statin, the patient should be alert for evidence of myopathy (muscle pain or weakness) or myoglobinuria (dark urine) ; CK concentrations are usually high.