A 62-year-old diabetic man on simvastatin 40 mg daily is prescribed clarithromycin for an acute exacerbation of COPD. One week later he presents with proximal muscle pain, weakness and creatine kinase elevated to 20 times normal. The mechanism of this interaction is:

• A Inhibition of intestinal P-glycoprotein increasing statin efflux
• B Inhibition of CYP3A4 reducing statin metabolism and raising serum levels ✓
• C Induction of hepatic CYP3A4 increasing statin metabolism
• D Competition for renal organic anion transporters delaying statin excretion

Explanation

Simvastatin undergoes extensive first-pass metabolism by CYP3A4. Clarithromycin is a potent CYP3A4 inhibitor, so coadministration markedly raises statin plasma concentrations and precipitates rhabdomyolysis. Erythromycin behaves similarly. If a macrolide is required, azithromycin, which does not inhibit CYP3A4 meaningfully, is the safer alternative.

Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.

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