A 62-year-old man on simvastatin develops severe proximal muscle pain and dark urine three days after starting erythromycin for bronchitis. The most likely mechanism of this interaction is:

• A Inhibition of CYP3A4-mediated statin metabolism by erythromycin ✓
• B Induction of intestinal P-glycoprotein by erythromycin
• C Competition between both drugs for renal tubular secretion
• D Displacement of simvastatin from plasma protein binding sites

Explanation

Erythromycin is a strong inhibitor of CYP3B4. Simvastatin undergoes extensive first-pass CYP3B4 metabolism, so co-administration sharply raises statin plasma concentrations and precipitates rhabdomyolysis. This interaction also underlies erythromycin's dangerous combinations with carbamazepine, cyclosporine and terfenadine. Renal excretion is irrelevant here since simvastatin is cleared hepatically, and erythromycin inhibits rather than induces P-glycoprotein.

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

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