A 66-year-old diabetic man on simvastatin 40 mg daily starts clarithromycin for an acute infective exacerbation of bronchiectasis. Five days later he presents with severe proximal muscle pain and creatine kinase of 18,000 U/L. What is the mechanism of this interaction?

• A Clarithromycin induces CYP3A4, accelerating conversion of simvastatin to myotoxic metabolites
• B Clarithromycin inhibits CYP3A4, raising plasma concentrations of simvastatin ✓
• C Clarithromycin displaces simvastatin from plasma albumin binding sites
• D Clarithromycin inhibits renal tubular secretion of simvastatin lactone

Explanation

Clarithromycin is a strong inhibitor of CYP3A4, the enzyme metabolising simvastatin and lovastatin. Co-administration sharply raises statin levels and can produce rhabdomyolysis, so the statin should be suspended during macrolide therapy. Erythromycin shares this inhibition while azithromycin does not, a common discriminating point. Induction, displacement and tubular secretion are not involved here.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

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