A 62-year-old man on simvastatin 40 mg daily is started on clarithromycin for an exacerbation of bronchiectasis. Five days later he presents with severe proximal muscle pain and creatine kinase of 18,000 U/L. The mechanism responsible is:

• A Clarithromycin inhibition of intestinal P-glycoprotein raising statin absorption
• B Competition between the two drugs for renal organic anion transporters
• C Additive direct skeletal muscle toxicity of both drugs
• D Clarithromycin inhibition of CYP3A4, increasing plasma concentrations of simvastatin ✓

Explanation

Clarithromycin and erythromycin are potent CYP3A4 inhibitors, and simvastatin and lovastatin are CYP3A4 substrates, so coadministration sharply raises statin levels and risks rhabdomyolysis. Azithromycin lacks significant CYP3A4 inhibition and is the safer macrolide in this setting. Renal transporter competition is irrelevant because these drugs are largely eliminated by metabolism or biliary routes, and the interaction involves metabolism rather than absorption.

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

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