An elderly woman with gout on stable low-dose colchicine is given clarithromycin for an exacerbation of COPD. A week later she presents with severe diarrhoea, pancytopenia and proximal muscle weakness. The interaction responsible is:

• A Clarithromycin displaces colchicine from plasma protein binding sites
• B Clarithromycin inhibits CYP3A4 and P-glycoprotein, sharply raising colchicine levels ✓
• C Clarithromycin induces CYP2C9, converting colchicine to a myotoxic metabolite
• D Additive direct toxicity of macrolides on bone marrow

Explanation

Colchicine is a substrate of both CYP3A4 and the efflux transporter P-glycoprotein. Clarithromycin inhibits both, producing a marked rise in colchicine exposure that leads to gastrointestinal toxicity, myelosuppression, and neuromyopathy, particularly in renal or hepatic impairment. Protein binding displacement is not a recognised mechanism here, and macrolides are inhibitors, not inducers, of CYP enzymes. This combination is best avoided entirely in such patients.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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