A 62-year-old diabetic man on long-term simvastatin is started on clarithromycin for an acute infective exacerbation of bronchiectasis. Three days later he presents with severe proximal muscle pain and a creatine kinase of 12,000 U/L. The interaction responsible is mediated by:
- A Induction of intestinal P-glycoprotein by clarithromycin
- B Competition between the two drugs for renal tubular secretion
- C Inhibition of hepatic CYP3A4 by clarithromycin, raising simvastatin levels ✓
- D Displacement of simvastatin from plasma protein binding sites
Correct answer: C. Inhibition of hepatic CYP3A4 by clarithromycin, raising simvastatin levels
Explanation
Clarithromycin is a potent inhibitor of CYP3A4, the enzyme that metabolizes simvastatin and other statins metabolized via this pathway. Co-administration sharply raises plasma statin concentrations and precipitates myopathy or frank rhabdomyolysis. Simvastatin should be suspended during clarithromycin therapy. Azithromycin does not inhibit CYP3A4 appreciably and is the preferred macrolide in patients on statins, which is the discriminating point between the two commonly used agents.
Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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