A 58-year-old woman on simvastatin develops severe myalgia and a creatine kinase of 12,000 U/L five days after starting clarithromycin for acute bronchitis. The interaction underlying her rhabdomyolysis is:
- A Clarithromycin-induced inhibition of hepatic CYP3A4, raising statin levels ✓
- B Competition between the two drugs for renal organic anion transporters
- C Additive mitochondrial toxicity of both drugs in skeletal muscle
- D Clarithromycin displacement of simvastatin from plasma albumin
Correct answer: A. Clarithromycin-induced inhibition of hepatic CYP3A4, raising statin levels
Explanation
Simvastatin is extensively metabolized by CYP3A4. Clarithromycin and erythromycin are potent CYP3A4 inhibitors, so coadministration sharply raises statin exposure and precipitates myopathy and rhabdomyolysis. Azithromycin lacks significant CYP3A4 inhibition and is the preferred macrolide in patients on statins. Transporter competition and protein-binding displacement are not relevant mechanisms for this pair, and the toxicity is dose-related statin excess rather than additive mitochondrial injury.
Reference: Katzung Basic and Clinical Pharmacology, 15th ed.
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