Minor
Azithromycin × Simvastatin
Macrolides×HMG-CoA reductase inhibitors (statins)
Mechanism
Azithromycin does not significantly inhibit CYP3A4, unlike clarithromycin and erythromycin (the FDA labels these as absolute contraindications with simvastatin due to rhabdomyolysis risk). Simvastatin does not accumulate.
Symptoms
The combination usually causes no specific symptoms. Each drug's individual side effects remain.
Management
No dose adjustment needed. When a macrolide is needed on simvastatin, azithromycin is the preferred choice. Clarithromycin and erythromycin are not combined with simvastatin — switch to azithromycin or to pravastatin/rosuvastatin (minimal CYP3A4 metabolism).