Statin-induced rhabdomyolysis from azithromycin interaction in a patient with heterozygous SLCO1B1 polymorphism.

WHAT IS KNOWN AND OBJECTIVE: Unlike other macrolide antibiotics, azithromycin is considered safe to co-prescribe with simvastatin. We aim to elucidate the mechanism of a rare azithromycin-simvastatin interaction. CASE DESCRIPTION: We report a case of simvastatin-induced rhabdomyolysis caused by an azithromycin drug interaction in a patient with heterozygous SLCO1B1 loss-of-function polymorphism. We propose a dual-hit mechanism for this drug-drug-genome interaction. Azithromycin mildly inhibits simvastatin's CYP 3A4 hepatic metabolism, and the SLCO1B1 polymorphism reduces simvastatin hepatic uptake. The combination increases simvastatin serum concentrations significantly, inducing rhabdomyolysis. WHAT IS NEW AND CONCLUSION: Patients with statin-induced myopathy associated with non-classic CYP inhibitors should be considered for genetic testing and alternative statins with less risk of future interactions.