An updated review of interactions of statins with antibacterial and antifungal agents

Numerous antimicrobial agents interact with statins. It is important to prevent these drug interactions and resulting statin toxicity and/or reduced efficacy. We review and highlight major drug-drug interactions between statins and antibacterial and antifungal agents; interactions with antiviral agents were not considered. Daptomycin interacts with statins via additive skeletal muscle toxicity. One possibility is to discontinue statins during daptomycin therapy, though no retrospective studies to date have shown a statistically significant elevation of adverse outcome risk. Multiple doses of rifampin induce cytochrome P450 (CYP), particularly 3A4 and 2C9, resulting in reduced systemic exposures to all statins, except rosuvastatin, for which the response was variable. Macrolide antibiotics are inhibitors of CYP3A4 and organic anion-transporting polypeptide-1B1. Azithromycin has the fewest drug interactions, while clarithromycin and erythromycin increase systemic exposure to all statins except rosuvastatin and fluvastatin. Azole antifungals are CYP450 inhibitors. Itraconazole and posaconazole are strong CYP3A4 inhibitors and mainly affect simvastatin, lovastatin, and atorvastatin, while fluconazole is an inhibitor of CYP2C9 and potentially CYP2C19 and mainly affects fluvastatin; however, risk cannot be ruled out with rosuvastatin.