Statin toxicity from macrolide antibiotic coprescription: a population-based cohort study

Clarithromycin and erythromycin, but not azithromycin, inhibit cytochrome P450 isoenzyme 3A4 (CYP3A4), and inhibition increases blood concentrations of statins that are metabolized by CYP3A4.

To measure the frequency of statin toxicity after coprescription of a statin with clarithromycin or erythromycin.

Population-based cohort study.

Ontario, Canada, from 2003 to 2010.

Continuous statin users older than 65 years who were prescribed clarithromycin (n = 72,591) or erythromycin (n = 3267) compared with those prescribed azithromycin (n = 68,478).

The primary outcome was hospitalization with rhabdomyolysis within 30 days of the antibiotic prescription.

Atorvastatin was the most commonly prescribed statin (73%) followed by simvastatin and lovastatin. Compared with azithromycin, coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis (absolute risk increase, 0.02% [95% CI, 0.01% to 0.03%]; relative risk [RR], 2.17 [CI, 1.04 to 4.53]) or with acute kidney injury (absolute risk increase, 1.26% [CI, 0.58% to 1.95%]; RR, 1.78 [CI, 1.49 to 2.14]) and for all-cause mortality (absolute risk increase, 0.25% [CI, 0.17% to 0.33%]; RR, 1.56 [CI, 1.36 to 1.80]).

Only older adults were included in the study. The absolute risk increase for rhabdomyolysis may be underestimated because the codes used to identify it were insensitive.

In older adults, coprescription of clarithromycin or erythromycin with a statin that is metabolized by CYP3A4 increases the risk for statin toxicity.

Academic Medical Organization of Southwestern Ontario.