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

BACKGROUND

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

OBJECTIVE

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

DESIGN

Population-based cohort study.

SETTING

Ontario, Canada, from 2003 to 2010.

PATIENTS

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).

MEASUREMENTS

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

RESULTS

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]).

LIMITATIONS

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.

CONCLUSION

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

PRIMARY FUNDING SOURCE

Academic Medical Organization of Southwestern Ontario.