Evidencias Medicas : Concurrent Macrolide Antibiotic Associated With Statin ToxicityMedicina General y Familiar

30 junio, 2013

Concurrent Macrolide Antibiotic Associated With Statin Toxicity

266 (Photo credit: Wikipedia)

Ann. Intern. Med. 2013 Jun 01;158(12)869-876, AM Patel, S Shariff, DG Bailey, DN Juurlink, S Gandhi, M Mamdani, T Gomes, J Fleet, YJ Hwang, AX Garg

TAKE-HOME MESSAGE

A retrospective population-based cohort study of statin users > 65 years found that concurrent clarithromycin or erythromycin use with statins increases the risk of rhabdomyolysis, acute kidney injury, and all-cause mortality. Clinicians should consider prescribing alternative macrolides, or other antibiotic classes, when patients are taking statins.

SUMMARY

PracticeUpdate Editorial Team

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.

Annals of Internal Medicine