AIM：克拉霉素或红霉素升高他汀药物毒性反应风险

　　美国一项研究表明，在老年人群中，他汀类与克拉霉素或红霉素同时应用可升高他汀类药物的毒性反应风险。论文发表于《内科学年鉴》[Ann Intern Med 2013；158（12）：869]。

　　此项基于人群的队列研究纳入了年龄大于65岁的他汀类持续应用者，并对同时应用克拉霉素（72591例）或红霉素（3267例）的受试者和同时应用阿奇霉素者（68478例）进行了比较。主要转归为抗生素处方开具30天内因横纹肌溶解而住院治疗。

　　结果显示，阿托伐他汀（73%）为最常开具的他汀类，其次为辛伐他汀和洛伐他汀。与阿奇霉素相比，他汀类和克拉霉素或红霉素同时应用与横纹肌溶解住院风险升高具有相关性（绝对风险升高0.02%；相对危险度[RR] 2.17），同时亦与急性肾损伤（绝对风险升高1.26%，RR 1.78）和全因死亡风险升高相关（绝对风险升高0.25%；RR 1.56）。

Statin Toxicity From Macrolide Antibiotic Coprescription: A Population-Based Cohort Study
ABSTRACT
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.