Statin Toxicity From Macrolide Antibiotic Coprescription:A Population-Based Cohort Study
标题：他汀类与大环内酯类抗生素联用的毒性反应：人群队列研究
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.
背景：克拉霉素或红霉素（但不包括阿奇霉素），均可抑制细胞色素P450同工酶3A4（CYP3A4）。而他汀类的代谢依赖于CYP3A4，因此，两者联用可能会增加他汀类的血药浓度。
Objective: To measure the frequency of statin toxicity after coprescription of a statin with clarithromycin or erythromycin.
目的：明确克拉霉素或红霉素与他汀类联用后的毒性反应发生频率。
Design: Population-based cohort study.
设计：人群队列研究
Setting: Ontario, Canada, from to .
设置：~，加拿大渥太华
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).
病人：65岁以上需长期服用他汀类的群体，分别联用克拉霉素（n = 72 591）或红霉素（n = 3267），并与联用阿奇霉素（n = 68 478）的群体进行对比。
Measurements: The primary outcome was hospitalization with rhabdomyolysis within 30 days of the antibiotic prescription.
测定：主要终点为处方抗生素30天内的横纹肌溶解症入院。
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]).
结果：阿托伐他汀是处方量最大的抗生素，其次为辛伐他汀和洛伐他汀。与阿奇霉素相比，他汀类与克拉霉素或红霉素联用的病人因横纹肌溶解症入院的风险更高（绝对风险增加0.02%，RR 2.17）、出现肾损伤的风险更高（绝对风险增加1.26%，RR 1.78）。全因死亡率也出现上升（绝对风险增加0.25%，RR 1.56）。
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.
局限：本研究仅纳入老年病人。横纹肌溶解症的风险可能被低估，因为研究采纳的评估指标不够敏感。
Conclusion: In older adults, coprescription of clarithromycin or erythromycin with a statin that is metabolized by CYP3A4 increases the risk for statin toxicity.
结论：对于老年人，克拉霉素或红霉素与CYP3A4代谢的他汀类联用时，可增加他汀类毒性反应的风险。
