Department of Pharmacy/Evidence-based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, 610041, China.
Eur J Clin Pharmacol. 2020 Dec;76(12):1709-1721. doi: 10.1007/s00228-020-02956-3. Epub 2020 Jul 17.
To evaluate the toxicity of azithromycin in neonates, infants, and children.
A systematic review was performed for relevant studies using Medline (Ovid), PubMed, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, and International Pharmaceutical Abstracts. We calculated the pooled incidence of adverse drug reactions (ADRs) associated with azithromycin based on prospective studies (RCTs and prospective cohort studies) and analyzed the risk difference (RD) of ADRs between azithromycin and placebo or other antibiotics using meta-analysis of RCTs.
We included 133 studies with 4243 ADRs reported in 197,675 neonates, infants, and children who received azithromycin. The safety of azithromycin as MDA in pediatrics was poorly monitored. The main ADRs were diarrhea and vomiting. In prospective non-MDA studies, the most common toxicity was gastrointestinal ADRs (938/1967; 47.7%). The most serious toxicities were cardiac (prolonged QT or irregular heart beat) and idiopathic hypertrophic pyloric stenosis (IHPS). Compared with placebo, azithromycin did not show increased risk ADRs based on RCTs (risk difference - 0.17 to 0.07). The incidence of QT prolonged was higher in the medium-dosage group (10-30 mg/kg/day) than that of low-dosage group (≤ 10 mg/kg/day) (82.0% vs 1.2%).
The safety of azithromycin as MDA needs further evaluation. The most common ADRs are diarrhea and vomiting. The risk of the most serious uncommon ADRs (cardiac-prolonged QT and IHPS) is unknown.
评估阿奇霉素在新生儿、婴儿和儿童中的毒性。
使用 Medline（Ovid）、PubMed、Cochrane 对照试验中心注册库、EMBASE、CINAHL 和国际药学文摘进行了相关研究的系统评价。我们根据前瞻性研究（RCT 和前瞻性队列研究）计算了与阿奇霉素相关的不良反应（ADR）的合并发生率，并使用 RCT 的荟萃分析分析了阿奇霉素与安慰剂或其他抗生素之间 ADR 的风险差异（RD）。
我们纳入了 133 项研究，共纳入 197675 名接受阿奇霉素治疗的新生儿、婴儿和儿童的 4243 例 ADR 报告。儿童中 MDA 用阿奇霉素的安全性监测较差。主要 ADR 为腹泻和呕吐。在非 MDA 的前瞻性研究中，最常见的毒性是胃肠道 ADR（938/1967；47.7%）。最严重的毒性是心脏（QT 延长或心律失常）和特发性肥厚性幽门狭窄（IHPS）。与安慰剂相比，阿奇霉素基于 RCT 并未显示出增加的 ADR 风险（风险差异 -0.17 至 0.07）。中剂量组（10-30mg/kg/天）QT 延长的发生率高于低剂量组（≤10mg/kg/天）（82.0% vs 1.2%）。
作为 MDA 的阿奇霉素的安全性需要进一步评估。最常见的 ADR 是腹泻和呕吐。最严重的不常见 ADR（心脏-QT 延长和 IHPS）的风险未知。
