Safety of azithromycin in pediatrics: a systematic review and meta-analysis

Eur J Clin Pharmacol. 2020 Dec;76(12):1709-1721. doi: 10.1007/s00228-020-02956-3. Epub 2020 Jul 17.


Purpose: To evaluate the toxicity of azithromycin in neonates, infants, and children.

Methods: 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.

Results: 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%).

Conclusion: 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.

Keywords: Azithromycin; Meta-analysis; Pediatrics; Safety; Systematic review.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Age of Onset
  • Anti-Bacterial Agents / adverse effects*
  • Azithromycin / adverse effects*
  • Child
  • Diarrhea / chemically induced
  • Diarrhea / epidemiology*
  • Humans
  • Incidence
  • Long QT Syndrome / chemically induced
  • Long QT Syndrome / epidemiology
  • Placebos / administration & dosage
  • Placebos / adverse effects
  • Prospective Studies
  • Pyloric Stenosis, Hypertrophic / chemically induced
  • Pyloric Stenosis, Hypertrophic / epidemiology
  • Randomized Controlled Trials as Topic
  • Risk Assessment / statistics & numerical data
  • Vomiting / chemically induced
  • Vomiting / epidemiology*


  • Anti-Bacterial Agents
  • Placebos
  • Azithromycin