Comparative safety and efficacy of paracetamol versus non-steroidal anti-inflammatory agents in neonates with patent ductus arteriosus: A systematic review and meta-analysis of randomized controlled trials

Br J Clin Pharmacol. 2022 Jul;88(7):3078-3100. doi: 10.1111/bcp.15291. Epub 2022 Mar 15.

Abstract

Aim: Ibuprofen and indomethacin are the preferred drug treatment for patent ductus arteriosus (PDA) in preterm neonates. The comparative safety and efficacy of paracetamol as an alternative has not yet been well established. The aim of our study was to define the comparative efficacy and safety of paracetamol versus ibuprofen and indomethacin for PDA.

Methods: We performed a systematic literature search in PubMed, Scopus and Cochrane databases on randomized controlled trials comparing the efficacy and/or the safety of paracetamol versus ibuprofen and/or indomethacin and meta-analysed the available data.

Results: There were 1718 neonates from 20 eligible studies. Paracetamol did not differ from ibuprofen or indomethacin regarding the primary (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.69-1.26, P-value: 0.650, when compared to ibuprofen, and OR: 0.78; 95% CI: 0.20-3.02, P-value: 0.716, when compared to indomethacin) and overall (OR: 1.17; 95% CI: 0.82-1.66, P-value: 0.394, when compared to ibuprofen, and OR: 1.12; 95% CI: 0.58-2.15, P-value: 0.733, when compared to indomethacin) PDA closure rates. Paracetamol resulted in significantly reduced risk of oliguria and a tendency towards less gastrointestinal bleeding.

Conclusion: There was no significant difference between paracetamol and ibuprofen or indomethacin in the PDA closure rates. However, paracetamol caused fewer adverse effects.

Keywords: acetaminophen; ibuprofen; indomethacin; paracetamol; patent ductus arteriosus.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Acetaminophen / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Ductus Arteriosus, Patent* / chemically induced
  • Ductus Arteriosus, Patent* / drug therapy
  • Humans
  • Ibuprofen / adverse effects
  • Indomethacin / adverse effects
  • Infant, Low Birth Weight
  • Infant, Newborn
  • Infant, Premature
  • Randomized Controlled Trials as Topic

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Acetaminophen
  • Ibuprofen
  • Indomethacin