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

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.

The impact of the route of administration on the efficacy and safety of the drug therapy for patent ductus arteriosus in premature infants: a systematic review and meta-analysis

“…Secondly, our study places an emphasis on the utilization of paracetamol in PDA closure therapy. Several studies have illuminated that paracetamol can effectively and safely close PDA of the premature in premature infants while incurring fewer adverse events compared to ibuprofen or indomethacin ( Balachander et al, 2020 ; Katsaras et al, 2022 ; Karabulut & Paytoncu, 2019 ; Nishizaki et al, 2020 ; Guimarães et al, 2009 ).…”

Acetaminophen, Nonsteroidal Anti-Inflammatory Drugs, and Hypertension

“…More recently, acetaminophen has been shown to be an effective and potentially safer alternative. 15 COX inhibition is thought to be fundamental to NSAID-associated gastrointestinal adverse effects such as ulcer formation, because prostaglandins produced in the GI wall play roles in epithelial mucus production, microvascular mucosal perfusion, bicarbonate formation, and wound healing. 16 Again consistent with its common mechanism of action, acetaminophen at doses that approach the degree of COX inhibition achieved clinically by ibuprofen and naproxen share their GI toxicity profile.…”

“…More recently, acetaminophen has been shown to be an effective and potentially safer alternative. 15…”

Association of the EPAS1 rs7557402 Polymorphism with Hemodynamically Significant Patent Ductus Arteriosus Closure Failure in Premature Newborns under Pharmacological Treatment with Ibuprofen

“…Cyclooxygenase (COX) inhibitors are administered as a pharmacological treatment for hemodynamically significant PDA: the most commonly used inhibitors are indomethacin and ibuprofen, although the use of acetaminophen has recently been approved [8][9][10][11][12].…”

“…Up to 30% of pharmacological treatment failure has been observed in preterm infants. Both indomethacin and ibuprofen have shown similar efficacy [8][9][10][11][12]. In the National Institute of Perinatology, the most commonly used pharmacological treatment is ibuprofen.…”