The dark side of ibuprofen in the treatment of patent ductus arteriosus: could paracetamol be the solution?

ABSTRACT

Introduction: Patent ductus arteriosus (PDA) persistence is associated, in prematures, to several complications. The optimal PDA management is still under debate, especially regarding the best therapeutic approach and the time to treat. The available drugs are not exempt from contraindications and side effects; ibuprofen itself, although representing the first-choice therapy, can show nephrotoxicity and other complications. Paracetamol seems a valid alternative to classic nonsteroidal anti-inflammatory Drugs, with a lower toxicity.

Areas covered: Through an analysis of the published literature on ibuprofen and paracetamol effects in preterm neonates, this review compares the available treatments for PDA, analyzing the mechanisms underlining ibuprofen-associated nephrotoxicity and the eventual paracetamol-induced hepatic damage, also providing an update of what has been yet demonstrated and a clear description of the still open issues.

Expert Opinion: Paracetamol is an acceptable alternative in case of contraindication to ibuprofen; its toxicity, in this setting, is very low. Lower doses may be effective, with even fewer risks. In the future, paracetamol could represent an efficacious first-line therapy, although its safety, optimal dosage, and global impact have to be fully clarified through long-term trials, also in the perspective of an individualized and person-based therapy taking into account the extraordinary individual variability.

KEYWORDS:

• Ibuprofen
• paracetamol
• PDA treatment
• nephrotoxicity
• hepatotoxicity

Article highlights

• In preterm newborns, PDA persistence can lead to several complications and its management still remains a controversial topic, particularly regarding the moment and the modality of intervention

• The most common approach is a pharmacological treatment with ibuprofen when PDA is hemodynamically significant. In presence of drug contraindications or failure after repeated cycles, a surgical ligation can be evaluated

• Ibuprofen shows a good success rate in PDA closure, but its use has been associated with several side effects included nephrotoxicity, being able to cause transient kidney injury

• Paracetamol, proposed as a possible alternative to classical NSAIDs in PDA management, has been demonstrated very promising, with comparable success rates and a good safety profile if used at the dose of 15 mg/kg every 6 h for 3–7 days: a transient elevation in liver transaminases has been observed only in a few number of patients

• However, aspects such as real efficacy in extremely low birth weight (ELBW) newborns, the best route of administration and dosage, timing of the first dose, long-lasting effects, remain largely unexplored. Therefore, more studies are needed before to propose this medication as a first-line therapy

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.