Paracetamol to induce ductus arteriosus closure: is it valid?

Archives of disease in childhood (2013-04-23)
Karel Allegaert, Brian Anderson, Sinno Simons, Bart van Overmeire

There remains a need for alternative medical treatments for patent ductus arteriosus (PDA) closure in extreme preterm neonates because of therapeutic failure and adverse effects associated with non-selective cyclo-oxygenase inhibitors. Reports of an association between paracetamol exposure and PDA closure in a limited number of extreme preterm neonates have been published. However, causality cannot be taken for granted because a link between the current knowledge of the clinical pharmacology of paracetamol and (patho)physiology of ductal closure is not known. In contrast to non-selective cyclo-oxygenase inhibitors, paracetamol has limited effects at peripheral sites, is a poor antithrombotic and anti-inflammatory drug and exerts its effects primarily within the central nervous system. Although paracetamol appears an effective and safe analgesic in term and near term neonates, its effectiveness and safety for PDA closure are uncertain because the drug is administered in high doses and there remain a limited number of observations in this specific subpopulation so far. Prospective comparative trials are reasonable and are urgently needed to establish both the effectiveness and safety data of paracetamol when used for this indication.

Product Number
Product Description

Acetaminophen, Pharmaceutical Secondary Standard; Certified Reference Material
Acetaminophen, BioXtra, ≥99.0%
Acetaminophen, meets USP testing specifications, 98.0-102.0%, powder
Acetaminophen, analytical standard
Paracetamol, European Pharmacopoeia (EP) Reference Standard
Acetaminophen, United States Pharmacopeia (USP) Reference Standard
Acetaminophen solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®