Intravenous Paracetamol Dosing Guidelines for Pain Management in (pre)term Neonates Using the Paediatric Study Decision Tree

Title:Intravenous Paracetamol Dosing Guidelines for Pain Management in (pre)term Neonates Using the Paediatric Study Decision Tree

Volume: 23 Issue: 38

Author(s): P. Mian*, C.A.J. Knibbe, E.A.M. Calvier, D. Tibboel and K. Allegaert

Affiliation:

• Erasmus MC Sophia Children's Hospital, Intensive Care and Department of Paediatric Surgery, Rotterdam,Netherlands

Keywords: Paracetamol, propacetamol, pharmacokinetics, neonates, intravenous, pain, paediatric study decision tree.

Abstract: Background: Intravenous paracetamol (acetaminophen) has not been licensed for analgesia in preterm neonates or infants < 2 years, respectively, in Europe and the United States. A variety of dosing regimens is therefore used off-label. Because evidence supports the use of the same target mean steady state paracetamol concentration (Cssmean, 9-11 mg/L) for pain relief in neonates compared to older children and adults, dosing regimens based on this Cssmean were evaluated in a two-step approach.

Methods: First, a systematic search was performed to provide pharmacokinetic (PK)-based dosing guidelines for pain in neonates (with subsequent searches on safety in these papers). Second, concentration-time profiles based on these dosing guidelines were generated to provide a dosing advice for paracetamol to treat neonatal pain.

Results: Of 2334 potentially relevant articles, 9 studies were included. For typical term neonates, dosages specified in packaging (labels) resulted in Cssmean below target (7.65 mg/L), while dosages from investigator-initiated studies resulted in either a Cssmean above (15.31), or around the target (11.78 and 10.21) for (pre)term neonates >32 weeks. Only one study suggested a dosing resulting in a tailored concentration (8.7) in preterm neonates <32 weeks.

Conclusion: A loading dose 20 mg/kg, followed by 10 mg/kg/6h is recommended for 32-44 weeks' neonates, which is supported by short-term safety. For neonates < 32 weeks, a loading dose of 12 mg/kg and a maintenance dose of 6mg/kg/6h seems to lead to the target Cssmean, though additional clinical studies are needed to support its safety.

Cite this article as:

Mian P.*, Knibbe C.A.J., Calvier E.A.M., Tibboel D. and Allegaert K., Intravenous Paracetamol Dosing Guidelines for Pain Management in (pre)term Neonates Using the Paediatric Study Decision Tree, Current Pharmaceutical Design 2017; 23 (38) . https://dx.doi.org/10.2174/1381612823666170921143104

DOI https://dx.doi.org/10.2174/1381612823666170921143104	Print ISSN 1381-6128
Publisher Name Bentham Science Publisher	Online ISSN 1873-4286