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

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

Journal Name: Current Pharmaceutical Design

Volume 23 , Issue 38 , 2017

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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.

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

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Article Details

Year: 2017
Published on: 09 February, 2018
Page: [5839 - 5849]
Pages: 11
DOI: 10.2174/1381612823666170921143104
Price: $65

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