Intravenous paracetamol dosing guidelines for pain management in (Pre)term neonates using the paediatric study decision tree

P. Mian*, C. A.J. Knibbe, E. A.M. Calvier, D. Tibboel, K. Allegaert

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

12 Citations (Scopus)


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 (C ssmean 9-11 mg/L) for pain relief in neonates compared to older children and adults, dosing regimens based on this C ssmean 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 C ssmean below target (7.65 mg/L), while dosages from investigator-initiated studies resulted in either a C ssmean 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 Css mean , though additional clinical studies are needed to support its safety.

Original languageEnglish
Pages (from-to)5839-5849
Number of pages11
JournalCurrent Pharmaceutical Design
Issue number38
Publication statusPublished - 1 Oct 2017

Bibliographical note

Funding Information:
We thank Wichor Bramer, from the Medical Library Erasmus Medical Centre, for helping developing the systematic search strategy. We thank Ko Hagoort for editorial assistance. P. Mian has been supported by the Sophia Stichting Wetenschappelijk Onder-zoek (SSWO S16-08). K Allegaert has been supported by the Fund for Scientific Research, Flanders (fundamental clinical investigator-ship 1800214N) and his research activities are further facilitated by the agency for innovation by Science and Technology in Flanders (IWT) through the SAFEPEDRUG (IWT/SBO 130033).

Publisher Copyright:
© 2017 Bentham Science Publishers.


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