Neonatal Intensive Care Drug Manual

The dosing schedule in this formulary is equivalent to a target paracetamol concentration of approximately 11 mg/l.¹

Recommendations are primarily based on intravenous pharmacokinetic analyses as paracetamol has good oral bioavailability. The rectal dosing is safe but may not achieve target paracetamol concentrations as rectal bioavailability is variable depending on the formulation used. Oral or intravenous routes are preferred.^1-3 (LOE IV GOR C)

Recommendations are adapted from dosing schedules used in randomised controlled trials. The majority of studies have used 15 mg/kg every 6 hours for 3–7 days. The maintenance doses in extreme preterm infants are lower, consistent with studies focused on this population.

1. 
   Wang C, Allegaert K, Tibboel D, Danhof M, van der Marel CD, Mathot RA, et al. Population pharmacokinetics of paracetamol across the human age-range from (pre)term neonates, infants, children to adults. Journal of Clinical Pharmacology. 2014;54:619-29.
   
2. 
   Allegaert K, Palmer GM, Anderson BJ. The pharmacokinetics of intravenous paracetamol in neonates: size matters most. Arch Dis Child 2011;96:575-80.
   
3. 
   Anderson BJ, van Lingen RA, Hansen TG, Lin YC, Holford NH. Acetaminophen developmental pharmacokinetics in premature neonates and infants: a pooled population analysis. Anesthesiology 2002;96:1336-45.
   
4. 
   Ohlsson A, Shah PS. Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low birth weight infants. Cochrane Database of Systematic Reviews 2020;1:CD010061.
   
5. 
   Schindler T, Smyth J, Bolisetty S, Michalowski J, Mallitt KA, Singla A, et al. Early PARacetamol (EPAR) trial: a randomized controlled trial of early paracetamol to promote closure of the ductus arteriosus in preterm infants. Neonatology 2021 [in press].
   
6. 
   Ohlsson A, Shah PS. Paracetamol (acetaminophen) for prevention or treatment of pain in newborns. Cochrane Database of Systematic Reviews. 2020;1:CD011219.
   
7. 
   Terrin G, Conte F, Oncel MY, Scipione A, McNamara PJ, Simons S, et al. Paracetamol for the treatment of patent ductus arteriosus in preterm neonates: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2016;101:F127-36.
   
8. 
   Pacifici GM, Allegaert K. Clinical Pharmacology of Paracetamol in Neonates: A Review. Curr Ther Res Clin Exp. 2015;77:24–30.
   
9. 
   Heubi JE, Barbacci MB, Zimmerman HJ. Therapeutic misadventures with acetaminophen: hepatoxicity after multiple doses in children. J Pediatr. 1998;132:22-7.