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Neonatal Intensive Care Drug Manual
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| bet | 441/654 | | Sana | 03.01.2022 | | Hajmi | 1,5 Mb. | | #14803 |
Hepatic toxicity
Individual cases with hepatic toxicity related to paracetamol in newborns have been reported. Overall, the number of cases reported is limited to significant overdoses (75–446 mg/kg), most commonly as a result of an in-hospital, 10-fold drug error.8 In infants and children, hepatotoxicity has been reported over a wide dosage range (60–420 mg/kg/day for 1–42 days).9
Pharmacokinetics
Model‐based dosing regimen of intravenous paracetamol aiming for a target paracetamol concentration of 9 mg/l based on population pharmacokinetic analysis from preterm neonates to adults, including 108 neonates (post-natal age 1–76 days, gestational age 27–42 weeks):1
BW 0.5 kg – Loading 11.2 mg/kg; maintenance q6h 5.1 mg/kg
BW 1.0 kg – Loading 12.1 mg/kg; maintenance q6h 6.0 mg/kg
BW 1.5 kg – Loading 12.2 mg/kg; maintenance q6h 6.8 mg/kg
BW 2.0 kg – Loading 13.3 mg/kg; maintenance q6h 7.4 mg/kg
BW 3.0 kg –Loading 12.8 mg/kg; maintenance q6h 8.5 mg/kg
BW 5.0 kg – Loading 13.5 mg/kg; maintenance q6h 10.4 mg/kg
NB. The above numbers can be converted to any target concentration by dividing by 9 and multiplying by the desired target concentration.
Population pharmacokinetic analysis of 943 paracetamol observations from 158 neonates (27–45 weeks' postmenstrual age [PMA]) showed a mean paracetamol serum concentration of 11 mg/l is predicted in neonates of 32–44 weeks' PMA given a standard dose of intravenous paracetamol of 10 mg/kg every 6 hours.2
A population pharmacokinetic analysis of acetaminophen time-concentration profiles in 283 children (124 aged ≤ 6 months) reported that a mean, steady state, target concentration greater than 10 mg/l at trough can be achieved by an oral dose of 25 mg/kg/day in premature neonates at 30 weeks' post-conception, 45 mg/kg/day at 34 weeks' gestation, 60 mg/kg/day at term. Similar concentrations can be achieved with maintenance rectal doses of 25 (capsule suppository) or 30 (triglyceride suppository) mg/kg/day in premature neonates at 30 weeks' gestation, increasing to 90 (capsule suppository) or 120 (triglyceride suppository) mg/kg/day at 6 months.3
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