Perinatal and neonatal use of paracetamol for pain relief

Paracetamol (acetaminophen) is the most widely used drug to treat pain or fever in pregnant women or neonates, but its pharmacokinetics (PK) and pharmacodynamics (PD) warrant a focused analysis. During pregnancy, there is an important increase in paracetamol clearance. Consequently, it is reasonable to anticipate that the analgesic effect of paracetamol will decrease faster, whereas higher doses may result in even higher oxidative toxic metabolites. Therefore, most peripartal PD data relate to multimodal analgesia strategies. In neonates, weight/size is the most relevant covariate of paracetamol PK. This resulted in proposed dosing regimens containing higher doses than currently prescribed in the label for term neonates. Using adequate dosing, paracetamol is a poor procedural analgesic, is effective for mild-to-moderate pain, and has morphine-sparing effects. Short-term safety has been well documented, and there is active research investigating the potential association between paracetamol exposure and atopy, fertility, and neurobehavior.