Comparing the efficacy of NSAIDs and paracetamol in children.

Paracetamol (acetaminophen) and the nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in children for antipyresis and analgesia. The anti-inflammatory properties of the NSAIDs have, in addition, been used in such diverse disorders as juvenile idiopathic arthritis, Kawasaki disease and cystic fibrosis (1–4). The NSAIDs indomethacin and ibuprofen are also used to treat delayed closure of patent ductus arteriosus (PDA) in premature infants (5). Paracetamol and NSAIDs are often given together for the management of pain or fever. Despite the widespread use of these medications there are few data comparing efficacy of these drugs. The combined effectiveness of paracetamol and a NSAID is insufficiently documented in children and it is unknown if there is synergy or additivity of effect when the two drugs are used together. Litalien and Jacqz-Aigrain (6) have recently reviewed the risks and benefits of NSAIDs and paracetamol in children. Knowledge of individual drug pharmacokinetics (PK) and pharmacodynamics (PD) is essential to compare effectiveness. Pharmacokinetic age-related changes and covariate effects are poorly documented for many of the NSAIDs. Pharmacodynamic data are often a simple comparison of one drug to another without quantifying effect. There is a paucity of analgesia concentration–effect relationship data in children, although fever control (7–10) and PDA closure (11) relationships are emerging. In order to use these drugs properly, effectiveness data must be balanced against the drugs safety profiles. Currently this is not carried out and often the safety profile of one NSAID is extrapolated to another. This current review examines the methods used to compare NSAIDs with paracetamol, the difficulties associated with such comparisons and the impact of drug side effects on dosing regimens in children.