Abstract
Background: Pain following tonsillectomy is often poorly managed in the home setting. Multimodal analgesia with acetaminophen (paracetamol) and nonsteroidal anti-inflammatory drugs offers superior analgesia over monotherapy but may be difficult for caregivers to manage. A fixed-dose combination oral suspension product containing paracetamol and ibuprofen has been developed to facilitate pediatric dosing.
Aims: The aims of this study are to determine the analgesic effectiveness, pharmacokinetics, and safety of the fixed-dose combination at two doses in the pediatric population.
Methods: In this prospective, multicenter, randomized, single-blind, parallel group trial, 251 children aged 2-12 years undergoing day-stay (adeno) tonsillectomy were randomized to two dose groups of the fixed-dose combination. A doubled loading dose was given preoperatively, followed by treatment for up to 11 days (Higher dose: paracetamol 15 mg/kg + ibuprofen 4.5 mg/kg, Lower dose: paracetamol 12 mg/kg + ibuprofen 3.6 mg/kg). Blood samples were collected for pharmacokinetic analysis for up to 6 hours after the loading dose. The analgesic effectiveness was examined on the first day after surgery using both Parents Postoperative Pain Measurement and modified Wong-Baker Faces pain scales. Rescue medication consumption was recorded throughout the study.
Results: Differences in maximum plasma concentration (C-max) and total exposure (AUC(0 -> t)) between the treatment groups for both analytes were consistent with a 25% increase in dose; there was no difference in time to peak concentration (T-max). On the first postoperative day, there was no difference in pain scores or rescue medication use between treatment groups (approximately 30% in both groups). The combination was well tolerated by both groups. The most common adverse events were vomiting and nausea. The incidence of postoperative bleeding was 4.4%.
Conclusion: The shallow dose-response relationship and good tolerability of the fixed-dose combination over an extended study period supports the utility of both doses of the fixed-dose combination in the home setting.