OBJECTIVES: This was the first meta-analysis to compare the efficacy and safety outcomes of the ibuprofen/paracetamol FDC against placebo, administered postoperatively, for moderate to severe pain relief in adults.

METHODS: The literature was comprehensively searched for clinical trials until April 2020, to identify comparative literature studies of the ibuprofen/paracetamol FDC in acute postoperative pain in adults. Independent reviewers performed the study selection, data extraction, and the risk-of-bias and quality-of-evidence assessments based on the Cochrane criteria. The outcome measures of interest in the meta-analysis were ≥ 50% pain relief, need for rescue medications, and occurrence of adverse drug events. A trial sequential analysis (TSA) was conducted to assess how precise and conclusive the meta-analysis outcomes are.

RESULTS: Seven double-blind, randomized controlled trials with 2947 participants were included. The FDC dose was at three different levels: 75–100 mg ibuprofen/250 mg paracetamol, 150–200 mg ibuprofen/500 mg paracetamol (FDA-approved dose level), and 292.5–400 mg ibuprofen/975–1000 mg paracetamol. The ≥ 50% pain relief outcome was more achieved with the FDC compared to placebo (risk ratio [RR] 2.60, 95% confidence interval [CI] 2.11–3.20, p < 0.00001), as was the reduced need for rescue medications (RR 0.51, 95% CI 0.37–0.71, p < 0.0001). While inconclusive based on TSA, the FDC was at the highest doses at least as well tolerated as placebo regarding the occurrence of adverse events, including severe, common, and treatment-related adverse events, as well as those that lead to discontinuation, but it was also significantly associated with lower rates of headache and nausea. Subgroup analyses confirmed that the efficacy and safety of the FDC were maintained regardless of doses and formulations.

CONCLUSIONS: The ibuprofen plus paracetamol FDC is conclusively an effective analgesic against placebo in acute postoperative, moderate to severe pain in adults. It is also superiorly well tolerated, including at the higher dose of 292.5–400 mg ibuprofen/975–1000 mg paracetamol.