Short-term Dual Therapy or Mono Therapy With Acetaminophen and Ibuprofen for Fever: A Network Meta-Analysis

CONTEXT: There is uncertainty whether acetaminophen and ibuprofen are similar in their effects and safety when used as single or dual (alternating or combined) therapies. OBJECTIVE: To assess the comparative efficacy of acetaminophen, ibuprofen alone, alternating, or combined through a systematic review and network meta-analysis. DATA SOURCES: Medline, Embase, and CENTRAL from inception to September 20, 2023. STUDY SELECTION: Randomized trials comparing acetaminophen, ibuprofen, both alternating, and both combined, for treating children with fever. DATA EXTRACTION: Two reviewers independently screened abstracts and full texts, extracted the data, and assessed the risk of bias. We performed pairwise and network meta-analysis using the random-effects model. RESULTS: We included 31 trials (5009 children). We found that combined (odds ratio [OR], 0.19; confidence interval [CI], 0.09–0.42) and alternating therapies (OR, 0.20; CI, 0.06–0.63) may be superior to acetaminophen, whereas ibuprofen at a high dose may be comparable (OR, 0.98; CI, 0.63–1.59) in terms of proportion of afebrile children at the fourth hour. These results were similar at the sixth hour. There were no differences between ibuprofen (low or high dose), or alternating, or combined with acetaminophen in terms of adverse events. LIMITATIONS: We only evaluated the efficacy and safety during the first 6 hours. CONCLUSIONS: Dual may be superior to single therapies for treating fever in children. Acetaminophen may be inferior to combined or alternating therapies to get children afebrile at 4 and 6 hours. Compared with ibuprofen, acetaminophen was also inferior to ibuprofen alone at 4 hours, but similar at 6 hours. PROSPERO registration: CRD42016035236.