Comparison of Acetaminophen and Ibuprofen as a Short-Term Dual Therapy or Monotherapy for Fever in Children

There is a dearth of data depicting the similarities in efficacy and safety between acetaminophen and ibuprofen when used as a monotherapy or dual (alternating or combination) therapies for the treatment of fever in children. This systematic review and network meta-analysis aimed to evaluate the comparative efficacy of acetaminophen and ibuprofen, both alone and in alternating or combined regimens.

The review included data from Medline, Embase, and CENTRAL, covering studies from inception to September 20, 2023. The researchers included randomized trials comparing the effects of acetaminophen, ibuprofen, and their combinations or alternations in treating fever in children.

The findings of the study revealed:

• A total of 31 trials involving 5,009 children were included.
• The analysis indicated 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 more effective than acetaminophen alone in achieving afebrile status by the fourth hour.
• Ibuprofen at a high dose showed comparable efficacy (OR, 0.98; CI, 0.63–1.59) to acetaminophen. Similar results were observed at the sixth hour. 
• There were no significant differences in adverse events between ibuprofen (both low and high doses), alternating, or combined therapies with acetaminophen.

Thus, the researchers concluded that dual therapies might be more efficacious than single therapies for reducing fever in children. Acetaminophen appears to be less effective than combined or alternating therapies for achieving afebrile status at four and six hours., Additionally, acetaminophen was also found to be less effective at four hours but similar at six hours as compared to ibuprofen. 

Source: De la Cruz-Mena JE, Veroniki AA, Acosta-Reyes J, Estupiñán-Bohorquez A, Ibarra JA, Pana MC, Sierra JM, Florez ID. Short-term Dual Therapy or Mono Therapy With Acetaminophen and Ibuprofen for Fever: A Network Meta-Analysis. Pediatrics. 2024 Oct 1;154(4):e2023065390. doi: 10.1542/peds.2023-065390. PMID: 39318339.