Most parents become distressed when their child gets a fever and are anxious to get rid of the fever (and the underlying illness). I am frequently asked about giving acetaminophen and ibuprofen in combination or alternating doses. While there may be some benefit in giving both medicines, there is also the potential for increased side effects.
So I was intrigued to see the title of an article being early released this week in Pediatrics entitled, “Short-Term Dual or Mono Therapy with Acetaminophen and Ibuprofen for Fever: A Network Meta-Analysis,” by a team of investigators in Colombia, led by Dr. Juan Esteban de la Cruz from the Universidad de Antioquia, Medellin (10.1542/peds.2023-065390).
The authors conducted a meta-analysis that included 31 randomized controlled trials and 5000 children to look at the effectiveness of antipyretics at 4–6 hours in reducing discomfort and fever:
- Acetaminophen 10–15 mg/kg/dose
- Low-dose ibuprofen 5–7.5 mg/kg/dose
- High-dose ibuprofen 7.5–10 mg/kg/dose
- Combined: Acetaminophen 10–15 mg/kg/dose + ibuprofen 5–10 mg/kg/dose given simultaneously
- Alternating: Acetaminophen 10–15 mg/kg/dose given first, followed by ibuprofen 5–10 mg/kg/dose in 4 hours
For reducing fever at 6 hours:
- Acetaminophen and high-dose ibuprofen were similarly effective.
- Combined acetaminophen + ibuprofen was more effective than acetaminophen alone.
- Alternating doses of acetaminophen and ibuprofen were more effective than acetaminophen alone.
- Combined and alternating acetaminophen and ibuprofen were similar in effectiveness.
The rate of adverse events was similar for all the drug regimens.
While the results of this study may be reassuring for advocates of combined or alternating doses of acetaminophen and ibuprofen, Kelly Wade, MD, PhD, from Children’s Hospital of Philadelphia and Cheryl Mathis, PhD, from the University of Utah, in an invited commentary, remind us that this study only looked at impact at 6 hours (10.1542/peds.2024-067408). This is a huge limitation to this study. Most children with febrile illnesses will have fever for more than 6 hours and will thus take more than 1 or 2 doses of these medicines, and adverse events are more likely when children are taking these medicines for longer periods of time. Additionally, Wade and Mathis note that medication errors are more likely when both acetaminophen and ibuprofen are used.
I encourage you to read the meta-analysis and commentary to see if you are reassured enough by these findings to recommend combined or alternating doses of acetaminophen and ibuprofen to your patients.
