Systematic review and meta-analysis of the clinical safety and tolerability of ibuprofen compared with paracetamol in paediatric pain and fever

Curr Med Res Opin. 2009 Sep;25(9):2207-22. doi: 10.1185/03007990903116255.


Objective: The main aim of this review was to compare the tolerability and safety between ibuprofen and paracetamol when used as anti-pyretic and analgesic agents in children up to 18 years of age.

Methods: MEDLINE (1950 to November 2008), EMBASE (1980 to November 2008), The Cochrane Library (2007, Issue 3), ACP Journal Club (1991 to November 2007) and Pascal (1987 to November 2007) were searched for randomised controlled trails (RCTs) (comparing ibuprofen and/or paracetamol with placebo), controlled observational studies and large case series comprised more than 1000 participants.

Main outcome measures: Adverse events (AEs) requiring discontinuation of medication; systemic reactions related to ibuprofen or paracetamol; serious AEs that are fatal, life-threatening or require hospitalisation; and serious AEs not requiring hospitalisation.

Results: A total of 24 RCTs examined either ibuprofen and/or paracetamol versus placebo for AE data. Twelve other studies meeting our criteria were also included for AE data. Meta-analysis of systemic reactions demonstrated that tolerability and safety of ibuprofen was similar to placebo, as was paracetamol: ibuprofen versus placebo relative risk (RR) 1.39 (95% CI: 0.92, 2.10); paracetamol versus placebo RR 1.57 (95% CI 0.74, 3.33). A total of 2937 systemic AEs occurred in 21,305 patients taking ibuprofen compared with 1,466 systemic AEs in 11,164 patients taking paracetamol: RR 1.03 (95% CI 0.98, 1.10). There was no significant difference between the two groups. Narrative analysis of AE data identified conflicting evidence regarding hepatic injury with paracetamol and group A streptococcal infections with ibuprofen or paracetamol treatment.

Conclusions: Ibuprofen, paracetamol and placebo have similar tolerability and safety profiles in terms of gastrointestinal symptoms, asthma and renal adverse effects. While the study data investigated here may not reflect over-the-counter use, these results are still relevant in the context of any safety concerns relating to general ibuprofen or paracetamol treatment in children.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Acetaminophen / adverse effects*
  • Acetaminophen / therapeutic use*
  • Algorithms
  • Analgesics, Non-Narcotic / adverse effects
  • Analgesics, Non-Narcotic / therapeutic use
  • Anaphylaxis / epidemiology
  • Anaphylaxis / etiology
  • Child
  • Fever / complications
  • Fever / drug therapy*
  • Gastrointestinal Hemorrhage / epidemiology
  • Gastrointestinal Hemorrhage / etiology
  • Hospitalization / statistics & numerical data
  • Humans
  • Ibuprofen / adverse effects*
  • Ibuprofen / therapeutic use*
  • Liver Diseases / epidemiology
  • Liver Diseases / etiology
  • Pain / complications
  • Pain / drug therapy*


  • Analgesics, Non-Narcotic
  • Acetaminophen
  • Ibuprofen