Alternating ibuprofen and acetaminophen in the treatment of febrile children: a pilot study [ISRCTN30487061]

BMC Med. 2006 Mar 4;4:4. doi: 10.1186/1741-7015-4-4.

Abstract

Background: Alternating ibuprofen and acetaminophen for the treatment of febrile children is a prevalent practice among physicians and parents, despite the lack of evidence on effectiveness or safety. This randomized, double-blind and placebo-controlled clinical trial aims at comparing the antipyretic effectiveness and safety of a single administration of alternating ibuprofen and acetaminophen doses to that of ibuprofen mono-therapy in febrile children.

Methods: Seventy febrile children were randomly allocated to receive either a single oral dose of 10 mg/kg ibuprofen and 15 mg/kg oral acetaminophen after 4 hours, or a similar dose of ibuprofen and placebo at 4 hours. Rectal temperature was measured at baseline, 4, 5, 6, 7 and 8 hours later. Endpoints included proportions of afebrile children at 6, 7 and 8 hours, maximum decline in temperature, time to recurrence of fever, and change in temperature from baseline at each time point. Intent-to-treat analysis was planned with statistical significance set at P < 0.05.

Results: A higher proportion of subjects in the intervention group (83.3%) became afebrile at 6 hours than in the control group (57.6%); P = 0.018. This difference was accentuated at 7 and 8 hours (P < 0.001) with a significantly longer time to recurrence of fever in the intervention group (mean +/- SD of 7.4 +/- 1.3 versus 5.7 +/- 2.2 hours), P < 0.001. Odds ratios (95%CI) for defervescence were 5.6 (1.3; 23.8), 19.5 (3.5; 108.9) and 15.3 (3.4; 68.3) at 6, 7 and 8 hours respectively. Two-way ANOVA with repeated measures over time revealed a significantly larger decline in temperature in the intervention group at times 7 (P = 0.026) and 8 (P = 0.002) hours.

Conclusion: A single dose of alternating ibuprofen and acetaminophen appears to be a superior antipyretic regimen than ibuprofen mono-therapy. Further studies are needed to confirm these findings.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / adverse effects*
  • Acetaminophen / therapeutic use*
  • Administration, Oral
  • Analgesics, Non-Narcotic / administration & dosage*
  • Analgesics, Non-Narcotic / adverse effects
  • Analgesics, Non-Narcotic / therapeutic use*
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Child
  • Child, Preschool
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Fever / drug therapy*
  • Humans
  • Ibuprofen / adverse effects*
  • Ibuprofen / therapeutic use
  • Infant
  • Male
  • Placebos

Substances

  • Analgesics, Non-Narcotic
  • Anti-Inflammatory Agents, Non-Steroidal
  • Placebos
  • Acetaminophen
  • Ibuprofen

Associated data

  • ISRCTN/ISRCTN30487061