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


CONCLUSIONS
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.
Nabulsi
Mona M
MM
Department of Pediatrics, American University of Beirut Medical Center, Beirut, Lebanon. mn04@aub.edu.lb
Tamim
Hala
H
Mahfoud
Ziyad
Z
Itani
Mohammad
M
Sabra
Ramzi
R
Chamseddine
Fadi
F
Mikati
Mohammad
M
D000082:Acetaminophen / Q000009:adverse effects* / Q000627:therapeutic use*; D000284:Administration, Oral; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005334:Fever / Q000188:drug therapy*; D006801:Humans; D007052:Ibuprofen / Q000009:adverse effects* / Q000627:therapeutic use; D007223:Infant; D008297:Male; D010919:Placebos
D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D010919:Placebos; D000082:Acetaminophen; D007052:Ibuprofen