An assessment of the safety of pediatric ibuprofen. A practitioner-based randomized clinical trial

S. M. Lesko and A. A. Mitchell
Slone Epidemiology Unit, School of Public Health, Boston University School of Medicine, Brookline, MA 02146.

OBJECTIVE--To test the hypothesis that ibuprofen increases the risk of hospitalization for gastrointestinal bleeding, renal failure, or anaphylaxis among febrile children. DESIGN--Randomized double-blind acetaminophen-controlled trial. SETTING--Outpatient pediatric and family medicine practices. PATIENTS--A total of 84,192 children. INTERVENTION--Patients were randomly assigned to receive 12 mg/kg of acetaminophen, 5 mg/kg of ibuprofen, or 10 mg/kg of ibuprofen. MAIN OUTCOME MEASURES--Hospitalizations for acute gastrointestinal bleeding, acute renal failure, and anaphylaxis. RESULTS--A total of 277 patients (0.3%) were unavailable for follow-up. Overall, 795 participants (1%) were hospitalized, primarily for infectious diseases; hospitalization rates did not differ according to treatment group. Four children had diagnoses of acute, nonmajor gastrointestinal bleeding (two in each ibuprofen dosage group); among ibuprofen-treated children, the observed risk of gastrointestinal bleeding, 7.2 per 100,000 (95% confidence interval, 2 to 18 per 100,000), was not significantly different from the risk among acetaminophen-treated children (P = .31). There were no hospitalizations for acute renal failure or anaphylaxis; the upper 95% confidence bound for the risk of either of these outcomes was 5.4 per 100,000 ibuprofen-treated children. Among a number of other possibly serious adverse drug events, low white blood cell count was marginally associated with ibuprofen treatment. Because this association was observed in the setting of multiple comparisons and white blood cell counts may have been low before treatment, causation is unclear. CONCLUSIONS--The risk of hospitalization for gastrointestinal bleeding, renal failure, or anaphylaxis was not increased following short-term use of ibuprofen in children. These data, however, provide no information on the risks of less severe outcomes or the risks of prolonged ibuprofen use.

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