Equivalent antipyretic activity of ibuprofen and paracetamol in febrile children

doi:10.1016/S0022-3476(97)70093-3

The Journal of Pediatrics

Volume 131, Issue 5, November 1997, Pages 683-687

https://doi.org/10.1016/S0022-3476(97)70093-3 Get rights and content

Abstract

The antipyretic activity of ibuprofen in the Sparklets form was compared, in an equivalence study, with that of paracetamol in the same formulation. The study was conducted as a double-blind multicenter trial, with random allocation of the treatments. One hundred sixteen children of both sexes, aged 4.1 ± 2.6 years, with a fever related to an infectious disease and a mean temperature of 39° ± 0.5° C at the time of inclusion, were treated with single doses of either 10.3 ± 1.9 mg/kg of ibuprofen or 9.8 ± 1.9 mg/kg of paracetamol. The subjects’ rectal temperature was regularly monitored for 6 hours. The statistical analysis of the results confirmed that ibuprofen and paracetamol are equivalent with respect to the following criteria (1) time elapsed between dosing and the lowest temperature: 3.61 ± 1.34 hours for ibuprofen and 3.65 ± 1.47 hours for paracetamol (95% confidence interval [CI] of the difference: –0.48; +0.56); (2) extent of the temperature decrease: 1.65° C ± 0.80° C for ibuprofen and 1.50° C ± 0.61° C for paracetamol, (95% CI of the difference: –0.41; +0.11); (3) rate of temperature decrease: 0.52 ± 0.32° C/hr for ibuprofen and 0.51° C ± 0.38° C/hr for paracetamol (95% CI of the difference: –0.45; +0.55); (4) duration of temperature below 38.5° C: 3.79 ± 1.33 hours for ibuprofen and 3.84 ± 1.22 hours for paracetamol (95% CI of the difference: –0.14; +0.12). (J Pediatr 1997;131:683-7)

Section snippets

Methods

The study was approved by the local ethics committee and was conducted in accordance with the European Good Clinical Practice standards (1989) and the Declaration of Helsinki and subsequent amendments.

Results

No significant difference was found for the two treatment groups (Table I) with respect to age, weight, height, sex, dosage relative to body weight, or rectal temperature at the time of inclusion in the study. For 2 of the 116 assessable patients, the main parameter was missing. Therefore these patients, who belonged to the ibuprofen group, could not be taken into account in the analysis of equivalence.

The rectal temperatures (θ°) of the two treatment groups at the different evaluation times

Discussion

The intention-to-treat analysis showed equivalence between 10 mg/kg ibuprofen and 10 mg/kg paracetamol, with both drugs administered as Sparklets, with respect to the time elapsed between dosing and the lowest observed temperature (T _max ) within 6 hours. On the basis of the calculated 95% CI, the difference between the two treatment groups could at most have been equal to 0.56 hour. This equivalence also applied to the extent and to the rate of temperature decrease in the two groups. The lack

Acknowledgements

We gratefully acknowledge all the physicians who recruited the patients for the study (Drs. G. Almodovar, A. Assouline, J. Azoulay, M. Behar, N. Castaing, J. Castel, B. Cohen, J. Fridman, P. Grandsenne, A. Meyer, F. Moureau, J. Rebot, F. Richoux, J. Sultan, and L. Van).

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Table IV summarizes these key end points. The literature search identified 40 clinical trials which met the selection criteria, specifically containing single oral-dose data, which were included in the review.17–56 Each of the listed published studies evaluated the antipyretic efficacy of acetaminophen using standard antipyretic measurement techniques.
A standardized approach to dosing acetaminophen in pediatric populations was published in 1983. That review proposed specific weight-related dosing for infants and children weighing 6 through 95 lb and an age-based schedule for children aged <4 months through 11 years. Subsequent clinical studies evaluating these and alternative doses of acetaminophen supported the recommended 10–15-mg/kg dose.
This article reviewed published and unpublished pediatric antipyretic data to provide a critical assessment of the 10–15-mg/kg oral dose and the current pediatric oral dosing schedules for acetaminophen.
Published literature and unpublished clinical trials that evaluated the antipyretic efficacy of acetaminophen in children were reviewed. The PubMed database was searched using the term acetaminophen or paracetamol, with study criteria limited to randomized, controlled trials; oral dosing; patient age <12 years; and publication between 1982 and August 2012. All of the sponsor’s unpublished antipyretic clinical studies completed between 1980 and August 2012 and involving at least 1 oral-formulation acetaminophen-only treatment arm were identified. Data from published literature containing sufficient detail to verify doses; dosing frequency; and, when necessary, estimates from figures, and from acetaminophen arms of the unpublished studies were analyzed.
Thirteen unpublished trials enrolled 705 children to receive an oral dose of 10–15 mg/kg of acetaminophen. This dose resulted in a rapid onset of temperature reduction, with a maximum temperature decrement of ~3 hours following administration. Results from 40 published clinical trials in which 2332 children received oral acetaminophen for fever support these findings. The most common adverse events reported in any of the reported studies were gastrointestinal in nature and generally mild in intensity.
Data support the recommended 10–15-mg/kg oral dose and demonstrate that the age and weight schedules for over-the-counter acetaminophen proposed in 1983 remain appropriate.
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Antipyretic effectiveness of ibuprofen and paracetamol
2005, Anales de Pediatria
El objetivo del estudio es analizar comparativamente la eficacia de ibuprofeno y paracetamol, y evaluar la possible repercusión sobre la misma de sexo, peso, talla y enfermedad subyacente.
Se recogieron los datos de filiación de 166 niños con temperatura axilar igual o superior a 38 °C. Se administraron 15 mg/kg de paracetamol a 80 de ellos y 7 mg/kg de ibuprofeno a 86. Se recogió después la temperatura que presentaban a los 60, 120, 180 y 240 min de su administración. Con estos datos se realizó un análisis estadístico, incluyendo un análisis de datos apareados.
Ibuprofeno y paracetamol consiguieron dejar afebriles en algún momento del estudio al 90 % de los niños. El 74% de los pacientes permanecieron afebriles 4 h después de administrarlos. En la muestra global, las temperaturas obtenidas con ibuprofeno frente a paracetamol fueron:37,66 ± 0,73 frente a 37,80 ± 0,65 (p = 0,22) a la hora de su administración; 37,09 ± 0,83 frente a 37,29 ± 0,71 a las 2 h; 37,12 ± 1,05 frente a 37,28 ± 0,87 (p = 0,64) a las 3 h; 37,40 ± 1,12 frente a 37,46 ± 1,00 (p = 0,72) a las 4 h. La máxima velocidad de descenso se alcanzó durante los primeros 60 min (–1,32 ± 0,83 para ibuprofeno frente a –1,09 ± 0,77 con paracetamol; p = 0,10). En cuanto al factor edad, en los niños de edad comprendida entre 5 y 12 años se lograron temperaturas significativamente menores con ibuprofeno que con paracetamol (38,00 ± 0,65 frente a 37,45 ± 0,43 [p = 0,02] en la primera hora; 36,71 ± 0,66 frente a 37,60 ± 0,93 [p = 0,01] en la segunda hora; 36,80 ± 0,79 frente a 37,67 ± 1,12 [p = 0,03] en la tercera hora). El análisis de datos en función del peso,sexo y enfermedad no mostró diferencias significativas.
Ibuprofeno y paracetamol demostraron ser efectivos a la hora de descender la temperatura. Ambos fármacos mostraron una eficacia antitérmica similar, salvo en los niños mayores de 5 años, donde se demostró mayor eficacia con ibuprofeno. Peso, sexo y enfermedad de base no determinaron diferencias de eficacia.
To compare the antipyretic effectiveness of ibuprofen and paracetamol and to evaluate the possible influence of patients’ sex, weight, height and underlying disease on effectiveness.
A total of 166 children with fever, defined as a temperature equal to or above 38 °C, were enrolled. Of these, 80 were given paracetamol at a dose of 15 mg per kg and 86 were given 7 mg of ibuprofen per kg. Temperature was recorded at 60, 120,180 and 240 minutes after drug administration. Data were statistically analyzed, including analysis of paired data.
Ninety percent of the children became afebrile at some time during the study with both paracetamol and ibuprofen.Seventy-four percent of the patients remained afebrile 4 hours after drug administration. The mean temperatures obtained with ibuprofen versus paracetamol were 37.66 ± 0.73 vs 37.8 ± 0.65, p = 0.22 one hour after drug administration;37.09 ± 0.83 vs 37.29 ± 0.71, p = 0.14 two hours after drug administration; 37.12 ± 1.05 vs 37.28 ± 0.87,p = 0.64 three hours after drug administration; and 37.40 ± 1.12 vs 37.46 ± 1.00, p = 0.72 four hours after drug administration. The maximum rate of temperature decrease was achieved during the first 60 minutes after drug administration (–1.32 ± 0.83 with ibuprofen vs –1.09 ± 0.77 with paracetamol, p = 0.10). In children aged between 5 and 12 years, ibuprofen achieved significantly lower temperatures than paracetamol (38.00 ± 0.65 vs 37.45 ± 0.43, p = 0.02 at 1 hour; 36.71 ± 0.66 vs 37.60 ± 0.93,p = 0.01 at 2 hours; 36.80 ± 0.79 vs 37.67 ± 1.12, p = 0.03 at 3 hours). Analysis by weight, height or underlying disease revealed no significant differences.
Both ibuprofen and paracetamol proved to be successful in reducing temperature. The effectiveness of ibuprofen and paracetamol was similar, except in children aged more than 5 years old, in whom ibuprofen was more effective. Weight, sex and underlying disease had no influence on effectiveness.
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We determined a priori that a difference in measured temperature decrease of 0.3°C could have clinical significance. We expected the mean temperature decrease 60 minutes after antipyretic drug administration to have a SD of 0.5°C.11,12 Assuming α = 0.05 and β = 0.90, we calculated the need for 44 subjects to detect a difference in temperature decrease of 0.3°C.
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Equivalent antipyretic activity of ibuprofen and paracetamol in febrile children☆,☆☆,★

Abstract

Section snippets

Methods

Results

Discussion

Acknowledgements

J Pediatr

Considerations on data analysis using computer methods and currently available software for personal computers

Ibuprofen, paracetamol and placebo treatment of febrile children

Clin Pharmacol Ther

Measurement of antipyretic activity of ibuprofen and paracetamol in children

J Clin Pharmacol

Oral antipyretic therapy. Evaluation of ibuprofen

Scand J Rheumatol

Antipyretic activity of ibuprofen and paracetamol in children with pyrexia

Br J Clin Pract