Rapid health technology assessment of ibuprofen and acetaminophen in the treatment of fever in children with asthma

doi:10.5246/jcps.2026.05.034

Abstract

Abstract:

This study aimed to assess the efficacy, safety, and cost-effectiveness of ibuprofen and acetaminophen for managing fever in children with asthma, providing evidence-based guidance for clinical decision-making and treatment regimen selection. A rapid health technology assessment approach was employed. Following a comprehensive literature search of PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, official websites, and relevant health technology assessment databases, the retrieved studies were screened, and data were extracted and evaluated for quality. A total of nine studies were included, comprising two reviews, five systematic reviews/meta-analyses (SRs/MAs), one randomized controlled trial, and one health technology assessment report. Regarding efficacy, combined or alternating therapy demonstrated superior temperature reduction compared with monotherapy, resulting in a lower proportion of children remaining febrile and a longer afebrile period after 4 h. Within the initial 4-hour window, ibuprofen monotherapy was more effective than acetaminophen monotherapy. In terms of safety, the overall incidence of adverse drug reactions was comparable across combined therapy, alternating therapy, and monotherapy; however, the included studies reported inconsistent findings concerning the risk of asthma onset or exacerbation. Concerning cost-effectiveness, although specific analyses in asthmatic populations were lacking, evidence from the United Kingdom indicated that, from the perspective of the National Health Service, combined therapy was more cost-effective than monotherapy in reducing fever, whereas from the parental perspective, this advantage emerged only after 5 d of treatment. Overall, compared with monotherapy, combined and alternating therapies exhibit greater efficacy in treating fever in children with asthma; nonetheless, further high-quality studies are warranted to clarify their safety profile and cost-effectiveness.

Key words: Ibuprofen, Acetaminophen, Children with asthma, Fever, Rapid health technology assessment

Supporting:

Minzhe Shen, Longhui Shen, Yingyan Yan. Rapid health technology assessment of ibuprofen and acetaminophen in the treatment of fever in children with asthma[J]. Journal of Chinese Pharmaceutical Sciences, 2026, 35(5): 481-490.

Figures/Tables 3

References 26

[1]	Just, J.; Bourgoin-Heck, M.; Amat, F. Clinical phenotypes in asthma during childhood. Clin. Exp. Allergy. 2017, 47, 848–855.
[2]	Porsbjerg, C.; Melén, E.; Lehtimäki, L.; Shaw, D. Asthma. Lancet. 2023, 401, 858–873.
[3]	Yi, N.; Liu, T.T.; Zhou, Y.C.; Qi, J.L.; Shen, K.L.; Zhou, M.G. Disease burden of asthma among children and adolescents in China, 1990–2019. Chin. J. Epidemiol. 2023, 44, 235–242.
[4]	Wu, P.; Xu, B.P.; Shen, A.D.; He, Z.L.; Zhang, C.J.P.; Ming, W.K.; Shen, K.L. The economic burden of medical treatment of children with asthma in China. BMC Pediatr. 2020, 20, 386.
[5]	Luo, S.H.; Ran, M.D.; Luo, Q.H.; Shu, M.; Guo, Q.; Zhu, Y.; Xie, X.P.; Zhang, C.F.; Wan, C.M. Alternating acetaminophen and ibuprofen versus monotherapies in improvements of distress and reducing refractory fever in febrile children: a randomized controlled trial. Pediatr. Drugs. 2017, 19, 479–486.
[6]	Pereira, G.L.; Tavares, N.U.L.; Mengue, S.S.; Dal Pizzol, T.D. Therapeutic procedures and use of alternating antipyretic drugs for fever management in children. Jornal De Pediatr. 2013, 89, 25–32.
[7]	Gu, T.T.; Zhang, H.; Cheng, C.H.; Huang, B.B. Comparative analysis on adverse drug reactions between ibuprofen and acetaminophen. Eval. Anal. Drug-use Hosp. Chin. 2022, 22, 1145–1148, 1152.
[8]	Thomsen, S.F.; Kyvik, K.O.; Skadhauge, L.R.; Steffensen, I.; Backer, V. Regular use of non-steroidal anti-inflammatory drugs increases the risk of adult-onset asthma: a population-based follow-up study. Clin. Respir. J. 2009, 3, 82–84.
[9]	Kanabar, D.; Dale, S.; Rawat, M. A review of ibuprofen and acetaminophen use in febrile children and the occurrence of asthma-related symptoms. Clin. Ther. 2007, 29, 2716–2723.
[10]	Kanabar, D.J. A clinical and safety review of paracetamol and ibuprofen in children. Inflammopharmacology. 2017, 25, 1–9.
[11]	Baxter, L.; Cobo, M.M.; Bhatt, A.; Slater, R.; Sanni, O.; Shinde, N. The association between ibuprofen administration in children and the risk of developing or exacerbating asthma: a systematic review and meta-analysis. BMC Pulm. Med. 2024, 24, 412.
[12]	Sherbash, M.; Furuya-Kanamori, L.; Nader, J.D.; Thalib, L. Risk of wheezing and asthma exacerbation in children treated with paracetamol versus ibuprofen: a systematic review and meta-analysis of randomised controlled trials. BMC Pulm. Med. 2020, 20, 72.
[13]	Southey, E.R.; Soares-Weiser, K.; Kleijnen, J. 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, 25, 2207–2222.
[14]	Tan, E.; Braithwaite, I.; McKinlay, C.J.D.; Dalziel, S.R. Comparison of acetaminophen (paracetamol) with ibuprofen for treatment of fever or pain in children younger than 2 years: a systematic review and meta-analysis. JAMA Netw. Open. 2020, 3, e2022398.
[15]	Wong, T.; Stang, A.S.; Ganshorn, H.; Hartling, L.; Maconochie, I.K.; Thomsen, A.M.; Johnson, D.W. Combined and alternating paracetamol and ibuprofen therapy for febrile children. Cochrane Database Syst. Rev. 2013, 2013, CD009572.
[16]	Sheehan, W.J.; Mauger, D.T.; Paul, I.M.; Moy, J.N.; Boehmer, S.J.; Szefler, S.J.; Fitzpatrick, A.M.; Jackson, D.J.; Bacharier, L.B.; Cabana, M.D.; Covar, R.; Holguin, F.; Lemanske, R.F. Jr, Martinez, F.D.; Pongracic, J.A.; Beigelman, A.; Baxi, S.N.; Benson, M.; Blake, K.; Chmiel, J.F.; Daines, C.L.; Daines, M.O.; Gaffin, J.M.; Gentile, D.A.; Gower, W.A.; Israel, E.; Kumar, H.V.; Lang, J.E.; Lazarus, S.C.; Lima, J.J.; Ly, N.; Marbin, J.; Morgan, W.J.; Myers, R.E.; Olin, J.T.; Peters, S.P.; Raissy, H.H.; Robison, R.G.; Ross, K.; Sorkness, C.A.; Thyne, S.M.; Wechsler, M.E.; Phipatanakul, W. Acetaminophen versus ibuprofen in young children with mild persistent asthma. N Engl. J. Med. 2016, 375, 619–630.
[17]	Hay, A.; Redmond, N.; Costelloe, C.; Montgomery, A.; Fletcher, M.; Hollinghurst, S.; Peters, T. Paracetamol and ibuprofen for the treatment of fever in children: the PITCH randomised controlled trial. Health Technol. Assess. 2009, 13, iii–iv, ix–x, 1–163.
[18]	Yan, Y.Y.; Mao, P.Z.; Chen, Y.; Shen, L.H. Analysis of alternation with ibuprofen and acetaminophen in outpatient and emergency departments of a children’s hospital. J. Chin. Pharm. Sci. 2022, 31, 369–373.
[19]	Beasley, R.; Clayton, T.; Crane, J.; von Mutius, E.; Lai, C.K.; Montefort, S.; Stewart, A. Association between paracetamol use in infancy and childhood, and risk of asthma, rhinoconjunctivitis, and eczema in children aged 6–7 years: analysis from Phase Three of the ISAAC programme. Lancet. 2008, 372, 1039–1048.
[20]	Chung, R.S.; Huang, Y.C.; Chen, Y.H.; Fu, L.S.; Lin, C.H. Impact of antipyretics on acute asthma exacerbation during respiratory infection: a nationwide population-based study. Pediatr. Neonatol. 2020, 61, 475–480.
[21]	Fu, L.S.; Lin, C.-C.; Wei, C.Y.; Lin, C.H.; Huang, Y.C. Risk of acute exacerbation between acetaminophen and ibuprofen in children with asthma. PeerJ. 2019, 7, e6760.
[22]	Levy, S.; Volans, G. The use of analgesics in patients with asthma. Drug Saf. 2001, 24, 829–841.
[23]	Dworski, R. Oxidant stress in asthma. Thorax. 2000, 55, 51S–553.
[24]	Nuttall, S.L.; Khan, J.N.; Thorpe, G.H.; Langford, N.; Kendall, M.J. The impact of therapeutic doses of paracetamol on serum total antioxidant capacity: Impact of paracetamol on serum total antioxidant capacity. J. Clin. Pharm. Ther. 2003, 28, 289–294.
[25]	Matok, I.; Elizur, A.; Perlman, A.; Ganor, S.; Levine, H.; Kozer, E. Association of acetaminophen and ibuprofen use with wheezing in children with acute febrile illness. Ann. Pharmacother. 2017, 51, 239–244.
[26]	Sordillo, J.E.; Scirica, C.V.; Rifas-Shiman, S.L.; Gillman, M.W.; Bunyavanich, S.; Camargo, C.A. Jr, Weiss, S.T.; Gold, D.R.; Litonjua, A.A. Prenatal and infant exposure to acetaminophen and ibuprofen and the risk for wheeze and asthma in children. J. Allergy Clin. Immunol. 2015, 135, 441–448.