Acetaminophen and ibuprofen in the treatment of pediatric fever: a narrative review

Figures & data

Table 1. Summary of single-dose studies comparing acetaminophen versus ibuprofen at physician-directed and over-the-counter dosing strengths.

Author, year	Study design; temperature measurement technique; study duration	Dose; n		Primary outcome result	Key secondary outcome result	Adverse events
		Acetaminophen; N	Ibuprofen; N
Single-dose comparison of acetaminophen vs ibuprofen at physician-directed dosing
Autret-Leca et al. 2007^18	Randomized, double-blind, parallel-group; Tympanic; 8 h	15 mg/kg; n = 150	10 mg/kg; n = 151	Area under the temperature reduction curve from 0–6 h: Acetaminophen = ibuprofen	For (1) area under the temperature reduction curve from 0‒4 and 0‒8 h; (2) individual temperature readings at each time point from 30 min to 8 h; (3) time to recurrence of a temperature > 38.5 °C; (4) time to reach a temperature of  ≤ 38 °C; (5) time to maximal temperature reduction and time to reach apyrexia (≤37.4 °C): Acetaminophen = ibuprofen For parental global assessment: Ibuprofen > acetaminophen (p < .001 after double-blind period and p < .01 after the open-label period)	Ibuprofen: 11.2% of patients Acetaminophen: 10.6% of patients
Single-dose comparisons of acetaminophen vs ibuprofen at over-the-counter dosing
Jayawardena and Kellstein^19	Randomized, double-blind, parallel-group; Oral, rectal; 8 h for each study	10–15 mg/kg: Study 1, n = 82; Study 2, n = 74	7.5 mg/kg: Study 1, n = 78; Study 2, n = 85	TWSTD0–8 : Study 1: Ibuprofen >  acetaminophen (p<.001) Study 2: Acetaminophen  = ibuprofen Studies 1 and 2 pooled: Ibuprofen > acetaminophen (p<.001)	TWSTD0–2, 0–4, 0–6: Ibuprofen > acetaminophen (Study 1, p = .015 at 2 h; p<.001 at 4 and at 6 h) Maximum temperature difference from baseline: Ibuprofen > acetaminophen, (Study 1, p < .001) Greater temperature reductions 1–8 h: Ibuprofen >  acetaminophen (Study 1, p < .05 for each) Faster onset of temperature control: Ibuprofen >  acetaminophen (Study 1, p=.003; Study 2, p=.007) Longer duration of temperature control: Ibuprofen > acetaminophen (Study 1, p < .001) Treatment failures: Ibuprofen > acetaminophen (Study 1, p = .018 at 8 h) Longer time to treatment failure: Ibuprofen > acetaminophen (Study 1, p = .015) Faster onset temperature control: Ibuprofen > acetaminophen (pooled, p < .001) Longer duration of temperature control: Ibuprofen > acetaminophen (pooled, p = .042)	Pooled AE rates: Ibuprofen, 7.5% of patients Acetaminophen, 7.5% of patients; Most common AE was vomiting: 6.3% with acetaminophen; 4.6% with ibuprofen; NS
Figueras Nadal et al.^20	Double-blind, double-dummy; Tympanic; 8 h	10.7 mg/kg , n = 87	6.7 mg/kg, n = 88	Mean temperature change at 4 h: Acetaminophen = ibuprofen	For (1) percentage of patients with temperature reduction at 4 h; (2) maximum temperature decrease; (3) mean time to apyrexia; (4) patients with temperature reduction of ≥ 1.5 °C; and (5) percentage of patients reaching normal temperature: Acetaminophen  = ibuprofen For temperature reduction of ≥ 2 °C: Ibuprofen >  acetaminophen (p = .043)	AEs occurred in 10.0% of patients taking ibuprofen and 9.1% of patients taking acetaminophen. Twelve patients vomited within 30 min of receiving medication (acetaminophen, 5; ibuprofen, 7)
Wong et al.^21	Randomized, double-blind, parallel-group; Tympanic; 6 h	12 mg/kg, n = 210	5 mg/kg for temperature < 39.2 °C; 10 mg/kg for temperature ≥ 39.2 °C; n = 209 total	Percentage achieving ≥ 1.5 °C reduction from baseline in tympanic membrane temperature: Acetaminophen = ibuprofen	For 1) time to achieve 1.5 °C reduction or 2) time to normalization of temperature: Acetaminophen = ibuprofen For percentage achieving ≤ 37.5 °C (i.e. temperature normalization): Ibuprofen > acetaminophen (p=.004)	Ibuprofen, n = 22; Acetaminophen, n = 19; NS
Vauzelle-Kervroëdan et al.^22	Randomized, double-blind; Rectal; 6 h	9.8 ± 1.9 mg/kg, n = 56	10.3 ± 1.9 mg/kg, n = 60	Time to the lowest observed temperature between 0–6 h: Acetaminophen = ibuprofen	For (1) extent of temperature decrease; (2) rate of temperature decrease; (3) duration of temperature < 38.5 °C; 4) percentage of children whose temperature fell < 38.5 °C: Acetaminophen = ibuprofen	Vomiting: Ibuprofen, 0% acetaminophen, 3.6%
Kauffman et al.^23	Randomized, double-blind, placebo-controlled (placebo, n = 9), double-dummy; Oral; 8 h	10 mg/kg, n = 8	7.5 mg/kg, n = 12; 10 mg/kg, n = 8	Antipyresis vs placebo: Significant for acetaminophen at hours 3‒5 (p ≤ .05); significant for both ibuprofen doses at hours 1‒6 (p ≤ .05): Ibuprofen 7.5 mg/kg > acetaminophen 10 mg/kg at hours 3‒5 (p≤ .05)	For (1) faster onset; (2) greater maximum temperature reduction; (3) longer duration of action: Ibuprofen >  acetaminophen (p≤.05)	No AEs or laboratory abnormalities were attributed to either of the 2 treatments
Wilson et al.^24	Randomized, double-blind, placebo-controlled (placebo, n = 22); Rectal; up to 12 h	12.5 mg/kg, n = 52	5 mg/kg, n = 43; 10 mg/kg, n = 47	Temperature reduction at 4 h: Ibuprofen 10 mg/kg > ibuprofen 5 mg/kg and > acetaminophen (p≤ .05)	Ibuprofen 10 mg/kg had longest duration of action than any other group (p ≤ .05); For area under the curve measures for (1) temperature; (2) change in temperature; and (3) Percentage achieving antipyresis: Ibuprofen 10 mg/kg > ibuprofen 5 mg/kg and acetaminophen 12.5 mg/kg (p ≤ .05)	Ibuprofen 10 mg/kg, n = 1 event (transient hypothermia without sequelae in the context of profuse night sweats from pulmonary tuberculosis); Ibuprofen 5 mg/kg, n = 1 event (transient hypothermia (< 97 °F) that occurred 12 h after dosing; Acetaminophen, n = 0 events; Placebo, n = 0 events.
Sidler et al.^25	Randomized, double-blind, parallel-group; Rectal; up to 24 h	10 mg/kg, n = 30	7 mg/kg, n = 30; 10 mg/kg, n = 29	Temperature reduction at 3 h: Ibuprofen 10 mg/kg > acetaminophen (p ≤ 0.01); Ibuprofen 7 mg/kg > acetaminophen (p≤.05)	Percentage achieving ≥ 1 °C reduction: Acetaminophen  = ibuprofen	Ibuprofen 7 mg/kg, n = 3 (10%) patients (vomiting, abdominal pain, rash) Ibuprofen 10 mg/kg, n = 1 (3.4%) patients (hypothermia) Acetaminophen, 10 mg/kg, n = 2 (6.7%) patients (vomiting in both)
Walson et al.^26	Randomized, double-blind, placebo-controlled (placebo, n = 34), parallel-group; Oral, rectal; 8 h	10 mg/kg, n = 33	5 mg/kg, n = 32; 10 mg/kg, n = 28	Area under the percentage reduction time curve at 4, 6, and 8 h: Ibuprofen 10 mg/kg > acetaminophen 10 mg/kg (p<.05 for each time point); acetaminophen 10 mg/kg = ibuprofen 5 mg/kg	For oral temperature > 102.5 °F, antipyretic efficacy ranking was ibuprofen 10 mg/kg > ibuprofen 5 mg/kg > acetaminophen 10 mg/kg > placebo	Mild drug-related GI AEs in 31% treated with ibuprofen 5 mg/kg, 21% of those treated with ibuprofen 10 mg/kg, 18% of those treated with acetaminophen 10 mg/kg, and 6% of those treated with placebo; NS

Abbreviations. AE, adverse event; GI, gastrointestinal; NR, not reported; NS, not significant; q6h, every 6 h; TWSTD 0–2/4/6/8, time-weighted sum of temperature differences from baseline through 2/4/6/8 h.

Table 2. Summary of multiple-dose studies comparing acetaminophen versus ibuprofen at physician-directed and over-the-counter dosing strengths.

Author, year	Study design; temperature measurement technique; study duration	Dose; n		Primary outcome result	Key secondary outcome result	Adverse events
		Acetaminophen; N	Ibuprofen; N
Multiple-dose comparisons of acetaminophen vs ibuprofen at physician-directed dosing
Walson et al.^27	Randomized, double-blind, parallel-group Oral, rectal; up to 48 h	15 mg/kg q6h, n = 16	10 mg/kg q6h, n = 15	Temperature reduction 0–6 h: Ibuprofen 10 mg/kg = acetaminophen 15 mg/kg	Temperature reduction at 0‒12, 0‒24, and 0‒48 h: Ibuprofen 10 mg/kg = acetaminophen 15 mg/kg	Ibuprofen groups combined, most common AEs were sweating (n = 8); GI (n = 7); Acetaminophen, most common AEs were hypothermia (n = 3); abdominal pain (n = 3); agitation and/or nervousness (n = 3)
Multiple-dose comparisons of acetaminophen vs ibuprofen at over-the-counter dosing
Vinh et al.^28	Randomized, double-blind; Axillary; until 36 h after defervescence	12 mg/kg q6h, n = 40	10 mg/kg q6h, n = 40	Fever “clearance”: Acetaminophen = ibuprofen	Temperature duration and severity: Ibuprofen > acetaminophen (p = .013)	Ibuprofen, n = 13 (32.5%); Acetaminophen, n = 7 (17.5%; p = .12; NS)
McIntyre and Hull,^29	Double-blind, parallel-group; Axillary; maximum of 3 days	50 mg/kg/24 h (i.e. 12.5 mg/kg q6h), n = 74	20 mg/kg/24 h (i.e. 5 mg/kg q6h); n = 76	Change in temperature at 4 h: Acetaminophen = ibuprofen	Distribution of times until temperature fell below 37.5 °C and distribution of times to second dose: Acetaminophen = ibuprofen	Ibuprofen AE rate, 13% (when administered at the minimal dosing level of 5 mg/kg); Acetaminophen AE rate, 19% (when administered at full over-the-counter dosing level; p = .34, NS) 8 acetaminophen- and 7 ibuprofen-treated patients withdrew from the study due to AEs or lack of efficacy
Van Esch et al.^30	Randomized, double-blind, crossover; Rectal; 24 h	10 mg/kg q6h, n = 36	5 mg/kg q6h, n = 34	Temperature at 4 h after first dose: Ibuprofen > acetaminophen (p = .05; p = .04 after adjusting for covariates)	Mean and highest temperature during treatment: Acetaminophen = ibuprofen	14 AEs recorded in 9 patients overall; 8 occurred with acetaminophen and 6 with ibuprofen
Autret et al.^31	Randomized, double-blind, parallel-group Rectal; 72 h	10 mg/kg q6h, n = 74	7.5 mg/kg q6h, n = 77	Area under the percentage reduction in temperature curve from 1–12 h: Acetaminophen = ibuprofen	Percentage temperature reduction from 0–4 h: Ibuprofen > acetaminophen (p<.04) Mean temperature reduction from 0‒4 h and time to maximum antipyresis: Acetaminophen = ibuprofen	Ibuprofen, 9 patients (11.7%): 5 with GI symptoms 3 skin reactions, 1 epistaxis Acetaminophen, 5 (6.5%): 2 with GI symptoms, 2 skin reactions, 1 epistaxis
Walson et al.^27	Randomized, double-blind, parallel-group Oral, rectal; up to 48 h	15 mg/kg q6h, n = 16	2.5 mg/kg q6h, n = 15; 5 mg/kg q6h, n = 15	Temperature reduction 0–6 h: Ibuprofen 10 mg/kg > ibuprofen 2.5 mg/kg and 5 mg/kg; acetaminophen 15 mg/kg > ibuprofen 2.5 mg/kg (p<.05)	Temperature reduction at 0‒12, 0‒24, and 0‒48 h: Acetaminophen 15 mg/kg > ibuprofen 5 mg/kg at 0‒12 and 0‒24 h (p < .05 for each), but not at 0‒48 h	Ibuprofen groups combined, most common AEs were sweating (n = 8); GI (n = 7); Acetaminophen, most common AEs were hypothermia (n = 3); abdominal pain (n = 3); agitation and/or nervousness (n = 3)

Abbreviations. AE, adverse event; GI, gastrointestinal; NR, not reported; NS, not significant; q6h, every 6 h.

Table 3. Studies of combination acetaminophen and ibuprofen administration.

Author, year	Study design; temperature measurement technique; study duration	Dose; n			Primary outcome result	Key secondary outcome result	Adverse events
		Acetaminophen; N	Ibuprofen; N	Acetaminophen + ibuprofen combined or alternating; N
Vyas et al.^40	Randomized, investigator-blind, parallel-group Tympanic; 4 h	15 mg/kg, n = 33	10 mg/kg, n = 33	Acetaminophen 15 mg/kg + Ibuprofen 10 mg/kg, n = 33	Temperature reduction over 4 h: Combination > ibuprofen or acetaminophen alone (p = .013)	Post hoc multiple comparison test at 4 h: Combination  > acetaminophen (p=.03); acetaminophen = ibuprofen; ibuprofen = combination	Ibuprofen, 3 (9.3%), abdominal pain, nausea, and maculopapular skin rash; Acetaminophen, 2 (6.7%), abdominal pain and vomiting; Combination, 4 (12.9%), abdominal pain^2, vomiting and skin rash; No serious or severe AEs were reported in any group
Paul et al.^11	Randomized, controlled Temporal artery; 6 h	NA	Single dose of 10 mg/kg, n = 20 febrile episodes	Single-dose ibuprofen 10 mg/kg followed 3 h later by single-dose acetaminophen 15 mg/kg; n = 20 febrile episodes	Antipyresis at 4–6 h: Combination > ibuprofen alone (4 h, p = .002; 5 h and 6 h, p < .001 for each)	NR	Not collected
Hay et al.^41	Randomized, blinded Axillary; 48 h	15 mg/kg q4–6h (maximum 4 doses/24 h) for 48 h, n = 52	10 mg/kg q6–8h (maximum 3 doses/24 h) for 48 h, n = 52	Ibuprofen 10 mg/kg + acetaminophen 15 mg/kg for 48 h, n = 52	Time without fever 0–4 h: Combination and ibuprofen > acetaminophen (p<.001 for both)	Temperature reduction at 24 h: Combination > ibuprofen (p = .008) and acetaminophen (p = .001)	Most common AEs:Diarrhea: ibuprofen, 9 (17.3%); acetaminophen, 10 (19.2%); combination, 12 (23.1%); Vomiting: ibuprofen, 3 (5.8%); acetaminophen, 6 (11.5%); combination, 2 (3.8%); Rash: ibuprofen, 2 (3.8%); acetaminophen, 2 (3.8%); combination, 1 (1.9%) Cough: ibuprofen, 0; acetaminophen, 2 (3.8%); combination, 1 (1.9%) Cold to the touch: ibuprofen, 3 (5.8%); acetaminophen, 0; combination, 2 (3.8%); AEs were equally distributed between groups.
Lal et al.^42	Randomized, double-blind, parallel-group Axillary; 5 days	10 mg/kg thrice-daily for 5 days, n = 33	NA	Acetaminophen 10 mg/kg + ibuprofen 10 mg/kg thrice daily for 5 days, n = 18	Temperature reduction: Acetaminophen = combination	NR	“Only a few adverse effects namely, epigastric pain, vomiting were encountered”; there were no differences between groups

Abbreviations. AE, adverse event; NA, not applicable; NR, not reported; q4–6h, every 4–6 h; q6h, every 6 h; q6–8h, every 6–8 h.

Table 4. Studies of alternating acetaminophen and ibuprofen administration.

Author, year	Study design/temperature measurement technique; treatment duration	Dose; n			Primary outcome result	Key secondary outcome result	Adverse events
		Acetaminophen; N	Ibuprofen; N	Acetaminophen + ibuprofen combined or alternating; N
Luo et al.^43	Randomized, controlled Axillary; 24 h	10 mg/kg q4h, for 24 h; n = 158	10 mg/kg q6h, for 24 h; n = 158	Acetaminophen Acetaminophen 10 mg/kg ≥ q4h alternating with ibuprofen 10 mg/kg ≥ q6h, for 24 h; n = 158; shortest interval between acetaminophen and ibuprofen was ≥ 2 h	Temperature or Non-Communicating Children’s Pain Checklist: Acetaminophen and ibuprofen = alternating treatment	Percentage with persistent fever at 4 and 6 h: Alternating treatment > ibuprofen and acetaminophen (4 h, p = .003; 6 h, p<.001)	No significant differences in rates of AEs between groups For the combination, acetaminophen, and ibuprofen groups, respectively, rates of AEs were as follows: low body temperature, 1.92%, 2.53%, and 1.91%; rash, 8.33%, 8.86%, and 8.28%; asthma, 0%, 0%, and 1.27%; and GI AEs, 84.62%, 84.18%, and 85.35%
Paul et al.^11	Randomized, controlled Temporal artery; 6 h	NA	Single dose of 10 mg/kg, n = 20 febrile episodes	Single dose of ibuprofen 10 mg/kg followed by single dose of acetaminophen 15 mg/kg 3 h later, n = 20 febrile episodes	Antipyresis at 4–6 h: Ibuprofen alternating with acetaminophen > ibuprofen alone (4 h, p = .003; 5 h and 6 h, p < .001 for each)	NR	Not collected
Pashapour et al.^44	Randomized, controlled Rectal; 8 h	15 mg/kg q4h for 2 doses, n = 35	NA	Acetaminophen 15 mg/kg alternating with ibuprofen 10 mg/kg 4 h later; patients received 1 dose of each medication in the study; n = 35	Antipyresis at 2 h: Acetaminophen = alternating treatment Antipyresis at 4, 5, 7, and 8 h: Alternating treatment > acetaminophen (4 h, p = .048; 5 h, p = .04; 7 h, p = .04; 8 h, p = .02)	NR	No “major complications” of treatment were observed in any group
Kramer et al.^45	Randomized, double-blind, placebo-controlled, prospective; Oral; 6 h	15 mg/kg alternating with placebo, n = 19; Acetaminophen at hour 0, placebo at hour 3, then acetaminophen at hour 4	NA	Acetaminophen 15 mg/kg alternating with ibuprofen 10 mg/kg, n = 19; Acetaminophen at hour 0, ibuprofen at hour 3, and placebo at hour 4	Temperature reduction between groups: Alternating treatment > acetaminophen/placebo at 4 h (p = .05) and 5 h (p = .003) Alternating treatment = acetaminophen/placebo at 0, 3, and 6 h	NR	21% of patients had AEs including diarrhea, flatulence, emesis, decreased appetite, epigastric pain, nausea, headache, and insomnia; there were no difference in the rates of any of these AEs between groups
Nabulsi et al.^46	Randomized, double-blind, placebo-controlled; Rectal; 8 h	NA	Single dose of 10 mg/kg initial dose, with a single dose of placebo 4 h later, n = 33	Single dose of ibuprofen 10 mg/kg initially, then acetaminophen 15 mg/kg 4 h later, n = 37	Percentage afebrile at 6 (primary efficacy time point), 7, 8 h: Ibuprofen alternating with acetaminophen > ibuprofen (6 h, p = .018	Percentage afebrile at 7 or 8 h: Ibuprofen alternating with acetaminophen > ibuprofen at 7 h, p < .001; 8 h, p < .001); Duration of antipyresis: Ibuprofen alternating with acetaminophen > ibuprofen at 8 h (p < .001)	Low body temperature (i.e. < 36.5 °C rectally): ibuprofen alternating with acetaminophen, 5 (13.9%); ibuprofen, 6 (18.2%); (p = .6, NS). No serious AEs were observed. No symptoms suggestive of GI, hepatic, or renal toxicity
Sarrell et al.^47	Randomized, double-blind, parallel-group; Each treatment group received a loading dose of either ibuprofen 10 mg/kg (half of each treatment group) or acetaminophen 25 mg/kg (half of each treatment group); 3 days	12.5 mg/kg q6h for 3 days, n = 154	5 mg/kg q8h for 3 days, n = 155	Study medication was administered every 4 h; Administration began with acetaminophen 12.5 mg/kg and was followed with ibuprofen 5 mg/kg 4 h later; the drugs were given in this alternating fashion for 3 days, n = 155	Temperature reduction, less antipyretic medication use, less stress, (regardless of initial loading dose): Ibuprofen alternating with acetaminophen > ibuprofen or acetaminophen alone (p < .001 for all measures)	Fever recurrence at day 5: Ibuprofen alternating with acetaminophen > ibuprofen or acetaminophen alone (p = .02) Less absenteeism from day care: Ibuprofen alternating with acetaminophen > ibuprofen alone or acetaminophen alone (p < .001)	No drug-related AEs or serious illnesses were reported

Abbreviations. AE, adverse event; GI, gastrointestinal; NA, not applicable; NR, not reported; q4h, every 4 h; q6h, every 6 h; q8h, every 8 h.

Autret-Leca E, Gibb IA, Goulder MA. Ibuprofen versus paracetamol in pediatric fever: objective and subjective findings from a randomized, blinded study. Curr Med Res Opin. 2007;23(9):2205–2211.

 PubMed Web of Science ®Google Scholar

Jayawardena S, Kellstein D. Antipyretic efficacy and safety of ibuprofen versus acetaminophen suspension in febrile children: results of 2 randomized, double-blind, single-dose studies. Clin Pediatr. 2017;56(12):1120–1127.

 PubMed Web of Science ®Google Scholar

Figueras Nadal C, Garcia de Miguel MJ, Gomez Campdera A, et al. Effectiveness and tolerability of ibuprofen-arginine versus paracetamol in children with fever of likely infectious origin. Acta Paediatr. 2002;91(4):383–390.

 PubMed Web of Science ®Google Scholar

Wong A, Sibbald A, Ferrero F, et al. Antipyretic effects of dipyrone versus ibuprofen versus acetaminophen in children: results of a multinational, randomized, modified double-blind study. Clin Pediatr. 2001;40(6):313–324.

 PubMed Web of Science ®Google Scholar

Vauzelle-Kervroedan F, d'Athis P, Pariente-Khayat A, et al. Equivalent antipyretic activity of ibuprofen and paracetamol in febrile children. J Pediatr. 1997;131(5):683–687.

 PubMed Web of Science ®Google Scholar

Kauffman RE, Sawyer LA, Scheinbaum ML. Antipyretic efficacy of ibuprofen vs acetaminophen. Am J Dis Child. 1992;146(5):622–625.

 PubMedGoogle Scholar

Wilson JT, Brown RD, Kearns GL, et al. Single-dose, placebo-controlled comparative study of ibuprofen and acetaminophen antipyresis in children. J Pediatr. 1991;119(5):803–811.

 PubMed Web of Science ®Google Scholar

Sidler J, Frey B, Baerlocher K. A double-blind comparison of ibuprofen and paracetamol in juvenile pyrexia. Br J Clin Pract Suppl. 1990;70:22–25.

 PubMedGoogle Scholar

Walson PD, Galletta G, Braden NJ, et al. Ibuprofen, acetaminophen, and placebo treatment of febrile children. Clin Pharmacol Ther. 1989;46(1):9–17.

 PubMed Web of Science ®Google Scholar

Walson PD, Galletta G, Chomilo F, et al. Comparison of multidose ibuprofen and acetaminophen therapy in febrile children. Am J Dis Child. 1992;146(5):626–632.

 PubMedGoogle Scholar

Vinh H, Parry CM, Hanh VT, et al. Double blind comparison of ibuprofen and paracetamol for adjunctive treatment of uncomplicated typhoid fever. Pediatr Infect Dis J. 2004;23(3):226–230.

 PubMed Web of Science ®Google Scholar

McIntyre J, Hull D. Comparing efficacy and tolerability of ibuprofen and paracetamol in fever. Arch Dis Child. 1996;74(2):164–167.

 PubMed Web of Science ®Google Scholar

Van Esch A, Van Steensel-Moll HA, Steyerberg EW, et al. Antipyretic efficacy of ibuprofen and acetaminophen in children with febrile seizures. Arch Pediatr Adolesc Med. 1995;149(6):632–637.

 PubMedGoogle Scholar

Autret E, Breart G, Jonville AP, et al. Comparative efficacy and tolerance of ibuprofen syrup and acetaminophen syrup in children with pyrexia associated with infectious diseases and treated with antibiotics. Eur J Clin Pharmacol. 1994;46(3):197–201.

 PubMed Web of Science ®Google Scholar

Vyas FI, Rana DA, Patel PM, et al. Randomized comparative trial of efficacy of paracetamol, ibuprofen and paracetamol-ibuprofen combination for treatment of febrile children. Perspect Clin Res. 2014;5(1):25–31.

 PubMedGoogle Scholar

Sullivan JE, Farrar HC. Fever and antipyretic use in children. Pediatrics. 2011;127(3):580–587.

 PubMed Web of Science ®Google Scholar

Paul IM, Sturgis SA, Yang C, et al. Efficacy of standard doses of ibuprofen alone, alternating, and combined with acetaminophen for the treatment of febrile children. Clin Ther. 2010;32(14):2433–2440.

 PubMed Web of Science ®Google Scholar

Hay AD, Costelloe C, Redmond NM, et al. Paracetamol plus ibuprofen for the treatment of fever in children (PITCH): randomised controlled trial. BMJ. 2008;337(2):a1302–a1302.

 PubMed Web of Science ®Google Scholar

Lal A, Gomber S, Talukdar B. Antipyretic effects of nimesulide, paracetamol and ibuprofen-paracetamol. Indian J Pediatr. 2000;67(12):865–870.

 PubMedGoogle Scholar

Luo S, Ran M, Luo Q, et al. 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(5):479–486.

 PubMed Web of Science ®Google Scholar

Pashapour N, Macooei AA, Golmobammadlou S. Alternating ibuprofen and acetaminophen in the treatment of febrile hospitalized children aged 9-24 months. Iran J Pediatr. 2009;19:164–168.

 Web of Science ®Google Scholar

Kramer LC, Richards PA, Thompson AM, et al. Alternating antipyretics: antipyretic efficacy of acetaminophen versus acetaminophen alternated with ibuprofen in children. Clin Pediatr. 2008;47(9):907–911.

 PubMed Web of Science ®Google Scholar

Nabulsi MM, Tamim H, Mahfoud Z, et al. Alternating ibuprofen and acetaminophen in the treatment of febrile children: a pilot study [ISRCTN30487061]. BMC Med. 2006;4(1):4.

 PubMed Web of Science ®Google Scholar

Sarrell EM, Wielunsky E, Cohen HA. Antipyretic treatment in young children with fever: acetaminophen, ibuprofen, or both alternating in a randomized, double-blind study. Arch Pediatr Adolesc Med. 2006;160(2):197–202.

 PubMedGoogle Scholar