Table 2.

Characteristics of the included studies.

References	Country/setting	Patients	Diagnosis of fever	Intervention	Outcomes
Erlewyn-Lajeunesse et al. (34)	UK/single center – ED	123 children aged 6 months to 10 years with temperature > 38°C	tympanometric thermometer	Group 1: paracetamol 15 mg/kg single dose Group 2: ibuprofen 5 mg/kg single dose Group 3: paracetamol 15 mg/kg + ibuprofen 5 mg/kg single dose of each	Primary 1. Temperature at 1 h Secondary 1. Temperature at 2 h 2. Time spent in department
Hay et al. (43)	UK/multi-center-−35 primary care sites and households	156 children aged 6 months to 6 years with temperature between 37.8°C and up to 41°C	axillary thermometer	Group A: paracetamol 15 mg/kg every 4–6 h Group B: ibuprofen 10 mg/kg every 6–8 h Group C: paracetamol + ibuprofen	Primary 1. Min without fever (<37.2°C) in the first 4 h 2. Proportion of children normal on the discomfort scale at 48 h Secondary 1. Time to fever clearance in the first 24 h 2. Time spent without fever over 24 h 3. Proportion of children without fever associated symptoms: discomfort, reduced activity, reduced appetite and disturbed sleep at 48 h and day 5 4. Adverse effects
Kramer et al. (47)	USA/single center—pediatric clinic	38 children aged 6 months to 6 years with temperature > 38°C	children > 2 years oral, children <2 years rectal thermometer	Group A: paracetamol (15 mg/kg) alternated with placebo Group B: paracetamol (15 mg/kg) alternating with Ibuprofen (10 mg/kg)	Primary 1. Temperature at enrolment and• h 3, 4, 5, 6 Secondary 1. Symptom checklist at h 3 and 4 2. Parental perception of efficacy at h 3 and 4
Luo et al. (41)	China/single center—ED and pediatric department	474 children aged 6 months to 5 years with temperature > 38.5 C	axillary thermometer	Group 1: alternating acetaminophen 10 mg/kg per dose and ibuprofen 10 mg/kg per dose (acetaminophen with shortest interval of 4 h and ibuprofen with shortest interval of 6 h and the shortest interval between acetaminophen and ibuprofen of 2 h) Group 2: acetaminophen 10 mg/kg per dose with shortest interval of 4 h Group 3: ibuprofen 10 mg/kg per dose with shortest interval of 6 h	Primary 1. NCCPC scores throughout 24 h 2. Mean temperature throughout 24 h Secondary 1. Proportion of children with refractory fever for 4 h 2. Low body temperature 3. Antipyretic use 4. Incidence of adverse events
Nabulsi et al. (45)	Lebanon/multi-center—pediatric inpatient services	70 children aged 6 months to 14 years with temperature > 38.8°C	rectal thermometer	Control: ibuprofen 10 mg/kg followed by placebo 4 h later Treatment group: single oral dose ibuprofen 10 mg/kg followed by single oral dose paracetamol 15 mg/kg 4 h later	Primary 1. Proportion of children with normal body temperature at 6 h Secondary 1. Proportions of afebrile children at 7 and 8 h
Noori et al. (42)	Iran/single center – ED	540 children aged 6 months to 10 years terwith temperature between 38°C and 41°C	not specified	Group 1: acetaminophen 15 mg/kg/dose Group 2: ibuprofen 10 mg/kg/dose Group 3: a combination of acetaminophen plus ibuprofen	Primary 1. Temperature at 2–4–6 h
Paul et al. (44)	USA/single center—outpatient clinics and child day-care facilities	46 children aged 6 months to 8 years with temperature > 38.8°C	temporal artery thermometer	Group A: single dose ibuprofen 10 mg/kg (oral suspension 100 mg/5 mL) Group B: single dose acetaminophen 15 mg/kg (oral solution 160 mg/5 mL) plus ibuprofen 10 mg/kg Group C: ibuprofen 10 mg/kg at the beginning of the study followed by 15 mg/kg of acetaminophen 3 h later	Primary 1. Effect of treatment on temperature over 6 h
Sarrell et al. (46)	Central Israel/multi-center—primary pediatric community ambulatory centers	480 children aged 6 to 36 months with temperature > 38.4°C	rectal thermometer	Group 1: paracetamol 12.5 mg/kg every 6 h Group 2: ibuprofen 5 mg/kg every 8 h Group 3: paracetamol 12.5 mg/kg/dose alternating with ibuprofen 5 mg/kg/dose every 4 h Half of every groups received initial loading with paracetamol (25 mg/kg) and the other half received initial loading with ibuprofen (10 mg/kg)	Primary 1. Body temperature 2. Stress score 3. Amount of antipyretic used at the 3 day time point Secondary 1. Total days that a primary caretaker had to stay home from work 2. Recurrence of fever (≥37.8°C) within 5 and 10 days after initiation of treatment 3. Number of emergency department visits within 10 days of enrolment 4. Hepatic and renal function 5. Appearance of gastrointestinal symptoms or bleeding
Vyas et al. (36)	India/single center—pediatric department	99 children aged 6 months to 12 years with temperature > 38°C	tympanometric thermometer	Group 1: ibuprofen 10 mg/kg single dose Group 2: paracetamol 15 mg/kg single dose Group 3: paracetamol 15 mg/kg + ibuprofen 10 mg/kg single dose of each	Primary 1. Reduction in temperature at h 4 Secondary 1. Percent reduction of temperature at h 4 2. Proportion of afebrile children at 1, 2, 3, and 4 h 3. Adverse drug events occurring in the 4 h period

ED, emergency department, NCCPC, non-communicating children's pain checklist.