Ibuprofen as an antipyretic and analgesic drug in pediatric practice (a literature review)





children, antipyretic drugs, analgesics, efficacy, safety, Ibuprofen


Ibuprofen, along with paracetamol, is the drug of choice for lowering fever and pain relief in children; it is a drug sold without a prescription in most countries of the world, in particular in Ukraine, and can be taken by patients at home without prior doctor's examination. It is clear that such an application implies significant advantages over potential risks. In particular, an important condition for «home» use of drugs is the speed of action, the absence of severe side effects, low toxicity, good compatibility with other drugs and a wide therapeutic applicability. Ibuprofen meets these basic requirements, and therefore belongs to the most commonly used molecules in pediatric practice.

The question of home use of drugs based on this molecule by parents to lower the temperature in children with acute respiratory diseases remains controversial, because there is an opinion regarding the negative effect of lowering the temperature on the patient's immune response. At the beginning of the COVID-19 pandemic, the question was generally raised about the negative effect of lowering the temperature with ibuprofen on the prognosis of the disease, caused by the Sars-Cov-2 virus.

It is the issues of assessing the benefit-risk ratio for the ibuprofen molecule that this literature review is devoted to. Long-term widespread use experience, numerous studies, systematic reviews and meta-analyzes prove the safety, efficacy and good tolerability of Ibuprofen compared to other medications, including OTC analgesics. Current research suggests that its use may go beyond the usual management of pain and fever in common clinical situations in children. Ibuprofen is not only safe for children at standard dosages, but it is also much safer during accidental or deliberate overdose compared to other analgesics that can lead to fatal consequences if misused.

Thus, the overall benefit-risk ratio for the use of Ibuprofen to control pain and fever in children remains positive.

The author declares no conflicts of interest.


Adams SS, McCullough MF and Nicholson JS. (1969). The pharmacological properties of ibuprofen, an anti-inflammatory, analgesic and antipyretic agent. Arch Int Pharmacodyn Ther 178(1): 115-129.

Ali S, Drendel AL, Kircher J, Beno S. (2010, Jul). Pain management of musculoskeletal injuries in children: current state and future directions. Pediatr Emerg Care. 26(7):518-24; quiz 525-8. https://doi.org/10.1097/PEC.0b013e3181e5c02b; PMid:20622635

Allan GM, Ivers N, Shevchuk Y. (2010, Aug). Treatment of pediatric fever: Are acetaminophen and ibuprofen equivalent? Canadian Family Physician Journal. 56(8): 773. URL: https://www.ncbi.nlm.nih.gov/pubmed/?term=Shevchuk%20Y%5BAuthor%5D&cau-thor=true&cauthor_uid=20705883

Autret-Leca E, Breart G, Jonville AP et al. (1994). 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. 46: 197-201. https://doi.org/10.1007/BF00192548

Autret-Leca E, Reboul-Marty J, Henry-Launois B, Laborde C, Courcier S, Goehrs JM, Languilat G, Launois R. (1997). Evaluation of ibuprofen versus aspirin and paracetamol on efficacy and comfort in children with fever. Eur J Clin Pharmacol. 51(5):367-71. https://doi.org/10.1007/s002280050215; PMid:9049576

Autret-Leca E, Bensouda-Grimaldi L, Maurage C, Jonville-Bera AP. (2007). Therapie Mars: Avril; 62 (2): 173-176. https://doi.org/10.2515/therapie:2007032; PMid:17582320

Autret-Leca E. (2003, Apr). A general overview of the use of ibuprofen in paediatrics. Int J Clin Pract Suppl. (135):9-12.

Autret-Leca E. (2002). Expert report on the clinical documentation of Nureflex 20 mg/ml in children from the age of 3 months. Ref Type: Report. URL: https://www.google.com/search?q=Autret Leca+E.+Expert+ report+on+the+clinical+documentation+of+Nureflex%EF%83%A2+20+mg%2Fml+in+children+from+the+age+of+3+months&ei=0oZVYfaCO6mFwPAP3pu_2AQ&oq=Autret-Leca+E.+Expert+report+on+the+clinical+documentation+of+Nureflex%EF%83%A2+20+mg%2Fml+in+children+from+the+age+of+3+months&gs_lcp=Cgdnd3Mtd2l6EANKBAhBGABQ_RZY_RZg2TdoAHACeACAAQCIAQCSAQCYAQCgAQHAAQE&sclient=gws-wiz&ved=0ahUKEwj2s4LEtKbzAhWpAhAIHd7ND0sQ4dUDCA4&uact=5

Bailey B, McManus BC. (2008, May). Treatment of children with migraine in the emergency department: a qualitative systematic review. Pediatr Emerg Care. 24(5):321-30. https://doi.org/10.1097/PEC.0b013e31816ed047; PMid:18496120

Balottin U, Termine C. (2007, Apr). Recommendations for the management of migraine in paediatric patients. Expert Opin Pharmacother. 8(6):731-44. https://doi.org/10.1517/14656566.8.6.731; PMid:17425470

Baygin O, Tuzuner T, Isik B, Kusgoz A, Tanriver M. (2011, Jul). Comparison of pre-emptive ibuprofen, paracetamol, and placebo administration in reducing post-operative pain in primary tooth extraction. Int J Paediatr Dent. 21(4):306-13. Epub 2011 Apr 6. https://doi.org/10.1111/j.1365-263X.2011.01124.x; PMid:21470320

Beaver WT. (2003, Apr). Review of the analgesic efficacy of ibuprofen. Int J Clin Pract Suppl. (135):13-7.

Bernhardt MK, Southard KA, Batterson KD, Logan HL, Baker KA, Jakobsen JR. (2001, Jul). The effect of preemptive and/or postoperative ibuprofen therapy for orthodontic pain. Am J Orthod Dentofacial Orthop. 120(1):20-7. https://doi.org/10.1067/mod.2001.115616; PMid:11455373

Bertin L, Pons G, d'Athis P, Lasfargues G, Maudelonde C, Duhamel JF, Olive G. (1991, Nov). Randomized, double-blind, multicenter, controlled trial of ibuprofen versus acetaminophen (paracetamol) and placebo for treatment of symptoms of tonsillitis and pharyngitis in children. J Pediatr. 119(5):811-4. https://doi.org/10.1016/S0022-3476(05)80308-7

Bertin L, Pons G, d'Athis P, Lasfargues G, Maudelonde C, Duhamel JF, Olive G. Guillot M, Marsac A, Debregeas B. (1996). A randomized, double-blind, multicentre, controlled trial of ibuprofen versus acetaminophen and placebo for symptoms of acute otitis media in children. Fudam Clin Pharmacol. 10(4):387-92. https://doi.org/10.1111/j.1472-8206.1996.tb00590.x; PMid:8871138

Bradley RL, Ellis PE, Thomas P, Bellis H, Ireland AJ, Sandy JR. (2007, Oct). A randomized clinical trial comparing the efficacy of ibuprofen and paracetamol in the control of orthodontic pain. Am J Orthod Dentofacial Orthop. 132(4):511-7. https://doi.org/10.1016/j.ajodo.2006.12.009; PMid:17920505

Brown RD, Wilson JT, Kearns GL et al. (1992). Single-dose pharmacokinetics of ibuprofen and acetaminophen in febrile children. J Clin Pharmacol. 32: 231-241. https://doi.org/10.1002/j.1552-4604.1992.tb03831.x; PMid:1564127

Bushra R, Aslam N. (2010, Jul). An overview of clinical pharmacology of Ibuprofen. Oman Med J. 25(3):155-1661. https://doi.org/10.5001/omj.2010.49; PMid:22043330 PMCid:PMC3191627

Castelo-Branco C, Casals G, Haya J, Cancelo MJ, Manasanch J. (2004). Efficacy and safety of Ibuprofen arginine in the treatment of primary dysmenorrhoea. Clin Drug Investig. 24(7):385-93. https://doi.org/10.2165/00044011-200424070-00002; PMid:17516725

Clark E, Plint AC, Correll R, Gaboury I, Passi B. (2007, Mar). A randomized, controlled trial of acetaminophen, ibuprofen, and codeine for acute pain relief in children with musculoskeletal trauma. Pediatrics. 119; 3. https://doi.org/10.1542/peds.2006-1347; PMid:17332198

Czaykowski D, et al. (1994, Apr). Evaluation of the antipyretic efficacy of single dose ibuprofen suspension compared to acetaminophen elixir in febrile children. Pediatric Research, 35; 4; Part 2; Abstr. 829.

Damen L, Bruijn JK, Verhagen AP, Berger MY, Passchier J, Koes BW. (2005, Aug). Symptomatic treatment of migraine in children: a systematic review of medication trials. Pediatrics. 116(2):e295-302. https://doi.org/10.1542/peds.2004-2742; PMid:16061583

Dani C, Bertini G, Reali MF, Murru P, Fabris C, Vangi V, Rubaltelli FF. (2000). Prophylaxis of patent ductus arteriosus with ibuprofen in preterm infants. Acta Paediatr. 89(11): 1369-74. https://doi.org/10.1111/j.1651-2227.2000.tb00767.x

Dawood MY, Khan-Dawood FS. (2007, Jan). Clinical efficacy and differential inhibition of menstrual fluid prostaglandin F2alpha in a randomized, double-blind, crossover treatment with placebo, acetaminophen, and ibuprofen in primary dysmenorrhoea. Am J Obstet Gynecol. 196(1):35.e1-5. https://doi.org/10.1016/j.ajog.2006.06.091; PMid:17240224

Debley JS, Carter ER, Gibson RL, Rosenfeld M, Redding GJ. (2005, Aug). The prevalence of ibuprofen- sensitive asthma in children: a randomized controlled bronchoprovocation challenge study. J Pediatr. 147(2):233-8. https://doi.org/10.1016/j.jpeds.2005.03.055; PMid:16126056

Diez-Domingo J et al. (1998). Ibuprofen prophylaxis for adverse reactions to diptheria-tetanus pertussis vaccination: a randomised trial. Current Therapeutic Research. 59(8): 579-588. https://doi.org/10.1016/S0011-393X(98)85098-4

Dills R, Anderson LA, Pierce CA. (2012, Jan). The role of nonsteroidal anti-inflammatory drugs in pediatric patients. Pharmacol Res. 65(1): 5-8. Epub 2011 Sep 8. https://doi.org/10.1016/j.phrs.2011.08.010; PMid:21924358

Dlugosz CK, Chater RW, Engle JP. (2006, Sep-Oct). Appropriate use of nonprescription analgesics in pediatric patients. Source College of Pharmacy, University of Illinois at Chicago, IL 60612, USA. J Pediatr Health Care. 20(5):316-25; quiz 326-8. https://doi.org/10.1016/j.pedhc.2006.07.001; PMid:16962437

Drendel AL, Gorelick MH, Weisman SJ, Lyon R, Brousseau DC, Kim MK. (2009, Oct). A randomized clinical trial of ibuprofen versus acetaminophen with codeine for acute pediatric arm fracture pain. Ann Emerg Med. 54(4):553-60. Epub 2009 Aug 19. https://doi.org/10.1016/j.annemergmed.2009.06.005; PMid:19692147

Du Y, Ellert U, Zhuang W, Knopf H. (2012, Jul). Analgesic use in a national community sample of German children and adolescents. Eur J Pain. 16(6):934-43. Epub 2011 Dec 23. https://doi.org/10.1002/j.1532-2149.2011.00093.x; PMid:22337610

Eccles R. (2006, Aug). Efficacy and safety of over-the-counter analgesics in the treatment of common cold and flu. J Clin Pharm Ther. 31(4):309-19. https://doi.org/10.1111/j.1365-2710.2006.00754.x; PMid:16882099

Eigenbrodt AK, Ashina H, Khan S, et al. (2021). Diagnosis and management of migraine in ten steps. Nat Rev Neurol. 17(8):501-514. https://doi.org/10.1038/s41582-021-00509-5; PMid:34145431 PMCid:PMC8321897

Evers S, Rahmann A, Kraemer C, Kurlemann G, Debus O, Husstedt IW, Frese A. (2006, Aug 8). Treatment of childhood migraine attacks with oral zolmitriptan and ibuprofen. Neurology. 67(3):497-9. Epub 2006 Jun 14. https://doi.org/10.1212/01.wnl.0000231138.18629.d5; PMid:16775229

Fosbol EL, Gislason GH, Jacobsen S, Abildstrom SZ, Hansen ML, Schramm TK, Folke F, Sorensen R, Rasmussen JN, Kober L, Madsen M, Torp-Pedersen C. (2008, Aug). The pattern of use of non-steroidal antiinflammatory drugs (NSAIDs) from 1997 to 2005: a nationwide study on 4.6 million people. Pharmacoepidemiol Drug Saf. 17(8):822-33. https://doi.org/10.1002/pds.1592; PMid:18383428

Friday JH, Kanegaye JT, McCaslin I, Zheng A, Harley JR. (2009, Aug). Ibuprofen provides analgesia equivalent to acetaminophen-codeine in the treatment of acute pain in children with extremity injuries: a randomized clinical trial. Acad Emerg Med. 16(8):711-6. Epub 2009 Jul 14. https://doi.org/10.1111/j.1553-2712.2009.00471.x; PMid:19624576

Frye R, Bailey J, Blevins AE. (2011, May). Clinical inquiries. Which treatments provide the most relief for pharyngitis pain? J Fam Pract. 60(5):293-4.

Gazal G, Mackie IC. (2007, May). A comparison of paracetamol, ibuprofen or their combination for pain relief following extractions in children under general anaesthesia: a randomized controlled trial. Int J Paediatr Dent. 17(3):169-77. https://doi.org/10.1111/j.1365-263X.2006.00806.x; PMid:17397460

Geraud G, Lanteri-Minet M, Lucas C, Valade D. (2004, Aug). French guidelines for the diagnosis and management of migraine in adults and children. Clin Ther. 26(8):1305-18. https://doi.org/10.1016/S0149-2918(04)80161-9

Grebe W, Ionescu E, Gold MS, Liu JM, Frank WO. (2003, Feb). A multicenter, randomized, double-blind, double-dummy, placebo- and active-controlled, parallel-group comparison of diclofenac-K and ibuprofen for the treatment of adults with influenza-like symptoms. Clin Ther. 25(2):444-58. https://doi.org/10.1016/S0149-2918(03)80088-7

Giannini EH, Brewer EJ, Miller ML, Gibbas D, Passo MH, Hoyeraal HM, Bernstein B, Person DA, Fink CW, Sawyer LA. (1990). Ibuprofen suspension in the treatment of juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group. J Pediatr. 117: 645- 652. https://doi.org/10.1016/S0022-3476(05)80708-5

Gineyts E, Mo JA, Ko A et al. (2004). Effects of ibuprofen on molecular markers of cartilage and synovium turnover in patients with knee OA. Ann Rheum Dis. 63:857-861. https://doi.org/10.1136/ard.2003.007302; PMid:15194584 PMCid:PMC1755067

Gournay V, Savagner C, Thiriez G Kuster A, Roze J-C. (2002). Pulmonary hypertension after ibuprofen prophylaxis in very pre-term infants. Lancet. 359:1486-8. https://doi.org/10.1016/S0140-6736(02)08424-6

Gregoire N, Gualano V, Geneteau A et al. (2004). Population pharmacokinetics of ibuprofen enantiomers in very premature neonates. J Clin Pharmacol. 44: 1114-1124. https://doi.org/10.1177/0091270004268320; PMid:15342612

Grimaldi-Bensouda L, Abenhaim L, Michaud L, Mouterde O, Jonville-Bera AP, Giraudeau B, David B, Autret-Leca E. (2010, Aug). Clinical features and risk factors for upper gastrointestinal bleeding in children: a case-crossover study. Eur J Clin Pharmacol. 66(8):831-7. Epub 2010 May 16. https://doi.org/10.1007/s00228-010-0832-3; PMid:20473658

Halpern SM, Fitzpatrick R, Volans GN. (1993). Ibuprofen toxicity. A review of adverse reactions and overdose. Adverse Drug React Toxicol Rev. 12(2):107-28.

Hamalainen ML, Hoppu K, Valkeila E, Santavuori P. (1997, Jan). Ibuprofen or acetaminophen for the acute treatment of migraine in children: a double-blind, randomized, placebo-controlled, crossover study. Neurology. 48(1):103-7. https://doi.org/10.1212/WNL.48.1.103; PMid:9008503

Hamilton Jl, Evans SG, Bakshi M. (2020, Jun 15). Management of Fever in Infants and Young Children. Am Fam Physician. 101(12): 721-729.

Hargreaves K, Abbott PV. (2005, Dec). Drugs for pain management in dentistry. Aust Dent J. 50(4; Suppl 2):S14-22. https://doi.org/10.1111/j.1834-7819.2005.tb00378.x; PMid:16416713

Hasiba U, Scranton PE, Lewis JH and Spero JA. (1980). Efficacy and safety of ibuprofen for hemophilic arthropathy. Arch Intern Med. 140:1583-1585. https://doi.org/10.1001/archinte.140.12.1583; PMid:7006539

Hassani A, Ponvert C, Karila C, Le Bourgeois M, De Blic J, Scheinmann P. (2008, Sep-Oct). Hypersensitivity to cyclooxygenase inhibitory drugs in children: a study of 164 cases. Eur J Dermatol. 18(5):561-5. Epub 2008 Aug 8.

Henry D, McGettigan P. (2003, Apr). Epidemiology overview of gastrointestinal and renal toxicity of NSAIDs. Int J Clin Suppl. (135):43-9.

Heremans G, Dehaen F, Rom N, Ramet J, Verboven M, Loeb H. (1988). A single blind parallel group study investigating the antipyretic properties of ibuprofen syrup versus acetylsalicylic acid syrup in febrile children. Br J Clin Pract. 42:245-7.

Heyman E, Morag I. (2003). Closure of patent ductus arteriosus with oral ibuprofen suspension in premature newborns: a pilot study. Pediatrics. 112(5): 354-8. https://doi.org/10.1542/peds.112.5.e354; PMid:14595076

Hocevar S, Kennedy SA, Darden PM, Reigart JR. (2008, Aug). Headache in children. J S C Med Assoc. 104(6):191-3.

Inwood MJ, Killackey B and Startup SJ. (1983). The use and safety of Ibuprofen in the hemophiliac. Blood. 61:709-711. https://doi.org/10.1182/blood.V61.4.709.bloodjournal614709; PMid:6338972

Jeyakumar A, Brickman TM, Williamson ME, Hirose K, Krakovitz P, Whittemore K, Discolo C. (2008, Jan). Nonsteroidal anti-inflammatory drugs and postoperative bleeding following adenotonsillectomy in pediatric patients. Arch Otolaryngol Head Neck Surg. 134(1):24-7. https://doi.org/10.1001/archoto.2007.11; PMid:18209131

Jick H. (1999). Boston Collaborative Drug Surveillance Program. Report on ibuprofen safety study in infants under one year of age. Data on file at Reckitt Benckiser Healthcare International. 58. Joshi YM, Sovani VB, Joshi VV et al. (1990). Comparative evaluation of the antipyretic efficacy of ibuprofen and paracetamol. Indian Paediatr. 27:803-806.

Kacperski J, Kabbouche M, O'Brien H, Weberding J (2015). The optimal management of headaches in children and adolescents. Therapeutic Advances in Neurological Disorders. 9(1): 53-68. https://doi.org/10.1177/1756285615616586; PMid:26788131 PMCid:PMC4710107

Kauffman RE, Lieh-Lai M. (2004). Ibuprofen and increased morbidity in children with asthma: fact or fiction? Paediatr Drugs. 6(5):267-72. https://doi.org/10.2165/00148581-200406050-00001; PMid:15449966

Kauffman RE, Sawyer LA and Scheinbaum ML. (1992). Antipyretic efficacy of ibuprofen vs. acetominophen. AJDC. 146: 622-5. https://doi.org/10.1001/archpedi.1992.02160170102024; PMid:1621668

Kidon MI, Kang LW, Chin CW, Hoon LS, Hugo VB. (2007, Dec 15). Nonsteroidal anti-inflammatory drug hypersensitivity in preschool children. Allergy Asthma Clin Immunol. 3(4):114-22. Epub 2007 Dec 15. https://doi.org/10.1186/1710-1492-3-4-114; PMid:20525116 PMCid:PMC2873607

Klein, J. and Koch, T. (2020). Headache in Children. Pediatrics in Review. 41(4): 159-171. https://doi.org/10.1542/pir.2017-0012; PMid:32238545

Kokki H. (2003). Nonsteroidal anti-inflammatory drugs for postoperative pain: a focus on children. Paediatr Drugs. 5(2):103-23. https://doi.org/10.2165/00128072-200305020-00004; PMid:12529163

Koller DM, Myers AB, Lorenz D, Godambe SA. (2007, Sep). Effectiveness of oxycodone, ibuprofen, or the combination in the initial management of orthopedic injury-related pain in children. Pediatr Emerg Care. 23(9):627-33. https://doi.org/10.1097/PEC.0b013e31814a6a39; PMid:17876251

Krause I, Cleper R, Eisenstein B, Davidovits M. (2005, Sep). Acute renal failure, associated with non- steroidal anti-inflammatory drugs in healthy children. Pediatr Nephrol. 20(9):1295-8. Epub 2005 Jun 23. https://doi.org/10.1007/s00467-005-1966-x; PMid:15973524

Kyllonen M, Olkkola KL, Seppala T, Ryhanen P. (2005). Perioperative pharmacokinetics of ibuprofen enantiomers after rectal administration. Pediatric Anesthesia. 15: 566-573. https://doi.org/10.1111/j.1460-9592.2005.01499.x; PMid:15960640

Lago P, Bettiol T, Salvadori S, Pitassi I, Vianello A, Chiandetti L, Saia O. (2002). Safety and efficacy of ibuprofen vs. indomethacin in preterm infants treated for patent ductus arteriosus: a randomised controlled trial. Eur J Pediatr. 161(4): 202-7. https://doi.org/10.1007/s00431-002-0915-y; PMid:12014386

Lasky T, Ernst FR, Greenspan J. (2012, May 10). Use of Analgesic, Anesthetic, and Sedative Medications During Pediatric Hospitalizations in the United States 2008. Anesth Analg. (Epub ahead of print). https://doi.org/10.1213/ANE.0b013e31825b6fb2; PMid:22575570

Le Parc JM, Van Ganse E, Moore N, Wall R, Schneid H, Verriere F. (2002, Feb). Comparative tolerability of paracetamol, aspirin and ibuprofen for short-term analgesia in patients with musculoskeletal conditions: results in 4291 patients. Clin Rheumatol. 21(1):28-31. https://doi.org/10.1007/s100670200007; PMid:11954880

Lesko SM, Mitchell AA. (1999). The safety of acetaminophen and ibuprofen among children younger than two years old. Paediatrics. 104: e39. https://doi.org/10.1542/peds.104.4.e39; PMid:10506264

Lesko SM, Louik C, Vezina RM, Mitchell AA. (2002). Asthma morbidity after the short term use of ibuprofen in children. Pediatrics. 109 (2). https://doi.org/10.1542/peds.109.2.e20; PMid:11826230

Lewis DW, Kellstein D, Dahl G, Burke B, Frank LM, Toor S, Northam RS, White LW, Lawson L. (2002, Sep). Children's ibuprofen suspension for the acute treatment of pediatric migraine. Headache. 42(8):780-6. https://doi.org/10.1046/j.1526-4610.2002.02180.x; PMid:12390641

Lewis DW, Yonker M, Winner P, Sowell M. (2005, Jun). The treatment of pediatric migraine. Pediatr Ann. 34(6):448-60. https://doi.org/10.3928/0090-4481-20050601-10; PMid:16018227

McIntyre J, Hull D. (1996). Comparing efficacy and tolerability of ibuprofen and paracetamol in fever. Archives of Disease in Childhood. 74: 164-167. https://doi.org/10.1136/adc.74.2.164; PMid:8660083 PMCid:PMC1511501

Moore N, Le Parc JM, van Ganse E, Wall R, Schneid H, Cairns R. (2002, Dec). Tolerability of ibuprofen, aspirin and paracetamol for the treatment of cold and flu symptoms and sore throat pain. Int J Clin Pract. 56(10):732-4.

Moore N. (2003, Apr). Forty years of ibuprofen use. Int J Clin Pract. Suppl. (135):28-31.

Moore PA, Acs G, Hargreaves JA. (1985). Postextraction pain relief in children: a clinical trial of liquid analgesics. Int J Clin Pharmacology, Therapy and Toxicology. 23(11): 573-577.

Morales-Carpi C, Estan L, Rubio E, Lurbe E, Morales-Olivas FJ. (2010, Mar). Drug utilization and off-label drug use among Spanish emergency room paediatric patients. Eur J Clin Pharmacol. 66(3):315-20. https://doi.org/10.1007/s00228-009-0747-z; PMid:19936729

Mossad SB. (2003, Dec). Current and future therapeutic approaches to the common cold. Expert Rev Anti-Infect. Ther. 1(4): 619-626. Future Drugs Ltd. https://doi.org/10.1586/14787210.1.4.619; PMid:15482159

Nahata MC, Durell DE, Powel DA, Gupta N. (1991). Pharmacokinetics of ibuprofen in febrile children. Eur J Clin Pharmacol. 40: 427-428. https://doi.org/10.1007/BF00265858; PMid:2050181

Nahata MC, Powell DA, Durrell DE, et al. (1992). Efficacy of ibuprofen in pediatric patients with fever. Int J Clin Pharmacol Ther Toxicol. 30(3): 94-96.

Neubert A, Verhamme K, Murray ML, Picelli G, Hsia Y, Sen FE, Giaquinto C, Ceci A, Sturkenboom M, Wong IC; TEDDY Network of Excellence. (2010, Sep). The prescribing of analgesics and non-steroidal anti-inflammatory drugs in paediatric primary care in the UK, Italy and the Netherlands. Pharmacol Res. 62(3):243-8. Epub 2010 May 6. https://doi.org/10.1016/j.phrs.2010.04.006; PMid:20451614

NICE guideline (2019, Nov 7). Fever in under 5s: assessment and initial management. (NG143). URL: https://www.nice.org.uk/guidance/ng143

Niehues T. (2013, Nov). Thе Febrile Child: Diagnosis and Treatment. Deutsches Arzteblatt international. 110(45):764-774. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3849992/.

O'Brien HL, Kabbouche MA, Hershey AD. (2012, May). Treating pediatric migraine: an expert opinion. Expert Opin Pharmacother. 13(7):959-66. Epub 2012 Apr 14. https://doi.org/10.1517/14656566.2012.677434; PMid:22500646

Oskoui M., Pringsheim T., Holler-Managan Y. et al. (2019). Practice guideline update summary: Acute treatment of migraine in children and adolescents: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 93(11): 487-499. https://doi.org/10.1212/WNL.0000000000008095; PMid:31413171

Ozkiris M, Kapusuz Z, Yildirim YS, Saydam L. (2012, Jul). The effect of paracetamol, metamizole sodium and ibuprofen on postoperative hemorrhage following pediatric tonsillectomy. Int J Pediatr Otorhinolaryngol. 76(7):1027-9. Epub 2012 May 15. https://doi.org/10.1016/j.ijporl.2012.03.025; PMid:22595462

Pappas DE and Hendley JO. (2011, Feb). The common cold and decongestant therapy. Pediatrics in Review. 32(2): 47-55. American Academy of Pediatrics. https://doi.org/10.1542/pir.32-2-47; PMid:21285300

Paul BR. (1999). A double blind comparison of the safety and efficacy of a single dose of Children's Advil ibuprofen suspension (10 mg/kg), acetaminophen (15 mg/kg) and a control vehicle in the relief of sore throat pain in children. 1990; WM-375A. Whitehall Laboratories. Pharmaceutical Press: 925-926.

Pelen F et al. (1998). Treatment of Fever: monotherapy with ibuprofen. Ibuprofen pediatric suspension containing 100mg/5ml, Multicentre acceptability study conducted in hospital. (in French) Ann. Pediatr. (Paris). 45, 10: 719-728.

Perrie Y. (2006, Sep 30). Influenza: Treatment and prevention. Pharmaceutical Journal. 277:399-402.

Perry SJ, Streete PJ, Volans GN. (1987, Mar). Ibuprofen overdose: the first two years of over-the-counter sales. Hum Toxicol. 6(2):173-8. https://doi.org/10.1177/096032718700600211; PMid:3557476

Perrott DA, Piira T, Goodenough B, Champion GD. (2004, Jan). Efficacy and safety of acetaminophen vs. ibuprofen for treating children's pain or fever: a meta-analysis. Arch Pediatr Adolesc Med. 158(6):521-6. https://doi.org/10.1001/archpedi.158.6.521; PMid:15184213

Pierce CA, Voss B. (2010, Mar). Efficacy and safety of ibuprofen and acetaminophen in children and adults: a meta-analysis and qualitative review. Ann Pharmacother. 4(3):489-506. Epub 2010 Feb 11. https://doi.org/10.1345/aph.1M332; PMid:20150507

Pilotto A, Seripa D, Franceschi M, Scarcelli C, Colaizzo D, Grandone E, Niro V, Andriulli A, Leandro G, Di Mario F, Dallapiccola B. (2007, Aug). Genetic susceptibility to nonsteroidal anti-inflammatory drug-related gastroduodenal bleeding: role of cytochrome P450 2C9 polymorphisms. Gastroenterology. 133(2):465-71. Epub 2007 May 21. https://doi.org/10.1053/j.gastro.2007.05.025; PMid:17681167

Rainsford KD, Roberts SC, Brown S. (1997, Apr). Ibuprofen and paracetamol: relative safety in non- prescription dosages. J Pharm Pharmacol. 49(4):345-76. https://doi.org/10.1111/j.2042-7158.1997.tb06809.x; PMid:9232533

Rainsford KD. (2003, Apr). Discovery, mechanisms of action and safety of ibuprofen. Int J Clin Pract Suppl. (135):3-8.

Rainsford KD. (2009, Dec). Ibuprofen: pharmacology, efficacy and safety. Inflammopharmacology. 17(6):275-342. Epub 2009 Nov 21. https://doi.org/10.1007/s10787-009-0016-x; PMid:19949916

Raju NV, Bharadwaj RA, Thomas R, Konduri GG. (2000, Jan-Feb). Ibuprofen use to reduce the incidence and severity of bronchopulmonary dysplasia: a pilot study. J Perinatal. 20 (1):13-6. https://doi.org/10.1038/sj.jp.7200296; PMid:10693094

Richer LP, Laycock K, Millar K, Fitzpatrick E, Khangura S, Bhatt M, Guimont C, Neto G, Noseworthy S, Siemens R, Gouin S, Rowe BH. (2010, Jul). Treatment of children with migraine in emergency departments: national practice variation study. Pediatrics. 126(1):e150- 5. Epub 2010 Jun 7. https://doi.org/10.1542/peds.2009-2337; PMid:20530076

Richy F, Bruyere O, Ethgen O et al. (2004). Time dependent risk of gastrointestinal complications induced by non-steroidal anti-inflammatory drug use: a consensus statement using a meta- analytic approach. Ann Rheum Dis. 63; 759-766. https://doi.org/10.1136/ard.2003.015925; PMid:15194568 PMCid:PMC1755051

Rogovik AL, Goldman RD. (2007, May). Prehospital use of analgesics at home or en route to the hospital in children with extremity injuries. Am J Emerg Med. 25(4):400-5. https://doi.org/10.1016/j.ajem.2006.11.021; PMid:17499657

Sachs CJ. (2005, Mar 1). Oral analgesics for acuter non-specific pain. American Family Physician. 71(5):913-918.

Schachtel BP, Thoden WR. (1993, May). A placebo-controlled model for assaying systemic analgesics in children. Clin Pharmacol Ther. 53(5):593-601. https://doi.org/10.1038/clpt.1993.75; PMid:8491069

Schaffer D, Florin T, Eagle C, Marschner I, Singh G, Grobler M, Fenn C, Schou M, Curnow KM. (2006, Nov 6). Risk of serious NSAID-related gastrointestinal events during long-term exposure: a systematic review. Med J Aust. 185(9):501-6. https://doi.org/10.5694/j.1326-5377.2006.tb00665.x; PMid:17137455

Shah UH, Kalra V. (2009). Pediatric migraine. Int J Pediatr. 2009:424192. Epub 2009 May 27. https://doi.org/10.1155/2009/424192; PMid:20041017 PMCid:PMC2778404

Sharma PK, Garg SK, Narang A. (2003). Pharmacokinetics of oral ibuprofen in premature infants. J Clin Pharmacol. 43: 968-973. https://doi.org/10.1177/0091270003254635; PMid:12971028

Sidler J, Frey B, Baerlocher K. (1990). A double-blind comparison of ibuprofen and paracetamol in juvenile pyrexia. Br J Clin Prac. 44; suppl 70: 22-25.

Silver S, Gano D, Gerretsen P. (2008, Jan). Acute treatment of paediatric migraine: a meta-analysis of efficacy. J Paediatr Child Health. 44(1-2):3-9. Epub 2007 Sep 14.

Southey ER, Soares-Weiser K, Kleijnen J. (2009, Sep). 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. 25(9):2207-22. https://doi.org/10.1185/03007990903116255; PMid:19606950

Star K, Caster O, Bate A, Edwards IR. (2011, Apr 1). Dose variations associated with formulations of NSAID prescriptions for children: a descriptive analysis of electronic health records in the UK. Drug Saf. 34(4): 307-17. https://doi.org/10.2165/11586610-000000000-00000; PMid:21417503

Stewart DW, Ragg PG, Sheppard S, Chalkiadis GA. (2012, Feb). The severity and duration of postoperative pain and analgesia requirements in children after tonsillectomy, orchidopexy, or inguinal hernia repair. Paediatr Anaesth. 22(2):136-43. Epub 2011 Oct 25. https://doi.org/10.1111/j.1460-9592.2011.03713.x; PMid:22023485

Stillings M, Little S, Sykes J. (2003). Common cold and influenza symptom management: The use of pharmacokinetic considerations to predict the efficacy of a twice-daily treatment for colds and flu. Current Medical Research and Opinion. 19(8): 791-799. Librapharm.

Supapannachart S, Limrungsikul A, Khowsathit P. (2002, Nov). Oral ibuprofen and indomethacin for treatment of patent ductus arteriosus in premature infants: a randomised trial at Ramathibodi Hospital. J Med Assoc Thai. 85; Suppl 4: S1252-8.

Terrie YC. (2012, Feb). Stopping the symptoms of cough, cold and flu. Pharmacy Times. 78(2). Intellisphere LLC.

Thoden W, Bornhofen J. (2000). Antipyretic efficacy of ibuprofen and acetaminophen in children with fever. J Clin Pharmacol. 40(9), 1053.

Thoden WR. (1990). Whitehall Laboratories Final Study Report: WM-3666, July 30th 1990. A double-blind comparison of the safety and efficacy of a single dose of children's Advil ibuprofen suspension (10 mg/Kg), acetaminophen (15 mg/Kg) and control vehicle in the relief of sore throat pain in children.

Thomson SA, Goulder MA. (1995). An open study to evaluate the use of ibuprofen suspension in the treatment of post-immunisation pyrexia in children (BR1148). Knoll Pharmaceuticals Internal Report No. CI95090: 1-39.

Titchen T, Cranswick N, Beggs S. (2005, Jun). Adverse drug reactions to nonsteroidal anti-inflammatory drugs, COX-2 inhibitors and paracetamol in a paediatric hospital. Br J Clin Pharmacol. 59(6):718-23. https://doi.org/10.1111/j.1365-2125.2005.02444.x; PMid:15948937 PMCid:PMC1884871

Trajanovska M, Manias E, Cranswick N, Johnston L. (2010, Jan). Use of over-the-counter medicines for young children in Australia. J Paediatr Child Health. 46(1-2):5-9. Epub 2009 Nov 23. https://doi.org/10.1111/j.1440-1754.2009.01609.x; PMid:19943869

Turturro MA, Paris PM, Seaberg DC. (1995, Aug). Intramuscular ketorolac versus oral ibuprofen in acute musculoskeletal pain. Ann Emerg Med. 26(2):117-20. https://doi.org/10.1016/S0196-0644(95)70138-9

Ulinski T, Guigonis V, Dunan O, Bensman A. (2004, Mar). Acute renal failure after treatment with non- steroidal anti-inflammatory drugs. Eur J Pediatr. 163(3):148-50. Epub 2004 Jan 24. https://doi.org/10.1007/s00431-003-1392-7; PMid:14745553

Van Overmeire B, Foilens I, Hartmann S et al. (1997). Treatment of patent ductus arteriosus with ibuprofen. Arch Dis Child. 76: F179-F184. https://doi.org/10.1136/fn.76.3.F179; PMid:9175948 PMCid:PMC1720646

Van Overmeire B, Smets K, Lecoutere D, Van de Broek H, Weyler J, Degroote K, Langhendries JP. (2000). A comparison of ibuprofen and indomethacin for closure of patent ductus arteriosus. N Engl J Med. 343:674-681. https://doi.org/10.1056/NEJM200009073431001; PMid:10974130

Varvarigou A, Bardin CL, Beharry K et al. (1996). Early ibuprofen administration to prevent patent ductus arteriosus in premature newborn infants. J Amer Med Assoc. 275 (7): 539-44. https://doi.org/10.1001/jama.275.7.539; PMid:8606475

Vauzelle-Kervroedan F et al. (1997). Equivalent antipyretic activity of ibuprofen ad paracetamol in febrile children. J Paediatr. 131: 683-687. https://doi.org/10.1016/S0022-3476(97)70093-3

Vernacchio L, Kelly JP, Kaufman DW, Mitchell AA. (2009, Aug). Medication use among children <12 years of age in the United States: results from the Slone Survey. Pediatrics. 124(2):446-54. Epub 2009 Jul 27. https://doi.org/10.1542/peds.2008-2869; PMid:19651573

Vinh H, Parry CM, Vo TNH et al. (2004). Double-blind comparison of ibuprofen and paracetamol for adjunctive treatment of uncomplicated typhoid fever. Paediatr Infect Dis J. 23; 226-230. https://doi.org/10.1097/01.inf.0000114905.87426.c2; PMid:15014297

Volans G, Monaghan J, Colbridge M. (2003, Apr). Ibuprofen overdose. Int J Clin Pract Suppl. (135):54-60.

Walker DM, Teach SJ. (2008, Jun). Emergency department treatment of primary headaches in children and adolescents. Curr Opin Pediatr. 20(3):248-54. https://doi.org/10.1097/MOP.0b013e3282ff6308; PMid:18475091

Walson PD, Galletta G, Chomilo F et al. (1992). Comparison of multidose ibuprofen and acetaminophen therapy in febrile children. Am J Dis Child. 146:626-632. https://doi.org/10.1001/archpedi.1992.02160170106025; PMid:1621669

Walson PD, Mortensen ME. (1989). Pharmacokinetics of common analgesics, anti-inflammatories and antipyretics in children. Clin Pharmacokinet. 17; Suppl 1:116-37. https://doi.org/10.2165/00003088-198900171-00009; PMid:2692935

Wilson G, Guerra AJMJ, Santos NT. (1984). Comparative study of the antipyretic effect of ibuprofen (oral suspension) and paracetamol (suppositories) in paediatrics. J Int Med Res. 12:250-4. https://doi.org/10.1177/030006058401200405; PMid:6468748

Wilson JT, Brown RD, Kearns GL et al. (1991). Single dose, placebo-controlled comparative study of ibuprofen and acetaminophen antipyresis n children. J Pediatr. 119: 803-811. https://doi.org/10.1016/S0022-3476(05)80307-5

Wolfe MM. (2003, Apr). Risk factors associated with the development of gastroduodenal ulcers due to the use of NSAIDs. Int J Clin Pract Suppl. (135):32-7.

Yaman H, Belada A, Yilmaz S. (2011, Apr). The effect of ibuprofen on post-operative hemorrhage following tonsillectomy in children. Eur Arch Otorhinolaryngol. 268(4):615-7. Epub 2010 Oct 2. https://doi.org/10.1007/s00405-010-1393-x; PMid:20890608

Zernikow B, Hechler T. (2008, Jul). Pain therapy in children and adolescents. Dtsch Arztebl Int. 105(28-29):511-21; quiz 521-2. Epub 2008 Jul 14.





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