{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T22:49:37Z","timestamp":1784933377787,"version":"3.55.0"},"reference-count":140,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006546","name":"Angelini","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006546","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background\/Objectives: Fever and pain are among the most common symptoms in pediatric infections and chronic diseases, causing significant discomfort for children and concern for caregivers. Effective management is essential to relieve distress while avoiding overtreatment or undertreatment. Paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs), particularly ibuprofen, are the primary antipyretic and analgesic agents in pediatric care, but their use in children with chronic conditions might be challenging. Methods: A narrative review and clinical expert judgment were used to synthesize current evidence on the use of paracetamol and NSAIDs (especially ibuprofen) in children with some common chronic diseases. Results: Paracetamol is often considered a first-line option in several chronic conditions. Caution is warranted in children with pre-existing malnutrition, obesity, and neuromuscular disorders as these factors might increase the risk of hepatotoxicity. NSAIDs provide additional anti-inflammatory effects and comparable analgesic efficacy but should be used cautiously in some high-risk populations due to potential gastrointestinal, renal, and bleeding complications. Their use is contraindicated in children with dehydration, renal impairment, nephrotic syndrome relapses, while careful risk-benefit assessment is required in small and vulnerable neonates. Some data also suggests NSAIDs may worsen outcomes in certain acute bacterial and viral infections. Data on chronic infections such as tuberculosis, HIV, and viral hepatitis are limited, highlighting the need for further research. Combination therapy with paracetamol and ibuprofen may enhance analgesia in postoperative settings without significantly increasing adverse events. Overall, available evidence is limited and largely observational. Conclusions: This narrative review synthesizes current evidence and clinical expertise to provide practical guidance on the rational use of paracetamol and NSAIDs in children, emphasizing individualized therapy according to comorbidities, risk factors, and clinical context, particularly in vulnerable populations. A risk-adapted, evidence-based approach ensures optimal symptom control while minimizing harm, supporting safer, more effective, and family-centered care for children with fever and pain.<\/jats:p>","DOI":"10.3390\/children13010071","type":"journal-article","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T12:23:44Z","timestamp":1767356624000},"page":"71","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Efficacy and Safety of Paracetamol and NSAIDs for Fever and Pain Management in Children with Chronic Diseases: A Narrative Review"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3829-4254","authenticated-orcid":false,"given":"Gregorio Paolo","family":"Milani","sequence":"first","affiliation":[{"name":"Pediatric Unit, Foundation Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4259-4540","authenticated-orcid":false,"given":"Giangiacomo","family":"Nicolini","sequence":"additional","affiliation":[{"name":"Pediatric Care Unit, Conegliano Hospital, 31015 Conegliano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Cananzi","sequence":"additional","affiliation":[{"name":"Unit of Paediatric Gastroenterology, Digestive Endoscopy, Hepatology and Care of the Child with Liver Transplantation, Department of Women\u2019s and Children\u2019s Health, University Hospital of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4339-8525","authenticated-orcid":false,"given":"Luca","family":"Spiezia","sequence":"additional","affiliation":[{"name":"General Medicine and Thrombotic and Haemorrhagic Diseases Unit, Department of Medicine, University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3963-0803","authenticated-orcid":false,"given":"Enrico","family":"Vidal","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology Unit, University Hospital of Padova, 35128 Padova, Italy"},{"name":"Department of Medicine (DMED), University of Udine, 33100 Udine, Italy"},{"name":"Institute of Pediatric Research \u201cCitt\u00e0 Della Speranza\u201d, 35127 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Barbi, E., Marzuillo, P., Neri, E., Naviglio, S., and Krauss, B.S. (2017). Fever in Children: Pearls and Pitfalls. Children, 4.","DOI":"10.3390\/children4090081"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/apa.13221","article-title":"Fever phobia 35 years later: Did we fail?","volume":"105","author":"Bertille","year":"2016","journal-title":"Acta Paediatr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1007\/s00431-017-2944-6","article-title":"Acute pain management: Acetaminophen and ibuprofen are often under-dosed","volume":"176","author":"Milani","year":"2017","journal-title":"Eur. J. Pediatr."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Doria, M., Careddu, D., Iorio, R., Verrotti, A., Chiappini, E., Barbero, G.M., Ceschin, F., Dell\u2019Era, L., Fabiano, V., and Mencacci, M. (2021). Paracetamol and Ibuprofen in the Treatment of Fever and Acute Mild-Moderate Pain in Children: Italian Experts\u2019 Consensus Statements. Children, 8.","DOI":"10.3390\/children8100873"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s40122-015-0040-z","article-title":"Recent Advances in Pediatric Use of Oral Paracetamol in Fever and Pain Management","volume":"4","author":"Chiarugi","year":"2015","journal-title":"Pain Ther."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Mboma, O., Wirth, S., and Aydin, M. (2021). The Risk of Nonsteroidal Anti-Inflammatory Drugs in Pediatric Medicine: Listen Carefully to Children with Pain. Children, 8.","DOI":"10.3390\/children8111048"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nri3843","article-title":"Fever and the thermal regulation of immunity: The immune system feels the heat","volume":"15","author":"Evans","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/nn2027","article-title":"A thermosensory pathway that controls body temperature","volume":"11","author":"Nakamura","year":"2008","journal-title":"Nat. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1097\/j.pain.0000000000000559","article-title":"Pain and infection: Pathogen detection by nociceptors","volume":"157","author":"Chiu","year":"2016","journal-title":"Pain"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1096\/fj.03-0645rev","article-title":"Cyclooxygenases: New forms, new inhibitors, and lessons from the clinic","volume":"18","author":"Warner","year":"2004","journal-title":"FASEB J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"13926","DOI":"10.1073\/pnas.162468699","article-title":"COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic\/antipyretic drugs: Cloning, structure, and expression","volume":"99","author":"Chandrasekharan","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ohashi, N., and Kohno, T. (2020). Analgesic Effect of Acetaminophen: A Review of Known and Novel Mechanisms of Action. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.580289"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"817","DOI":"10.2165\/00128072-200103110-00004","article-title":"Risks and benefits of nonsteroidal anti-inflammatory drugs in children: A comparison with paracetamol","volume":"3","author":"Litalien","year":"2001","journal-title":"Paediatr. Drugs"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.curtheres.2014.12.001","article-title":"Clinical Pharmacology of Paracetamol in Neonates: A Review","volume":"77","author":"Pacifici","year":"2014","journal-title":"Curr. Ther. Res. Clin. Exp."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1096\/fj.05-4434fje","article-title":"Influence of plasma protein on the potencies of inhibitors of cyclooxygenase-1 and -2","volume":"20","author":"Warner","year":"2006","journal-title":"FASEB J."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Idasiak-Piechocka, I., Lewandowski, D., \u015awigut, W., Kalinowski, J., Mikosza, K., Suchowiejski, P., Sza\u0142ek, E., Karbownik, A., and Miedziaszczyk, M. (2025). Effect of hypoalbuminemia on drug pharmacokinetics. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1546465"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/nature15817","article-title":"Pharmacogenomics in the Clinic","volume":"526","author":"Relling","year":"2015","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.1185\/03007990903116255","article-title":"Systematic review and meta-analysis of the clinical safety and tolerability of ibuprofen compared with paracetamol in paediatric pain and fever","volume":"25","author":"Southey","year":"2009","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1345\/aph.1M332","article-title":"Efficacy and safety of ibuprofen and acetaminophen in children and adults: A meta-analysis and qualitative review","volume":"44","author":"Pierce","year":"2010","journal-title":"Ann. Pharmacother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1001\/archpedi.158.6.521","article-title":"Efficacy and safety of acetaminophen vs ibuprofen for treating children\u2019s pain or fever: A meta-analysis","volume":"158","author":"Perrott","year":"2004","journal-title":"Arch. Pediatr. Adolesc. Med."},{"key":"ref_21","first-page":"9","article-title":"A general overview of the use of ibuprofen in paediatrics","volume":"135","year":"2003","journal-title":"Int. J. Clin. Pract. Suppl."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1001\/jama.1995.03520360043037","article-title":"An assessment of the safety of pediatric ibuprofen. A practitioner-based randomized clinical trial","volume":"273","author":"Lesko","year":"1995","journal-title":"JAMA"},{"key":"ref_23","first-page":"26","article-title":"Optimising the management of fever and pain in children","volume":"178","year":"2013","journal-title":"Int. J. Clin. Pract. Suppl."},{"key":"ref_24","first-page":"e46907","article-title":"Comparing the Efficacy of Paracetamol, Ibuprofen, and a Combination of the Two Drugs in Relieving Pain and Fever in the Pediatric Age Group: A Prospective Observational Study","volume":"15","author":"Charde","year":"2023","journal-title":"Cureus"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e2022398","DOI":"10.1001\/jamanetworkopen.2020.22398","article-title":"Comparison of Acetaminophen (Paracetamol) with Ibuprofen for Treatment of Fever or Pain in Children Younger Than 2 Years: A Systematic Review and Meta-analysis","volume":"3","author":"Tan","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3310\/hta13270","article-title":"Paracetamol and Ibuprofen for the Treatment of Fever in Children: The PITCH Randomised Controlled Trial","volume":"13","author":"Hay","year":"2009","journal-title":"Health Technol. Assess."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.jpeds.2016.09.043","article-title":"2016 Update of the Italian Pediatric Society Guidelines for Management of Fever in Children","volume":"180","author":"Chiappini","year":"2017","journal-title":"J. Pediatr."},{"key":"ref_28","unstructured":"NICE (National Institute for Health and Care Excellence) (2019). NICE Guideline NG143, NICE. Available online: https:\/\/www.nice.org.uk\/guidance\/ng143."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10787-016-0302-3","article-title":"A clinical and safety review of paracetamol and ibuprofen in children","volume":"25","author":"Kanabar","year":"2017","journal-title":"Inflammopharmacology"},{"key":"ref_30","first-page":"82","article-title":"Ibuprofen in the treatment of children\u2019s inflammatory pain: A clinical and pharmacological overview","volume":"71","author":"Barbagallo","year":"2019","journal-title":"Minerva Pediatr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.phrs.2011.08.010","article-title":"The role of nonsteroidal anti-inflammatory drugs in pediatric patients","volume":"65","author":"Dills","year":"2012","journal-title":"Pharmacol. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1007\/s40265-017-0751-z","article-title":"Working Towards an Appropriate Use of Ibuprofen in Children: An Evidence-Based Appraisal","volume":"77","author":"Chiarugi","year":"2017","journal-title":"Drugs"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/s40272-022-00514-1","article-title":"Efficacy and Safety of NSAIDs in Infants: A Comprehensive Review of the Literature of the Past 20 Years","volume":"24","author":"Ziesenitz","year":"2022","journal-title":"Pediatr. Drugs"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1001\/jamapediatrics.2024.5920","article-title":"Pharmacologic Management of Acute Pain in Children: A Systematic Review and Network Meta-Analysis","volume":"179","author":"Olejnik","year":"2025","journal-title":"JAMA Pediatr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1136\/archdischild-2012-302100","article-title":"Drug use and upper gastrointestinal complications in children: A case\u2013control study","volume":"98","author":"Bianciotto","year":"2013","journal-title":"Arch. Dis. Child."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1007\/s00228-010-0832-3","article-title":"Clinical features and risk factors for upper gastrointestinal bleeding in children: A case-crossover study","volume":"66","author":"Abenhaim","year":"2010","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.3748\/wjg.v22.i5.1877","article-title":"Italian survey on non-steroidal anti-inflammatory drugs and gastrointestinal bleeding in children","volume":"22","author":"Cardile","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1248\/bpb.b19-00722","article-title":"Toxicological Property of Acetaminophen: The Dark Side of a Safe Antipyretic\/Analgesic Drug?","volume":"43","author":"Ishitsuka","year":"2020","journal-title":"Biol. Pharm. Bull."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"324","DOI":"10.3934\/Allergy.2024020","article-title":"Challenges and management of bleeding in Kawasaki disease with aspirin treatment","volume":"8","author":"Jiao","year":"2024","journal-title":"AIMS Allergy Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/S0022-3476(96)80140-5","article-title":"Gastrointestinal hemorrhage complicating aspirin therapy in acute Kawasaki disease","volume":"128","author":"Matsubara","year":"1996","journal-title":"J. Pediatr."},{"key":"ref_41","unstructured":"(2025, December 22). LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012. Nonsteroidal Antiinflammatory Drugs (NSAIDs) [Updated 18 March 2020], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK548614\/."},{"key":"ref_42","unstructured":"(2025, December 22). LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012. Ibuprofen [Updated 20 July 2025], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK547845\/."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Maris, B.R., Grama, A., and Pop, T.L. (2025). Drug-Induced Liver Injury-Pharmacological Spectrum Among Children. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26052006"},{"key":"ref_44","unstructured":"(2025, December 22). LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012. Acetaminophen [Updated 28 January 2016], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK548162\/."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1002\/j.1552-4604.1996.tb05025.x","article-title":"Acetaminophen Toxicity in Children: Diagnostic Confirmation Using a Specific Antigenic Biomarker","volume":"36","author":"Webster","year":"1996","journal-title":"J. Clin. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.jhep.2019.10.030","article-title":"Early Acetaminophen-Protein Adducts Predict Hepatotoxicity Following Overdose (ATOM-5)","volume":"72","author":"Chiew","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_47","unstructured":"Agrawal, S., Murray, B.P., and Khazaeni, B. (2025, November 20). Acetaminophen Toxicity, StatPearls [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK441917\/."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1016\/j.jpeds.2012.11.069","article-title":"Nonsteroidal anti-inflammatory drugs are an important cause of acute kidney injury in children","volume":"162","author":"Misurac","year":"2013","journal-title":"J. Pediatr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3109","DOI":"10.1007\/s00467-023-05916-y","article-title":"NSAID-associated acute kidney injury in hospitalized children\u2014A prospective Pediatric Nephrology Research Consortium study","volume":"38","author":"Misurac","year":"2023","journal-title":"Pediatr. Nephrol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/pds.5385","article-title":"Nonsteroidal anti-inflammatory drugs associated acute kidney injury in hospitalized children: A systematic review and meta-analysis","volume":"31","author":"Gong","year":"2022","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e047059","DOI":"10.1136\/bmjopen-2020-047059","article-title":"Aetiology, course and treatment of acute tubulointerstitial nephritis in paediatric patients: A cross-sectional web-based survey","volume":"11","author":"Aksenova","year":"2021","journal-title":"BMJ Open"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s00467-025-06909-9","article-title":"From survival to surveillance: The long-term kidney legacy of preterm birth","volume":"41","author":"Vidal","year":"2025","journal-title":"Pediatr. Nephrol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/S0140-6736(17)30576-7","article-title":"A developmental approach to the prevention of hypertension and kidney disease: A report from the Low Birth Weight and Nephron Number Working Group","volume":"390","author":"Luyckx","year":"2017","journal-title":"Lancet"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6847","DOI":"10.1021\/acs.jmedchem.0c00225","article-title":"Albumin-Based Transport of Nonsteroidal Anti-Inflammatory Drugs in Mammalian Blood Plasma","volume":"63","author":"Czub","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Clav\u00e9, S., Rousset-Rouvi\u00e8re, C., Daniel, L., and Tsimaratos, M. (2019). The Invisible Threat of Non-steroidal Anti-inflammatory Drugs for Kidneys. Front. Pediatr., 7.","DOI":"10.3389\/fped.2019.00520"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/j.0306-5251.2004.2188.x","article-title":"Drug combinations and impaired renal function\u2014The \u2018triple whammy\u2019","volume":"59","author":"Loboz","year":"2005","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/j.2040-4603.2014.tb00544.x","article-title":"Fever, immunity, and molecular adaptations","volume":"4","author":"Hasday","year":"2014","journal-title":"Compr. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1007\/s11096-015-0184-2","article-title":"NSAIDs in paediatrics: Caution with varicella!","volume":"37","author":"Durand","year":"2015","journal-title":"Int. J. Clin. Pharm."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"227","DOI":"10.2165\/00002018-200528030-00004","article-title":"Tolerability of paracetamol","volume":"28","author":"Graham","year":"2005","journal-title":"Drug Saf."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.therap.2025.02.012","article-title":"Impact d\u00e9l\u00e9t\u00e8re d\u2019un anti-inflammatoire non st\u00e9ro\u00efdien pris pour fi\u00e8vre ou douleur aigu\u00eb en cas d\u2019infection streptococcique [Deleterious impact of a non-steroidal anti-inflammatory taken for fever or acute pain in case of streptococcal infection]","volume":"80","author":"Micallef","year":"2025","journal-title":"Therapie"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.jped.2015.04.007","article-title":"Analysis of analgesic, antipyretic, and nonsteroidal anti-inflammatory drug use in pediatric prescriptions","volume":"92","author":"Ferreira","year":"2016","journal-title":"J. Pediatr."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s12325-019-01144-9","article-title":"Ibuprofen safety at the Golden anniversary: Are all NSAIDs the same? A Narrative Review","volume":"37","author":"Varrassi","year":"2020","journal-title":"Adv. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s40121-023-00899-7","article-title":"Global Prevalence of Varicella-Associated Complications: A Systematic Review and Meta-Analysis","volume":"13","author":"Shah","year":"2024","journal-title":"Infect. Dis. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.jpeds.2016.05.025","article-title":"Nonsteroidal Anti-Inflammatory Drug without Antibiotics for Acute Viral Infection Increases the Empyema Risk in Children: A Matched Case-Control Study","volume":"175","author":"Ferroni","year":"2016","journal-title":"J. Pediatr."},{"key":"ref_65","unstructured":"Taylor, N.P. (2025, December 22). EU Regulatory Roundup: France\u2019s ANSM Warns About NSAIDs Following Safety Review. Roundups, Available online: https:\/\/www.raps.org\/news-and-articles\/news-articles\/2019\/4\/eu-regulatory-roundup-frances-ansm-warns-about-n."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1097\/QCO.0000000000000160","article-title":"The roles of injury and nonsteroidal antiinflammatory drugs in the development and outcomes of severe group A streptococcal soft tissue infections","volume":"28","author":"Bryant","year":"2015","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1542\/peds.103.4.783","article-title":"A case\u2013control study of necrotizing fasciitis during primary varicella","volume":"103","author":"Zerr","year":"1999","journal-title":"Pediatrics"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1542\/peds.107.5.1108","article-title":"Invasive group A streptococcal infection and nonsteroidal antiinflammatory drug use among children with primary varicella","volume":"107","author":"Lesko","year":"2001","journal-title":"Pediatrics"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.3201\/eid1107.040900","article-title":"Risk factors for pediatric invasive group A streptococcal disease","volume":"11","author":"Factor","year":"2005","journal-title":"Emerg. Infect. Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/j.1365-2125.2007.02997.x","article-title":"Nonsteroidal anti-inflammatory drug use and the risk of severe skin and soft tissue complications in patients with varicella or zoster disease","volume":"65","author":"Mikaeloff","year":"2008","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"179","DOI":"10.2165\/11532890-000000000-00000","article-title":"Hospitalization for severe bacterial infections in children after exposure to NSAIDs: A prospective adverse drug reaction reporting study","volume":"30","author":"Leroy","year":"2010","journal-title":"Clin. Drug Investig."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e33","DOI":"10.1016\/j.ejim.2017.03.004","article-title":"Bacterial infections and NSAIDs exposure? Seek septic complications","volume":"41","author":"Boutoille","year":"2017","journal-title":"Eur. J. Intern. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"104716","DOI":"10.1016\/j.idnow.2023.104716","article-title":"Does the use of antipyretics prolong illness? A systematic review of the literature and meta-analysis on the effects of antipyretics in acute upper and lower respiratory tract infections","volume":"53","author":"Nicholas","year":"2023","journal-title":"Infect. Dis. Now"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e077365","DOI":"10.1136\/bmjopen-2023-077365","article-title":"NSAID prescribing and adverse outcomes in common infections: A population-based cohort study","volume":"14","author":"Stuart","year":"2024","journal-title":"BMJ Open"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.anorl.2019.10.004","article-title":"Ibuprofen as risk-factor for complications of acute anterior sinusitis in children","volume":"137","author":"Nicollas","year":"2020","journal-title":"Eur. Ann. Otorhinolaryngol. Head Neck Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1093\/fampra\/cmy111","article-title":"Non-steroids anti-inflammatory drugs and risk of peritonsillar abscess in pharyngitis: A French longitudinal study in primary care","volume":"36","author":"Piroulas","year":"2019","journal-title":"Fam. Pract."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s10096-016-2770-1","article-title":"Is there an association between prior anti-inflammatory drug exposure and occurrence of peritonsillar abscess (PTA)? A national multicenter prospective observational case-control study","volume":"36","author":"Lepelletier","year":"2017","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1111\/j.1651-2227.2010.01734.x","article-title":"Prevalence and risk factors of suppurative complications in children with pneumonia","volume":"99","author":"Desrumaux","year":"2010","journal-title":"Acta Paediatr."},{"key":"ref_79","first-page":"230","article-title":"Risk factors for the development of pleural empyema in children","volume":"49","author":"Elemraid","year":"2014","journal-title":"Pediatr. Pulmonol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1111\/crj.12524","article-title":"Risk factors for local complications in children with community-acquired pneumonia","volume":"12","author":"Krenke","year":"2018","journal-title":"Clin. Respir. J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1378\/chest.09-3102","article-title":"Nonsteroidal antiinflammatory drugs may affect the presentation and course of community-acquired pneumonia","volume":"139","author":"Voiriot","year":"2011","journal-title":"Chest"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"26","DOI":"10.2340\/00015555-0333","article-title":"Bacterial skin infections in children hospitalized with varicella: A possible negative impact of non-steroidal anti-inflammatory drugs?","volume":"88","author":"Dubos","year":"2008","journal-title":"Acta Derm. Venereol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"202","DOI":"10.3201\/eid1402.070888","article-title":"Severe Streptococcus pyogenes infections, United Kingdom, 2003\u20132004","volume":"14","author":"Lamagni","year":"2008","journal-title":"Emerg. Infect. Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e063023","DOI":"10.1136\/bmjopen-2022-063023","article-title":"Prognostic factors for streptococcal toxic shock syndrome: Systematic review and meta-analysis","volume":"12","author":"Bartoszko","year":"2022","journal-title":"BMJ Open"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"5113","DOI":"10.1111\/bcp.15512","article-title":"Prevalence of NSAID use among people with COVID-19 and the association with COVID-19-related outcomes: Systematic review and meta-analysis","volume":"88","author":"Zhao","year":"2022","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1186\/s13052-021-01132-2","article-title":"Treatment of children with COVID-19: Update of the Italian Society of Pediatric Infectious Diseases position paper","volume":"47","author":"Venturini","year":"2021","journal-title":"Ital. J. Pediatr."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"m1086","DOI":"10.1136\/bmj.m1086","article-title":"COVID-19: Ibuprofen should not be used for managing symptoms, say doctors and scientists","volume":"368","author":"Day","year":"2020","journal-title":"BMJ"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1093\/bmb\/ldw019","article-title":"Repurposing drugs for treatment of tuberculosis: A role for non-steroidal anti-inflammatory drugs","volume":"118","author":"Maitra","year":"2016","journal-title":"Br. Med. Bull."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Wu, C.W., Wu, J.Y., Lee, M.G., Lai, C.C., Wu, I.L., Tsai, Y.W., Chang, S.S., and Lee, C.C. (2017). Risk of incident active tuberculosis disease in patients treated with non-steroidal anti-inflammatory drugs: A population-based study. BMC Pulm. Med., 17.","DOI":"10.1186\/s12890-017-0425-3"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"102418","DOI":"10.1016\/j.tube.2023.102418","article-title":"Exploring COX-2 inhibitors in tuberculosis: A whole-blood model approach for immune response and adjunct therapy evaluation","volume":"143","author":"Carranza","year":"2023","journal-title":"Tuberculosis"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1093\/infdis\/jiad390","article-title":"The Cyclooxygenase 2 Inhibitor Etoricoxib as Adjunctive Therapy in Tuberculosis Impairs Macrophage Control of Mycobacterial Growth","volume":"229","author":"Nore","year":"2024","journal-title":"J. Infect. Dis."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1177\/106002809402800306","article-title":"Pharmacokinetics of zidovudine and acetaminophen in a patient on chronic acetaminophen therapy","volume":"28","author":"Burger","year":"1994","journal-title":"Ann. Pharmacother."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.3851\/IMP1468","article-title":"Non-steroidal anti-inflammatory drugs increase the antiretroviral activity of nucleoside reverse transcriptase inhibitors in HIV type-1-infected T-lymphocytes: Role of multidrug resistance protein 4","volume":"14","author":"Clemente","year":"2009","journal-title":"Antivir. Ther."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"567","DOI":"10.5414\/CNP71567","article-title":"Tenofovir-related acute kidney injury and proximal tubule dysfunction precipitated by diclofenac: A case of drug-drug interaction","volume":"71","author":"Morelle","year":"2009","journal-title":"Clin. Nephrol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1111\/jvh.13201","article-title":"Use of cyclooxygenase inhibitor and the risk of hepatocellular carcinoma in patients with chronic hepatitis B: A nested case-control study using a nationwide population-based data","volume":"27","author":"Cho","year":"2020","journal-title":"J. Viral Hepat."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"E22","DOI":"10.1055\/a-0978-4881","article-title":"NSAIDs-induced upper gastrointestinal bleeding in hepatitis B virus-positive patient with acute kidney injury\u2014Nonocclusive mesenteric ischemia","volume":"52","author":"Lisotti","year":"2020","journal-title":"Endoscopy"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"584","DOI":"10.14309\/ajg.0000000000002941","article-title":"Association of Acetaminophen (Paracetamol) Use with Severity and Outcomes in Patients with Viral Hepatitis-Associated Acute Liver Failure","volume":"120","author":"Lee","year":"2025","journal-title":"Am. J. Gastroenterol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1056\/NEJMoa003199","article-title":"Cyclooxygenase inhibitors and the antiplatelet effects of aspirin","volume":"345","author":"Reilly","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/j.1552-4604.1995.tb04050.x","article-title":"Effects of nonsteroidal antiinflammatory drugs on platelet function and systemic hemostasis","volume":"35","author":"Schafer","year":"1995","journal-title":"J. Clin. Pharmacol."},{"key":"ref_100","first-page":"CD003591","article-title":"Nonsteroidal anti-inflammatory drugs and perioperative bleeding in paediatric tonsillectomy","volume":"7","author":"Lewis","year":"2013","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1080\/17474086.2021.1935852","article-title":"Pain management in people with hemophilia in childhood and young adulthood","volume":"14","year":"2021","journal-title":"Expert Rev. Hematol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jpain.2015.12.008","article-title":"Management of postoperative pain: A clinical practice guideline from the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists\u2019 Committee on Regional Anesthesia, Executive Committee, and Administrative Council","volume":"17","author":"Chou","year":"2016","journal-title":"J. Pain"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1111\/j.1365-263X.2006.00806.x","article-title":"A comparison of paracetamol, ibuprofen or their combination for pain relief following extractions in children under general anaesthesia: A randomized controlled trial","volume":"17","author":"Gazal","year":"2007","journal-title":"Int. J. Paediatr. Dent."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1093\/bja\/88.1.72","article-title":"Double-blind, placebo-controlled analgesic study of ibuprofen or rofecoxib in combination with paracetamol for tonsillectomy in children","volume":"88","author":"Pickering","year":"2002","journal-title":"Br. J. Anaesth."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1111\/j.1460-9592.2011.03644.x","article-title":"Explaining the acetaminophen-ibuprofen analgesic interaction using a response surface model","volume":"21","author":"Hannam","year":"2011","journal-title":"Paediatr. Anaesth."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1007\/s12630-013-0043-3","article-title":"Randomized comparison between the combination of acetaminophen and ibuprofen and each constituent alone for analgesia following tonsillectomy in children","volume":"60","author":"Merry","year":"2013","journal-title":"Can. J. Anaesth."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1542\/peds.2014-1906","article-title":"Morphine or Ibuprofen for post-tonsillectomy analgesia: A randomized trial","volume":"135","author":"Kelly","year":"2015","journal-title":"Pediatrics"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1111\/pan.13517","article-title":"Analgesic effectiveness, pharmacokinetics, and safety of a paracetamol\/ibuprofen fixed-dose combination in children undergoing adenotonsillectomy: A randomized, single-blind, parallel group trial","volume":"28","author":"Playne","year":"2018","journal-title":"Paediatr. Anaesth."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1056\/NEJMoa1515990","article-title":"Acetaminophen versus Ibuprofen in Young Children with Mild Persistent Asthma","volume":"375","author":"Sheehan","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"E20","DOI":"10.1542\/peds.109.2.e20","article-title":"Asthma morbidity after the short-term use of ibuprofen in children","volume":"109","author":"Lesko","year":"2002","journal-title":"Pediatrics"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Baxter, L., Cobo, M.M., Bhatt, A., Slater, R., Sanni, O., and Shinde, N. (2024). The association between ibuprofen administration in children and the risk of developing or exacerbating asthma: A systematic review and meta-analysis. BMC Pulm. Med., 24.","DOI":"10.1186\/s12890-024-03179-3"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1177\/1060028016678006","article-title":"Association of Acetaminophen and Ibuprofen Use with Wheezing in Children with Acute Febrile Illness","volume":"51","author":"Matok","year":"2017","journal-title":"Ann. Pharmacother."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Sherbash, M., Furuya-Kanamori, L., Nader, J.D., and Thalib, L. (2020). 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., 20.","DOI":"10.1186\/s12890-020-1102-5"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.jaci.2014.07.065","article-title":"Prenatal and infant exposure to acetaminophen and ibuprofen and the risk for wheeze and asthma in children","volume":"135","author":"Sordillo","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1001\/jama.2024.3172","article-title":"Acetaminophen Use During Pregnancy and Children\u2019s Risk of Autism, ADHD, and Intellectual Disability","volume":"331","author":"Ahlqvist","year":"2024","journal-title":"JAMA"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"e088141","DOI":"10.1136\/bmj-2025-088141","article-title":"Maternal Paracetamol (Acetaminophen) Use During Pregnancy and Risk of Autism Spectrum Disorder and Attention Deficit\/Hyperactivity Disorder in Offspring: Umbrella Review of Systematic Reviews","volume":"391","author":"Sheikh","year":"2025","journal-title":"BMJ"},{"key":"ref_117","unstructured":"American College of Obstetricians and Gynecologists (2025). Acetaminophen Use in Pregnancy and Neurodevelopmental Outcomes. Practice Advisory, American College of Obstetricians and Gynecologists. Available online: https:\/\/www.acog.org\/clinical\/clinical-guidance\/practice-advisory\/articles\/2025\/09\/acetaminophen-use-in-pregnancy-and-neurodevelopmental-outcomes."},{"key":"ref_118","unstructured":"American Academy of Pediatrics (2025). Acetaminophen Is Safe for Children When Taken as Directed: No Link to Autism, American Academy of Pediatrics. Available online: https:\/\/www.aap.org\/en\/news-room\/fact-checked\/acetaminophen-is-safe-for-children-when-taken-as-directed-no-link-to-autism\/."},{"key":"ref_119","unstructured":"Society for Maternal-Fetal Medicine (2025). SMFM Statement on Acetaminophen Use During Pregnancy and Autism, Society for Maternal-Fetal Medicine. Available online: https:\/\/www.smfm.org\/news\/smfm-statement-on-acetaminophen-use-during-pregnancy-and-autism."},{"key":"ref_120","unstructured":"Medicines and Healthcare Products Regulatory Agency (2025, December 22). MHRA Confirms Taking Paracetamol During Pregnancy Remains Safe and There Is No Evidence It Causes Autism in Children, Available online: https:\/\/www.gov.uk\/government\/news\/mhra-confirms-taking-paracetamol-during-pregnancy-remains-safe-and-there-is-no-evidence-it-causes-autism-in-children."},{"key":"ref_121","unstructured":"Italian Medicines Agency (AIFA) (2025, December 22). Uso del Paracetamolo in Gravidanza: Confermate le Raccomandazioni Europee, Available online: https:\/\/www.aifa.gov.it\/en\/-\/uso-del-paracetamolo-in-gravidanza-confermate-le-raccomandazioni-europee."},{"key":"ref_122","unstructured":"World Health Organization (2025). WHO Statement on Autism-Related Issues, World Health Organization. Available online: https:\/\/www.who.int\/news\/item\/24-09-2025-who-statement-on-autism-related-issues."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"e20171002","DOI":"10.1542\/peds.2017-1002","article-title":"Pain Assessment and Treatment in Children with Significant Impairment of the Central Nervous System","volume":"139","author":"Hauer","year":"2017","journal-title":"Pediatrics"},{"key":"ref_124","unstructured":"World Health Organization (2012). WHO Guidelines on the Pharmacological Treatment of Persisting Pain in Children with Medical Illnesses, World Health Organization. Available online: https:\/\/iris.who.int\/items\/0f4115f0-06dd-4e27-9901-9347db5bba15."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1097\/CCM.0b013e318206cc8f","article-title":"Acute Liver Failure after Recommended Doses of Acetaminophen in Patients with Myopathies","volume":"39","author":"Ceelie","year":"2011","journal-title":"Crit. Care Med."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1002\/bcp.70028","article-title":"Paracetamol and Its Metabolites in Children and Adults with Spinal Muscular Atrophy\u2014A Population Pharmacokinetic Model","volume":"91","author":"Zhao","year":"2025","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e015404","DOI":"10.1136\/bmjopen-2016-015404","article-title":"Guidelines for the symptomatic management of fever in children: Systematic review of the literature and quality appraisal with AGREE II","volume":"7","author":"Chiappini","year":"2017","journal-title":"BMJ Open"},{"key":"ref_128","unstructured":"World Health Organization (2013). Pocket Book of Hospital Care for Children: Guidelines for the Management of Common Childhood Illnesses, World Health Organization. [2nd ed.]. Available online: https:\/\/www.who.int\/publications\/i\/item\/978-92-4-154837-3."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Anderson, B.J., and Cort\u00ednez, L.I. (2023). Perioperative Acetaminophen Dosing in Obese Children. Children, 10.","DOI":"10.3390\/children10040625"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1001\/archpedi.160.2.197","article-title":"Antipyretic Treatment in Young Children with Fever: Acetaminophen, Ibuprofen, or Both Alternating in a Randomized, Double-Blind Study","volume":"160","author":"Sarrell","year":"2006","journal-title":"Arch. Pediatr. Adolesc. Med."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"289","DOI":"10.2223\/JPED.2204","article-title":"Alternating Antipyretics in the Treatment of Fever in Children: A Systematic Review of Randomized Clinical Trials","volume":"88","author":"Pereira","year":"2012","journal-title":"J. Pediatr."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1002\/ebch.1979","article-title":"Cochrane in Context: Combined and Alternating Paracetamol and Ibuprofen Therapy for Febrile Children","volume":"9","author":"Wong","year":"2014","journal-title":"Evid. Based Child. Health"},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Trippella, G., Ciarci\u00e0, M., de Martino, M., and Chiappini, E. (2019). Prescribing Controversies: An Updated Review and Meta-Analysis on Combined\/Alternating Use of Ibuprofen and Paracetamol in Febrile Children. Front. Pediatr., 7.","DOI":"10.3389\/fped.2019.00217"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1186\/s13052-024-01791-x","article-title":"Paracetamol and Ibuprofen Fixed-Dose Combination for the Management of Acute Mild-to-Moderate Pain in Children: Strengthening and Enhancing of Result of Nominal Group Technique through Delphi Consensus","volume":"50","author":"Castagno","year":"2024","journal-title":"Ital. J. Pediatr."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s40263-020-00777-7","article-title":"Efficacy and Safety of Ibuprofen Plus Paracetamol in a Fixed-Dose Combination for Acute Postoperative Pain in Adults: Meta-Analysis and a Trial Sequential Analysis","volume":"35","author":"Abushanab","year":"2021","journal-title":"CNS Drugs"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1136\/adc.2005.087874","article-title":"Randomised Controlled Trial of Combined Paracetamol and Ibuprofen for Fever","volume":"91","author":"Coppens","year":"2006","journal-title":"Arch. Dis. Child."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1136\/archdischild-2011-300424","article-title":"Systematic Review of Studies Comparing Combined Treatment with Paracetamol and Ibuprofen, with Either Drug Alone","volume":"96","author":"Purssell","year":"2011","journal-title":"Arch. Dis. Child."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1080\/00325481.2021.1912466","article-title":"Safety and Tolerability of Fixed-Dose Combinations of Ibuprofen and Acetaminophen: Pooled Analysis of Phase 1\u20133 Clinical Trials","volume":"133","author":"Su","year":"2021","journal-title":"Postgrad. Med."},{"key":"ref_139","unstructured":"European Medicines Agency (2019). Paracetamol\/Ibuprofen 500 mg\/150 mg\u2014Article 29(4) Referral: Annex II, European Medicines Agency. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/referral\/paracetamolibuprofen-500mg150mg-article-294-referral-annex-ii_en.pdf."},{"key":"ref_140","unstructured":"Italian Medicines Agency (AIFA) (2025, December 22). Summary of Product Characteristics\u2014Tachifenekid 32 mg\/mL + 9.6 mg\/mL Oral Suspension, Available online: https:\/\/api.aifa.gov.it\/aifa-bdf-eif-be\/1.0.0\/organizzazione\/219\/farmaci\/49580\/stampati?ts=RCP."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/13\/1\/71\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T05:11:25Z","timestamp":1767417085000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/13\/1\/71"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,1]]},"references-count":140,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["children13010071"],"URL":"https:\/\/doi.org\/10.3390\/children13010071","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,1]]}}}