{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T20:54:41Z","timestamp":1785876881284,"version":"3.56.0"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017594","name":"Medical Science and Technology Project of Zhejiang Province","doi-asserted-by":"publisher","award":["2021KY1034"],"award-info":[{"award-number":["2021KY1034"]}],"id":[{"id":"10.13039\/501100017594","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Influenza virus is a widespread pathogen that poses significant health risks to humans. Oseltamivir and Baloxavir Marboxil are commonly utilized medications for both treating and preventing influenza infections. Despite their widespread use, there remains a need to thoroughly investigate their safety profiles and potential adverse reactions.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Objective<\/jats:title>\n<jats:p>This study aims to comprehensively analyze the adverse events associated with oseltamivir and baloxavir marboxil in real-world clinical settings, with the goal of assessing their safety and potential risks in the management of influenza virus infections.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We conducted a retrospective analysis utilizing data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database, spanning from the first quarter of 2004 to the third quarter of 2023. The analysis encompassed examination of drug utilization patterns, types of adverse events reported, patient demographics, and other pertinent factors.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>From the first quarter of 2004 to the third quarter of 2023, FAERS collected over 17,035,521 adverse event reports (AE reports). Among these reports, there were 38,384 reports associated with oseltamivir, and 3,364 reports associated with baloxavir marboxil. Oseltamivir and Baloxavir Marboxil were primarily used for the treatment of influenza virus infections, accounting for 62.43% and 67.49% of their total usage, respectively. The main adverse reactions reported for oseltamivir were vomiting (case reports = 1402) followed by confusional state (case reports = 353), while for baloxavir marboxil, adverse reactions mainly centered around off-label use (case reports = 378) and intentional product use issues (case reports = 278). In terms of systemic adverse reactions, oseltamivir primarily affected psychiatric disorders (n = 45), whereas baloxavir marboxil mainly impacted the gastrointestinal system (n = 7). Additionally, regarding adverse reactions in pregnant women, the occurrence of normal newborns was a significant signal for oseltamivir, suggesting a certain level of safety during maternal use. Conversely, reports of adverse reactions such as respiratory arrest were documented for baloxavir marboxil, while no such reports were associated with oseltamivir.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>This study provides a comprehensive analysis of the adverse reactions observed with the clinical use of oseltamivir and baloxavir marboxil, revealing the safety and risks associated with these two drugs in the treatment and prevention of influenza virus infections. Firstly, although both drugs are used for influenza treatment, they exhibit different types of adverse reactions. Oseltamivir predominantly affects the psychiatric system, while baloxavir marboxil primarily impacts the gastrointestinal system. Additionally, oseltamivir demonstrates a certain level of safety for use in pregnant women, while reports of adverse reactions such as respiratory arrest are associated with baloxavir marboxil. Despite the clinical significance of this study, limitations exist due to the voluntary nature of data reporting, which may lead to reporting biases and incomplete information. Future research could employ more rigorous prospective study designs, integrating clinical trials and epidemiological studies, to more accurately assess the safety risks of oseltamivir and baloxavir marboxil.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0308998","type":"journal-article","created":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T18:27:27Z","timestamp":1731522447000},"page":"e0308998","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Adverse events associated with oseltamivir and baloxavir marboxil in against influenza virus therapy: A pharmacovigilance study using the FAERS database"],"prefix":"10.1371","volume":"19","author":[{"given":"Yixia","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9834-4108","authenticated-orcid":true,"given":"Liuyin","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolong","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindan","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoming","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjiang","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,11,13]]},"reference":[{"issue":"9244","key":"pone.0308998.ref001","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1016\/S0140-6736(00)03232-3","article-title":"Clinical progression, survival, and immune recovery during antiretroviral therapy in patients with HIV-1 and hepatitis C virus coinfection: the Swiss HIV Cohort Study","volume":"356","author":"G Greub","year":"2000","journal-title":"Lancet"},{"key":"pone.0308998.ref002","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.ijbiomac.2021.01.076","article-title":"Trends and strategies to combat viral infections: A review on FDA approved antiviral drugs","volume":"172","author":"DR Tompa","year":"2021","journal-title":"Int J Biol Macromol"},{"key":"pone.0308998.ref003","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1146\/annurev.pathmechdis.3.121806.154316","article-title":"The pathology of influenza virus infections","volume":"3","author":"JK Taubenberger","year":"2008","journal-title":"Annu Rev Pathol"},{"key":"pone.0308998.ref004","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/978-1-4614-0980-9_9","article-title":"Influenza virus entry","volume":"726","author":"M. Luo","year":"2012","journal-title":"Adv Exp Med Biol"},{"issue":"SI-1","key":"pone.0308998.ref005","doi-asserted-by":"crossref","first-page":"515","DOI":"10.3906\/sag-2004-133","article-title":"Understanding dynamics of pandemics.","volume":"50","author":"L Akin","year":"2020","journal-title":"Turk J Med Sci."},{"issue":"5","key":"pone.0308998.ref006","doi-asserted-by":"crossref","DOI":"10.3390\/ijerph19053018","article-title":"Antiviral Drugs in Influenza","volume":"19","author":"M Swierczynska","year":"2022","journal-title":"Int J Environ Res Public Health"},{"issue":"9206","key":"pone.0308998.ref007","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/S0140-6736(99)11433-8","article-title":"Influenza virus neuraminidase inhibitors","volume":"355","author":"LV Gubareva","year":"2000","journal-title":"Lancet"},{"issue":"6128","key":"pone.0308998.ref008","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1126\/science.1232552","article-title":"Mechanism-based covalent neuraminidase inhibitors with broad-spectrum influenza antiviral activity","volume":"340","author":"JH Kim","year":"2013","journal-title":"Science"},{"issue":"11","key":"pone.0308998.ref009","doi-asserted-by":"crossref","first-page":"e223261","DOI":"10.1001\/jamapediatrics.2022.3261","article-title":"Association of Early Oseltamivir With Improved Outcomes in Hospitalized Children With Influenza, 2007\u20132020","volume":"176","author":"PS Walsh","year":"2022","journal-title":"JAMA Pediatr"},{"issue":"1","key":"pone.0308998.ref010","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1001\/jamainternmed.2023.0699","article-title":"Evaluation of Oseltamivir Used to Prevent Hospitalization in Outpatients With Influenza: A Systematic Review and Meta-Analysis.","volume":"184","author":"R Hanula","year":"2024","journal-title":"JAMA Intern Med"},{"issue":"10217","key":"pone.0308998.ref011","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/S0140-6736(19)32982-4","article-title":"Oseltamivir plus usual care versus usual care for influenza-like illness in primary care: an open-label, pragmatic, randomised controlled trial","volume":"395","author":"CC Butler","year":"2020","journal-title":"Lancet"},{"key":"pone.0308998.ref012","article-title":"FDA approves new drug to treat influenza.","author":"Food and Drug Administration","year":"2019"},{"issue":"1","key":"pone.0308998.ref013","first-page":"9","article-title":"Xofluza (Baloxavir Marboxil) for the Treatment Of Acute Uncomplicated Influenza","volume":"44","author":"N KE","year":"2019","journal-title":"P T."},{"issue":"6","key":"pone.0308998.ref014","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1007\/s40265-018-0899-1","article-title":"Baloxavir: First Global Approval.","volume":"78","author":"YA Heo","year":"2018","journal-title":"Drugs"},{"issue":"10","key":"pone.0308998.ref015","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1002\/pds.1459","article-title":"Applying quantitative methods for detecting new drug safety signals in pharmacovigilance national database.","volume":"16","author":"G Shalviri","year":"2007","journal-title":"Pharmacoepidemiol Drug Saf"},{"issue":"7","key":"pone.0308998.ref016","doi-asserted-by":"crossref","first-page":"796","DOI":"10.7150\/ijms.6048","article-title":"Data mining of the public version of the FDA Adverse Event Reporting System.","volume":"10","author":"T Sakaeda","year":"2013","journal-title":"Int J Med Sci"},{"issue":"6","key":"pone.0308998.ref017","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.jbi.2011.07.005","article-title":"Identifying potential adverse effects using the web: a new approach to medical hypothesis generation.","volume":"44","author":"A Benton","year":"2011","journal-title":"J Biomed Inform"},{"issue":"1","key":"pone.0308998.ref018","doi-asserted-by":"crossref","first-page":"3116","DOI":"10.1038\/s41598-020-60068-5","article-title":"Assessment of adverse events related to anti-influenza neuraminidase inhibitors using the FDA adverse event reporting system and online patient reviews.","volume":"10","author":"N Han","year":"2020","journal-title":"Sci Rep."},{"issue":"8","key":"pone.0308998.ref019","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1007\/s40264-021-01082-y","article-title":"Reporting of Thromboembolic Events with JAK Inhibitors: Analysis of the FAERS Database 2010\u20132019.","volume":"44","author":"J Setyawan","year":"2021","journal-title":"Drug Saf."},{"key":"pone.0308998.ref020","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.meegid.2018.08.007","article-title":"Transmissibility and severity of influenza virus by subtype","volume":"65","author":"JE Park","year":"2018","journal-title":"Infect Genet Evol"},{"key":"pone.0308998.ref021","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/B978-0-12-405880-4.00006-8","article-title":"Influenza virus resistance to antiviral therapy.","volume":"67","author":"E van der Vries","year":"2013","journal-title":"Adv Pharmacol"},{"key":"pone.0308998.ref022","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.jad.2023.11.025","article-title":"Safety assessment of Brexpiprazole: Real-world adverse event analysis from the FAERS database","volume":"346","author":"Y Jiang","year":"2024","journal-title":"J Affect Disord"},{"issue":"8","key":"pone.0308998.ref023","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1080\/14740338.2023.2204228","article-title":"High risks adverse events associated with trastuzumab emtansine and trastuzumab deruxtecan for the treatment of HER2-positive\/mutated malignancies: a pharmacovigilance study based on the FAERS database.","volume":"22","author":"P Ma","year":"2023","journal-title":"Expert Opin Drug Saf"},{"key":"pone.0308998.ref024","doi-asserted-by":"crossref","first-page":"851246","DOI":"10.3389\/fphar.2022.851246","article-title":"Adverse Event Profiles of PARP Inhibitors: Analysis of Spontaneous Reports Submitted to FAERS.","volume":"13","author":"X Tian","year":"2022","journal-title":"Front Pharmacol."},{"issue":"1","key":"pone.0308998.ref025","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1136\/ard.2011.200087","article-title":"Paracetamol and cyclooxygenase inhibition: is there a cause for concern?","volume":"71","author":"B Hinz","year":"2012","journal-title":"Ann Rheum Dis"},{"key":"pone.0308998.ref026","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.redox.2018.04.019","article-title":"Mechanisms of acetaminophen-induced liver injury and its implications for therapeutic interventions","volume":"17","author":"M Yan","year":"2018","journal-title":"Redox Biol"},{"issue":"2","key":"pone.0308998.ref027","doi-asserted-by":"crossref","first-page":"85","DOI":"10.4103\/sjg.sjg_406_21","article-title":"N-acetylcysteine for non-acetaminophen induced acute liver failure: A review","volume":"28","author":"SX Jiang","year":"2022","journal-title":"Saudi J Gastroenterol"},{"issue":"2","key":"pone.0308998.ref028","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":"Y Ishitsuka","year":"2020","journal-title":"Biol Pharm Bull"},{"issue":"1","key":"pone.0308998.ref029","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1007\/s12011-022-03114-9","article-title":"Acetaminophen-Induced Nephrotoxicity: Suppression of Apoptosis and Endoplasmic Reticulum Stress Using Boric Acid","volume":"201","author":"FK Coban","year":"2023","journal-title":"Biol Trace Elem Res"},{"issue":"1","key":"pone.0308998.ref030","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/s12931-019-1078-y","article-title":"Efficacy and safety profile of mucolytic\/antioxidant agents in chronic obstructive pulmonary disease: a comparative analysis across erdosteine, carbocysteine, and N-acetylcysteine.","volume":"20","author":"P Rogliani","year":"2019","journal-title":"Respir Res."},{"issue":"6","key":"pone.0308998.ref031","doi-asserted-by":"crossref","DOI":"10.3390\/pharmaceutics14061261","article-title":"Clinical Efficacy of Carbocysteine in COPD: Beyond the Mucolytic Action.","volume":"14","author":"E Pace","year":"2022","journal-title":"Pharmaceutics."},{"issue":"23","key":"pone.0308998.ref032","doi-asserted-by":"crossref","first-page":"4030","DOI":"10.3889\/oamjms.2019.697","article-title":"Effects of a Long-Term Use of Carbocysteine on Frequency and Duration of Exacerbations in Patients with Bronchiectasis.","volume":"7","author":"J Minov","year":"2019","journal-title":"Open Access Maced J Med Sci."},{"issue":"9979","key":"pone.0308998.ref033","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1016\/S0140-6736(14)62449-1","article-title":"Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials","volume":"385","author":"J Dobson","year":"2015","journal-title":"Lancet"},{"issue":"4","key":"pone.0308998.ref034","article-title":"Neuraminidase inhibitors for preventing and treating influenza in adults and children.","volume":"2014","author":"T Jefferson","year":"2014","journal-title":"Cochrane Database Syst Rev."},{"issue":"3","key":"pone.0308998.ref035","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1080\/17460441.2019.1567487","article-title":"Successes, failures, and future prospects of prodrugs and their clinical impact.","volume":"14","author":"A Najjar","year":"2019","journal-title":"Expert Opin Drug Discov"},{"issue":"12","key":"pone.0308998.ref036","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1016\/j.jiac.2019.05.009","article-title":"Acute ischemic colitis with hematochezia related to baloxavir marboxil treatment for influenza A.","volume":"25","author":"N Kanai","year":"2019","journal-title":"J Infect Chemother"},{"issue":"8","key":"pone.0308998.ref037","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1053\/j.semperi.2014.08.015","article-title":"Oseltamivir for influenza in pregnancy.","volume":"38","author":"RH Beigi","year":"2014","journal-title":"Semin Perinatol."},{"issue":"8","key":"pone.0308998.ref038","doi-asserted-by":"crossref","first-page":"631","DOI":"10.2165\/11536370-000000000-00000","article-title":"Safety of oseltamivir in pregnancy: a review of preclinical and clinical data.","volume":"33","author":"B Donner","year":"2010","journal-title":"Drug Saf."},{"issue":"6","key":"pone.0308998.ref039","doi-asserted-by":"crossref","DOI":"10.1093\/bib\/bbab347","article-title":"Detection algorithms and attentive points of safety signal using spontaneous reporting systems as a clinical data source","volume":"22","author":"Y Noguchi","year":"2021","journal-title":"Brief Bioinform"},{"issue":"10","key":"pone.0308998.ref040","doi-asserted-by":"crossref","DOI":"10.3390\/pharmaceutics13101531","article-title":"Verification of the \"Upward Variation in the Reporting Odds Ratio Scores\" to Detect the Signals of Drug-Drug Interactions.","volume":"13","author":"Y Noguchi","year":"2021","journal-title":"Pharmaceutics."},{"issue":"6","key":"pone.0308998.ref041","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1007\/s40264-024-01423-7","article-title":"The REporting of A Disproportionality Analysis for DrUg Safety Signal Detection Using Individual Case Safety Reports in PharmacoVigilance (READUS-PV): Explanation and Elaboration.","volume":"47","author":"M Fusaroli","year":"2024","journal-title":"Drug Saf."},{"key":"pone.0308998.ref042","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.jclinepi.2021.06.022","article-title":"High prevalence of spin was found in pharmacovigilance studies using disproportionality analyses to detect safety signals: a meta-epidemiological study.","volume":"138","author":"A Mouffak","year":"2021","journal-title":"J Clin Epidemiol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0308998","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T18:27:42Z","timestamp":1731522462000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0308998"}},"subtitle":[],"editor":[{"given":"Naveen","family":"Kumar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,11,13]]},"references-count":42,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11,13]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0308998","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,13]]}}}