{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T18:48:03Z","timestamp":1768589283148,"version":"3.49.0"},"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82374311"],"award-info":[{"award-number":["82374311"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005891","name":"State Administration of Traditional Chinese Medicine of the People's Republic of China","doi-asserted-by":"publisher","award":["zyyzdxk-2023118"],"award-info":[{"award-number":["zyyzdxk-2023118"]}],"id":[{"id":"10.13039\/501100005891","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2022LZY016"],"award-info":[{"award-number":["ZR2022LZY016"]}],"id":[{"id":"10.13039\/501100007129","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>Objective<\/jats:title>\n                    <jats:p>Edaravone is a neuroprotective agent, but the characteristics of its adverse events (AEs) remain insufficiently explored. This study aims to examine AEs associated with edaravone use by analyzing real-world data from the FDA Adverse Event Reporting System (FAERS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective study extracted adverse event reports related to edaravone from the FAERS database, spanning from the second quarter of 2017 to the second quarter of 2024. Disproportionality analysis methods, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Bayesian Confidence Propagation Neural Network (BCPNN), were employed to detect AE signals associated with edaravone use.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 2,931 adverse event reports (AERs) in which edaravone was identified as the primary suspected drug, 86 preferred terms (PTs) and 20 system organ classes (SOCs) were included. At the PTs level, the significant drug-related adverse events were death (n\u2009=\u2009589, ROR\u2009=\u20098.64), disease progression (n\u2009=\u2009266, ROR\u2009=\u200928.26) and drug ineffectiveness (n\u2009=\u2009252, ROR\u2009=\u20092.16). Additionally, rare but notably strong adverse event signals were observed, including thrombosis at the catheter site thrombosi, gastric fistula, and vein collapse.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our research found that edaravone has some overlooked adverse reactions. Further epidemiological studies are needed to more comprehensively explore and assess the risk-benefit profile of edaravone.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0335362","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T17:29:47Z","timestamp":1761240587000},"page":"e0335362","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Safety assessment of Edaravone: A real-world adverse event analysis based on the FAERS 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Jiang","year":"2024","journal-title":"J Affect Disord"},{"key":"pone.0335362.ref020","doi-asserted-by":"crossref","first-page":"3031","DOI":"10.2147\/DDDT.S81998","article-title":"Effect of database profile variation on drug safety assessment: an analysis of spontaneous adverse event reports of Japanese cases","volume":"9","author":"K Nomura","year":"2015","journal-title":"Drug Des Devel Ther"},{"key":"pone.0335362.ref021","doi-asserted-by":"crossref","first-page":"621691","DOI":"10.3389\/fphar.2021.621691","article-title":"Head-to-Head Comparison of Sedation and Somnolence Among 37 Antipsychotics in Schizophrenia, Bipolar Disorder, Major Depression, Autism Spectrum Disorders, Delirium, and Repurposed in COVID-19, Infectious Diseases, and Oncology From the FAERS, 2004-2020","volume":"12","author":"AR Eugene","year":"2021","journal-title":"Front 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Neurol"},{"issue":"7","key":"pone.0335362.ref034","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S1474-4422(17)30115-1","article-title":"Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial","volume":"16","author":"Group Writing","year":"2017","journal-title":"Lancet Neurol"},{"issue":"4","key":"pone.0335362.ref035","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1080\/146608202760839009","article-title":"Subjective experience and coping in ALS","volume":"3","author":"M Hecht","year":"2002","journal-title":"Amyotroph Lateral Scler Other Motor Neuron Disord"},{"issue":"2","key":"pone.0335362.ref036","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1111\/1460-6984.12357","article-title":"Speech deterioration in amyotrophic lateral sclerosis (ALS) after manifestation of bulbar symptoms","volume":"53","author":"T Makkonen","year":"2018","journal-title":"Int J 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