{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:01:20Z","timestamp":1792598480702,"version":"4.5.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T00:00:00Z","timestamp":1725580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>This study aimed to characterize the safety profiles of rivaroxaban-associated suspected adverse events by mining the Food and Drug Administration Adverse Event Reporting System (FAERS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A disproportionality analysis of spontaneously reported suspected adverse drug reactions (ADRs) was conducted. The reports in FAERS from 2014 to 2024 were compiled. Frequentist and Bayesian statistics were both applied to calculate drug-AE combinations in system organ classes and preferred-term levels. Reporting odds ratio (ROR), proportional reporting ratio (PRR), the Medicines and Healthcare products Regulatory Agency (MHRA), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) methods were analyzed and used to compare the suspected AEs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 77,384 ADR reports, 66,705 (86.20%) were serious rivaroxaban AE reports. The most common age group was above 65\u00a0years. The suspected adverse effects of rivaroxaban emerging for system organ classes (SOCs) primarily included \u201cGastrointestinal disorders\u201d; \u201cInjury, poisoning, and procedural complications\u201d, \u201cNervous system disorders\u201d and \u201cVascular disorders\u201d. Ranked by EBGM, the top signal strength of suspected AE signals of rivaroxaban under ROR algorithm at the preferred-term (PT) level were \u201cHaemorrhagic arteriovenous malformation\u201d (<jats:italic>N<\/jats:italic> = 571, ROR = 756.520, PRR = 754.029, Information Component (IC) = 7.197, Empirical Bayesian Geometric Mean (EBGM) = 146.725), \u201cGastrointestinal vascular malformation haemorrhagic\u201d (<jats:italic>N<\/jats:italic> = 197, ROR = 211.138, PRR = 210.950, IC = 6.614, EBGM = 97.923), and \u201cDiverticulum intestinal haemorrhagic\u201d (<jats:italic>N<\/jats:italic> = 722, ROR = 169.898, PRR = 169.210, IC = 6.458, EBGM = 97.920). Moreover, uncommon but significantly suspected AE signals, such as \u201cCoagulation factor X level increased\u201d, \u201cBasal ganglia haematoma\u201d, and \u201cProctitis haemorrhagic\u201d were observed. Notably, \u201cGastrointestinal haemorrhage\u201d (<jats:italic>N<\/jats:italic> = 13,436, ROR = 80.477, PRR = 74.460, IC = 5.729, EBGM = 53.042), \u201cUpper gastrointestinal haemorrhage\u201d(<jats:italic>N<\/jats:italic> = 2,872, ROR = 73.978, PRR = 72.797, IC = 5.706, EBGM = 52.198) and \u201cInternal haemorrhage\u201d (<jats:italic>N<\/jats:italic> = 2,368, ROR = 91.979, PRR = 80.899, IC = 5.813, EBGM = 56.212) exhibited relatively high occurrence rates and signal strengths. From 2014 to 2024, the IC values of rivaroxaban-associated suspected AEs for \u201cSurgical and medical procedures\u201d and \u201cCardiac disorders\u201d showed an annual increasing trend in the time-span analysis. Based on the various visulization plots, a key discovery is that \u201cGastrointestinal hemorrhage\u201d emerged as the most significant suspected AE across five algorithms. The exciting finding was that the MGPS algorithm revealed a higher risk of suspected AEs under the \u201cInvestigations\u201d category. However, the results of the analyses of the other algorithms at the SOC level were not akin to this. Moreover, the results of signal mining for the three main types of indication populations with adverse drug reactions (ADRs), including Atrial fibrillation, Cerebrovascular accident prophylaxis, and Deep vein thrombosis were shown that \u201cGastrointestinal haemorrhage\u201d, \u201cEpistaxis\u201d, \u201cHaematuria\u201d, \u201cRectal haemorrhage\u201d, and \u201cUpper gastrointestinal haemorrhage\u201d were detected as the most common and significant signals of suspected adverse events.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Rivaroxaban has risks of various suspected adverse reactions while providing therapeutic effects and being used widely. Our pharmacovigilance study may provide valuable hints that practitioners should closely monitor occurrences of \u201cGastrointestinal disorders\u201d, \u201cInjury, poisoning, and procedural complications\u201d and \u201cNervous system disorders\u201d, and other events in clinical applications. Consequently, it remains to persist in monitoring rivaroxaban, assessing the associated risks in the future.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2024.1399172","type":"journal-article","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T04:47:21Z","timestamp":1725598041000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Suspected adverse drug reactions of rivaroxaban reported in the United States food and drug administration adverse event reporting system database: a pharmacovigilance study"],"prefix":"10.3389","volume":"15","author":[{"given":"Jingying","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianru","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biyu","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinru","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenfang","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongqiao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,9,6]]},"reference":[{"key":"B1","volume-title":"Xarelto1 summary of product characteristics","year":"2016"},{"key":"B2","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1080\/14740338.2017.1325463","article-title":"Methods for safety signal detection in healthcare databases: a literature review","volume":"16","author":"Arnaud","year":"2017","journal-title":"Expert Opin. Drug Saf."},{"key":"B3","doi-asserted-by":"publisher","first-page":"932085","DOI":"10.3389\/fped.2022.932085","article-title":"Adverse events of DOACs in children","volume":"10","author":"Bosch","year":"2022","journal-title":"Front. Pediatr."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1466","DOI":"10.3390\/medicina59081466","article-title":"Plasma drug values of DOACs in patients presenting with gastrointestinal bleeding: a prospective observational study","volume":"59","author":"Bozic","year":"2023","journal-title":"Med. Kaunas."},{"key":"B5","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1053\/j.tvir.2004.02.001","article-title":"Epidemiology of acute deep vein thrombosis","volume":"7","author":"Bulger","year":"2004","journal-title":"Tech. Vasc. Interv. Radiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1080\/14740338.2018.1550069","article-title":"A characterization and disproportionality analysis of medication error related adverse events reported to the FAERS database","volume":"17","author":"Carnovale","year":"2018","journal-title":"Expert Opin. Drug Saf."},{"key":"B7","doi-asserted-by":"publisher","first-page":"32","DOI":"10.3928\/0098-9134-20050401-09","article-title":"Teaching older adults to self-manage medications: preventing adverse drug reactions","volume":"31","author":"Curry","year":"2005","journal-title":"J. Gerontol. Nurs."},{"key":"B8","doi-asserted-by":"publisher","first-page":"79","DOI":"10.2174\/157488607779315507","article-title":"Adverse drug reactions in hospitals: a narrative review","volume":"2","author":"Davies","year":"2007","journal-title":"Curr. Drug Saf."},{"key":"B9","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1111\/tmi.12201","article-title":"Registering medicines for low-income countries: how suitable are the stringent review procedures of the World Health Organisation, the US Food and Drug Administration and the European Medicines Agency?","volume":"19","author":"Doua","year":"2014","journal-title":"Trop. Med. Int. Health"},{"key":"B10","doi-asserted-by":"publisher","first-page":"250","DOI":"10.3390\/jpm11040250","article-title":"Drug-drug interactions leading to adverse drug reactions with rivaroxaban: a systematic review of the literature and analysis of VigiBase","volume":"11","author":"Fernandez","year":"2021","journal-title":"J. Pers. Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"293476","DOI":"10.1155\/2014\/293476","article-title":"Bleeding complication of triple therapy of rivaroxaban, prasugrel, and aspirin: a case report and general discussion","volume":"2014","author":"Gruenebaum","year":"2014","journal-title":"Case Rep. Cardiol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"892503","DOI":"10.3389\/fphar.2022.892503","article-title":"Development of a drug risk analysis and assessment system and its application in signal excavation and analysis of 263 cases of fluoroquinolone-induced adverse reactions","volume":"13","author":"Guan","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"928","DOI":"10.12998\/wjcc.v8.i5.928","article-title":"Acute thrombocytopenia after anticoagulation with rivaroxaban: a case report","volume":"8","author":"He","year":"2020","journal-title":"World J. Clin. Cases"},{"key":"B14","doi-asserted-by":"publisher","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":"Jiang","year":"2024","journal-title":"J. Affect Disord."},{"key":"B15","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s12913-019-4651-7","article-title":"Adverse drug reactions in primary care: a scoping review","volume":"20","author":"Khalil","year":"2020","journal-title":"BMC Health Serv. Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"2513","DOI":"10.2147\/DDDT.S417096","article-title":"ABCG2 gene polymorphisms may affect the bleeding risk in patients on apixaban and rivaroxaban","volume":"17","author":"Kim","year":"2023","journal-title":"Drug Des. Devel Ther."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1069504","DOI":"10.3389\/fped.2022.1069504","article-title":"Disproportionality analysis of quinolone safety in children using data from the FDA adverse event reporting system (FAERS)","volume":"10","author":"Kong","year":"2023","journal-title":"Front. Pediatr."},{"key":"B18","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.thromres.2018.07.022","article-title":"Efficacy and safety of direct oral anticoagulants during pregnancy; a systematic literature review","volume":"169","author":"Lameijer","year":"2018","journal-title":"Thromb. Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2423","DOI":"10.1111\/bcp.15710","article-title":"Evidence of potential pro-haemorrhagic drug interactions between CYP3A4 inhibitors and direct oral anticoagulants: analysis of the FAERS database","volume":"89","author":"Li","year":"2023","journal-title":"Br. J. Clin. Pharmacol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1097\/MEG.0000000000001030","article-title":"Rivaroxaban-induced hepatotoxicity: review of the literature and report of new cases","volume":"30","author":"Licata","year":"2018","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"6940183","DOI":"10.1155\/2020\/6940183","article-title":"Acute renal failure in a patient with rivaroxaban-induced hypersensitivity syndrome: a case report with a review of the literature and of pharmacovigilance registries","volume":"2020","author":"Marcelino","year":"2020","journal-title":"Case Rep. Nephrol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"6105320","DOI":"10.1155\/2023\/6105320","article-title":"Pharmacogenetic approach for the prevention of rivaroxaban's ADRs: a systematic review and meta-analysis","volume":"2023","author":"Mardi","year":"2023","journal-title":"Genet. Res. (Camb)"},{"key":"B23","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.thromres.2022.12.008","article-title":"Rivaroxaban plus aspirin versus acenocoumarol to manage recurrent venous thromboembolic events despite systemic anticoagulation with rivaroxaban","volume":"222","author":"Maximiliano","year":"2023","journal-title":"Thromb. Res."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e021765","DOI":"10.1161\/JAHA.120.021765","article-title":"Thromboprophylaxis for children post-fontan procedure: insights from the UNIVERSE study","volume":"10","author":"McCrindle","year":"2021","journal-title":"J. Am. Heart Assoc."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1345\/aph.1A333","article-title":"Hospital admissions resulting from preventable adverse drug reactions","volume":"36","author":"McDonnell","year":"2002","journal-title":"Ann. Pharmacother."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.7754\/Clin.Lab.2023.230101","article-title":"Gender-associated variation in DOAC levels","volume":"69","author":"Moldenhauer","year":"2023","journal-title":"Clin. Lab."},{"key":"B27","doi-asserted-by":"publisher","first-page":"203","DOI":"10.2165\/00003088-200847030-00006","article-title":"Population pharmacokinetics and pharmacodynamics of rivaroxaban \u2013 an oral, direct factor Xa inhibitor \u2013 in patients undergoing major orthopaedic surgery","volume":"47","author":"Mueck","year":"2008","journal-title":"Clin. Pharmacokinet."},{"key":"B28","doi-asserted-by":"publisher","first-page":"10760296231184216","DOI":"10.1177\/10760296231184216","article-title":"Risk of bleeding associated with outpatient use of rivaroxaban in VTE management at a national referral hospital in western Kenya","volume":"29","author":"Njuguna","year":"2023","journal-title":"Clin. Appl. Thromb. Hemost."},{"key":"B29","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1161\/ATVBAHA.110.202978","article-title":"Rivaroxaban: a new oral factor Xa inhibitor","volume":"30","author":"Perzborn","year":"2010","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1007\/s40273-016-0397-9","article-title":"A systematic review of economic evaluations of pharmacogenetic testing for prevention of adverse drug reactions","volume":"34","author":"Plumpton","year":"2016","journal-title":"Pharmacoeconomics"},{"key":"B31","doi-asserted-by":"publisher","first-page":"2395","DOI":"10.1001\/jama.2021.21222","article-title":"Association of rivaroxaban vs apixaban with major ischemic or hemorrhagic events in patients with atrial fibrillation","volume":"326","author":"Ray","year":"2021","journal-title":"JAMA"},{"key":"B32","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1177\/0897190017722872","article-title":"Probable rivaroxaban-induced full body rash: a case report","volume":"31","author":"Sasson","year":"2018","journal-title":"J. Pharm. Pract."},{"key":"B33","doi-asserted-by":"publisher","first-page":"789","DOI":"10.2147\/CLEP.S365513","article-title":"A real-world disproportionality analysis of olaparib: data mining of the public version of FDA adverse event reporting system","volume":"14","author":"Shu","year":"2022","journal-title":"Clin. Epidemiol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1007\/s10557-020-07110-w","article-title":"Hemorrhage risk profiles among different antithrombotic regimens: evidence from a real-world analysis of postmarketing surveillance data","volume":"36","author":"Sun","year":"2022","journal-title":"Cardiovasc. Drugs Ther."},{"key":"B35","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1038\/eye.2016.265","article-title":"Risk of intraocular hemorrhage with new oral anticoagulants","volume":"31","author":"Talany","year":"2017","journal-title":"Eye (Lond)"},{"key":"B36","doi-asserted-by":"publisher","first-page":"e850","DOI":"10.5435\/JAAOS-D-24-00232","article-title":"Venous thromboembolism after knee arthroscopy: incidence, risk factors, prophylaxis, and management","volume":"32","author":"Wollenman","year":"2024","journal-title":"J. Am. Acad. Orthop. Surg."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1719","DOI":"10.12659\/AJCR.917492","article-title":"Rivaroxaban-induced acute interstitial nephritis: a case report","volume":"20","author":"Zafar","year":"2019","journal-title":"Am. J. Case Rep."},{"key":"B38","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.jad.2023.11.076","article-title":"Mining and analysis of adverse event signals of Cariprazine based on the real-world data of FAERS database","volume":"347","author":"Zhu","year":"2024","journal-title":"J. Affect Disord."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1399172\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T04:47:23Z","timestamp":1725598043000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1399172\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,6]]},"references-count":38,"alternative-id":["10.3389\/fphar.2024.1399172"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2024.1399172","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,6]]},"article-number":"1399172"}}