{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T15:21:30Z","timestamp":1777044090340,"version":"3.51.4"},"reference-count":28,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T00:00:00Z","timestamp":1725235200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009954","name":"Taiho Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009954","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>This study was conducted to examine disproportionality, times to onset, incidence rates and outcomes of lenvatinib\u2010associated cardiac adverse events (AEs) using the Japanese Adverse Drug Event Report database.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analysed data for the period between April 2004 and May 2023. Data on cardiac AEs were extracted and the relative disproportionality of AEs was estimated using reporting odds ratios (RORs). Furthermore, Weibull distribution parameters were calculated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 2\u2009230\u2009863 reports analysed, we identified 7684 reports of AEs associated with lenvatinib, including 317 cardiac AEs. Signals were detected for eight cardiac AEs: hypertension, cardiac failure, myocarditis, myocardial infarction, immune\u2010mediated myocarditis, cardiomyopathy, angina unstable and cardiotoxicity. Among these, fatal outcomes were observed for cardiac failure, myocarditis and myocardial infarction. Histograms of median times to onset for the eight detected cardiac AE signals showed that AEs occurred at a median of 3.5\u2013134.5\u00a0days after lenvatinib administration. The Weibull distributions showed that cardiac failure occurred early after administration (early failure type), myocarditis occurred in a dose\u2010dependent manner (wearout failure type), and myocardial infarction occurred constantly throughout the exposure period (random failure type).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We focused on cardiac AEs associated with lenvatinib as post\u2010marketing AEs. Serious outcomes can arise after lenvatinib administration. Patients should be monitored for signs of onset of these AEs not only at the start of administration, but also over an extended period.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.16237","type":"journal-article","created":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T08:54:20Z","timestamp":1725267260000},"page":"3348-3354","source":"Crossref","is-referenced-by-count":2,"title":["Disproportionality analysis of cardiac adverse events associated with lenvatinib using the Japanese Adverse Drug Event Report database"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0095-2293","authenticated-orcid":false,"given":"Yuko","family":"Kanbayashi","sequence":"first","affiliation":[{"name":"Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmacy Osaka Medical and Pharmaceutical University  Takatsuki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sakura","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Education and Research Center for Pharmacy Practice, Faculty of Pharmaceutical Sciences Doshisha Women's College of Liberal Arts  Kyotanabe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asuka","family":"Kojima","sequence":"additional","affiliation":[{"name":"Department of Education and Research Center for Pharmacy Practice, Faculty of Pharmaceutical Sciences Doshisha Women's College of Liberal Arts  Kyotanabe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruka","family":"Wakabayashi","sequence":"additional","affiliation":[{"name":"Department of Education and Research Center for Pharmacy Practice, Faculty of Pharmaceutical Sciences Doshisha Women's College of Liberal Arts  Kyotanabe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadashi","family":"Shimizu","sequence":"additional","affiliation":[{"name":"School of Pharmacy Hyogo Medical University  Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayako","family":"Uchida","sequence":"additional","affiliation":[{"name":"Department of Education and Research Center for Pharmacy Practice, Faculty of Pharmaceutical Sciences Doshisha Women's College of Liberal Arts  Kyotanabe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,9,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265\u2010019\u201001116\u2010x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.10019"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20103\u2010319\u201091442\u20108_13"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1406470"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(15)00290\u20109"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/onco.13566"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2018.10.002"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2021.12.024"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.02152"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2023.2251398"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/JCMA.0000000000001026"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.4103\/0973\u20101482.168182"},{"key":"e_1_2_10_14_1","unstructured":"PMDA.Homepage.https:\/\/www.pmda.go.jp\/english\/index.html; Drug Adverse Reaction Report Data Set Bulk Download.https:\/\/www.info.pmda.go.jp\/fukusayoudb\/CsvDownload.jsp. 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