{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T01:11:44Z","timestamp":1770685904422,"version":"3.49.0"},"reference-count":39,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T00:00:00Z","timestamp":1596672000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K20731"],"award-info":[{"award-number":["19K20731"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Stevens\u2010Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are immune\u2010mediated diseases characterized by an extensive loss of the epidermal skin layer, often resulting in death. SJS and TEN are often triggered by certain drugs, including antiepileptic drugs (AEDs). Epilepsy is very difficult to treat and often involves the combination of two or more AEDs. In this study, we quantified not only the risk of SJS or TEN associated with single\u2010AED therapy but also the risk related to concomitant AED treatment using reporting\u2010derived signals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>An analysis of the Japanese Adverse Drug Event Report (JADER) database was performed from the first quarter of 2004 to the fourth quarter of 2018. The single\u2010AED signals were evaluated using the proportional reporting ratio (PRR), and the combination therapy signals were evaluated using <jats:italic>\u03a9<\/jats:italic> shrinkage measure and combination risk ratio (CRR).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>SJS signals were associated with 11 AEDs, and TEN signals were related to 12 AEDs. Moreover, the following AED combinations were associated with SJS signals: carbamazepine\u2010lorazepam (<jats:italic>\u03a9<\/jats:italic><jats:sub>025<\/jats:sub>: 0.33, CRR: 2.18) and fosphenytoin\u2010lorazepam (<jats:italic>\u03a9<\/jats:italic><jats:sub>025<\/jats:sub>: 0.99, CRR: 39.20). The TEN signals were related to the following combinations: clobazam\u2010gabapentin (<jats:italic>\u03a9<\/jats:italic><jats:sub>025<\/jats:sub>: 0.35, CRR: 3.14), phenytoin\u2010gabapentin (<jats:italic>\u03a9<\/jats:italic><jats:sub>025<\/jats:sub>: 0.03, CRR: 2.18), valproic acid\u2013gabapentin (<jats:italic>\u03a9<\/jats:italic><jats:sub>025<\/jats:sub>: 0.15, CRR: 2.25), clobazam\u2010clonazepam (<jats:italic>\u03a9<\/jats:italic><jats:sub>025<\/jats:sub>: 0.03, CRR: 2.93), clobazam\u2013valproic acid (<jats:italic>\u03a9<\/jats:italic><jats:sub>025<\/jats:sub>: 0.29, CRR: 1.55), fosphenytoin\u2010lamotrigine (<jats:italic>\u03a9<\/jats:italic><jats:sub>025<\/jats:sub>: 0.05, CRR: 7.37), and lacosamide\u2010levetiracetam (<jats:italic>\u03a9<\/jats:italic><jats:sub>025<\/jats:sub>: 0.74, CRR: 1.85).<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>This study identified two AED combinations that increased the SJS signals and seven combinations that increased the TEN signals. Although AED monotherapies require attention for SJS and TEN, some AED combinations require extra caution.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.16626","type":"journal-article","created":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T00:06:51Z","timestamp":1596758811000},"page":"1979-1989","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Antiepileptic combination therapy with Stevens\u2010Johnson syndrome and toxic epidermal necrolysis: Analysis of a Japanese pharmacovigilance database"],"prefix":"10.1111","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9110-9604","authenticated-orcid":false,"given":"Yoshihiro","family":"Noguchi","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Pharmacy Gifu Pharmaceutical University Gifu 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