Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan.
Clin Drug Investig. 2019 Apr;39(4):363-368. doi: 10.1007/s40261-019-00754-z.
Adverse cutaneous drug reactions associated with antiepileptic drugs (AEDs) are a serious problem in the clinical setting. New-generation AEDs have been reported to be better tolerated than old-generation forms; however, information about the risks of adverse cutaneous drug reactions to new-generation AEDs is limited.
The purpose of this study was to clarify the association of AEDs with adverse cutaneous drug reactions using a spontaneous reporting database.
We performed a retrospective pharmacovigilance disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database. Adverse event reports submitted to the Pharmaceuticals and Medical Devices Agency between April 2004 and January 2017 were analyzed. Based on reports of all adverse events, we obtained 4805 reports of adverse cutaneous drug reactions associated with AEDs, and calculated the reporting odds ratio (ROR) and 95% confidence interval (CI) for drug rash, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN).
Individual AEDs had variable signals for drug rash, SJS, and TEN. The strongest signals were detected for drug rash caused by lamotrigine (ROR 9.18, 95% CI 8.65-9.74), SJS caused by zonisamide (ROR 9.85, 95% CI 8.23-11.78), and TEN caused by phenobarbital (ROR 14.08, 95% CI 11.28-17.57).
There are clear differences in the risk of cutaneous reactions among AEDs, and further studies are needed to confirm these findings.
抗癫痫药物（AED）相关的不良反应是临床中的一个严重问题。有报道称新一代 AED 比老一代 AED 具有更好的耐受性；然而，关于新一代 AED 不良反应风险的信息有限。
本研究旨在使用自发报告数据库阐明 AED 与不良反应之间的关系。
我们使用日本药物不良事件报告（JADER）数据库进行了回顾性药物警戒性比例失衡分析。分析了 2004 年 4 月至 2017 年 1 月期间向药品和医疗器械管理局提交的不良事件报告。基于所有不良反应报告，我们获得了与 AED 相关的 4805 例不良反应报告，并计算了皮疹、史蒂文斯-约翰逊综合征（SJS）和中毒性表皮坏死松解症（TEN）的报告比值比（ROR）和 95%置信区间（CI）。
个别 AED 对皮疹、SJS 和 TEN 具有不同的信号。拉莫三嗪引起皮疹的信号最强（ROR 9.18，95%CI 8.65-9.74），左乙拉西坦引起 SJS 的信号最强（ROR 9.85，95%CI 8.23-11.78），苯巴比妥引起 TEN 的信号最强（ROR 14.08，95%CI 11.28-17.57）。
AED 之间的皮肤反应风险存在明显差异，需要进一步研究来证实这些发现。
