Food and Drug Administration, Center for Drug Evaluation and Research, Office of Surveillance and Epidemiology, Silver Spring, MD, USA.
Neurology. 2012 Mar 20;78(12):921-7. doi: 10.1212/WNL.0b013e31824c4634. Epub 2012 Feb 22.
The purpose of this case series is to characterize a recently identified association of the antiepileptic drug (AED) lamotrigine with aseptic meningitis based on cases reported to the Food and Drug Administration (FDA)'s Adverse Event Reporting System (AERS) database.
We performed a data mining analysis of 9 AEDs from the FDA's AERS database. We applied the multi-item gamma Poisson shrinker (MGPS) algorithm to the entire AERS database through November 2, 2009, to generate empirical Bayes geometric mean (EBGM) values with corresponding confidence intervals for 9 AEDs and the adverse event code "meningitis aseptic." The AERS database was also searched for postmarketing reports of aseptic meningitis associated with lamotrigine and a detailed review of each case was performed.
Forty AERS cases were identified in this review. Findings from the AERS reports revealed CSF profiles with features of both bacterial as well as viral meningitis. Fifteen cases documented a positive rechallenge; the median time to onset of symptoms upon rechallenge was only 60 minutes. Data mining analysis of several anticonvulsants resulted in disproportionate reporting solely for lamotrigine.
There appears to be an association between lamotrigine use and aseptic meningitis. It is notable that nearly 40% of cases in this case series reported a positive rechallenge. Lamotrigine-associated aseptic meningitis should be considered in the differential diagnosis of culture-negative meningitis. This case series highlights the need for continued pharmacovigilance and the importance of systematic monitoring of patients treated with antiepileptic medications.
本病例系列旨在根据食品和药物管理局(FDA)不良事件报告系统(AERS)数据库报告的病例,描述最近发现的抗癫痫药物(AED)拉莫三嗪与无菌性脑膜炎之间的关联。
我们对 FDA 的 AERS 数据库中的 9 种 AED 进行了数据挖掘分析。我们通过 2009 年 11 月 2 日应用多项伽马泊松收缩器(MGPS)算法对整个 AERS 数据库进行分析,生成 9 种 AED 和不良事件代码“无菌性脑膜炎”的经验贝叶斯几何均值(EBGM)值及其相应的置信区间。还对 AERS 数据库中与拉莫三嗪相关的无菌性脑膜炎的上市后报告进行了搜索,并对每个病例进行了详细审查。
在本次审查中发现了 40 例 AERS 病例。AERS 报告的结果显示,CSF 特征既有细菌性也有病毒性脑膜炎。15 例记录了阳性再挑战;再挑战时症状发作的中位时间仅为 60 分钟。对几种抗惊厥药物的数据分析导致仅对拉莫三嗪进行了不成比例的报告。
拉莫三嗪的使用与无菌性脑膜炎之间似乎存在关联。值得注意的是,本病例系列中近 40%的病例报告阳性再挑战。在鉴别诊断培养阴性脑膜炎时应考虑拉莫三嗪相关的无菌性脑膜炎。本病例系列强调了需要持续进行药物警戒,并强调了系统监测接受抗癫痫药物治疗的患者的重要性。