PrimeVigilance d.o.o, Belgrade, Serbia.
Department of Pharmacokinetics and Clinical Pharmacy, University of Belgrade - Faculty of Pharmacy, Belgrade, Serbia.
Expert Opin Drug Metab Toxicol. 2023 Mar;19(3):175-183. doi: 10.1080/17425255.2023.2203859. Epub 2023 Apr 23.
Data on drug-induced liver injury (DILI) caused by newer antiseizure medications (ASMs) in the elderly are scarce and mainly come from literature case reports. We analyzed Individual Case Safety Reports (ICSRs) of DILI in elderly patients treated with newer ASMs reported to VigiBase.
Empirica™ Signal software was used to retrieve ICSRs reported to VigiBase up to 31 December 2021 and to calculate Empirical Bayesian Geometric Mean and corresponding 90% confidence intervals (EB05, EB95) for each drug-event pair. EB05 > 2, > 0 was considered a signal. Analysis by age subgroups and gender was performed to assess the influence of these factors on ICSR characteristics and identified signals.
There were 1399 ICSRs reporting 1947 events of hepatotoxicity. 56.97% of the reports were reported in females, 67.05% were serious, and 3.36% resulted in death. For one or more events of hepatotoxicity, signals were detected for lamotrigine, levetiracetam, oxcarbazepine, topiramate, and zonisamide. Age- and gender-biased reporting frequency was identified for topiramate-induced hyperammonemia, with disproportionally higher reporting frequency in ≥75-year-old male patients.
The results of our study indicate differences among newer ASMs in their potential to cause DILI in the elderly. Further studies are needed to confirm the associations identified in this study.
老年人新型抗癫痫药物（ASMs）引起的药物性肝损伤（DILI）的数据很少，主要来自文献病例报告。我们分析了报告给 VigiBase 的老年人新型 ASMs 治疗引起的 DILI 的个别病例安全报告（ICSRs）。
使用 Empirica™ Signal 软件检索截至 2021 年 12 月 31 日报告给 VigiBase 的 ICSRs，并计算每个药物-事件对的经验贝叶斯几何均值和相应的 90%置信区间（EB05、EB95）。EB05 > 2、> 0 被认为是信号。进行年龄亚组和性别分析，以评估这些因素对 ICSR 特征和识别信号的影响。
共收到 1399 份报告 1947 例肝毒性事件的 ICSRs。报告中 56.97%为女性，67.05%为严重，3.36%导致死亡。拉莫三嗪、左乙拉西坦、奥卡西平、托吡酯和唑尼沙胺在一个或多个肝毒性事件中检测到信号。还发现了托吡酯引起的高血氨在年龄和性别报告频率上的偏倚，≥75 岁的男性患者报告频率更高。
本研究结果表明新型 ASMs 引起老年人 DILI 的潜力存在差异。需要进一步研究来证实本研究中确定的相关性。
