Division of Clinical and Experimental Pharmacology, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy; IRCCS Mondino Foundation, Pavia, Italy.
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
Epilepsy Behav. 2021 Jun;119:107989. doi: 10.1016/j.yebeh.2021.107989. Epub 2021 May 1.
Spontaneous reports of adverse drug reactions (ADRs) are a valuable supplement to clinical studies in informing about the safety of medications. This is especially relevant for pediatric populations, which are not often included in large-scale clinical trials.
To evaluate patterns of pediatric ADRs to antiseizure medications (ASMs) reported to the Italian Spontaneous Reporting System (SRS) database during the period November 1, 2001─May 31, 2019.
Suspected ADRs ascribed to medications listed under ATC code N03, plus clobazam (code N05BA09), and affecting individuals below age 18 years were sourced from the Italian SRS database, categorized based on a modification of the MedDRA® high-level term, and analyzed using descriptive statistics.
A total of 956 reports listing a total of 1806 ADRs ascribed to one or more ASMs were received for individuals in pediatric age. The most commonly reported ADRs were skin rashes (24.0% of all reports), epileptic seizures (12.6%), gastrointestinal disturbances (11.8%), and somnolence (10.6%). A more detailed analysis was conducted on 675 reports listing a single ASM as suspected drug and occurring in patients with a specified or presumed diagnosis of epilepsy. Adverse drug reaction patterns differed widely across ASMs. Skin rashes were the most commonly reported ADR for lamotrigine (62.3%), carbamazepine (50.3%), phenobarbital (42.3%), and oxcarbazepine (33.0%). Other most commonly reported ADRs were gastrointestinal symptoms for ethosuximide (44%), irritability/aggression for levetiracetam (25.0%), epileptic seizures for valproic acid (16.1%), fever (often associated with hypohidrosis) for topiramate (17.9%), and utilization error (mostly accidental drug administration) for clonazepam (34.6%).
Patterns of spontaneous ADR reports are indicative of major differences in safety profile among individual ASMs. Most, but not all, frequently reported ADRs were in line with findings from clinical trials and observational studies.
药物不良反应（ADR）自发报告是补充药物安全性信息的重要手段，尤其对于儿科人群，其在大规模临床试验中通常不被纳入。
评估 2001 年 11 月 1 日至 2019 年 5 月 31 日期间，意大利自发报告系统（SRS）数据库中报告的抗癫痫药物（ASM）致儿科 ADR 模式。
从意大利 SRS 数据库中获取 ATC 代码 N03 下列出的药物（加氯巴占[N05BA09]）所致疑似 ADR 报告，这些药物影响 18 岁以下个体，基于 MedDRA®高级术语进行修改进行分类，并使用描述性统计进行分析。
共收到 956 份报告，涉及 1806 例儿科年龄个体的 ASM 相关 ADR。最常见的 ADR 是皮疹（占所有报告的 24.0%）、癫痫发作（12.6%）、胃肠道紊乱（11.8%）和嗜睡（10.6%）。对 675 份报告进行了更详细的分析，这些报告列出了一种被怀疑的 ASM，且发生在特定或假定的癫痫诊断患者中。ASM 之间的不良反应模式差异很大。皮疹是拉莫三嗪（62.3%）、卡马西平（50.3%）、苯巴比妥（42.3%）和奥卡西平（33.0%）最常见的报告 ADR。其他常见的报告 ADR 是乙琥胺的胃肠道症状（44%）、左乙拉西坦的易激惹/攻击性（25.0%）、丙戊酸的癫痫发作（16.1%）、托吡酯的发热（常伴有少汗）（17.9%）和氯硝西泮的用药错误（大多是意外用药）（34.6%）。
自发 ADR 报告模式表明，个别 ASM 的安全性特征存在显著差异。大多数但并非所有常见报告的 ADR 与临床试验和观察性研究结果一致。
