An Pengjiao, Liu Xin, Zhang Bo
Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China.
Expert Opin Drug Saf. 2024 Jan;23(1):119-128. doi: 10.1080/14740338.2023.2204227. Epub 2023 Apr 19.
Most of the safety data of clobazam came from well-designed clinical trials, while the real-world information is insufficient.
We performed a disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database through OpenVigil 2 and conducted a systematic review of case reports regarding adverse drug reactions (ADR) linked to clobazam.
The analysis of FAERS identified 595 ADR signals. Nervous system disorders cantains the most positive signals among all system organ classes (SOCs). Except for seizure ( = 1696) and somnolence ( = 813), drug interactions ( = 492) were the most frequently reported positive signals. A total of 502 unique citations were initially retrieved and 31 individual cases from 28 publications were included. Skin reactions were the most reactions ( = 9), containing three types of severe reactions not alerted in the instruction. Five cases were caused by interactions between clobazam and other antiepileptic drugs, etravirine-based antiretroviral therapy, omeprazole, or meropenem. One patient died of aspiration pneumonia.
Clinicians must pay attention to severe skin reactions and monitor the signs of suspicious respiratory infections/inflammations and central sedation. Patients with skin reactions will benefit from the withdrawal of clobazam and the treatment with glucocorticoids. The drug reactions between clobazam with severe or moderate cytochrome P450 (CYP) 3A4 or CYP2C19 inhibitors or other antiepileptic drugs should also be alerted.
氯巴占的大部分安全性数据来自精心设计的临床试验，而真实世界的信息不足。
我们通过OpenVigil 2对美国食品药品监督管理局不良事件报告系统（FAERS）数据库进行了不成比例分析，并对与氯巴占相关的药物不良反应（ADR）病例报告进行了系统评价。
对FAERS的分析确定了595个ADR信号。在所有系统器官类别（SOCs）中，神经系统疾病的阳性信号最多。除癫痫（=1696）和嗜睡（=813）外，药物相互作用（=492）是报告最频繁的阳性信号。最初共检索到502条独特的文献引用，纳入了28篇出版物中的31个个体病例。皮肤反应是最常见的反应（=9），包括三种在说明书中未警示的严重反应。5例是由氯巴占与其他抗癫痫药物、基于依曲韦林的抗逆转录病毒疗法、奥美拉唑或美罗培南之间的相互作用引起的。1例患者死于吸入性肺炎。
临床医生必须注意严重的皮肤反应，监测可疑的呼吸道感染/炎症和中枢镇静迹象。出现皮肤反应的患者停用氯巴占并用糖皮质激素治疗将有益。还应警惕氯巴占与重度或中度细胞色素P450（CYP）3A4或CYP2C19抑制剂或其他抗癫痫药物之间的药物相互作用。
