Hatano Masakazu, Araki Haruna, Saito Takeo, Yamada Shigeki
Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine, Aichi, Japan.
Department of Psychiatry, Fujita Health University School of Medicine, Aichi, Japan.
Clin Psychopharmacol Neurosci. 2024 Aug 31;22(3):442-450. doi: 10.9758/cpn.24.1174. Epub 2024 Jun 7.
This pharmacovigilance study evaluated the profile of clozapine-related adverse events by region using the Food and Drug Administration Adverse Event Reporting System (FAERS).
We categorized each case into five regions (America, Europe/West Asia, Oceania, Asia, and Africa) based on the reporting country information in the FAERS database. The number of clozapine-related adverse events reported in each region was aggregated according to the preferred term (PT) and the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query (SMQ).
A total of 101,872 clozapine-related adverse events were registered in the FAERS database. In America and Europe, leukocyte or neutrophil count abnormalities accounted for half of the top 10 PTs by relative reporting rate. However, Asia had higher relative reporting rates of pyrexia and salivary hypersecretion (13.91% and 10.85%, respectively). Regarding the SMQ, the relative reporting rates of infective pneumonia, convulsions, extrapyramidal syndrome, gastrointestinal obstruction, and hyperglycaemia/new onset diabetes mellitus were higher in Asia than in other regions (5.26%, 9.72%, 12.65%, 5.13%, and 8.26%, respectively), with significant differences even after adjusting for confounding factors using multivariate logistic regression analysis.
Spontaneous reports of adverse events associated with clozapine show regional disparities, particularly in Asia, where concentration-dependent adverse events are more frequently reported. However, the spontaneous reporting system has several limitations, requiring further research for validation.
本药物警戒研究使用美国食品药品监督管理局不良事件报告系统（FAERS）按地区评估氯氮平相关不良事件的概况。
我们根据FAERS数据库中的报告国家信息将每个病例分为五个地区（美洲、欧洲/西亚、大洋洲、亚洲和非洲）。每个地区报告的氯氮平相关不良事件数量根据首选术语（PT）和监管活动医学标准词典（MedDRA）查询（SMQ）进行汇总。
FAERS数据库中共记录了101,872例氯氮平相关不良事件。在美洲和欧洲，白细胞或中性粒细胞计数异常在相对报告率最高的前10个PT中占一半。然而，亚洲发热和唾液分泌过多的相对报告率较高（分别为13.91%和10.85%）。关于SMQ，亚洲感染性肺炎、惊厥、锥体外系综合征、胃肠道梗阻和高血糖/新发糖尿病的相对报告率高于其他地区（分别为5.26%、9.72%、12.65%、5.13%和8.26%），即使在使用多变量逻辑回归分析调整混杂因素后仍有显著差异。
氯氮平相关不良事件的自发报告显示出地区差异，特别是在亚洲，浓度依赖性不良事件报告更为频繁。然而，自发报告系统有几个局限性，需要进一步研究以进行验证。
