Int J Clin Pharmacol Ther. 2021 May;59(5):372-377. doi: 10.5414/CP203898.
The development of new xanthine oxidase (XO) inhibitors, such as febuxostat and topiroxostat, could offer an alternative to treatment with allopurinol. The purpose of this study was to compare safety profiles of new XO inhibitors with allopurinol using a spontaneous reporting system database.
A retrospective pharmacovigilance disproportionality analysis was conducted using the Japanese Adverse Drug Event Report database. Adverse event reports submitted to the Pharmaceuticals and Medical Devices Agency were analyzed, and the reporting odds ratio (ROR) and 95% confidence interval (CI) for each adverse event were calculated.
Among 7,305 reports of adverse events associated with XO inhibitors, 64.5% involved males, who were frequently in their 70s (25.9%). A large number of skin-related adverse events were detected with the use of allopurinol, but not with febuxostat or topiroxostat. As for individual XO inhibitors, the signal values showing associations between drug reaction with eosinophilia and systemic symptoms (DRESS) and allopurinol, drug-induced liver injury and febuxostat, and blood urea increase and topiroxostat were noteworthy.
The strength of the associations of XO inhibitors with adverse events is variable, and further studies are required to evaluate the identified signals.
新型黄嘌呤氧化酶（XO）抑制剂如非布司他和托匹司他的开发为别嘌醇治疗提供了另一种选择。本研究旨在使用自发报告系统数据库比较新型 XO 抑制剂与别嘌醇的安全性。
采用日本药物不良反应报告数据库进行回顾性药物警戒非比例性分析。对向药品和医疗器械管理局提交的不良事件报告进行分析，并计算每个不良事件的报告比值比（ROR）和 95%置信区间（CI）。
在与 XO 抑制剂相关的 7305 份不良事件报告中，64.5%涉及男性，且年龄多在 70 多岁（25.9%）。使用别嘌醇时会出现大量皮肤相关的不良事件，但非布司他或托匹司他没有。就个别 XO 抑制剂而言，药物相关性嗜酸性粒细胞增多和全身症状（DRESS）与别嘌醇、药物性肝损伤与非布司他以及血尿素升高与托匹司他之间的关联信号值值得关注。
XO 抑制剂与不良事件的关联强度各不相同，需要进一步研究来评估所确定的信号。
