Zhang Ruoyu, Tao Yunwen, Bao Ziwei, Zhang Jianping, Zeng Lingwu, Fang Chen, Wu Meiying
Department of Tuberculosis, The Fifth People's Hospital of Suzhou (The Affiliated Infectious Disease Hospital of Soochow University), Suzhou, 215000, China.
Department of Clinical Nutrition, Second Affiliated Hospital of Soochow University, Suzhou, China.
Infect Dis Ther. 2025 Sep 13. doi: 10.1007/s40121-025-01224-0.
Clofazimine (CFZ) is an antimycobacterial agent used primarily for leprosy and multidrug-resistant tuberculosis. Despite its long clinical history, comprehensive pharmacovigilance data remain limited. This study aimed to analyze CFZ-associated adverse events (AEs) reported in the FDA Adverse Event Reporting System (FAERS), identifying and pharmacovigilance signals.
We conducted a retrospective pharmacovigilance analysis of the FAERS database from 2004 to 2025 Q1. ASCII-format data were imported into R 4.4.2 and deduplicated using FDA guidelines. Reports Listing CFZ as the primary suspect drug were identified using generic and brand names. AEs were coded using MedDRA 27.1. Disproportionality analyses, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayesian geometric mean (EBGM), identified signals of disproportionate reporting. Subgroup analyses examined sex differences, while time-to-onset (TTO) analyses characterized latency patterns.
A total of 1287 CFZ-related AE reports were identified, with 995 (77.3%) classified as serious. Death (11.6%) and hospitalization (18.1%) were the most frequent serious outcomes. The majority of reports originated from the United States (59.4%). Demographic analysis showed higher reporting among females (49.6%) and patients aged 18-64 years (46.5%). Disproportionality analyses identified 135 preferred terms with positive safety signals. The most prominent signals included QT prolongation (ROR ~ 37.61), drug resistance (ROR ~ 17.31), skin hyperpigmentation (ROR ~ 13.07), and respiratory failure (ROR ~ 7.46), ranging from moderate to strong signal intensity. Subgroup analyses revealed significant sex differences in specific AE signals. TTO analysis indicated varied latency distributions across System Organ Class (SOC) and preferred term levels.
Our pharmacovigilance assessment of FAERS data from 2004 to 2025 not only identified multiple serious and consistent safety signals associated with clofazimine such as prolonged QT intervals but also revealed a life-threatening AE respiratory failure. Although the analysis of these AEs cannot directly reflect causal relationships due to the nature of the FAERS data from spontaneous reporting, our findings highlight the critical importance of continuous pharmacovigilance, targeted clinical monitoring, and consideration of sex-based risk differences to ensure the safe use of clofazimine in clinical practice.
氯法齐明（CFZ）是一种抗分枝杆菌药物，主要用于治疗麻风病和耐多药结核病。尽管其临床应用历史悠久，但全面的药物警戒数据仍然有限。本研究旨在分析美国食品药品监督管理局不良事件报告系统（FAERS）中报告的与CFZ相关的不良事件（AE），识别并评估药物警戒信号。
我们对2004年至2025年第一季度的FAERS数据库进行了回顾性药物警戒分析。将ASCII格式的数据导入R 4.4.2，并根据美国食品药品监督管理局的指南进行去重。使用通用名和品牌名识别将CFZ列为主要可疑药物的报告。使用MedDRA 27.1对AE进行编码。通过不成比例分析，包括报告比值比（ROR）、比例报告比值（PRR）、贝叶斯置信传播神经网络（BCPNN）和经验贝叶斯几何均值（EBGM），识别报告不成比例的信号。亚组分析检查了性别差异，而发病时间（TTO）分析则描述了潜伏期模式。
共识别出1287份与CFZ相关的AE报告，其中995份（77.3%）被归类为严重不良事件。死亡（11.6%）和住院（18.1%）是最常见的严重后果。大多数报告来自美国（59.4%）。人口统计学分析显示，女性（49.6%）和18至64岁患者（46.5%）的报告率较高。不成比例分析确定了135个具有阳性安全信号的首选术语。最突出的信号包括QT间期延长（ROR约为37.61）、耐药性（ROR约为17.31）、皮肤色素沉着（ROR约为13.07）和呼吸衰竭（ROR约为7.46），信号强度从中度到强度不等。亚组分析揭示了特定AE信号中存在显著的性别差异。TTO分析表明，不同系统器官分类（SOC）和首选术语水平的潜伏期分布各不相同。
我们对2004年至2025年FAERS数据的药物警戒评估不仅识别出了多个与氯法齐明相关的严重且一致的安全信号，如QT间期延长，还揭示了一种危及生命的AE——呼吸衰竭。尽管由于FAERS自发报告数据的性质，对这些AE的分析不能直接反映因果关系，但我们的研究结果凸显了持续药物警戒、针对性临床监测以及考虑基于性别的风险差异对于确保氯法齐明在临床实践中安全使用的至关重要性。
