Analysis of Adverse Drug Reactions of Clofazimine Reported in the FDA Adverse Event Reporting System from 2004 to 2025 Q1.

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.