Safety and efficacy of clofazimine are correlated with its serum concentration:

Abstract

Background: Although clofazimine (CFZ) has promising effects against non-tuberculosis mycobacteria pulmonary disease (NTM-PD), the appropriate dosage remains unknown. Objective: To clarify the relationship between CFZ steady-state concentration and its adverse effects and efficacy. Methods: This prospective observational study was conducted among NTM-PD patients who were treated with CFZ (UMIN 000041053). The serum trough concentration of CFZ was quantified with validated high-performance liquid chromatography-mass spectrometry. CFZ-induced pigmentation grade, QTc interval, and negative conversion outcomes were analyzed based on measured CFZ serum concentrations by using t-test, concentration-QTc model, and logistic regression analysis, respectively. Results: Out of the 64 enrolled patients, 35 received a CFZ dosage of 50 mg/day and 29 received 100 mg/day. CFZ concentration was higher in patients with more severe pigmentation than in those with less severe pigmentation (P＜0.001). When the CFZ concentration was 1 mg/L, the QTc interval was estimated to be prolonged to 17.3 (95% confidence interval [CI], 3.9 to 25.4) msec from baseline. Negative conversion was achieved in 33 (51.6%) patients. The steady-state CFZ concentration tends to be high in culture-converted groups of patients with NTM-PD (not significant). Conclusions: The adverse effects and efficacy of CFZ were related to its serum concentration, and therapeutic drug monitoring may enable the maximization of drug efficacy and minimization of its side effects.