Pharmacokinetics and Safety of Clofazimine in Children With Rifampicin-Resistant Tuberculosis

Background We described the pharmacokinetics and safety of clofazimine in children treated for multidrug/rifampicin-resistant tuberculosis (MDR/RR-TB). Methods Children aged Results Twenty children were included: median age was 6.0 years (IQR, 1.6-14.4); 6 (30%) were male. Median clofazimine wAUC was 162.94 (IQR, 130.06-263.95), >25% higher than the target adult wAUC in adults with MDR/RR-TB (111.79; IQR, 81.9-151.9). No serious or grade ≥3 cardiac events occurred. There was a QT interval increase of 0.02 milliseconds for every 1-µg/L increase in clofazimine concentration. One severe adverse event (elevated alanine transferase) led to temporary withdrawal of clofazimine. Conclusions The clofazimine doses used achieved substantially higher exposures in children than adults receiving standard clofazimine doses. The association of higher clofazimine exposures and QT interval prolongation may pose unnecessary risk to children, particularly in combination with other QT-prolonging drugs. Clinical trials registration South African National Clinical Trials Register (https://sanctr.samrc.ac.za/; DOH-27-0620-6415).