Effect of Clofazimine Concentration on QT Prolongation in Patients Treated for Tuberculosis
Mahmoud Tareq Abdelwahab, Richard Court, Daniel E. Everitt, Andreas H. Diacon, Rodney Dawson, Elin M. Svensson, Gary Maartens, Paolo Denti
Abstract
) function. We predicted clofazimine exposures using 100-mg daily doses and 2 weeks of loading with 200 and 300 mg daily, respectively. The expected proportions of patients with QTcF change from baseline above 30 ms (ΔQTcF > 30) were 2.52%, 11.6%, and 23.0% for 100-, 200-, and 300-mg daily doses, respectively. At steady state, the expected proportion with ΔQTcF of >30 ms was 23.7% and with absolute QTcF of >450 ms was 3.42% for all simulated regimens. The use of loading doses of 200 and 300 mg is not predicted to expose patients to an increased risk of QT prolongation, compared with the current standard treatment, and is, therefore, an alternative option for more quickly achieving therapeutic concentrations.