Comparison of the cardiac effects of the antimalarials co-artemether and halofantrine in healthy participants

Co-artemether (Coartem(R), Riamet(R)) is a tablet containing 20 mg artemether and 120 mg lumefantrine for treatment of falciparum malaria. Lumefantrine has some chemical similarities to halofantrine (Halfan(R)), an antimalarial known for QTc prolongation. Effects on the QTc interval of fed single oral doses of 500 mg halofantrine and 80/480 mg co-artemether were compared in 13 healthy males in a randomized double-blind crossover study. Electrocardiograms (ECGc) were recorded from 48 hours before dosing until 48 hours thereafter. The maximum QTc interval (QTc = QT/rootRR) was compared before and after treatment and between treatments, fitting a general linear model. Drug plasma concentrations were determined concomitantly. After halofantrine, all participants showed an increase in the QTc interval; the mean maximum increase was 28 ms. The length of the QTc interval was positively correlated to halofantrine exposure. The QTc interval remained unchanged after co-artemether. The difference between treatments was statistically significant. In conclusion, hatofantrine caused a significant, exposure-dependent increase in the QTe interval. No such effect was seen with co-artemether.