Comparison of the cardiac effects of the antimalarials co-artemether and halofantrine in healthy participants
indschedler M, Lefèvre G, Degen P, Sioufi A
Co-artemether (Coartem®, Riamet®) is a tablet containing 20 mg artemether and 120 mg lumefantrine for treatment of falciparum malaria. Lumefantrine has some chemical similarities to halofantrine (Halfan®), 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 male subjects in a randomized double-blind crossover study. Electrocardiograms (ECGs) were recorded from 48 hours before dosing until 48 hours thereafter. The maximum QTc-interval (QTc = QT/√RR) was compared before and after treatment and between treatments, fitting a general linear model. Drug plasma concentrations were determined concomitantly. After halofantrine all subjects showed an increase in the QTc-interval, the mean maximum increase being 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, halofantrine caused a significant, exposure dependent increase in the QTc interval. No such effect was seen with co-artemether.
