Patterns of change in the electrocardiogram after halofantrine treatment of acute uncomplicated falciparum malaria in children

Objective: To examine the cardiac effects of halofantrine by evaluating the patterns of change in the EGG, including the PR and QT(c) intervals and th e presence or absence of rhythm disturbances, following treatment with halo fantrine of children with acute, symptomatic, uncomplicated falciparum mala ria. Design and Setting: This was an observational study performed in Nigeria in 1994 to 1995 and in 1997. Patients and Participants: 63 children who were enrolled in studies on the antimalarial efficacy of halofantrine. Methods: A 12-lead ECG was recorded before and at specific intervals after administration of halofantrine (24 mg/kg of bodyweight) for a total monitor ing period of 1 to 2 weeks. Changes in the ECG intervals and the patterns o f change were analysed using defined criteria. Results: There was no clinical cardiac intolerance to halofantrine. 76% of the children (48 of 63) showed changes in their EGG. There was a significan t increase in PR interval only at 8 hours after treatment. The rate-correct ed QT (QTc) interval increased following treatment, with significant differ ences from time zero from 6 or 8 to 96 hours. A grouping of the patterns of the ECG change based on the type of interval prolongation, the relationshi p to the time-course of therapy or drug administration, the duration of pro longation and the absence or presence of rhythm disturbance showed the foll owing patterns: no change (24%), early or late monophasic prolongation of P R interval (3%), early monophasic (60%) or late monophasic (1.5%) prolongat ion of QT, interval, biphasic prolongation of QT(c) interval (4.7%), early monophasic prolongation of both PR and QT(c) intervals (1.5%), biphasic pro longation of both PR and QTe intervals (1.5%), other patterns (3%). Conclusion: Halofantrine has significant effects on ECG intervals with vary ing patterns of change; the biphasic and late monophasic changes suggest th at adverse cardiac effects may be early, early and late, or late in appeari ng, In children, the currently recommended dose of halofantrine for the tre atment of malaria may produce serious cardiac effects.