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

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

Author by Prof. Christiana Sowunmi

Journal/Publisher: Clinical Drug Investigation

Volume/Edition: 20

Language: English

Pages: 229 - 235

Abstract

Objective: To examine the cardiac effects of halofantrine by evaluating the apatterns of change in the ECG, including the PR and QTC intervals and the presence or absence of rhythm disturbances, following treatment with halofantrine of children with acute, symptomatic, uncomplicated falciparum malaria.

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 monitoring period of 1 to 2 weeks. Changes in the ECG intervals and the patterns of 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 ECG. There was a significant increase in PR interval only at 8 hours after treatment. The rate-corrected QT (QTC) interval increased following treatment, with significant differences 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 relationship to the time-course of therapy or drug administration, the duration of prolongation and the absence or presence of rhythm disturbance showed the following patterns: no change (24%), early or late monophasic prolongation of PR interval (3%), early monophasic (60%) or late monophasic (1.5%) prolongation of QTC interval, biphasic prolongation of QTC interval (4.7%), early monophasic prolongation of both PR and QTC intervals (1.5%), biphasic prolongation of both PR and QTC intervals (1.5%), other patterns (3%).

Conclusion: Halofantrine has significant effects on ECG intervals with varying patterns of change; the biphasic and late monophasic changes suggest that adverse cardiac effects may be early, early and late, or late in appearing. In children, the currently recommended dose of halofantrine for the treatment of malaria may produce serious cardiac effects.


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