Cardiac effects of standard-dose halofantrine therapy

The antimalarial drug halofantrine hydrochloride has been associated with cardiac arrhythmias. This is a report of a study on the cardiac effects of standard-dose halofantrine (24 mg/kg) on a sample of 48 patients selected from a group of 402 Dega (Montagnard) refugees treated for Plasmodium falciparum infection. Prolongation of the rate-corrected QT interval (QTc) on the electrocardiogram (ECG) was used as an indicator of risk for halofantrine-associated cardiac arrhythmias. We found that standard-dose halofantrine was associated with a lengthening of the mean QTc from 0.04 sec(1/2) to 0.44 sec(1/2). Two patients had a QTc increase of greater than 25%, but none had a follow-up QTc of more than 0.55 sec(1/2), an interval length generally considered to be a risk factor for ventricular arrhythmias. Regression analysis indicated that pretreatment ECGs were poorly predictive of QTc lengthening during therapy, although pretreatment ECGs may be useful to evaluate patients with pre-existing cardiac conditions. The manufacturer has recommended that the halofantrine dose not exceed 24 mg/kg and revised the list of medication contraindications to include some cardiac conditions. Clinicians should weigh a patient's risk, including history of cardiac disease and availability of alternative therapy before use of halofantrine.