Halofantrine

General adverse effects and adverse reactions

Adverse reactions with the dosages originally recommended have in general been mild, no more than nausea, diarrhea, headache, and pruritus [ ]. Pruritus occurred markedly less often with halofantrine than with chloroquine [ ]. A comparison between high-dose chloroquine (35 mg/kg total in three daily doses) and halofantrine in the standard dose (total 25 mg/kg given at 6-hour intervals) in patients 4–14 years old showed a fairly similar frequency of adverse reactions. Itching was a common adverse reaction to chloroquine [ ].

Cardiovascular

In 1993, the sudden cardiac death of a 37-year-old woman after her ninth dose of halofantrine was reported. A subsequent prospective study showed that halofantrine was associated with a dose-related lengthening of the QT interval by more than 25% [ ]. Mefloquine did not cause such changes, but the combination of mefloquine with halofantrine had a more pronounced effect on the electrocardiogram. However, in the region where this investigation was carried out (on the Thai–Burmese border area) thiamine deficiency is common, and patients in this area have longer baseline QT intervals than are usually reported [ ]. Two patients, mother and son, both with congenital prolongation of the QT interval, suffered sustained episodes of torsade de pointes after a total dose of 1000 mg of halofantrine, and there have been other reports of dysrhythmias, including death in a patient who took mefloquine and halofantrine [ ]. Dysrhythmias due to halofantrine may respond to propranolol [ ].

African children who received halofantrine (three doses of 8 mg/kg 6-hourly) for uncomplicated P . falciparum malaria had increases in both the PR interval and the QT _c interval; out of 42 children in the study, two children developed first-degree heart block and one child second-degree heart block; the QT _c interval either increased by more than 125% of baseline value or by more than 0.44 seconds (an effect that persisted for at least 48 hours) [ ].

There have been recent reports in the French medical press of cases of significant QT _c prolongation in children returning to France, and caution in its use has been urged [ ]. A small trial in non-immune adults in the Netherlands and France also showed increased QT _c dispersion with halofantrine but not artemether + lumefantrine [ ].

• Death due to a dysrhythmia was reported in a woman who had taken halofantrine for malaria [ ]. She had a normal electrocardiogram before treatment and no family history of heart disease.

Prolongation of the QT interval occurred in 10 of 25 children treated with halofantrine (24 mg/kg oral suspension in three divided doses) for acute falciparum malaria [ ].

Electrocardiographic monitoring is recommended for children and adults taking halofantrine.