Halofantrine was developed in the 1960s by the Walter Reed Army
Institute of Research. It is a phenanthrene methanol structurally related to quinine. Its
mechanism of action may be similar to that of chloroquine, quinine, and mefloquine; by
forming toxic complexes with ferritoporphyrin IX that damage the membrane of the parasite.
This synthetic anti malarial is effective against multi drug resistant (including
mefloquine resistant) P. falciparum malaria.
It is available only as a tablet, its bioavailability is low and variable
(may be doubled if taken with a fatty meal). The peak plasma concentration is achieved in
4-8 hours after the oral dose. The elimination half-life is 1-3 days for the parent drug
and 3-7 days for the active metabolite. A parenteral preparation is being developed.
Halofantrine is used in the treatment of
chloroquine resistant and multi-drug resistant, uncomplicated P. falciparum malaria. The
clinical response to treatment may be unpredictable due to the variable drug absorption.
Dose: For adults, three tablets of
500 mg each, 6 hours apart. For children, three doses of 8 mg/kg of the salt 6 hours
apart. Treatment should be repeated after 7 days.
Side effects include abdominal
pain, diarrhoea, prolongation of QTC interval and arrhythmias that could be
fatal. It is contraindicated in patients with prolonged QTC interval
(congenital, electrolyte disorders, myocardial disease). However, it appears less toxic
than quinine and mefloquine. It is also contraindicated in pregnancy and lactation,
infants, and patients who have received mefloquine in the preceding 3 weeks.