Halofantrine is a drug used to treat malaria. Halofantrine's structure contains a substituted phenanthrene, and is related to the antimalarial drugsquinine and lumefantrine. Marketed as Halfan, halofantrine is never used to prevent malaria and its mode of action is unknown, although a crystallographic study showed that it binds to hematinin vitro, suggesting a possible mechanism of action.[1] Halofantrine has also been shown to bind to plasmepsin, a haemoglobin degrading enzyme unique to the malarial parasites.[2]
Halofantrine can cause abdominal pain, diarrhoea, vomiting, rash, headache, itching and elevated liver enzymes.
It can be associated with cardiotoxicity.[4] The most dangerous side effect is cardiac arrhythmias: halofantrine causes significant QT prolongation,[5] and this effect is seen even at standard doses. The drug should therefore not be given to patients with cardiac conduction defects and should not be combined with mefloquine. A survey from 2009 suggests that the drug is safe when correctly administered.[6]
Other adverse reactions
Consumption of grapefruit combined with certain medications can cause serious side effects, even death. Halofantrine combined with this fruit or grapefruit juice is dangerous. The mechanism of action is inhibition of CYP3A4, which is necessary to metabolize the drug and eliminate it from the body. Without CYP3A4, levels of the drug will become toxic in the body.
Pharmacology
The mechanism of action of halofantrine is unknown. The absorption of halofantrine is erratic, but is increased when taken with fatty food. Because of fears of toxicity due to increased halofantrine blood levels, halofantrine should be taken on an empty stomach.
Plasma levels peak at 16 hours and the half-life of the drug is about 4 days.
Uses
Halofantrine is only used to treat malaria. It is not used to prevent malaria (prophylaxis) because of the risk of toxicity and unreliable absorption.
Dosing
Adult dose: three doses of 500mg six hours apart. Halofantrine should be taken on an empty stomach.
Manufacturing information and availability
Halfan (GlaxoSmithKline) is available as 250mg tablets. A full course of treatment (6 tablets) costs US$1.40 in the developing world. Halofantrine is not available in the UK or U.S.
References
↑de Villiers KA, Marques HM, Egan TJ (2008). "The crystal structure of halofantrine-ferriprotoporphyrin IX and the mechanism of action of arylmethanol antimalarials". J. Inorg. Biochem. 102 (8): 1660–7. doi:10.1016/j.jinorgbio.2008.04.001. PMID18508124.
