Halofantrine is a drug used to treat

malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...

. Halofantrine's structure contains a substituted phenanthrene, and is related to the

antimalarial drug Antimalarial medications or simply antimalarials are a type of antiparasitic chemical agent, often naturally derived, that can be used to treat or to prevent malaria, in the latter case, most often aiming at two susceptible target groups, young c ...

quinine Quinine is a medication used to treat malaria and babesiosis. This includes the treatment of malaria due to '' Plasmodium falciparum'' that is resistant to chloroquine when artesunate is not available. While sometimes used for nocturnal le ...

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 hematin ''in vitro'', suggesting a possible mechanism of action. Halofantrine has also been shown to bind to

plasmepsin Plasmepsins are a class of at least 10 enzymes ( and ) produced by the ''Plasmodium falciparum'' parasite. There are ten different isoforms of these proteins and ten genes coding them respectively in ''Plasmodium'' (Plm I, II, III, IV, V, VI, VII ...

, a

haemoglobin Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyte ...

degrading enzyme unique to the malarial parasites. Halofantrine was developed at

SRI International SRI International (SRI) is an American nonprofit scientific research institute and organization headquartered in Menlo Park, California. The trustees of Stanford University established SRI in 1946 as a center of innovation to support economic ...

for the Walter Reed Army Institute of Research from 1965 to 1975 by a team led by medicinal chemist William Colwell.

Adverse reactions

Halofantrine can cause abdominal pain,

diarrhoea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...

, vomiting, rash, headache, itching and elevated liver enzymes. It can be associated with cardiotoxicity. The most dangerous side effect is

cardiac arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...

s: halofantrine causes significant

QT prolongation Long QT syndrome (LQTS) is a condition affecting repolarization (relaxing) of the heart after a heartbeat, giving rise to an abnormally lengthy QT interval. It results in an increased risk of an irregular heartbeat which can result in fainting ...

, 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.

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 Preventive healthcare, or prophylaxis, consists of measures taken for the purposes of disease prevention.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental hea ...

) because of the risk of toxicity and unreliable absorption.

Dosing

Adult dose: three doses of 500 mg six hours apart. Halofantrine should be taken on an empty stomach.

Manufacturing information and availability

Halfan ( GlaxoSmithKline) is available as 250 mg 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

{{Antimalarials Secondary alcohols Antimalarial agents Chloroarenes CYP2D6 inhibitors Trifluoromethyl compounds Phenanthrenes SRI International Butyl compounds