Halofantrine is a drug used to treat

malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...

. Halofantrine's structure contains a substituted

phenanthrene Phenanthrene is a polycyclic aromatic hydrocarbon (PAH) with formula C14H10, consisting of three fused benzene rings. It is a colorless, crystal-like solid, but can also appear yellow. Phenanthrene is used to make dyes, plastics, pesticides, expl ...

, 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 leg ...

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, a

haemoglobin Hemoglobin (haemoglobin, Hb or Hgb) is a protein containing iron that facilitates the transportation of oxygen in red blood cells. Almost all vertebrates contain hemoglobin, with the sole exception of the fish family Channichthyidae. Hemoglobi ...

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

SRI International SRI International (SRI) is a nonprofit organization, nonprofit scientific research, scientific research institute and organization headquartered in Menlo Park, California, United States. It was established in 1946 by trustees of Stanford Univer ...

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 (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

, 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, are irregularities in the heartbeat, including when it is too fast or too slow. Essentially, this is anything but normal sinus rhythm. A resting heart rate that is too fast – above 100 beat ...

s: halofantrine causes significant QT prolongation, 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 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...

, 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, is the application of healthcare measures to prevent diseases.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental health a ...

) 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 GSK plc (an acronym from its former name GlaxoSmithKline plc) is a British Multinational corporation, multinational Pharmaceutics, pharmaceutical and biotechnology company with headquarters in London. It was established in 2000 by a Mergers an ...

) is available as 250 mg tablets. A full course of treatment (6 tablets) costs

US$ The United States dollar (Currency symbol, symbol: Dollar sign, $; ISO 4217, currency code: USD) is the official currency of the United States and International use of the U.S. dollar, several other countries. The Coinage Act of 1792 introdu ...

1.40 in the developing world. Halofantrine is not available in the UK or U.S.

References

{{Antimalarials Dibutylamino compounds Secondary alcohols Antimalarial agents Chloroarenes CYP2D6 inhibitors Trifluoromethyl compounds Phenanthrenes SRI International Drugs developed by GSK plc