HALOFANTRINE & LUMEFANTRINE
hydrochloride, a phenanthrene-methanol, is effec-tive against erythrocytic (but
not other) stages of all four human malaria species. Oral absorption is
variable and is enhanced with food. Because of toxicity concerns, it should not
be taken with meals. Plasma levels peak 16 hours after dosing, and the
half-life is about 4 days. Excretion is mainly in the feces. The mechanism of
action of halofantrine is unknown. The drug is not available in the USA
(although it has been approved by the FDA), but it is widely available in
500-mg doses at 6-hour intervals, repeated in 1 week for nonimmune individuals)
is rapidly effective against most strains of P falciparum, but its use is limited by irregular absorption and
cardiac toxicity. It should not be used for chemopro-phylaxis. Halofantrine is
generally well tolerated. The most com-mon adverse effects are abdominal pain,
diarrhea, vomiting, cough, rash, headache, pruritus, and elevated liver
enzymes. Of greater concern, the drug alters cardiac conduction, with
dose-related pro-longation of QT and PR intervals. This effect is seen with
standard doses and is worsened by prior mefloquine therapy. Rare instances of
dangerous arrhythmias and deaths have been reported. The drug is
contraindicated in patients who have cardiac conduction defects or who have
recently taken mefloquine. Halofantrine is embryo-toxic in animals and
therefore contraindicated in pregnancy.
Lumefantrine, an aryl alcohol related to halofantrine, is avail-able only as a
fixed-dose combination with artemether (Coartem), which is now the first-line
therapy for uncomplicated falciparum malaria in many countries. In addition,
Coartem is approved in many nonendemic countries, including the USA. The
half-life of lumefantrine, when used in combination, is approximately 4 days.
Drug levels may be altered by interactions with other drugs, including those
that affect CYP3A4 metabolism, but this area has not been well studied. As with
halofantrine, oral absorption is highly variable and improved when the drug is
taken with food.
lumefantrine does not engender the dangerous toxicity con-cerns of
halofantrine, Coartem should be administered with fatty food to maximize
antimalarial efficacy. Coartem is highly effective in the treatment of
falciparum malaria when administered twice daily for 3 days. Coartem can cause
minor prolongation of the QT interval, but this appears to be clinically
insignificant, and the drug does not carry the risk of dangerous arrhythmias
seen with halofantrine and quinidine. Indeed, Coartem is very well toler-ated.
The most commonly reported adverse events in drug trials have been
gastrointestinal disturbances, headache, dizziness, rash, and pruritus, and in
many cases these toxicities may have been due to underlying malaria or
concomitant medications rather than to Coartem.