Halofantrine. A review of its antimalarial activity, pharmacokinetic properties and therapeutic potential

Halofantrine is an orally administered blood schizontocide which is active against both chloroquine-sensitive and chloroquine-resistant plasmodia. Dose-finding and noncomparative clinical trials have confirmed the efficacy of halofantrine in the treatment of falciparum malaria in areas of chloroquine- and sulfonamide/pyrimethamine-resistant malaria and vivax malaria. However, poor results obtained in patients who failed mefloquine prophylaxis suggest that the efficacy of halofantrine may not extend to mefloquine-resistant P. falciparum, although more studies are needed to confirm this. Data concerning halofantrine in the treatment of P. ovale and P. malariae infections are still limited. One comparative study indicates that halofantrine has an efficacy equivalent to that of mefloquine and may be better tolerated. Halofantrine is generally well tolerated in both adults and children, the most common drug-associated effects being abdominal pain, pruritus, vomiting, diarrhoea, headache and rash, although it is difficult to distinguish between disease- and treatment-related events. The development of parasite resistance to halofantrine, like other blood schizontocides, is inevitable. Poor absorption resulting in variable peak plasma halofantrine concentrations, and possible cross-resistance with mefloquine, may accelerate the emergence of resistance to halofantrine. Thus, it is of primary importance that halofantrine is used only in areas where chloroquine- and sulfonamide/pyrimethamine-resistance are established in order to preserve and sustain its efficacy. If used with care, halofantrine will provide an important treatment option for falciparum malaria, a widespread parasitic disease associated with considerable morbidity against which the number of effective drugs available is being increasingly compromised by the spread of resistance.