Clinical experience with halofantrine in the treatment of malaria.

Halofantrine hydrochloride (HF) belongs to a new class of antimalarials, the phenanthrene methanols. Preliminary clinical studies suggested that an adult dose of 500 mg 6-hourly for three doses, with a weight-based regimen of 8 mg/kg 6-hourly for three doses in children, would be effective. In an ongoing clinical programme, 1973 patients with acute malaria were analysed, of whom 1474 (1315 with P. falciparum and 122 with P. vivax malaria) received the above regimen. In the studies 931 adults and older children were treated (61 with capsules and 870 with tablets) while 520 infants and young children used 5% or 2% suspension. The majority of studies were performed in areas of high chloroquine or multidrug resistance. Only eight (0.6%) of 1282 evaluable patients with falciparum malaria failed to clear their parasitaemias within 7 days. Recrudescence of parasitaemia occurred in 77 patients (6.0%). Reinfection cannot be excluded in several of the cases, where protection from malaria transmission was not maintained. The majority of recrudescent patients were either non-immune (normally residing in malaria-free areas) or were infants below 2 years of age. In vivax malaria cases, there were six recrudescences (5.4%). The mean parasite clearance time was 57.9 h and the fever clearance time 50.2 h in falciparum malaria cases, while the clearance times for vivax cases were 57.3 h and 49.6 h respectively. Clinical events were uncommon and consisted of mild transient diarrhoea or abdominal pain in less than 5% of cases. Laboratory findings were generally abnormalities related to the acute disease rather than drug treatment. Experience to date would indicate that HF is a safe and useful drug for the treatment of acute malaria, particularly in areas where there is extensive resistance to current antimalarials.