Evaluation of the safety and efficacy of micronized halofantrine in the treatment of semi-immune patients with acute, Plasmodium falciparum malaria.

The efficacy of the standard formulation of halofantrine hydrochloride has been compromised by the formulation's irregular bio-availability. A micronized preparation of the drug has now been evaluated in the treatment of malaria in northern Tanzania. Overall, 100 patients with mild to moderate Plasmodium falciparum malaria were recruited and treated with the preparation over 18 h. Those weighing > 40 kg were each given three, 500-mg doses and those weighing less were given roughly equivalent doses/kg. The 95 evaluable patients were all successfully treated, with a mean fever-clearance time of 22.5 h (range 4-76 h) and a mean parasite-clearance time of 35.6 h (range 15-66 h). There were no relapses. Abdominal pain was the commonest adverse event reported (22 cases). A single patient died suddenly in the recovery phase; the cause of this event was not determined. Further studies are required to evaluate the pharmacokinetics of the halofantrine formulation under field conditions.

A new micronized formulation of halofantrine hydrochloride in the treatment of acute Plasmodium falciparum malaria.

The current formulation of halofantrine hydrochloride has poor absorption and bioavailability. A newly developed micronized formulation was evaluated for efficacy, safety and tolerance in the treatment of acute Plasmodium falciparum malaria. The study was conducted at a plantation hospital in northern Tanzania, where chloroquine resistance is common. Sixty in-patients with mild or moderate malaria were treated with 375-750 mg micronized halofantrine hydrochloride given in 3 equal doses, 6 h apart. Patients were followed up for 28 d after therapy. Treatment was associated with rapid parasite clearance (mean clearance time = 34.8 h), fever clearance (mean time = 20 h), and clinical improvement (70% of patients were free of all presenting symptoms within 2 d). The formulation was well tolerated clinically, although 3 patients (5%) developed mild pruritus after treatment which may have been drug-related. Haematological and biochemical studies did not indicate any significant toxicity. One patient, whose immediate recovery was uneventful, was found to have a headache and low parasitaemia 3 weeks after treatment. He was readmitted to the study and treated as before. Parasitaemia, fever and headache cleared rapidly and he remained aparasitaemic for 28 d.