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Clinical Trial
. 1993 Apr 24;341(8852):1044-9.
doi: 10.1016/0140-6736(93)92409-m.

Halofantrine Versus Mefloquine in Treatment of Multidrug-Resistant Falciparum Malaria

Clinical Trial

Halofantrine Versus Mefloquine in Treatment of Multidrug-Resistant Falciparum Malaria

F O ter Kuile et al. Lancet. .


The continuing spread of multidrug resistance in Plasmodium falciparum malaria makes the search for alternative treatments ever more urgent. We have investigated the relative efficacy of halofantrine and mefloquine in two paired randomised trials on the Thai-Burmese border, a multidrug-resistant area. In the first trial, 198 patients with acute uncomplicated falciparum malaria were randomly assigned either the standard halofantrine regimen (24 mg/kg) or mefloquine (25 mg/kg). The cumulative failure rates by day 28 were 35% with halofantrine and 10% with mefloquine (p = 0.0002). In the second study of 437 patients, a higher dose of halofantrine (8 mg/kg every 8 h for 3 days = 72 mg/kg) was both more effective and better tolerated than mefloquine 25 mg/kg; the failure rates were 3% and 8% (p = 0.03), respectively, or 1% vs 6% after adjustment for possible reinfections (p = 0.009). The rate of failure was higher after retreatment than after primary treatment in all study groups. Halofantrine 72 mg/kg was especially effective in the retreatment of these recrudescent infections; the failure rate was 44% with mefloquine and 15% with high-dose halofantrine (relative risk 3.0 [95% CI 1.2-7.3], p = 0.008). Thus, high-dose halofantrine is better tolerated and more effective than mefloquine for the treatment of uncomplicated falciparum malaria in this area. However, evidence of possible cardiotoxicity will need to be investigated fully before a role can be established for halofantrine in the treatment of multidrug-resistant malaria.

Comment in

  • Prolonged QT interval with halofantrine.
    Castot A, Rapoport P, Le Coz P. Castot A, et al. Lancet. 1993 Jun 12;341(8859):1541. Lancet. 1993. PMID: 8099419 No abstract available.
  • Prolonged QT interval with halofantrine.
    Monlun E, Pillet O, Cochard JF, Favarel Garrigues JC, le Bras M. Monlun E, et al. Lancet. 1993 Jun 12;341(8859):1541-2. Lancet. 1993. PMID: 8099420 No abstract available.
  • Mefloquine.
    Burke BM. Burke BM. Lancet. 1993 Jun 19;341(8860):1605-6. doi: 10.1016/0140-6736(93)90751-2. Lancet. 1993. PMID: 8099690 No abstract available.

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