Miltefosine, an oral agent, for the treatment of Indian visceral leishmaniasis

N Engl J Med. 1999 Dec 9;341(24):1795-800. doi: 10.1056/NEJM199912093412403.


Background: There is no effective orally administered medication for any leishmania infection. We investigated miltefosine, which can be taken orally, for the treatment of Indian visceral leishmaniasis. Miltefosine is a phosphocholine analogue that affects cell-signaling pathways and membrane synthesis.

Methods: The study was an open-label, multicenter, phase 2 trial in which four 30-person cohorts received 50, 100, or 150 mg of miltefosine per day for four or six weeks. The 120 patients, who ranged in age from 12 to 50 years, had anorexia, fever, and splenomegaly with at least moderate (2+) leishmania in a splenic aspirate. A parasitologic cure was defined by the absence of parasites in a splenic aspirate obtained two weeks after completion of treatment. The clinical response was assessed at six months.

Results: In all 120 patients there was an initial parasitologic cure. Six patients had clinical and parasitologic relapses; the remaining 114 patients had not relapsed by six months after treatment, for a cure rate of 95 percent (95 percent confidence interval, 89 to 98 percent). With the regimen of 100 mg of miltefosine per day (approximately 2.5 mg per kilogram of body weight per day) for four weeks, 29 of 30 patients (97 percent) were cured. Gastrointestinal side effects were frequent (occurring in 62 percent of patients) but mild to moderate in severity, and no patient discontinued therapy because of gastrointestinal side effects. In two patients, treatment was discontinued because of elevated levels of aspartate aminotransferase or creatinine; in both patients the levels rapidly returned to normal. In 12 other patients, the level of aspartate aminotransferase increased to 100 to 150 U per liter during treatment.

Conclusions: Orally administered miltefosine appears to be an effective treatment for Indian visceral leishmaniasis.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Antiprotozoal Agents / adverse effects
  • Antiprotozoal Agents / therapeutic use*
  • Aspartate Aminotransferases / drug effects
  • Female
  • Gastrointestinal Diseases / chemically induced
  • Humans
  • Leishmaniasis, Visceral / drug therapy*
  • Male
  • Middle Aged
  • Phosphorylcholine / adverse effects
  • Phosphorylcholine / analogs & derivatives*
  • Phosphorylcholine / therapeutic use
  • Recurrence
  • Treatment Outcome


  • Antiprotozoal Agents
  • Phosphorylcholine
  • miltefosine
  • Aspartate Aminotransferases