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

Background: There is no effective orally administered medication for any le ishmania infection. We investigated miltefosine, which can be taken orally, for the treatment of Indian visceral leishmaniasis. Miltefosine is a phosp hocholine analogue that affects cell-signaling pathways and membrane synthe sis. Methods: The study was an open-label, multicenter, phase 2 trial in which f our 30-person cohorts received 50, 100, or 150 mg of miltefosine per day fo r four or six weeks. The 120 patients, who ranged in age from 12 to 50 year s, had anorexia, fever, and splenomegaly with at least moderate (2+) leishm ania 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 p atients had clinical and parasitologic relapses; the remaining 114 patients had not relapsed by six months after treatment, for a cure rate of 95 perc ent (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 w eight per day) for four weeks, 29 of 30 patients (97 percent) were cured. G astrointestinal side effects were frequent (occurring in 62 percent of pati ents) but mild to moderate in severity, and no patient discontinued therapy because of gastrointestinal side effects. In two patients, treatment was d iscontinued because of elevated levels of aspartate aminotransferase or cre atinine; in both patients the levels rapidly returned to normal. In 12 othe r 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 tre atment for Indian visceral leishmaniasis. (N Engl J Med 1999;341:1795-800.) (C)1999, Massachusetts Medical Society.