title: Oral miltefosine for the treatment of Indian visceral leishmaniasis.
abstract: Large-scale antimony resistance in the treatment of visceral leishmaniasis (VL) in north Bihar, India, has led to the development of miltefosine as an alternative therapy. In a pilot study and later in three Phase II studies involving 249 patients, oral miltefosine, 100-150 mg/day for 28 days, was shown to cure approximately 90% patients with reasonable safety. In the pivotal Phase III trial, 299 patients were treated at three centres with amphotericin B as the comparator drug (99 patients). In this trial 38% and 20% patients had mild to moderate vomiting and diarrhoea respectively, similar to previous studies. Asymptomatic transient elevation of hepatic transaminases and mild renal dysfunction were observed in 15% and 10% patients respectively. The final cure rate was 94% with miltefosine and 97% with amphotericin B; based on these results, the drug was approved in India. Subsequently in two paediatric studies involving 119 patients in the age group of 2-11 years, the safety and efficacy of miltefosine (2.5 mg/kg daily for 28 days) was established with a cure rate (94%) similar to that seen in adults. Miltefosine is the first oral antileishmanial drug with a high degree of safety and efficacy for the treatment of VL.
authors.affiliation: Kala-azar Medical Research Center, Banaras Hindu University, Varanasi, India. drshyamsundar@dataone.in
authors.forename: Shyam
authors.initials: S
authors.lastname: Sundar
authors.forename: T K
authors.initials: TK
authors.lastname: Jha
authors.forename: C P
authors.initials: CP
authors.lastname: Thakur
authors.forename: S K
authors.initials: SK
authors.lastname: Bhattacharya
authors.forename: M
authors.initials: M
authors.lastname: Rai
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002986:Clinical Trials as Topic; D006801:Humans; D007194:India; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D015337:Multicenter Studies as Topic; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D010865:Pilot Projects; D016896:Treatment Outcome
chemical_list: D000981:Antiprotozoal Agents; D010767:Phosphorylcholine; C039128:miltefosine