Miltefosine is an alkylphosphocholine
drug with demonstrated activity against various parasite species and
cancer cells as well as some pathogenic bacteria and fungi. For 10 years it has been licensed in India for the treatment of
visceral leishmaniasis (VL), a fatal neglected
parasitic disease. It is the first and still the only oral
drug that can be used to treat VL and
cutaneous leishmaniasis (CL). The standard 28 day
miltefosine monotherapy regimen is well tolerated, except for mild gastrointestinal side effects, although its teratogenic potential severely hampers its general use in the clinic and roll-out in national elimination programmes. The pharmacokinetics of
miltefosine are mainly characterized by its long residence time in the body, resulting in extensive
drug accumulation during treatment and long elimination half-lives. At the moment, different combination
therapy strategies encompassing
miltefosine are being tested in multiple controlled clinical trials in various geographical areas of endemicity, both in South Asia and East Africa. We here review the most salient pre-clinical and clinical pharmacological aspects of
miltefosine, its mechanism of action against Leishmania parasites and other pathogens, and provide a systematic overview of the efficacy and safety data from all clinical trials of
miltefosine, either alone or in combination, in the treatment of VL and CL.