Miltefosine, sold under the trade name Impavido among others, is a medication mainly used to treat leishmaniasis and free-living amoeba infections such as Naegleria fowleri and Balamuthia mandrillaris.

[5] Common side effects include vomiting, abdominal pain, fever, headaches, and decreased kidney function.

[9][10] Miltefosine is primarily used for the treatment of visceral and New World cutaneous leishmaniasis, and is undergoing clinical trials for this use in several countries.

[23] Miltefosine exerts its activity by interacting with lipids, inhibiting cytochrome c oxidase and causing apoptosis-like cell death.

[29][30] It was subsequently found that miltefosine was structurally unique among lipids having anticancer property in that it lacks the glycerol group, is highly selective on cell types and acts through different mechanism.

[31][32] In the same year as the discovery of the anticancer property, miltefosine was reported by S. L. Croft and his team at the London School of Hygiene and Tropical Medicine as having antileishmanial effect as well.

In 1992 a new research was reported in which the compound was highly effective in mouse against different life cycle stages of different Leishmania species, and in fact, more potent than the conventional sodium stibogluconate therapy by a factor of more than 600.

[34] Results of the first clinical trial in humans were reported from Indian patients with chronic leishmaniasis with high degree of success and safety.

[35] This promising development promulgated a unique public–private partnership collaboration between ASTA Medica (later Zentaris GmbH), the World Health Organization (WHO) Special Programme for Research and Training in Tropical Diseases, and the Government of India.

Eventually, several successful Phase II and III trials led to the approval of miltefosine in 2002 as the first and only oral drug for leishmaniasis.

[37][38] In 2016 after treatment that included miltefosine, another child became the fourth person in the United States to survive Naegleria fowleri infection.

Animal and in vitro studies suggest it may have broad anti-protozoal and anti-fungal properties: Miltefosine targets HIV infected macrophages, which play a role in vivo as long-lived HIV-1 reservoirs.