Miltefosine

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Antileishmaniasis medicines

Danger

H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]

P203, P233, P260, P264, P264+P265, P270, P271, P280, P284, P301+P316, P304+P340, P305+P351+P338, P318, P319, P321, P330, P337+P317, P342+P316, P403, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 79 reports by companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Serum aminotransferase levels are frequently elevated in patients with visceral leishmaniasis and miltefosine therapy regularly results in a decline in mean values into the normal range. In prospective studies of miltefosine therapy, however, as many as half of patients had mild-to-moderate ALT elevations during therapy, although values above 5 times ULN were rare (

Drug Induced Liver Injury Rank (DILIrank 2.0)

Miltefosine

Ambiguous-DILI-concern

4

Warnings & precautions

DOI:10.1016/j.drudis.2016.02.015

P - Antiparasitic products, insecticides and repellents

QP - Antiparasitic products, insecticides and repellents

P01CX04

Miltefosine has demonstrated activity against Leishmania parasites and neoplastic cells primarily due to its effects on apoptosis and disturbance of lipid-dependent cell signalling pathways. Several potential antileishmanial mechanisms of action have been proposed, however no mechanism has been identified definitely. Within the mitochondria, miltefosine inhibits cytochrome-c oxidase leading to mitochondrial dysfunction and apoptosis-like cell death. Antineoplastic mechanisms of action are related to antileishmanial targets and include inhibition of phosphatidylcholine biosynthesis and inhibition of Akt (also known as protein kinase B), which is a crucial protein within the PI3K/Akt/mTOR intracellular signalling pathway involved in regulating the cell cycle. Animal studies also suggest it may be effective against Trypanosome cruzi (the organism responsible for Chagas' disease), metronidazole-resistant strains of Trichonomas vaginalis, and it may have broad-spectrum anti-fungal activity.

Miltefosine is metabolized mainly by phospholipase D, releasing choline, choline-containing metabolites, and hexadecanol, which are likely to enter the intermediary metabolism. The metabolites produced by this reaction are all endogenous and are likely used for bio-synthesis of acetylcholine, cell membranes, and long-chain fatty acids.