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.

53EY29W7EC

MILTEFOSINE

Established Pharmacologic Class [EPC] - Antileishmanial

Miltefosine is an Antileishmanial.

MILTEFOSINE

Antileishmanial [EPC]

Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues.

Substances that inhibit or prevent the proliferation of NEOPLASMS.

Substances that are destructive to protozoans.

After oral administration, miltefosine is slowly absorbed from the gastrointestinal tract with an absolute bioavailability of 82% in rats and 94% in dogs. Absolute bioavailability has not been assessed in humans, however GI absorption rate in a two-compartment model is estimated to be 0.416 hr-1.

Miltefosine is almost completely eliminated by degradation via phospholipase D. Drug keeps accumulating until the end of treatment due to the extremely slow elimination, as seen by the long elimination half lives.

Radioactivity studies have found that miltefosine has a wide distribution with high levels in the kidney, intestinal mucosa, liver, and spleen.

Plasma clearance is very low and the terminal elimination half life was found to be 84 and 159 hours in rats and dogs respectively.