Miltefosine

Source: Wikipedia, the free encyclopedia.
Miltefosine
Clinical data
Trade namesImpavido, Miltex, others
AHFS/Drugs.comMonograph
License data
QP51DX07 (WHO)
Legal status
Legal status
  • BR: Class C1 (Other controlled substances)[2]
  • US: WARNING[1]Rx-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
BioavailabilityHigh
Protein binding~98%
MetabolismSlow hepatic (non-CYP-dependent)
Elimination half-life6 to 8 days and 31 days[3]
ExcretionPrimarily fecal
Identifiers
  • 2-(hexadecoxy-oxido-phosphoryl)oxyethyl-trimethyl-azanium
JSmol)
Melting point232 to 234 °C (450 to 453 °F)
  • [O-]P(=O)(OCCCCCCCCCCCCCCCC)OCC[N+](C)(C)C
  • InChI=1S/C21H46NO4P/c1-5-6-7-8-9-10-11-12-13-14-15-16-17-18-20-25-27(23,24)26-21-19-22(2,3)4/h5-21H2,1-4H3 checkY
  • Key:PQLXHQMOHUQAKB-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Miltefosine, sold under the trade name Impavido among others, is a medication mainly used to treat

liposomal amphotericin B or paromomycin.[6] It is taken by mouth.[5]

Common side effects include

headaches, and decreased kidney function.[4] More severe side effects may include Stevens–Johnson syndrome or low blood platelets.[4] Use during pregnancy appears to cause harm to the baby and use during breastfeeding is not recommended.[4] How it works is not entirely clear.[4]

Miltefosine was first made in the early 1980s and studied as a treatment for cancer.[7] A few years later it was found to be useful for leishmaniasis and was approved for this use in 2002 in India.[8] It is on the World Health Organization's List of Essential Medicines.[9][10]

Medical uses

Leishmaniasis

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.[11][12] This drug is now listed as a core medication for the treatment of leishmaniasis under the WHO Model List of Essential Medicines.[13] Several medical agents have some efficacy against visceral or cutaneous leishmaniasis, however, a 2005 survey concluded that miltefosine is the only effective oral treatment for both forms of leishmaniasis.[14]

Amoeba infections

Miltefosine has been used successfully in some cases of the very rare, but highly lethal, brain infection by the amoeba,

primary amebic meningoencephalitis (PAM).[16][17]

Pregnancy and breastfeeding

Miltefosine is listed as pregnancy category D by the FDA. This means there is evidence-based adverse reaction data from investigational or marketing experience or studies in humans of harm to the human fetus.[18] Despite this evidence, the potential benefits of miltefosine may warrant use of the drug in pregnant women despite potential risks. A pregnancy test should be done prior to starting treatment. Effective birth control should be used while on miltefosine and 5 months after discontinuation of treatment. Its use during breast feeding is most likely unsafe.[3]

Contraindications

Miltefosine is contraindicated in individuals who have a

contraception is required beyond the end of treatment in women of child-bearing age.[20]

Side effects

Common side effects from miltefosine treatment are nausea and vomiting, which occur in 60% of people. Other common side effects are dizziness, headache, and daytime sleepiness.[21]

Serious side effects include rash, diarrhea, and arthritis.[21] The side effects are more severe in women and young children. The overall effects are quite mild and easily reversed.[22]

Mechanism of action

Miltefosine primarily acts on Leishmania by affecting the species's promastigote and amastigote stages.[23] Miltefosine exerts its activity by interacting with lipids, inhibiting cytochrome c oxidase and causing apoptosis-like cell death.[24] This may affect membrane integrity and mitochondrial function of the parasite.[citation needed]

History

Cancer

While initially studied as a cancer medication, due to side effects it was never used for this purpose.[25]

colonic tumors of rats.[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]

Leishmaniasis

In the same year as the discovery of the anticancer property, miltefosine was reported by S. L. Croft and his team at the

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.[3]

Naegleria fowleri and Acanthamoeba

In 2013, the US

primary amoebic meningoencephalitis, two fatal protozoal diseases.[36] Historically, only four survivors have been recorded out of 138 confirmed infections in North America. One American survived the infection in 1978 and one individual from Mexico in 2003. In 2013, two children survived and recovered from primary amoebic meningoencephalitis after treatment with miltefosine.[37][38] In 2016 after treatment that included miltefosine, another child became the fourth person in the United States to survive Naegleria fowleri infection.[39]

Society and culture

Availability

Since 2017 Miltefosine is commercially available in the United States through Profounda.

primary amoebic meningoencephalitis caused by Naegleria fowleri and granulomatous amoebic encephalitis caused by Balamuthia mandrillaris and Acanthamoeba species.[37] Miltefosine is almost exclusively produced by Profounda, a private pharmaceutical company.[41]

Economics

In the

developed world treatment may be 10 to 50 times greater.[6]

Further research

It is active against some

trematode Schistosoma mansoni and the snail that spreads it Biomphalaria alexandrina.[43]

Antiprotozoal and antifungal activities

Miltefosine is being investigated by researchers interested in finding treatments for infections which have become resistant to existing drugs. Animal and in vitro studies suggest it may have broad anti-protozoal and anti-fungal properties:

Anti-HIV activity

Miltefosine targets HIV infected

CD4+ T cells, which is due to a rapid secretion of soluble factors and is associated with induction of type-I interferon (IFN) in the human cells.[58]

References

  1. FDA
    . Retrieved 22 Oct 2023.
  2. ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  3. ^
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  4. ^ a b c d e American Society of Health-System Pharmacists (26 February 2016). "Miltefosine Monograph for Professionals". www.drugs.com. Archived from the original on 17 November 2016. Retrieved 16 November 2016.
  5. ^ a b "FDA approves Impavido to treat tropical disease leishmaniasis". U.S. Food and Drug Administration (FDA) (Press release). 19 March 2014. Archived from the original on 3 September 2014. Retrieved 30 August 2014.
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  10. hdl:10665/345533
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  17. ^ "FDA Orphan Drug Designation Granted to Profounda Inc. for the treatment of Acanthamoeba Keratitis with miltefosine". Profounda Inc. Archived from the original on 2016-12-21. Retrieved 2017-05-25 – via www.prnewswire.com.
  18. ^ "New FDA Pregnancy Categories Explained". Drugs.com. Archived from the original on 2016-11-16. Retrieved 2016-11-16.
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External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Miltefosine&oldid=1199339013"