Peringatan Keamanan

Preclinical reproductive toxicity studies in animals showed fetal death and teratogenicity at doses lower than the recommended human dose. Use of miltefosine during pregnancy is therefore strictly contraindicated, and contraceptive use is mandatory for females of child-bearing age during therapy and for 5 months afterwards. Preclinical studies additionally showed impaired female and male fertility in animals. Stevens-Johnson syndrome has been reported, therefore therapy should be discontinued if an exfoliative or bullous rash occurs during treatment.

Miltefosine

DB09031

small molecule approved investigational

Deskripsi

Miltefosine is a broad spectrum antimicrobial, anti-leishmanial, phospholipid drug that was originally developed in the 1980s as an anti-cancer agent. It is currently the only recognized oral agent used to treat visceral, cutaneous, and mucosal forms of leishmaniasis, a neglected tropical disease. It can be administered topically or orally and is only indicated in patients aged 12 years or older. The CDC has also recommended it as a first line treatment for free-living amebae (FLA) infections such as primary amebic meningoencephalitis and granulomatous amebic encephalitis.

Struktur Molekul 2D

Berat 407.576
Wujud solid

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) The primary elimination half life is 7.05 days (range: 5.45-9.10 days) and the terminal half-life is 30.9 days (range: 30.8-31.2 days).
Volume Distribusi Radioactivity studies have found that miltefosine has a wide distribution with high levels in the kidney, intestinal mucosa, liver, and spleen.
Klirens (Clearance) Plasma clearance is very low and the terminal elimination half life was found to be 84 and 159 hours in rats and dogs respectively.

Absorpsi

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.

Metabolisme

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.

Rute Eliminasi

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.

Interaksi Makanan

2 Data
  • 1. Drink plenty of fluids. Preventing dehydration is important to prevent kidney injury.
  • 2. Take with food. Food reduces gastric irritation.

Interaksi Obat

52 Data
Dicoumarol The therapeutic efficacy of Dicoumarol can be increased when used in combination with Miltefosine.
Phenindione The therapeutic efficacy of Phenindione can be increased when used in combination with Miltefosine.
Warfarin The therapeutic efficacy of Warfarin can be increased when used in combination with Miltefosine.
Phenprocoumon The therapeutic efficacy of Phenprocoumon can be increased when used in combination with Miltefosine.
Acenocoumarol The therapeutic efficacy of Acenocoumarol can be increased when used in combination with Miltefosine.
4-hydroxycoumarin The therapeutic efficacy of 4-hydroxycoumarin can be increased when used in combination with Miltefosine.
Coumarin The therapeutic efficacy of Coumarin can be increased when used in combination with Miltefosine.
(R)-warfarin The therapeutic efficacy of (R)-warfarin can be increased when used in combination with Miltefosine.
Ethyl biscoumacetate The therapeutic efficacy of Ethyl biscoumacetate can be increased when used in combination with Miltefosine.
Fluindione The therapeutic efficacy of Fluindione can be increased when used in combination with Miltefosine.
Clorindione The therapeutic efficacy of Clorindione can be increased when used in combination with Miltefosine.
Diphenadione The therapeutic efficacy of Diphenadione can be increased when used in combination with Miltefosine.
Tioclomarol The therapeutic efficacy of Tioclomarol can be increased when used in combination with Miltefosine.
(S)-Warfarin The therapeutic efficacy of (S)-Warfarin can be increased when used in combination with Miltefosine.
Darbepoetin alfa The risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Miltefosine.
Erythropoietin The risk or severity of Thrombosis can be increased when Erythropoietin is combined with Miltefosine.
Peginesatide The risk or severity of Thrombosis can be increased when Peginesatide is combined with Miltefosine.
Methoxy polyethylene glycol-epoetin beta The risk or severity of Thrombosis can be increased when Methoxy polyethylene glycol-epoetin beta is combined with Miltefosine.
Lidocaine The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Lidocaine.
Ropivacaine The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Ropivacaine.
Bupivacaine The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Bupivacaine.
Cinchocaine The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Cinchocaine.
Dyclonine The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Dyclonine.
Procaine The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Procaine.
Prilocaine The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Prilocaine.
Proparacaine The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Proparacaine.
Meloxicam The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Meloxicam.
Oxybuprocaine The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Oxybuprocaine.
Cocaine The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Cocaine.
Mepivacaine The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Mepivacaine.
Levobupivacaine The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Levobupivacaine.
Diphenhydramine The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Diphenhydramine.
Benzocaine The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Benzocaine.
Chloroprocaine The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Chloroprocaine.
Phenol The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Phenol.
Tetrodotoxin The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Tetrodotoxin.
Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Benzyl alcohol.
Capsaicin The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Capsaicin.
Etidocaine The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Etidocaine.
Articaine The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Articaine.
Tetracaine The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Tetracaine.
Propoxycaine The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Propoxycaine.
Pramocaine The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Pramocaine.
Butamben The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Butamben.
Butacaine The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Butacaine.
Oxetacaine The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Oxetacaine.
Ethyl chloride The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Ethyl chloride.
Butanilicaine The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Butanilicaine.
Metabutethamine The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Metabutethamine.
Quinisocaine The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Quinisocaine.
Ambroxol The risk or severity of methemoglobinemia can be increased when Miltefosine is combined with Ambroxol.
Etrasimod The risk or severity of immunosuppression can be increased when Miltefosine is combined with Etrasimod.

Target Protein

Phospholipase A2 PLA2G1B
ATP-dependent translocase ABCB1 ABCB1

Referensi & Sumber

Synthesis reference: Eibl H, Engel J: Synthesis of hexadecylphosphocholine (miltefosine). Prog Exp Tumor Res. 1992;34:1-5. Pubmed(http://www.ncbi.nlm.nih.gov/pubmed/1438793)
Artikel (PubMed)
  • PMID: 25601455
    Monge-Maillo B, Lopez-Velez R: Miltefosine for visceral and cutaneous leishmaniasis: drug characteristics and evidence-based treatment recommendations. Clin Infect Dis. 2015 May 1;60(9):1398-404. doi: 10.1093/cid/civ004. Epub 2015 Jan 18.
  • PMID: 18519729
    Dorlo TP, van Thiel PP, Huitema AD, Keizer RJ, de Vries HJ, Beijnen JH, de Vries PJ: Pharmacokinetics of miltefosine in Old World cutaneous leishmaniasis patients. Antimicrob Agents Chemother. 2008 Aug;52(8):2855-60. doi: 10.1128/AAC.00014-08. Epub 2008 Jun 2.
  • PMID: 22833634
    Dorlo TP, Balasegaram M, Beijnen JH, de Vries PJ: Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis. J Antimicrob Chemother. 2012 Nov;67(11):2576-97. doi: 10.1093/jac/dks275. Epub 2012 Jul 24.
  • PMID: 16730362
    Sindermann H, Engel J: Development of miltefosine as an oral treatment for leishmaniasis. Trans R Soc Trop Med Hyg. 2006 Dec;100 Suppl 1:S17-20. Epub 2006 May 26.
  • PMID: 12384352
    Saraiva VB, Gibaldi D, Previato JO, Mendonca-Previato L, Bozza MT, Freire-De-Lima CG, Heise N: Proinflammatory and cytotoxic effects of hexadecylphosphocholine (miltefosine) against drug-resistant strains of Trypanosoma cruzi. Antimicrob Agents Chemother. 2002 Nov;46(11):3472-7.
  • PMID: 16344287
    Blaha C, Duchene M, Aspock H, Walochnik J: In vitro activity of hexadecylphosphocholine (miltefosine) against metronidazole-resistant and -susceptible strains of Trichomonas vaginalis. J Antimicrob Chemother. 2006 Feb;57(2):273-8. Epub 2005 Dec 12.
  • PMID: 16436691
    Widmer F, Wright LC, Obando D, Handke R, Ganendren R, Ellis DH, Sorrell TC: Hexadecylphosphocholine (miltefosine) has broad-spectrum fungicidal activity and is efficacious in a mouse model of cryptococcosis. Antimicrob Agents Chemother. 2006 Feb;50(2):414-21.

Contoh Produk & Brand

Produk: 2 • International brands: 1
Produk
  • Impavido
    Capsule • 50 mg/1 • Oral • US • Approved
  • Impavido
    Capsule • 50 mg/1 • Oral • US • Approved
International Brands
  • Miltex — Baxter

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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