Fosine
Fosine Uses, Dosage, Side Effects, Food Interaction and all others data.
Fosine 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.
Little is known about the clinical pharmacodynamics of miltefosine and other antileishmanial drugs.
| Trade Name | Fosine |
| Availability | Prescription only |
| Generic | Miltefosine |
| Miltefosine Other Names | HDPC, Hexadecylphosphocholine, Hexadecylphosphorylcholine, Miltefosin, Miltefosina, Miltéfosine, Miltefosine, Monohexadecylphosphocholine, Monohexadecylphosphorylcholine |
| Related Drugs | amphotericin b, pentamidine, AmBisome, Abelcet |
| Weight | 50mg |
| Type | Capsule |
| Formula | C21H46NO4P |
| Weight | Average: 407.576 Monoisotopic: 407.316445963 |
| Protein binding | Plasma protein binding ranges from 96% to 98%. Miltefosine binds to both serum albumin (97% bound) and low-density lipoprotein (3% bound). |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | Nimrall Laboratories |
| Available Country | Pakistan |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Fosine is an antileishmanial agent used to treat leishmaniasis, a group of disease caused by parasites of the Leishmania type.
For the treatment of mucosal (caused by Leishmania braziliensis), cutaneous (caused by L. braziliensis, L. guyanensis, and L. panamensis), and visceral leishmaniasis (caused by L. donovani). In comparing Leishmania drug susceptibility, it has been found that L. donovani is the most susceptible to miltefosine while L. major is the least susceptible. Off-label use includes treatment of free-living amebae (FLA) infections (unlabeled use; CDC, 2013).
Fosine is also used to associated treatment for these conditions: Leishmaniasis, Cutaneous, Mucocutaneous Leishmaniasis, Specific infections by free-living amoebae, Visceral Leishmaniasis
How Fosine works
Fosine 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.
Toxicity
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.
Food Interaction
- Drink plenty of fluids. Preventing dehydration is important to prevent kidney injury.
- Take with food. Food reduces gastric irritation.
[Moderate] ADJUST DOSING INTERVAL: Administration of miltefosine with food may help reduce gastrointestinal adverse effects such as nausea, vomiting, abdominal pain, and diarrhea.
MANAGEMENT: Fosine should be administered with meals to help improve gastrointestinal tolerance.
Patients should be advised to contact their physician if they develop severe or persistent vomiting or diarrhea, and to drink plenty of fluids to help prevent dehydration and kidney injury.
Fosine Disease Interaction
Major: Sjogren-Larsson syndromeModerate: liver disease, renal dysfunction, thrombocytopenia
Volume of Distribution
Radioactivity studies have found that miltefosine has a wide distribution with high levels in the kidney, intestinal mucosa, liver, and spleen.
Elimination Route
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.
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).
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.
Elimination Route
Fosine 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.
Innovators Monograph
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