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| Clinical data | |
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| Trade names | Ancobon, Ancotil, others |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a601132 |
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| Routes of administration | By mouth,intravenous |
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| Pharmacokinetic data | |
| Bioavailability | 75 to 90% (by mouth) |
| Protein binding | 2.9 to 4% |
| Metabolism | minimal, in theGI tract |
| Eliminationhalf-life | 2.4 to 4.8 hours |
| Excretion | kidney (90%) |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.016.336 |
| Chemical and physical data | |
| Formula | C4H4FN3O |
| Molar mass | 129.094 g·mol−1 |
| 3D model (JSmol) | |
| Melting point | 295 to 297 °C (563 to 567 °F) (dec.) |
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Flucytosine, also known as5-fluorocytosine (5-FC), is anantifungal medication.[1] It is specifically used, together withamphotericin B, for seriousCandida infections andcryptococcosis.[1] It may be used by itself or with other antifungals forchromomycosis.[1] Flucytosine is usedby mouth and byinjection into a vein.[1][2]
Common side effects includebone marrow suppression, loss of appetite,diarrhea, vomiting, andpsychosis.[1]Anaphylaxis and otherallergic reactions occasionally occur.[1] It is unclear if use inpregnancy is safe for the baby.[3] Flucytosine is in the fluorinatedpyrimidine analogue family of medications.[1] It works by being converted intofluorouracil inside the fungus, which impairs its ability tomakeprotein.[1]
Flucytosine was first made in 1957.[4] It is on theWorld Health Organization's List of Essential Medicines.[5] It is not available in much of thedeveloping world.[6]
Flucytosine by mouth is used for the treatment of serious infections caused by susceptible strains ofCandida orCryptococcus neoformans. It can also be used for the treatment ofchromomycosis (chromoblastomycosis), if susceptible strains cause the infection. Flucytosine must not be used as a sole agent in life-threatening fungal infections due to relatively weak antifungal effects and fast development of resistance, but rather in combination with amphotericin B and/orazole antifungals such asfluconazole oritraconazole. Minor infections such as candidalcystitis may be treated with flucytosine alone. In some countries, treatment with slowintravenous infusions for no more than a week is also a therapeutic option, particular if the disease is life-threatening.[citation needed]
Serious fungal infections may occur in those who are immunocompromised. These people benefit from combination therapy including flucytosine, but the incidence of side-effects of a combination therapy, particular with amphotericin B, may be higher.[citation needed]
In animal models (rats), flucytosine has been found to beteratogenic. Sufficient human data does not exist.Pregnant women should be given flucytosine only if the potential benefits exceed the potential harm to the fetus.[citation needed]
It is not known if flucytosine is distributed in human breast milk. Given the potential risk to the child, the patient should notbreastfeed during treatment with flucytosine.[citation needed]
The efficacy and safety in patients under 18 years of age has not been determined.[citation needed]
It is not known if flucytosine is a humancarcinogen. The issue has been raised because traces of5-fluorouracil, which is a known carcinogen, are found in the colon resulting from the metabolization of flucytosine.
Flucytosine may increase the toxicity ofamphotericin B and vice versa, although the combination may be life-saving and should be used whenever indicated (e.g.,cryptococcal meningitis). The cytostaticcytarabine inhibits the antimycotic activity of flucytosine.[citation needed]
Symptoms and their severities are unknown, because flucytosine is used under close medical supervision, but expected to be an excess of the usually encounteredside effects on thebone marrow, gastrointestinal tract,liver andkidney function. Vigorous hydration andhemodialysis may be helpful in removing the drug from the body. Hemodialysis is particular useful in patients with impaired renal function.[citation needed]
Two major mechanisms of action have been elucidated:
Flucytosine is activein vitro as well asin vivo against some strains ofCandida andCryptococcus. Limited studies demonstrate that flucytosine may be of value against infections withSporothrix,Aspergillus,Cladosporium,Exophiala, andPhialophora.Resistance is quite commonly seen as well in treatment-naive patients and under current treatment with flucytosine. In different strains ofCandida resistance has been noted to occur in 1 to 50% of all specimens obtained from patients.[citation needed]
Flucytosine is well absorbed (75 to 90%) from thegastrointestinal tract. Intake with meals slows the absorption, but does not decrease the amount absorbed. Following an oral dose of 2 grams peak serum levels are reached after approximately 6 hours. The time to peak level decreases with continued therapy. After 4 days peak levels are measured after 2 hours. The drug is eliminated renally. In normal patients flucytosine has reportedly a half-life of 2.5 to 6 hours. In patients with impaired renal function higher serum levels are seen and the drug tends to accumulate. The drug is mainly excreted unchanged in the urine (90% of an oral dose) and only traces are metabolized and excreted in the feces. Therapeutic serum levels range from 25 to 100 μg/ml. Serum levels in excess of 100 μg are associated with a higher incidence of side effects. Periodic measurements of serum levels are recommended for all patients and are a must in patients with renal damage.[citation needed]
Although a generic, off patent medication in the U.S., as of January 2016, there was only one FDA-approved pharmaceutical supplier,Valeant Pharmaceuticals.In the United Kingdom and Europe its available viaMeda AB Pharmaceuticals.
In some countries, such asSwitzerland, flucytosine has been licensed to treat cats, dogs and birds (in most cases together with amphotericin B) for the same indications as in humans.[citation needed]
