Flucytosine
Flucytosine (5-fluorocytosine; 5-FC; 4-amino-5-fluoro-2-pyrimidone) is an antimetabolite type of antifungal drug. It is chemically a pyrimidine. It is activated by deamination within the fungal cells to 5-fluorouracil. Flucytosine is marketed as AncobonTM by Roche Laboratories. It is available as oral capsules since 1972 in USA. Its intravenous formulation is no longer available.
Usual Doses
Flucytosine has traditionally been administered at a dose of 37.5 mg/kg/day four times daily. However, recent data suggest that lower doses may be equally efficacious . The recent major studies of cryptococcal meningitis have, for example, used doses of 25 mg/kg/day four times daily . Monitoring of creatinine levels is required, as it is necessary to adjust the dose of flucytosine in cases whose renal functions are disturbed due to concommittant amphotericin B therapy. Creatinine levels at and above 1.7 mg/dl necessitate dose reduction . Methods to detect flucytosine blood levels are also available.
Side-Effects
Gastrointestinal intolerance and bone marrow depression may be observed. Rash, hepatotoxicity, headache, confusion, hallucinations, sedation and euphoria have also been reported.
Since flucytosine is commonly combined with amphotericin B, the renal impairment caused by amphotericin B may increase the flucytosine levels in the body and thus potentiate its toxicity. The toxicity of flucytosine is presumably due to 5-fluorouracil which is produced from flucytosine by bacteria in gut lumen .
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