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Flucytosine is the only antimetabolite (a substance that closely re-sembles one required for normal physiologic functioning and that exerts its effect by interfering with metabolism) that acts as an an-timycotic. It’s a purine and pyrimidine inhibitor that’s used primar-ily with another antimycotic drug, such as amphotericin B, to treat systemic fungal infections.
After oral administration, flucytosine is well absorbed from the GI tract and widely distributed. It undergoes little metabolism and is excreted primarily by the kidneys.
Flucytosine penetrates fungal cells, where it’s converted to its ac-tive metabolite fluorouracil. Fluorouracil then is incorporated into the RNA of the fungal cells, altering their protein synthesis and causing cell death.
Although amphotericin B is effective in treating candidal and cryp-tococcal meningitis alone, flucytosine is given with it to reduce the dosage and the risk of toxicity. This combination therapy is the treatment of choice for cryptococcal meningitis.
Flucytosine can be used alone to treat candidal infections of the lower urinary tract because it reaches a high urinary concentra-tion. It’s also effective in treating infections caused by T. glabrata,Phialophora, Aspergillus, and Cladosporium.
Cytarabine may antagonize the antifungal activity of flucytosine, possibly by competitive inhibition. Hematologic, kidney, and liver function must be closely monitored during flucytosine therapy be-cause of the drug’s serious risk of toxicity. (See Adverse reactionsto flucytosine.)
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