Walsh & Hoyt: Flucytosine

Flucytosine (5-fluorocytosine) is the fluorine analogue of the naturally occurring nucleic acid pyrimidine base, cytosine. Flucytosine inhibits deoxyribonucleic acid (DNA) synthesis within fungi by acting as a noncompetitive inhibitor of thymidylate synthetase. Penetration of flucytosine into most tissues is excellent, and cerebrospinal fluid (CSF) concentrations reach about 75% of simultaneous concentrations in the serum. About 90% of the drug is ultimately excreted unchanged in the urine. Flucytosine is most helpful in the treatment of candidiasis, chromomycosis, and cryptococcosis. Its efficacy is limited, however, by the common development of secondary resistance to the drug during treatment. For this reason, it usually is used in combination with amphotericin B rather than alone. Flucytosine has minor adverse effects in patients with normal gastrointestinal and renal function; however, patients with azotemia and those concurrently receiving amphotericin B may develop leukopenia, thrombocytopenia, and enterocolitis that may be fatal.