Leukopenia flucytosine

The dosage of flucytosine is 150—200 mg/kg orally in four portions every six hours. A 1% flucytosine solution has been developed for intravenous adrninistration. In some countries, a 10% ointment is also available. In patients with normal renal function, flucytosine is seldom toxic, but occasionally severe toxicity may be observed (leukopenia and thrombocytopenia). Plasma levels should be determined and the dose in patients with impaired renal function should be checked. Liver function tests (transaininases and alkaline phosphatase) should be performed regularly. In some patients with high flucytosine plasma levels, hepatic disorders have been observed (24). 

Adverse Effects. Flucytosine may cause hepatotoxicity and may also impair bone marrow function, resulting in anemia, leukopenia, and several other blood dyscrasias.69 This drug may also produce severe gastrointestinal disturbances, including nausea, vomiting, diarrhea, and loss of appetite. 

Bone marrow suppression is a recognized toxic effect of flucytosine anemia, leukopenia, and thrombocytopenia occur in about 5% of cases. The hematological effects are dose-related and occur after prolonged high blood concentrations of flucytosine (over 100 pg/ml). Hematotoxicity is seen more often in the presence of renal insufficiency and hence during the use of flucytosine in combination with amphotericin. If bone marrow reserve has already been depleted by underlying disease or by medications, the risk of hematotoxicity increases. 

In a pilot study in six patients receiving intravenous flucytosine, hematotoxicity was monitored by measuring platelet and leukocyte counts flucytosine and 5-fluorouracil serum concentrations were measured using HPLC (19). The concentrations of 5-fluorouracil in the 34 available serum samples were below the limit of quantification (0.05 pg/ml), but flucytosine was detectable in all samples and the 5-fluorouracil metabolite, a-fluoro-P-alanine (FBAL), was detected at low concentrations in several samples. One patient developed thrombocytopenia (50 X 10 /1) during therapy, and one developed leukopenia (2.6 X 10 /1). The fact that 5-fluorouracil was not detected... 

Flucytosine generally is associated with very few side effects in patients with normal renal, GI, and hematologic function, although rash, GI discomfort, diarrhea (5% to 10%), and reversible elevations in hepatic enzymes are observed occasionally. In patients with renal dysfunction or concomitant amphotericin B therapy, leukopenia, thrombocytopenia, and (rarely) enterocolitis may occur. Although studies have suggested that little or no conversion of flucytosine to fluorouracil occurs in vitro, serum concentrations of greater than 1000 ng/mL (therapeutic for the treatment of malignancies) have been... 

Flucytosine (Ancoben) Deaminated to 5-fluoro-uradl by the fungus. Incorporated into RNA. Metabolized to 5-fluorodeoxyuridine (5-FdURD) which inhibits thymidilate synthetase. Leukopenia, nausea, diarrhea, T LFTs, bone marrow depression. 

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