Interactions
Flucytosine may increase the toxicity of amphotericin B and vice versa, although the combination may be life-saving and should be used whenever indicated (e.g., cryptococcal meningitis). The cytostatic cytarabine inhibits the antimycotic activity of flucytosine. Overdose
Symptoms and their severities are unknown, because flucytosine is used under close medical supervision, but expected to be an excess of the usually encountered side effects on the bone marrow, gastrointestinal tract, liver and kidney function. Vigorous hydration and hemodialysis may be helpful in removing the drug from the body. Hemodialysis is particular useful in patients with impaired renal function. Pharmacology
Mechanisms of action
Two major mechanisms of action have been elucidated:

Flucytosine is intrafungally converted into the cytostatic fluorouracil which undergoes further steps of activation and finally interacts as 5-fluorouridinetriphosphate with RNA biosynthesis thus disturbing the building of certain essential proteins. Flucytosine also undergoes conversion into 5-fluorodeoxyuridinemonophosphate which inhibits fungal DNA synthesis. Spectrum of susceptible fungi and resistance
Flucytosine is active in vitro as well as in vivo against some strains of Candida and Cryptococcus. Limited studies demonstrate that flucytosine may be of value against infections with Sporothrix, Aspergillus, Cladosporium, Exophiala, and Phialophora. Resistance is quite commonly seen as well in treatment-naive patients and under current treatment with flucytosine. In different strains of Candida resistance has been noted to occur in 1 to 50% of all specimens obtained from patients. Pharmacokinetic data
Flucytosine is well absorbed (75 to 90%) from the gastrointestinal tract. Intake with meals slows the absorption, but does not decrease the amount absorbed.
In some countries, treatment with slow intravenous infusions for no more than a week is also a therapeutic option, particular if the disease is life-threatening. 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. Pregnancy and breastfeeding
In animal models (rats), flucytosine has been found to be teratogenic. Sufficient human data does not exist. Pregnant women should be given flucytosine only if the potential benefits exceed the potential harm to the fetus. It is not known if flucytosine is distributed in human breast milk. Given the potential risk to the child, the patient should not breastfeed during treatment with flucytosine. Children
The efficacy and safety in patients under 18 years of age has not been determined. Side effects
Patients treated with drugs compromising bone marrow function (e.g. cytostatics) should be treated carefully. Blood cell counts should be taken very frequently. Patients with renal disease should receive flucytosine cautiously and in reduced doses. Guidelines for proper dosing exist. Serum level determinations are mandatory for these patients. All patients receiving flucytosine should be under strict medical supervision. Hematological, renal and liver function studies should be done frequently during therapy (initially daily, twice a week for the rest of treatment). Patients with preexisting bone marrow depression and liver impairment should be treated with caution.