Flucytosine - Antifungal

Flucytosine

Flucytosine is a fluorinated pyrimidine related to fluorouracil. It is sometimes used (orally) in combination with amphotericin B for systemic fungal infections. Its use as a single drug is greatly restricted owing to rapid emergence of resistant strains. It is used today mainly to treat serious systemic fungal infections due to Candida and Cryptococcus species.

Flucytosine is known for causing bone marrow suppres-sion, and also GI toxicity manifesting as vomiting, diarrhoea, abdominal distension, and even bowel perforation. Patients with a history of haematological disorders, symptomatic HIV infec-tion, radiation, or myelosuppressive therapy are more likely to develop bone-marrow depression following flucytosine treat-ment. Hepatotoxicity has been reported during therapeutic use of flucytosine. Infrequent problems that have occurred during therapeutic use include neurological effects (convulsions, headache, sedation, vertigo), psychological effects (confusion, hallucinations), allergic reactions, rash, pruritus, urticaria, toxic epidermal necrolysis and cardiac toxicity.

Treatment involves stomach wash, stabilisation, and supportive measures. Monitor CBC with differential and platelet count, as well as, hepatic and renal function tests in symptomatic patients or following exposure as indicated. Serum flucytosine levels may be useful following an acute or an acute-on-chronic exposure. There is an increased risk of toxicity with prolonged serum levels of 100 mcg/mL or higher. Haemodialysis is said to be beneficial, since flucytosine is minimally protein bound (4% or less) and the volume of distribution is similar to total body water.

Since flucytosine is metabolised to 5-fluorouracil (a cyto-toxic drug), a detailed follow-up is necessary in cases of over-dose. Flucytosine has been shown to be teratogenic.