(1997; 132 pages) [French] [Spanish]
Capsule, 250 mg
Solution for injection, 2.5 g in 250 ml
Flucytosine is a synthetic fluorinated pyrimidine with selective antifungal activity, particularly against Cryptococcus and Candida spp. and chromomycosis. It acts by penetrating into sensitive fungi where it is deaminated to fluorouracil, a competitive inhibitor of fungal uracil metabolism.
Flucytosine is readily absorbed from the gastrointestinal tract and widely distributed in body tissues and fluids, including the cerebrospinal fluid. Peak plasma concentrations occur within 2 hours after oral administration. The plasma half-life is about 2.5-5.0 hours and it is excreted, largely unchanged, in the urine.
Treatment of cryptococcosis, candidosis and chromomycosis.
It is also sometimes used in combination with amphotericin B in treating systemic infections with skin involvement due to Cryptococcus neoformans,1Candida albicans and certain other Candida species.
1 For further information, see WHO model prescribing information: drugs used in sexually transmitted diseases and HIV infection. Geneva, World Health Organization, 1995.
Dosage and administration
All doses are suitable for adults and children.
Oral administration: 150 mg/kg in four divided doses daily.
Intravenous infusion for severely ill patients: 150 mg/kg daily in four divided doses, each administered in physiological saline, 5% glucose or 5% glucose + saline over a period of 20-40 minutes. No other drugs should be added to the solution or to the infusion line. Serum concentrations of 25-50 μg/ ml are usually effective but should not exceed 100 μg/ml, since with these levels there is an increased risk of myelotoxicity.
Dosage must be reduced in accordance with the creatinine clearance rate in patients with renal impairment. The maximum daily dose recommended for a patient with a creatinine clearance rate of 10-20 ml/min is 50 mg/kg.
Patients should be transferred to oral treatment at the earliest opportunity and, whenever possible, within 1 week. The duration of treatment should be determined primarily on clinical grounds.
• Known hypersensitivity to flucytosine.
• Severe renal or hepatic insufficiency.
• Thrombocytopenia and other blood dyscrasias.
Serum creatinine concentrations should be monitored twice weekly and the dosage adjusted appropriately. Serum levels of flucytosine must be repeatedly measured in patients with renal insufficiency. These samples should be withdrawn shortly before the subsequent dose is scheduled. Particular vigilance is required when flucytosine is administered in combination with amphotericin B, since the latter may lead to reduced clearance of flucytosine.
Vigilance is also required when flucytosine is administered in combination with other myelosuppressive drugs.
Blood counts and hepatic function tests should be performed at regular intervals in all patients and at least every month in patients with bone marrow depression or hepatic impairment.
Use in pregnancy
Teratogenic effects have been demonstrated in rats. Flucytosine should be used only when the need of the mother outweighs the risk of harm to the fetus.
Rashes, nausea, vomiting and diarrhoea sometimes occur and are usually transient. However, diarrhoea can become protracted if flucytosine is continued. Mild changes in liver function tests occur in about 10% of patients.
Leukopenia and potentially fatal thrombocytopenia have been reported rarely.
The action of amphotericin B is potentiated.
Gastric lavage and forced diuresis are of value if undertaken within a few hours of ingestion. Haemodialysis results in a rapid fall in serum flucytosine concentrations.
Capsules and infusion should be stored in tightly closed containers, protected from light.