Flucytosine

ANCOBON

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What it isAntifungal converted to 5-fluorouracil by fungal cytosine deaminase; cryptococcal meningitis with amphotericin.

Why this oneCombined with amphotericin it sterilizes CSF faster than amphotericin alone, improving survival.

What limits itMyelosuppression tracks blood levels, so monitoring is needed, and it is renally cleared. Never use alone — resistance emerges rapidly.

FDA-approved for

Serious Candida and Cryptococcus infections (1971)

FDA label

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BOXED WARNING Extreme caution in renal impairment; close hematologic, renal, and hepatic monitoring of all patients is essential.

FDA dosing	Population	Start	Target	Max
Systemic candidiasis & cryptococcosis (in combination with amphotericin B)	Adults	50 mg/kg/day divided q6h (QID)	50-150 mg/kg/day divided q6h	150 mg/kg/day

Renal Elevated BUN/creatinine or other signs of renal impairment: start at the lower dose level (50 mg/kg/day); extreme caution (boxed)

Hepatic Undefined

Instructions

Give capsules a few at a time over a 15-minute period to reduce nausea/vomiting
Use in combination with amphotericin B for systemic candidiasis and cryptococcosis (resistance emerges on monotherapy)

Contraindications

Known complete dihydropyrimidine dehydrogenase (DPD) enzyme deficiency

Cautions

Use with extreme caution in impaired renal function (boxed)
Monitor hematologic, renal, and hepatic status closely in all patients (boxed)

Adverse reactions

Nausea, vomiting, diarrhea, anorexia, abdominal pain
Hepatic injury incl. necrosis (possibly fatal in debilitated patients), jaundice, enzyme elevations
Marrow toxicity: anemia, leukopenia, thrombocytopenia, agranulocytosis, pancytopenia, fatal bone marrow aplasia
Azotemia, BUN/creatinine elevation, crystalluria, renal failure
Cardiac arrest, myocardial toxicity, ventricular dysfunction
Confusion, hallucinations, psychosis, sedation, convulsions, ataxia, paresthesia, peripheral neuropathy, hearing loss
Rash, pruritus, urticaria, photosensitivity; Lyell's syndrome
Hypoglycemia, hypokalemia

Pregnancy Teratogenic in rats (vertebral fusions; cleft lip/palate at higher doses); no adequate human studies — use only if potential benefit justifies fetal risk.

Lactation Undefined

⚠ BOXED WARNING