ANCOBON

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ANCOBON (ANCOBON).

How it works

Flucytosine is converted intracellularly to 5-fluorouracil, which inhibits fungal RNA and DNA synthesis by incorporating into RNA and inhibiting thymidylate synthase.

What the body does with it

Metabolism	Deaminated to 5-fluorouracil in the body; further metabolized via same pathways as fluorouracil.
Excretion	Primarily renal excretion of unchanged drug (75-90% within 24 hours). Less than 1% eliminated as 5-fluorouracil metabolite. Biliary/fecal excretion negligible.
Half-life	Terminal elimination half-life 2.5-6 hours (normal renal function). Prolonged to 30-250 hours in renal impairment (CrCl < 20 mL/min). Half-life correlates with creatinine clearance.
Protein binding	2-4% bound to plasma proteins (albumin).
Volume of Distribution	0.6-0.9 L/kg, indicating distribution into total body water. Penetrates well into cerebrospinal fluid (50-100% of serum levels), aqueous humor, and peritoneal fluid.
Bioavailability	Oral: 76-89% (well absorbed).
Onset of Action	Oral: 1-2 hours to therapeutic plasma concentrations. IV: immediate onset (within minutes).
Duration of Action	Dosing interval 6 hours (normal renal function) to 24-48 hours (severe renal impairment). Duration of antifungal effect corresponds to maintenance of plasma levels above MIC.

Classification & Brands

Dosing & administration

50-150 mg/kg/day orally divided every 6 hours; intravenous dosing: 50-150 mg/kg/day divided every 12 hours.

Dosage form	CAPSULE
Renal impairment	GFR >50 mL/min: no adjustment; GFR 10-50 mL/min: 50-100 mg/kg/day divided every 12-24 hours; GFR <10 mL/min: 50-100 mg/kg/day every 24-48 hours; intermittent hemodialysis: 50-100 mg/kg/day with each dialysis session; peritoneal dialysis: 50-100 mg/kg/day every 48 hours.
Liver impairment	No specific pediatric dosing based on Child-Pugh; use with caution and monitor liver function, potential reduced clearance. No standard adjustment defined.
Pediatric use	Weight-based: 50-150 mg/kg/day orally divided every 6 hours, or 50-150 mg/kg/day intravenously divided every 12 hours; neonates: 25-100 mg/kg/day intravenously divided every 12 hours.
Geriatric use	Start at lower end of dosing range (50 mg/kg/day), adjust based on renal function; monitor for hematologic toxicity.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ANCOBON (ANCOBON).

Breastfeeding	Flucytosine is excreted into human breast milk; milk-to-plasma ratio approximately 1.0. Potential for serious adverse reactions in nursing infants; decision to discontinue nursing or drug depends on importance of drug to mother.
Teratogenic Risk	Flucytosine (ANCOBON) is teratogenic in animal studies, causing cleft palate, skeletal anomalies, and fetal resorption. Human data are limited; use in pregnancy only if clearly needed. Potential fetal risk in all trimesters. Contraindicated in first trimester unless life-threatening maternal infection.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to flucytosine or any component.

Clinical Precautions

Precautions	Hematologic toxicity (leukopenia, thrombocytopenia); renal impairment requires dose adjustment; hepatotoxicity; monitoring of blood counts and renal function recommended.
Food/Dietary	May be taken with food to reduce gastrointestinal upset. No specific dietary restrictions. Avoid alcohol.

Clinical Tips & Counseling

Clinical Pearls

Monitor for hepatotoxicity and bone marrow suppression; adjust dose in renal impairment (CrCl <50 mL/min requires dose interval extension). Obtain serum levels (desired peak 50-100 mcg/mL, trough <50 mcg/mL) to avoid toxicity. Use with caution in patients with pre-existing hematologic disorders or hepatic dysfunction. Synergistic with amphotericin B for cryptococcal meningitis; avoid concurrent use with nucleoside analogues (e.g., cytarabine) due to antagonism.

Drug interactions

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ANCOBON

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ANCOBON (ANCOBON).

How it works

Flucytosine is converted intracellularly to 5-fluorouracil, which inhibits fungal RNA and DNA synthesis by incorporating into RNA and inhibiting thymidylate synthase.

What the body does with it

Metabolism	Deaminated to 5-fluorouracil in the body; further metabolized via same pathways as fluorouracil.
Excretion	Primarily renal excretion of unchanged drug (75-90% within 24 hours). Less than 1% eliminated as 5-fluorouracil metabolite. Biliary/fecal excretion negligible.
Half-life	Terminal elimination half-life 2.5-6 hours (normal renal function). Prolonged to 30-250 hours in renal impairment (CrCl < 20 mL/min). Half-life correlates with creatinine clearance.
Protein binding	2-4% bound to plasma proteins (albumin).
Volume of Distribution	0.6-0.9 L/kg, indicating distribution into total body water. Penetrates well into cerebrospinal fluid (50-100% of serum levels), aqueous humor, and peritoneal fluid.
Bioavailability	Oral: 76-89% (well absorbed).
Onset of Action	Oral: 1-2 hours to therapeutic plasma concentrations. IV: immediate onset (within minutes).
Duration of Action	Dosing interval 6 hours (normal renal function) to 24-48 hours (severe renal impairment). Duration of antifungal effect corresponds to maintenance of plasma levels above MIC.

Classification & Brands

Dosing & administration

50-150 mg/kg/day orally divided every 6 hours; intravenous dosing: 50-150 mg/kg/day divided every 12 hours.

Dosage form	CAPSULE
Renal impairment	GFR >50 mL/min: no adjustment; GFR 10-50 mL/min: 50-100 mg/kg/day divided every 12-24 hours; GFR <10 mL/min: 50-100 mg/kg/day every 24-48 hours; intermittent hemodialysis: 50-100 mg/kg/day with each dialysis session; peritoneal dialysis: 50-100 mg/kg/day every 48 hours.
Liver impairment	No specific pediatric dosing based on Child-Pugh; use with caution and monitor liver function, potential reduced clearance. No standard adjustment defined.
Pediatric use	Weight-based: 50-150 mg/kg/day orally divided every 6 hours, or 50-150 mg/kg/day intravenously divided every 12 hours; neonates: 25-100 mg/kg/day intravenously divided every 12 hours.
Geriatric use	Start at lower end of dosing range (50 mg/kg/day), adjust based on renal function; monitor for hematologic toxicity.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ANCOBON (ANCOBON).

Breastfeeding	Flucytosine is excreted into human breast milk; milk-to-plasma ratio approximately 1.0. Potential for serious adverse reactions in nursing infants; decision to discontinue nursing or drug depends on importance of drug to mother.
Teratogenic Risk	Flucytosine (ANCOBON) is teratogenic in animal studies, causing cleft palate, skeletal anomalies, and fetal resorption. Human data are limited; use in pregnancy only if clearly needed. Potential fetal risk in all trimesters. Contraindicated in first trimester unless life-threatening maternal infection.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to flucytosine or any component.

Clinical Precautions

Precautions	Hematologic toxicity (leukopenia, thrombocytopenia); renal impairment requires dose adjustment; hepatotoxicity; monitoring of blood counts and renal function recommended.
Food/Dietary	May be taken with food to reduce gastrointestinal upset. No specific dietary restrictions. Avoid alcohol.

Clinical Tips & Counseling

Clinical Pearls

Drug interactions

Loading safety data…