Flucytosine
5-fluorocytosine
Also known as: Ancobon · Ancotil · Alcobon · 5-FC · 5-fluorocytosine · flucytosinum · Ro-2-9915
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Cryptococcosis | 50-75 mg/kg PO q8h | PO | q8h | 1-12 months | 🌎 NA |
| Candidiasis | 25-50 mg/kg PO q6h or 50-65 mg/kg PO q8h | PO | q6h or q8h | 42 days | 🌎 NA |
- Cryptococcosis: Must be given with a polyene or azole antifungal agent.
- Candidiasis: Must be given with a polyene or azole antifungal agent.
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Cryptococcosis | 30 mg/kg PO q6h or 50 mg/kg PO q8h or 75 mg/kg PO q12h | PO | q6h, q8h, or q12h | 1-9 months | 🌎 NA |
| Candidiasis | 25-50 mg/kg PO q6h or 50-65 mg/kg PO q8h | PO | q6h or q8h | 42 days | 🌎 NA |
- Cryptococcosis: Cats 3.5 kg or greater should receive 250 mg (total) q6-8h. Must be given with a polyene (amphotericin B) or azole antifungal agent.
- Candidiasis: Must be given with a polyene or azole antifungal agent.
Birds
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Susceptible fungal infections (Psittacines) | 250 mg/kg twice daily as a gavage | PO | q12h | Extended periods | 🌎 NA |
| Susceptible fungal infections (Raptors) | 18-30 mg/kg q6h as a gavage | PO | q6h | — | 🌎 NA |
| Susceptible fungal infections (Psittacines and Mynahs) | 100-250 mg/lb in feed | PO | Continuous | — | 🌎 NA |
| Susceptible fungal infections (Ratites) | 80-100 mg/kg PO twice daily | PO | q12h | — | 🌎 NA |
- Susceptible fungal infections (Psittacines): May cause bone marrow toxicity; periodic hematologic assessment is recommended.
- Susceptible fungal infections (Psittacines and Mynahs): For flock treatment of severe aspergillosis or Candida. Apply to favorite food mix or mixed with mash.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Flucytosine (also known as 5-FC) is a fluorinated pyrimidine antifungal agent primarily active against strains of Cryptococcus and Candida.
Key Clinical Points:
- Combination Therapy is Mandatory: When used as a monotherapy, fungal resistance develops rapidly (especially with Cryptococcus). It is almost exclusively used synergistically with amphotericin B or azole antifungals.
- CNS Penetration: It penetrates the blood-brain barrier exceptionally well, making it highly valuable for treating central nervous system cryptococcosis.
- Toxicity Concerns: It carries a risk of dose-dependent bone marrow suppression. Dogs are particularly sensitive and may develop severe drug reactions if treated for more than 10-14 days.
- Species Differences: Mammalian cells generally lack the enzyme needed to convert flucytosine to its toxic metabolite (5-fluorouracil), but gut flora or specific species metabolism (like in rats) can lead to systemic toxicity.
Mechanism of action
Flucytosine acts as a prodrug that exploits specific fungal enzymes:
- Cellular Entry: Flucytosine enters the fungal cell via the enzyme cytosine permease.
- Conversion to Active Metabolite: Inside the fungal cell, it is deaminated by cytosine deaminase → 5-fluorouracil (5-FU). (Note: Human and most mammalian cells lack this enzyme, providing selective toxicity).
- RNA Inhibition: 5-FU acts as an antimetabolite, competing with uracil → incorporates into fungal RNA → disrupts pyrimidine metabolism and halts protein synthesis.
- DNA Inhibition: 5-FU is also converted to fluorodeoxyuridylic acid → potently inhibits thymidylate synthetase → halts DNA synthesis and cell division.
Safety & warnings
Contraindications
- Known hypersensitivity to flucytosine
Adverse effects
- Gastrointestinal disturbances (nausea, vomiting, diarrhea)
- Dose-dependent bone marrow depression (anemia, leukopenia, thrombocytopenia)
- Cutaneous eruption and rash (primarily on scrotum and nasal planum in dogs)
- Oral ulceration
- Increased hepatic enzymes
- Severe drug reaction in dogs within 10-14 days of treatment
- Aberrant behavior and seizures (reported in cats)
- Toxic epidermal necrolysis (anecdotal in cats)
Precautions
Extreme Caution: Use with extreme care in patients with renal impairment, as the drug is renally excreted. Dosage intervals must be adjusted based on creatinine clearance to prevent toxic accumulation.
- Hematologic Risk: Use with extreme caution in patients with preexisting bone marrow depression, hematologic diseases, or those receiving other bone marrow suppressant drugs.
- Hepatic Disease: Use cautiously with enhanced monitoring in patients with liver disease.
- Pregnancy: Teratogenic in rats (FDA Category C). Use only when benefits outweigh risks. Consider milk replacer for nursing offspring.
- Laboratory Interference: May cause false elevations in serum creatinine levels when using the Ektachem® analyzer.
Drug interactions
Synergistic antifungal efficacy against Cryptococcus and Candida. However, amphotericin B-induced nephrotoxicity can decrease flucytosine excretion, leading to flucytosine accumulation and enhanced bone marrow toxicity. Dosage adjustments and strict monitoring are required.
Monitoring
- Renal function (BUN, Creatinine, Urinalysis) - at least twice weekly if also receiving amphotericin B
- CBC with platelets (to monitor for bone marrow suppression)
- Hepatic enzymes (at least monthly)
- Serum flucytosine levels (target < 100 mcg/mL) in patients with renal impairment, if available
Pharmacokinetics
Absorption
Well absorbed after oral administration. The rate, but not the extent, of absorption is decreased if given with food.
Distribution
Distributed widely throughout the body. Penetrates the CNS well, with CSF concentrations reaching 60-100% of serum levels. Volume of distribution is ~0.7 L/kg in healthy humans. Only 2-4% is bound to plasma proteins.
Metabolism
Minimal metabolism in humans. Rats metabolize some of the drug to fluorouracil (explaining teratogenic effects). The extent of cytosine deaminase activity in dog and cat cells is unclear.
Elimination
Excreted basically unchanged in the urine via glomerular filtration.
Overdose
Specific information regarding flucytosine overdosage in veterinary species is limited.
Management:
- For substantial acute overdoses, standard gastrointestinal decontamination (gut emptying, activated charcoal, and cathartic administration) is recommended unless contraindicated.
- Monitor hematologic and renal parameters closely, providing supportive care as needed.
Available products
Formulations
- Oral capsules
- Compounded oral suspension
Human-labeled
- Flucytosine Oral Capsules: 250 mg & 500 mg (Ancobon®)
Regulatory status
No regulatory data for: 🇺🇸 US · 🇪🇺 EU · 🇬🇧 UK · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store capsules in tight, light-resistant containers at temperatures less than 40°C, preferably at room temperature (15-30°C). Compounded oral suspensions (10 mg/mL in Ora-Plus/Ora-Sweet) retain >95% potency for 60 days when stored at 5°C or 25°C.
Client information
Understanding the Medication: Flucytosine is a specialized antifungal medication used to treat severe, deep-seated fungal infections (like Cryptococcosis). It is almost always prescribed alongside another antifungal drug to prevent the fungus from becoming resistant.
What to Watch For:
- Bleeding or Bruising: This drug can suppress the bone marrow's ability to make blood cells. Contact your veterinarian immediately if you notice unusual bleeding, bruising, pale gums, or extreme lethargy.
- Stomach Upset: Nausea, vomiting, or diarrhea can occur. Let your vet know if these signs persist.
- Skin Changes: In dogs, rashes or sores may develop, particularly on the nose or scrotum.
Commitment to Therapy: Treating deep fungal infections requires a significant commitment. Treatment often lasts for several months, and frequent blood tests are necessary to ensure the medication is not harming your pet's kidneys, liver, or bone marrow.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.