Flucytosine
**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.
Mecanismo: Flucytosine acts as a prodrug that exploits specific fungal enzymes: 1. **Cellular Entry:** Flucytosine enters the fungal cell via the enzyme **cytosine permease**. 2. **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).* 3. **RNA Inhibition:** 5-FU acts as an antimetabolite, competing with **uracil** → incorporates into fungal RNA → disrupts pyrimidine metabolism and halts protein synthesis. 4. **DNA Inhibition:** 5-FU is also converted to **fluorodeoxyuridylic acid** → potently inhibits **thymidylate synthetase** → halts DNA synthesis and cell division.
Dosificación por especie
- 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 · 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 · 25-50 mg/kg PO q6h or 50-65 mg/kg PO q8h · PO · q6h or q8h · 42 days · Must be given with a polyene or azole antifungal agent.
- Susceptible fungal infections (Psittacines) · 250 mg/kg twice daily as a gavage · PO · q12h · Extended periods · May cause bone marrow toxicity; periodic hematologic assessment is recommended.
- Susceptible fungal infections (Raptors) · 18-30 mg/kg q6h as a gavage · PO · q6h
- Susceptible fungal infections (Psittacines and Mynahs) · 100-250 mg/lb in feed · PO · Continuous · For flock treatment of severe aspergillosis or Candida. Apply to favorite food mix or mixed with mash.
- Susceptible fungal infections (Ratites) · 80-100 mg/kg PO twice daily · PO · q12h
- Cryptococcosis · 50-75 mg/kg PO q8h · PO · q8h · 1-12 months · Must be given with a polyene or azole antifungal agent.
- Candidiasis · 25-50 mg/kg PO q6h or 50-65 mg/kg PO q8h · PO · q6h or q8h · 42 days · Must be given with a polyene or azole antifungal agent.
Las dosis son una referencia clínica para veterinarios colegiados. Confirme siempre con la ficha técnica vigente y el paciente individual.
Vías de administración
Contraindicaciones
- Known hypersensitivity to flucytosine
Efectos adversos
- 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)
Interacciones farmacológicas
- Amphotericin B · 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.
Monitorización
- 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
Sobredosis
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.
La referencia de fármacos de VetSheet está destinada a veterinarios colegiados como apoyo a la decisión clínica, no sustituye el juicio profesional ni la ficha técnica vigente del fabricante.