Flucytosine 💊
Related Subjects:
|Amphotericin B
|CNS fungal Infections
|AIDS HIV Infection and a Fever
💊 Flucytosine (5-fluorocytosine) is an antifungal used only in combination - usually with amphotericin B for cryptococcal meningitis - because resistance develops rapidly when it is used alone. Therapeutic drug monitoring is essential.
📖 About
- In the UK it is given by IV infusion (oral preparations are unlicensed imports).
- Excellent CSF and urine penetration.
- Always check the BNF for current dosing.
⚙️ Mode of Action
- Taken up into fungal cells by cytosine permease and deaminated to 5-fluorouracil (5-FU).
- 5-FU is incorporated into fungal RNA and inhibits thymidylate synthase → blocks DNA synthesis.
- Human cells lack cytosine deaminase, but gut flora can convert it to 5-FU → GI and marrow toxicity.
🎯 Indications
- Cryptococcal meningitis - induction with liposomal amphotericin B (WHO and BHIVA regimens).
- Severe systemic candidiasis (e.g. *Candida* endocarditis, meningitis, endophthalmitis) and some mould infections, in combination.
💊 Dose (adult, IV infusion over 20–40 minutes)
| Situation | Dose |
|---|
| Usual (BNF) | 200 mg/kg daily in 4 divided doses, usually for no more than 7 days |
| Sensitive organisms | 100–150 mg/kg daily may be enough |
| Cryptococcal meningitis induction (with liposomal amphotericin B) | 100 mg/kg daily in 4 divided doses, for the duration in the regimen used (commonly 14 days) |
| Renal impairment | Reduce dose and/or extend the interval - guided by levels |
🧪 Monitoring
- Plasma levels: pre-dose 25–50 mg/L; do not exceed 80 mg/L (marrow and liver toxicity).
- FBC and LFTs at least twice weekly; renal function (amphotericin co-therapy reduces flucytosine clearance).
🔄 Interactions
- Amphotericin B: synergistic, but its nephrotoxicity raises flucytosine levels.
- Myelosuppressive drugs (e.g. zidovudine, ganciclovir, cytotoxics): additive marrow toxicity.
- Cytarabine may antagonise its antifungal activity.
⚠️ Cautions
- Renal impairment - accumulation; dose by levels.
- Pre-existing bone marrow suppression or blood disorders; HIV (higher toxicity risk).
- Liver disease.
- Pregnancy: teratogenic in animals - use only if benefit outweighs risk.
🚫 Contraindications
- Hypersensitivity.
- DPD (dihydropyrimidine dehydrogenase) deficiency - risk of life-threatening 5-FU toxicity (MHRA 2020).
💥 Side Effects
- Haematological: leucopenia, thrombocytopenia, anaemia, aplastic anaemia (dose-related).
- GI: nausea, vomiting, diarrhoea, enterocolitis.
- Hepatic: raised transaminases, hepatitis.
- Other: rash, confusion, hallucinations, convulsions, cardiotoxicity (rare).
📚 References
- BNF: Flucytosine
- WHO (2022): Guidelines for diagnosing, preventing and managing cryptococcal disease
- MHRA Drug Safety Update (2020): flucytosine - new contraindication in DPD deficiency
