Skip to content
ClinCalc Pro
Menu
Calculators Drugs Pathways AI Dx Donate Get the App
Antifungal (pyrimidine analogue) Pregnancy: §4.6: Flucytosine is partially metabolised into 5-fluorouracil, which is genotoxic and considered a potential human teratogen. In animal studies flucytosine and 5-fluorouracil showed reproductive toxicity (teratogenicity and embryotoxicity). In humans flucytosine crosses the placenta; there are very limited data in pregnant women, so harmful impact on the embryo/foetus cannot be excluded, especially in the first trimester. 'Ancotil should not be used during pregnancy and in women of childbearing potential not using contraception unless strictly necessary in case of life-threatening infections and lack of an effective alternative treatment.' If given in pregnancy, advise of the teratogenic risk, with careful prenatal and postnatal monitoring; if given up to delivery, neonatal (haematologic and hepatic) monitoring. Contraception: females of childbearing potential must use effective contraception during treatment and for 6 months after; male patients (or their female partners) during treatment and for three months after; in renal impairment the contraception period should be prolonged by a further two months. Breastfeeding is contraindicated during flucytosine treatment (§4.3).

Flucytosine

Brand names: Ancotil

Flucytosine is an antifungal agent used, usually in combination with amphotericin B, for serious systemic fungal infections such as cryptococcal meningitis and severe candidiasis.

Adult dose

Dose: Systemic yeast and fungal infections due to sensitive organisms (cryptococcosis, candidiasis, chromomycosis, infections due to Candida glabrata and Hansenula): recommended daily dosage 200 mg/kg/day body-weight, divided into four doses over 24 hours. In patients harbouring extremely sensitive organisms a total daily dose of 100 to 150 mg/kg/day may be sufficient. In combination with amphotericin B: the recommended dose of flucytosine is 100-150 mg/kg/day Ancotil. Product: Ancotil 2.5 g in 250 ml solution for infusion (flucytosine 2.5 g per 250 ml)
Route: Intravenous infusion
Frequency: Four divided doses over 24 hours (each infusion over 20 to 40 minutes if balanced with the patient's fluid requirements)
Product: UK SPC via MHRA Products - ANCOTIL 2.5G/250 ML SOLUTION FOR INFUSION (PL463020116), Viatris Products Limited; §2: flucytosine Ph. Eur. 2.5 g in 250 ml. §4.1 (verbatim): 'Ancotil is indicated for the treatment of systemic yeast and fungal infections due to sensitive organisms: such infections include: Cryptococcosis, Candidiasis, Chromomycosis, infections due to Candida glabrata and Hansenula. In the treatment of cryptococcal meningitis and severe systemic candidiasis it is recommended that Ancotil should be given in combination with amphotericin-B.' Where amphotericin B toxicity or a flucytosine/amphotericin B combination is dose limiting in cryptococcal meningitis, a combination of flucytosine with fluconazole has demonstrated successful cure, 'but at a lower rate than in combination with amphotericin B'. ROUTE COVERED: the INTRAVENOUS infusion only. The SPC (§4.2) also lists 'directly into a vein, through a central venous catheter, or by intra-peritoneal infusion' - the intra-peritoneal route is not this page's route and no separate intraperitoneal dose is printed. The ORAL (capsule) route listed on this page is NOT covered by this SPC and no oral dose is given. VERBATIM §4.2: 'Ancotil for Infusion should be administered using a giving set. ... The recommended daily dosage is 200 mg/kg body-weight divided into four doses over 24 hours. In patients harbouring extremely sensitive organisms a total daily dose of 100 to 150 mg/kg body-weight may be sufficient. Adequate effects can, however, often be obtained with a lower dose. It is suggested that the duration of the infusion should be of the order of 20 to 40 minutes provided this is balanced with the fluid requirements of the patient.' COMBINATION (§4.2): 'The recommended dose of flucytosine for this combination therapy is 100-150 mg/kg Ancotil daily. Particularly careful monitoring of renal function is necessary when flucytosine is combined with amphotericin B.' The SPC prints no maximum daily dose, so none is given; per-dose mg/kg figures are not printed and none is derived. DURATION (§4.2): 'As a rule, treatment with Ancotil for Infusion should rarely be required for periods of more than one week.' and 'The duration of treatment should be determined on an individual basis.' The SPC's duration guide reads: systemic candidosis 2 - 4 weeks; cryptococcus meningitis 6 - 10 weeks; chromoblastomycosis 6 - 12 months; elsewhere it also states 'In cases of cryptococcal meningitis, treatment should last for at least four months' (the SPC prints both - verify against the full SPC and local guidance). SERUM LEVELS (§4.4): steady-state serum level should average 35 to 70 μg/ml; levels greater than 25 μg/ml should be maintained (risk of resistance at low concentrations); prolonged serum levels above 100 μg/ml should be avoided (haematological toxicity). Do not mix any other agent with Ancotil for Infusion; it may be given concurrently with separate infusions of normal saline, glucose or glucose/saline (§4.2). Sodium content 138 millimole/litre (§4.4). Older people (§4.2): dosage requirements and side-effect profile similar to younger patients; particular attention to renal function. CHILDREN (no paediatric dose is written): §4.2 'Available data are not sufficient to support evidence-based dosing recommendations in paediatric patients, including term and preterm neonates. Flucytosine should not be used as first line or monotherapy in paediatric patients.' The old openFDA record in this bundle (US capsules) was not used. §4.4 was truncated at the source-fetch limit part-way through its paediatric paragraph.

Dose adjustments

Renal

§4.2 (verbatim): 'Since Ancotil is excreted primarily by the kidneys, smaller doses should be administered with extended intervals in patients with renal impairment based on creatinine clearance. The following is suggested as a guide for dosage in patients with severe infection associated with renal impairment: Creatinine clearance > 40 ml /min: 25-50 mg/kg every 6 hours. Creatinine clearance <40 to >20 ml /min: 25-50 mg/kg every 12 hours. Creatinine clearance <20 to >10 ml /min: 25-50 mg/kg every 24 hours. Creatinine clearance <10 ml /min: an initial single dose of 25-50 mg/kg; subsequent doses should be calculated according to the results of regular monitoring of the serum concentration of the drug, which should not be allowed to exceed 80 micrograms/ml. Blood levels of 25 to 50 micrograms/ml are normally effective.' Haemodialysis (§4.2): flucytosine is filtered and excreted during haemodialysis, so the dosage must be repeated after the session; in anuric or nephrectomized haemodialysis patients, 'under no circumstances should the initial single dose be repeated prior to performing the next dialysis session' (§4.4: 65 to 75 % is excreted by haemodialysis). §4.4: 'Ancotil should not be used in patients with impaired renal function in the absence of facilities for monitoring blood levels of the drug.'

Hepatic

§4.2: 'Patients with impaired liver function may be treated with flucytosine, but they require particularly careful monitoring.' No numeric hepatic dose adjustment is printed.

Dose independently re-sourced from UK Summary of Product Characteristics (SPC) via MHRA Products — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • Patients who have shown hypersensitivity to flucytosine or any of the excipients (§4.3)
  • Co-administration with antiviral nucleoside drugs e.g. ganciclovir and valganciclovir, brivudine, sorivudine and their analogues (irreversible inhibitors of dihydropyrimidine dehydrogenase, DPD) (§4.3)
  • Known complete dihydropyrimidine dehydrogenase (DPD) deficiency (§4.3)
  • Concomitant administration of flucytosine and tegafur/gimeracil/oteracil (§4.3)
  • Breastfeeding women (§4.3)

Side effects

  • §4.8: undesirable effects primarily affect the gastrointestinal tract, liver and bone marrow; serious effects may occur with elevated serum concentrations (e.g. renal insufficiency if the dose is not adjusted). In the majority of cases these disorders occur within the first 2 to 3 weeks of treatment
  • Blood: anaemia, leukopenia, neutropenia, granulocytopenia and thrombocytopenia, dependent on possibly elevated serum levels; agranulocytosis, eosinophilia, aplastic anaemia, irreversible bone marrow toxicity with pancytopenia and bone marrow suppression in immunosuppressed patients with fatal outcome (§4.8)
  • Gastrointestinal: discomfort (nausea, vomiting, diarrhoea), abdominal pain, ulcerative colitis (§4.8)
  • Hepatobiliary: impaired liver function, reversible elevation of serum transaminases, hepatitis, liver cell necrosis with fatal outcome (§4.8)
  • Skin and immune: skin rash, allergic reactions, Lyell's syndrome, pruritus, urticaria (§4.8)
  • Metabolism: hypokalaemia; Renal: renal insufficiency (§4.8)
  • Nervous system and psychiatric: confusion, hallucinations, convulsions, headache, sedation, paraesthesia, peripheral neuropathy, vertigo (§4.8)
  • Cardiac and respiratory: cardiotoxicity, ventricular dysfunction, arrhythmias; acute respiratory insufficiency, dyspnoea, chest pain, respiratory arrest (§4.8)
  • Undesirable effects may occur more frequently with combination therapy with amphotericin B and other potentially nephrotoxic compounds (§4.8)

Interactions

  • Brivudine, sorivudine and analogues, and tegafur/gimeracil/oteracil: potent DPD inhibition leading to raised 5-fluorouracil (a flucytosine metabolite) - contraindicated (§4.3, §4.5); allow at least four weeks after brivudine/sorivudine or analogues and at least 7 days after tegafur/gimeracil/oteracil before giving flucytosine (§4.4)
  • Cytarabine: contradictory evidence; the antimycotic effect of flucytosine might be impaired - strict monitoring of blood levels is required if given together (§4.5)
  • Phenytoin: increased phenytoin plasma levels cannot be excluded - patients should be regularly monitored for increased phenytoin concentrations (§4.4, §4.5)
  • Myelosuppressive agents: caution because of a potential risk of increased toxicity (§4.5)
  • Nephrotoxic substances: require extremely careful monitoring of renal function; medicines which affect glomerular filtration prolong the half-life of flucytosine (§4.5)
  • Amphotericin B: synergistic effect but the combination increases the risk of side effects; particularly careful renal monitoring (§4.2, §4.4)

Monitoring

  • Haematological status and liver function (SGOT, SGPT, alkaline phosphatase) before starting treatment and regularly thereafter - recommended daily during the first week of treatment and twice weekly thereafter (§4.4)
  • Renal function (preferably endogenous creatinine clearance) before and during treatment (§4.4); flucytosine may interfere with the two-stage enzymatic creatinine measurement on the manual Vitros DT 60 analyser - use other methods (§4.4)
  • Serum flucytosine levels: steady-state average 35 to 70 μg/ml; keep above 25 μg/ml; avoid prolonged levels above 100 μg/ml; take samples shortly before starting the next infusion because levels during or just after an infusion are not a reliable guide (§4.4)
  • Great caution in bone marrow depression or blood dyscrasias; more frequent blood counts in patients on cytostatic or immunosuppressive therapy (§4.4)
  • Sensitivity cultures before treatment and repeated at regular intervals during therapy, without delaying treatment (§4.4)
  • Consider determining DPD activity where toxicity is confirmed or suspected; in suspected toxicity consider stopping treatment (§4.4)
  • Fluid and electrolyte intake should allow for the volume and sodium content (138 millimole/litre) of the infusion in renal impairment, cardiac failure or electrolyte imbalance (§4.4)

Clinical monograph

How it works

It is taken up by fungal cells and converted to 5-fluorouracil, which disrupts fungal RNA and DNA synthesis; it is given with another antifungal to enhance efficacy and limit resistance.

Prescribing in practice

  • Dose-related bone marrow suppression (leucopenia and thrombocytopenia) is the principal toxicity, so blood counts and drug levels must be monitored closely.
  • It is almost always combined with another antifungal because resistance develops rapidly when used alone.
  • It is largely renally excreted, so renal impairment markedly increases the risk of toxicity and requires dose adjustment and level monitoring.

Monitoring

Monitor full blood count, renal and hepatic function, and plasma flucytosine concentrations to avoid toxic accumulation.

Counselling the patient

  • Regular blood tests are needed to check your blood counts and drug levels.
  • Report any signs of infection, unusual bruising or bleeding.
  • This is given alongside another antifungal medicine as part of your treatment.

Evidence & guidelines

Flucytosine combined with amphotericin B is standard induction therapy for cryptococcal meningitis in UK and international guidance.

Reference: BHIVA opportunistic infection guidance; SmPC; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

Pathways