- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Infusion of flucytosine.
Candidiasis - severe systematic (adjunctive)
Cryptococcal meningitis (adjunctive)
Other sensitive chronic infections (adjunct)
Systemic yeast and fungal infections
Treatment of systemic yeast and fungal infections due to sensitive organisms. Types of infections include cryptococcosis, candidiasis, chromomycosis, torulopsis glabrata and hansenula.
When treating cryptococcal meningitis and severe systemic candidiasis, flucytosine should be given in combination with amphotericin B. Where amphotericin B is not suitable for the treatment of cryptococcal meningitis, flucytosine may be given with fluconazole (although rate of cure may be slower). Amphotericin B may also be given in combination with flucytosine when treating severe or long-standing infections due to other organisms.
200mg/kg daily, given divided into four doses over 24 hours.
Adequate effects can be obtained with a lower dose. For extremely sensitive organisms, a reduced daily dose of 100mg/kg to 150mg/kg may be sufficient.
Duration of treatment should be determined on an individual basis but flucytosine should rarely be required for longer than one week. Although, in cryptococcal meningitis treatment should continue for at least four months.
Patients with Renal Impairment
Flucytosine is primarily excreted via the kidneys, so renally impaired patients should be given reduced doses:
Creatinine clearance 20 to 40ml/minute: 50mg/kg every 12 hours
Creatinine clearance 10 to 20ml/minute: 50mg/kg every 24 hours
Creatinine clearance less than 10ml/minute: Initial single dose of 50mg/kg. Subsequently, titrate to serum drug concentration, which should not exceed 80micrograms/ml. Blood levels of 25 to 50micrograms/ml are normally effective.
Duration of treatment is dependent on individual response.
The infusion contains 138millimole/litre of sodium. This should be taken into account when calculating the fluid and electrolyte intake of patients with renal impairment.
For intravenous infusion through a central venous catheter or intra-peritoneal infusion.
Flucytosine infusion should be administered using a giving set.
Suggested duration of infusion should be 20-40 minutes.
Therapeutic Drug Monitoring
Flucytosine has a narrow therapeutic window and there is a risk of potential toxicity at high systemic concentrations.
Therapeutic drug monitoring is required as serum levels may vary considerably between patients.
Serum levels should be monitored shortly before starting each infusion. Levels for optimum response are 25 to 50micrograms/ml. Blood levels should not exceed 80micrograms/ml.
Complete dihydropyrimidine dehydrogenase deficiency
Precautions and Warnings
Children under 18 years
Partial dihydropyrimidine dehydrogenase deficiency
Sodium content of formulation may be significant
DPD deficiency phenotype/genotype testing is recommended prior to treatment
Monitor blood values before and during treatment
Monitor renal and hepatic function before and during treatment
Take cultures for sensitivity testing before and regularly during treatment
Do not allow drug serum concentrations to exceed 80mcg/ml
Monitor drug serum levels before next infusion (not after)
Monitor renal & hepatic function weekly in renal impairment/blood disorders
Narrow therapeutic range - monitoring levels useful to assess toxicity
May affect results of some laboratory tests
Female: Contraception required during and for 1 month after treatment
Male: Contraception required for partners for 3 months after treatment
Blood samples taken to determine drug serum levels during or immediately after the infusion are unreliable. It is advised that samples for testing should be taken shortly before starting the next infusion.
The infusion contains 138 millimole/litre of sodium. This should be taken into account when calculating the fluid and electrolyte intake of patients with renal impairment, cardiac failure or electrolyte imbalance.
Resistance to flucytosine can develop during therapy.
To determine sensitivities, Shadomy and Scholer methods are recommended.
When testing, it is essential that the culture media is free of flucytosine antagonists.
Monitor plasma flucytosine levels in paediatric patients in line with national guidelines and dose adjustments to avoid excessive exposure to flucytosine due to prolonged elimination of flucytosine in paediatric patients.
Pregnancy and Lactation
Use flucytosine with caution during pregnancy.
The manufacturer does not recommend using flucytosine during pregnancy or in women of childbearing potential not using contraception, unless treatment is vital. Animal studies have shown teratogenic effects. Human data is limited and as such a potential risk cannot be ruled out.
Flucytosine is contraindicated during breastfeeding.
Use of flucytosine when breastfeeding is contraindicated by the manufacturer. The presence of flucytosine in human breast milk and the effects on exposed infants are unknown.
Acute hepatic disorders
Altered liver function tests
Bone marrow toxicity
Toxic epidermal necrolysis
Effects on Laboratory Tests
Flucytosine may interfere with the dual slide enzymatic measurement of creatinine used with the manual desk top Vitros DT 60 analyser, resulting in the false impression of azotaemia. Other suitable methods such as the automated Vitros analysers should be used instead.
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Last Full Review Date: November 2019
Summary of Product Characteristics: Ancotil 2.5g/250ml solution for infusion. Mylan. April 2019.
MHRA Drug Safety Update October 2020
Available at: https://www.mhra.gov.uk
Last accessed: 25 January 2021
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 25 January 2021
Already a member? Log in
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.