Drugs List

Therapeutic Indications

Uses

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.

Administration

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.

Contraindications

Breastfeeding
Complete dihydropyrimidine dehydrogenase deficiency

Precautions and Warnings

Children under 18 years
Debilitation
Immunosuppression
Cardiac failure
Electrolyte imbalance
Haematological disorder
Myelosuppression
Partial dihydropyrimidine dehydrogenase deficiency
Pregnancy
Renal impairment

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

Pregnancy

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.

Lactation

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.

Side Effects

Acute hepatic disorders
Agranulocytosis
Allergic reaction
Altered liver function tests
Aplastic anaemia
Blood disorders
Bone marrow toxicity
Cardiotoxicity
Confusion
Convulsions
Diarrhoea
Hallucinations
Headache
Hepatic necrosis
Hepatitis
Leucopenia
Lyell's syndrome
Nausea
Rash
Sedation
Thrombocytopenia
Toxic epidermal necrolysis
Ventricular dysfunction
Vertigo
Vomiting

Presentation

Infusion of flucytosine.

Drugs List

Therapeutic Indications

Uses

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.

Dosage

Adults

Patients with Renal Impairment

Administration

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.

Contraindications

Breastfeeding
Complete dihydropyrimidine dehydrogenase deficiency

Precautions and Warnings

Children under 18 years
Debilitation
Immunosuppression
Cardiac failure
Electrolyte imbalance
Haematological disorder
Myelosuppression
Partial dihydropyrimidine dehydrogenase deficiency
Pregnancy
Renal impairment

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

Pregnancy

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.

Lactation

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.

Side Effects

Acute hepatic disorders
Agranulocytosis
Allergic reaction
Altered liver function tests
Aplastic anaemia
Blood disorders
Bone marrow toxicity
Cardiotoxicity
Confusion
Convulsions
Diarrhoea
Hallucinations
Headache
Hepatic necrosis
Hepatitis
Leucopenia
Lyell's syndrome
Nausea
Rash
Sedation
Thrombocytopenia
Toxic epidermal necrolysis
Ventricular dysfunction
Vertigo
Vomiting

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.

Overdosage

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 ).

Further Information

Last Full Review Date: November 2019

Reference Sources

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