Adult

Flucytosine

General Information

Unlicensed Restricted formulary antimicrobial: For details see OUH netFormulary

IV flucytosine has been discontinued globally. Unlicensed oral flucytosine remains available - for further information about supply discuss with pharmacy.

Dosage

Standard Dose - 50 mg/kg po qds 

Cryptococcal meningitis – 25mg/kg po qds in combination with amphotericin B liposomal 

Obesity

Use ideal body weight to calculate dose. Carry out therapeutic drug monitoring.

Renal and hepatic impairment

Renal impairment

For dosing information see table below.

In patients with renal impairment monitor U&Es, LFTs and FBC regularly. Also carry out therapeutic drug monitoring.

eGFR

(ml/min/1.73m2)

Where usual dose would be

25mg/kg po qds

Where usual dose would be

50mg/kg po qds
Over 40 No adjustment No adjustment
20-40 25mg/kg bd 50mg/kg bd
10-20 25mg/kg od 50mg/kg od
Less than 10 25mg/kg 48 hourly

Discuss with Pharmacy

Dosing usually 50mg/kg stat then 0.5-1g daily

Dosing for patients with HD/HDF/High Flux or PD should be discussed with pharmacy or Micro/ID

 

Hepatic impairment

No dose adjustment. In patients with hepatic impairment monitor LFTs closely and carry out therapeutic drug monitoring.

 

Therapeutic Drug Monitoring

Therapeutic Drug Monitoring is required. See Therapeutic Drug Monitoring (TDM) for Antifungal Agents

Notable interactions

Before flucytosine is started see the Summary of Product Characteristics (SPC) for flucytosine for information about interactions, cautions and contraindications.

  • The co-administration of flucytosine with several medications is contraindicated. See SPC for more information.
  • Caution is recommended for the use of flucytosine with several medications. See SPC for more information.
  • Some medications require a dose adjustment of either flucytosine or the other medication when they are used concomitantly. See SPC for more information.

Contraception, pregnancy and breastfeeding

Contraception: 

 Flucytosine is partially metabolised into 5-fluorouracil, which is genotoxic and considered as a potential human teratogen.

  • Females of childbearing potential must use effective contraception during treatment with flucytosine and for 6 months after discontinuation of treatment. In case of renal impairment, the contraception period should be prolonged for an additional 2 months.
  • Male patients (or their female partners of childbearing potential) must use effective contraception during treatment and for 3 months after discontinuation of treatment. In case of renal impairment, the contraception period should be prolonged for an additional 2 months.

Pregnancy: Discuss with pharmacy and Micro/ID. Limited data for use in pregnant women. Teratogenicity and embryotoxicity have been shown in animal studies.

Breastfeeding: Avoid. Use is contraindicated.

Additional information

  • Use in caution in patients with depression of bone marrow function or blood dyscrasias as well as in patients treated with immunosuppressive or cytostatic agents. Due to a high risk of haematological damage, monitor FBC and carry out therapeutic drug monitoring.
  • Blood counts and tests of renal and hepatic function should be performed before and during treatment. This should occur at least weekly in patient with renal insufficiency or blood dyscrasias. Some resources say monitor daily for first week then twice a week thereafter during treatment.
  • Flucytosine can cause life-threatening and severe toxicity in patients with complete and partial dihydropyrimidine dehydrogenase (DPD) deficiency. See MHRA Drug Safety Update Flucytosine (Ancotil): new contraindication in patients with DPD deficiency  Do not delay therapy with flucytosine for pre-treatment testing of DPD deficiency; however, consider determination of DPD activity if drug toxicity is confirmed or suspected. In cases of drug toxicity, consider stopping treatment with flucytosine.

References

Editorial Information

Next review date: 01 May 2028