|Reviewed by Dr
Lesley Voss, Brenda Hughes, Mandy Hodgson, Ruth Tramschek
Dose and Administration
- 25 - 37.5 mg/kg/dose every 6 hours 8,9 .
- The oral route should be the
first line option, as the drug is well absorbed by this route. Use I.V. if
- 25 mg/kg/dose every 6 hours
- Congenital candidiasis, candida
meningitis, fungal endocarditis, systemic candidiasis and, systemic fungal
infections caused by other sensitive fungi.
- Usually used in combination with Amphotericin.
- Known hypersensitivity to flucytosine
- Known sensitivity to trometamol (excipient in infusion solution).
- Bone marrow depression
- Preterm infants, especially extreme immaturity.
- Renal dysfunction.
- Amphotericin; Possible decrease
in kidney function, resulting in reduced clearance of flucytosine
- Caution with other drugs with nephrotoxic potential.
An antifungal agent with activity
against Candida species, Cryptococcus neoformans and the pathogens of
The drug penetrates the cell, is transformed to 5-fluorouracil which interferes
with RNA synthesis. Resistance can develop during treatment and it is
recommended that sensitivity tests are conducted before and during treatment
6. Synergism has been demonstrated in several species of pathogens
when flucytosine is combined with amphotericin
Flucytosine is well absorbed from the gastrointestinal
tract. Widely distributed through body tissues and fluids and into the CSF
5. Low binding to plasma proteins. Approximately 80-90% of a given
dose is excreted, unchanged via the kidney.
Possible Adverse Effects
- Venous irritation, soft tissue injury at site of IV injection.
- Gastrointestinal disturbances (vomiting, diarrhoea).
- Alterations in liver function tests- possibly dose related and reversible. Hepatotoxicity
- Bone marrow depression: especially
leucopenia and thrombocytopenia (usually associated with toxic blood levels plus
concurrent amphotericin administration, and with renal function impairment.
Fatal agranulocytosis and aplastic anaemia have been reported5 .
- The oral preparation is unlicensed in New Zealand
- Usually given in conjunction with amphotericin due to high risk of resistance when used alone.
- Sensitivity of isolate before and during treatment
- Renal Function:
Mild renal failure- extend dose interval to every 12 hours
Moderate renal failure – extend dose interval to every 24 hours
Severe renal failure – dose according to serum levels 8.
- Full blood count and liver function – daily at start of treatment, then
- Therapeutic Drug Monitoring (TDM):
Steady state achieved in approximately one day.
Peak level: 250 – 400 μmol/L. Take level at 15 to 30 minutes
after end of I.V. infusion
10 or 2 hours after an oral dose
Trough level: > 80
μmol/L (to avoid resistance)
Infusion contains chloride (34.4mmol/250 mL)