II. Indications
- Systemic Fungal Infections (used with Amphotericin; risk of induced resistance when used alone)
III. Mechanism
- Flucytosine is a Fluorouracil prodrug, a fluorinated cytosine analog with Antifungal activity
- Within fungal cells, Flucytosine is deaminated to the active metabolite 5-Fluorouracil
- 5-Fluorouracil substitutes for the Pyrimidine uracil during RNA synthesis
- Inhibits fungal Protein synthesis
-
Fluorouracil is also metabolized to the active 5-Fluorodeoxyuridine monophosphate (FdUMP)
- FdUMP inhibits thymidylate synthetase
- Blocks Nucleotide metabolism, and secondarily DNA synthesis and Protein synthesis
IV. Medications
- Capsules: 250 mg, 500 mg
V. Dosing
- Typically combined with Amphotericin
- Induced resistance may occur rapidly when Flucytosine is used alone
- Dose: 100 mg/kg/day orally divided four times daily for >=14 days
- Although not FDA approved in children, it is used off-label (not in renal dysfunction)
- Decrease dose to 75 mg/kg/day in weight <2 kg or age <60 days
-
Renal Dosing: Adults
- Creatinine Clearance 20 to 40 ml/min: Take 25 mg/kg every 12 hours
- Creatinine Clearance 10 to 20 ml/min: Take 25 mg/kg every 24 hours
- Creatinine Clearance <10 ml/min: Take 25 mg/kg every 48 hours
- Hemodialysis: 25 to 50 mg/kg every 48 to 72 hours (dosing after Hemodialysis run)
VI. Adverse Effects
- Induced resistance
- Myelosuppression (Bone Marrow toxicity)
- Colitis
- Hepatotoxicity
-
Nausea
- Spread capsule doses out over 15 minutes
VII. Safety
- Avoid in pregnancy (although listed as Pregnancy Category C)
- Avoid in Lactation
VIII. Pharmacokinetics
- Target peak level (2 hours after dose): 30 to 90 mcg/ml
- Drug levels >100 mcg/ml risk increased toxicity
IX. Monitoring
- Therapeutic drug levels (see Pharmacokinetics above)
- Liver function
- Hematologic labs
- Renal Function
X. Resources
- Flucytosine Capsule (DailyMed)
XI. References
- Hamilton (2020) Tarascon Pocket Pharmacopoeia
- (2012) Med Lett Drugs Ther 10(120): 61-8 [PubMed]