Flucytosine

Systemic Fungal Infections (used with Amphotericin; risk of induced resistance when used alone)
1. Cryptococcal Meningitis
2. CNS Candidiasis (HIV Infection)
3. Candida Pyelonephritis

Flucytosine is a Fluorouracil prodrug, a fluorinated cytosine analog with Antifungal activity
Within fungal cells, Flucytosine is deaminated to the active metabolite 5-Fluorouracil
1. 5-Fluorouracil substitutes for the Pyrimidine uracil during RNA synthesis
2. Inhibits fungal Protein synthesis
Fluorouracil is also metabolized to the active 5-Fluorodeoxyuridine monophosphate (FdUMP)
1. FdUMP inhibits thymidylate synthetase
2. Blocks Nucleotide metabolism, and secondarily DNA synthesis and Protein synthesis

Typically combined with Amphotericin
1. Induced resistance may occur rapidly when Flucytosine is used alone
Dose: 100 mg/kg/day orally divided four times daily for >=14 days
1. Although not FDA approved in children, it is used off-label (not in renal dysfunction)
2. Decrease dose to 75 mg/kg/day in weight <2 kg or age <60 days
Renal Dosing: Adults
1. Creatinine Clearance 20 to 40 ml/min: Take 25 mg/kg every 12 hours
2. Creatinine Clearance 10 to 20 ml/min: Take 25 mg/kg every 24 hours
3. Creatinine Clearance <10 ml/min: Take 25 mg/kg every 48 hours
4. Hemodialysis: 25 to 50 mg/kg every 48 to 72 hours (dosing after Hemodialysis run)

Target peak level (2 hours after dose): 30 to 90 mcg/ml
1. Drug levels >100 mcg/ml risk increased toxicity