Flucytosine Dosing for Adults
The recommended dose of flucytosine for adults is 25 mg/kg orally four times daily (every 6 hours) for patients with normal renal function. 1
Standard Dosing Parameters
- Route of administration: Oral only—flucytosine is not available as an intravenous formulation in the United States 1
- Standard dose: 25 mg/kg administered four times daily 1
- Bioavailability: Excellent oral absorption at 80-90% 1
- Half-life: Short (2.4-4.8 hours), necessitating four-times-daily dosing 1
Critical Dosing Adjustments
Renal Impairment
Dose reduction is mandatory in renal dysfunction because >90% of flucytosine is excreted unchanged in the urine. 1
- Creatinine clearance >50 mL/min: 150 mg/kg per day (37.5 mg/kg four times daily) 2
- Creatinine clearance 26-50 mL/min: 75 mg/kg per day (18.75 mg/kg four times daily) 2
- Creatinine clearance 13-25 mL/min: 37 mg/kg per day (9.25 mg/kg four times daily) 2
Therapeutic Drug Monitoring
Serum flucytosine levels should be monitored to prevent concentration-dependent toxicity (bone marrow suppression and hepatitis). 1
- Target peak level: 50-100 μg/mL measured 2 hours after an oral dose 2
- Monitoring frequency: Weekly during therapy 2
- Toxic threshold: Peak levels ≥100 μg/mL for ≥2 weeks significantly increase toxicity risk 2
Clinical Context and Combination Therapy
Flucytosine is rarely used as monotherapy due to rapid emergence of resistance and should be combined with another antifungal agent. 1
Common Combination Regimens
- Cryptococcal meningitis: Amphotericin B plus flucytosine for induction therapy 1
- Candida endocarditis/meningitis/endophthalmitis: Amphotericin B plus flucytosine 1
- Fluconazole-resistant C. glabrata urinary tract infections: Flucytosine 25 mg/kg four times daily for 7-10 days (cystitis) or 2 weeks (pyelonephritis) 1
Important Caveats
Spectrum Limitations
- Not active against C. krusei—do not use for this pathogen 3, 4
- Broad activity against most other Candida species 1
Special Populations
- Neonates and very low birth-weight infants: Use discouraged without careful serum level monitoring due to immature renal function and drug accumulation 1
- Pregnancy: Contraindicated due to potential fetal harm 1
- Continuous hemofiltration: Significant drug removal occurs; dosing adjustments and therapeutic monitoring essential 5