Flucytosine Data - Uses, Dosage, Drug class, Brand name, Warnings, etc

Pharmacology	Flucytosine (5-FC), a fluorinated cytosine analogue, is deaminated to the cytotoxic antimetabolite fluorouracil by fungal cytosine deaminase, absent in human cells. It has a narrow spectrum, primarily against Candida and Cryptococcus spp., and is used with other antifungals due to rapid resistance development when used alone.
Administration and Adult Dosage	- PO: 50–150 mg/kg/day in 4 divided doses; higher doses may prevent resistance - Duration: Guided by infection severity and treatment response
Special Populations - Pediatric Dosage	- PO: Same as adult dosage (mg/kg)
Special Populations - Geriatric Dosage	Same as adult dosage, adjusted for age-related renal function decline (see Other Conditions).
Other Conditions	- Renal impairment: • Dose interval (hr) = 4 × Crs (mg/dL) • Alternative: Reduced doses every 6 hr • Maintenance hemodialysis (every 48–72 hr): 20–50 mg/kg post-dialysis - Liver disease: Use normal dosage
Dosage Forms	- Capsule: 250, 500 mg
Patient Instructions	- Take capsules for a single dose over 15 min with food to minimize stomach upset - Report nausea, vomiting, diarrhea, or signs of bone marrow suppression (e.g., bruising, bleeding) to your physician
Missed Doses	- Take missed dose as soon as remembered; if near next dose, take only that dose, leaving ≥4 hr between doses; do not double dose
Pharmacokinetics - Serum Levels	- Toxicity likely >100 mg/L (780 µmol/L)
Pharmacokinetics - Fate	- Absorption: ~90%, peak 8–12 mg/L (62–93 µmol/L) 1–2 hr post 500 mg dose (normal renal function) - Protein Binding: Negligible - Distribution: Vd = 0.7 L/kg; penetrates CSF, eye - Elimination: ~90% unchanged via glomerular filtration; urine levels far exceed serum - Metabolism: Low serum fluorouracil levels may cause hematologic toxicity
Pharmacokinetics - t¹⁄₂	- 6 ± 0.6 hr (normal); up to ≥100 hr (renal impairment)
Adverse Reactions & Side Effects	Occasional: - Nausea, vomiting, diarrhea, bone marrow suppression (dose-limiting in HIV patients), elevated liver function tests (asymptomatic, reversible) Rare: - Ulcerating enteritis
Contraindications	- Hypersensitivity to flucytosine
Precautions & Warnings	- Use cautiously in pregnancy, severe renal impairment (monitor serum levels, keep peaks <100 mg/L), hepatic impairment, hematologic disorders, or history of myelosuppressive therapy (e.g., zidovudine, ganciclovir, chemotherapy) or radiation
Drug Interactions	- Amphotericin B increases flucytosine toxicity by enhancing cellular penetration and impairing elimination via nephrotoxicity
Parameters to Monitor	- BUN, Crs, Clcr, full hematology, liver function tests before and frequently during therapy - Serum flucytosine levels in renal impairment to avoid toxicity (>100 mg/L)
Class and Drug Brand Name	- Class: Fluorinated Pyrimidine Antifungals - Brand Name: Ancobon
Notes	- Often synergistic with amphotericin B, useful for cryptococcal meningitis in AIDS/non-AIDS patients, though superiority in AIDS unclear - Potential additive/synergistic effect with fluconazole for cryptococcal meningitis; requires further clinical trial validation - Narrow spectrum necessitates combination therapy to prevent resistance

References

Hand of Clinical Drug Data