Flucytosine

Summary

Flucytosine is an antifungal drug that is converted into 5-fluorouracil, which inhibits both fungal DNA polymerase and RNA polymerase. Flucytosine is most commonly used to treat cryptococcal meningitis in combination with amphotericin B. You should remember that a common side effect of flucytosine is bone marrow suppression.

Key Points

• Flucytosine
  • Mechanism
    • Inhibits fungal DNA and RNA synthesis
      • Converted into 5-fluorouracil (5-FU) by cytosine deaminase
        • Fluorinated analog of cytosine inhibits DNA and RNA polymerase
      • Inhibits both DNA replication and fungal protein synthesis
    • Cleared renally
  • Clinical Use
    • Systemic fungal infections
      • Cryptococcal meningitis
        • Used in combination with amphotericin B
  • Adverse Effects
    • Bone marrow suppression
      • 5-fluorouracil is used as a chemotherapy with similar effects on bone marrow
      • May present as anemia, thrombocytopenia, or leukopenia
    • Nephrotoxicity
      • Renal toxicity caused by amphotericin may be accentuated by concomitant administration of flucytosine
    • Hepatotoxicity
      • About 5% of patients will develop elevated liver enzymes and evidence of hepatitis
    • Nausea/vomiting
      • Seen in about 6% of patients