Flucytosine (5-Fluorocytosine): A Comprehensive Pharmacological and Clinical Monograph

Executive Summary

Flucytosine, also known as 5-fluorocytosine (5-FC), is a fluorinated pyrimidine analogue classified as an antimetabolite antifungal agent. It functions as a prodrug, which, following selective uptake into susceptible fungal cells, undergoes intracellular conversion to the active cytotoxic agent, 5-fluorouracil (5-FU). This active metabolite subsequently disrupts fungal DNA and RNA synthesis through dual pathways, leading to fungal cell death. Crucially, human cells lack the necessary enzyme, cytosine deaminase, for this activation, which forms the basis of the drug's selective antifungal activity.

Despite its targeted mechanism, Flucytosine has a narrow therapeutic index. Its clinical utility is significantly limited by the rapid development of fungal resistance when used as monotherapy. Consequently, its primary role in modern medicine is as a synergistic partner in combination therapy, most notably with the polyene antifungal Amphotericin B. This combination is the established standard of care for the induction treatment of severe systemic mycoses, particularly cryptococcal meningitis, where it demonstrates a more rapid and potent fungicidal effect than either agent alone.