• Flucytosine (25 mg/kg PO q6h) exerts its fungicidal effects on susceptible Candida and Cryptococcus species by interfering with DNA synthesis. Main clinical uses are in the treatment of cryptococcal meningitis and severe Candida infections in combination with amphotericin B, which results in synergy. This agent should not be used as monotherapy, apart from treatment of fluconazole-resistant Candida cystitis, because of risk for rapid emergence of resistance.
    • Adverse events include dose-related bone marrow suppression and bloody diarrhea due to intestinal flora conversion of flucytosine to 5-fluorouracil.
    • Peak drug concentrations, drawn 1 hour after oral administration, should be kept between 50 and 100 μg/mL. Close monitoring of serum concentrations and dose adjustments are critical in the setting of renal insufficiency. LFTs should be obtained at least once weekly.
  • Terbinafine (250 mg PO q24h for 6–12 wk) is an allylamine antifungal agent that kills fungi by inhibiting ergosterol synthesis. It is FDA-approved for the treatment of onychomycosis of the fingernails (6 wk of treatment) or toenails (12 wk of treatment). It is not generally used for systemic infections.
    • Adverse events include headache, GI disturbances, rash, LFT abnormalities, and taste disturbances. This drug should not be used in patients with hepatic cirrhosis or a CrCl of <50 mL/min. It does not significantly inhibit the metabolism of cyclosporine (15% decrease) or warfarin.

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