Flucytosine: a review of its pharmacology, clinical indications, pharmacokinetics, toxicity and drug interactions

Flucytosine (5-FC) is a synthetic antimycotic compound, first synthesized i n 1957. It has no intrinsic antifungal capacity, but after it has been take n up by susceptible fungal cells, it is converted Into 5-fluorouracil (5-FU ), which is further converted to metabolites that inhibit fungal RNA and DN A synthesis. Monotherapy with 5-FC is limited because of the frequent devel opment of resistance. In combination with amphotericin B, 5-FC can be used to treat severe systemic mycoses, such as cryptococcosis, candidosis, chrom oblastomycosis and aspergillosis. Recently, 5-FC has been combined with new er azole antifungal agents; it also plays an Important role In a new approa ch to the treatment of cancer. The severe side effects of 5-FC include hepa totoxicity and bone-marrow depression. In most patients, these side effects are concentration dependent, predictable, possibly avoidable with close mo nitoring to maintain 5-FC concentrations at <100 mg/L, and reversible with drug discontinuation or reduction of dose. 5-FC is well absorbed after oral administration, penetrates into body tissues well and is excreted mainly b y the kidneys. In renal failure, major dose adjustments have to be made. Th e most Important drug interaction of 5-FC occurs with concomitant administr ation of 5-FC and nephrotoxic drugs, especially amphotericin B. Owing to th e crucial role of glomerular filtration in 5-FC elimination, drugs that imp air this mechanism will decrease the elimination of 5-FC and thus prolong i ts half-life.