Antimetabolites

Agent: flucytosine (5-FC)

Flucytosine has a mechanism of action that is distinct from that of other antifungals in that it has an antimetabolite that interferes with DNA synthesis. Flucytosine was originally investigated as an oncology drug, but it was found to be significantly more active against fungi than against human cancer cells. The primary role of flucytosine is in com-bination therapy with amphotericin B formulations for cryptococcal disease. Because of its toxicity and relative lack of efficacy, it is rarely used for other infections.

Spectrum

Good: in combination with amphotericin B: Cryptococcus neoformans, most species of Candida

Moderate: monotherapy: Cryptococcus neoformans, most species of Candida

Poor: moulds, Candida krusei

Adverse Effects

Flucytosine, which is also called 5-FC, is fluorouracil for fungi. When this fact is considered, the adverse effects are predictable. Flucytosine is only relatively selective for fungi and can cause considerable bone marrow suppression, particularly in higher doses or during prolonged courses. GI complaints are more common, but they are less severe.

Important Facts

• Drug concentration monitoring is available for flucytosine: check a peak concentration about 2 hours after the dose is given. However, do not rely on flucytosine concentrations alone to monitor for toxicity—hematology values are more important than drug levels.

• Flucytosine generally should not be used as monotherapy for invasive candidiasis because of the potential emergence of resistance in vivo.

 • The most common use for flucytosine is in com-bination with an amphotericin B formulation for cryptococcal meningitis. Though this combination is recommended in guidelines and very common, some clinicians question the value of flucytosine. In the main clinical study for this indication, flucytosine use was associated with more rapid sterility of cerebrospinal fluid cultures but showed no obvious clinical benefit.

What It’s Good For

As stated above, most flucytosine use is in combination with an amphotericin B formulation for treatment of cryptococcal meningitis. This combination may also be used to treat other forms of cryptococcal infection and, uncommonly, to treat Candida infection. It may be an acceptable option for the clearance of candiduria in patients who cannot receive fluconazole because of allergy or resistance,  but the number of patients who require this therapy is small.

Don’t Forget!

Follow your patient’s cell counts closely and recon-sider the value of flucytosine therapy if hematologic toxicity develops.

References

Gallagher ,J.C. and MacDougall ,c. (2012). Antibiotics Simplified. Second Edition. Jones & Bartlett Learning, LLC.