Antifungal Antimetabolites

Question 1

Antifungal Antimetabolites

Answer 1

Flucytosine (5-FC)

Originally investigated as oncology drug; found to be more active against fungal cells than human cancer cells

Used in combo with AmphoB for cryptococcal disease

Rarely used for infections (due to toxicity and relative lack of efficacy)

Question 2

Antifungal Antimetabolites MOA

Answer 2

It is deaminated inside fungal cells to 5-fluorouracil- further converted into metabolites that interfere with protein and DNA synthesis

Question 3

Antifungal Antimetabolites Spectrum

Answer 3

Good (in combo with AmphoB)
Cryptococcus neoformans and most species of Candida

Moderate (monotherapy)
Cryptococcus neoformans and most species of Candida

Poor
Molds
C. krusei

Question 4

Antifungal Antimetabolites Adverse Effects

Answer 4

It is fluorouracil for fungi
Is only relatively selective for fungi; can cause considerable bone marrow suppression (particularly in higher doses or during prolonged courses)

GI complaints more common but less severe

Question 5

Antifungal Antimetabolites Important Facts

Answer 5

Drug concentration monitoring available
Check peak about 2 hours after first dose
Hematology values are more important than drug levels when monitoring for toxicity
In most hospital it is a sendout lab (can take up to a week to be resulted); most common duration of therapy is 2 weeks so practical utility of doing labs is limited

Generally should not be used as monotherapy for invasive candidiasis because of potential emergence of in vivo resistance

Most common use is in combo with AmphoB for cryptococcal meningitis
The combo is recommended in guidelines and very common but clinicians have questioned flucytosine’s value
Early study associated it with more rapid sterility of CSF cultures but showed no obvious clinical benefit
More recent studies have shown survival benefit
It is difficult to obtain or afford in resource poor counties where HIV is highly endemic

Flucytosine commonly abbreviated as 5-FC
Avoid because it could be confused with the more toxic fluorouracil (5-FU)

If hematologic toxicity develops, consider dose modification or discontinuation

Question 6

Antifungal Antimetabolites Good For

Answer 6

Most commonly in combo with AmphoB for cryptococcal meningitis
This combo may also be used to treat other forms of cryptococcal infections and uncommonly Candida

May be acceptable option for clearance of candiduria in patients who cannot receive fluconazole (due to allergy or resistance); only a small number of patients will require this therapy