Brands, Medical Use, Clinical Data
Drug Category
- Antimetabolites
- Antifungals
Dosage Forms
- Capsule (250mg and 500mg)
Brands / Synonyms
5-FC; 5-Fluorocystosine; 5-Fluorocytosin; 5-Fluorocytosine; 5-Fluorocytosine (Flucytosine); 5-Flurocytosine; Ancobon; Ancobon (TN); Ancotil; Flucytosin; Flucytosine (JP14/USP); Flucytosine(USAN); Fluocytosine; Fluorcytosine
Indications
For the treatment (in combination with amphotericin B) of serious infections caused by susceptible strains of Candida (septicemia, endocarditis and urinary system infections) and/or Cryptococcus (meningitis and pulmonary infections).
Pharmacology
Flucytosine is an antimetabolite that acts as an antifungal agent with in vitro and in vivo activity against Candida and Cryptococcus. Flucytosine enters the fungal cell via cytosine permease; thus, flucytosine is metabolized to 5-fluorouracil within fungal organisms. The 5-fluorouracil is extensively incorporated into fungal RNA and inhibits synthesis of both DNA and RNA. The result is unbalanced growth and death of the fungal organism. Antifungal synergism between Ancobon and polyene antibiotics, particularly amphotericin B, has been reported.
Mechanism of Action
Although the exact mode of action is unknown, it has been proposed that flucytosine acts directly on fungal organisms by competitive inhibition of purine and pyrimidine uptake and indirectly by intracellular metabolism to 5-fluorouracil. Flucytosine enters the fungal cell via cytosine permease; thus, flucytosine is metabolized to 5-fluorouracil within fungal organisms. The 5-fluorouracil is extensively incorporated into fungal RNA and inhibits synthesis of both DNA and RNA. The result is unbalanced growth and death of the fungal organism. It also appears to be an inhibitor of fungal thymidylate synthase.
Absorption
Rapidly and virtually completely absorbed following oral administration. Bioavailability 78% to 89%.
Toxicity
Oral, rat: LD50 = >15 gm/kg.
Biotrnasformation / Drug Metabolism
Flucytosine is deaminated, possibly by gut bacteria or by the fungal targets, to 5-fluorouracil, the active metabolite.
Contraindications
5-Flucytosine should not be used in patients with a known hypersensitivity to the drug.
Drug Interactions
Cytosine arabinoside, a cytostatic agent, has been reported to inactivate the antifungal activity of flucytosine by competitive inhibition. Drugs which impair glomerular filtration may prolong the biological half-life of flucytosine.
Drug/Laboratory Test Interactions: Measurement of serum creatinine levels should be determined by the Jaffe reaction, since Ancobon does not interfere with the determination of creatinine values by this method. Most automated equipment for measurement of creatinine makes use of the Jaffe reaction.
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