No

Antifungal Agent, Oral

Adjunctive treatment of susceptible fungal infections (usually Candida or Cryptococcus); synergy with amphotericin B for certain fungal infections ( Cryptococcus spp., Candida spp.)

C

Hypersensitivity to flucytosine or any component

Use with extreme caution in patients with renal impairment, bone marrow suppression, or in patients with AIDS; dosage modification required in patients with impaired renal function

1% to 10%:

Dermatologic: Rash

Gastrointestinal: Abdominal pain, diarrhea, loss of appetite, nausea, vomiting

Hematologic: Anemia, leukopenia, thrombocytopenia

Hepatic: Hepatitis, jaundice

<1%: Cardiac arrest, confusion, hallucinations, dizziness, drowsiness, headache, parkinsonism, psychosis, ataxia, photosensitivity, temporary growth failure, hypoglycemia, hypokalemia, bone marrow suppression, elevated liver enzymes, paresthesia, hearing loss, respiratory arrest, anaphylaxis

Symptoms of overdose include nausea, vomiting, diarrhea, bone marrow suppression

Treatment is supportive

Increased effect/toxicity with concurrent amphotericin administration; cytosine may inactivate flucytosine activity

Protect from light

Penetrates fungal cells and is converted to fluorouracil which competes with uracil interfering with fungal RNA and protein synthesis

Absorption: Oral: 75% to 90%

Distribution: Into CSF, aqueous humor, joints, peritoneal fluid, and bronchial secretions

Metabolism: Minimal

Protein binding: 2% to 4%

Half-life: 3-8 hours

Anuria: May be as long as 200 hours

End-stage renal disease: 75-200 hours

Time to peak serum concentration: Within 2-6 hours

Elimination: 75% to 90% excreted unchanged in the urine by glomerular filtration

Children and Adults: Oral: 50-150 mg/kg/day in divided doses every 6 hours

Cl_cr >50 mL/minute: Administer every 12 hours

Cl_cr 10-50 mL/minute: Administer every 16 hours

Cl_cr <10 mL/minute: Administer every 24 hours

Hemodialysis: Dialyzable (50% to 100%); administer dose posthemodialysis

Peritoneal dialysis: Adults: Administer 0.5-1 g every 24 hours

Continuous arteriovenous or venovenous hemodiafiltration (CAVH) effects: Dose as for Cl_cr 10-50 mL/minute

Food decreases the rate, but not the extent of absorption

Serum creatinine, BUN, alkaline phosphatase, AST, ALT, CBC; serum flucytosine concentrations

Therapeutic: 25-100 mg/mL (SI: 195-775 mmol/L); levels should not exceed 100-120 mg/mL to avoid toxic bone marrow depressive effects

Trough: Draw just prior to dose administration

Peak: Draw 2 hours after an oral dose administration

Flucytosine causes markedly false elevations in serum creatinine values when the Ektachem® analyzer is used

May rarely cause drowsiness, confusion, or hallucinations

May cause bone marrow suppression; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

Take capsules one at a time over a few minutes with food to reduce GI upset. Take full course of medication as ordered. Do not discontinue without consulting prescriber. Practice good hygiene measures to prevent reinfection. Frequent blood tests may be required. You may experience nausea and vomiting (small, frequent meals may help). Report rash, respiratory difficulty, CNS changes (eg, confusion, hallucinations, ataxia, acute headache), yellowing of skin or eyes, and changes in color of stool or urine, unresolved diarrhea or anorexia, or unusual bleeding or fatigue and weakness. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Breast-feeding is not recommended.

Administer around-the-clock rather than 4 times/day, 3 times/day, etc, (ie, 12-6-12-6, not 9-1-5-9) to promote less variation in peak and trough serum levels; perform hematologic, renal and hepatic function tests

Capsule: 250 mg, 500 mg

Flucytosine oral liquid has been prepared by using the contents of ten 500 mg capsules triturated in a mortar and pestle with a small amount of distilled water; the mixture was transferred to a 500 mL volumetric flask; the mortar was rinsed several times with a small amount of distilled water and the fluid added to the flask; sufficient distilled water was added to make a total volume of 500 mL of a 10 mg/mL liquid; oral liquid was stable for 70 days when stored in glass or plastic prescription bottles at 4°C or for up to 14 days at room temperature.

Baley JE, Meyers C, Kliegman RM, et al, "Pharmacokinetics, Outcome of Treatment, and Toxic Effects of Amphotericin B and 5-Fluorocytosine in Neonates," J Pediatr, 1990, 116(5):791-7.

Lau AH and Kronfol NO, "Elimination of Flucytosine by Continuous Hemofiltration," Am J Nephrol, 1995, 15(4):327-31.

Lyman CA and Walsh TJ, "Systemically Administered Antifungal Agents. A Review of Their Clinical Pharmacology and Therapeutic Applications," Drugs, 1992, 44(1):9-35.

Patel R, "Antifungal Agents. Part I. Amphotericin B Preparations and Flucytosine," Mayo Clin Proc, 1998, 73(12):1205-25.