flucytosine

Following penetration into fungi, converted to fluorouracil, which interferes with fungal DNA and RNA synthesis.
Synergistic action with amphotericin B against some fungi.

Therapeutic effects:

Fungicidal action against susceptible organisms.

Spectrum:

Active against only a small number of fungi, mainly:
- Candida albicans,
- Cryptococcus neoformans.

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed (80–90%) from the GI tract following oral administration.

Distribution: Widely distributed. Crosses the blood-brain barrier.

Metabolism/Excretion: Undergoes minimal hepatic metabolism; deaminated by gut bacteria to 5–fluorouracil (metabolized by dihydopyrimidine dehydrogenase); 80–90% excreted unchanged by the kidneys.

Half-Life: 2.5–5 hr (↑ in renal impairment).

Time/Action Profile ⬆ ⬇

(antifungal blood levels)

ROUTE	ONSET	PEAK	DURATION
PO	rapid	1–2 hr	6 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Complete dihydropyrimidine dehydrogenase (DPD) enzyme deficiency (↑ risk of 5–fluorouracil toxicity);
Lactation: Lactation.

Use Cautiously in:

Bone marrow depression (especially following radiation therapy or antineoplastics);
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk.

Renal impairment (blood level monitoring, ↓ dose, and ↑ dosage interval recommended if CCr <40 mL/min).

Adv. Reactions/Side Effects ⬆ ⬇

CV: chest pain

Derm: photosensitivity, pruritus, rash, urticaria

EENT: hearing loss

Endo: hypoglycemia

F and E: hypokalemia

GI: diarrhea, nausea, vomiting, abdominal pain, dry mouth

GU: azotemia

Hemat: leukopenia, pancytopenia, anemia, APLASTIC ANEMIA, eosinophilia, thrombocytopenia

Neuro: dizziness, ataxia, confusion, drowsiness, fatigue, headache, peripheral neuropathy, SEIZURES

Resp: dyspnea

Misc: fever

Interactions ⬆ ⬇

Drug-drug:

Additive bone marrow depression with other bone marrow depressant drugs, including antineoplastics and radiation therapy.
Amphotericin B may ↑ toxicity of flucytosine but may also increase its antifungal activity.
Cytarabine may ↓ its antifungal activity.

Route/Dosage ⬆ ⬇

PO (Adults ): 12.5–37.5 mg/kg every 6 hr.
PO (Children ): 12.5–37.5 mg/kg every 6 hr.

Renal Impairment

PO (Adults ): CCr 20–40 mL/min: 12.5 mg/kg every 12 hr; CCr 10–20 mL/min: 12.5 mg/kg every 24 hr; CCr <10 mL/min: 12.5 mg/kg every 24–48 hr.

Availability ⬆ ⬇

(Generic available)

Capsules: 250 mg; 500 mg

Assessment ⬆ ⬇

Assess patient for signs and symptoms of systemic fungal infection prior to and periodically during therapy.
Obtain specimens for culture prior to initiating therapy. First dose may be given before receiving results.

Lab Test Considerations:

Monitor AST, ALT, serum bilirubin, and alkaline phosphatase prior to and frequently during therapy.
- Monitor BUN and serum creatinine prior to and periodically during therapy. Dose should be reduced in renal impairment. Monitor serum flucytosine concentrations in patients with renal impairment to prevent accumulation. Side effects are more common with serum concentrations >100 mcg/mL.
- Monitor hematologic function periodically during therapy. May cause anemia, leukopenia, or thrombocytopenia.

Toxicity and Overdose:

Therapeutic peak serum flucytosine levels range from 25–100 mcg/mL. Peak levels should be obtained 2 hours after a dose.

Implementation ⬆ ⬇

PO: To reduce nausea and vomiting, administer capsules a few at a time over 15 min.

Patient/Family Teaching ⬆ ⬇

Advise patient to take medication as directed, even if feeling better. Missed doses should be taken as soon as remembered, if not almost time for next dose; do not double doses.
May cause dizziness or drowsiness. Caution patient to avoid driving and other activities requiring alertness until response to medication is known.
Caution patient to use sunscreen and wear protective clothing to prevent photosensitivity reactions.
Instruct patient to notify health care professional promptly if rash, fever, sore throat, yellowing of skin or eyes, changes in color of stool or urine, diarrhea, unusual bleeding or bruising, unusual tiredness, or weakness occurs.
Emphasize the importance of follow-up exams to determine effectiveness of treatment.
Rep: May cause fetal harm. Instruct females to notify health care professional immediately if pregnancy is planned or suspected or if breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇