Flucytosine

Pronunciation: flew-SITE-oh-seen
Class: Anti-infective, Antifungal

Trade Names

Ancobon
- Capsules 250 mg
- Capsules 500 mg

Pharmacology

Exact mechanism is unknown; interferes with DNA and RNA synthesis. Active against Candida and Cryptococcus .

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Pharmacokinetics

Absorption

Bioavailability is 78% to 89%. C _max is 30 to 40 mcg/mL; T _max is 1 to 2 h.

Distribution

The drug is 2.9% to 4% protein bound. It readily penetrates the blood-brain barrier achieving clinically significant concentrations in the CSF.

Elimination

Primarily renally excreted via glomerular filtration. The t _½ is 2.4 to 4.8 h. More than 90% is excreted in the urine unchanged and about 1% in the urine as metabolite (α-fluoro-β-ureido-propionic acid).

Special Populations

Prolonged t _½ (29.9 to 250 h in anuric or nephrectomized patients).

Indications and Usage

Treatment of serious infections caused by susceptible strains of Candida or Cryptococcus .

Contraindications

Standard considerations.

Dosage and Administration

PO 50 to 150 mg/kg/day in divided doses every 6 h.

Drug Interactions

Increased therapeutic action and toxicity of flucytosine.

Inactivates antifungal activity of flucytosine.

Laboratory Test Interactions

Interferes with creatinine value determinations with dry-slide enzymatic method (Kodak Ektachem analyzer); use Jaffe method.

Adverse Reactions

Cardiovascular

Cardiac arrest, myocardial toxicity, ventricular dysfunction.

CNS

Ataxia, hearing loss, headache, sedation, confusion, fatigue, weakness, dizziness, vertigo, paresthesia, parkinsonism, peripheral neuropathy, pyrexia, hallucinations, psychosis, convulsions.

Dermatologic

Rash, pruritus, urticaria, photosensitivity.

GI

Nausea, emesis, abdominal pain, diarrhea, anorexia, duodenal ulcer, GI hemorrhage, dry mouth.

Genitourinary

Azotemia, creatinine and BUN elevation, crystalluria, renal failure.

Hematologic

Anemia, agranulocytosis, aplastic anemia, eosinophilia, leukopenia, pancytopenia, thrombocytopenia.

Hepatic

Hepatic function impairment, jaundice, ulcerative colitis, increased bilirubin, elevated hepatic enzymes, acute hepatic injury.

Metabolic

Hypoglycemia, hypokalemia.

Respiratory

Respiratory arrest, chest pain, dyspnea.

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Hepatic Function

Adjust dose according to blood levels and monitor hepatic function.

Bone marrow depression

Use with extreme caution in patients with bone marrow depression or those at risk (eg, hematologic disease, radiation treatment, other bone marrow suppressant drugs).

Overdosage

Symptoms

Nausea, vomiting, diarrhea, CNS changes, leukopenia, thrombocytopenia, hepatitis.

Patient Information

• Advise patient to read patient information leaflet before starting therapy and with each refill.
• Review dosing schedule and prescribed length of therapy with patient. Advise patient that treatment may be prolonged (eg, several weeks or months) and to continue medication until advised to stop using by health care provider.
• Advise patient that medication may cause nausea and/or vomiting. Inform patient that these adverse reactions may be prevented or reduced in severity by taking flucytosine capsules a few at a time over a 15-min period.
• Advise patient that if a dose is missed to take as soon as remembered. However, if it is nearing the time for the next dose, to skip the dose and take the next dose at regularly scheduled time. Caution patient never to double the dose to catch up.
• Remind patient to complete entire course of therapy, even if symptoms of infection have disappeared.
• Advise patient to inform health care provider if infection does not appear to be improving or is getting worse.
• Advise patient to contact health care provider immediately if any of the following occur: fever, sore throat, or other signs of infection; bleeding or unusual bruising; skin rash; persistent nausea or vomiting; dark urine; yellowing of skin or eyes; changes in thinking; abnormal muscle movements or skin sensations.
• Caution patient that drug may cause drowsiness or dizziness and to use caution while driving or performing other tasks requiring mental alertness or coordination until tolerance is determined.
• Advise patient that medication may cause photosensitivity (sensitivity to sunlight) and to avoid unnecessary exposure to sunlight or tanning lamps and to use sunscreens and wear protective clothing until tolerance is determined.

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