Ancobon

flucytosine

Ancobon, Ancotil (UK)

Pharmacologic class: Fluorinated pyrimidine analog

Therapeutic class: Antifungal

Pregnancy risk category C

Action

Unclear. Thought to interfere with protein synthesis in cells of susceptible fungi after conversion to fluorouracil.

Availability

Capsules: 250 mg, 500 mg

Indications and dosages

➣ Severe fungal infections caused by susceptible strains of Candida species (including septicemia, endocarditis, urinary tract infections [UTIs]), and pulmonary infections) and Cryptococcus species (including meningitis, pulmonary infections, and UTIs)

Adults: 50 to 150 mg/kg P.O. daily in four equally divided doses q 6 hours

Dosage adjustment

• Renal impairment (glomerular filtration rate below 50 ml/minute)

Off-label uses

• Chromomycosis

Contraindications

• Hypersensitivity to drug or other antifungals

Precautions

Use cautiously in:

• renal impairment, underlying hepatic disease, bone marrow depression

• pregnant or breastfeeding patients

• children (safety not established).

Administration

• Give capsules a few at a time over 15 minutes to minimize nausea and vomiting.

• Know that drug is rarely used alone. Expect to give another antifungal or amphotericin B concurrently.

Adverse reactions

CNS: headache, dizziness, confusion, hallucinations, vertigo, psychosis, ataxia, paresthesia, parkinsonism, peripheral neuropathy

CV: chest pain, cardiac arrest

EENT: hearing loss

GI: nausea, vomiting, diarrhea, dyspepsia, ulcerative colitis, abdominal discomfort, anorexia, duodenal ulcer, hemorrhage

GU: azotemia, crystalluria, renal failure

Hematologic: eosinophilia, anemia, leukopenia, aplastic anemia, thrombocytopenia, bone marrow depression, agranulocytosis

Hepatic: jaundice

Metabolic: hypokalemia, hypoglycemia

Respiratory: dyspnea, respiratory arrest

Skin: rash, pruritus, urticaria, photosensitivity

Interactions

Drug-drug. Amphotericin B: synergistic effects, increased risk of toxicity

Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, bilirubin, gamma-glutamyltransferase: increased levels

Glucose, granulocytes, hemoglobin, platelets, potassium, white blood cells: decreased levels

Patient monitoring

• Monitor kidney and liver function test results.

• Carefully monitor blood glucose level and hematologic test results.

See Assess for serious cardiovascular, renal, respiratory, and hematologic adverse reactions.

• Evaluate electrolyte levels, particularly potassium.

• Assess for signs and symptoms of bleeding.

Patient teaching

• Advise patient to take capsules over 15-minute period to reduce GI upset.

See Instruct patient to immediately report unusual bleeding or bruising.

• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.

• Instruct patient to minimize GI upset by eating frequent, small servings of food and drinking adequate fluids.

• Advise female patient to inform prescriber if she is pregnant or breastfeeding.

• Tell patient he'll undergo regular blood testing during therapy.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

flucytosine

(floo-sye-toe-seen) flucytosine,

Ancobon

(trade name)

Classification

Therapeutic: antifungals
Pregnancy Category: C

Indications

Treatment of serious fungal infections including:

Endocarditis,

Meningitis,

Septicemia,

Urinary tract infections,

Pulmonary infections.

Action

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.Active against only a small number of fungi, mainly:

Candida,

Cryptococcus.

Pharmacokinetics

Absorption: Well absorbed (80–90%) from the GI tract following oral administration.Distribution: Widely distributed. Crosses the blood-brain barrier.Metabolism and Excretion: 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

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Obstetric / Lactation: Pregnancy or lactation.Use Cautiously in: Bone marrow depression (especially following radiation therapy or antineoplastics).Exercise Extreme Caution in: Renal impairment (blood level monitoring, ↓ dose, and ↑ dosage interval recommended if CCr <40 mL/min).

Adverse Reactions/Side Effects

Central nervous system

seizures (life-threatening)
ataxia
confusion
dizziness
drowsiness
fatigue
headache

Cardiovascular

chest pain

Ear, Eye, Nose, Throat

hearing loss

Gastrointestinal

diarrhea (most frequent)
nausea (most frequent)
vomiting (most frequent)
abdominal pain
dry mouth

Dermatologic

photosensitivity
pruritis
rash
urticaria

Endocrinologic

hypoglycemia

Fluid and Electrolyte

hypokalemia

Genitourinary

azotemia

Hematologic

aplastic anemia (life-threatening)
eosinophilia
leukopenia (most frequent)
pancytopenia (most frequent)
anemia
thrombocytopenia

Neurologic

peripheral neuropathy

Respiratory

dyspnea

Miscellaneous

fever

Interactions

Drug-Drug interaction

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

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

Renal Impairment

Oral (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

Nursing implications

Nursing assessment

Assess patient for signs and symptoms of systemic fungal infection prior to and periodically throughout 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.

Potential Nursing Diagnoses

Risk for infection (Indications)
Risk for deficient fluid volume (Adverse Reactions)
Deficient knowledge, related to medication regimen (Patient/Family Teaching)

Implementation

The number 5 in 5-FC is part of the drug name and not the dose.
Oral: 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.
Instruct patient to notify health care professional immediately if planning to become pregnant.

Evaluation/Desired Outcomes

Resolution of the signs and symptoms of fungal infection. Duration of therapy is generally 4–6 wk but may continue for several months.