flucytosine

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.