flucytosine


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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.

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.

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

/flu·cy·to·sine/ (floo-si´to-sēn″) an antifungal used in the treatment of severe candidal and cryptococcal infections.

flucytosine

[flo̅o̅sī′təsēn]
an antifungal.
indications It is prescribed as an adjunct in the treatment of certain serious fungal infections, usually Candida or Cryptococcus.
contraindications Known hypersensitivity to this drug prohibits its use. Close monitoring is required when administering it to patients with renal disorders, bone marrow depression, or AIDS.
adverse effects Among the more serious adverse effects are GI disturbances, including enterocolitis, abnormal liver function, hepatomegaly, and bone marrow depression. Also causes hallucinations, confusion and other CNS effects, respiratory depression, peripheral neuropathy, and hearing loss.

flucytosine

5-FC, Ancobon Infectious disease An anti-fungal given with amphotericin B to ↓ emergence of resistant strains Adverse effects Liver damage. See AIDS.

flucytosine

A drug used to treat fungus infections within the body. It can be taken by mouth and is effective against CRYPTOCOCCOSIS, chromomycosis and thrush (CANDIDIASIS). Side effects are minor.

antifungal agent 

Any substance which destroys or prevents the growth of fungi. It is one of the antibiotic groups. There are several classes of antifungal drugs: Polyenes, which cause an increase in fungal cell wall permeability leading to its death. Examples: amphotericin B, natamycin, nystatin. Azoles, which act either by inhibiting the synthesis of ergosterol, a component of fungal cell wall or by causing direct wall damage. Examples: clotrimazole, econazole, fluconazole, itraconazole, ketoconazole, miconazole. Pyrimidines, which interfere with the normal function of fungal cells. Example: flucytosine. Syn antimycotic agent.

flucytosine

(floosī´təsēn´),
n brand name: Ancobon;
drug class: antifungal;
action: converted to fluorouracil after entering fungi, which inhibits DNA and RNA synthesis;
uses: Candida infections.
References in periodicals archive ?
Access to flucytosine is limited because this agent is not registered in SA and only available on a compassionate basis.
Comparison of the early fungicidal activity of high-dose fluconazole, voriconazole, and flucytosine as second-line drugs given in combination with amphotericin B for the treatment of HIV-associated cryptococcal meningitis.
In North America, caspofungin, flucytosine, and voriconazole all inhibited >90% of C.
As reviewed by Neofytos et al, the available data for Rhodotorula infections suggests that the combination of device removal and amphotericin B is the most conservative therapeutic approach, with the possible addition of flucytosine (5FC) to amphotericin B for severe or refractory disease.
In some cases, it makes sense to add flucytosine, 100 mg/kg per day, and then fluconazole, 400 mg per day for 10 weeks.
2) Without treatment, a fatal outcome from cryptococcal meningitis is imminent; amphotericin B is the drug of choice for cryptococcal meningitis, and combination therapy with flucytosine has cured patients and reduced relapses.
Treatment of HIV-associated cryptococcal meningitis is with intravenous amphotericin B for 2 weeks with or without flucytosine, followed by oral fluconazole for 8 to 10 weeks.
After Toca 511 spreads through the tumor, the CD gene in the cancer cells converts the prodrug, flucytosine, into the anti-cancer drug 5-fluorouracil (5-FU).
To the Editor: The addition of oral flucytosine to an amphotericin B-containing induction regimen for HIV-associated cryptococcal meningitis (CM) is associated with improved fungal clearance and a 39% reduction in 10-week mortality.
Chemiluminescence - High Pressure Liquid Chromatography (HPLC) - Gas Chromatography/Mass Spectrometry - Liquid Chromatography/Mass Spectrometry - Flucytosine - Triazoles - Itraconazole - Voriconazole - Posaconazole - Enzyme Immunoassays - Enzyme Multiplied Immunoassay Technique - Cloned Enzyme Donor Immunoassays - Radio Immunoassays - Fluorescence Polarization Immunoassays - Lateral Flow Immunoassays - Particle Enhanced Turbidimetric Inhibition Immunoassays - Affinity Chrome Mediated Immunoassays
In the absence of flucytosine, the expert panel advocates that Southern African patients should be treated with the following induction therapy for the first two weeks: amphotericin B deoxycholate (1 mg/kg/day intravenous (IV) administration) plus fluconazole (800 mg per os (PO) daily).
5) Boric acid was compared with nystatin, terconazole, flucytosine, itraconazole, clotrimazole, ketoconazole, fluconazole, buconazole, and miconazole.