Flucytosine (Ancobon) is a synthetic antifungal medicine that is used to treat serious infections caused by candida and cryptococcus.

Indications of Flucytosine:

• Candida/Cryptococcus infections:

  • It is used as an adjuvant treatment for systemic fungal infections brought on by susceptible strains of Candida or Cryptococcus, such as septicemia, endocarditis, UTI, meningitis, or pulmonary infections.

Flucytosine (Ancobon) dose in adults:

Usual dosage ranges:

• Every six hours in divided dosages, 50 to 150 mg/kg/day.

Flucytosine (Ancobon) dose in candidiasis (off-label dose):

• Candidiasis of the central nervous system (eg, meningitis):

  • Up until step-down therapy is clinically acceptable, provide 25 mg/kg/dose orally four times per day (with amphotericin B [liposomal]).

• Symptomatic Cystitis:

  • Fluconazole-resistant C. glabrata: Dosage of 25 mg/kg 4 oral times per day, as a single dose, for 7 to 10 days.

• Endocarditis (native or prosthetic valve) or infected implantable cardiac devices (eg, pacemaker, ICD, VAD):

  • 25 mg/kg/dose orally, four times per day (with an amphotericin B lipid formulation).
  • In order to treat native or prosthetic valve endocarditis, treatment should be continued for at least 6 weeks after valve replacement surgery (for longer periods in patients with abscesses or other problems).
  • Infections confined to generator pockets should be treated for 4 to 6 weeks after surgery, and infections involving the wire should be treated for at least 6 weeks in patients with implantable cardiac devices.
  • Note: The switch to fluconazole can be made if the patient has fluconazole-susceptible isolates and Candida has been eliminated from the bloodstream.

• Endophthalmitis (with or without vitritis):

  • Isolates that are resistant to fluconazole or voriconazole should be treated with amphotericin B (liposomal) at a dose of 25 mg/kg four times per day for at least four to six weeks, or until an examination reveals resolution.
  • In individuals with vitritis or macular involvement, voriconazole or amphotericin B deoxycholate should be administered intravitreally (with or without vitritis).

• Symptomatic Pyelonephritis:

  • Fluconazole-resistant C. glabrata: For 1 to 7 days, 25 mg/kg/dose orally four times per day in conjunction with amphotericin B deoxycholate, or for 14 days as monotherapy.

Flucytosine (Ancobon) dose in the treatment of Cryptococcal meningitis: 

• Non-HIV-infected, non-transplant:

  • Induction: For at least 4 weeks, provide 25 mg/kg/dose (with amphotericin B) orally every 6 hours.
  • If there is a clinical improvement, flucytosine and amphotericin can be withdrawn, and an extended term of fluconazole can be administered.

• HIV-infected or solid organ transplant recipients:

  • Induction:For at least two weeks, provide 25 mg/kg/dose (with amphotericin B) orally every six hours.
  • Flucytosine and amphotericin should be terminated, and in the event that things get better, an extended course of fluconazole should be administered.

• Cerebral cryptococcomas:

  • Induction: Fluconazole is administered after a prolonged course of amphotericin B at a dosage of 25 mg/kg/dose (with amphotericin B and corticosteroids) via mouth every 6 hours for at least 6 weeks.

Flucytosine (Ancobon) dose in children:

Note: Combinations with amphotericin B or another susceptible antifungal should be used due to the possibility of resistance.

Flucytosine (Ancobon) General dosing in susceptible infections:

• Infants, Children, and Adolescents:

  • Every six hours in divided dosages, 50 to 150 mg/kg/day.

Flucytosine (Ancobon) Dose in the treatment of Aspergillosis and endocarditis: Limited data available:

• Children and Adolescents:

  • Combining amphotericin B and an oral dose of 37.5 mg/kg every 6 hours.

Candidiasis:

Flucytosine (Ancobon) Dose in the treatment of Chorioretinitis caused by candida:

• Infants, Children, and Adolescents:

  • Combining amphotericin B with an oral dose of 25 mg/kg every six hours.

Flucytosine (Ancobon) dose in the treatment of CNS disease caused by candida:

• Infants, Children, and Adolescents:

  • Combining amphotericin B with an oral dose of 25 mg/kg every six hours.

Flucytosine (Ancobon) dose in the candidal endocarditis or implanted cardiovascular device:

• Infants:

  • Combining 25 mg/kg/dose oral every six hours with amphotericin B and replacing or removing hardware from the valve is highly advised.

• Children and Adolescents:

  • Combining amphotericin B with a dose of 25 to 37.5 mg/kg orally every six hours is highly advised; valve replacement or hardware removal is also advised.

Flucytosine (Ancobon) dose in the treatment of Urinary tract infections caused by Candida:

• Infants, Children, and Adolescents:

  • Symptomatic Cystitis:

    • For seven to ten days, take 25 mg/kg/dose orally every six hours.

  • Pyelonephritis:

    • Every six hours for two weeks, with or without amphotericin B, at a dose of 25 mg/kg.
  • In the event of fungal balls, a combination of amphotericin B should be used, and treatment should last until symptoms disappear and a clear urine culture.

Flucytosine (Ancobon) dose in the treatment of disseminated Cryptococcal disease including CNS disease (independent of HIV status):

• Infants, Children, and Adolescents:

  • Combining fluconazole or amphotericin B with a dose of 25 mg/kg every six hours, the recommended minimum treatment time is two weeks.
  • The length of treatment varies on the patient's HIV status, the infection's origin, and any concurrent antifungal therapy.

Flucytosine pregnancy Risk Category: N (Not assigned)

• Studies on animal reproduction revealed negative outcomes.
• Flucytosine can cause side effects in pregnancy when it is metabolized into fluorouracil.
• For more information, refer to the Fluorouracil Systemic monograph

Use flucytosine while breastfeeding

• It is unknown if breast milk secretes flucytosine.
• The potential for serious adverse reactions in breastfeeding infants should be considered.
• The decision to discontinue breastfeeding or to take the drug is dependent on the importance to the mother.

Flucytosine (Ancobon) Dose adjustment in kidney disease:

• Dose reduction is neededfor elevated BUN or serum creatinine (or other signs of renal impairment) as per manufacturer, however, no specific dosage adjustments are provided.

• The following adjustments have been recommended (based on a usual dose of 25 mg/kg/dose every 6 hours):

  • CrCl >40 mL/minute:
    • No dosage adjustment necessary.
  • CrCl 20 to 40 mL/minute:
    • 25 mg/kg/dose every 12 hours.
  • CrCl 10 to 20 mL/minute:
    • 25 mg/kg/dose every 24 hours.
  • CrCl <10 mL/minute:
    • 25 mg/kg/dose every 48 hours.
  • ESRD on intermittent hemodialysis (IHD):
    • 25 to 50 mg/kg/dose every 48 to 72 hours.
  • The dose should be given after hemodialysis.

Flucytosine (Ancobon) Dose adjustment in liver disease:

There are no dosage adjustments provided in the manufacturer's labeling; Use with caution.

Side effects of Flucytosine (Ancobon):

• Cardiovascular:

  • Cardiotoxicity
  • Chest Pain
  • Ventricular Dysfunction

• Central Nervous System:

  • Ataxia
  • Confusion
  • Fatigue
  • Hallucination
  • Headache
  • Paresthesia
  • Parkinsonian-Like Syndrome
  • Peripheral Neuropathy
  • Psychosis
  • Sedation
  • Seizure
  • Vertigo

• Dermatologic:

  • Pruritus
  • Skin Photosensitivity
  • Skin Rash
  • Toxic Epidermal Necrolysis
  • Urticaria

• Endocrine & Metabolic:

  • Hypoglycemia
  • Hypokalemia

• Gastrointestinal:

  • Abdominal Pain
  • Anorexia
  • Diarrhea
  • Duodenal Ulcer
  • Enterocolitis
  • Gastrointestinal Hemorrhage
  • Nausea
  • Ulcerative Colitis
  • Vomiting
  • Xerostomia

• Genitourinary:

  • Azotemia
  • Crystalluria

• Hematologic & Oncologic:

  • Agranulocytosis
  • Anemia
  • Aplastic Anemia
  • Bone Marrow Aplasia
  • Eosinophilia
  • Leukopenia
  • Pancytopenia
  • Thrombocytopenia

• Hepatic:

  • Hepatic Injury (Acute)
  • Hepatic Insufficiency
  • Hepatic Necrosis
  • Increased Liver Enzymes
  • Increased Serum Bilirubin
  • Jaundice

• Hypersensitivity:

  • Hypersensitivity Reaction

• Neuromuscular & Skeletal:

  • Weakness

• Otic:

  • Hearing Loss

• Renal:

  • Increased Blood Urea Nitrogen
  • Increased Serum Creatinine
  • Renal Failure

• Respiratory:

  • Dyspnea

• Miscellaneous:

  • Fever

Contraindications to Flucytosine (Ancobon):

Hypersensitivity to flucytosine and any component of the formulation

Warnings and precautions

• Hematologic disease

  • Flucytosine can cause irreversible suppression of bone marrow.
  • This risk is higher if you have a history of bone marrow disease, hematologic diseases, or treatment with radiation.

• Hepatic impairment

  • Flucytosine can cause hepatotoxicity, so patients with hepatic impairment should be cautious.

• Renal impairment: [US-Boxed Warning]

  • Patients with kidney disease should be cautious and adjust their dosages.

Flucytosine: Drug Interaction

Monitoring parameters:

Pretreatment:

• CBC with differential
• RFTs,BUN
• Serum electrolytes (especially potassium)
• Blood culture

During treatment:

• CBC with differential
• LFTs (eg, alkaline phosphatase, AST/ALT)
• RFTs
• Antifungal Agents (Systemic, Oral) may do so (eg, following dosage adjustment, change in renal function, bone marrow toxicity).

How to administer Flucytosine (Ancobon)?

• It ought to be administered in divided doses to encourage reduced fluctuation in peak and trough serum levels.
• To avoid nausea and vomiting, a few capsules should be administered at a time over a period of 15 minutes until the entire dose is consumed.

Mechanism of action of Flucytosine (Ancobon):

Flucytosine is a fungal-cell-permeable drug that converts to fluorouracil. This interferes with fungal protein synthesis and fungal RNA by competing with uracil.

Absorption:

• Serum concentrations in neonates are very variable and rapid. Close monitoring is required. Children aged 12 years had higher serum concentrations.

Distribution:

• Into CSF (aqueous humor), joints, peritoneal fluid; v : 0.6 L/kg

Protein binding:

• 3% to 4%.

Metabolism:

• Minimally hepatic; deaminated both in yeasts and possibly via gut bacteria to 5 fluorouracil.

Bioavailability:

• 78% to 89%; decreased in neonates.

Half-life elimination:

• Neonates: 4 to 34 hours. Infants: 7.4 hours. Adults: 2 to 5 hours. Anuria: 85 hours. End-stage renal disease (ESRD): 75 to 200 hours.

Time to peak, serum:

• 1 to 2 hours. Neonates: 2.5 ± 1.3 hours. Adults: 1 to 2 hours.

Excretion:

• Urine (>90% as unchanged drug).

International Brands of Flucytosine:

• Ancobon
• Alcobon
• Ancotil
• Ancotyl
• Cocol
• Flusine

Flucytosine Brand Names in Pakistan:

No Brands Available in Pakistan.