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 adjunctive therapy for systemic fungal infections (eg, septicemia, endocarditis, UTI, meningitis, or pulmonary) caused by susceptible strains of Candida or Cryptococcus

Flucytosine (Ancobon) dose in adults:

Usual dosage ranges:

• 50 to 150 mg/kg/day per oral in divided doses every 6 hours.

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

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

  • 25 mg/kg/dose per oral 4 times daily (with amphotericin B [liposomal]) until step-down therapy is clinically appropriate.

• Symptomatic Cystitis:

  • Fluconazole-resistant C. glabrata: 25 mg/kg/dose 4 per oral times daily for 7 to 10 days as single agent.

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

  • 25 mg/kg/dose per oral 4 times daily (with an amphotericin B lipid formulation).
  • Treatment should be continued for at least 6 weeks following valve replacement surgery (longer durations in patients with abscesses or other complications) for native or prosthetic valve endocarditis.
  • Treatment should be continued for 4 to 6 weeks post-surgery (4 weeks for infections limited to generator pockets and at least 6 weeks for infections involving the wire for patients with implantable cardiac devices.
  • Note: If the patient is clinically stable with fluconazole-susceptible isolates in whom Candida has cleared from the bloodstream, the transition to fluconazole can be done.

• Endophthalmitis (with or without vitritis):

  • Fluconazole- or voriconazole-resistant isolates: 25 mg/kg/dose per oral 4 times daily (with amphotericin B [liposomal]) for at least 4 to 6 weeks until examination indicates the resolution.
  • Intravitreal injection with voriconazole or amphotericin B deoxycholate should be given to patients with vitritis or with macular involvement (with or without vitritis).

• Symptomatic Pyelonephritis:

  • Fluconazole-resistant C. glabrata: 25 mg/kg/dose per oral 4 times daily in combination with amphotericin B deoxycholate for 1 to 7 days or as monotherapy for 14 days.

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

• Non-HIV-infected, non-transplant:

  • Induction: 25 mg/kg/dose (with amphotericin B) per oral every 6 hours for at least 4 weeks.
  • Both amphotericin and flucytosine can be stopped and an extended course of fluconazole can be given in case of clinical improvement.

• HIV-infected or solid organ transplant recipients:

  • Induction: 25 mg/kg/dose (with amphotericin B) per oral every 6 hours for at least 2 weeks.
  • Both amphotericin and flucytosine should be stopped and an extended course of fluconazole should be given in case of improvement.

• Cerebral cryptococcomas:

  • Induction: 25 mg/kg/dose (with amphotericin B and corticosteroids) per oral every 6 hours for at least 6 weeks, followed with an extended course of fluconazole.

Flucytosine (Ancobon) dose in children:

Note: Due to the chance of resistance,combination with amphotericin B or another susceptible antifungal should be used.

Flucytosine (Ancobon) General dosing in susceptible infections:

• Infants, Children, and Adolescents:

  • 50 to 150 mg/kg/day per oral in divided doses every 6 hours.

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

• Children and Adolescents:

  • 37.5 mg/kg/dose per oral every 6 hours in combination with amphotericin B.

Candidiasis:

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

• Infants, Children, and Adolescents:

  • 25 mg/kg/dose per oral every 6 hours in combination with amphotericin B.

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

• Infants, Children, and Adolescents:

  • 25 mg/kg/dose per oral every 6 hours in combination with amphotericin B.

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

• Infants:

  • 25 mg/kg/dose per oral every 6 hours in combination with amphotericin B;
  • Valve replacement or removal of hardware is strongly recommended.

• Children and Adolescents:

  • 25 to 37.5 mg/kg/dose per oral every 6 hours in combination with amphotericin B; valve replacement or removal of hardware is strongly recommended.

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

• Infants, Children, and Adolescents:

  • Symptomatic Cystitis:

    • 25 mg/kg/dose per oral every 6 hours for 7 to 10 days.

  • Pyelonephritis:

    • 25 mg/kg/dose per oral every 6 hours for 2 weeks with or without amphotericin B.
  • A combination with amphotericin B should be given and treatment duration should be until symptom resolution and clear urine culture in case of fungal balls.

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

• Infants, Children, and Adolescents:

  • 25 mg/kg/dose per oral every 6 hours in combination with amphotericin B or fluconazole;
  • minimum treatment duration: ≥2 weeks.
  • Duration of treatment depends on HIV status, source of infection, and concomitant 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
• serum flucytosine concentrations (2 hours after administration of a dose) after 3 days of treatment and as clinically indicated (eg, following dosage adjustment, change in renal function, bone marrow toxicity).

How to administer Flucytosine (Ancobon)?

• To promote less variation in peak and trough serum levels, it should be given in divided doses.
• A few capsules should be given at a time over 15 minutes until full dose is taken to prevent nausea and vomiting.

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.