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Flucytosine: Drug information

Flucytosine: Drug information
2025© UpToDate, Inc. and its affiliates and/or licensors. All Rights Reserved.
For additional information see "Flucytosine: Patient drug information" and "Flucytosine: Pediatric drug information"

For abbreviations, symbols, and age group definitions show table
ALERT: US Boxed Warning
Monitoring:

Use with extreme caution in patients with renal impairment. Close monitoring of hematologic, renal, and hepatic status of all patients is essential.

Brand Names: US
  • Ancobon
Pharmacologic Category
  • Antifungal Agent, Oral
Dosing: Adult

Usual dosage range: Oral: 50 to 150 mg/kg/day in divided doses every 6 hours.

Candidiasis

Candidiasis:

Cardiac infection, native or prosthetic valve endocarditis, or device infection (eg, implantable cardiac defibrillator, pacemaker, ventricular assist device): Oral: 25 mg/kg/dose 4 times daily (in combination with an amphotericin B lipid formulation). For device infection without endocarditis, duration is 4 weeks after device removal for generator pocket infections and ≥6 weeks after device removal for wire infections. For endocarditis, duration is ≥6 weeks after valve replacement surgery, with longer durations for perivalvular abscesses or other complications. Note: May transition to step-down therapy with fluconazole in patients with fluconazole-susceptible isolates who are clinically stable with negative repeat blood cultures (Ref).

Central nervous system (eg, meningitis): Oral: 25 mg/kg/dose 4 times daily (in combination with amphotericin B [liposomal]) until step-down therapy is clinically appropriate (Ref).

Endophthalmitis (with or without vitritis): Fluconazole- or voriconazole-resistant isolates: Oral: 25 mg/kg/dose 4 times daily (in combination with amphotericin B [liposomal]) for ≥4 to 6 weeks until examination indicates resolution; for patients with vitritis or with macular involvement, intravitreal antifungal therapy is also recommended (Ref).

Urinary tract infection:

Cystitis, symptomatic: Oral: Fluconazole-resistant C. glabrata: 25 mg/kg/dose 4 times daily for 7 to 10 days as monotherapy (Ref).

Pyelonephritis: Fluconazole-resistant C. glabrata: Oral: 25 mg/kg/dose 4 times daily in combination with amphotericin B deoxycholate for 1 to 7 days or as monotherapy for 14 days (Ref).

Vulvovaginal, caused by C. glabrata (alternative agent) (off-label use): Intravaginal: 16% extemporaneously compounded cream: 1 applicatorful (~5 g) once daily (at bedtime) for 14 days (Ref). Note: Reserve for patients with no other clear cause of symptoms (Ref). May also be used in combination with intravaginal amphotericin B (Ref).

Cryptococcal meningitis, disseminated disease, or severe pulmonary infection

Cryptococcal meningitis, disseminated disease, or severe pulmonary infection:

Oral: Induction: 25 mg/kg/dose 4 times daily, as part of an appropriate combination regimen. Duration of induction therapy is ≥2 weeks, but should be extended in patients with evidence of neurological complications; for cerebral cryptococcomas, recommended duration is ≥6 weeks. Induction therapy is followed by consolidation and maintenance therapy with fluconazole (Ref).

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function (Ref):

The following adjustments are based on a usual dose of 25 mg/kg/dose every 6 hours: Oral:

CrCl >40 mL/minute: No dosage adjustment necessary.

CrCl 21 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.

Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Note: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal SCr concentrations. Younger patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).

Note: No data are available on flucytosine clearance in ARC, although it is likely clearance is increased. Oral: Initiate therapy at usual recommended doses; use clinical response and therapeutic drug monitoring if available to guide further dose adjustments (Ref).

Hemodialysis, intermittent (thrice weekly): Dialyzable (66% to 75%) (Ref):

Oral: Initial: 25 to 50 mg/kg/dose 3 times per week, administered after dialysis on dialysis days (Ref). Use clinical response and therapeutic drug monitoring if available to guide further dose adjustments (Ref).

Peritoneal dialysis: Limited data available.

Oral: Initial: Dose 25 mg/kg/dose every 48 hours. Use clinical response and therapeutic drug monitoring if available to guide further dose adjustments (Ref). Note: For severe infection (eg, cryptococcal meningitis), one case report describes tolerated and effective use of 25 mg/kg every 24 hours (Ref).

CRRT: Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) and minimal residual kidney function unless otherwise noted. Close monitoring of response and adverse reactions (eg, leukopenia, thrombocytopenia) due to drug accumulation is important.

Oral: Initial: 25 mg/kg every 12 to 24 hours (Ref). Use clinical response and therapeutic drug monitoring if available to guide further dose adjustments (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Close monitoring of response and adverse reactions (eg, leukopenia, thrombocytopenia) due to drug accumulation is important. Note: No clinical or pharmacokinetic data available.

Oral: Initial: 25 mg/kg every 12 to 24 hours, with one of the doses administered after PIRRT (Ref). Use clinical response and therapeutic drug monitoring if available to guide further dose adjustments (Ref).

Dosing: Liver Impairment: Adult

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

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Flucytosine: Pediatric drug information")

Note: Administer as part of an appropriate combination regimen to avoid development of flucytosine resistance. Doses provided are initial and should be adjusted based on therapeutic drug monitoring.

General dosing: Infants, Children, and Adolescents: Oral: 25 mg/kg/dose every 6 hours as part of an appropriate combination regimen (Ref).

Aspergillosis, endocarditis

Aspergillosis, endocarditis: Limited data available: Note: Flucytosine is not included in IDSA guidelines for management of aspergillosis (Ref).

Children and Adolescents: Oral: 37.5 mg/kg/dose every 6 hours in combination with amphotericin B (Ref).

Candidiasis

Candidiasis:

Chorioretinitis: Infants, Children, and Adolescents: Oral: 25 mg/kg/dose every 6 hours in combination with amphotericin B (Ref).

CNS disease, treatment: Infants, Children, and Adolescents: Oral: 25 mg/kg/dose every 6 hours in combination with amphotericin B (Ref).

Endocarditis or implanted cardiovascular device:

Infants: Oral: 25 mg/kg/dose every 6 hours in combination with amphotericin B; valve replacement or removal of hardware is strongly recommended (Ref).

Children and Adolescents: Oral: 25 to 37.5 mg/kg/dose every 6 hours in combination with amphotericin B; valve replacement or removal of hardware is strongly recommended (Ref).

Urinary tract infection: Infants, Children, and Adolescents:

Cystitis, symptomatic: Oral: 25 mg/kg/dose every 6 hours for 7 to 10 days (Ref).

Pyelonephritis: Oral: 25 mg/kg/dose every 6 hours for 2 weeks with or without amphotericin B (Ref); if fungal balls present, use in combination with amphotericin B and treatment duration should be until symptom resolution and clear urine culture.

Cryptococcal disease; disseminated; treatment

Cryptococcal disease; disseminated (including CNS disease); treatment (independent of HIV status):

Infants, Children, and Adolescents: Oral: 25 mg/kg/dose every 6 hours as part of an appropriate combination regimen. Duration of induction therapy is ≥2 weeks and is dependent upon multiple factors including immune or HIV status, source of infection and concomitant antifungal therapy; induction therapy should be followed by consolidation and maintenance therapy with fluconazole (Ref).

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; however, the following guidance has been used by some clinicians:

Infants, Children, and Adolescents without HIV infection:

Note: Dosing adjustment based on a usual initial dose of 25 to 37.5 mg/kg/dose every 6 hours (Ref). Doses should be adjusted based on therapeutic drug monitoring.

GFR >50 mL/minute/1.73 m2: No adjustment recommended.

GFR 30 to 50 mL/minute/1.73 m2: Oral: 25 to 37.5 mg/kg/dose every 8 hours.

GFR 10 to 29 mL/minute/1.73 m2: Oral: 25 to 37.5 mg/kg/dose every 12 hours.

GFR <10 mL/minute/1.73 m2: Oral: 25 to 37.5 mg/kg/dose every 24 hours.

Hemodialysis or peritoneal dialysis: Oral: 25 to 37.5 mg/kg/dose every 24 hours.

Adolescents with HIV:

Note: Dosing adjustment based on a usual dose of 25 mg/kg/dose every 6 hours (Ref); doses should be adjusted based on therapeutic drug monitoring.

CrCl >40 mL/minute: No adjustment recommended.

CrCl >20 to 40 mL/minute: Oral: 25 mg/kg/dose every 12 hours.

CrCl 10 to 20 mL/minute: Oral: 25 mg/kg/dose every 24 hours.

CrCl <10 mL/minute: Oral: 25 mg/kg/dose every 48 hours.

Hemodialysis: Oral: 25 to 50 mg/kg every 48 to 72 hours; administer dose after hemodialysis.

Dosing: Liver Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; however, flucytosine has minimal hepatic metabolism; use caution.

Adverse Reactions

The following adverse drug reactions are derived from product labeling unless otherwise specified. Frequency not defined.

Frequency not defined:

Cardiovascular: Cardiotoxicity, chest pain, ventricular dysfunction

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 necrosis, increased liver enzymes, increased serum bilirubin, jaundice

Hypersensitivity: Hypersensitivity reaction

Nervous system: Asthenia, ataxia, confusion, fatigue, hallucination, headache, paresthesia, parkinsonism, peripheral neuropathy, psychosis, sedated state, seizure, vertigo

Otic: Hearing loss

Renal: Increased blood urea nitrogen, increased serum creatinine, kidney failure

Respiratory: Dyspnea

Miscellaneous: Fever

Postmarketing: Gastrointestinal: Colitis (Sohail 2014)

Contraindications

Hypersensitivity to flucytosine or any component of the formulation; known complete dihydropyrimidine dehydrogenase enzyme deficiency.

Warnings/Precautions

Disease-related concerns:

• Hematologic disease: Use with caution in patients with bone marrow depression, hematologic disease, or those who have been treated with radiation or drugs that suppress the bone marrow; bone marrow toxicity may be dose related and irreversible.

• Hepatic impairment: Use with caution in patients with hepatic impairment; hepatotoxicity that appears to be dose related may occur.

• Renal impairment: Dosage adjustment recommended in patients with renal impairment.

Special populations:

• Dihydropyrimidine dehydrogenase enzyme deficiency: Severe toxicity, including diarrhea, mucositis, neurotoxicity, and neutropenia, may be increased in patients with dihydropyrimidine dehydrogenase enzyme deficiency; consider determination of dihydropyrimidine dehydrogenase enzyme deficiency in patients who develop drug toxicity.

Other warnings/precautions:

• Monotherapy: Generally should not be used as monotherapy, as resistance can rapidly develop.

Warnings: Additional Pediatric Considerations

Serum flucytosine concentrations are highly variable in neonates and tend to be higher in children <12 years of age; monitor closely (Baley 1990; Pasqualotto 2007; Soltani 2006).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Ancobon: 250 mg, 500 mg

Generic: 250 mg, 500 mg

Generic Equivalent Available: US

Yes

Pricing: US

Capsules (Ancobon Oral)

250 mg (per each): $92.21

500 mg (per each): $178.43

Capsules (Flucytosine Oral)

250 mg (per each): $37.50 - $100.40

500 mg (per each): $70.83 - $158.91

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Administration: Adult

Oral: To reduce or avoid nausea and vomiting, administer a few capsules at a time over 15 minutes until full dose is taken.

Vaginal (off-label route): Gently insert full applicator of cream and press plunger to release the medication (Ref).

Administration: Pediatric

Oral: To reduce or avoid nausea and vomiting, administer a few capsules at a time over 15 minutes until full dose is taken.

Use: Labeled Indications

Candida/Cryptococcus infections: Treatment of systemic fungal infections (eg, bloodstream infection, endocarditis, urinary tract infection, meningitis, pulmonary) caused by susceptible strains of Candida or Cryptococcus, in combination with other antifungal agents.

Use: Off-Label: Adult

Candidiasis, vulvovaginal, caused by Candida glabrata

Medication Safety Issues
Sound-alike/look-alike issues:

Flucytosine may be confused with fludarabine, fluorouracil

Ancobon may be confused with Oncovin

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor

Amphotericin B: May increase adverse/toxic effects of Flucytosine. Amphotericin B may increase serum concentration of Flucytosine. Risk C: Monitor

Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor

BCG (Intravesical): Myelosuppressive Agents may decrease therapeutic effects of BCG (Intravesical). Myelosuppressive Agents may increase adverse/toxic effects of BCG (Intravesical). Risk X: Avoid

Brivudine: May increase adverse/toxic effects of Flucytosine. Risk X: Avoid

Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor

Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid

Cladribine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk X: Avoid

CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor

Cytarabine (Conventional): May decrease therapeutic effects of Flucytosine. Risk C: Monitor

Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification

Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid

Gimeracil: May increase active metabolite exposure of Flucytosine. Specifically, gimeracil may increase concentrations of fluorouracil. Risk X: Avoid

Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor

Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor

Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor

Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification

Saccharomyces boulardii: Antifungal Agents (Systemic and Oral [Non-Absorbable]) may decrease therapeutic effects of Saccharomyces boulardii. Risk X: Avoid

Food Interactions

Food decreases the rate, but not the extent of absorption.

Pregnancy Considerations

Adverse events have been observed in some animal reproduction studies. Flucytosine is metabolized to fluorouracil which may cause adverse events if administered during pregnancy; refer to the Fluorouracil (Systemic) monograph for additional information.

Breastfeeding Considerations

It is not known if flucytosine is present in breast milk. Due to the potential for serious adverse reactions in the breastfeeding infant, a decision should be made whether to discontinue breastfeeding or the drug, taking into account the importance of treatment to the mother.

Monitoring Parameters

Pretreatment: Electrolytes (especially potassium), CBC with differential, BUN, renal function.

During treatment: CBC with differential and LFTs (eg, alkaline phosphatase, AST/ALT) frequently; renal function; serum flucytosine concentrations (2 hours after administration of a dose) after 3 to 5 doses and as clinically indicated (eg, following dosage adjustment, change in renal function, bone marrow toxicity) (BSMM [Ashbee 2014]; HHS [OI adult 2022]); if serum flucytosine concentrations cannot be monitored, monitor CBC at least twice weekly (HHS [OI adult 2022]).

Reference Range

Target serum concentration: 30 to 80 mcg/mL (2 hours post dose); obtain level after 3 to 5 doses. Serum concentrations should not exceed 100 mcg/mL to avoid bone marrow toxicity and hepatotoxicity (AST-IDCOP [Baddley 2019]; HHS [OI adult] 2022; IDSA [Perfect 2010]). Repeat serum concentrations should be obtained following dosage adjustment, change in renal function, or if bone marrow toxicity occurs (BSMM [Ashbee 2014]).

In some areas, trough monitoring may be utilized; target troughs of 25 to 50 mcg/mL or >20 to 40 mcg/mL have been suggested to minimize resistance development (BSMM [Ashbee 2014]; Gómez-López 2020; Vermes 2000).

Mechanism of Action

Penetrates fungal cells and is converted to fluorouracil; after further bioconversion, it competes with uridylic acid, interfering with fungal RNA and protein synthesis, and inhibits thymidylate synthetase, inhibiting fungal DNA synthesis (Vermes 2000).

Pharmacokinetics (Adult Data Unless Noted)

Absorption: Rapid.

Distribution: Into CSF, aqueous humor, joints, peritoneal fluid; Vd: 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 (Baley 1990).

Infants: 7.4 hours.

Adults: 2 to 5 hours.

Anuria: 85 hours (range: 30 to 250).

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).

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: Prolonged half-life (29.9 to 250 hours in anuric or nephrectomized patients).

Pediatric: Serum flucytosine concentrations are highly variable in neonates and tend to be higher in children <12 years of age; monitor closely (Baley 1990; Pasqualotto 2007; Soltani 2006).

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AR) Argentina: Ancotil;
  • (AT) Austria: Ancotil;
  • (AU) Australia: Ancobon | Ancotil;
  • (CH) Switzerland: Ancotil;
  • (CO) Colombia: Ancobon;
  • (CZ) Czech Republic: Ancotil;
  • (FI) Finland: Ancotil;
  • (FR) France: Ancotil;
  • (GB) United Kingdom: Alcobon;
  • (GR) Greece: Ancotil;
  • (HK) Hong Kong: Ancotil;
  • (HU) Hungary: Ancotil;
  • (IT) Italy: Ancotil;
  • (LT) Lithuania: Ancotil;
  • (LV) Latvia: Ancotil;
  • (MA) Morocco: Ancotil;
  • (NL) Netherlands: Ancotil;
  • (NZ) New Zealand: Alcobon | Ancobon;
  • (PL) Poland: Ancotil | Ancotil Roche;
  • (PR) Puerto Rico: Ancobon;
  • (PT) Portugal: Ancobon;
  • (SE) Sweden: Ancotil;
  • (SG) Singapore: Ancotil;
  • (SI) Slovenia: Ancotil;
  • (SK) Slovakia: Ancotil;
  • (SR) Suriname: Ancotil
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