U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C4H4FN3O
Molecular Weight 129.0926
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FLUCYTOSINE

SMILES

c1c(c(=N)[nH]c(n1)O)F

InChI

InChIKey=XRECTZIEBJDKEO-UHFFFAOYSA-N
InChI=1S/C4H4FN3O/c5-2-1-7-4(9)8-3(2)6/h1H,(H3,6,7,8,9)

HIDE SMILES / InChI

Description
Curator's Comment:: http://www.ncbi.nlm.nih.gov/pubmed/10933638

Flucytosine (5-flucytosine, Ancobon) is an antifungal agent used for treatment of serious fungal infections caused by Candida or Cryptococcus. A fluorinated cytosine analog it was originally developed as an anti-tumor agent, but was found to be non-effective against tumors. Monotherapy with 5-FC is limited because of the frequent development of pathogens resistance. It is often used in in combination with amphotericin B. The severe side effects of 5-flucytosine include hepatotoxicity and bone-marrow depression. 5-fluorocytosine is a prodrug to the cytotoxic compound 5-fluorouracil. Although the exact mode of action is unknown, it has been proposed that flucytosine acts directly on fungal organisms by competitive inhibition of purine and pyrimidine uptake and indirectly by intracellular metabolism to 5-fluorouracil. Flucytosine is taken up by fungal organisms via the enzyme cytosine permease. Inside the fungal cell, flucytosine is rapidly converted to fluorouracil by the enzyme cytosine deaminase. Fluorouracil exerts its antifungal activity through the subsequent conversion into several active metabolites, which inhibit protein synthesis by being falsely incorporated into fungal RNA or interfere with the biosynthesis of fungal DNA through the inhibition of the enzyme thymidylate synthetase.

Originator

Curator's Comment:: Originally synthesized in 1957 by Duschinsky R. and Pleven E. from Hoffmann-LaRoche as an anti-cancer agent # Hoffmann-LaRoche, Inc

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
ANCOBON

Approved Use

INDICATIONS & USAGE Flucytosine Capsules is indicated only in the treatment of serious infections caused by susceptible strains of Candida and/or Cryptococcus. Candida: Septicemia, endocarditis and urinary system infections have been effectively treated with flucytosine. Limited trials in pulmonary infections justify the use of flucytosine. Cryptococcus: Meningitis and pulmonary infections have been treated effectively. Studies in septicemias and urinary tract infections are limited, but good responses have been reported. Flucytosine Capsules should be used in combination with amphotericin B for the treatment of systemic candidiasis and cryptococcosis because of the emergence of resistance to Flucytosine Capsules (see MICROBIOLOGY).

Launch Date

59961600000
Curative
ANCOBON

Approved Use

INDICATIONS & USAGE Flucytosine Capsules is indicated only in the treatment of serious infections caused by susceptible strains of Candida and/or Cryptococcus. Candida: Septicemia, endocarditis and urinary system infections have been effectively treated with flucytosine. Limited trials in pulmonary infections justify the use of flucytosine. Cryptococcus: Meningitis and pulmonary infections have been treated effectively. Studies in septicemias and urinary tract infections are limited, but good responses have been reported. Flucytosine Capsules should be used in combination with amphotericin B for the treatment of systemic candidiasis and cryptococcosis because of the emergence of resistance to Flucytosine Capsules (see MICROBIOLOGY).

Launch Date

59961600000
Curative
ANCOBON

Approved Use

INDICATIONS & USAGE Flucytosine Capsules is indicated only in the treatment of serious infections caused by susceptible strains of Candida and/or Cryptococcus. Candida: Septicemia, endocarditis and urinary system infections have been effectively treated with flucytosine. Limited trials in pulmonary infections justify the use of flucytosine. Cryptococcus: Meningitis and pulmonary infections have been treated effectively. Studies in septicemias and urinary tract infections are limited, but good responses have been reported. Flucytosine Capsules should be used in combination with amphotericin B for the treatment of systemic candidiasis and cryptococcosis because of the emergence of resistance to Flucytosine Capsules (see MICROBIOLOGY).

Launch Date

59961600000
Curative
ANCOBON

Approved Use

INDICATIONS & USAGE Flucytosine Capsules is indicated only in the treatment of serious infections caused by susceptible strains of Candida and/or Cryptococcus. Candida: Septicemia, endocarditis and urinary system infections have been effectively treated with flucytosine. Limited trials in pulmonary infections justify the use of flucytosine. Cryptococcus: Meningitis and pulmonary infections have been treated effectively. Studies in septicemias and urinary tract infections are limited, but good responses have been reported. Flucytosine Capsules should be used in combination with amphotericin B for the treatment of systemic candidiasis and cryptococcosis because of the emergence of resistance to Flucytosine Capsules (see MICROBIOLOGY).

Launch Date

59961600000
Curative
ANCOBON

Approved Use

INDICATIONS & USAGE Flucytosine Capsules is indicated only in the treatment of serious infections caused by susceptible strains of Candida and/or Cryptococcus. Candida: Septicemia, endocarditis and urinary system infections have been effectively treated with flucytosine. Limited trials in pulmonary infections justify the use of flucytosine. Cryptococcus: Meningitis and pulmonary infections have been treated effectively. Studies in septicemias and urinary tract infections are limited, but good responses have been reported. Flucytosine Capsules should be used in combination with amphotericin B for the treatment of systemic candidiasis and cryptococcosis because of the emergence of resistance to Flucytosine Capsules (see MICROBIOLOGY).

Launch Date

59961600000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
57.3 mg/L
1500 mg single, oral
dose: 1500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLUCYTOSINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
506 mg × h/L
1500 mg single, oral
dose: 1500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLUCYTOSINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
8.11 h
1500 mg single, oral
dose: 1500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLUCYTOSINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
96.6%
FLUCYTOSINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
150 mg/kg 1 times / day multiple, oral
Recommended
Dose: 150 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg/kg, 1 times / day
Sources:
unhealthy, 34
Health Status: unhealthy
Age Group: 34
Sex: M
Sources:
Disc. AE: Vomiting, Nausea...
AEs leading to
discontinuation/dose reduction:
Vomiting (9.4%)
Nausea (9.4%)
Diarrhea (6.25%)
Granulocytopenia (6.25%)
Thrombocytopenia (3.1%)
Rash (3.1%)
Sources:
150 mg/kg 4 times / day multiple, oral
Recommended
Dose: 150 mg/kg, 4 times / day
Route: oral
Route: multiple
Dose: 150 mg/kg, 4 times / day
Sources:
unhealthy
AEs

AEs

AESignificanceDosePopulation
Rash 3.1%
Disc. AE
150 mg/kg 1 times / day multiple, oral
Recommended
Dose: 150 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg/kg, 1 times / day
Sources:
unhealthy, 34
Health Status: unhealthy
Age Group: 34
Sex: M
Sources:
Thrombocytopenia 3.1%
Disc. AE
150 mg/kg 1 times / day multiple, oral
Recommended
Dose: 150 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg/kg, 1 times / day
Sources:
unhealthy, 34
Health Status: unhealthy
Age Group: 34
Sex: M
Sources:
Diarrhea 6.25%
Disc. AE
150 mg/kg 1 times / day multiple, oral
Recommended
Dose: 150 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg/kg, 1 times / day
Sources:
unhealthy, 34
Health Status: unhealthy
Age Group: 34
Sex: M
Sources:
Granulocytopenia 6.25%
Disc. AE
150 mg/kg 1 times / day multiple, oral
Recommended
Dose: 150 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg/kg, 1 times / day
Sources:
unhealthy, 34
Health Status: unhealthy
Age Group: 34
Sex: M
Sources:
Nausea 9.4%
Disc. AE
150 mg/kg 1 times / day multiple, oral
Recommended
Dose: 150 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg/kg, 1 times / day
Sources:
unhealthy, 34
Health Status: unhealthy
Age Group: 34
Sex: M
Sources:
Vomiting 9.4%
Disc. AE
150 mg/kg 1 times / day multiple, oral
Recommended
Dose: 150 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg/kg, 1 times / day
Sources:
unhealthy, 34
Health Status: unhealthy
Age Group: 34
Sex: M
Sources:
PubMed

PubMed

TitleDatePubMed
Update on HER-2 as a target for cancer therapy: the ERBB2 promoter and its exploitation for cancer treatment.
2001
[Mycosis in kidney transplant patients].
2001
Hypoxia and oxidative stress. Tumour hypoxia--therapeutic considerations.
2001
The therapeutic monitoring of antimicrobial agents.
2001
Gene therapy for colorectal cancer: therapeutic potential.
2001
Vaginal mucormycosis: a case report.
2001
Sinocranial aspergillosis: a form of central nervous system aspergillosis in south India.
2001
In vitro antifungal activities of voriconazole and reference agents as determined by NCCLS methods: review of the literature.
2001
Synthesis and antiproliferative activity of some 4'-C-hydroxymethyl-alpha- and -beta-D-arabino-pentofuranosyl pyrimidine nucleosides.
2001 Apr-Jul
Hepatic intra-arterial delivery of a retroviral vector expressing the cytosine deaminase gene, controlled by the CEA promoter and intraperitoneal treatment with 5-fluorocytosine suppresses growth of colorectal liver metastases.
2001 Aug
In vivo suicide gene therapy model using a newly discovered prostate-specific membrane antigen promoter/enhancer: a potential alternative approach to androgen deprivation therapy.
2001 Aug
In vitro antifungal susceptibility testing.
2001 Aug
A phase I trial of genetically modified Salmonella typhimurium expressing cytosine deaminase (TAPET-CD, VNP20029) administered by intratumoral injection in combination with 5-fluorocytosine for patients with advanced or metastatic cancer. Protocol no: CL-017. Version: April 9, 2001.
2001 Aug 10
Carcinoembryonic antigen-specific suicide gene therapy of cytosine deaminase/5-fluorocytosine enhanced by the cre/loxP system in the orthotopic gastric carcinoma model.
2001 Aug 15
Phenotypic characterization of Microsporum canis isolated from cats and dogs.
2001 Dec
Candida lusitaniae catheter-related sepsis.
2001 Dec
Mycetoma of the renal pelvis caused by Fusarium species.
2001 Dec
In vitro susceptibility of clinical isolates of Zygomycota to amphotericin B, flucytosine, itraconazole and voriconazole.
2001 Dec
Stereoselective synthesis of 7 alpha- and 7 beta-aminocholestanol as potent fungicidal drugs.
2001 Dec 3
Systemic antifungal agents.
2001 Jul
[A case of SLE presenting the features of antiphospholipid antibody syndrome during a treatment for complicated cryptococcal meningitis].
2001 Jul
Multimodality therapy with a replication-conditional herpes simplex virus 1 mutant that expresses yeast cytosine deaminase for intratumoral conversion of 5-fluorocytosine to 5-fluorouracil.
2001 Jul 15
Discontinuation of secondary prophylaxis against cryptococcosis in patients with AIDS receiving highly active antiretroviral therapy.
2001 Jul 27
Tumor-specific chemo-radio-gene therapy for colorectal cancer cells using adenovirus vector expressing the cytosine deaminase gene.
2001 Jul-Aug
Transduction of thymidine phosphorylase cDNA facilitates efficacy of cytosine deaminase/5-FC gene therapy for malignant brain tumor.
2001 Jul-Aug
Evaluation of the acute and subchronic toxic effects in mice, rats, and monkeys of the genetically engineered and Escherichia coli cytosine deaminase gene-incorporated Salmonella strain, TAPET-CD, being developed as an antitumor agent.
2001 Jul-Aug
In vitro susceptibility pattern of Sporothrix schenckii strains isolated from three centers in India.
2001 Jun
[In vitro antifungal susceptibility of dematiaceous filamentous fungi using the E-test].
2001 Jun
Replicating adenoviral vector-mediated transfer of a heat-inducible double suicide gene for gene therapy.
2001 Jun
Pharmacotherapy of fungal eye infections.
2001 Nov
The echinocandins, first novel class of antifungals in two decades: will they live up to their promise?
2001 Nov
Evaluation of amphotericin B and flucytosine in combination against Candida albicans and Cryptococcus neoformans using time-kill methodology.
2001 Nov
Cytometric approach for a rapid evaluation of susceptibility of Candida strains to antifungals.
2001 Nov
Crystallization and preliminary X-ray analysis of bacterial cytosine deaminase.
2001 Nov
Effect of the growth medium on the in vitro antifungal activity of micafungin (FK-463) against clinical isolates of Candida dubliniensis.
2001 Nov
Development of azole resistance during fluconazole maintenance therapy for AIDS-associated cryptococcal disease.
2001 Nov 23
Enantiomeric synthesis of D- and L-cyclopentenyl nucleosides and their antiviral activity against HIV and West Nile virus.
2001 Nov 8
Sertaconazole: in-vitro antifungal activity against vaginal and other superficial yeast isolates.
2001 Oct
In vivo gene therapy for colon cancer using adenovirus-mediated, transfer of the fusion gene cytosine deaminase and uracil phosphoribosyltransferase.
2001 Oct
[Combined gene therapy for murine liver cancer with interleukin-18 and cytosine deaminase genes].
2001 Oct
Development of Saccharomyces cerevisiae as a model pathogen. A system for the genetic identification of gene products required for survival in the mammalian host environment.
2001 Oct
Sensitization of prostate cancer cell lines to 5-fluorocytosine induced by adenoviral vector carrying a CD transcription unit.
2001 Sep
Successful treatment of cryptococcal osteomyelitis and paraspinous abscess with fluconazole and flucytosine.
2001 Sep
Post-antifungal effect of polyene, azole and DNA-analogue agents against oral Candida albicans and Candida tropicalis isolates in HIV disease.
2001 Sep
Adenovirus gene transfer vectors inhibit growth of lymphatic tumor metastases independent of a therapeutic transgene.
2001 Sep 1
Neonatal candidosis: clinical picture, management controversies and consensus, and new therapeutic options.
2002 Feb
Synthesis and biological activity of the new 5-fluorocytosine derivatives, 5'-deoxy-N-alkyloxycarbonyl-5-fluorocytosine-5'-carboxylic acid.
2002 Feb 11
Quantitation of cytosine deaminase mRNA by real-time reverse transcription polymerase chain reaction: a sensitive method for assessing 5-fluorocytosine toxicity in vitro.
2002 Feb 15
Negative selection of Plasmodium falciparum reveals targeted gene deletion by double crossover recombination.
2002 Jan
The structure of Escherichia coli cytosine deaminase.
2002 Jan 25
Patents

Sample Use Guides

The usual dosage is 50 to 150 mg/kg/day administered in divided doses at 6-
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment:: Standardized procedure of flucytosine MIC determination based on a dilution method with standardized inoculum and flucytosine powder concentrations.
MIC ≤4 ug/ml for susceptible pathogen
Name Type Language
FLUCYTOSINE
EP   HSDB   INN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD   WHO-IP  
USAN   INN  
Official Name English
5-FLUOROCYTOSINE [WHO-IP]
Common Name English
RO-29915
Code English
RO 2-9915
Code English
ANCOBON
Brand Name English
FLUCYTOSINE [WHO-IP]
Common Name English
5-FLUOROCYTOSINE
WHO-IP  
Systematic Name English
FLUOROCYTOSINE
Systematic Name English
FLUCYTOSINE [MI]
Common Name English
NSC-103805
Code English
RO-2-9915
Code English
FLUCYTOSINE [HSDB]
Common Name English
FLUCYTOSINE [USAN]
Common Name English
FLUCYTOSINE [ORANGE BOOK]
Common Name English
CYTOSINE, 5-FLUORO-
Systematic Name English
4-AMINO-5-FLUOROPYRIMIDIN-2(1H)-ONE [WHO-IP]
Systematic Name English
FLUCYTOSINE [EP MONOGRAPH]
Common Name English
FLUCYTOSINE [WHO-DD]
Common Name English
FLUCYTOSINE [MART.]
Common Name English
FLUCYTOSINE [USP-RS]
Common Name English
FLUCYTOSINE [USP MONOGRAPH]
Common Name English
FLUCYTOSINE [JAN]
Common Name English
FLUCYTOSINE [USP]
Common Name English
EMTRICITABINE IMPURITY E [WHO-IP]
Common Name English
FLUCYTOSINUM [WHO-IP LATIN]
Common Name English
FLUCYTOSINE [INN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1557
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
WHO-ATC D01AE21
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
WHO-ATC J02AX01
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
EU-Orphan Drug EU/3/18/1978
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
WHO-VATC QJ02AX01
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
NDF-RT N0000175467
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
NDF-RT N0000175459
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
WHO-VATC QD01AE21
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
NDF-RT N0000175459
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
LIVERTOX 420
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
NDF-RT N0000175459
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
FDA ORPHAN DRUG 327910
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 6.3
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
Code System Code Type Description
WHO INTERNATIONAL PHARMACOPEIA
FLUCYTOSINE
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
PRIMARY Description: A white or almost white, crystalline powder; odourless or almost odourless. Solubility: Sparingly soluble in water; slightly soluble in ethanol (~750 g/l) TS; practically insoluble in ether R. Category: Antifungal drug. Storage: Flucytosine should be kept in a tightly closed container, protected from light.Additional information: Flucytosine melts at about 295 ?C. Definition: Flucytosine contains not less than 98.5% and not more than 101.0% of C4H4FN3O, calculated with reference to the dried substance.
USP_CATALOG
1272000
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
PRIMARY USP-RS
DRUG BANK
DB01099
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
PRIMARY
FDA UNII
D83282DT06
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
PRIMARY
NCI_THESAURUS
C501
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
PRIMARY
PUBCHEM
3366
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
PRIMARY
WIKIPEDIA
FLUCYTOSINE
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
PRIMARY
ChEMBL
CHEMBL1463
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
PRIMARY
CAS
2022-85-7
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
PRIMARY
DRUG CENTRAL
1188
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
PRIMARY
ECHA (EC/EINECS)
217-968-7
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
PRIMARY
EPA CompTox
2022-85-7
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
PRIMARY
MERCK INDEX
M5426
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
PRIMARY Merck Index
INN
2729
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
PRIMARY
HSDB
3082
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
PRIMARY
EVMPD
SUB07676MIG
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
PRIMARY
MESH
D005437
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
PRIMARY
RXCUI
4451
Created by admin on Fri Jun 25 20:59:32 UTC 2021 , Edited by admin on Fri Jun 25 20:59:32 UTC 2021
PRIMARY RxNorm