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

Details

Stereochemistry ACHIRAL
Molecular Formula CH4N2O2
Molecular Weight 76.0547
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of HYDROXYUREA

SMILES

C(=N)(NO)O

InChI

InChIKey=VSNHCAURESNICA-UHFFFAOYSA-N
InChI=1S/CH4N2O2/c2-1(4)3-5/h5H,(H3,2,3,4)

HIDE SMILES / InChI
Hydroxyurea is an oral antimetabolite; inhibits ribonucleotide reductase and DNA synthesis. It is used for resistant chronic myeloid leukemia, locally advanced squamous cell carcinomas of the head and neck (excluding lip) in combination with concurrent chemoradiation, and to reduce the frequency of painful crises and the need for blood transfusions in patients with sickle cell anemia with recurrent moderate to severe painful crises. Hydroxyurea, a myelosuppressive agent, is the only effective drug proven to reduce the frequency of painful episodes. It raises the level of HbF and the haemoglobin level. It usually decreases the rate of painful episodes by 50%. It was first tested in sickle cell disease in 1984. It also decreases the rate of ACS episodes and blood transfusions by ~50 % in adults. It was developed as an anticancer drug and has been used to treat myeloproliferative syndromes-leukemia, melanoma, and ovarian cancer. It was approved for use by FDA in adults. Side effects includes neutropenia, bone marrow suppression, elevation of hepatic enzymes, anorexia, nausea, vomiting and infertility.

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
DROXIA

Approved Use

DROXIA is an antimetabolite indicated to reduce the frequency of painful crises and to reduce the need for blood transfusions in patients with sickle cell anemia with recurrent moderate to severe painful crises

Launch Date

-6.53184E10
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
793.75 μM
2000 mg single, oral
dose: 2000 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HYDROXYUREA plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
3934 μM × h
2000 mg single, oral
dose: 2000 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HYDROXYUREA plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
3.32 h
2000 mg single, oral
dose: 2000 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HYDROXYUREA plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
40 mg/kg 2 times / day single, oral
Highest studied dose
Dose: 40 mg/kg, 2 times / day
Route: oral
Route: single
Dose: 40 mg/kg, 2 times / day
Sources:
unhealthy, 2-18 years
n = 10
Health Status: unhealthy
Condition: allogeneic transplantation
Age Group: 2-18 years
Population Size: 10
Sources:
26.7 mg/kg 1 times / day multiple, oral
MTD
Dose: 26.7 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 26.7 mg/kg, 1 times / day
Sources:
unhealthy, 2-18 years
Health Status: unhealthy
Condition: sickle cell anemia
Age Group: 2-18 years
Sources:
20 mg/kg 1 times / day multiple, oral
Recommended
Dose: 20 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg/kg, 1 times / day
Sources:
unhealthy, 2-18 years
Health Status: unhealthy
Age Group: 2-18 years
Sources:
Other AEs: Myelosuppression...
20 mg/kg 1 times / day steady, oral
Dose: 20 mg/kg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg/kg, 1 times / day
Sources:
unhealthy
n = 104
Health Status: unhealthy
Condition: Malaria
Population Size: 104
Sources:
Other AEs: Sudden death, Thrombocytopenia...
Other AEs:
Sudden death (serious, 1 patient)
Thrombocytopenia (below serious, 11 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
Myelosuppression
20 mg/kg 1 times / day multiple, oral
Recommended
Dose: 20 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg/kg, 1 times / day
Sources:
unhealthy, 2-18 years
Health Status: unhealthy
Age Group: 2-18 years
Sources:
Thrombocytopenia below serious, 11 patient
20 mg/kg 1 times / day steady, oral
Dose: 20 mg/kg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg/kg, 1 times / day
Sources:
unhealthy
n = 104
Health Status: unhealthy
Condition: Malaria
Population Size: 104
Sources:
Sudden death serious, 1 patient
20 mg/kg 1 times / day steady, oral
Dose: 20 mg/kg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg/kg, 1 times / day
Sources:
unhealthy
n = 104
Health Status: unhealthy
Condition: Malaria
Population Size: 104
Sources:
Overview

Overview

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
likely [IC50 >10 uM]
no [Activation 39.8107 uM]
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >133 uM]
no [IC50 >133 uM]
no [IC50 >133 uM]
no [IC50 >133 uM]
no
no
yes
yes
yes
Drug as victimTox targets
PubMed

PubMed

TitleDatePubMed
In vivo and in vitro comparison of the short-term hematopoietic toxicity between hydroxyurea and trimidox or didox, novel ribonucleotide reductase inhibitors with potential anti-HIV-1 activity.
1999
Oral ulcers caused by hydroxyurea.
2000 Dec
Myeloblastoma (chloroma) in leukemia: case 2. Meningeal granulocytic sarcoma (chloroma) in essential thrombocythemia.
2000 Dec 1
Excess peripheral neuropathy in patients treated with hydroxyurea plus didanosine and stavudine for HIV infection.
2000 Feb 18
Ser45 plays an important role in managing both the equilibrium and transition state energetics of the streptavidin-biotin system.
2000 May
Hydroxyurea inhibits the transactivation of the HIV-long-terminal repeat (LTR) promoter.
2000 May
Synergistic inhibition of HIV-1 in activated and resting peripheral blood mononuclear cells, monocyte-derived macrophages, and selected drug-resistant isolates with nucleoside analogues combined with a natural product, resveratrol.
2000 Nov 1
The super anti-apoptotic factor Bcl-xFNK constructed by disturbing intramolecular polar interactions in rat Bcl-xL.
2000 Nov 24
Hydroxyurea-induced oxidative damage of normal and sickle cell hemoglobins in vitro: amelioration by radical scavengers.
2001
Chromosomal aberrations in lymphocytes of employees in transformer and generator production exposed to electromagnetic fields and mineral oil.
2001 Apr
Role of petasin in the potential anti-inflammatory activity of a plant extract of petasites hybridus.
2001 Apr 15
Hydroxyurea promotes the reduction of spontaneous BFU-e to normal levels in SS and S/beta thalassemic patients.
2001 Feb
The predictive value of vascular risk factors and gender for the development of thrombotic complications in essential thrombocythemia.
2001 Feb
A compromised yeast RNA polymerase II enhances UV sensitivity in the absence of global genome nucleotide excision repair.
2001 Feb
Improved cerebrovascular patency following therapy in patients with sickle cell disease: initial results in 4 patients who received HLA-identical hematopoietic stem cell allografts.
2001 Feb
Sickle cell anemia and antisickling agents then and now.
2001 Feb
Inhibition of N-myc expression and induction of apoptosis by iron chelation in human neuroblastoma cells.
2001 Feb 1
Dynamic changes in subnuclear NP95 location during the cell cycle and its spatial relationship with DNA replication foci.
2001 Feb 15
The biology and treatment of chronic myelogenous leukemia.
2001 Jan
Current management in polycythemia vera.
2001 Jan
Predominantly BCR-ABL negative myeloid precursors in interferon-alpha treated chronic myelogenous leukemia: a follow-up study of peripheral blood colony-forming cells with fluorescence in situ hybridization.
2001 Jan
Inhibition of hepatitis B virus production associated with high levels of intracellular viral DNA intermediates in iron-depleted HepG2.2.15 cells.
2001 Jan
Thioguanine for refractory psoriasis: a 4-year experience.
2001 Jan
De novo activation of the beta-phaseolin promoter by phosphatase or protein synthesis inhibitors.
2001 Jan 19
JP-8 jet fuel-induced DNA damage in H4IIE rat hepatoma cells.
2001 Jan 25
Management of patients with essential thrombocythemia: current concepts and perspectives.
2001 Mar
Efficacy and safety of hydroxyurea in patients with essential thrombocythemia.
2001 Mar
Myeloproliferative syndromes. Current opinions from the European Hematology Association Working Group on Myeloproliferative Disorders.
2001 Mar
Hydrogenosome morphological variation induced by fibronectin and other drugs in Trichomonas vaginalis and Tritrichomonas foetus.
2001 Mar
Clinical predictors of health-related quality of life depend on asthma severity.
2001 Mar
Localised chronic eyedlid disease resulting from long term hydroxyurea therapy.
2001 Mar
Prognostic impact of bone marrow erythropoietic precursor cells and myelofibrosis at diagnosis of Ph1+ chronic myelogenous leukaemia--a multicentre study on 495 patients.
2001 Mar
The Saccharomyces cerevisiae MUM2 gene interacts with the DNA replication machinery and is required for meiotic levels of double strand breaks.
2001 Mar
Bloom helicase is involved in DNA surveillance in early S phase in vertebrate cells.
2001 Mar 8
Patents

Sample Use Guides

Usual Adult Dose for Chronic Myelogenous Leukemia 15 mg/kg/day orally as a single dose Usual Adult Dose for Head and Neck Cancer 15 mg/kg/day orally as a single dose Usual Adult Dose for Sickle Cell Anemia 15 mg/kg orally once a day; increase 5 mg/kg/day every 12 weeks Maximum dose: 35 mg/kg/day Usual Pediatric Dose for Sickle Cell Anemia 2 years and older: 20 mg/kg orally once a day; increase 5 mg/kg/day every 8 weeks or if a painful crisis occurs; increase dosing only if blood counts are in the acceptable range; do not increase dosing if myelosuppression occurs; if blood counts are considered toxic, discontinue therapy until hematologic recovery Duration of therapy: Give until mild myelosuppression (absolute neutrophil count 2000/microliter to 4000/microliter) is achieved, up to 35 mg/kg/day Maximum dose: 35 mg/kg/day
Route of Administration: Oral
Name Type Language
HYDROXYUREA
HSDB   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF  
USAN  
Official Name English
HYDROXYUREA [HSDB]
Common Name English
SIKLOS
Brand Name English
HYDROXYCARBAMIDE [WHO-DD]
Common Name English
SQ 1089
Code English
HYDREA
Brand Name English
HYDROXYCARBAMIDE [EMA EPAR]
Common Name English
HYDROXYCARBAMIDE
EMA EPAR   EP   INN   JAN   MART.   WHO-DD  
INN  
Official Name English
HYDROXYUREA [VANDF]
Common Name English
SQ-1089
Code English
UREA, HYDROXY-
Systematic Name English
HYDROXYCARBAMIDE [INN]
Common Name English
HYDROXYUREA [USP]
Common Name English
HYDROXYUREA [IARC]
Common Name English
HYDROXYUREA [USP-RS]
Common Name English
DROXIA
Brand Name English
HYDROXYCARBAMIDE [EP MONOGRAPH]
Common Name English
HYDROXYCARBAMIDE [JAN]
Common Name English
NSC-32065
Code English
HYDROXYUREA [MI]
Common Name English
HYDROXYUREA [ORANGE BOOK]
Common Name English
HYDROXYUREA [USAN]
Common Name English
HYDROXYCARBAMIDE [MART.]
Common Name English
Classification Tree Code System Code
WHO-ESSENTIAL MEDICINES LIST 8.2
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
WHO-ATC L01XX05
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
FDA ORPHAN DRUG 202605
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 10.3
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
FDA ORPHAN DRUG 555116
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
NCI_THESAURUS C2150
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
NDF-RT N0000006999
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
LIVERTOX 491
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
FDA ORPHAN DRUG 463414
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
NDF-RT N0000180853
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
EU-Orphan Drug EU/3/03/154
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
NCI_THESAURUS C272
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
EMA ASSESSMENT REPORTS SIKLOS (AUTHORIZED: ANEMIA, SICKLE-CELL)
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
FDA ORPHAN DRUG 400413
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
FDA ORPHAN DRUG 49590
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
WHO-VATC QL01XX05
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
Code System Code Type Description
USP_CATALOG
1332000
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
PRIMARY USP-RS
RXCUI
5552
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
PRIMARY RxNorm
ECHA (EC/EINECS)
204-821-7
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
PRIMARY
LACTMED
Hydroxyurea
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
PRIMARY
HSDB
6887
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
PRIMARY
DRUG BANK
DB01005
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
PRIMARY
CAS
127-07-1
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
PRIMARY
INN
1991
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
PRIMARY
NCI_THESAURUS
C560
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
PRIMARY
MESH
D006918
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
PRIMARY
WIKIPEDIA
HYDROXYCARBAMIDE
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
PRIMARY
EVMPD
SUB08076MIG
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
PRIMARY
ChEMBL
CHEMBL467
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
PRIMARY
PUBCHEM
3657
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
PRIMARY
MERCK INDEX
M6158
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
PRIMARY Merck Index
EPA CompTox
127-07-1
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
PRIMARY
DRUG CENTRAL
1399
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
PRIMARY
IUPHAR
6822
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
PRIMARY
FDA UNII
X6Q56QN5QC
Created by admin on Fri Jun 25 21:09:13 UTC 2021 , Edited by admin on Fri Jun 25 21:09:13 UTC 2021
PRIMARY