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
SMILES
NC(=O)NO
InChI
InChIKey=VSNHCAURESNICA-UHFFFAOYSA-N
InChI=1S/CH4N2O2/c2-1(4)3-5/h5H,(H3,2,3,4)
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
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL3301398 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | DROXIA Approved UseDROXIA 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 Date1967 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
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793.75 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9473217 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3934 μM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9473217 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3.32 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9473217 |
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
Dose | Population | Adverse 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: |
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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: |
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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... Other AEs: Myelosuppression Sources: |
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) Sources: Thrombocytopenia (below serious, 11 patient) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
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OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
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Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
likely [IC50 >10 uM] | yes (pharmacogenomic study) Comment: Of the 73 children completing the study, 42 had reduced-functioning alleles; 82% of the 27 children taking hydoxyurea had reduced-functioning alleles, versus 47% of 36 those with mild disease (P < .05). |
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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 victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
weak | ||||
weak | ||||
weak | ||||
weak | ||||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
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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 |
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Hydroxyurea inhibits intracellular Toxoplasma gondii multiplication. | 2000 Apr 1 |
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Pure red cell aplasia in a patient with chronic granulocytic leukaemia treated with interferon-alpha. | 2000 Feb |
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Hydroxyurea-induced cutaneous ulceration in older patients. | 2000 Feb |
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Excess peripheral neuropathy in patients treated with hydroxyurea plus didanosine and stavudine for HIV infection. | 2000 Feb 18 |
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A case of bilateral heel ulcers associated with hydroxyurea therapy for chronic myelogenous leukemia. | 2000 Mar |
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Systematic review of combination antiretroviral therapy with didanosine plus hydroxyurea: a partial solution to Africa's HIV/AIDS problem? | 2001 |
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Stroke prevention and treatment in sickle cell disease. | 2001 Apr |
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Chromosomal aberrations in lymphocytes of employees in transformer and generator production exposed to electromagnetic fields and mineral oil. | 2001 Apr |
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The anti-malarial artesunate is also active against cancer. | 2001 Apr |
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A new molecular role for iron in regulation of cell cycling and differentiation of HL-60 human leukemia cells: iron is required for transcription of p21(WAF1/CIP1) in cells induced by phorbol myristate acetate. | 2001 Apr |
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Role of petasin in the potential anti-inflammatory activity of a plant extract of petasites hybridus. | 2001 Apr 15 |
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Replication and G2 checkpoints: their response to caffeine. | 2001 Feb |
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Induction of unscheduled DNA synthesis in hairless mouse epidermis by 8-methoxypsoralen plus ultraviolet A (PUVA). | 2001 Feb |
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A compromised yeast RNA polymerase II enhances UV sensitivity in the absence of global genome nucleotide excision repair. | 2001 Feb |
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Coupling of Saccharomyces cerevisiae early meiotic gene expression to DNA replication depends upon RPD3 and SIN3. | 2001 Feb |
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Dynamics of seminal plasma HIV-1 decline after antiretroviral treatment. | 2001 Feb 16 |
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Chronic neutrophilic leukemia (CNL): a clinical, pathologic and cytogenetic study. | 2001 Jan |
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Current management in polycythemia vera. | 2001 Jan |
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Inhibition of hepatitis B virus production associated with high levels of intracellular viral DNA intermediates in iron-depleted HepG2.2.15 cells. | 2001 Jan |
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N-(Hydroxyaminocarbonyl)phenylalanine: a novel class of inhibitor for carboxypeptidase A. | 2001 Jan |
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Drug Points: pancreatitis associated with hydroxyurea in combination with didanosine. | 2001 Jan 13 |
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Reduction of telomerase activity in human liver cancer cells by a histone deacetylase inhibitor. | 2001 Jun |
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Management of patients with essential thrombocythemia: current concepts and perspectives. | 2001 Mar |
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Hydrogenosome morphological variation induced by fibronectin and other drugs in Trichomonas vaginalis and Tritrichomonas foetus. | 2001 Mar |
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Localised chronic eyedlid disease resulting from long term hydroxyurea therapy. | 2001 Mar |
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The Saccharomyces cerevisiae MUM2 gene interacts with the DNA replication machinery and is required for meiotic levels of double strand breaks. | 2001 Mar |
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Topoisomerase IV, alone, unknots DNA in E. coli. | 2001 Mar 15 |
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The BARD1-CstF-50 interaction links mRNA 3' end formation to DNA damage and tumor suppression. | 2001 Mar 9 |
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Body composition in women with sickle cell disease. | 2001 Winter |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/dosage/hydroxyurea.html
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
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Classification Tree | Code System | Code | ||
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WHO-ESSENTIAL MEDICINES LIST |
8.2
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WHO-ATC |
L01XX05
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FDA ORPHAN DRUG |
202605
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WHO-ESSENTIAL MEDICINES LIST |
10.3
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FDA ORPHAN DRUG |
555116
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NCI_THESAURUS |
C2150
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NDF-RT |
N0000006999
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LIVERTOX |
NBK548724
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FDA ORPHAN DRUG |
463414
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NDF-RT |
N0000180853
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EU-Orphan Drug |
EU/3/03/154
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NCI_THESAURUS |
C272
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EMA ASSESSMENT REPORTS |
SIKLOS (AUTHORIZED: ANEMIA, SICKLE-CELL)
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FDA ORPHAN DRUG |
400413
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FDA ORPHAN DRUG |
49590
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WHO-VATC |
QL01XX05
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Hydroxyurea
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m6158
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DTXSID6025438
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ACTIVE MOIETY