hydroxycarbamide indications/contra

Stem definitionDrug idCAS RN
1399 127-07-1

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • siklos
  • hydroxyurea
  • biosupressin
  • carbamohydroxamic acid
  • carbamohydroximic acid
  • carbamoyl oxime
  • oxyrea
  • oxyurea
  • hydroxycarbamide
An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.
  • Molecular weight: 76.06
  • Formula: CH4N2O2
  • CLOGP: -1.80
  • LIPINSKI: 0
  • HAC: 4
  • HDO: 3
  • TPSA: 75.35
  • ALOGS: 0.55
  • ROTB: 0

Drug dosage:

None

Approvals:

DateAgencyCompanyOrphan
Dec. 7, 1967 FDA BRISTOL MYERS SQUIBB

FDA Adverse Event Reporting System

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MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Anaemia 235.94 31.88 103 1614 54230 3329912
Thrombocytopenia 235.28 31.88 91 1626 35177 3348965
Skin ulcer 205.77 31.88 53 1664 5387 3378755
Acute myeloid leukaemia 183.97 31.88 48 1669 5125 3379017
Pyrexia 160.04 31.88 90 1627 81025 3303117
Platelet count increased 137.92 31.88 35 1682 3336 3380806
Mucosal inflammation 137.32 31.88 42 1675 7941 3376201
Tumour lysis syndrome 135.11 31.88 32 1685 2287 3381855
Pancytopenia 133.72 31.88 51 1666 18769 3365373
Malignant neoplasm progression 118.44 31.88 46 1671 17747 3366395
White blood cell count decreased 109.90 31.88 48 1669 24899 3359243
Pneumonia 106.84 31.88 66 1651 70077 3314065
Neutropenia 96.54 31.88 48 1669 33338 3350804
Product use in unapproved indication 92.14 31.88 26 1691 3700 3380442
Platelet count decreased 89.90 31.88 43 1674 27425 3356717
Febrile neutropenia 85.08 31.88 37 1680 18938 3365204
Squamous cell carcinoma 82.02 31.88 22 1695 2592 3381550
Bone marrow failure 78.60 31.88 28 1689 8459 3375683
Interstitial lung disease 78.41 31.88 32 1685 13984 3370158
Fatigue 75.21 31.88 63 1654 107177 3276965
Off label use 74.99 31.88 48 1669 53929 3330213
Haemoglobin decreased 74.27 31.88 39 1678 30255 3353887
Chronic myeloid leukaemia 73.59 31.88 17 1700 1085 3383057
Myelofibrosis 73.55 31.88 16 1701 776 3383366
Pleural effusion 69.40 31.88 32 1685 18747 3365395
Disease progression 69.18 31.88 38 1679 32221 3351921
Second primary malignancy 67.86 31.88 17 1700 1530 3382612
Nail pigmentation 64.53 31.88 10 1707 67 3384075
Asthenia 61.90 31.88 46 1671 65619 3318523
Leukopenia 61.71 31.88 28 1689 15795 3368347

Pharmacologic Action:

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SourceCodeDescription
ATC L01XX05 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Other antineoplastic agents
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:50846 immunomodulator
FDA EPC N0000180853 Antimetabolite
FDA Chemical/Ingredient N0000006999 Urea
MeSH PA D000970 Antineoplastic Agents
MeSH PA D000986 Antisickling Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D006401 Hematologic Agents
MeSH PA D019384 Nucleic Acid Synthesis Inhibitors

Drug Use (View source of the data)

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DiseaseRelationSNOMED_IDDOID
Chronic myeloid leukemia indication 92818009 DOID:8552
Hb SS disease indication 127040003 DOID:10923
Malignant tumor of head and/or neck indication 255056009
Malignant tumor of ovary indication 363443007 DOID:2394
Malignant melanoma indication 372244006 DOID:1909
Hemoglobin SS disease with crisis indication 417425009
Vasculitis of the skin contraindication 53312001
Leukopenia contraindication 84828003 DOID:615
Kidney disease contraindication 90708001 DOID:2527
Anemia contraindication 271737000 DOID:2355
Pregnancy, function contraindication 289908002
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Breastfeeding (mother) contraindication 413712001
Postirradiation Erythema contraindication
Severe Bone Marrow Depression contraindication
Polycythemia vera off-label use 109992005 DOID:8432
Essential thrombocythemia off-label use 109994006 DOID:2224

Acid dissociation constants calculated using MoKa v3.0.0

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Dissociation levelDissociation constantType (acidic/basic)
pKa1 10.38 acidic
pKa2 12.5 acidic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

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Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
100MG SIKLOS ADDMEDICA SAS N208843 Dec. 21, 2017 RX TABLET ORAL Dec. 21, 2020 NEW PRODUCT
1GM SIKLOS ADDMEDICA SAS N208843 Dec. 21, 2017 RX TABLET ORAL Dec. 21, 2020 NEW PRODUCT

Bioactivity Summary:

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TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Ribonucleoside-diphosphate reductase subunit M2 Enzyme INHIBITOR WOMBAT-PK CHEMBL
Ribonucleoside-diphosphate reductase large subunit Enzyme INHIBITOR WOMBAT-PK CHEMBL
Carbonic anhydrase 5A, mitochondrial Enzyme Ki 4.51 CHEMBL
Carbonic anhydrase 9 Enzyme Ki 4.64 CHEMBL
Carbonic anhydrase 2 Enzyme Ki 4.55 CHEMBL

External reference:

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IDSource
CHEBI:44423 CHEBI
4017733 VUID
N0000146101 NUI
C0020402 UMLSCUI
D00341 KEGG_DRUG
CHEMBL467 ChEMBL_ID
DB01005 DRUGBANK_ID
1763 MMSL
56602009 SNOMEDCT_US
4856 MMSL
d01373 MMSL
4017733 VANDF
5552 RXNORM
N0000146101 NDFRT
N0000007293 NDFRT
002635 NDDF
387314007 SNOMEDCT_US
D006918 MESH_DESCRIPTOR_UI
X6Q56QN5QC UNII
1991 INN_ID
3657 PUBCHEM_CID

Pharmaceutical products:

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ProductCategoryIngredientsNDCFormQuantityRoute MarketingLabel
HYDREA HUMAN PRESCRIPTION DRUG LABEL 1 0003-0830 CAPSULE 500 mg ORAL NDA 17 sections
DROXIA HUMAN PRESCRIPTION DRUG LABEL 1 0003-6335 CAPSULE 200 mg ORAL NDA 20 sections
DROXIA HUMAN PRESCRIPTION DRUG LABEL 1 0003-6336 CAPSULE 300 mg ORAL NDA 20 sections
DROXIA HUMAN PRESCRIPTION DRUG LABEL 1 0003-6337 CAPSULE 400 mg ORAL NDA 20 sections
HYDROXYUREA HUMAN PRESCRIPTION DRUG LABEL 1 0093-0882 CAPSULE 500 mg ORAL ANDA 16 sections
HYDROXYUREA HUMAN PRESCRIPTION DRUG LABEL 1 0555-0882 CAPSULE 500 mg ORAL ANDA 17 sections
HYDROXYUREA HUMAN PRESCRIPTION DRUG LABEL 1 42291-321 CAPSULE 500 mg ORAL ANDA 13 sections
Hydroxyurea HUMAN PRESCRIPTION DRUG LABEL 1 49884-724 CAPSULE 500 mg ORAL ANDA 17 sections
HYDROXYUREA HUMAN PRESCRIPTION DRUG LABEL 1 54868-4773 CAPSULE 500 mg ORAL ANDA 13 sections
Hydroxyurea HUMAN PRESCRIPTION DRUG LABEL 1 55154-7143 CAPSULE 500 mg ORAL ANDA 17 sections
Hydroxyurea HUMAN PRESCRIPTION DRUG LABEL 1 60429-265 CAPSULE 500 mg ORAL ANDA 17 sections
Hydroxyurea HUMAN PRESCRIPTION DRUG LABEL 1 68084-284 CAPSULE 500 mg ORAL ANDA 17 sections
Hydroxyurea HUMAN PRESCRIPTION DRUG LABEL 1 70518-0916 CAPSULE 500 mg ORAL ANDA 17 sections
Siklos HUMAN PRESCRIPTION DRUG LABEL 1 71770-100 TABLET, FILM COATED 100 mg ORAL NDA 21 sections
Siklos HUMAN PRESCRIPTION DRUG LABEL 1 71770-120 TABLET, FILM COATED 1000 mg ORAL NDA 21 sections