hydroxycarbamide Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
1399 127-07-1

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • xromi
  • 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

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 50 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 80 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 1502.57 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 79 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.52 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 1.50 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 1 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 3.40 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
July 1, 2019 EMA NOVA LABORATORIES IRELAND LIMITED
Dec. 7, 1967 FDA BRISTOL MYERS SQUIBB

FDA Adverse Event Reporting System (Female)

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
Sickle cell anaemia with crisis 372.56 14.10 105 13087 3887 46668983
Platelet count increased 193.32 14.10 91 13101 14783 46658087
Acute myeloid leukaemia 188.21 14.10 91 13101 15687 46657183
Chronic myeloid leukaemia 122.89 14.10 40 13152 2418 46670452
Splenomegaly 106.89 14.10 53 13139 9635 46663235
White blood cell count increased 92.60 14.10 86 13106 44133 46628737
Thrombocytosis 91.85 14.10 39 13153 4963 46667907
Myelofibrosis 90.28 14.10 27 13165 1232 46671638
Blast crisis in myelogenous leukaemia 83.86 14.10 21 13171 487 46672383
Serum ferritin increased 83.32 14.10 37 13155 5246 46667624
Pancytopenia 81.62 14.10 110 13082 84948 46587922
Acute chest syndrome 81.46 14.10 21 13171 549 46672321
Haemoglobin decreased 78.62 14.10 135 13057 128814 46544056
Thrombocytopenia 77.80 14.10 133 13059 126448 46546422
Leukocytosis 61.94 14.10 52 13140 23346 46649524
Platelet count decreased 61.29 14.10 105 13087 99919 46572951
Anaemia 58.82 14.10 182 13010 255597 46417273
Erythromelalgia 56.04 14.10 12 13180 135 46672735
Differentiation syndrome 50.34 14.10 16 13176 895 46671975
Tumour lysis syndrome 42.18 14.10 26 13166 7210 46665660
Myeloproliferative neoplasm 41.67 14.10 12 13180 479 46672391
Blood iron increased 40.67 14.10 15 13177 1316 46671554
Skin ulcer 40.67 14.10 48 13144 32410 46640460
Blood lactate dehydrogenase increased 37.44 14.10 37 13155 20463 46652407
Nail pigmentation 36.88 14.10 9 13183 187 46672683
Chronic myeloid leukaemia transformation 35.61 14.10 8 13184 114 46672756
Sickle cell anaemia 35.22 14.10 11 13181 581 46672289
Transformation to acute myeloid leukaemia 35.05 14.10 8 13184 123 46672747
Aquagenic pruritus 32.81 14.10 6 13186 27 46672843
Drug hypersensitivity 32.70 14.10 14 13178 243811 46429059
Toxicity to various agents 32.04 14.10 10 13182 211756 46461114
Cytogenetic analysis abnormal 31.35 14.10 10 13182 566 46672304
Leukaemia 30.44 14.10 16 13176 3279 46669591
Essential thrombocythaemia 28.61 14.10 7 13185 147 46672723
Laryngitis 27.36 14.10 22 13170 9294 46663576
Malignant neoplasm progression 26.02 14.10 57 13135 64869 46608001
Intentional product use issue 25.45 14.10 50 13142 52730 46620140
Bone marrow failure 24.87 14.10 36 13156 29633 46643237
Laryngeal inflammation 24.43 14.10 6 13186 128 46672742
Leukostasis syndrome 24.17 14.10 5 13187 47 46672823
Polycythaemia vera 23.84 14.10 6 13186 142 46672728
Gene mutation identification test positive 23.53 14.10 6 13186 150 46672720
Myelodysplastic syndrome 22.66 14.10 25 13167 15686 46657184
Drug ineffective 22.51 14.10 107 13085 677731 45995139
Adenocarcinoma metastatic 22.41 14.10 5 13187 69 46672801
Febrile neutropenia 22.28 14.10 68 13124 94559 46578311
Acute febrile neutrophilic dermatosis 21.90 14.10 12 13180 2673 46670197
Sinusitis 21.74 14.10 5 13187 129763 46543107
Rheumatoid arthritis 21.17 14.10 22 13170 240193 46432677
Immunodeficiency 20.92 14.10 22 13170 13084 46659786
Splenic rupture 20.80 14.10 9 13183 1198 46671672
Haematocrit decreased 20.39 14.10 36 13156 35021 46637849
Injection site pain 20.37 14.10 3 13189 107149 46565721
Blood bilirubin increased 19.74 14.10 35 13157 34149 46638721
Chronic myelomonocytic leukaemia 19.19 14.10 6 13186 318 46672552
Tonsillitis bacterial 18.73 14.10 5 13187 150 46672720
Gestational trophoblastic tumour 18.68 14.10 4 13188 45 46672825
Posterior reversible encephalopathy syndrome 18.32 14.10 22 13170 15119 46657751
Serum ferritin decreased 18.10 14.10 9 13183 1643 46671227
Anxiety 17.99 14.10 15 13177 181942 46490928
Head banging 17.60 14.10 6 13186 418 46672452
Hyperleukocytosis 17.58 14.10 6 13186 420 46672450
Normal newborn 17.26 14.10 14 13178 5987 46666883
Red blood cell count decreased 17.06 14.10 32 13160 32591 46640279
Desmoid tumour 17.04 14.10 4 13188 70 46672800
Hypoperfusion 16.47 14.10 8 13184 1389 46671481
Dermatitis bullous 16.24 14.10 15 13177 7628 46665242
Cytopenia 16.03 14.10 15 13177 7753 46665117
Transfusion 15.64 14.10 19 13173 13212 46659658
Red blood cell count increased 15.13 14.10 9 13183 2341 46670529
White blood cell count decreased 14.87 14.10 67 13125 112164 46560706
Joint swelling 14.86 14.10 15 13177 166058 46506812
Blast cell count increased 14.56 14.10 5 13187 356 46672514
Pleural effusion 14.54 14.10 54 13138 82898 46589972
Decreased appetite 14.45 14.10 99 13093 193737 46479133
Subdural haematoma 14.29 14.10 18 13174 12979 46659891
Anaemia macrocytic 14.12 14.10 9 13183 2644 46670226

FDA Adverse Event Reporting System (Male)

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
Sickle cell anaemia with crisis 298.26 14.41 87 13062 2315 29937014
Chronic myeloid leukaemia 159.86 14.41 55 13094 2522 29936807
Myelofibrosis 139.61 14.41 44 13105 1527 29937802
Acute myeloid leukaemia 139.52 14.41 91 13058 17915 29921414
Differentiation syndrome 135.12 14.41 40 13109 1120 29938209
White blood cell count increased 110.48 14.41 110 13039 39563 29899766
Blast crisis in myelogenous leukaemia 101.42 14.41 27 13122 507 29938822
Splenomegaly 99.23 14.41 66 13083 13414 29925915
Tumour lysis syndrome 89.84 14.41 61 13088 12824 29926505
Platelet count increased 84.86 14.41 51 13098 8691 29930638
Leukocytosis 77.83 14.41 69 13080 21433 29917896
Thrombocytopenia 68.26 14.41 171 12978 136873 29802456
Philadelphia chromosome positive 60.06 14.41 15 13134 216 29939113
Serum ferritin increased 56.10 14.41 33 13116 5404 29933925
Blast cell count increased 55.90 14.41 20 13129 1029 29938300
Cytogenetic analysis abnormal 55.72 14.41 16 13133 401 29938928
Skin ulcer 55.65 14.41 54 13095 18795 29920534
Hyperleukocytosis 54.38 14.41 22 13127 1587 29937742
Endocarditis noninfective 52.81 14.41 12 13137 112 29939217
Haemoglobin decreased 51.23 14.41 137 13012 113961 29825368
Anaemia 50.98 14.41 203 12946 207789 29731540
Granulomatous rosacea 48.16 14.41 12 13137 171 29939158
Idiopathic intracranial hypertension 46.45 14.41 15 13134 563 29938766
Chronic myelomonocytic leukaemia 44.59 14.41 15 13134 641 29938688
Essential thrombocythaemia 38.31 14.41 8 13141 48 29939281
Actinic keratosis 37.51 14.41 22 13127 3581 29935748
Drug resistance 33.91 14.41 43 13106 20090 29919239
Acute chest syndrome 33.70 14.41 10 13139 282 29939047
Posterior reversible encephalopathy syndrome 33.61 14.41 29 13120 8678 29930651
Toxicity to various agents 32.13 14.41 19 13130 177164 29762165
Blood lactate dehydrogenase increased 31.58 14.41 42 13107 20559 29918770
Intentional product use issue 31.49 14.41 57 13092 36383 29902946
Platelet count decreased 30.39 14.41 109 13040 106020 29833309
Myeloproliferative neoplasm 29.51 14.41 10 13139 437 29938892
Splenic infarction 26.86 14.41 14 13135 1811 29937518
Pleural effusion 26.46 14.41 82 13067 73984 29865345
Squamous cell carcinoma 25.90 14.41 27 13122 10223 29929106
Parainfluenzae virus infection 25.41 14.41 14 13135 2024 29937305
Subacute combined cord degeneration 25.37 14.41 7 13142 151 29939178
Spermatogenesis abnormal 25.35 14.41 6 13143 68 29939261
Chronic myeloid leukaemia transformation 24.55 14.41 7 13142 171 29939158
Mucosal inflammation 24.21 14.41 46 13103 30448 29908881
Leukaemia recurrent 23.04 14.41 12 13137 1549 29937780
Acinetobacter sepsis 22.80 14.41 5 13144 39 29939290
Stenotrophomonas infection 22.60 14.41 12 13137 1612 29937717
Sickle cell disease 22.32 14.41 6 13143 117 29939212
Leukoerythroblastosis 22.22 14.41 4 13145 9 29939320
Completed suicide 22.15 14.41 8 13141 99484 29839845
Marrow hyperplasia 22.04 14.41 10 13139 955 29938374
Thrombocytosis 21.06 14.41 15 13134 3398 29935931
Anaemia vitamin B12 deficiency 20.72 14.41 7 13142 303 29939026
Haematocrit decreased 20.40 14.41 43 13106 30656 29908673
Gene mutation 20.32 14.41 9 13140 812 29938517
Erdheim-Chester disease 20.20 14.41 3 13146 0 29939329
Capillary fragility 20.15 14.41 5 13144 70 29939259
Red blood cell count decreased 20.03 14.41 39 13110 26282 29913047
Blood count abnormal 19.80 14.41 25 13124 11627 29927702
Myelodysplastic syndrome 19.67 14.41 32 13117 18746 29920583
Malignant neoplasm progression 19.61 14.41 73 13076 72214 29867115
Blood uric acid increased 19.18 14.41 18 13131 6005 29933324
Gangrene 19.10 14.41 16 13133 4598 29934731
Hip deformity 18.98 14.41 5 13144 90 29939239
Drug interaction 18.81 14.41 37 13112 199531 29739798
Pyrexia 18.55 14.41 204 12945 294285 29645044
Hyperchromic anaemia 18.50 14.41 4 13145 29 29939300
Pancytopenia 17.61 14.41 79 13070 84973 29854356
Product use in unapproved indication 17.22 14.41 71 13078 73622 29865707
Graft versus host disease in skin 16.96 14.41 13 13136 3294 29936035
Toxic epidermal necrolysis 16.70 14.41 29 13120 17911 29921418
Spermatozoa morphology abnormal 16.59 14.41 3 13146 7 29939322
Interstitial granulomatous dermatitis 15.66 14.41 5 13144 181 29939148
Cerebral haemorrhage 15.23 14.41 40 13109 32847 29906482
Myelodysplastic syndrome transformation 15.14 14.41 6 13143 410 29938919
Leukaemic infiltration pulmonary 15.00 14.41 3 13146 14 29939315
Second primary malignancy 14.74 14.41 16 13133 6340 29932989
Drug hypersensitivity 14.43 14.41 6 13143 68513 29870816

Pharmacologic Action:

SourceCodeDescription
ATC L01XX05 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Other antineoplastic agents
FDA CS M0022315 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
FDA EPC N0000180853 Antimetabolite
CHEBI has role CHEBI:35221 antimetabolite
CHEBI has role CHEBI:35610 cytostatic
CHEBI has role CHEBI:48578 free-radical scavenger
CHEBI has role CHEBI:50846 biomodulator
CHEBI has role CHEBI:50902 genotoxic agent
CHEBI has role CHEBI:50905 teratogen
CHEBI has role CHEBI:59517 dna synthesis inhibitors
CHEBI has role CHEBI:64911 mitosis inhibitors
CHEBI has role CHEBI:74213 ribonucleotide diphosphate reductase inhibitor

Drug Use (View source of the data)

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
Hemoglobin SS disease with crisis indication 417425009
Polycythemia vera off-label use 109992005
Essential thrombocythemia off-label use 109994006 DOID:2224
Vasculitis of the skin contraindication 53312001
Leukopenia contraindication 84828003 DOID:615
Kidney disease contraindication 90708001 DOID:557
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

Acid dissociation constants calculated using MoKa v3.0.0

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)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
100MG SIKLOS ADDMEDICA SAS N208843 Dec. 21, 2017 RX TABLET ORAL Dec. 21, 2024 TO REDUCE THE FREQUENCY OF PAINFUL CRISES AND TO REDUCE THE NEED FOR BLOOD TRANSFUSIONS IN PEDIATRIC PATIENTS, 2 YEARS OF AGE AND OLDER, WITH SICKLE CELL ANEMIA WITH RECURRENT MODERATE TO SEVERE PAINFUL CRISIS
1GM SIKLOS ADDMEDICA SAS N208843 Dec. 21, 2017 RX TABLET ORAL Dec. 21, 2024 TO REDUCE THE FREQUENCY OF PAINFUL CRISES AND TO REDUCE THE NEED FOR BLOOD TRANSFUSIONS IN PEDIATRIC PATIENTS, 2 YEARS OF AGE AND OLDER, WITH SICKLE CELL ANEMIA WITH RECURRENT MODERATE TO SEVERE PAINFUL CRISIS

Bioactivity Summary:

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:

IDSource
4017733 VUID
N0000146101 NUI
D00341 KEGG_DRUG
4017733 VANDF
C0020402 UMLSCUI
CHEBI:44423 CHEBI
NHY PDB_CHEM_ID
CHEMBL467 ChEMBL_ID
DB01005 DRUGBANK_ID
D006918 MESH_DESCRIPTOR_UI
3657 PUBCHEM_CID
6822 IUPHAR_LIGAND_ID
1991 INN_ID
X6Q56QN5QC UNII
1999309 RXNORM
148307 MMSL
1763 MMSL
4856 MMSL
d01373 MMSL
002635 NDDF
387314007 SNOMEDCT_US
56602009 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
HYDREA HUMAN PRESCRIPTION DRUG LABEL 1 0003-0830 CAPSULE 500 mg ORAL NDA 26 sections
DROXIA HUMAN PRESCRIPTION DRUG LABEL 1 0003-6335 CAPSULE 200 mg ORAL NDA 29 sections
DROXIA HUMAN PRESCRIPTION DRUG LABEL 1 0003-6336 CAPSULE 300 mg ORAL NDA 29 sections
DROXIA HUMAN PRESCRIPTION DRUG LABEL 1 0003-6337 CAPSULE 400 mg ORAL NDA 29 sections
HYDROXYUREA HUMAN PRESCRIPTION DRUG LABEL 1 0555-0882 CAPSULE 500 mg ORAL ANDA 23 sections
Hydroxyurea HUMAN PRESCRIPTION DRUG LABEL 1 0904-6939 CAPSULE 500 mg ORAL ANDA 24 sections
HYDROXYUREA HUMAN PRESCRIPTION DRUG LABEL 1 42291-321 CAPSULE 500 mg ORAL ANDA 22 sections
Hydroxyurea HUMAN PRESCRIPTION DRUG LABEL 1 49884-724 CAPSULE 500 mg ORAL ANDA 23 sections
HYDROXYUREA HUMAN PRESCRIPTION DRUG LABEL 1 54868-4773 CAPSULE 500 mg ORAL ANDA 19 sections
Hydroxyurea HUMAN PRESCRIPTION DRUG LABEL 1 55154-7143 CAPSULE 500 mg ORAL ANDA 24 sections
Hydroxyurea HUMAN PRESCRIPTION DRUG LABEL 1 60429-265 CAPSULE 500 mg ORAL ANDA 23 sections
Hydroxyurea HUMAN PRESCRIPTION DRUG LABEL 1 68084-284 CAPSULE 500 mg ORAL ANDA 26 sections
HYDROXYUREA HUMAN PRESCRIPTION DRUG LABEL 1 69315-164 CAPSULE 500 mg ORAL ANDA 17 sections
Hydroxyurea HUMAN PRESCRIPTION DRUG LABEL 1 70518-0916 CAPSULE 500 mg ORAL ANDA 23 sections
Siklos HUMAN PRESCRIPTION DRUG LABEL 1 71770-100 TABLET, FILM COATED 100 mg ORAL NDA 34 sections
Siklos HUMAN PRESCRIPTION DRUG LABEL 1 71770-105 TABLET, FILM COATED 100 mg ORAL NDA 34 sections
Siklos HUMAN PRESCRIPTION DRUG LABEL 1 71770-120 TABLET, FILM COATED 1000 mg ORAL NDA 34 sections