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

Stem definitionDrug idCAS RN
nucleosides antiviral or antineoplastic agents, cytarabine or azacitidine derivatives 790 2353-33-5

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • decitabine mesylate
  • decitabine mesilate
  • decitabine
  • dacogen
An azacitidine derivative and antineoplastic antimetabolite. It inhibits DNA methyltransferase to re-activate silent genes, limiting METASTASIS and NEOPLASM DRUG RESISTANCE. Decitabine is used in the treatment of MYELODISPLASTIC SYNDROMES, and ACUTE MYELOID LEUKEMIA.
  • Molecular weight: 228.21
  • Formula: C8H12N4O4
  • CLOGP: -1.90
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 3
  • TPSA: 120.74
  • ALOGS: -1.62
  • ROTB: 2

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
MRTD (Maximum Recommended Therapeutic Daily Dose) 4.87 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
Vd (Volume of distribution) 4.60 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 130 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) 0.58 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
May 2, 2006 FDA Astex Pharmaceuticals, Inc.

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
Febrile neutropenia 279.60 32.47 128 2747 104808 53241383
Acute myeloid leukaemia 167.76 32.47 54 2821 16878 53329313
Neutropenia 86.19 32.47 70 2805 159115 53187076
Bone marrow failure 77.40 32.47 36 2839 30079 53316112
Myelodysplastic syndrome 76.32 32.47 30 2845 16630 53329561
Pneumonia 65.62 32.47 94 2781 407075 52939116
Pancytopenia 59.97 32.47 45 2830 90883 53255308
Sepsis 58.12 32.47 54 2821 146375 53199816
Thrombocytopenia 56.68 32.47 52 2823 138675 53207516
Acute myeloid leukaemia recurrent 53.04 32.47 13 2862 1500 53344691
Haematotoxicity 46.16 32.47 17 2858 7880 53338311
Off label use 44.82 32.47 86 2789 472126 52874065
Product use in unapproved indication 41.80 32.47 40 2835 112249 53233942
Pyrexia 40.14 32.47 75 2800 403118 52943073

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
Febrile neutropenia 283.43 25.07 183 4137 119383 32389823
Acute myeloid leukaemia 266.97 25.07 99 4221 19075 32490131
Neutropenia 88.00 25.07 101 4219 142074 32367132
Bone marrow failure 87.75 25.07 53 4267 30351 32478855
Pancytopenia 68.82 25.07 72 4248 91163 32418043
Off label use 60.26 25.07 128 4192 306192 32203014
Infection 57.07 25.07 63 4257 84652 32424554
Pneumonia 54.97 25.07 135 4185 355117 32154089
Sepsis 50.83 25.07 82 4238 158752 32350454
Product use in unapproved indication 47.25 25.07 58 4262 87146 32422060
Acute myeloid leukaemia recurrent 46.32 25.07 15 4305 1915 32507291
Platelet count decreased 44.86 25.07 65 4255 114526 32394680
Acute myeloid leukaemia refractory 42.63 25.07 7 4313 37 32509169
Aspergillus infection 40.81 25.07 23 4297 11551 32497655
Pyrexia 34.76 25.07 107 4213 319861 32189345
Cytopenia 32.80 25.07 19 4301 10045 32499161
Thrombocytopenia 32.53 25.07 65 4255 148234 32360972
Myelodysplastic syndrome 31.49 25.07 24 4296 20014 32489192
Respiratory failure 29.75 25.07 52 4268 107130 32402076
Mucormycosis 27.72 25.07 14 4306 5640 32503566
Choroidal effusion 27.31 25.07 6 4314 170 32509036
Haematotoxicity 25.34 25.07 14 4306 6762 32502444

Pharmacologic Action:

SourceCodeDescription
ATC L01BC08 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
ANTIMETABOLITES
Pyrimidine analogues
FDA MoA N0000000233 Nucleic Acid Synthesis Inhibitors
FDA EPC N0000175595 Nucleoside Metabolic Inhibitor
MeSH PA D000963 Antimetabolites
MeSH PA D000964 Antimetabolites, Antineoplastic
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D009676 Noxae

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Acute myeloid leukemia, disease indication 91861009
Myelodysplastic syndrome indication 109995007
Diabetes mellitus contraindication 73211009 DOID:9351
Kidney disease contraindication 90708001 DOID:557
Disease of liver contraindication 235856003 DOID:409
Pregnancy, function contraindication 289908002
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Neutropenic disorder contraindication 303011007 DOID:1227
Breastfeeding (mother) contraindication 413712001

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 12.94 acidic
pKa2 13.68 acidic
pKa3 4.39 Basic
pKa4 2.93 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
100MG;35MG INQOVI OTSUKA N212576 July 7, 2020 RX TABLET ORAL 8618075 Oct. 16, 2028 METHOD FOR INHIBITING CYTIDINE DEAMINASE BY ADMINISTERING CEDAZURIDINE
100MG;35MG INQOVI OTSUKA N212576 July 7, 2020 RX TABLET ORAL 8618075 Oct. 16, 2028 METHOD FOR INHIBITING DEGRADATION OF A CDA SUBSTRATE BY ADMINISTERING CEDAZURIDINE
100MG;35MG INQOVI OTSUKA N212576 July 7, 2020 RX TABLET ORAL 8268800 Aug. 22, 2030 METHOD FOR INHIBITING CYTIDINE DEAMINASE BY ADMINISTERING CEDAZURIDINE
100MG;35MG INQOVI OTSUKA N212576 July 7, 2020 RX TABLET ORAL 8268800 Aug. 22, 2030 METHOD FOR INHIBITING DEGRADATION OF A CDA SUBSTRATE BY ADMINISTERING CEDAZURIDINE
100MG;35MG INQOVI OTSUKA N212576 July 7, 2020 RX TABLET ORAL 8268800 Aug. 22, 2030 TREATMENT OF CHRONIC MYELOMONOCYTIC LEUKEMIA
100MG;35MG INQOVI OTSUKA N212576 July 7, 2020 RX TABLET ORAL 8268800 Aug. 22, 2030 TREATMENT OF MYELODYSPLASTIC SYNDROME

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
100MG;35MG INQOVI OTSUKA N212576 July 7, 2020 RX TABLET ORAL July 7, 2025 NEW CHEMICAL ENTITY
100MG;35MG INQOVI OTSUKA N212576 July 7, 2020 RX TABLET ORAL July 7, 2027 TREATMENT OF ADULT PATIENTS WITH MYELODYSPLASTIC SYNDROMES (MDS), INCLUDING PREVIOUSLY TREATED AND UNTREATED, DE NOVO AND SECONDARY MDS WITH THE FOLLOWING FRENCH-AMERICAN-BRITISH SUBTYPES (REFRACTORY ANEMIA, REFRACTORY ANEMIA WITH RINGED SIDEROBLASTS, REFRACTORY ANEMIA WITH EXCESS BLASTS, AND CHRONIC MYELOMONOCYTIC LEUKEMIA [CMML]) AND INTERMEDIATE-1, INTERMEDIATE-2, AND HIGH-RISK INTERNATIONAL PROGNOSTIC SCORING SYSTEM GROUPS.

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
DNA (cytosine-5)-methyltransferase 1 Enzyme INHIBITOR IC50 7.52 CHEMBL CHEMBL
DNA (cytosine-5)-methyltransferase 3A Enzyme INHIBITOR CHEMBL CHEMBL

External reference:

IDSource
4025438 VUID
N0000179023 NUI
D03665 KEGG_DRUG
879492-57-6 SECONDARY_CAS_RN
C0049065 UMLSCUI
CHEBI:50131 CHEBI
CHEMBL1201129 ChEMBL_ID
DB01262 DRUGBANK_ID
D000077209 MESH_DESCRIPTOR_UI
451668 PUBCHEM_CID
6374 INN_ID
6805 IUPHAR_LIGAND_ID
776B62CQ27 UNII
15657 RXNORM
203877 MMSL
21366 MMSL
81707 MMSL
d05788 MMSL
011499 NDDF
420517007 SNOMEDCT_US
420759005 SNOMEDCT_US
4025438 VANDF

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Decitabine Human Prescription Drug Label 1 0781-3296 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS ANDA 27 sections
Decitabine HUMAN PRESCRIPTION DRUG LABEL 1 16714-749 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS ANDA 25 sections
Decitabine HUMAN PRESCRIPTION DRUG LABEL 1 16714-928 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS ANDA 27 sections
Decitabine HUMAN PRESCRIPTION DRUG LABEL 1 16729-224 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS ANDA 27 sections
decitabine HUMAN PRESCRIPTION DRUG LABEL 1 25021-231 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS ANDA 27 sections
Decitabine HUMAN PRESCRIPTION DRUG LABEL 1 43598-348 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS ANDA 27 sections
Decitabine HUMAN PRESCRIPTION DRUG LABEL 1 43598-427 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS ANDA 27 sections
DECITABINE HUMAN PRESCRIPTION DRUG LABEL 1 50742-430 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS ANDA 24 sections
Decitabine HUMAN PRESCRIPTION DRUG LABEL 1 55111-556 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS ANDA 27 sections
Decitabine Human Prescription Drug Label 1 55150-376 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS ANDA 27 sections
Dacogen HUMAN PRESCRIPTION DRUG LABEL 1 59148-046 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS NDA 30 sections
Decitabine HUMAN PRESCRIPTION DRUG LABEL 1 63323-825 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS ANDA 27 sections
Decitabine HUMAN PRESCRIPTION DRUG LABEL 1 64679-067 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS ANDA 24 sections
INQOVI HUMAN PRESCRIPTION DRUG LABEL 2 64842-0727 TABLET, FILM COATED 35 mg ORAL NDA 31 sections
Decitabine HUMAN PRESCRIPTION DRUG LABEL 1 67184-0535 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS ANDA 28 sections
Decitabine HUMAN PRESCRIPTION DRUG LABEL 1 67457-316 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS ANDA 27 sections
Decitabine HUMAN PRESCRIPTION DRUG LABEL 1 68001-422 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS ANDA 27 sections
decitabine Human Prescription Drug Label 1 68083-528 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS ANDA 27 sections
decitabine HUMAN PRESCRIPTION DRUG LABEL 1 68180-738 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS ANDA 25 sections
Decitabine HUMAN PRESCRIPTION DRUG LABEL 1 69097-285 INJECTION 50 mg INTRAVENOUS ANDA 24 sections
Decitabine HUMAN PRESCRIPTION DRUG LABEL 1 69097-905 INJECTION 50 mg INTRAVENOUS ANDA 21 sections
Decitabine Human Prescription Drug Label 1 69539-115 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS ANDA 27 sections
Decitabine HUMAN PRESCRIPTION DRUG LABEL 1 70121-1644 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS ANDA 28 sections
Decitabine HUMAN PRESCRIPTION DRUG LABEL 1 70860-219 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS ANDA 28 sections
Decitabine HUMAN PRESCRIPTION DRUG LABEL 1 71288-119 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS ANDA 27 sections
Decitabine Human Prescription Drug Label 1 72205-031 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS ANDA 27 sections
Decitabine Human Prescription Drug Label 1 72205-036 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS ANDA 27 sections
Decitabine Human Prescription Drug Label 1 72603-107 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS ANDA 27 sections
DECITABINE Human Prescription Drug Label 1 75834-190 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS ANDA 27 sections