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

Stem definitionDrug idCAS RN
nucleosides antiviral or antineoplastic agents, cytarabine or azacitidine derivatives 25 320-67-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • 5-azacytidine
  • azacitidine
  • azacytidine
  • ladakamycin
  • ledakamycin
  • vidaza
  • U-18496
A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent.
  • Molecular weight: 244.21
  • Formula: C8H12N4O5
  • CLOGP: -2.20
  • LIPINSKI: 0
  • HAC: 9
  • HDO: 4
  • TPSA: 140.97
  • ALOGS: -1.30
  • 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) 177.10 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 89 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 62 % Benet LZ, Broccatelli F, Oprea TI
Vd (Volume of distribution) 0.47 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 35 mL/min/kg Lombardo F, Berellini G, Obach RS
t_half (Half-life) 0.36 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Aug. 2, 2019 EMA Celgene Europe BV
May 19, 2004 FDA CELGENE

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 1330.69 55.67 314 2479 10568 2344724
Acute myeloid leukaemia 968.84 55.67 190 2603 2520 2352772
Pneumonia 674.02 55.67 263 2530 49033 2306259
Death 599.60 55.67 280 2513 81188 2274104
Sepsis 519.26 55.67 169 2624 18319 2336973
Thrombocytopenia 449.58 55.67 153 2640 18978 2336314
Myelodysplastic syndrome 368.47 55.67 85 2708 2475 2352817
Pyrexia 332.43 55.67 165 2628 53543 2301749
Pancytopenia 321.73 55.67 105 2688 11347 2343945
Platelet count decreased 266.26 55.67 99 2694 15714 2339578
Anaemia 254.08 55.67 120 2673 34672 2320620
Neutropenia 243.29 55.67 101 2692 21447 2333845
Septic shock 211.26 55.67 68 2725 6986 2348306
Neutrophil count decreased 175.10 55.67 58 2735 6509 2348783
White blood cell count decreased 170.99 55.67 75 2718 18133 2337159
Constipation 149.44 55.67 72 2721 21557 2333735
Respiratory failure 144.24 55.67 61 2732 13467 2341825
Myelodysplastic syndrome transformation 142.74 55.67 24 2769 118 2355174
Acute myeloid leukaemia recurrent 127.04 55.67 23 2770 185 2355107
Bronchopulmonary aspergillosis 121.40 55.67 29 2764 975 2354317
Infection 121.37 55.67 59 2734 17970 2337322
General physical health deterioration 119.01 55.67 54 2739 14085 2341207
Cardiac failure 117.22 55.67 51 2742 12043 2343249
Pleural effusion 99.53 55.67 45 2748 11623 2343669
Haemoglobin decreased 97.49 55.67 51 2742 18100 2337192
Multiple organ dysfunction syndrome 93.30 55.67 38 2755 7603 2347689
Nausea 89.24 55.67 100 2693 112089 2243203
Cellulitis 83.27 55.67 37 2756 9164 2346128
Vomiting 82.51 55.67 78 2715 71524 2283768
Blast cell count increased 80.19 55.67 14 2779 89 2355203
Pneumonia fungal 78.18 55.67 17 2776 371 2354921
Therapy non-responder 77.88 55.67 34 2759 8070 2347222
Transformation to acute myeloid leukaemia 76.29 55.67 12 2781 35 2355257
Cerebral haemorrhage 76.29 55.67 30 2763 5474 2349818
Pericarditis 72.25 55.67 21 2772 1519 2353773
Bone marrow failure 71.87 55.67 29 2764 5657 2349635
Acute febrile neutrophilic dermatosis 70.04 55.67 16 2777 440 2354852
Organising pneumonia 69.33 55.67 18 2775 853 2354439
Interstitial lung disease 66.15 55.67 30 2763 7782 2347510
Epistaxis 65.69 55.67 32 2761 9747 2345545
Disease progression 64.23 55.67 38 2755 17057 2338235
Hypotension 61.21 55.67 47 2746 32389 2322903
Asthenia 59.49 55.67 54 2739 46872 2308420
Cytopenia 57.42 55.67 16 2777 993 2354299
Bacteraemia 57.12 55.67 18 2775 1712 2353580
Pneumonitis 55.90 55.67 22 2771 4017 2351275

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 2084.13 54.70 551 4062 10549 1731619
Acute myeloid leukaemia 1446.52 54.70 321 4292 2720 1739448
Pneumonia 1370.67 54.70 568 4045 45614 1696554
Sepsis 943.42 54.70 344 4269 19094 1723074
Myelodysplastic syndrome 705.32 54.70 183 4430 3106 1739062
Death 685.87 54.70 441 4172 87002 1655166
Platelet count decreased 655.68 54.70 253 4360 16270 1725898
Anaemia 523.92 54.70 256 4357 29201 1712967
Neutrophil count decreased 514.33 54.70 164 4449 5917 1736251
White blood cell count decreased 452.47 54.70 182 4431 12967 1729201
Neutropenia 420.24 54.70 190 4423 18070 1724098
Thrombocytopenia 414.12 54.70 197 4416 21052 1721116
Pyrexia 381.73 54.70 243 4370 46157 1696011
Pancytopenia 358.79 54.70 148 4465 11209 1730959
Septic shock 315.96 54.70 123 4490 7986 1734182
Infection 247.33 54.70 117 4496 12243 1729925
Myelodysplastic syndrome transformation 230.18 54.70 43 4570 126 1742042
Blast cell count increased 211.24 54.70 41 4572 156 1742012
Constipation 180.83 54.70 101 4512 14899 1727269
Pneumonia fungal 153.17 54.70 37 4576 454 1741714
Cardiac failure 152.19 54.70 85 4528 12517 1729651
General physical health deterioration 146.32 54.70 84 4529 13034 1729134
Haemoglobin decreased 142.93 54.70 91 4522 17023 1725145
Acute myeloid leukaemia recurrent 135.76 54.70 30 4583 240 1741928
Respiratory failure 128.26 54.70 80 4533 14425 1727743
Organising pneumonia 126.49 54.70 36 4577 862 1741306
Therapy non-responder 121.03 54.70 58 4555 6208 1735960
Cerebral haemorrhage 120.93 54.70 58 4555 6219 1735949
Interstitial lung disease 113.17 54.70 64 4549 9632 1732536
Acute kidney injury 107.93 54.70 103 4510 34841 1707327
Chronic myelomonocytic leukaemia 107.39 54.70 23 4590 156 1742012
Disseminated intravascular coagulation 103.31 54.70 44 4569 3570 1738598
Acute febrile neutrophilic dermatosis 103.07 54.70 25 4588 312 1741856
Pleural effusion 102.52 54.70 63 4550 11047 1731121
Injection site reaction 96.32 54.70 41 4572 3321 1738847
Multiple organ dysfunction syndrome 94.52 54.70 56 4557 9186 1732982
Diarrhoea 91.63 54.70 116 4497 53736 1688432
Cellulitis 90.07 54.70 48 4565 6420 1735748
Transformation to acute myeloid leukaemia 86.09 54.70 16 4597 45 1742123
Bronchopulmonary aspergillosis 83.60 54.70 30 4583 1536 1740632
Epistaxis 78.88 54.70 48 4565 8258 1733910
C-reactive protein increased 77.25 54.70 42 4571 5843 1736325
Atrial fibrillation 76.04 54.70 59 4554 15052 1727116
Asthenia 75.85 54.70 85 4528 34585 1707583
Pyoderma gangrenosum 75.08 54.70 19 4594 285 1741883
Neutropenic sepsis 73.73 54.70 27 4586 1465 1740703
Renal failure 71.32 54.70 64 4549 19953 1722215
Leukopenia 67.93 54.70 44 4569 8436 1733732
Disease progression 67.10 54.70 58 4555 17205 1724963
Bone marrow failure 65.17 54.70 36 4577 5164 1737004
Red blood cell count decreased 64.74 54.70 32 4581 3654 1738514
Enteritis infectious 61.26 54.70 15 4598 195 1741973
Bacteraemia 60.78 54.70 25 4588 1855 1740313
Subdural haematoma 60.68 54.70 30 4583 3427 1738741
Blood creatinine increased 60.64 54.70 50 4563 13896 1728272
Blood urea increased 60.09 54.70 33 4580 4678 1737490
Febrile bone marrow aplasia 59.10 54.70 20 4593 858 1741310
Urinary tract infection 58.48 54.70 43 4570 10110 1732058
Blood product transfusion dependent 57.00 54.70 12 4601 74 1742094
Hyponatraemia 56.12 54.70 40 4573 8960 1733208
Dyspnoea 55.65 54.70 90 4523 51969 1690199
Renal impairment 55.32 54.70 45 4568 12269 1729899
Colitis 55.30 54.70 30 4583 4150 1738018
Pericarditis 55.03 54.70 22 4591 1516 1740652

Pharmacologic Action:

SourceCodeDescription
ATC L01BC07 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
ANTIMETABOLITES
Pyrimidine analogues
FDA MoA N0000000233 Nucleic Acid Synthesis Inhibitors
FDA EPC N0000175595 Nucleoside Metabolic Inhibitor
CHEBI has role CHEBI:35610 antineoplastic agent
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
Chronic myelomonocytic leukemia indication 127225006
Hepatic failure contraindication 59927004
Kidney disease contraindication 90708001 DOID:557
Pregnancy, function contraindication 289908002
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Neutropenic disorder contraindication 303011007 DOID:1227
Breastfeeding (mother) contraindication 413712001
Advanced Malignant Neoplasm of Liver contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 12.32 acidic
pKa2 12.92 acidic
pKa3 13.79 acidic
pKa4 4.43 Basic
pKa5 2.98 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

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

External reference:

IDSource
D001374 MESH_DESCRIPTOR_UI
4021468 VUID
N0000148852 NUI
C0004475 UMLSCUI
D03021 KEGG_DRUG
412328000 SNOMEDCT_US
88551000 SNOMEDCT_US
412329008 SNOMEDCT_US
1251 RXNORM
4021468 VANDF
18639 MMSL
d05293 MMSL
008661 NDDF
205981 MMSL
9444 PUBCHEM_CID
CHEBI:2038 CHEBI
CHEMBL1489 ChEMBL_ID
DB00928 DRUGBANK_ID
M801H13NRU UNII
4520 INN_ID
5AE PDB_CHEM_ID
6796 IUPHAR_LIGAND_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Azacitidine HUMAN PRESCRIPTION DRUG LABEL 1 0781-3253 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg SUBCUTANEOUS NDA authorized generic 18 sections
Azacitidine HUMAN PRESCRIPTION DRUG LABEL 1 0781-9253 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg SUBCUTANEOUS NDA AUTHORIZED GENERIC 18 sections
Azacitidine HUMAN PRESCRIPTION DRUG LABEL 1 16714-777 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg INTRAVENOUS ANDA 17 sections
Azacitidine HUMAN PRESCRIPTION DRUG LABEL 1 16714-927 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg SUBCUTANEOUS ANDA 17 sections
Azacitidine HUMAN PRESCRIPTION DRUG LABEL 1 16729-306 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg INTRAVENOUS ANDA 17 sections
Azacitidine HUMAN PRESCRIPTION DRUG LABEL 1 43598-305 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg SUBCUTANEOUS ANDA 17 sections
Azacitidine HUMAN PRESCRIPTION DRUG LABEL 1 43598-465 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg SUBCUTANEOUS ANDA 17 sections
AZACITIDINE HUMAN PRESCRIPTION DRUG LABEL 1 43598-678 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg INTRAVENOUS ANDA 17 sections
Azacitidine HUMAN PRESCRIPTION DRUG LABEL 1 43817-906 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg SUBCUTANEOUS ANDA 18 sections
Azacitidine HUMAN PRESCRIPTION DRUG LABEL 1 51991-797 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg SUBCUTANEOUS ANDA 18 sections
VIDAZA HUMAN PRESCRIPTION DRUG LABEL 1 59572-102 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg INTRAVENOUS NDA 16 sections
Azacitidine HUMAN PRESCRIPTION DRUG LABEL 1 63323-771 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg INTRAVENOUS ANDA 18 sections
AZACITIDINE HUMAN PRESCRIPTION DRUG LABEL 1 64679-096 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg INTRAVENOUS ANDA 17 sections
Azacitidine HUMAN PRESCRIPTION DRUG LABEL 1 67457-254 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg INTRAVENOUS ANDA 17 sections
Azacitidine HUMAN PRESCRIPTION DRUG LABEL 1 68001-313 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg INTRAVENOUS NDA 17 sections
Azacitidine HUMAN PRESCRIPTION DRUG LABEL 1 69097-368 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg INTRAVENOUS ANDA 17 sections
azacitidine for HUMAN PRESCRIPTION DRUG LABEL 1 69097-805 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg INTRAVENOUS ANDA 17 sections
AZACITIDINE HUMAN PRESCRIPTION DRUG LABEL 1 72485-201 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg INTRAVENOUS ANDA 18 sections
AZACITIDINE HUMAN PRESCRIPTION DRUG LABEL 1 72606-558 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg INTRAVENOUS ANDA 17 sections