decitabine Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |
| Stem definition | Drug id | CAS RN |
|---|---|---|
| nucleosides antiviral or antineoplastic agents, cytarabine or azacitidine derivatives | 790 | 2353-33-5 |
Description:
| Molecule | Description |
|---|---|
|
Synonyms:
|
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.
Legend: OFP - off patent OFM - off market ONP - on patent |
Drug dosage:
None
ADMET properties:
| Property | Value | Reference |
|---|---|---|
| MRTD (Maximum Recommended Therapeutic Daily Dose) | 4.87 µM/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:
| Date | Agency | Company | Orphan |
|---|---|---|---|
| May 2, 2006 | FDA | Astex Pharmaceuticals, Inc. |
FDA Adverse Event Reporting System (Female)
| MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients 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 term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients 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:
| Source | Code | Description |
|---|---|---|
| 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)
| Disease | Relation | SNOMED_ID | DOID |
|---|---|---|---|
| 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 level | Dissociation constant | Type (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 strength | Trade name | Applicant | Application number | Approval date | Type | Dose form | Route | Patent number | Patent expiration date | Patent 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 strength | Trade name | Applicant | Application number | Approval date | Type | Dose form | Route | Exclusivity date | Description |
|---|---|---|---|---|---|---|---|---|---|
| 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:
| Target | Class | Pharos | UniProt | Action | Type | Activity value (-log[M]) | Mechanism action | Bioact source | MoA source |
|---|---|---|---|---|---|---|---|---|---|
| DNA (cytosine-5)-methyltransferase 1 | Enzyme | INHIBITOR | IC50 | 7.52 | CHEMBL | CHEMBL | |||
| DNA (cytosine-5)-methyltransferase 3A | Enzyme | INHIBITOR | CHEMBL | CHEMBL |
External reference:
| ID | Source |
|---|---|
| 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:
| Product | Category | Ingredients | NDC | Form | Quantity | Route | Marketing | Label |
|---|---|---|---|---|---|---|---|---|
| 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 |