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
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

Molecule

Description

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:

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	234.94	34.17	107	2200	94520	46589235
Acute myeloid leukaemia	163.55	34.17	51	2256	15727	46668028
Bone marrow failure	77.76	34.17	35	2272	29634	46654121
Myelodysplastic syndrome	73.33	34.17	28	2279	15683	46668072
Neutropenia	55.24	34.17	50	2257	143154	46540601
Pancytopenia	54.61	34.17	40	2267	85018	46598737
Pneumonia	50.31	34.17	76	2231	376244	46307511
Haematotoxicity	49.78	34.17	17	2290	6916	46676839
Off label use	45.57	34.17	73	2234	379768	46303987
Acute myeloid leukaemia recurrent	44.89	34.17	11	2296	1385	46682370
Sepsis	43.81	34.17	43	2264	135971	46547784
Pyrexia	36.35	34.17	63	2244	348739	46335016
Product use in unapproved indication	35.68	34.17	32	2275	90241	46593514

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	248.88	24.96	154	3337	106539	29842448
Acute myeloid leukaemia	236.44	24.96	86	3405	17920	29931067
Bone marrow failure	95.29	24.96	53	3438	29732	29919255
Pancytopenia	56.50	24.96	59	3432	84993	29863994
Pneumonia	53.76	24.96	119	3372	334187	29614800
Product use in unapproved indication	52.32	24.96	53	3438	73640	29875347
Off label use	50.89	24.96	98	3393	249192	29699795
Sepsis	46.28	24.96	70	3421	146325	29802662
Neutropenia	44.26	24.96	64	3427	128476	29820511
Infection	41.14	24.96	48	3443	78026	29870961
Acute myeloid leukaemia refractory	40.03	24.96	6	3485	18	29948969
Acute myeloid leukaemia recurrent	38.54	24.96	12	3479	1540	29947447
Aspergillus infection	37.67	24.96	20	3471	10194	29938793
Respiratory failure	35.91	24.96	51	3440	100591	29848396
Platelet count decreased	35.27	24.96	52	3439	106077	29842910
Myelodysplastic syndrome	31.02	24.96	22	3469	18756	29930231
Choroidal effusion	28.41	24.96	6	3485	161	29948826
Haematotoxicity	28.31	24.96	14	3477	6156	29942831
Mucormycosis	27.32	24.96	13	3478	5255	29943732
Pyrexia	26.78	24.96	85	3406	294404	29654583

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)

None

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 INTERNULLTIONULLL 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	P26358	DNMT1_HUMAN	INHIBITOR				WOMBAT-PK	CHEMBL
DNA (cytosine-5)-methyltransferase 3A	Enzyme	Q9Y6K1	DNM3A_HUMAN	INHIBITOR				CHEMBL	CHEMBL

External reference:

ID	Source
4025438	VUID
N0000179023	NUI
D03665	KEGG_DRUG
879492-57-6	SECONDARY_CAS_RN
4025438	VANDF
C1712036	UMLSCUI
CHEBI:50131	CHEBI
CHEMBL1201129	ChEMBL_ID
DB01262	DRUGBANK_ID
D000077209	MESH_DESCRIPTOR_UI
451668	PUBCHEM_CID
6805	IUPHAR_LIGAND_ID
6374	INN_ID
776B62CQ27	UNII
15657	RXNORM
203877	MMSL
21366	MMSL
81707	MMSL
d05788	MMSL
011499	NDDF
420517007	SNOMEDCT_US
420759005	SNOMEDCT_US

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
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	68001-347	INJECTION	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	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	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	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