dacarbazine 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
	773	4342-03-4

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: deticene dacarbazine	An antineoplastic agent. It has significant activity against melanomas. (from Martindale, The Extra Pharmacopoeia, 31st ed, p564) Molecular weight: 182.19 Formula: C6H10N6O CLOGP: 0.47 LIPINSKI: 0 HAC: 7 HDO: 2 TPSA: 99.73 ALOGS: -2.12 ROTB: 3 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

deticene
dacarbazine

An antineoplastic agent. It has significant activity against melanomas. (from Martindale, The Extra Pharmacopoeia, 31st ed, p564)

Molecular weight: 182.19
Formula: C6H10N6O
CLOGP: 0.47
LIPINSKI: 0
HAC: 7
HDO: 2
TPSA: 99.73
ALOGS: -2.12
ROTB: 3

Status: OFP

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

Drug dosage:

None

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	3	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	4.20 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	39 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	24.70 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
Vd (Volume of distribution)	1.20 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	2.60 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)	6.20 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
May 27, 1975	FDA	BAYER HLTHCARE

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	169.29	27.40	109	4726	97558	50502731
Neutropenia	137.04	27.40	113	4722	147852	50452437
Pulmonary toxicity	124.93	27.40	38	4797	5524	50594765
Disease progression	88.11	27.40	73	4762	95793	50504496
Malignant neoplasm progression	64.88	27.40	53	4782	68071	50532218
Tissue infiltration	64.19	27.40	14	4821	539	50599750
Basal ganglion degeneration	62.58	27.40	13	4822	395	50599894
Second primary malignancy	59.37	27.40	23	4812	6891	50593398
Uterine enlargement	55.05	27.40	14	4821	1052	50599237
Exposure during pregnancy	48.95	27.40	59	4776	120956	50479333
Inguinal hernia	48.53	27.40	14	4821	1692	50598597
Anaesthesia	46.77	27.40	10	4825	350	50599939
Dysaesthesia	45.23	27.40	16	4819	3719	50596570
Cardiotoxicity	45.22	27.40	19	4816	7008	50593281
Psychogenic seizure	45.05	27.40	13	4822	1572	50598717
Myelodysplastic syndrome	44.92	27.40	24	4811	15108	50585181
Product use in unapproved indication	44.46	27.40	55	4780	115764	50484525
Interstitial lung disease	43.66	27.40	38	4797	53138	50547151
Neurological decompensation	40.45	27.40	13	4822	2257	50598032
Hypochromic anaemia	39.83	27.40	12	4823	1684	50598605
Monoplegia	37.85	27.40	13	4822	2770	50597519
Pneumocystis jirovecii pneumonia	37.30	27.40	21	4814	14642	50585647
Acute myeloid leukaemia	36.75	27.40	21	4814	15053	50585236
Premature menopause	34.11	27.40	9	4826	781	50599508
Pancytopenia	34.00	27.40	41	4794	83989	50516300
Pyrexia	33.99	27.40	96	4739	380107	50220182
Febrile bone marrow aplasia	33.83	27.40	15	4820	6296	50593993
Sarcoidosis	33.74	27.40	14	4821	5003	50595286
Pleuroparenchymal fibroelastosis	33.65	27.40	5	4830	18	50600271
Hyperpyrexia	32.93	27.40	12	4823	3037	50597252
Klebsiella infection	31.95	27.40	15	4820	7179	50593110
Lung disorder	30.83	27.40	29	4806	44770	50555519
Meningitis streptococcal	30.08	27.40	6	4829	148	50600141
Foetal exposure during pregnancy	29.67	27.40	23	4812	27336	50572953
Intervertebral disc disorder	28.76	27.40	12	4823	4348	50595941
Premature baby	28.07	27.40	19	4816	18318	50581971

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	180.17	23.44	150	4875	112090	29457412
Second primary malignancy	163.56	23.44	56	4969	6649	29562853
Acute myeloid leukaemia	114.74	23.44	56	4969	16457	29553045
Malignant neoplasm progression	108.50	23.44	94	4931	73765	29495737
Cardiotoxicity	97.91	23.44	35	4990	4709	29564793
Neutropenia	85.11	23.44	108	4917	131603	29437899
Pulmonary toxicity	82.12	23.44	31	4994	4859	29564643
Endocarditis noninfective	70.15	23.44	13	5012	115	29569387
Neutrophil count decreased	64.96	23.44	56	4969	43511	29525991
Product use in unapproved indication	62.04	23.44	75	4950	86800	29482702
Interstitial lung disease	58.74	23.44	60	4965	57658	29511844
Chronic myeloid leukaemia	57.88	23.44	19	5006	1975	29567527
Myositis	54.29	23.44	29	4996	10254	29559248
Off label use	52.98	23.44	140	4885	300660	29268842
Disease progression	46.29	23.44	63	4962	81853	29487649
Autoimmune neutropenia	43.72	23.44	10	5015	265	29569237
Pneumonitis	39.65	23.44	35	4990	28009	29541493
Acute lymphocytic leukaemia	38.17	23.44	15	5010	2616	29566886
Pneumocystis jirovecii pneumonia	36.61	23.44	27	4998	16752	29552750
Cardiac dysfunction	36.02	23.44	13	5012	1794	29567708
Ichthyosis	34.90	23.44	7	5018	97	29569405
Pneumonia salmonella	32.80	23.44	6	5019	49	29569453
Pyrexia	30.16	23.44	112	4913	287510	29281992
Spindle cell sarcoma	27.43	23.44	6	5019	129	29569373
Pulmonary fibrosis	25.17	23.44	21	5004	15561	29553941
Oropharyngeal squamous cell carcinoma	25.11	23.44	6	5019	193	29569309
Systemic candida	24.11	23.44	11	5014	2769	29566733
Pancreatic neuroendocrine tumour metastatic	23.75	23.44	5	5020	89	29569413
Vasogenic cerebral oedema	23.61	23.44	7	5018	520	29568982

FDA Adverse Event Reporting System (Geriatric)

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	294.95	20.87	228	8726	187429	64302349
Second primary malignancy	248.99	20.87	85	8869	12252	64477526
Neutropenia	200.88	20.87	204	8750	239420	64250358
Pulmonary toxicity	196.53	20.87	65	8889	8496	64481282
Malignant neoplasm progression	170.04	20.87	134	8820	112737	64377041
Acute myeloid leukaemia	167.64	20.87	80	8874	27383	64462395
Disease progression	110.04	20.87	116	8838	141564	64348214
Cardiotoxicity	101.59	20.87	42	8912	10232	64479546
Product use in unapproved indication	98.81	20.87	122	8832	176496	64313282
Interstitial lung disease	92.29	20.87	89	8865	97643	64392135
Neutrophil count decreased	81.88	20.87	75	8879	77121	64412657
Myelodysplastic syndrome	74.79	20.87	47	8907	27532	64462246
Myelitis	69.00	20.87	21	8933	2093	64487685
Endocarditis noninfective	66.84	20.87	13	8941	189	64489589
Pneumocystis jirovecii pneumonia	64.84	20.87	43	8911	27591	64462187
Off label use	59.95	20.87	208	8746	632598	63857180
Chronic myeloid leukaemia	55.57	20.87	20	8934	3354	64486424
Pyrexia	52.29	20.87	183	8771	558461	63931317
Tissue infiltration	47.87	20.87	12	8942	581	64489197
Myositis	47.15	20.87	29	8925	16348	64473430
Basal ganglion degeneration	47.02	20.87	11	8943	397	64489381
Uterine enlargement	44.60	20.87	12	8942	769	64489009
Acute lymphocytic leukaemia	43.64	20.87	18	8936	4353	64485425
Autoimmune neutropenia	41.56	20.87	10	8944	408	64489370
Sarcoidosis	40.83	20.87	19	8935	6127	64483651
Lung disorder	40.58	20.87	46	8908	60654	64429124
Pneumonitis	40.36	20.87	42	8912	50323	64439455
Pleuroparenchymal fibroelastosis	38.28	20.87	6	8948	21	64489757
Platelet toxicity	37.06	20.87	5	8949	3	64489775
Pancytopenia	36.84	20.87	69	8885	143240	64346538
Anaesthesia	36.44	20.87	9	8945	410	64489368
Intestinal perforation	36.33	20.87	24	8930	15289	64474489
Ichthyosis	34.59	20.87	7	8947	126	64489652
Psychogenic seizure	34.45	20.87	12	8942	1829	64487949
Pneumonia salmonella	34.01	20.87	6	8948	49	64489729
Ileus	33.90	20.87	27	8927	22939	64466839
Dysaesthesia	31.82	20.87	15	8939	4980	64484798
Hodgkin's disease recurrent	31.17	20.87	5	8949	21	64489757
Acute promyelocytic leukaemia	29.69	20.87	10	8944	1378	64488400
Therapy partial responder	29.12	20.87	18	8936	10230	64479548
Cytopenia	29.05	20.87	21	8933	15450	64474328
White blood cell count decreased	28.80	20.87	66	8888	157771	64332007
Respiratory failure	27.87	20.87	66	8888	161117	64328661
Left ventricular dysfunction	27.33	20.87	21	8933	16933	64472845
Lymphopenia	27.30	20.87	25	8929	25632	64464146
Metastatic malignant melanoma	27.20	20.87	11	8943	2530	64487248
Monoplegia	27.16	20.87	12	8942	3431	64486347
Hypothyroidism	25.92	20.87	30	8924	40427	64449351
Pulmonary fibrosis	25.90	20.87	26	8928	29852	64459926
Neoplasm progression	25.61	20.87	30	8924	40934	64448844
Spindle cell sarcoma	25.48	20.87	6	8948	223	64489555
Myelosuppression	24.93	20.87	23	8931	23807	64465971
Oropharyngeal squamous cell carcinoma	24.79	20.87	6	8948	251	64489527
Neuropathy peripheral	24.66	20.87	52	8902	117473	64372305
Hypochromic anaemia	24.49	20.87	10	8944	2358	64487420
Neurological decompensation	24.26	20.87	12	8942	4424	64485354
Pancreatic neuroendocrine tumour metastatic	24.11	20.87	5	8949	102	64489676
Hodgkin's disease nodular sclerosis	23.61	20.87	4	8950	25	64489753
Renal cyst	23.46	20.87	17	8937	12553	64477225
Abdominal tenderness	22.94	20.87	15	8939	9390	64480388
Rash	21.80	20.87	19	8935	458530	64031248
Inguinal hernia	21.66	20.87	12	8942	5569	64484209
Papilloma viral infection	21.59	20.87	8	8946	1456	64488322
Melanosis	21.43	20.87	4	8950	46	64489732
Intervertebral disc disorder	21.28	20.87	11	8943	4446	64485332
Cardiac valve thickening	21.28	20.87	4	8950	48	64489730
Autoimmune pancytopenia	20.95	20.87	5	8949	197	64489581
Aortic valve disease	20.93	20.87	8	8946	1585	64488193

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	L01AX04	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS ALKYLATING AGENTS Other alkylating agents
FDA MoA	N0000000236	Alkylating Activity
FDA EPC	N0000175558	Alkylating Drug
CHEBI has role	CHEBI:35610	antineoplastic agents
CHEBI has role	CHEBI:50266	Prodrugs
CHEBI has role	CHEBI:50903	carcinogen
MeSH PA	D000477	Alkylating Agents
MeSH PA	D000970	Antineoplastic Agents
MeSH PA	D018906	Antineoplastic Agents, Alkylating
MeSH PA	D009676	Noxae

Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID	DOID
Hodgkin's disease	indication	118599009
Metastatic malignant melanoma	indication	443493003
Pancreatic Neuroendocrine Tumor	off-label use	717919005
Hepatic vein thrombosis	contraindication	38739001	DOID:11512
Leukopenia	contraindication	84828003	DOID:615
Hepatic necrosis	contraindication	87248009
Kidney disease	contraindication	90708001	DOID:557
Disease of liver	contraindication	235856003	DOID:409
Anemia	contraindication	271737000	DOID:2355
Pregnancy, function	contraindication	289908002
Thrombocytopenic disorder	contraindication	302215000	DOID:1588
Bone marrow depression	contraindication	307762000
Breastfeeding (mother)	contraindication	413712001

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	11.06	acidic
pKa2	11.73	acidic
pKa3	4.18	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Matrix metalloproteinase-9	Enzyme	P14780	MMP9_HUMAN		IC50	6.26		DRUG MATRIX
DNA polymerase alpha subunit B	Enzyme	Q14181	DPOA2_HUMAN					WOMBAT-PK

External reference:

ID	Source
4018386	VUID
N0000146713	NUI
D00288	KEGG_DRUG
3098	RXNORM
4018386	VANDF
C0010927	UMLSCUI
CHEBI:4305	CHEBI
CHEMBL476	ChEMBL_ID
DB00851	DRUGBANK_ID
D003606	MESH_DESCRIPTOR_UI
135398738	PUBCHEM_CID
3232	INN_ID
9075	IUPHAR_LIGAND_ID
7GR28W0FJI	UNII
31748	MMSL
4528	MMSL
d00202	MMSL
002671	NDDF
387441003	SNOMEDCT_US
77750008	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Dacarbazine	HUMAN PRESCRIPTION DRUG LABEL	1	0143-9245	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	10 mg	INTRAVENOUS	ANDA	16 sections
Dacarbazine	HUMAN PRESCRIPTION DRUG LABEL	1	0703-5075	INJECTION, POWDER, FOR SOLUTION	200 mg	INTRAVENOUS	ANDA	17 sections
Dacarbazine	HUMAN PRESCRIPTION DRUG LABEL	1	63323-127	INJECTION, POWDER, FOR SOLUTION	10 mg	INTRAVENOUS	ANDA	14 sections
Dacarbazine	HUMAN PRESCRIPTION DRUG LABEL	1	63323-128	INJECTION, POWDER, FOR SOLUTION	10 mg	INTRAVENOUS	ANDA	14 sections