dacarbazine ๐Ÿถ Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
773 4342-03-4

Description:

MoleculeDescription

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:

PropertyValueReference
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 ยตM/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:

DateAgencyCompanyOrphan
May 27, 1975 FDA BAYER HLTHCARE

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 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 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 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 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 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:

SourceCodeDescription
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 (View source of the data)

DiseaseRelationSNOMED_IDDOID
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




๐Ÿถ Veterinary Drug Use

None

๐Ÿถ Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (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:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Matrix metalloproteinase-9 Enzyme IC50 6.26 DRUG MATRIX
DNA polymerase alpha subunit B Enzyme WOMBAT-PK

External reference:

IDSource
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:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
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