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

Stem definitionDrug idCAS RN
antineoplastic, alkylating agents, (beta-chloroethyl)amine derivatives 512 154-93-8

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • carmustine
  • becenun
  • carmubris
  • carmustin
  • nitrumon
A cell-cycle phase nonspecific alkylating antineoplastic agent. It is used in the treatment of brain tumors and various other malignant neoplasms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p462) This substance may reasonably be anticipated to be a carcinogen according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (From Merck Index, 11th ed)
  • Molecular weight: 214.05
  • Formula: C5H9Cl2N3O2
  • CLOGP: 1.32
  • LIPINSKI: 0
  • HAC: 5
  • HDO: 1
  • TPSA: 61.77
  • ALOGS: -2.15
  • ROTB: 5

  • Status: OFP

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

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 3.80 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 0.50 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.55 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 11.50 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 1.20 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 78 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.23 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 0.37 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
March 7, 1977 FDA EMCURE PHARMS LTD

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
Myelodysplastic syndrome 236.25 40.08 69 2646 16591 53329760
Malignant transformation 141.48 40.08 23 2692 333 53346018
Brain oedema 127.46 40.08 41 2674 13517 53332834
Febrile neutropenia 113.65 40.08 69 2646 104867 53241484
Mucosal inflammation 109.30 40.08 50 2665 42734 53303617
Acute myeloid leukaemia 103.22 40.08 37 2678 16895 53329456
Stem cell transplant 82.05 40.08 19 2696 1826 53344525
Second primary malignancy 77.06 40.08 24 2691 7108 53339243
Pneumocephalus 61.35 40.08 10 2705 147 53346204
Thrombocytopenia 61.29 40.08 53 2662 138674 53207677
Enterococcal infection 55.45 40.08 19 2696 7579 53338772
Haematotoxicity 54.73 40.08 19 2696 7878 53338473
Venoocclusive disease 54.70 40.08 14 2701 2041 53344310
Progressive multifocal leukoencephalopathy 50.25 40.08 20 2695 12109 53334242
Intracranial hypotension 47.95 40.08 9 2706 308 53346043
Chronic myelomonocytic leukaemia 47.29 40.08 9 2706 332 53346019
Aplasia 44.82 40.08 14 2701 4178 53342173
Cardiomyopathy acute 44.31 40.08 8 2707 220 53346131
Bacteraemia 42.24 40.08 19 2696 15530 53330821
Pneumocystis jirovecii pneumonia 41.30 40.08 19 2696 16359 53329992

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
Myelodysplastic syndrome 335.55 31.25 124 5007 19914 32488481
Venoocclusive liver disease 243.42 31.25 76 5055 7289 32501106
Malignant transformation 224.35 31.25 46 5085 777 32507618
Acute myeloid leukaemia 198.85 31.25 84 5047 19090 32489305
Febrile neutropenia 164.96 31.25 142 4989 119424 32388971
Second primary malignancy 127.22 31.25 46 5085 6895 32501500
Brain oedema 125.08 31.25 54 5077 12906 32495489
Off label use 119.00 31.25 189 4942 306131 32202264
Pneumocephalus 114.19 31.25 19 5112 90 32508305
Blood stem cell transplant failure 88.43 31.25 19 5112 405 32507990
Mucosal inflammation 77.10 31.25 54 5077 33380 32475015
Basal cell carcinoma 75.08 31.25 42 5089 17526 32490869
Venoocclusive disease 72.83 31.25 24 5107 2722 32505673
Aspergillus infection 70.29 31.25 35 5096 11539 32496856
Malignant neoplasm progression 60.48 31.25 68 5063 78428 32429967
Myositis 59.56 31.25 31 5100 11204 32497191
Febrile bone marrow aplasia 58.76 31.25 28 5103 8387 32500008
Bronchopulmonary aspergillosis 53.82 31.25 31 5100 13656 32494739
Transformation to acute myeloid leukaemia 53.80 31.25 14 5117 692 32507703
Hepatic infection fungal 53.77 31.25 11 5120 183 32508212
Stem cell transplant 53.23 31.25 18 5113 2209 32506186
Product use in unapproved indication 51.50 31.25 66 5065 87138 32421257
Neutropenic sepsis 50.57 31.25 29 5102 12670 32495725
Diffuse large B-cell lymphoma 49.63 31.25 25 5106 8437 32499958
Metastases to muscle 46.63 31.25 10 5121 211 32508184
Metastases to retroperitoneum 46.06 31.25 10 5121 224 32508171
Enteritis 44.20 31.25 22 5109 7239 32501156
Human herpesvirus 8 infection 42.17 31.25 12 5119 831 32507564
Metastases to spleen 41.45 31.25 10 5121 362 32508033
Cytomegalovirus infection 40.59 31.25 33 5098 25431 32482964
B-cell lymphoma recurrent 40.21 31.25 11 5120 659 32507736
Cytopenia 40.11 31.25 23 5108 10041 32498354
Expanded disability status scale score increased 39.95 31.25 9 5122 240 32508155
Metastases to bone marrow 38.10 31.25 10 5121 511 32507884
Intentional product use issue 34.93 31.25 38 5093 42173 32466222
Intracranial hypotension 33.78 31.25 8 5123 267 32508128
Staphylococcal infection 33.69 31.25 33 5098 32406 32475989
Retinal haemorrhage 32.90 31.25 16 5115 5005 32503390
Myelosuppression 31.98 31.25 21 5110 11655 32496740

Pharmacologic Action:

SourceCodeDescription
ATC L01AD01 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
ALKYLATING AGENTS
Nitrosoureas
FDA MoA N0000000236 Alkylating Activity
FDA EPC N0000175558 Alkylating Drug
CHEBI has role CHEBI:35610 cytostatic
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
Glioma, malignant indication 74532006
Diffuse non-Hodgkin's lymphoma, large cell indication 109969005
Multiple myeloma indication 109989006 DOID:9538
Hodgkin's disease indication 118599009
Non-Hodgkin's lymphoma indication 118601006
Glioblastoma multiforme of brain indication 276828006 DOID:3073
Malignant neoplasm of brain indication 428061005 DOID:1319
Astrocytoma, anaplastic off-label use 55353007 DOID:3078
Allogeneic bone marrow transplantation off-label use 58390007
Mycosis fungoides off-label use 118618005
Cerebral edema contraindication 2032001
Mycosis contraindication 3218000 DOID:1564
Meningitis contraindication 7180009 DOID:9471
Disorder of lung contraindication 19829001 DOID:850
Retinal hemorrhage contraindication 28998008
Viral disease contraindication 34014006 DOID:934
Infectious disease contraindication 40733004
Fibrosis of lung contraindication 51615001 DOID:3770
Epilepsy contraindication 84757009 DOID:1826
Leukopenia contraindication 84828003 DOID:615
Bacterial infectious disease contraindication 87628006
Kidney disease contraindication 90708001 DOID:557
Acute leukemia, disease contraindication 91855006 DOID:12603
Liver function tests abnormal contraindication 166603001
Obstructive hydrocephalus contraindication 230746009 DOID:14159
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
Abscess of brain contraindication 441806004
Protozoal Infection contraindication
Significant Bleeding contraindication
Pulmonary Infiltrates contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 11.09 acidic

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
Glutathione reductase, mitochondrial Enzyme INHIBITOR IC50 5.09 CHEMBL CHEMBL

External reference:

IDSource
4020993 VUID
N0000148463 NUI
D00254 KEGG_DRUG
C0007257 UMLSCUI
CHEBI:3423 CHEBI
CHEMBL513 ChEMBL_ID
DB00262 DRUGBANK_ID
D002330 MESH_DESCRIPTOR_UI
2578 PUBCHEM_CID
2959 INN_ID
6800 IUPHAR_LIGAND_ID
U68WG3173Y UNII
2105 RXNORM
251354 MMSL
4360 MMSL
d01342 MMSL
002640 NDDF
387281007 SNOMEDCT_US
51326002 SNOMEDCT_US
786790001 SNOMEDCT_US
4018136 VANDF
4020993 VANDF

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Gliadel HUMAN PRESCRIPTION DRUG LABEL 1 24338-050 WAFER 7.70 mg INTRACAVITARY NDA 25 sections