carmustine ๐Ÿถ Veterinary Use | 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 ยตM/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 255.08 38.04 73 2722 15059 50587270
Malignant transformation 139.60 38.04 23 2772 333 50601996
Brain oedema 127.85 38.04 41 2754 12329 50590000
Febrile neutropenia 115.57 38.04 70 2725 97597 50504732
Haematotoxicity 114.75 38.04 34 2761 7861 50594468
Mucosal inflammation 111.56 38.04 51 2744 40091 50562238
Acute myeloid leukaemia 104.45 38.04 37 2758 15037 50587292
Stem cell transplant 82.41 38.04 19 2776 1649 50600680
Second primary malignancy 75.86 38.04 24 2771 6890 50595439
Thrombocytopenia 69.62 38.04 57 2738 127616 50474713
Pneumocephalus 61.26 38.04 10 2785 136 50602193
Enterococcal infection 55.72 38.04 19 2776 6879 50595450
Venoocclusive disease 54.68 38.04 14 2781 1882 50600447
Progressive multifocal leukoencephalopathy 49.77 38.04 20 2775 11437 50590892
Intracranial hypotension 48.86 38.04 9 2786 255 50602074
Chronic myelomonocytic leukaemia 47.62 38.04 9 2786 294 50602035
Cardiomyopathy acute 44.66 38.04 8 2787 193 50602136
Bacteraemia 42.11 38.04 19 2776 14414 50587915
Pneumocystis jirovecii pneumonia 41.82 38.04 19 2776 14644 50587685
Aplasia 40.84 38.04 13 2782 3800 50598529
Neutropenia 40.18 38.04 45 2750 147920 50454409
Febrile bone marrow aplasia 38.08 38.04 14 2781 6297 50596032

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 339.73 32.72 125 5109 17669 29551624
Venoocclusive liver disease 239.53 32.72 76 5158 6841 29562452
Malignant transformation 218.48 32.72 46 5188 788 29568505
Acute myeloid leukaemia 208.43 32.72 86 5148 16427 29552866
Febrile neutropenia 183.00 32.72 154 5080 112086 29457207
Second primary malignancy 134.72 32.72 49 5185 6656 29562637
Brain oedema 122.17 32.72 54 5180 12166 29557127
Pneumocephalus 113.65 32.72 19 5215 81 29569212
Off label use 110.72 32.72 193 5041 300607 29268686
Blood stem cell transplant failure 86.53 32.72 19 5215 399 29568894
Basal cell carcinoma 77.43 32.72 44 5190 16866 29552427
Mucosal inflammation 74.27 32.72 54 5180 31541 29537752
Venoocclusive disease 71.98 32.72 24 5210 2515 29566778
Aspergillus infection 69.46 32.72 35 5199 10546 29558747
Myositis 61.65 32.72 32 5202 10251 29559042
Febrile bone marrow aplasia 59.30 32.72 28 5206 7323 29561970
Transformation to acute myeloid leukaemia 57.20 32.72 15 5219 680 29568613
Malignant neoplasm progression 55.85 32.72 67 5167 73792 29495501
Bronchopulmonary aspergillosis 53.49 32.72 31 5203 12313 29556980
Stem cell transplant 53.22 32.72 18 5216 1969 29567324
Hepatic infection fungal 52.91 32.72 11 5223 176 29569117
Neutropenic sepsis 49.62 32.72 29 5205 11698 29557595
Product use in unapproved indication 47.25 32.72 67 5167 86808 29482485
Metastases to muscle 45.49 32.72 10 5224 211 29569082
Metastases to retroperitoneum 45.22 32.72 10 5224 217 29569076
Enteritis 43.20 32.72 22 5212 6769 29562524
Human herpesvirus 8 infection 40.76 32.72 12 5222 835 29568458
Metastases to spleen 40.10 32.72 10 5224 370 29568923
Cytomegalovirus infection 39.94 32.72 33 5201 23182 29546111
B-cell lymphoma recurrent 39.75 32.72 11 5223 612 29568681
Expanded disability status scale score increased 38.71 32.72 9 5225 246 29569047
Cytopenia 38.10 32.72 23 5211 9836 29559457
Pancytopenia 37.82 32.72 59 5175 83109 29486184
Metastases to bone marrow 37.74 32.72 10 5224 472 29568821
Intracranial hypotension 34.68 32.72 8 5226 211 29569082
Retinal haemorrhage 32.81 32.72 16 5218 4488 29564805
Intentional product use issue 32.80 32.72 39 5195 42459 29526834

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
Myelodysplastic syndrome 544.00 30.53 178 7246 27401 64463907
Malignant transformation 332.50 30.53 64 7360 1077 64490231
Acute myeloid leukaemia 313.19 30.53 118 7306 27345 64463963
Febrile neutropenia 293.95 30.53 211 7213 187446 64303862
Venoocclusive liver disease 256.52 30.53 79 7345 9936 64481372
Brain oedema 223.43 30.53 87 7337 21988 64469320
Second primary malignancy 204.59 30.53 70 7354 12267 64479041
Pneumocephalus 144.75 30.53 25 7399 220 64491088
Mucosal inflammation 134.88 30.53 86 7338 62498 64428810
Haematotoxicity 134.58 30.53 52 7372 12844 64478464
Stem cell transplant 121.93 30.53 35 7389 3446 64487862
Off label use 114.91 30.53 235 7189 632571 63858737
Venoocclusive disease 108.64 30.53 33 7391 3952 64487356
Blood stem cell transplant failure 89.99 30.53 19 7405 516 64490792
Aspergillus infection 75.11 30.53 37 7387 16342 64474966
Pneumocystis jirovecii pneumonia 72.26 30.53 43 7381 27591 64463717
Malignant neoplasm progression 67.99 30.53 74 7350 112797 64378511
Basal cell carcinoma 67.91 30.53 43 7381 30795 64460513
Febrile bone marrow aplasia 65.62 30.53 30 7394 11225 64480083
Thrombocytopenia 64.52 30.53 102 7322 223699 64267609
Cytomegalovirus infection 62.90 30.53 44 7380 37155 64454153
Product use in unapproved indication 61.58 30.53 88 7336 176530 64314778
Myositis 60.56 30.53 32 7392 16345 64474963
Bronchopulmonary aspergillosis 58.68 30.53 33 7391 19052 64472256
Progressive multifocal leukoencephalopathy 57.34 30.53 32 7392 18200 64473108
Aplasia 55.07 30.53 23 7401 6930 64484378
Hemiplegia 53.11 30.53 27 7397 12741 64478567
Pneumonia respiratory syncytial viral 52.85 30.53 15 7409 1416 64489892
Intracranial hypotension 50.57 30.53 11 7413 345 64490963
Neutropenic sepsis 50.11 30.53 32 7392 23240 64468068
B-cell lymphoma recurrent 46.07 30.53 12 7412 820 64490488
Metastases to muscle 45.90 30.53 10 7414 316 64490992
Cytopenia 45.53 30.53 26 7398 15445 64475863
Metastases to retroperitoneum 44.56 30.53 10 7414 363 64490945
Human herpesvirus 8 infection 43.05 30.53 12 7412 1061 64490247
Lymphopenia 42.55 30.53 30 7394 25627 64465681
Metastases to spleen 41.52 30.53 10 7414 496 64490812
Conjunctival haemorrhage 41.08 30.53 17 7407 5004 64486304
Pancytopenia 40.79 30.53 65 7359 143244 64348064
Brain abscess 40.56 30.53 16 7408 4165 64487143
Enterococcal infection 39.99 30.53 23 7401 13843 64477465
Arthralgia 39.57 30.53 3 7421 442257 64049051
Acute respiratory distress syndrome 39.44 30.53 34 7390 38901 64452407
Metastases to bone marrow 38.76 30.53 10 7414 658 64490650
Hepatic infection fungal 38.68 30.53 8 7416 196 64491112
Neutropenia 38.47 30.53 85 7339 239539 64251769
Enteritis 37.43 30.53 21 7403 12056 64479252
Cardiomyopathy acute 37.31 30.53 8 7416 234 64491074
Transformation to acute myeloid leukaemia 36.25 30.53 10 7414 851 64490457
Staphylococcal infection 35.41 30.53 36 7388 50642 64440666
Fatigue 34.42 30.53 22 7402 748708 63742600
Respiratory tract infection fungal 33.90 30.53 10 7414 1082 64490226
Cystitis haemorrhagic 33.59 30.53 17 7407 7939 64483369
Dizziness 33.18 30.53 5 7419 430158 64061150
Chronic myelomonocytic leukaemia 32.85 30.53 9 7415 746 64490562
Human herpesvirus 6 infection 32.23 30.53 14 7410 4640 64486668
Implant site oedema 32.11 30.53 5 7419 21 64491287
Malaise 31.99 30.53 4 7420 396243 64095065
Expanded disability status scale score increased 31.96 30.53 8 7416 466 64490842
Myelosuppression 30.83 30.53 24 7400 23806 64467502
Herpes simplex reactivation 30.78 30.53 7 7417 270 64491038

FDA Adverse Event Reporting System (Pediatric)

None

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 antineoplastic agents
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|

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




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 11.09 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
2105 RXNORM
4018136 VANDF
4020993 VANDF
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
251354 MMSL
4360 MMSL
d01342 MMSL
002640 NDDF
387281007 SNOMEDCT_US
51326002 SNOMEDCT_US
786790001 SNOMEDCT_US

Pharmaceutical products:

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