carfilzomib Indications/Contra | FAERs | Orange Book | BioActivity |

Stem definitionDrug idCAS RN
proteasome inhibitors 4483 868540-17-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • carfilzomib
  • kyprolis
  • PR-171
  • PR 171
epoxomicin derivative proteasome inhibitor with antiproliferative and proapoptotic effects on primary human acute myeloid leukaemia cells
  • Molecular weight: 719.92
  • Formula: C40H57N5O7
  • CLOGP: 6.40
  • LIPINSKI: 3
  • HAC: 12
  • HDO: 4
  • TPSA: 158.47
  • ALOGS: -5.17
  • ROTB: 20

Drug dosage:

None

Approvals:

DateAgencyCompanyOrphan
July 20, 2012 FDA ONYX PHARMS
July 4, 2016 PMDA Ono Pharmaceutical

FDA Adverse Event Reporting System

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
Plasma cell myeloma 2152.07 41.32 595 8818 18734 4610845
Off label use 1745.51 41.32 831 8582 128282 4501297
Fatigue 964.90 41.32 586 8827 144980 4484599
Pneumonia 887.13 41.32 492 8921 102323 4527256
Death 881.12 41.32 621 8792 197542 4432037
Thrombocytopenia 854.32 41.32 376 9037 47297 4582282
Dyspnoea 730.12 41.32 484 8929 138501 4491078
Pyrexia 672.86 41.32 418 8995 106726 4522853
Disease progression 611.68 41.32 285 9128 40726 4588853
Intercepted product preparation error 589.29 41.32 93 9320 99 4629480
Platelet count decreased 530.16 41.32 246 9167 34756 4594823
Cardiac failure 496.29 41.32 218 9195 27070 4602509
Anaemia 467.57 41.32 287 9126 71273 4558306
Acute kidney injury 456.36 41.32 281 9132 70150 4559429
Asthenia 399.85 41.32 279 9134 85884 4543695
Unevaluable event 393.91 41.32 160 9253 16316 4613263
Neuropathy peripheral 388.19 41.32 176 9237 23493 4606086
Neutropenia 342.70 41.32 204 9209 47746 4581833
Sepsis 337.07 41.32 194 9219 42645 4586934
Cytopenia 297.27 41.32 81 9332 2345 4627234
Diarrhoea 293.76 41.32 295 9118 149890 4479689
Hypertension 276.79 41.32 182 9231 50616 4578963
Infection 248.17 41.32 150 9263 35992 4593587
Cardiac disorder 245.27 41.32 116 9297 16993 4612586
Malaise 241.03 41.32 211 9202 89946 4539633
Plasma cell myeloma recurrent 237.52 41.32 56 9357 886 4628693
Atrial fibrillation 236.32 41.32 138 9275 31077 4598502
Nausea 233.20 41.32 283 9130 177050 4452529
White blood cell count decreased 223.79 41.32 136 9277 32929 4596650
Pancytopenia 212.53 41.32 119 9294 24734 4604845
Product preparation error 204.63 41.32 56 9357 1646 4627933
Thrombotic microangiopathy 181.23 41.32 59 9354 3177 4626402
Renal failure 179.65 41.32 129 9284 41240 4588339
Back pain 177.90 41.32 139 9274 50460 4579119
Febrile neutropenia 172.25 41.32 106 9307 26206 4603373
Cardiac failure congestive 169.49 41.32 114 9299 32808 4596771
Feeling abnormal 168.39 41.32 118 9295 36287 4593292
Respiratory failure 168.17 41.32 110 9303 30216 4599363
Tumour lysis syndrome 167.91 41.32 56 9357 3253 4626326
Insomnia 166.85 41.32 128 9285 45217 4584362
Leukopenia 161.49 41.32 95 9318 21641 4607938
Hospitalisation 160.17 41.32 108 9305 31197 4598382
Influenza 152.44 41.32 90 9323 20633 4608946
Pulmonary hypertension 150.69 41.32 67 9346 8496 4621083
Infusion site extravasation 148.62 41.32 43 9370 1552 4628027
Cough 145.99 41.32 129 9284 55458 4574121
Neutrophil count decreased 145.96 41.32 76 9337 13647 4615932
Infusion site pain 145.15 41.32 43 9370 1688 4627891
Pulmonary embolism 144.03 41.32 105 9308 34321 4595258
Pulmonary oedema 142.45 41.32 77 9336 14909 4614670
Light chain analysis increased 142.15 41.32 30 9383 276 4629303
Thrombotic thrombocytopenic purpura 137.51 41.32 41 9372 1646 4627933
Septic shock 137.06 41.32 78 9335 16688 4612891
Haemoglobin decreased 133.44 41.32 104 9309 37553 4592026
Haemolytic anaemia 132.96 41.32 50 9363 4128 4625451
Renal disorder 129.33 41.32 62 9351 9334 4620245
Deep vein thrombosis 125.71 41.32 86 9327 25408 4604171
Ejection fraction decreased 122.15 41.32 51 9362 5545 4624034
Muscle spasms 110.75 41.32 91 9322 35399 4594180
Lymphopenia 110.08 41.32 47 9366 5400 4624179
Chills 109.47 41.32 83 9330 28756 4600823
Chest pain 108.49 41.32 105 9308 50595 4578984
Bone pain 105.54 41.32 61 9352 13425 4616154
Acute pulmonary oedema 103.67 41.32 37 9376 2632 4626947
Respiratory tract infection 103.49 41.32 49 9364 7171 4622408
Protein total increased 103.20 41.32 28 9385 795 4628784
Dehydration 102.76 41.32 94 9319 42196 4587383
Nasopharyngitis 100.53 41.32 84 9329 33433 4596146
Red blood cell count decreased 99.92 41.32 50 9363 8253 4621326
Hypoxia 99.10 41.32 58 9355 13063 4616516
Pain 95.98 41.32 132 9281 92738 4536841
Plasma cell leukaemia 95.63 41.32 23 9390 397 4629182
Posterior reversible encephalopathy syndrome 94.86 41.32 40 9373 4455 4625124
Pleural effusion 94.30 41.32 71 9342 24327 4605252
Peripheral swelling 92.94 41.32 73 9340 26619 4602960
Bone lesion 92.67 41.32 28 9385 1176 4628403
Brain natriuretic peptide increased 91.77 41.32 28 9385 1216 4628363
Constipation 91.46 41.32 88 9325 42066 4587513
Syncope 88.55 41.32 78 9335 33317 4596262
Atrial flutter 88.30 41.32 35 9378 3328 4626251
Vomiting 86.51 41.32 144 9269 119555 4510024
Upper respiratory tract infection 86.22 41.32 54 9359 13733 4615846
Plasmacytoma 85.74 41.32 25 9388 927 4628652
Laboratory test abnormal 85.09 41.32 48 9365 10085 4619494
Fluid overload 83.72 41.32 38 9375 5050 4624529
Blood creatinine increased 81.85 41.32 68 9345 26832 4602747
Bronchitis 81.19 41.32 60 9353 19980 4609599
Cardiomyopathy 79.63 41.32 39 9374 6145 4623434
Infusion site erythema 79.50 41.32 25 9388 1201 4628378
Confusional state 78.88 41.32 87 9326 48747 4580832
Haemolytic uraemic syndrome 78.73 41.32 25 9388 1240 4628339
Urinary tract infection 78.13 41.32 81 9332 42309 4587270
Decreased appetite 76.83 41.32 92 9321 56305 4573274
Cardiac failure acute 76.22 41.32 29 9384 2470 4627109
Hypertensive crisis 75.87 41.32 34 9379 4385 4625194
Mobility decreased 75.80 41.32 49 9364 13156 4616423
Pneumonitis 75.63 41.32 43 9370 9167 4620412
Acute myocardial infarction 74.13 41.32 50 9363 14409 4615170
Pain in extremity 74.05 41.32 96 9317 63643 4565936
Headache 72.56 41.32 135 9278 122238 4507341
Polyneuropathy 70.28 41.32 31 9382 3850 4625729
Hypercalcaemia 69.19 41.32 33 9380 4905 4624674
Myocardial infarction 67.98 41.32 81 9332 49295 4580284
Hypotension 65.36 41.32 93 9320 67307 4562272
Cardiotoxicity 64.57 41.32 27 9386 2943 4626636
General physical health deterioration 62.23 41.32 60 9353 28718 4600861
Hospice care 61.51 41.32 21 9392 1308 4628271
Electrocardiogram QT prolonged 60.16 41.32 45 9368 15250 4614329
Left ventricular dysfunction 59.83 41.32 25 9388 2720 4626859
Left ventricular failure 58.69 41.32 21 9392 1504 4628075
Oedema peripheral 57.99 41.32 69 9344 41903 4587676
Adverse event 57.93 41.32 45 9368 16127 4613452
Extravasation 57.64 41.32 22 9391 1889 4627690
Cellulitis 56.57 41.32 45 9368 16687 4612892
Tremor 55.77 41.32 63 9350 36196 4593383
Blood pressure increased 55.53 41.32 57 9356 29403 4600176
Renal impairment 55.10 41.32 53 9360 25285 4604294
Fluid retention 54.99 41.32 38 9375 11383 4618196
Cognitive disorder 53.13 41.32 36 9377 10445 4619134
Acute respiratory failure 52.96 41.32 30 9383 6346 4623233
Infusion related reaction 52.82 41.32 45 9368 18357 4611222
Cardiac dysfunction 52.44 41.32 14 9399 373 4629206
Lower respiratory tract infection 52.24 41.32 35 9378 9968 4619611
Infusion site swelling 50.43 41.32 16 9397 791 4628788
Gait disturbance 50.22 41.32 60 9353 36580 4592999
Muscular weakness 49.36 41.32 51 9362 26499 4603080
Therapeutic product effect incomplete 49.22 41.32 42 9371 17166 4612413
Dyspnoea exertional 49.04 41.32 34 9379 10238 4619341
Thrombosis 48.77 41.32 43 9370 18361 4611218
Hepatitis B reactivation 48.13 41.32 16 9397 918 4628661
Diastolic dysfunction 47.38 41.32 17 9396 1227 4628352
Lung infiltration 46.83 41.32 25 9388 4709 4624870
Monoclonal immunoglobulin present 46.80 41.32 12 9401 272 4629307
Sudden death 46.66 41.32 26 9387 5329 4624250
Device related infection 46.48 41.32 27 9386 5988 4623591
Acute respiratory distress syndrome 45.88 41.32 29 9384 7484 4622095
Pericarditis 45.72 41.32 22 9391 3333 4626246
Paraproteinaemia 45.43 41.32 10 9403 114 4629465
Platelet count abnormal 44.63 41.32 17 9396 1451 4628128
Parainfluenzae virus infection 44.58 41.32 13 9400 482 4629097
Acute coronary syndrome 43.61 41.32 23 9390 4227 4625352
Lung disorder 43.38 41.32 34 9379 12337 4617242
Hypophosphataemia 42.73 41.32 20 9393 2849 4626730
Phlebitis 42.72 41.32 18 9395 1999 4627580
Musculoskeletal chest pain 42.64 41.32 22 9391 3866 4625713
Supraventricular tachycardia 42.23 41.32 22 9391 3943 4625636

Pharmacologic Action:

SourceCodeDescription
ATC L01XX45 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Other antineoplastic agents
FDA MoA N0000175075 Proteasome Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:52726 proteasome inhibitor

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Multiple myeloma indication 109989006 DOID:9538
Relapse multiple myeloma indication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 13.37 acidic
pKa2 5.23 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
10MG/VIAL KYPROLIS ONYX THERAP N202714 June 7, 2018 RX POWDER INTRAVENOUS 7491704 April 14, 2025 KYPROLIS IS INDICATED AS A SINGLE AGENT FOR THE TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA WHO HAVE RECEIVED ONE OR MORE LINES OF THERAPY
10MG/VIAL KYPROLIS ONYX THERAP N202714 June 7, 2018 RX POWDER INTRAVENOUS 7491704 April 14, 2025 KYPROLIS IS INDICATED IN COMBINATION WITH DEXAMETHASONE OR WITH LENALIDOMIDE PLUS DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA WHO HAVE RECEIVED ONE TO THREE LINES OF THERAPY
10MG/VIAL KYPROLIS ONYX THERAP N202714 June 7, 2018 RX POWDER INTRAVENOUS 8129346 April 14, 2025 KYPROLIS IS INDICATED AS A SINGLE AGENT FOR THE TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA WHO HAVE RECEIVED ONE OR MORE LINES OF THERAPY
10MG/VIAL KYPROLIS ONYX THERAP N202714 June 7, 2018 RX POWDER INTRAVENOUS 8129346 April 14, 2025 KYPROLIS IS INDICATED IN COMBINATION WITH DEXAMETHASONE OR WITH LENALIDOMIDE PLUS DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA WHO HAVE RECEIVED ONE TO THREE LINES OF THERAPY
10MG/VIAL KYPROLIS ONYX THERAP N202714 June 7, 2018 RX POWDER INTRAVENOUS 8207127 April 14, 2025 KYPROLIS IS INDICATED AS A SINGLE AGENT FOR THE TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA WHO HAVE RECEIVED ONE OR MORE LINES OF THERAPY
10MG/VIAL KYPROLIS ONYX THERAP N202714 June 7, 2018 RX POWDER INTRAVENOUS 8207127 April 14, 2025 KYPROLIS IS INDICATED IN COMBINATION WITH DEXAMETHASONE OR WITH LENALIDOMIDE PLUS DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA WHO HAVE RECEIVED ONE TO THREE LINES OF THERAPY
30MG/VIAL KYPROLIS ONYX THERAP N202714 June 3, 2016 RX POWDER INTRAVENOUS 7491704 April 14, 2025 TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST TWO PRIOR THERAPIES INCLUDING BORTEZOMIB AND AN IMMUNOMODULATORY AGENT AND HAVE DEMONSTRATED DISEASE PROGRESSION ON OR WITHIN 60 DAYS OF COMPLETION OF THE LAST THERAPY
30MG/VIAL KYPROLIS ONYX THERAP N202714 June 3, 2016 RX POWDER INTRAVENOUS 8129346 April 14, 2025 TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST TWO PRIOR THERAPIES INCLUDING BORTEZOMIB AND AN IMMUNOMODULATORY AGENT AND HAVE DEMONSTRATED DISEASE PROGRESSION ON OR WITHIN 60 DAYS OF COMPLETION OF THE LAST THERAPY
30MG/VIAL KYPROLIS ONYX THERAP N202714 June 3, 2016 RX POWDER INTRAVENOUS 8207127 April 14, 2025 TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST TWO PRIOR THERAPIES INCLUDING BORTEZOMIB AND AN IMMUNOMODULATORY AGENT AND HAVE DEMONSTRATED DISEASE PROGRESSION ON OR WITHIN 60 DAYS OF COMPLETION OF THE LAST THERAPY
60MG/VIAL KYPROLIS ONYX THERAP N202714 July 20, 2012 RX POWDER INTRAVENOUS 7491704 April 14, 2025 TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST TWO PRIOR THERAPIES INCLUDING BORTEZOMIB AND AN IMMUNOMODULATORY AGENT AND HAVE DEMONSTRATED DISEASE PROGRESSION ON OR WITHIN 60 DAYS OF COMPLETION OF THE LAST THERAPY
60MG/VIAL KYPROLIS ONYX THERAP N202714 July 20, 2012 RX POWDER INTRAVENOUS 8129346 April 14, 2025 TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST TWO PRIOR THERAPIES INCLUDING BORTEZOMIB AND AN IMMUNOMODULATORY AGENT AND HAVE DEMONSTRATED DISEASE PROGRESSION ON OR WITHIN 60 DAYS OF COMPLETION OF THE LAST THERAPY
60MG/VIAL KYPROLIS ONYX THERAP N202714 July 20, 2012 RX POWDER INTRAVENOUS 8207127 April 14, 2025 TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST TWO PRIOR THERAPIES INCLUDING BORTEZOMIB AND AN IMMUNOMODULATORY AGENT AND HAVE DEMONSTRATED DISEASE PROGRESSION ON OR WITHIN 60 DAYS OF COMPLETION OF THE LAST THERAPY
10MG/VIAL KYPROLIS ONYX THERAP N202714 June 7, 2018 RX POWDER INTRAVENOUS 9511109 Oct. 21, 2029 KYPROLIS IS INDICATED IN COMBINATION WITH LENALIDOMIDE PLUS DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA WHO HAVE RECEIVED ONE TO THREE LINES OF THERAPY
30MG/VIAL KYPROLIS ONYX THERAP N202714 June 3, 2016 RX POWDER INTRAVENOUS 9511109 Oct. 21, 2029 KYPROLIS IS INDICATED IN COMBINATION WITH LENALIDOMIDE PLUS DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA WHO HAVE RECEIVED ONE TO THREE LINES OF THERAPY
60MG/VIAL KYPROLIS ONYX THERAP N202714 July 20, 2012 RX POWDER INTRAVENOUS 9511109 Oct. 21, 2029 KYPROLIS IS INDICATED IN COMBINATION WITH LENALIDOMIDE PLUS DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA WHO HAVE RECEIVED ONE TO THREE LINES OF THERAPY

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
10MG/VIAL KYPROLIS ONYX THERAP N202714 June 7, 2018 RX POWDER INTRAVENOUS Sept. 28, 2021 ADDITION OF A ONCE WEEKLY DOSING REGIMEN FOR CARFILZOMIB IN COMBINATION WITH DEXAMETHASONE FOR PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA WHO HAVE RECEIVED ONE TO THREE LINES OF THERAPY
30MG/VIAL KYPROLIS ONYX THERAP N202714 June 3, 2016 RX POWDER INTRAVENOUS Sept. 28, 2021 ADDITION OF A ONCE WEEKLY DOSING REGIMEN FOR CARFILZOMIB IN COMBINATION WITH DEXAMETHASONE FOR PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA WHO HAVE RECEIVED ONE TO THREE LINES OF THERAPY
60MG/VIAL KYPROLIS ONYX THERAP N202714 July 20, 2012 RX POWDER INTRAVENOUS Sept. 28, 2021 ADDITION OF A ONCE WEEKLY DOSING REGIMEN FOR CARFILZOMIB IN COMBINATION WITH DEXAMETHASONE FOR PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA WHO HAVE RECEIVED ONE TO THREE LINES OF THERAPY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Proteasome subunit beta type-5 Enzyme INHIBITOR IC50 8.22 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Cathepsin B Enzyme IC50 4.96 CHEMBL
Proteasome subunit beta type-8 Enzyme IC50 7.85 CHEMBL

External reference:

IDSource
D08880 KEGG_DRUG
4031662 VUID
N0000185509 NUI
C2001856 UMLSCUI
72X6E3J5AR UNII
8859 INN_ID
C519125 MESH_SUPPLEMENTAL_RECORD_UI
CHEMBL451887 ChEMBL_ID
3BV PDB_CHEM_ID
DB08889 DRUGBANK_ID
CHEBI:65347 CHEBI
7420 IUPHAR_LIGAND_ID
11556711 PUBCHEM_CID
C524865 MESH_SUPPLEMENTAL_RECORD_UI
714783001 SNOMEDCT_US
1302966 RXNORM
014536 NDDF
28679 MMSL
d07882 MMSL
4031662 VANDF
713463006 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
KYPROLIS HUMAN PRESCRIPTION DRUG LABEL 1 76075-101 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 60 mg INTRAVENOUS NDA 16 sections
KYPROLIS HUMAN PRESCRIPTION DRUG LABEL 1 76075-102 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 30 mg INTRAVENOUS NDA 16 sections
KYPROLIS HUMAN PRESCRIPTION DRUG LABEL 1 76075-103 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 10 mg INTRAVENOUS NDA 16 sections