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

Stem definitionDrug idCAS RN
proteasome inhibitors 5067 1072833-77-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • ixazomib
  • ixazomib citrate
  • MLN2238
  • MLN9708
  • ninlaro
an oral proteasome inhibitor with antineoplastic activity; MLN2238 is the biologically active form of MLN9708
  • Molecular weight: 361.03
  • Formula: C14H19BCl2N2O4
  • CLOGP: 1.10
  • LIPINSKI: 0
  • HAC: 6
  • HDO: 4
  • TPSA: 98.66
  • ALOGS: -4.47
  • ROTB: 7

  • Status: ONP

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

Drug dosage:

None

ADMET properties:

PropertyValueReference
Vd (Volume of distribution) 3.61 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 0.50 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.01 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 97 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
March 30, 2017 PMDA Takeda Pharmaceutical Company Limited
Nov. 21, 2016 EMA Takeda Pharma A/S
Nov. 20, 2015 FDA MILLENNIUM PHARMS

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
Plasma cell myeloma 1771.64 21.06 660 18616 47214 53282576
Diarrhoea 729.09 21.06 1000 18276 624546 52705244
Neuropathy peripheral 487.21 21.06 356 18920 102831 53226959
Death 436.69 21.06 587 18689 356645 52973145
Adverse event 277.32 21.06 177 19099 40884 53288906
Thrombocytopenia 256.65 21.06 282 18994 138445 53191345
Platelet count decreased 237.68 21.06 241 19035 107858 53221932
Pneumonia 204.91 21.06 452 18824 406717 52923073
Plasma cell myeloma recurrent 166.69 21.06 55 19221 2702 53327088
Off label use 157.12 21.06 448 18828 471764 52858026
Product physical issue 118.72 21.06 51 19225 5211 53324579
White blood cell count decreased 117.88 21.06 182 19094 124293 53205497
Nausea 113.68 21.06 555 18721 755536 52574254
No adverse event 111.62 21.06 101 19175 39164 53290626
Constipation 108.12 21.06 228 19048 198184 53131606
Full blood count decreased 104.26 21.06 79 19197 23950 53305840
Cytopenia 100.10 21.06 54 19222 9116 53320674
Neutrophil count decreased 82.31 21.06 95 19181 49003 53280787
Laboratory test abnormal 81.86 21.06 69 19207 24340 53305450
Product dose omission issue 81.84 21.06 200 19076 191420 53138370
Adverse drug reaction 72.40 21.06 93 19183 53532 53276258
Vomiting 64.54 21.06 351 18925 496788 52833002
Fatigue 61.05 21.06 461 18815 730045 52599745
Influenza 59.43 21.06 116 19160 95263 53234527
Drug ineffective 49.94 21.06 142 19134 817103 52512687
Plasmacytoma 45.34 21.06 21 19255 2560 53327230
Drug interaction 44.71 21.06 12 19264 219317 53110473
Neutropenia 44.04 21.06 142 19134 159043 53170747
Muscle spasms 42.63 21.06 126 19150 134669 53195121
Body dysmorphic disorder 42.50 21.06 11 19265 226 53329564
Rash 40.15 21.06 287 18989 445904 52883886
Toxicity to various agents 39.47 21.06 15 19261 219583 53110207
Dehydration 38.51 21.06 141 19135 168269 53161521
Product packaging quantity issue 37.55 21.06 15 19261 1274 53328516
Asthenia 36.89 21.06 231 19045 343359 52986431
Monoclonal immunoglobulin present 36.51 21.06 13 19263 804 53328986
Peripheral swelling 36.26 21.06 159 19117 205949 53123841
Condition aggravated 35.58 21.06 33 19243 297101 53032689
Paraesthesia 35.47 21.06 114 19162 127401 53202389
Arthralgia 34.26 21.06 67 19209 439716 52890074
Accidental exposure to product 33.42 21.06 42 19234 23632 53306158
Drug hypersensitivity 32.29 21.06 29 19247 265213 53064577
Cataract 31.67 21.06 61 19215 49559 53280231
Plasma cell leukaemia 31.31 21.06 13 19263 1220 53328570
COVID-19 30.80 21.06 51 19225 36837 53292953
Joint ankylosis 30.51 21.06 11 19265 705 53329085
Pain 30.39 21.06 110 19166 588288 52741502
Injection site pain 30.17 21.06 3 19273 113388 53216402
Product blister packaging issue 29.42 21.06 8 19268 200 53329590
Monoclonal immunoglobulin increased 29.05 21.06 7 19269 106 53329684
Light chain analysis increased 28.56 21.06 12 19264 1160 53328630
Treatment failure 28.16 21.06 6 19270 128397 53201393
Vitiligo 27.82 21.06 12 19264 1237 53328553
Cardiac amyloidosis 26.84 21.06 10 19266 704 53329086
Illness 25.85 21.06 36 19240 22360 53307430
Infusion related reaction 25.84 21.06 12 19264 155945 53173845
Glossodynia 25.79 21.06 3 19273 100288 53229502
Product packaging issue 25.73 21.06 11 19265 1110 53328680
COVID-19 pneumonia 25.46 21.06 21 19255 7182 53322608
Therapeutic product effect decreased 25.35 21.06 7 19269 125648 53204142
VIth nerve paresis 25.21 21.06 6 19270 86 53329704
Headache 24.73 21.06 105 19171 536716 52793074
Tachycardia 23.85 21.06 5 19271 108207 53221583
Ageusia 23.84 21.06 26 19250 12588 53317202
Hepatic enzyme increased 23.71 21.06 8 19268 126187 53203603
Hypertension 23.63 21.06 28 19248 225403 53104387
Blood immunoglobulin G increased 23.41 21.06 11 19265 1386 53328404
Decreased appetite 23.30 21.06 145 19131 214829 53114961
Hypoglossal nerve paresis 23.06 21.06 6 19270 126 53329664
Back pain 22.94 21.06 154 19122 234093 53095697
Blood potassium decreased 22.53 21.06 47 19229 40413 53289377
Product packaging difficult to open 22.48 21.06 5 19271 52 53329738
Discomfort 21.90 21.06 4 19272 95468 53234322
Tumour lysis syndrome 21.86 21.06 20 19256 7854 53321936
Pneumonia influenzal 21.76 21.06 11 19265 1624 53328166
Haemorrhoidal haemorrhage 21.62 21.06 15 19261 3963 53325827
Musculoskeletal stiffness 21.21 21.06 9 19267 123359 53206431

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
Plasma cell myeloma 1955.48 22.42 837 17000 56777 32438912
Death 441.88 22.42 764 17073 381753 32113936
Neuropathy peripheral 426.56 22.42 346 17491 76636 32419053
Pneumonia 291.68 22.42 615 17222 354637 32141052
Adverse event 264.22 22.42 144 17693 16328 32479361
Diarrhoea 257.89 22.42 595 17242 364207 32131482
Off label use 233.24 22.42 515 17322 305805 32189884
Thrombocytopenia 168.95 22.42 296 17541 148003 32347686
No adverse event 168.56 22.42 116 17721 19937 32475752
Plasma cell myeloma recurrent 162.95 22.42 66 17771 3811 32491878
Platelet count decreased 161.76 22.42 252 17585 114339 32381350
Full blood count decreased 149.12 22.42 101 17736 16909 32478780
Product physical issue 141.38 22.42 52 17785 2309 32493380
Laboratory test abnormal 114.26 22.42 90 17747 18997 32476692
Drug interaction 102.48 22.42 4 17833 218181 32277508
Constipation 98.26 22.42 215 17622 126158 32369531
Adverse drug reaction 96.23 22.42 93 17744 25768 32469921
Rash 95.28 22.42 291 17546 209042 32286647
Fatigue 87.88 22.42 402 17435 350299 32145390
Influenza 83.34 22.42 114 17723 45900 32449789
White blood cell count decreased 75.21 22.42 159 17678 91039 32404650
Light chain analysis increased 71.56 22.42 26 17811 1114 32494575
Peripheral swelling 69.37 22.42 130 17707 68215 32427474
Product dose omission issue 66.95 22.42 163 17674 102412 32393277
Toxicity to various agents 65.10 22.42 10 17827 178031 32317658
Cytopenia 52.89 22.42 44 17793 10020 32485669
Back pain 49.98 22.42 154 17683 110899 32384790
Accidental exposure to product 44.90 22.42 42 17795 11160 32484529
Monoclonal immunoglobulin present 42.98 22.42 17 17820 921 32494768
Product packaging issue 39.26 22.42 14 17823 568 32495121
Thrombosis 37.92 22.42 80 17757 45674 32450015
Product blister packaging issue 34.10 22.42 8 17829 68 32495621
Product use in unapproved indication 33.97 22.42 4 17833 87200 32408489
Lower respiratory tract infection 33.93 22.42 59 17778 29184 32466505
Muscle spasms 33.85 22.42 100 17737 70318 32425371
Product packaging quantity issue 31.02 22.42 13 17824 818 32494871
Full blood count increased 30.79 22.42 13 17824 833 32494856
Morganella infection 30.21 22.42 11 17826 474 32495215
Tachycardia 29.90 22.42 4 17833 79084 32416605
Hypertension 29.34 22.42 18 17819 131732 32363957
Neutropenia 28.24 22.42 153 17684 142022 32353667
Cryptosporidiosis infection 27.51 22.42 10 17827 429 32495260
COVID-19 26.54 22.42 56 17781 31959 32463730
Plasmacytoma 26.51 22.42 19 17818 3474 32492215
Rhabdomyolysis 26.41 22.42 3 17834 67262 32428427
Hypotension 26.40 22.42 49 17788 216061 32279628
Bronchial haemorrhage 25.95 22.42 11 17826 712 32494977
Unevaluable event 25.84 22.42 57 17780 33529 32462160
Nasopharyngitis 25.50 22.42 85 17752 63702 32431987
JC virus CSF test positive 25.45 22.42 7 17830 118 32495571
Light chain disease 25.18 22.42 7 17830 123 32495566
Condition aggravated 25.17 22.42 29 17808 155632 32340057
Seizure 23.38 22.42 14 17823 103840 32391849
Laryngeal cancer metastatic 23.33 22.42 6 17831 77 32495612
Nausea 23.10 22.42 273 17564 320576 32175113
Abdominal pain 22.96 22.42 29 17808 149500 32346189
Illness 22.65 22.42 22 17815 6124 32489565

Pharmacologic Action:

SourceCodeDescription
ATC L01XG03 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Proteasome inhibitors
FDA MoA N0000175075 Proteasome Inhibitors
FDA EPC N0000175604 Proteasome Inhibitor
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D011480 Protease Inhibitors
CHEBI has role CHEBI:35610 cytostatic
CHEBI has role CHEBI:50266 Prodrugs
CHEBI has role CHEBI:52726 proteasome inhibitors
CHEBI has role CHEBI:68495 Type I programmed cell-death inducer
CHEBI has role CHEBI:71031 orphan drugs
CHEBI has role CHEBI:49103 drug metabolites

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Multiple myeloma indication 109989006 DOID:9538

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 9.27 acidic
pKa2 12.17 acidic
pKa3 13.45 acidic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 2.3MG BASE NINLARO TAKEDA PHARMS USA N208462 Nov. 20, 2015 RX CAPSULE ORAL 9233115 Aug. 12, 2024 USE IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY
EQ 3MG BASE NINLARO TAKEDA PHARMS USA N208462 Nov. 20, 2015 RX CAPSULE ORAL 9233115 Aug. 12, 2024 USE IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY
EQ 4MG BASE NINLARO TAKEDA PHARMS USA N208462 Nov. 20, 2015 RX CAPSULE ORAL 9233115 Aug. 12, 2024 USE IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY
EQ 2.3MG BASE NINLARO TAKEDA PHARMS USA N208462 Nov. 20, 2015 RX CAPSULE ORAL 8003819 Aug. 6, 2027 USE IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY
EQ 2.3MG BASE NINLARO TAKEDA PHARMS USA N208462 Nov. 20, 2015 RX CAPSULE ORAL 8530694 Aug. 6, 2027 USE IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY
EQ 2.3MG BASE NINLARO TAKEDA PHARMS USA N208462 Nov. 20, 2015 RX CAPSULE ORAL 8871745 Aug. 6, 2027 USE IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY
EQ 3MG BASE NINLARO TAKEDA PHARMS USA N208462 Nov. 20, 2015 RX CAPSULE ORAL 8003819 Aug. 6, 2027 USE IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY
EQ 3MG BASE NINLARO TAKEDA PHARMS USA N208462 Nov. 20, 2015 RX CAPSULE ORAL 8530694 Aug. 6, 2027 USE IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY
EQ 3MG BASE NINLARO TAKEDA PHARMS USA N208462 Nov. 20, 2015 RX CAPSULE ORAL 8871745 Aug. 6, 2027 USE IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY
EQ 4MG BASE NINLARO TAKEDA PHARMS USA N208462 Nov. 20, 2015 RX CAPSULE ORAL 8003819 Aug. 6, 2027 USE IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY
EQ 4MG BASE NINLARO TAKEDA PHARMS USA N208462 Nov. 20, 2015 RX CAPSULE ORAL 8530694 Aug. 6, 2027 USE IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY
EQ 4MG BASE NINLARO TAKEDA PHARMS USA N208462 Nov. 20, 2015 RX CAPSULE ORAL 8871745 Aug. 6, 2027 USE IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY
EQ 2.3MG BASE NINLARO TAKEDA PHARMS USA N208462 Nov. 20, 2015 RX CAPSULE ORAL 9175017 June 16, 2029 USE IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY
EQ 3MG BASE NINLARO TAKEDA PHARMS USA N208462 Nov. 20, 2015 RX CAPSULE ORAL 9175017 June 16, 2029 USE IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY
EQ 4MG BASE NINLARO TAKEDA PHARMS USA N208462 Nov. 20, 2015 RX CAPSULE ORAL 9175017 June 16, 2029 USE IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY
EQ 2.3MG BASE NINLARO TAKEDA PHARMS USA N208462 Nov. 20, 2015 RX CAPSULE ORAL 7442830 Nov. 20, 2029 USE IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY
EQ 3MG BASE NINLARO TAKEDA PHARMS USA N208462 Nov. 20, 2015 RX CAPSULE ORAL 7442830 Nov. 20, 2029 USE IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY
EQ 4MG BASE NINLARO TAKEDA PHARMS USA N208462 Nov. 20, 2015 RX CAPSULE ORAL 7442830 Nov. 20, 2029 USE IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 2.3MG BASE NINLARO TAKEDA PHARMS USA N208462 Nov. 20, 2015 RX CAPSULE ORAL Nov. 20, 2022 USE IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY
EQ 3MG BASE NINLARO TAKEDA PHARMS USA N208462 Nov. 20, 2015 RX CAPSULE ORAL Nov. 20, 2022 USE IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY
EQ 4MG BASE NINLARO TAKEDA PHARMS USA N208462 Nov. 20, 2015 RX CAPSULE ORAL Nov. 20, 2022 USE IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Proteasome subunit beta type-5 Enzyme INHIBITOR IC50 8.47 SCIENTIFIC LITERATURE DRUG LABEL
Proteasome subunit beta type-1 Enzyme INHIBITOR IC50 7.51 SCIENTIFIC LITERATURE
Proteasome subunit beta type-2 Enzyme INHIBITOR IC50 5.46 SCIENTIFIC LITERATURE
ATP-dependent Clp protease proteolytic subunit Enzyme EC50 5.44 CHEMBL

External reference:

IDSource
71050168A2 UNII
D10130 KEGG_DRUG
1239908-20-3 SECONDARY_CAS_RN
4035138 VANDF
C3273711 UMLSCUI
CHEBI:90942 CHEBI
6V8 PDB_CHEM_ID
CHEMBL2141296 ChEMBL_ID
25183872 PUBCHEM_CID
DB09570 DRUGBANK_ID
CHEMBL3545432 ChEMBL_ID
CHEMBL1813256 ChEMBL_ID
C548400 MESH_SUPPLEMENTAL_RECORD_UI
C000595706 MESH_SUPPLEMENTAL_RECORD_UI
8450 IUPHAR_LIGAND_ID
9411 INN_ID
1723734 RXNORM
237159 MMSL
31293 MMSL
d08398 MMSL
016599 NDDF
016600 NDDF
715256005 SNOMEDCT_US
781324002 SNOMEDCT_US
784168005 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
NINLARO HUMAN PRESCRIPTION DRUG LABEL 1 63020-078 CAPSULE 2.30 mg ORAL NDA 29 sections
NINLARO HUMAN PRESCRIPTION DRUG LABEL 1 63020-079 CAPSULE 3 mg ORAL NDA 29 sections
NINLARO HUMAN PRESCRIPTION DRUG LABEL 1 63020-080 CAPSULE 4 mg ORAL NDA 29 sections
NINLARO HUMAN PRESCRIPTION DRUG LABEL 1 63020-230 CAPSULE 2.30 mg ORAL NDA 30 sections
NINLARO HUMAN PRESCRIPTION DRUG LABEL 1 63020-390 CAPSULE 3 mg ORAL NDA 30 sections
NINLARO HUMAN PRESCRIPTION DRUG LABEL 1 63020-400 CAPSULE 4 mg ORAL NDA 30 sections