nilotinib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 1932 641571-10-0

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • nilotinib hydrochloride hydrate
  • nilotinib
  • tasigna
  • nilotinib hydrochloride monohydrate
Nilotinib is an inhibitor of the BCR-ABL kinase. Nilotinib binds to and stabilizes the inactive conformation of the kinase domain of ABL protein. In vitro, nilotinib inhibited BCR-ABL mediated proliferation of murine leukemic cell lines and human cell lines derived from patients with Ph+ CML. Under the conditions of the assays, nilotinib was able to overcome imatinib resistance resulting from BCR-ABL kinase mutations, in 32 out of 33 mutations tested. In vivo, nilotinib reduced the tumor size in a murine BCR-ABL xenograft model.
  • Molecular weight: 529.53
  • Formula: C28H22F3N7O
  • CLOGP: 5.69
  • LIPINSKI: 2
  • HAC: 8
  • HDO: 2
  • TPSA: 97.62
  • ALOGS: -5.42
  • ROTB: 7
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.60 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 4 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 21.58 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 30 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Approvals:

DateAgencyCompanyOrphan
Oct. 29, 2007 FDA NOVARTIS

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
Cytogenetic analysis abnormal 492.32 15.84 102 20407 644 50583971
Peripheral arterial occlusive disease 351.86 15.84 106 20403 3431 50581184
Electrocardiogram QT prolonged 323.23 15.84 222 20287 51664 50532951
Blast crisis in myelogenous leukaemia 213.57 15.84 48 20461 464 50584151
Second primary malignancy 204.60 15.84 84 20425 6830 50577785
Chronic myeloid leukaemia transformation 191.11 15.84 34 20475 78 50584537
Drug resistance 187.87 15.84 109 20400 18880 50565735
Lipase increased 174.83 15.84 80 20429 8461 50576154
Philadelphia chromosome positive 155.19 15.84 35 20474 344 50584271
Rash 149.22 15.84 451 20058 437020 50147595
Pleural effusion 148.72 15.84 174 20335 81280 50503335
Peripheral artery stenosis 113.55 15.84 29 20480 500 50584115
Blood bilirubin increased 113.24 15.84 98 20411 31940 50552675
Bone pain 112.38 15.84 116 20393 47113 50537502
Intermittent claudication 112.08 15.84 37 20472 1618 50582997
Myocardial infarction 110.31 15.84 157 20352 88870 50495745
Malignant neoplasm progression 105.57 15.84 134 20375 67990 50516625
Off label use 91.63 15.84 39 20470 474387 50110228
Thrombocytopenia 87.92 15.84 173 20336 127500 50457115
Arteriosclerosis 84.20 15.84 50 20459 9027 50575588
Acute myocardial infarction 80.86 15.84 78 20431 29195 50555420
Chronic myeloid leukaemia recurrent 78.13 15.84 18 20491 196 50584419
Platelet count decreased 77.35 15.84 143 20366 100583 50484032
Pancreatitis 75.97 15.84 90 20419 42524 50542091
Myalgia 70.97 15.84 156 20353 124163 50460452
White blood cell count increased 70.05 15.84 86 20423 42154 50542461
Death 69.44 15.84 288 20221 325091 50259524
Angina pectoris 63.48 15.84 65 20444 26123 50558492
Labelled drug-food interaction medication error 62.52 15.84 11 20498 23 50584592
Acute lymphocytic leukaemia recurrent 61.85 15.84 25 20484 1950 50582665
Platelet count increased 60.73 15.84 49 20460 14491 50570124
Pruritus 59.67 15.84 250 20259 283318 50301297
Normal newborn 57.26 15.84 35 20474 6656 50577959
Peripheral vascular disorder 55.68 15.84 32 20477 5435 50579180
Condition aggravated 54.76 15.84 26 20483 297032 50287583
Pancytopenia 54.35 15.84 111 20398 83919 50500696
Blast cell crisis 52.86 15.84 11 20498 71 50584544
Joint swelling 52.55 15.84 17 20492 245269 50339346
Haematotoxicity 51.96 15.84 35 20474 7860 50576755
Rheumatoid arthritis 49.10 15.84 11 20498 202539 50382076
Polymerase chain reaction positive 48.54 15.84 10 20499 61 50584554
Therapeutic response delayed 48.07 15.84 15 20494 546 50584069
Pericardial effusion 47.18 15.84 55 20454 25534 50559081
Myocardial ischaemia 46.10 15.84 38 20471 11575 50573040
Hyperbilirubinaemia 45.90 15.84 35 20474 9535 50575080
Splenomegaly 45.61 15.84 35 20474 9625 50574990
Cerebrovascular accident 44.35 15.84 110 20399 94570 50490045
Drug ineffective 44.29 15.84 177 20332 819156 49765459
Carotid artery stenosis 43.72 15.84 26 20483 4705 50579910
Systemic lupus erythematosus 42.43 15.84 4 20505 140618 50443997
Blood glucose increased 42.36 15.84 91 20418 71233 50513382
Arthropathy 41.58 15.84 7 20502 157899 50426716
Anaemia 40.04 15.84 205 20304 252251 50332364
Exposure via father 39.91 15.84 11 20498 257 50584358
Arterial disorder 39.16 15.84 15 20494 1014 50583601
Dry skin 39.16 15.84 66 20443 43125 50541490
Drug hypersensitivity 39.05 15.84 27 20482 250983 50333632
Coronary artery disease 37.61 15.84 53 20456 29673 50554942
Exposure via partner 37.53 15.84 9 20500 118 50584497
Xanthelasma 37.40 15.84 8 20501 60 50584555
Thrombocytosis 34.93 15.84 23 20486 4973 50579642
Diabetes mellitus 34.36 15.84 67 20442 48966 50535649
Chronic myeloid leukaemia 34.34 15.84 17 20492 2139 50582476
Palpitations 33.41 15.84 99 20410 94407 50490208
Amylase increased 33.19 15.84 23 20486 5407 50579208
Bone marrow failure 33.10 15.84 48 20461 27576 50557039
Glossodynia 33.04 15.84 4 20505 115565 50469050
Leukaemia recurrent 32.94 15.84 14 20495 1240 50583375
Gene mutation identification test positive 32.61 15.84 8 20501 116 50584499
Basophil count increased 31.21 15.84 12 20497 820 50583795
Arterial occlusive disease 30.88 15.84 21 20488 4787 50579828
Skin disorder 30.62 15.84 43 20466 23987 50560628
Food interaction 30.22 15.84 11 20498 645 50583970
Hypercholesterolaemia 30.10 15.84 30 20479 11673 50572942
Abdominal pain upper 30.01 15.84 136 20373 159173 50425442
Acute coronary syndrome 29.76 15.84 27 20482 9347 50575268
Concomitant disease progression 29.27 15.84 15 20494 2030 50582585
Peripheral ischaemia 28.24 15.84 19 20490 4257 50580358
Peripheral artery occlusion 27.97 15.84 12 20497 1087 50583528
Toxicity to various agents 27.89 15.84 27 20482 212472 50372143
Cytopenia 27.32 15.84 25 20484 8750 50575865
Hypotension 26.43 15.84 34 20475 235435 50349180
Product use issue 26.12 15.84 14 20495 149461 50435154
Gamma-glutamyltransferase increased 25.18 15.84 44 20465 29579 50555036
Concomitant disease aggravated 25.09 15.84 23 20486 8068 50576547
Acute kidney injury 24.51 15.84 34 20475 228024 50356591
Pregnancy of partner 24.48 15.84 5 20504 29 50584586
Musculoskeletal stiffness 24.01 15.84 11 20498 128470 50456145
Pain in extremity 23.58 15.84 190 20319 272675 50311940
Abdominal pain 23.49 15.84 170 20339 236058 50348557
Blast cell count increased 23.43 15.84 8 20501 388 50584227
Wound 23.22 15.84 7 20502 105787 50478828
Sinusitis 23.16 15.84 21 20488 170537 50414078
Keratosis pilaris 22.77 15.84 5 20504 43 50584572
Alanine aminotransferase increased 22.64 15.84 83 20426 88276 50496339
Neoplasm malignant 22.51 15.84 37 20472 23678 50560937
Haemolytic transfusion reaction 22.24 15.84 4 20505 10 50584605
Muscle spasms 22.02 15.84 105 20404 125448 50459167
Cardiac failure 21.69 15.84 74 20435 75966 50508649
Collateral circulation 21.46 15.84 4 20505 13 50584602
Lower respiratory tract infection 21.44 15.84 6 20503 95195 50489420
Therapeutic response decreased 21.18 15.84 54 20455 47177 50537438
Chest pain 20.98 15.84 133 20376 176749 50407866
Alopecia 20.82 15.84 170 20339 244877 50339738
Confusional state 20.70 15.84 27 20482 185901 50398714
Blood lactate dehydrogenase increased 20.59 15.84 32 20477 19530 50565085
Gangrene 19.99 15.84 16 20493 4676 50579939
Delivery 19.51 15.84 8 20501 647 50583968
Overdose 19.48 15.84 8 20501 99719 50484896
Pancreatic enzymes increased 19.36 15.84 8 20501 660 50583955
Intentional product use issue 18.98 15.84 4 20505 76914 50507701
Hepatic infection 18.79 15.84 7 20502 438 50584177
Hepatic function abnormal 18.59 15.84 41 20468 32640 50551975
Impaired healing 18.57 15.84 3 20506 69783 50514832
Hypersensitivity 18.54 15.84 37 20472 215124 50369491
Dyslipidaemia 18.53 15.84 17 20492 5971 50578644
Leukocytosis 18.49 15.84 33 20476 22546 50562069
Transaminases increased 18.26 15.84 37 20472 27787 50556828
Hyperglycaemia 17.77 15.84 43 20466 36362 50548253
Atrial fibrillation 17.77 15.84 85 20424 101660 50482955
Discomfort 17.72 15.84 11 20498 108369 50476246
Oxygen saturation decreased 17.68 15.84 4 20505 73244 50511371
Exposure during pregnancy 17.52 15.84 14 20495 121001 50463614
Angiopathy 17.44 15.84 14 20495 4108 50580507
Gene mutation 17.26 15.84 9 20500 1262 50583353
Haemoglobin decreased 17.20 15.84 99 20410 127117 50457498
Jaundice 17.17 15.84 35 20474 26394 50558221
Calculus bladder 17.12 15.84 7 20502 562 50584053
Stomatitis 16.97 15.84 10 20499 101334 50483281
Coronary artery stenosis 16.95 15.84 14 20495 4275 50580340
Swelling 16.92 15.84 35 20474 200837 50383778
Hyponatraemia 16.80 15.84 9 20500 96130 50488485
Vertebral artery stenosis 16.12 15.84 4 20505 61 50584554
Extremity necrosis 16.03 15.84 9 20500 1462 50583153
Fluid retention 15.96 15.84 51 20458 50598 50534017

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
Cytogenetic analysis abnormal 424.11 15.06 96 22151 474 29551806
Blast crisis in myelogenous leukaemia 373.71 15.06 86 22161 463 29551817
Second primary malignancy 371.20 15.06 152 22095 6553 29545727
Peripheral arterial occlusive disease 368.49 15.06 140 22107 4936 29547344
Electrocardiogram QT prolonged 350.98 15.06 258 21989 35879 29516401
Drug resistance 220.77 15.06 159 22088 21381 29530899
Intermittent claudication 218.17 15.06 75 22172 1970 29550310
Pleural effusion 208.01 15.06 263 21984 71645 29480635
Angina pectoris 207.38 15.06 170 22077 27680 29524600
Rash 162.63 15.06 406 21841 189413 29362867
Lipase increased 156.17 15.06 90 22157 8247 29544033
Myocardial infarction 148.11 15.06 283 21964 110013 29442267
Death 137.25 15.06 563 21684 341521 29210759
Chronic myeloid leukaemia transformation 131.30 15.06 29 22218 125 29552155
Coronary artery stenosis 125.51 15.06 79 22168 8494 29543786
Off label use 123.08 15.06 37 22210 300763 29251517
Philadelphia chromosome positive 115.02 15.06 30 22217 290 29551990
Drug intolerance 109.24 15.06 157 22090 48222 29504058
Chronic myeloid leukaemia recurrent 106.03 15.06 25 22222 152 29552128
Blood bilirubin increased 96.27 15.06 123 22124 33770 29518510
Pancreatitis 92.95 15.06 122 22125 34392 29517888
Peripheral artery stenosis 90.09 15.06 31 22216 816 29551464
Malignant neoplasm progression 87.50 15.06 180 22067 73679 29478601
Acute kidney injury 82.25 15.06 49 22198 265218 29287062
White blood cell count increased 82.10 15.06 120 22127 37396 29514884
Arterial disorder 82.09 15.06 31 22216 1072 29551208
Acute myocardial infarction 79.78 15.06 136 22111 48302 29503978
Myocardial ischaemia 77.92 15.06 77 22170 15951 29536329
Peripheral vascular disorder 76.82 15.06 46 22201 4521 29547759
Platelet count decreased 75.13 15.06 210 22037 104462 29447818
Coronary artery disease 74.00 15.06 125 22122 44065 29508215
Toxicity to various agents 71.52 15.06 21 22226 173640 29378640
Hypotension 65.88 15.06 32 22215 194322 29357958
Abdominal pain upper 65.66 15.06 143 22104 60850 29491430
Concomitant disease aggravated 58.52 15.06 40 22207 4938 29547342
Chest pain 57.49 15.06 200 22047 111773 29440507
Acute coronary syndrome 55.84 15.06 57 22190 12268 29540012
Gene mutation identification test positive 55.60 15.06 14 22233 116 29552164
Polymerase chain reaction positive 55.39 15.06 14 22233 118 29552162
Carotid artery stenosis 55.13 15.06 37 22210 4432 29547848
Thrombocytopenia 52.10 15.06 220 22027 134603 29417677
Arteriosclerosis 51.20 15.06 50 22197 10206 29542074
Peripheral artery occlusion 51.10 15.06 24 22223 1438 29550842
Arterial stenosis 50.38 15.06 22 22225 1111 29551169
Splenomegaly 48.86 15.06 55 22192 13224 29539056
Concomitant disease progression 48.27 15.06 27 22220 2334 29549946
Exposure via father 46.48 15.06 12 22235 111 29552169
Bone pain 44.73 15.06 62 22185 18390 29533890
Pruritus 44.60 15.06 190 22057 116659 29435621
Blast cell crisis 44.25 15.06 11 22236 86 29552194
Gene mutation 42.38 15.06 19 22228 1022 29551258
Labelled drug-food interaction medication error 41.09 15.06 9 22238 37 29552243
Confusional state 38.99 15.06 24 22223 127853 29424427
Loss of therapeutic response 38.87 15.06 13 22234 313 29551967
Drug interaction 38.07 15.06 56 22191 197329 29354951
Overdose 35.98 15.06 8 22239 79811 29472469
Peripheral ischaemia 33.42 15.06 29 22218 5090 29547190
Angina unstable 33.32 15.06 41 22206 10824 29541456
Myalgia 32.69 15.06 126 22121 73893 29478387
Amylase increased 32.64 15.06 29 22218 5251 29547029
Cerebral infarction 32.60 15.06 63 22184 24612 29527668
Fall 32.49 15.06 52 22195 177126 29375154
Infarction 32.14 15.06 21 22226 2405 29549875
Paternal exposure during pregnancy 30.92 15.06 6 22241 11 29552269
Blood glucose increased 29.90 15.06 105 22142 58879 29493401
Hyperglycaemia 29.84 15.06 74 22173 34213 29518067
Condition aggravated 28.68 15.06 41 22206 146254 29406026
Cerebral artery stenosis 28.27 15.06 10 22237 286 29551994
Cerebrovascular accident 27.72 15.06 123 22124 76788 29475492
Drug hypersensitivity 26.81 15.06 9 22238 68397 29483883
Hypercholesterolaemia 26.66 15.06 30 22217 7208 29545072
Tremor 26.60 15.06 11 22236 73527 29478753
Acoustic neuroma 26.05 15.06 8 22239 145 29552135
Chronic myeloid leukaemia 25.78 15.06 17 22230 1977 29550303
Dehydration 25.76 15.06 29 22218 114719 29437561
Leukocytosis 25.54 15.06 52 22195 21090 29531190
Pancreatic toxicity 24.77 15.06 4 22243 0 29552280
Coronary artery occlusion 24.58 15.06 34 22213 10060 29542220
Pericardial effusion 24.25 15.06 51 22196 21157 29531123
Somnolence 24.25 15.06 21 22226 93934 29458346
Pain in extremity 24.24 15.06 154 22093 110279 29442001
Ischaemia 23.81 15.06 22 22225 4190 29548090
Gangrene 23.78 15.06 22 22225 4196 29548084
Hallucination 23.40 15.06 3 22244 44709 29507571
Therapeutic response decreased 23.28 15.06 55 22192 24656 29527624
Hyponatraemia 23.07 15.06 11 22236 67622 29484658
Arterial thrombosis 23.02 15.06 14 22233 1414 29550866
Clonal evolution 22.89 15.06 7 22240 125 29552155
Fatigue 22.34 15.06 348 21899 316473 29235807
Central nervous system leukaemia 21.74 15.06 8 22239 257 29552023
Product blister packaging issue 21.53 15.06 6 22241 76 29552204
Gamma-glutamyltransferase increased 21.49 15.06 56 22191 26681 29525599
Agitation 21.45 15.06 6 22241 51298 29500982
Basophil count increased 20.75 15.06 9 22238 447 29551833
Necrosis 20.52 15.06 22 22225 5008 29547272
Arteritis 20.37 15.06 8 22239 308 29551972
Diabetes mellitus 20.26 15.06 71 22176 39760 29512520
Chloroma 20.20 15.06 9 22238 477 29551803
Blast cells present 20.11 15.06 9 22238 482 29551798
Myeloproliferative neoplasm 19.95 15.06 9 22238 491 29551789
Hepatic infection 19.62 15.06 9 22238 511 29551769
Gelatinous transformation of the bone marrow 19.49 15.06 4 22243 11 29552269
Acne 19.44 15.06 29 22218 9191 29543089
Atrial fibrillation 19.40 15.06 141 22106 105505 29446775
Chest discomfort 19.25 15.06 77 22170 45906 29506374
Intentional overdose 19.19 15.06 3 22244 38525 29513755
Abdominal pain 19.07 15.06 170 22077 135187 29417093
B-cell small lymphocytic lymphoma 19.03 15.06 6 22241 119 29552161
Muscle spasms 19.03 15.06 98 22149 64984 29487296
Febrile neutropenia 18.67 15.06 35 22212 112205 29440075
Rectosigmoid cancer 17.69 15.06 6 22241 151 29552129
Leukaemia recurrent 17.67 15.06 12 22235 1465 29550815
Delirium 17.64 15.06 4 22243 39393 29512887
Arterial occlusive disease 17.46 15.06 18 22229 3916 29548364
Acquired gene mutation 16.93 15.06 11 22236 1247 29551033
Vascular stenosis 16.82 15.06 6 22241 176 29552104
Bone marrow failure 16.70 15.06 52 22195 27397 29524883
Cytopenia 16.63 15.06 28 22219 9831 29542449
Intentional product misuse 16.60 15.06 3 22244 34658 29517622
Seizure 16.41 15.06 28 22219 93095 29459185
Cardiovascular disorder 15.90 15.06 26 22221 8909 29543371
Oxygen saturation decreased 15.80 15.06 7 22240 44930 29507350
Haemoglobin decreased 15.71 15.06 137 22110 108238 29444042
Carotid arteriosclerosis 15.60 15.06 11 22236 1427 29550853
Liver disorder 15.45 15.06 51 22196 27698 29524582
Headache 15.36 15.06 199 22048 173808 29378472
Alopecia 15.36 15.06 40 22207 19044 29533236
Prinzmetal angina 15.35 15.06 9 22238 850 29551430
Aggression 15.15 15.06 4 22243 35537 29516743

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
Cytogenetic analysis abnormal 733.20 14.70 151 28438 830 64469313
Peripheral arterial occlusive disease 443.29 14.70 152 28437 6835 64463308
Electrocardiogram QT prolonged 413.99 14.70 316 28273 79132 64391011
Blast crisis in myelogenous leukaemia 407.78 14.70 90 28499 719 64469424
Second primary malignancy 399.65 14.70 164 28425 12173 64457970
Drug resistance 314.16 14.70 195 28394 34907 64435236
Pleural effusion 294.52 14.70 320 28269 126239 64343904
Chronic myeloid leukaemia transformation 245.12 14.70 48 28541 194 64469949
Lipase increased 241.60 14.70 121 28468 14281 64455862
Rash 214.09 14.70 561 28028 457988 64012155
Philadelphia chromosome positive 210.74 14.70 50 28539 567 64469576
Intermittent claudication 191.96 14.70 66 28523 2988 64467155
Angina pectoris 180.78 14.70 154 28435 44927 64425216
Myocardial infarction 178.25 14.70 287 28302 165534 64304609
Blood bilirubin increased 170.76 14.70 166 28423 57387 64412756
Platelet count decreased 159.79 14.70 275 28314 167436 64302707
Death 159.20 14.70 522 28067 482183 63987960
Peripheral artery stenosis 133.07 14.70 40 28549 1169 64468974
Malignant neoplasm progression 128.96 14.70 201 28388 112670 64357473
Off label use 125.75 14.70 62 28527 632744 63837399
Acute myocardial infarction 119.71 14.70 151 28438 69567 64400576
White blood cell count increased 110.20 14.70 141 28448 65873 64404270
Chronic myeloid leukaemia recurrent 107.24 14.70 25 28564 261 64469882
Pancreatitis 100.57 14.70 128 28461 59479 64410664
Bone pain 96.26 14.70 112 28477 47460 64422683
Coronary artery stenosis 91.82 14.70 59 28530 11189 64458954
Myocardial ischaemia 90.26 14.70 78 28511 23173 64446970
Thrombocytopenia 90.18 14.70 260 28329 223541 64246602
Arterial disorder 86.86 14.70 32 28557 1773 64468370
Acute coronary syndrome 83.63 14.70 69 28520 19241 64450902
Toxicity to various agents 81.00 14.70 30 28559 363483 64106660
Gene mutation identification test positive 75.87 14.70 18 28571 204 64469939
Arteriosclerosis 75.67 14.70 60 28529 15817 64454326
Hypotension 74.49 14.70 38 28551 380936 64089207
Carotid artery stenosis 73.22 14.70 45 28544 7896 64462247
Acute kidney injury 72.45 14.70 56 28533 449184 64020959
Polymerase chain reaction positive 70.97 14.70 18 28571 274 64469869
Splenomegaly 67.18 14.70 59 28530 17902 64452241
Blood glucose increased 66.20 14.70 139 28450 97934 64372209
Acute lymphocytic leukaemia recurrent 65.07 14.70 33 28556 3993 64466150
Pruritus 63.25 14.70 290 28299 312110 64158033
Coronary artery disease 62.61 14.70 103 28486 60330 64409813
Condition aggravated 61.84 14.70 45 28544 372381 64097762
Myalgia 61.63 14.70 182 28407 158435 64311708
Peripheral vascular disorder 61.53 14.70 39 28550 7222 64462921
Pericardial effusion 54.99 14.70 77 28512 39177 64430966
Rheumatoid arthritis 54.51 14.70 5 28584 164289 64305854
Cerebral infarction 52.35 14.70 77 28512 40967 64429176
Hyperbilirubinaemia 51.61 14.70 55 28534 21150 64448993
Amylase increased 51.37 14.70 39 28550 9646 64460497
Abdominal pain upper 50.11 14.70 181 28408 174849 64295294
Hyperglycaemia 49.04 14.70 93 28496 60875 64409268
Concomitant disease progression 47.66 14.70 25 28564 3244 64466899
Concomitant disease aggravated 47.40 14.70 40 28549 11502 64458641
Arterial stenosis 46.84 14.70 19 28570 1366 64468777
Confusional state 46.74 14.70 29 28560 261115 64209028
Gamma-glutamyltransferase increased 46.67 14.70 80 28509 48430 64421713
Haemoglobin decreased 46.24 14.70 190 28399 194873 64275270
Blast cell crisis 45.41 14.70 11 28578 137 64470006
Peripheral artery occlusion 45.02 14.70 21 28568 2117 64468026
Chest pain 44.72 14.70 215 28374 235765 64234378
Joint swelling 44.31 14.70 20 28569 215362 64254781
Bone marrow failure 43.43 14.70 77 28512 47875 64422268
Gene mutation 42.45 14.70 20 28569 2062 64468081
Drug hypersensitivity 41.74 14.70 27 28562 237788 64232355
Overdose 41.23 14.70 10 28579 159556 64310587
Acquired gene mutation 40.25 14.70 19 28570 1967 64468176
Therapeutic response delayed 40.10 14.70 15 28574 867 64469276
Pancytopenia 39.99 14.70 147 28442 143162 64326981
Drug ineffective 37.57 14.70 219 28370 840028 63630115
Arterial occlusive disease 36.59 14.70 28 28561 7005 64463138
Peripheral ischaemia 36.40 14.70 30 28559 8348 64461795
Platelet count increased 36.11 14.70 43 28546 18653 64451490
Chronic myeloid leukaemia 35.99 14.70 21 28568 3353 64466790
Acne 34.92 14.70 47 28542 23034 64447109
Fall 33.17 14.70 86 28503 416740 64053403
Leukaemia recurrent 32.67 14.70 18 28571 2576 64467567
Cerebrovascular accident 32.57 14.70 134 28455 137449 64332694
Hypercholesterolaemia 32.43 14.70 37 28552 15336 64454807
Drug intolerance 31.86 14.70 166 28423 187826 64282317
Therapeutic response decreased 31.80 14.70 71 28518 52117 64418026
Gangrene 31.31 14.70 26 28563 7312 64462831
Labelled drug-food interaction medication error 30.87 14.70 7 28582 64 64470079
Hyponatraemia 30.14 14.70 14 28575 148325 64321818
Dry skin 29.39 14.70 68 28521 51093 64419050
Cerebral artery stenosis 29.21 14.70 11 28578 648 64469495
Drug interaction 28.56 14.70 75 28514 362008 64108135
Blood lactate dehydrogenase increased 28.52 14.70 52 28537 33026 64437117
Angiopathy 28.41 14.70 23 28566 6242 64463901
Anaemia 28.32 14.70 274 28315 378406 64091737
Cardiac failure 28.29 14.70 125 28464 132248 64337895
Abdominal pain 27.94 14.70 235 28354 312140 64158003
Atrial fibrillation 27.56 14.70 149 28440 170940 64299203
Pancreatic toxicity 27.50 14.70 5 28584 12 64470131
Diabetes mellitus 27.44 14.70 78 28511 66396 64403747
Oxygen saturation decreased 27.13 14.70 7 28582 107169 64362974
Clonal evolution 27.07 14.70 8 28581 220 64469923
Chronic myeloid leukaemia (in remission) 26.89 14.70 4 28585 0 64470143
Arthropathy 26.86 14.70 10 28579 120957 64349186
Keratosis pilaris 26.64 14.70 6 28583 53 64470090
White blood cell count decreased 26.47 14.70 139 28450 157698 64312445
Pain in extremity 26.04 14.70 226 28363 302859 64167284
Alanine aminotransferase increased 25.81 14.70 126 28463 138905 64331238
Angina unstable 25.73 14.70 33 28556 15434 64454709
Haematotoxicity 25.46 14.70 30 28559 12866 64457277
Xanthelasma 24.96 14.70 7 28582 159 64469984
Muscle spasms 24.90 14.70 126 28463 140897 64329246
Palpitations 24.90 14.70 102 28487 104386 64365757
Hypersensitivity 24.12 14.70 31 28558 196421 64273722
Leukocytosis 23.73 14.70 52 28537 37688 64432455
Infarction 23.36 14.70 17 28572 3943 64466200
Hepatic function abnormal 23.25 14.70 72 28517 64241 64405902
Hepatic infection 23.13 14.70 10 28579 843 64469300
Central nervous system leukaemia 22.95 14.70 8 28581 377 64469766
Sinusitis 22.44 14.70 19 28570 145909 64324234
Liver disorder 22.41 14.70 63 28526 53288 64416855
Therapy non-responder 22.20 14.70 72 28517 65827 64404316
Basophil count increased 22.02 14.70 11 28578 1289 64468854
Intentional product misuse 21.95 14.70 3 28586 72292 64397851
Exposure during pregnancy 21.84 14.70 4 28585 77671 64392472
Urinary tract infection 21.44 14.70 44 28545 231552 64238591
Loss of therapeutic response 21.18 14.70 7 28582 280 64469863
Cytopenia 21.14 14.70 30 28559 15441 64454702
Haemolytic transfusion reaction 21.11 14.70 4 28585 13 64470130
Vascular stenosis 21.07 14.70 8 28581 482 64469661
Coronary artery occlusion 20.57 14.70 28 28561 13863 64456280
Arterial thrombosis 20.46 14.70 13 28576 2417 64467726
Splenitis 20.17 14.70 3 28586 0 64470143
Agitation 20.13 14.70 7 28582 88360 64381783
Thrombocytosis 20.01 14.70 20 28569 7136 64463007
Paternal exposure during pregnancy 19.73 14.70 4 28585 20 64470123
Myeloproliferative neoplasm 19.55 14.70 9 28580 880 64469263
Necrosis 19.54 14.70 21 28568 8150 64461993
Somnolence 19.44 14.70 38 28551 203607 64266536
Exposure via father 19.42 14.70 5 28584 81 64470062
Blast cell count increased 19.27 14.70 10 28579 1269 64468874
Suicide attempt 19.24 14.70 4 28585 71003 64399140
Mobility decreased 19.22 14.70 7 28582 85833 64384310
Dyslipidaemia 19.08 14.70 22 28567 9220 64460923
Chromosome analysis abnormal 18.71 14.70 6 28583 218 64469925
Tremor 18.59 14.70 23 28566 148207 64321936
Skin disorder 18.38 14.70 39 28550 27641 64442502
Acoustic neuroma 18.38 14.70 6 28583 231 64469912
Chloroma 18.26 14.70 8 28581 697 64469446
Ischaemic stroke 18.24 14.70 40 28549 28995 64441148
Normal newborn 18.15 14.70 17 28572 5600 64464543
Pyrexia 17.88 14.70 347 28242 558297 63911846
Product use issue 17.54 14.70 25 28564 151690 64318453
Suicidal ideation 17.51 14.70 4 28585 66538 64403605
Metabolic acidosis 17.27 14.70 5 28584 70953 64399190
Blood creatine phosphokinase increased 17.10 14.70 61 28528 58497 64411646
Transformation to acute myeloid leukaemia 16.72 14.70 8 28581 853 64469290
Musculoskeletal stiffness 16.66 14.70 18 28571 123188 64346955
Delirium 16.61 14.70 5 28584 69189 64400954
Intentional product use issue 16.48 14.70 11 28578 95353 64374790
Lower respiratory tract infection 16.23 14.70 11 28578 94603 64375540
Aspartate aminotransferase increased 15.81 14.70 99 28490 119689 64350454
Dyslalia 15.70 14.70 8 28581 977 64469166
Peripheral artery thrombosis 15.68 14.70 12 28577 3003 64467140
Hepatotoxicity 15.63 14.70 46 28543 39916 64430227
Supraventricular extrasystoles 15.56 14.70 16 28573 5899 64464244
Vertebral artery stenosis 15.53 14.70 5 28584 184 64469959
Febrile neutropenia 15.45 14.70 38 28551 187619 64282524
Coma 15.28 14.70 10 28579 87605 64382538
Glossodynia 14.95 14.70 5 28584 64691 64405452

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01EA03 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
BCR-ABL tyrosine kinase inhibitors
FDA MoA N0000020009 Bcr-Abl Tyrosine Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000182137 Cytochrome P450 2D6 Inhibitors
FDA MoA N0000185503 P-Glycoprotein Inhibitors
FDA MoA N0000187062 Cytochrome P450 2C8 Inhibitors
FDA MoA N0000187063 Cytochrome P450 2C8 Inducers
FDA MoA N0000187064 Cytochrome P450 2B6 Inducers
FDA MoA N0000191272 UGT1A1 Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agents
CHEBI has role CHEBI:38637 tyrosine kinase inhibitors
CHEBI has role CHEBI:149553 anticoronaviral drug

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Chronic phase chronic myeloid leukemia indication 413847001
Philadelphia Chromosome Positive Chronic Myelocytic Leukemia indication
Chronic Myelocytic Leukemia Accelerated Phase indication
Hypophosphatemia contraindication 4996001
Hypocalcemia contraindication 5291005
Hypercholesterolemia contraindication 13644009
Hyperkalemia contraindication 14140009
Hyperbilirubinemia contraindication 14783006 DOID:2741
Torsades de pointes contraindication 31722008
Hypertensive disorder contraindication 38341003 DOID:10763
Hypokalemia contraindication 43339004
Gastrectomy contraindication 53442002
Diabetes mellitus contraindication 73211009 DOID:9351
Pancreatitis contraindication 75694006 DOID:4989
Hyperglycemia contraindication 80394007 DOID:4195
Hyponatremia contraindication 89627008
Prolonged QT interval contraindication 111975006
Liver function tests abnormal contraindication 166603001
Hypomagnesemia contraindication 190855004
Disease of liver contraindication 235856003 DOID:409
Anemia contraindication 271737000 DOID:2355
Pregnancy, function contraindication 289908002
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Neutropenic disorder contraindication 303011007 DOID:1227
Breastfeeding (mother) contraindication 413712001
Congenital long QT syndrome contraindication 442917000
Elevated Serum Lipase contraindication




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 11.89 acidic
pKa2 6.03 Basic
pKa3 3.97 Basic
pKa4 2.2 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 50MG BASE TASIGNA NOVARTIS N022068 March 22, 2018 RX CAPSULE ORAL 7169791 July 4, 2023 A METHOD FOR THE TREATMENT OF LEUKEMIAS
EQ 50MG BASE TASIGNA NOVARTIS N022068 March 22, 2018 RX CAPSULE ORAL 8389537 July 18, 2026 TREATMENT OF PHILADELPHIA CHROMOSOME POSITIVE CHRONIC MYELOID LEUKEMIA (PH+CML)
EQ 50MG BASE TASIGNA NOVARTIS N022068 March 22, 2018 RX CAPSULE ORAL 8415363 July 18, 2026 TREATMENT OF NEWLY DIAGNOSED PHILADELPHIA CHROMOSOME POSITIVE CHRONIC MYELOID LEUKEMIA (PH + CML)
EQ 50MG BASE TASIGNA NOVARTIS N022068 March 22, 2018 RX CAPSULE ORAL 8415363 July 18, 2026 TREATMENT OF PHILADELPHIA CHROMOSOME POSITIVE CHRONIC MYELOID LEUKEMIA (PH+CML)
EQ 50MG BASE TASIGNA NOVARTIS N022068 March 22, 2018 RX CAPSULE ORAL 9061029 April 7, 2032 TREATMENT OF PHILADELPHIA CHROMOSOME POSITIVE CHRONIC MYELOID LEUKEMIA (PH+CML)
EQ 50MG BASE TASIGNA NOVARTIS N022068 March 22, 2018 RX CAPSULE ORAL 9061029 April 7, 2032 TREATMENT OF PHILADELPHIA CHROMOSOME POSITIVE CHRONIC MYELOID LEUKEMIA (PH+CML) BY ADMINISTERING NILOTINIB DISPERSED IN A FRUIT PREPARATION

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 50MG BASE TASIGNA NOVARTIS N022068 March 22, 2018 RX CAPSULE ORAL March 22, 2025 TREATMENT OF PEDIATRIC PATIENTS GREATER THAN OR EQUAL TO 1 YEAR OF AGE WITH CHRONIC PHASE PHILADELPHIA CHROMOSOME POSITIVE CHRONIC MYELOID LEUKEMIA WITH RESISTANCE OR INTOLERANCE TO PRIOR TYROSINE-KINASE INHIBITOR THERAPY
EQ 50MG BASE TASIGNA NOVARTIS N022068 March 22, 2018 RX CAPSULE ORAL March 22, 2025 TREATMENT OF PEDIATRIC PATIENTS GREATER THAN OR EQUAL TO 1 YEAR OF AGE WITH NEWLY DIAGNOSED PHILADELPHIA CHROMOSOME POSITIVE CHRONIC MYELOID LEUKEMIA (PH+CML) IN CHRONIC PHASE
EQ 50MG BASE TASIGNA NOVARTIS N022068 March 22, 2018 RX CAPSULE ORAL Sept. 22, 2025 PEDIATRIC EXCLUSIVITY
EQ 50MG BASE TASIGNA NOVARTIS N022068 March 22, 2018 RX CAPSULE ORAL Sept. 23, 2028 TREATMENT OF PEDIATRIC PATIENTS GREATER THAN OR EQUAL TO 1 YEAR OF AGE WITH ACCELERATED PHASE PHILADELPHIA CHROMOSOME POSITIVE CHRONIC MYELOID LEUKEMIA (PH+ CML) WITH RESISTANCE ORINTOLERANCE TO PRIOR TYROSINE-KINASE INHIBITOR (TKI) THERAPY
EQ 50MG BASE TASIGNA NOVARTIS N022068 March 22, 2018 RX CAPSULE ORAL March 23, 2029 PEDIATRIC EXCLUSIVITY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Tyrosine-protein kinase ABL1 Kinase INHIBITOR Kd 8.44 CHEMBL CHEMBL
Carbonic anhydrase 2 Enzyme Ki 8.39 CHEMBL
Carbonic anhydrase 1 Enzyme Ki 7.53 CHEMBL
Carbonic anhydrase 4 Enzyme Ki 6.35 CHEMBL
Ribosyldihydronicotinamide dehydrogenase [quinone] Enzyme IC50 6.42 CHEMBL
Carbonic anhydrase 9 Enzyme Ki 7.38 CHEMBL
Carbonic anhydrase 12 Enzyme Ki 6.52 CHEMBL
Platelet-derived growth factor receptor beta Kinase Kd 7.80 CHEMBL
Mast/stem cell growth factor receptor Kit Kinase Kd 7.77 CHEMBL
Carbonic anhydrase 5A, mitochondrial Enzyme Ki 5.26 CHEMBL
Carbonic anhydrase 5B, mitochondrial Enzyme Ki 4.83 CHEMBL
Carbonic anhydrase 7 Enzyme Ki 7 CHEMBL
Proto-oncogene tyrosine-protein kinase Src Kinase Kd 5.72 CHEMBL
Tyrosine-protein kinase Lck Kinase Kd 7.33 CHEMBL
Tyrosine-protein kinase Yes Kinase Kd 5.96 CHEMBL
Tyrosine-protein kinase Fyn Kinase Kd 5.80 CHEMBL
Ephrin type-A receptor 2 Kinase Kd 6.64 CHEMBL
RAF proto-oncogene serine/threonine-protein kinase Kinase Kd 5.41 CHEMBL
Serine/threonine-protein kinase B-raf Kinase Kd 6.24 CHEMBL
Receptor-type tyrosine-protein kinase FLT3 Kinase Kd 4.40 CHEMBL
Proto-oncogene tyrosine-protein kinase receptor Ret Kinase Kd 6.06 CHEMBL
Macrophage colony-stimulating factor 1 receptor Kinase Kd 7.35 CHEMBL
Platelet-derived growth factor receptor alpha Kinase Kd 7.13 CHEMBL
Phosphorylase b kinase gamma catalytic chain, liver/testis isoform Kinase Kd 6.48 CHEMBL
Insulin receptor Kinase Ki 5.39 PDSP
Mitogen-activated protein kinase 8 Kinase Kd 6.35 CHEMBL
Tyrosine-protein kinase HCK Kinase Kd 6.41 CHEMBL
Carbonic anhydrase 3 Enzyme Ki 6.35 CHEMBL
Carbonic anhydrase 6 Enzyme Ki 6.34 CHEMBL
Mitogen-activated protein kinase 10 Kinase Kd 5.70 CHEMBL
Tyrosine-protein kinase JAK2 Kinase Ki 5.07 PDSP
Tyrosine-protein kinase CSK Kinase Kd 5.62 CHEMBL
Angiopoietin-1 receptor Kinase Kd 6 CHEMBL
Ephrin type-A receptor 8 Kinase Kd 7.43 CHEMBL
Tyrosine-protein kinase Lyn Kinase Kd 7 CHEMBL
Cytoplasmic tyrosine-protein kinase BMX Kinase Ki 5.32 PDSP
Carbonic anhydrase 14 Enzyme Ki 6.65 CHEMBL
Fibroblast growth factor receptor 1 Kinase Ki 5.10 PDSP
Serine/threonine-protein kinase 10 Kinase Kd 5.17 CHEMBL
Abelson tyrosine-protein kinase 2 Kinase Kd 7.59 CHEMBL
Mitogen-activated protein kinase 11 Kinase Kd 7.44 CHEMBL
Ephrin type-A receptor 5 Kinase Kd 5.72 CHEMBL
Ephrin type-A receptor 4 Kinase Kd 6.48 CHEMBL
Fibroblast growth factor receptor 2 Kinase Ki 5.14 PDSP
Ephrin type-A receptor 6 Kinase Kd 6.19 CHEMBL
Tyrosine-protein kinase Fgr Kinase Kd 6.49 CHEMBL
Ephrin type-A receptor 3 Kinase Kd 6.96 CHEMBL
Mitogen-activated protein kinase 14 Kinase Kd 6.34 CHEMBL
Tyrosine-protein kinase FRK Kinase Kd 7.07 CHEMBL
Dual specificity protein kinase CLK1 Kinase Kd 5.68 CHEMBL
Ephrin type-B receptor 1 Kinase Kd 5.89 CHEMBL
Dual specificity protein kinase CLK4 Kinase Kd 5.15 CHEMBL
Mitogen-activated protein kinase 9 Kinase Kd 5.24 CHEMBL
Epithelial discoidin domain-containing receptor 1 Kinase Kd 8.96 CHEMBL
Ephrin type-B receptor 4 Kinase Kd 6.14 CHEMBL
BDNF/NT-3 growth factors receptor Kinase Kd 6.31 CHEMBL
Ephrin type-B receptor 2 Kinase Kd 6.19 CHEMBL
Mitogen-activated protein kinase kinase kinase MLT Kinase Kd 7.96 CHEMBL
Tyrosine-protein kinase receptor Tie-1 Kinase Kd 6 CHEMBL
NT-3 growth factor receptor Kinase Kd 6.22 CHEMBL
Serine/threonine-protein kinase TNNI3K Kinase Kd 6.44 CHEMBL
Discoidin domain-containing receptor 2 Kinase Kd 8.22 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 1 Kinase Kd 6.05 CHEMBL
Tyrosine-protein kinase Blk Kinase Kd 6.30 CHEMBL
Serine/threonine-protein kinase MRCK beta Kinase Kd 6.04 CHEMBL
Ephrin type-A receptor 1 Kinase Kd 6.23 CHEMBL
Ephrin type-B receptor 3 Kinase Kd 6 CHEMBL
Ephrin type-B receptor 6 Kinase Kd 6.30 CHEMBL
Serine/threonine-protein kinase TAO1 Kinase Kd 5.33 CHEMBL
Serine/threonine-protein kinase TAO3 Kinase Kd 5.77 CHEMBL
Phosphatidylinositol 5-phosphate 4-kinase type-2 gamma Kinase Kd 5.06 CHEMBL
Dual specificity mitogen-activated protein kinase kinase 5 Kinase Kd 6.72 CHEMBL
Bcr/Abl fusion protein Kinase IC50 9.48 CHEMBL
Ferrochelatase, mitochondrial Enzyme Kd 5.38 CHEMBL
Receptor-interacting serine/threonine-protein kinase 3 Kinase Kd 5.89 CHEMBL
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 6.35 CHEMBL
Integrin-linked protein kinase Kinase Kd 7.70 CHEMBL
Carbonic anhydrase 13 Enzyme Ki 5.33 CHEMBL
Carbonic anhydrase 15 Enzyme Ki 7.10 CHEMBL
Calcium-dependent protein kinase 1 Kinase Kd 6.10 CHEMBL

External reference:

IDSource
4026964 VUID
N0000176124 NUI
D06413 KEGG_DRUG
923288-90-8 SECONDARY_CAS_RN
4026964 VANDF
C1721377 UMLSCUI
CHEBI:52172 CHEBI
NIL PDB_CHEM_ID
CHEMBL255863 ChEMBL_ID
CHEMBL1201740 ChEMBL_ID
DB04868 DRUGBANK_ID
C498826 MESH_SUPPLEMENTAL_RECORD_UI
5697 IUPHAR_LIGAND_ID
8654 INN_ID
F41401512X UNII
644241 PUBCHEM_CID
662281 RXNORM
127956 MMSL
24733 MMSL
d07057 MMSL
012401 NDDF
427941004 SNOMEDCT_US
428468009 SNOMEDCT_US
438943005 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Tasigna HUMAN PRESCRIPTION DRUG LABEL 1 0078-0526 CAPSULE 200 mg ORAL NDA 33 sections
Tasigna HUMAN PRESCRIPTION DRUG LABEL 1 0078-0592 CAPSULE 150 mg ORAL NDA 33 sections
Tasigna HUMAN PRESCRIPTION DRUG LABEL 1 0078-0951 CAPSULE 50 mg ORAL NDA 33 sections