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

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 1548 231277-92-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • lapatinib tosilate hydrate
  • lapatinib tosilate
  • lapatinib
  • GW 572016X
  • tyverb
  • lapatinib ditosylate
  • GW572016F
  • lapatinib ditosilate
  • lapatinib ditosilate hydrate
  • lapatinib ditosylate hydrate
an EGFR-ErbB-2 inhibitor
  • Molecular weight: 581.06
  • Formula: C29H26ClFN4O4S
  • CLOGP: 5.82
  • LIPINSKI: 2
  • HAC: 8
  • HDO: 2
  • TPSA: 106.35
  • ALOGS: -4.42
  • ROTB: 11

Drug dosage:

None

Approvals:

DateAgencyCompanyOrphan
June 10, 2008 EMA
March 13, 2007 FDA NOVARTIS PHARMS CORP

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
Diarrhoea 4088.91 47.81 1324 4260 103024 3277251
Palmar-plantar erythrodysaesthesia syndrome 2112.09 47.81 451 5133 6081 3374194
Disease progression 1178.58 47.81 397 5187 31862 3348413
Vomiting 1037.97 47.81 479 5105 89052 3291223
Nausea 948.81 47.81 507 5077 129138 3251137
Dehydration 870.76 47.81 321 5263 33328 3346947
Neutropenia 788.45 47.81 298 5286 33088 3347187
Pyrexia 703.46 47.81 357 5227 80758 3299517
Breast cancer metastatic 648.45 47.81 137 5447 1696 3378579
Rash 578.86 47.81 300 5284 70521 3309754
Metastases to central nervous system 561.94 47.81 133 5451 2830 3377445
Fatigue 536.33 47.81 329 5255 106911 3273364
Decreased appetite 495.01 47.81 228 5356 41262 3339013
Paronychia 412.97 47.81 86 5498 983 3379292
Malignant neoplasm progression 411.70 47.81 157 5427 17636 3362639
Febrile neutropenia 408.99 47.81 159 5425 18816 3361459
Dyspnoea 404.93 47.81 272 5312 102662 3277613
Metastases to liver 387.54 47.81 105 5479 3891 3376384
Stomatitis 368.19 47.81 130 5454 11722 3368553
Hypokalaemia 367.27 47.81 135 5449 13670 3366605
Asthenia 366.77 47.81 217 5367 65448 3314827
Mucosal inflammation 352.22 47.81 114 5470 7869 3372406
Skin fissures 344.61 47.81 79 5505 1447 3378828
Breast cancer 330.13 47.81 109 5475 8008 3372267
Abdominal pain 328.49 47.81 179 5405 46046 3334229
Alanine aminotransferase increased 316.17 47.81 141 5443 23499 3356776
Ejection fraction decreased 297.13 47.81 86 5498 4061 3376214
Skin toxicity 288.39 47.81 66 5518 1198 3379077
General physical health deterioration 259.85 47.81 118 5466 20471 3359804
Blood bilirubin increased 254.48 47.81 96 5488 10413 3369862
Death 233.99 47.81 233 5351 152091 3228184
Jaundice 232.69 47.81 89 5495 10018 3370257
Dry skin 216.82 47.81 79 5505 7764 3372511
Erythema 216.54 47.81 116 5468 28694 3351581
Anaemia 213.37 47.81 144 5440 54189 3326086
Leukopenia 206.85 47.81 93 5491 15730 3364545
Hepatic function abnormal 196.07 47.81 81 5503 11146 3369129
Cellulitis 193.79 47.81 83 5501 12492 3367783
Aspartate aminotransferase increased 193.00 47.81 97 5487 21016 3359259
Hyperbilirubinaemia 187.00 47.81 57 5527 3214 3377061
Metastases to bone 186.40 47.81 56 5528 3005 3377270
Metastases to lung 184.87 47.81 53 5531 2411 3377864
Gastrointestinal toxicity 171.24 47.81 42 5542 1035 3379240
Pleural effusion 162.01 47.81 83 5501 18696 3361579
Nail disorder 160.37 47.81 41 5543 1201 3379074
Pneumonia 159.29 47.81 134 5450 70009 3310266
Hepatotoxicity 157.60 47.81 57 5527 5474 3374801
Pulmonary embolism 157.06 47.81 93 5491 27795 3352480
Weight decreased 149.35 47.81 103 5481 40008 3340267
Cough 140.54 47.81 99 5485 39759 3340516
Dizziness 135.47 47.81 127 5457 76385 3303890
Thrombocytopenia 134.63 47.81 92 5492 35176 3345099
Malaise 132.61 47.81 117 5467 65060 3315215
Pain in extremity 111.47 47.81 94 5490 49118 3331157
Dermatitis acneiform 110.99 47.81 32 5552 1483 3378792
Sepsis 108.47 47.81 78 5506 32295 3347980
Infection 105.82 47.81 70 5514 25332 3354943
Hepatic enzyme increased 102.53 47.81 55 5529 13570 3366705
Skin exfoliation 97.82 47.81 45 5539 7992 3372283
Neuropathy peripheral 97.00 47.81 57 5527 16750 3363525
Dysphagia 93.77 47.81 59 5525 19592 3360683
Headache 87.37 47.81 110 5474 91870 3288405
Constipation 86.97 47.81 67 5517 30745 3349530
Oedema peripheral 86.85 47.81 70 5514 34291 3345984
White blood cell count decreased 83.26 47.81 60 5524 24887 3355388
Cardiac failure congestive 82.32 47.81 64 5520 29758 3350517
Abdominal pain upper 81.05 47.81 59 5525 24857 3355418
Rash pustular 79.44 47.81 27 5557 2153 3378122
Acne 77.48 47.81 31 5553 3912 3376363
Drug ineffective 77.37 47.81 117 5467 115973 3264302
Cardiac failure 75.54 47.81 52 5532 20053 3360222
Chest pain 75.21 47.81 69 5515 40206 3340069
Ascites 73.75 47.81 39 5545 9338 3370937
Pruritus 73.71 47.81 73 5511 46760 3333515
Epistaxis 72.98 47.81 45 5539 14406 3365869
Interstitial lung disease 71.69 47.81 44 5540 13972 3366303
Blood alkaline phosphatase increased 69.43 47.81 39 5545 10514 3369761
Urinary tract infection 69.09 47.81 59 5525 31269 3349006
Nail infection 68.41 47.81 15 5569 221 3380054
Left ventricular dysfunction 67.21 47.81 23 5561 1872 3378403
Pneumonitis 67.02 47.81 32 5552 6171 3374104
Hypotension 66.72 47.81 71 5513 49443 3330832
Hyponatraemia 65.48 47.81 46 5538 18313 3361962
Blister 64.95 47.81 35 5549 8699 3371576
Skin ulcer 64.74 47.81 30 5554 5410 3374865
Pericardial effusion 64.67 47.81 31 5553 6030 3374245
Chills 62.35 47.81 48 5536 21974 3358301
Superior vena cava syndrome 61.99 47.81 13 5571 153 3380122
Lymphoedema 60.06 47.81 19 5565 1208 3379067
Oedema 59.97 47.81 40 5544 14640 3365635
Colitis 59.94 47.81 31 5553 7090 3373185
Pain 59.14 47.81 80 5504 71477 3308798
Cholangitis 58.90 47.81 20 5564 1589 3378686
Transaminases increased 58.28 47.81 30 5554 6794 3373481
Metastases to skin 58.00 47.81 13 5571 213 3380062
Abdominal discomfort 57.51 47.81 43 5541 18841 3361434
Dyspepsia 57.37 47.81 36 5548 11876 3368399
Cardiotoxicity 57.35 47.81 20 5564 1722 3378553
Liver function test abnormal 57.19 47.81 37 5547 12864 3367411
Confusional state 53.85 47.81 56 5528 37942 3342333
Gastritis 53.54 47.81 28 5556 6549 3373726
Oral pain 51.51 47.81 23 5561 3805 3376470
Mouth ulceration 51.22 47.81 24 5560 4436 3375839
Ingrowing nail 51.14 47.81 13 5571 371 3379904
Renal failure 51.14 47.81 51 5533 32889 3347386
Seizure 51.00 47.81 56 5528 40344 3339931
Calcium ionised increased 50.21 47.81 9 5575 42 3380233
Gamma-glutamyltransferase increased 50.12 47.81 30 5554 9098 3371177
Dyspnoea exertional 49.54 47.81 27 5557 6859 3373416
Deep vein thrombosis 48.60 47.81 41 5543 21348 3358927
Hepatic failure 48.32 47.81 31 5553 10621 3369654
Metastatic neoplasm 48.15 47.81 16 5568 1189 3379086
Rash maculo-papular 47.82 47.81 25 5559 5842 3374433

Pharmacologic Action:

SourceCodeDescription
ATC L01XE07 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Protein kinase inhibitors
FDA EPC N0000175605 Kinase Inhibitor
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
HER2 Positive Carcinoma of Breast indication
Torsades de pointes contraindication 31722008
Hypokalemia contraindication 43339004
Hepatic failure contraindication 59927004
Interstitial pneumonia contraindication 64667001 DOID:3082
Left heart failure contraindication 85232009
Prolonged QT interval contraindication 111975006
Liver function tests abnormal contraindication 166603001
Hypomagnesemia contraindication 190855004
Drug-induced hepatitis contraindication 235876009
Pregnancy, function contraindication 289908002
Severe diarrhea contraindication 409587002
Breastfeeding (mother) contraindication 413712001
Congenital long QT syndrome contraindication 442917000

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 5.62 Basic
pKa2 4.99 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 250MG BASE TYKERB NOVARTIS PHARMS CORP N022059 March 13, 2007 RX TABLET ORAL 6727256 Jan. 8, 2019 TREATMENT OF PATIENTS WITH ADVANCED OR METASTATIC BREAST CANCER WHOSE TUMORS OVEREXPRESS HER2 AND WHO HAVE RECEIVED PRIOR THERAPY INCLUDING ANTHRACYCLINE, A TAXANE AND TRASTUZUMAB
EQ 250MG BASE TYKERB NOVARTIS PHARMS CORP N022059 March 13, 2007 RX TABLET ORAL 6727256 Jan. 8, 2019 TREATMENT OF PATIENTS WITH BREAST CANCER WHOSE TUMORS OVEREXPRESS THE HER2 RECEPTOR
EQ 250MG BASE TYKERB NOVARTIS PHARMS CORP N022059 March 13, 2007 RX TABLET ORAL 6713485 Sept. 29, 2020 TREATMENT OF PATIENTS WITH ADVANCED OR METASTATIC BREAST CANCER WHOSE TUMORS OVEREXPRESS HER2 AND WHO HAVE RECEIVED PRIOR THERAPY INCLUDING ANTHRACYCLINE, A TAXANE AND TRASTUZUMAB
EQ 250MG BASE TYKERB NOVARTIS PHARMS CORP N022059 March 13, 2007 RX TABLET ORAL 6713485 Sept. 29, 2020 TREATMENT OF PATIENTS WITH BREAST CANCER WHOSE TUMORS OVEREXPRESS THE HER2 RECEPTOR

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Receptor tyrosine-protein kinase erbB-2 Kinase INHIBITOR Kd 8.15 CHEMBL CHEMBL
Epidermal growth factor receptor Kinase INHIBITOR Kd 9.04 CHEMBL CHEMBL
Multidrug resistance protein 1 Transporter WOMBAT-PK
Tyrosine-protein kinase ABL1 Kinase IC50 4.64 CHEMBL
Phosphatidylinositol 4-kinase beta Kinase Kd 6.03 CHEMBL
Insulin receptor Kinase AGONIST IC50 4.77 CHEMBL
Receptor-interacting serine/threonine-protein kinase 2 Kinase Kd 5.44 CHEMBL
Dual specificity mitogen-activated protein kinase kinase 5 Kinase Kd 5.96 CHEMBL
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit gamma Kinase Kd 5.12 CHEMBL
Serine/threonine-protein kinase 10 Kinase Kd 5.59 CHEMBL
Platelet-derived growth factor receptor beta Kinase IC50 5.07 CHEMBL
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta Kinase Kd 6.17 CHEMBL
Receptor tyrosine-protein kinase erbB-4 Kinase Kd 7.27 CHEMBL
STE20-like serine/threonine-protein kinase Kinase Kd 5.48 CHEMBL
Cyclin-dependent kinase 2 Kinase IC50 4.96 CHEMBL
Dual specificity mitogen-activated protein kinase kinase 7 Kinase Kd 5.36 CHEMBL
Solute carrier organic anion transporter family member 1B1 Transporter WOMBAT-PK
Receptor tyrosine-protein kinase erbB-3 Kinase Kd 5.26 CHEMBL
ATP-binding cassette sub-family G member 2 Transporter WOMBAT-PK
Tubulin alpha-1A chain Structural Kd 7.27 CHEMBL

External reference:

IDSource
4026029 VUID
N0000179782 NUI
C1506770 UMLSCUI
5692 IUPHAR_LIGAND_ID
D04024 KEGG_DRUG
CHEMBL554 ChEMBL_ID
0VUA21238F UNII
8378 INN_ID
480167 RXNORM
d06672 MMSL
4026029 VANDF
425466009 SNOMEDCT_US
425820005 SNOMEDCT_US
N0000176088 NDFRT
N0000179782 NDFRT
012022 NDDF
CHEMBL1201179 ChEMBL_ID
DB01259 DRUGBANK_ID
208908 PUBCHEM_CID
388082-78-8 SECONDARY_CAS_RN
C490728 MESH_SUPPLEMENTAL_RECORD_UI
FMM PDB_CHEM_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
TYKERB HUMAN PRESCRIPTION DRUG LABEL 1 0078-0671 TABLET 250 mg ORAL NDA 19 sections