lapatinib ๐Ÿถ Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | 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
A quinazoline derivative that inhibits EPIDERMAL GROWTH FACTOR RECEPTOR and HER2 (RECEPTOR, ERBB-2) tyrosine kinases. It is used for the treatment of advanced or metastatic breast cancer, where tumors overexpress HER2.
  • Molecular weight: 581.06
  • Formula: C29H26ClFN4O4S
  • CLOGP: 5.82
  • LIPINSKI: 2
  • HAC: 8
  • HDO: 2
  • TPSA: 106.35
  • ALOGS: -4.42
  • ROTB: 11

  • Status: OFP

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

Drug dosage:

DoseUnitRoute
1.25 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 0.00 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 1 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 30.73 ยตM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 0 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Approvals:

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

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
Palmar-plantar erythrodysaesthesia syndrome 1776.19 20.05 563 22311 19535 50562715
Diarrhoea 1457.85 20.05 1535 21339 586941 49995309
Disease progression 778.19 20.05 503 22371 95363 50486887
Metastases to central nervous system 595.48 20.05 215 22659 11067 50571183
Malignant neoplasm progression 359.21 20.05 275 22599 67849 50514401
Neutropenia 297.90 20.05 350 22524 147615 50434635
Paronychia 282.63 20.05 98 22776 4466 50577784
Metastases to liver 257.83 20.05 142 22732 19962 50562288
Metastases to lung 251.26 20.05 115 22759 10905 50571345
Dehydration 232.45 20.05 314 22560 152135 50430115
Metastases to bone 190.09 20.05 112 22762 17883 50564367
Ejection fraction decreased 187.10 20.05 112 22762 18408 50563842
Skin toxicity 185.67 20.05 69 22805 3844 50578406
Vomiting 176.56 20.05 531 22343 460227 50122023
Breast cancer metastatic 169.10 20.05 86 22788 10278 50571972
Blood bilirubin increased 161.34 20.05 126 22748 31912 50550338
Metastases to lymph nodes 149.80 20.05 70 22804 6954 50575296
Skin fissures 141.62 20.05 72 22802 8596 50573654
Death 134.79 20.05 386 22488 324993 50257257
Mucosal inflammation 126.96 20.05 121 22753 40021 50542229
Gastrointestinal toxicity 126.41 20.05 55 22819 4622 50577628
Jaundice 120.36 20.05 98 22776 26331 50555919
Metastases to skin 110.57 20.05 36 22838 1347 50580903
Dry skin 108.66 20.05 115 22759 43076 50539174
Stomatitis 107.08 20.05 176 22698 101168 50481082
Rash 104.55 20.05 432 22442 437039 50145211
Hypokalaemia 104.21 20.05 161 22713 87831 50494419
Hepatic function abnormal 100.47 20.05 97 22777 32584 50549666
Nausea 89.23 20.05 583 22291 704815 49877435
Febrile neutropenia 86.62 20.05 157 22717 97510 50484740
Lymphangiosis carcinomatosa 83.08 20.05 28 22846 1168 50581082
Hepatotoxicity 78.44 20.05 78 22796 27148 50555102
Pyrexia 77.35 20.05 358 22516 379845 50202405
Haematotoxicity 75.21 20.05 46 22828 7849 50574401
Decreased appetite 73.10 20.05 228 22646 200695 50381555
Alanine aminotransferase increased 72.02 20.05 137 22737 88222 50494028
Drug hypersensitivity 70.38 20.05 14 22860 250996 50331254
Cardiotoxicity 69.65 20.05 42 22832 6985 50575265
Hyperbilirubinaemia 67.11 20.05 46 22828 9524 50572726
Drug ineffective 62.75 20.05 178 22696 819155 49763095
Weight increased 61.56 20.05 9 22865 201882 50380368
Condition aggravated 61.07 20.05 29 22845 297029 50285221
Joint swelling 56.80 20.05 20 22854 245266 50336984
Arthralgia 54.73 20.05 71 22803 438631 50143619
Pleural effusion 54.08 20.05 116 22758 81338 50500912
Fall 53.28 20.05 44 22830 334888 50247362
Dermatitis acneiform 52.92 20.05 29 22845 4028 50578222
Therapeutic product effect decreased 49.51 20.05 3 22871 136047 50446203
Completed suicide 47.72 20.05 3 22871 131886 50450364
Skin exfoliation 47.67 20.05 67 22807 33545 50548705
Maternal exposure during pregnancy 46.71 20.05 8 22866 159770 50422480
Neoplasm progression 45.70 20.05 61 22813 29096 50553154
Off label use 44.07 20.05 93 22781 474333 50107917
Superior vena cava syndrome 41.26 20.05 14 22860 596 50581654
Breast cancer 40.61 20.05 71 22803 42819 50539431
Neurotoxicity 40.19 20.05 41 22833 14699 50567551
Asthenia 40.16 20.05 264 22610 318778 50263472
Biliary dilatation 40.06 20.05 19 22855 1950 50580300
Aspartate aminotransferase increased 39.60 20.05 100 22774 77898 50504352
Cellulitis 39.37 20.05 94 22780 70704 50511546
Neoplasm 38.07 20.05 27 22847 5901 50576349
Metastasis 37.90 20.05 24 22850 4351 50577899
Product dose omission issue 37.66 20.05 18 22856 183820 50398430
Onychalgia 37.64 20.05 14 22860 781 50581469
Sinusitis 37.62 20.05 15 22859 170543 50411707
Leukopenia 36.84 20.05 89 22785 67439 50514811
Glossodynia 35.56 20.05 5 22869 115564 50466686
Pain 35.07 20.05 139 22735 578764 50003486
Neuropathy peripheral 34.37 20.05 109 22765 96648 50485602
Second primary malignancy 34.36 20.05 27 22847 6887 50575363
Transaminases 34.12 20.05 8 22866 84 50582166
Nail disorder 34.01 20.05 31 22843 9677 50572573
Ascites 33.47 20.05 59 22815 35802 50546448
Limbal stem cell deficiency 33.30 20.05 6 22868 13 50582237
Hypertension 33.22 20.05 28 22846 211175 50371075
Feeling abnormal 33.11 20.05 8 22866 125484 50456766
Thrombocytopenia 32.59 20.05 129 22745 127544 50454706
Musculoskeletal stiffness 32.35 20.05 9 22865 128472 50453778
Radiation necrosis 31.82 20.05 10 22864 333 50581917
Metastatic neoplasm 31.04 20.05 20 22854 3734 50578516
Drug interaction 30.74 20.05 27 22847 199594 50382656
Onycholysis 30.70 20.05 14 22860 1314 50580936
Therapeutic product effect incomplete 30.53 20.05 3 22871 91512 50490738
Recurrent cancer 29.88 20.05 15 22859 1742 50580508
Metastases to spine 28.26 20.05 17 22857 2814 50579436
Left ventricular dysfunction 28.23 20.05 29 22845 10477 50571773
Tumour marker increased 28.21 20.05 19 22855 3821 50578429
Nail infection 28.18 20.05 15 22859 1966 50580284
Pericardial effusion 27.73 20.05 45 22829 25544 50556706
Breast neoplasm 27.72 20.05 13 22861 1300 50580950
Injection site pain 27.53 20.05 8 22866 111016 50471234
Radiation pneumonitis 27.52 20.05 13 22861 1322 50580928
Neoplasm malignant 27.48 20.05 43 22831 23672 50558578
Plantar erythema 27.10 20.05 8 22866 215 50582035
Erythema 26.81 20.05 134 22740 146280 50435970
Performance status decreased 26.37 20.05 17 22857 3178 50579072
Exposure during pregnancy 26.10 20.05 11 22863 121004 50461246
Infusion related reaction 26.02 20.05 23 22851 169534 50412716
Brain oedema 26.00 20.05 30 22844 12340 50569910
Breast cancer recurrent 25.98 20.05 18 22856 3790 50578460
Wound 25.55 20.05 8 22866 105786 50476464
Swelling 25.50 20.05 32 22842 200840 50381410
Discomfort 24.78 20.05 9 22865 108371 50473879
Botryomycosis 24.40 20.05 5 22869 26 50582224
Arthritis 23.93 20.05 5 22869 86716 50495534
Anal erythema 23.93 20.05 7 22867 182 50582068
Dyschezia 23.82 20.05 13 22861 1791 50580459
Skin mass 23.27 20.05 19 22855 5116 50577134
Neoplasm recurrence 23.06 20.05 14 22860 2355 50579895
Ingrowing nail 22.98 20.05 13 22861 1919 50580331
Asthma 22.97 20.05 6 22868 89331 50492919
Alopecia 22.71 20.05 48 22826 244999 50337251
Abdominal pain 21.96 20.05 182 22692 236046 50346204
Anxiety 21.81 20.05 29 22845 177577 50404673
Central nervous system lesion 21.63 20.05 24 22850 9465 50572785
Brain neoplasm 21.53 20.05 16 22858 3757 50578493
Contusion 21.45 20.05 12 22862 112171 50470079
Bone cancer metastatic 21.38 20.05 6 22868 134 50582116
Disease recurrence 21.33 20.05 35 22839 20046 50562204
Jaundice cholestatic 21.27 20.05 18 22856 5093 50577157
Psoriasis 21.18 20.05 3 22871 68997 50513253
Hyperhidrosis 21.17 20.05 7 22867 89419 50492831
General physical health deterioration 21.08 20.05 123 22751 142311 50439939
Hormone receptor positive breast cancer 20.98 20.05 8 22866 478 50581772
Malignant pleural effusion 20.73 20.05 13 22861 2317 50579933
Abdominal discomfort 20.13 20.05 47 22827 231594 50350656

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
Duodenal ulcer perforation 52.66 33.86 12 1076 1494 29571945
Diarrhoea 43.87 33.86 57 1031 332641 29240798
Metastases to lung 36.85 33.86 13 1075 7842 29565597

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
Palmar-plantar erythrodysaesthesia syndrome 1116.28 20.04 371 15167 28448 64454746
Diarrhoea 1014.11 20.04 1038 14500 721666 63761528
Disease progression 497.38 20.04 348 15190 141332 64341862
Metastases to central nervous system 367.86 20.04 135 15403 13777 64469417
Malignant neoplasm progression 270.46 20.04 221 15317 112650 64370544
Metastases to lung 237.59 20.04 101 15437 15163 64468031
Metastases to liver 197.09 20.04 102 15436 23839 64459355
Dehydration 167.25 20.04 232 15306 216531 64266663
Breast cancer metastatic 161.85 20.04 62 15476 7107 64476087
Paronychia 160.50 20.04 60 15478 6432 64476762
Metastases to bone 150.96 20.04 81 15457 20354 64462840
Vomiting 140.71 20.04 367 15171 550750 63932444
Ejection fraction decreased 135.37 20.04 85 15453 28622 64454572
Gastrointestinal toxicity 134.54 20.04 50 15488 5272 64477922
Metastases to lymph nodes 123.53 20.04 54 15484 8663 64474531
Metastases to skin 122.00 20.04 34 15504 1418 64481776
Neutropenia 104.41 20.04 198 15340 239426 64243768
Skin toxicity 100.43 20.04 43 15495 6559 64476635
Skin fissures 96.72 20.04 48 15490 10258 64472936
Mucosal inflammation 86.06 20.04 90 15448 62494 64420700
Death 81.43 20.04 278 15260 482427 64000767
Nausea 80.32 20.04 387 15151 785413 63697781
Blood bilirubin increased 74.22 20.04 80 15458 57473 64425721
Hypokalaemia 72.96 20.04 116 15422 121787 64361407
Rash 71.17 20.04 257 15281 458292 64024902
Hepatotoxicity 68.86 20.04 65 15473 39897 64443297
Lymphangiosis carcinomatosa 68.52 20.04 23 15515 1798 64481396
Jaundice 67.10 20.04 70 15468 48442 64434752
Cardiotoxicity 62.89 20.04 36 15502 10238 64472956
Haematotoxicity 62.82 20.04 39 15499 12857 64470337
Dry skin 60.56 20.04 68 15470 51093 64432101
Stomatitis 59.74 20.04 100 15438 109505 64373689
Hyperbilirubinaemia 51.64 20.04 42 15496 21163 64462031
Asthenia 41.42 20.04 208 15330 427836 64055358
Condition aggravated 41.39 20.04 19 15519 372407 64110787
Dermatitis acneiform 39.77 20.04 25 15513 8418 64474776
Onycholysis 36.47 20.04 14 15524 1612 64481582
Decreased appetite 36.38 20.04 149 15389 281140 64202054
Biliary dilatation 35.24 20.04 15 15523 2253 64480941
Tumour marker increased 35.15 20.04 17 15521 3433 64479761
Drug interaction 35.06 20.04 22 15516 362061 64121133
Metastases to spine 34.27 20.04 17 15521 3626 64479568
Transaminases 34.03 20.04 7 15531 76 64483118
Onychalgia 33.73 20.04 11 15527 786 64482408
Drug hypersensitivity 33.62 20.04 8 15530 237807 64245387
Fall 33.14 20.04 31 15507 416795 64066399
Limbal stem cell deficiency 32.62 20.04 6 15532 34 64483160
Abdominal pain 31.73 20.04 154 15384 312221 64170973
Weight increased 30.50 20.04 7 15531 213341 64269853
Hepatic function abnormal 30.23 20.04 55 15483 64258 64418936
Hormone receptor positive breast cancer 29.27 20.04 8 15530 310 64482884
Second primary malignancy 29.12 20.04 24 15514 12313 64470881
Neoplasm progression 27.29 20.04 41 15497 40923 64442271
Metastasis 27.17 20.04 17 15521 5678 64477516
Breast cancer recurrent 27.14 20.04 13 15525 2570 64480624
Neurotoxicity 26.73 20.04 33 15505 27371 64455823
Disease recurrence 26.11 20.04 35 15503 31475 64451719
Osteonecrosis of jaw 25.32 20.04 39 15499 39786 64443408
Metastases to the mediastinum 25.17 20.04 8 15530 526 64482668
Recurrent cancer 25.11 20.04 12 15526 2361 64480833
Pyrexia 24.97 20.04 224 15314 558420 63924774
Botryomycosis 23.93 20.04 5 15533 59 64483135
Cholangitis 23.40 20.04 20 15518 10782 64472412
Pleural effusion 23.06 20.04 75 15463 126484 64356710
Pericardial effusion 22.96 20.04 37 15501 39217 64443977
Left ventricular dysfunction 22.60 20.04 24 15514 16930 64466264
Hypertension 22.13 20.04 18 15520 259243 64223951
Breast cancer 22.07 20.04 31 15507 29117 64454077
Arthralgia 22.03 20.04 46 15492 442214 64040980
Neoplasm 21.63 20.04 16 15522 7015 64476179
Skin mass 21.48 20.04 16 15522 7090 64476104
Cellulitis 21.29 20.04 60 15478 93597 64389597
Radiation pneumonitis 21.28 20.04 12 15526 3316 64479878
Joint swelling 20.94 20.04 13 15525 215369 64267825
Nail disorder 20.82 20.04 17 15521 8607 64474587
Plantar erythema 20.69 20.04 6 15532 289 64482905
Performance status decreased 20.66 20.04 14 15524 5350 64477844
Gastric neoplasm 20.55 20.04 6 15532 296 64482898
Metastatic neoplasm 20.54 20.04 13 15525 4429 64478765
Onychoclasis 20.14 20.04 13 15525 4579 64478615

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01EH01 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitors
FDA MoA N0000175076 Protein Kinase Inhibitors
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor

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

DiseaseRelationSNOMED_IDDOID
HER2-positive carcinoma of breast indication 427685000
Torsades de pointes contraindication 31722008
Hypokalemia contraindication 43339004
Hepatic failure contraindication 59927004
Interstitial pneumonia contraindication 64667001
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




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 5.62 Basic
pKa2 4.99 Basic

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
Epidermal growth factor receptor Kinase INHIBITOR Kd 9.04 CHEMBL CHEMBL
Receptor tyrosine-protein kinase erbB-2 Kinase INHIBITOR Kd 8.15 CHEMBL CHEMBL
Platelet-derived growth factor receptor beta Kinase IC50 5.07 CHEMBL
Tyrosine-protein kinase ABL1 Kinase IC50 4.64 CHEMBL
Solute carrier organic anion transporter family member 1B1 Transporter WOMBAT-PK
Cyclin-dependent kinase 2 Kinase IC50 4.96 CHEMBL
Insulin receptor Kinase AGONIST IC50 4.77 CHEMBL
Receptor tyrosine-protein kinase erbB-4 Kinase Kd 7.27 CHEMBL
Serine/threonine-protein kinase 10 Kinase Kd 5.59 CHEMBL
Receptor-interacting serine/threonine-protein kinase 2 Kinase Kd 5.44 CHEMBL
STE20-like serine/threonine-protein kinase Kinase Kd 5.48 CHEMBL
Dual specificity mitogen-activated protein kinase kinase 7 Kinase Kd 5.36 CHEMBL
Receptor tyrosine-protein kinase erbB-3 Kinase Kd 5.26 CHEMBL
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta Kinase Kd 6.17 CHEMBL
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit gamma Kinase Kd 5.12 CHEMBL
Phosphatidylinositol 4-kinase beta Kinase Kd 6.03 CHEMBL
Multidrug resistance protein 1 Transporter WOMBAT-PK
Dual specificity mitogen-activated protein kinase kinase 5 Kinase Kd 5.96 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
D04024 KEGG_DRUG
388082-78-8 SECONDARY_CAS_RN
4026029 VANDF
C1506770 UMLSCUI
FMM PDB_CHEM_ID
CHEMBL554 ChEMBL_ID
CHEMBL1201179 ChEMBL_ID
D000077341 MESH_DESCRIPTOR_UI
DB01259 DRUGBANK_ID
5692 IUPHAR_LIGAND_ID
8378 INN_ID
0VUA21238F UNII
208908 PUBCHEM_CID
480167 RXNORM
339254 MMSL
d06672 MMSL
012020 NDDF
012022 NDDF
425466009 SNOMEDCT_US
425820005 SNOMEDCT_US
426238006 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
TYKERB HUMAN PRESCRIPTION DRUG LABEL 1 0078-0671 TABLET 250 mg ORAL NDA 34 sections
TYKERB HUMAN PRESCRIPTION DRUG LABEL 1 0078-0671 TABLET 250 mg ORAL NDA 34 sections
Lapatinib Human Prescription Drug Label 1 68180-801 TABLET 250 mg ORAL ANDA 28 sections