lapatinib 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:

None

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 ┬ÁM/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 1760.39 20.05 577 23044 19874 46642567
Diarrhoea 1452.74 20.05 1578 22043 558024 46104417
Disease progression 841.60 20.05 541 23080 90759 46571682
Metastases to central nervous system 580.25 20.05 217 23404 11004 46651437
Breast cancer metastatic 365.74 20.05 165 23456 13513 46648928
Malignant neoplasm progression 307.67 20.05 258 23363 64668 46597773
Paronychia 290.66 20.05 103 23518 4463 46657978
Metastases to liver 270.63 20.05 151 23470 19434 46643007
Neutropenia 261.17 20.05 341 23280 142863 46519578
Skin toxicity 230.95 20.05 82 23539 3572 46658869
Metastases to lung 214.96 20.05 106 23515 10590 46651851
Dehydration 212.48 20.05 327 23294 159213 46503228
Ejection fraction decreased 212.21 20.05 125 23496 17812 46644629
Skin fissures 193.73 20.05 89 23532 7591 46654850
Breast cancer 185.35 20.05 166 23455 45352 46617089
Metastases to bone 168.83 20.05 107 23514 17369 46645072
Vomiting 156.81 20.05 543 23078 452251 46210190
Blood bilirubin increased 153.85 20.05 132 23489 34052 46628389
Stomatitis 143.86 20.05 175 23446 68122 46594319
Gastrointestinal toxicity 137.55 20.05 59 23562 4272 46658169
Rash 127.03 20.05 432 23189 356080 46306361
Jaundice 124.95 20.05 109 23512 28736 46633705
Metastases to lymph nodes 110.72 20.05 58 23563 6573 46655868
Dry skin 108.04 20.05 118 23503 40898 46621543
Mucosal inflammation 107.69 20.05 115 23506 38861 46623580
Death 104.33 20.05 389 23232 335159 46327282
Metastases to skin 102.73 20.05 35 23586 1345 46661096
Hepatic function abnormal 85.42 20.05 96 23525 34325 46628116
Lymphangiosis carcinomatosa 84.61 20.05 29 23592 1135 46661306
Hypokalaemia 84.36 20.05 156 23465 87868 46574573
Haematotoxicity 81.13 20.05 48 23573 6885 46655556
Drug hypersensitivity 79.15 20.05 14 23607 243811 46418630
Pyrexia 78.22 20.05 366 23255 348436 46314005
Cardiotoxicity 77.25 20.05 46 23575 6676 46655765
Hyperbilirubinaemia 76.87 20.05 54 23567 10384 46652057
Febrile neutropenia 76.40 20.05 156 23465 94471 46567970
Nausea 74.68 20.05 597 23024 686857 45975584
Hepatotoxicity 71.20 20.05 75 23546 24934 46637507
Decreased appetite 68.83 20.05 235 23386 193601 46468840
Alanine aminotransferase increased 65.76 20.05 141 23480 88310 46574131
Fall 62.95 20.05 45 23576 329052 46333389
Completed suicide 61.33 20.05 3 23618 145917 46516524
Weight increased 54.32 20.05 9 23612 164464 46497977
Nail disorder 53.88 20.05 39 23582 7857 46654584
Dermatitis acneiform 52.44 20.05 30 23591 4040 46658401
Drug ineffective 50.82 20.05 175 23446 677663 45984778
Neurotoxicity 49.88 20.05 47 23574 13670 46648771
Arthralgia 48.90 20.05 68 23553 364535 46297906
Condition aggravated 48.82 20.05 32 23589 245020 46417421
Skin exfoliation 47.19 20.05 70 23551 32868 46629573
Off label use 44.13 20.05 78 23543 379763 46282678
Pleural effusion 41.99 20.05 114 23507 82838 46579603
Neoplasm 40.44 20.05 29 23592 5759 46656682
Superior vena cava syndrome 40.29 20.05 14 23607 571 46661870
Rash pustular 40.09 20.05 31 23590 6898 46655543
Hypertension 39.97 20.05 25 23596 196331 46466110
Product dose omission issue 39.36 20.05 18 23603 168502 46493939
Feeling abnormal 38.80 20.05 8 23613 125052 46537389
Drug interaction 38.47 20.05 28 23593 203066 46459375
Onychalgia 38.46 20.05 14 23607 655 46661786
Asthenia 36.71 20.05 276 23345 310799 46351642
Biliary dilatation 36.66 20.05 19 23602 2105 46660336
Neoplasm progression 35.79 20.05 55 23566 26628 46635813
Joint swelling 35.41 20.05 20 23601 166053 46496388
Calcium ionised increased 34.36 20.05 9 23612 136 46662305
Cellulitis 33.98 20.05 95 23526 70193 46592248
Aspartate aminotransferase increased 33.85 20.05 102 23519 78598 46583843
Transaminases 33.67 20.05 8 23613 79 46662362
Metastasis 33.37 20.05 23 23598 4289 46658152
Metastatic neoplasm 32.21 20.05 21 23600 3572 46658869
Neuropathy peripheral 31.14 20.05 109 23512 90784 46571657
Radiation necrosis 31.12 20.05 10 23611 319 46662122
Injection site pain 30.95 20.05 8 23613 107144 46555297
Therapeutic product effect decreased 30.92 20.05 3 23618 82598 46579843
Nail infection 30.81 20.05 16 23605 1780 46660661
Second primary malignancy 30.77 20.05 26 23595 6558 46655883
General physical health deterioration 30.74 20.05 128 23493 115641 46546800
Erythema 30.49 20.05 148 23473 142672 46519769
Tumour marker increased 30.05 20.05 20 23601 3521 46658920
Anxiety 29.65 20.05 29 23592 181928 46480513
Maternal exposure during pregnancy 28.97 20.05 8 23613 102541 46559900
Leukopenia 28.84 20.05 88 23533 68255 46594186
Therapeutic product effect incomplete 28.83 20.05 3 23618 78150 46584291
Sinusitis 28.57 20.05 15 23606 129753 46532688
Recurrent cancer 28.26 20.05 15 23606 1744 46660697
Ascites 27.94 20.05 59 23562 36525 46625916
Onycholysis 27.57 20.05 13 23608 1175 46661266
Metastases to spine 27.27 20.05 17 23604 2677 46659764
Radiation pneumonitis 26.87 20.05 13 23608 1244 46661197
Neoplasm malignant 26.81 20.05 45 23576 23454 46638987
Psoriasis 26.61 20.05 4 23617 78600 46583841
Exposure during pregnancy 26.14 20.05 11 23610 108201 46554240
Pain 25.86 20.05 139 23482 476809 46185632
Cheilitis 25.63 20.05 19 23602 3969 46658472
Depression 25.59 20.05 29 23592 170075 46492366
Musculoskeletal stiffness 25.26 20.05 9 23612 97984 46564457
Hyperhidrosis 25.16 20.05 7 23614 89301 46573140
Plantar erythema 24.88 20.05 8 23613 256 46662185
Lymphoedema 24.81 20.05 26 23595 8586 46653855
Left ventricular dysfunction 24.40 20.05 28 23593 10227 46652214
Asthma 24.30 20.05 8 23613 91534 46570907
Arthritis 23.86 20.05 5 23616 77311 46585130
Breast cancer recurrent 23.73 20.05 18 23603 3893 46658548
Bronchitis 23.69 20.05 12 23609 105967 46556474
Overdose 23.63 20.05 11 23610 101968 46560473
Malignant pleural effusion 23.60 20.05 15 23606 2443 46659998
Influenza 23.35 20.05 8 23613 89262 46573179
Brain oedema 23.08 20.05 30 23591 12448 46649993
Pericardial effusion 22.85 20.05 44 23577 25499 46636942
Anal erythema 22.79 20.05 7 23614 192 46662249
Breast cancer female 22.77 20.05 21 23600 5942 46656499
Disease recurrence 21.91 20.05 36 23585 18435 46644006
Brain neoplasm 21.88 20.05 17 23604 3807 46658634
Tremor 21.80 20.05 16 23605 115623 46546818
Metastases to meninges 21.65 20.05 13 23608 1914 46660527
Ejection fraction abnormal 21.50 20.05 9 23612 613 46661828
Bone cancer metastatic 21.33 20.05 6 23615 120 46662321
Bradycardia 21.06 20.05 4 23617 66294 46596147
Hormone receptor positive breast cancer 20.88 20.05 8 23613 432 46662009
Breast neoplasm 20.69 20.05 11 23610 1284 46661157
Ingrowing nail 20.58 20.05 13 23608 2095 46660346
Dysaesthesia 20.14 20.05 15 23606 3156 46659285

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
Diarrhoea 46.36 31.42 57 983 334046 29617392
Metastases to lung 37.52 31.42 13 1027 7882 29943556
Dehydration 32.96 31.42 30 1010 123509 29827929

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
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 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

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)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 250MG BASE TYKERB NOVARTIS N022059 March 13, 2007 RX TABLET ORAL Dec. 6, 2021 INFORMATION ADDED TO SECTION 14 OF THE LABELING TO DESCRIBE STUDY LAP016A2307 TO FULFILL POSTMARKETING STUDY REQUIREMENT 1586-1

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
D04024 KEGG_DRUG
388082-78-8 SECONDARY_CAS_RN
4026029 VANDF
C1506770 UMLSCUI
FMM PDB_CHEM_ID
CHEMBL1201179 ChEMBL_ID
CHEMBL554 ChEMBL_ID
D000077341 MESH_DESCRIPTOR_UI
DB01259 DRUGBANK_ID
5692 IUPHAR_LIGAND_ID
8378 INN_ID
0VUA21238F UNII
11557040 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
Lapatinib Human Prescription Drug Label 1 68180-801 TABLET 250 mg ORAL ANDA 28 sections