lapatinib indications/contra

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

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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

Pharmacologic Action:

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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)

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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

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

Orange Book patent data (new drug applications)

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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:

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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:

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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:

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