Details
Stereochemistry | ACHIRAL |
Molecular Formula | C29H26ClFN4O4S |
Molecular Weight | 581.058 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CS(=O)(=O)CCNCC1=CC=C(O1)C2=CC3=C(C=C2)N=CN=C3NC4=CC(Cl)=C(OCC5=CC(F)=CC=C5)C=C4
InChI
InChIKey=BCFGMOOMADDAQU-UHFFFAOYSA-N
InChI=1S/C29H26ClFN4O4S/c1-40(36,37)12-11-32-16-23-7-10-27(39-23)20-5-8-26-24(14-20)29(34-18-33-26)35-22-6-9-28(25(30)15-22)38-17-19-3-2-4-21(31)13-19/h2-10,13-15,18,32H,11-12,16-17H2,1H3,(H,33,34,35)
Molecular Formula | C29H26ClFN4O4S |
Molecular Weight | 581.058 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionCurator's Comment: Description was created based on several sources, including
http://adisinsight.springer.com/drugs/800015425
Curator's Comment: Description was created based on several sources, including
http://adisinsight.springer.com/drugs/800015425
Lapatinib is a small molecule and a member of the 4-anilinoquinazoline class of kinase inhibitors. It is present as the monohydrate of the ditosylate salt (trade name TYKERB). Lapatinib is dual inhibitor of the EGFR (epidermal growth factor receptor; also called HER1 or ErbB1) and HER2 receptor tyrosine kinases. Lapatinib was developed by GlaxoSmithKline, however, Novartis subsequently acquired all the rights to the drug from GlaxoSmithKline. TYKERB is indicated in combination therapy for the treatment of metastatic breast cancer that overexpresses the HER2 receptor.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25977884
Curator's Comment: Increased lapatinib uptake was observed in brain metastases but not in normal brain.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL203 |
3.0 nM [Ki] | ||
Target ID: CHEMBL1824 |
13.0 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | TYKERB Approved UseTYKERB® is indicated in combination with: •capecitabine for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab. Limitation of Use: Patients should have disease progression on trastuzumab prior to initiation of treatment with TYKERB in combination with capecitabine. •letrozole for the treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer that overexpresses the HER2 receptor for whom hormonal therapy is indicated. TYKERB in combination with an aromatase inhibitor has not been compared to a trastuzumab-containing chemotherapy regimen for the treatment of metastatic breast cancer. TYKERB, a kinase inhibitor, is indicated in combination with: (1) •capecitabine, for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab. Limitation of Use: Patients should have disease progression on trastuzumab prior to initiation of treatment with TYKERB in combination with capecitabine. •letrozole for the treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer that overexpresses the HER2 receptor for whom hormonal therapy is indicated. TYKERB in combination with an aromatase inhibitor has not been compared to a trastuzumab-containing chemotherapy regimen for the treatment of metastatic breast cancer. Launch Date2007 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2.43 μg/mL |
1250 mg 1 times / day steady-state, oral dose: 1250 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
LAPATINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
36.2 μg × h/mL |
1250 mg 1 times / day steady-state, oral dose: 1250 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
LAPATINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
24 h |
1250 mg 1 times / day steady-state, oral dose: 1250 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
LAPATINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1% |
LAPATINIB plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
1250 mg 1 times / day steady, oral MTD Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 50 years (range: 30–78 years) Health Status: unhealthy Age Group: 50 years (range: 30–78 years) Sex: F Sources: |
DLT: Rash, Diarrhea... Dose limiting toxicities: Rash (grade 3, 2 patients) Sources: Diarrhea (grade 3, 2 patients) Hypoxia (grade 3, 1 patient) Pulmonary embolus (grade 4, 2 patients) |
1500 mg 1 times / day steady, oral Dose: 1500 mg, 1 times / day Route: oral Route: steady Dose: 1500 mg, 1 times / day Sources: |
unhealthy, 50 years (range: 30–78 years) Health Status: unhealthy Age Group: 50 years (range: 30–78 years) Sex: F Sources: |
DLT: Mucositis, Rash... Dose limiting toxicities: Mucositis (grade 3, 2 patients) Sources: Rash (grade 3, 2 patients) |
1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Disc. AE: Diarrhea... Other AEs: Diarrhea, Diarrhea... AEs leading to discontinuation/dose reduction: Diarrhea (grade 4, 1%) Other AEs:Diarrhea (all grades, 65%) Sources: Diarrhea (grade 3, 13%) Nausea (all grades, 44%) Nausea (grade 3, 2%) Vomiting (all grades, 26%) Vomiting (grade 3, 2%) Stomatitis (all grades, 14%) Dyspepsia (all grades, 11%) Dyspepsia (grade 3, <1%) Palmar-plantar erythrodysesthesia syndrome (all grades, 53%) Palmar-plantar erythrodysesthesia syndrome (grade 3, 12%) Rash (all grades, 28%) Rash (grade 3, 2%) Dermatitis acneiform (grade 3, <1%) Dry skin (all grades, 10%) Mucosal inflammation (all grades, 15%) Pain in extremity (all grades, 12%) Pain in extremity (grade 3, 1%) Back pain (all grades, 11%) Back pain (grade 3, 1%) Dyspnea (all grades, 12%) Dyspnea (grade 3, 3%) Insomnia (all grades, 10%) Insomnia (grade 3, <1%) Hepatotoxicity (severe|grade 5) Bilirubin total increased (grade 3, 4%) Bilirubin total increased (grade 1-2, 41%) AST increased (grade 3, 2%) AST increased (grade 4, <1%) AST increased (grade 1-2, 46%) ALT increased (grade 3, 2%) ALT increased (grade 1-2, 35%) |
1800 mg 1 times / day steady, oral MTD Dose: 1800 mg, 1 times / day Route: oral Route: steady Dose: 1800 mg, 1 times / day Sources: |
unhealthy, 60 years (range: 37 – 73 years) Health Status: unhealthy Age Group: 60 years (range: 37 – 73 years) Sex: M+F Sources: |
DLT: Diarrhea, Gamma GT increased... Other AEs: Stomatitis, Rash... Dose limiting toxicities: Diarrhea (grade 3, 2 patients) Other AEs:Gamma GT increased (grade 3, 1 patient) Stomatitis (grade 1, 1 patient) Sources: Rash (grade 2, 2 patients) Seborrheic dermatitis (grade 1, 1 patient) Paronychia (grade 1, 1 patient) Anorexia (grade 1, 3 patients) Lymphocyte count decreased (grade 1, 1 patient) |
1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 63 years Health Status: unhealthy Age Group: 63 years Sex: F Sources: |
Other AEs: Hepatotoxicity, Bilirubin total increased... Other AEs: Hepatotoxicity (severe|grade 5) Sources: Bilirubin total increased (grade 3, <1%) Bilirubin total increased (grade 4, <1%) Bilirubin total increased (grade 1-2, 20%) AST increased (grade 3, 6%) AST increased (grade 1-2, 47%) ALT increased (grade 3, 5%) ALT increased (grade 4, <1%) ALT increased (grade 1-2, 40%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Hypoxia | grade 3, 1 patient DLT |
1250 mg 1 times / day steady, oral MTD Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 50 years (range: 30–78 years) Health Status: unhealthy Age Group: 50 years (range: 30–78 years) Sex: F Sources: |
Diarrhea | grade 3, 2 patients DLT |
1250 mg 1 times / day steady, oral MTD Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 50 years (range: 30–78 years) Health Status: unhealthy Age Group: 50 years (range: 30–78 years) Sex: F Sources: |
Rash | grade 3, 2 patients DLT |
1250 mg 1 times / day steady, oral MTD Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 50 years (range: 30–78 years) Health Status: unhealthy Age Group: 50 years (range: 30–78 years) Sex: F Sources: |
Pulmonary embolus | grade 4, 2 patients DLT |
1250 mg 1 times / day steady, oral MTD Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 50 years (range: 30–78 years) Health Status: unhealthy Age Group: 50 years (range: 30–78 years) Sex: F Sources: |
Mucositis | grade 3, 2 patients DLT |
1500 mg 1 times / day steady, oral Dose: 1500 mg, 1 times / day Route: oral Route: steady Dose: 1500 mg, 1 times / day Sources: |
unhealthy, 50 years (range: 30–78 years) Health Status: unhealthy Age Group: 50 years (range: 30–78 years) Sex: F Sources: |
Rash | grade 3, 2 patients DLT |
1500 mg 1 times / day steady, oral Dose: 1500 mg, 1 times / day Route: oral Route: steady Dose: 1500 mg, 1 times / day Sources: |
unhealthy, 50 years (range: 30–78 years) Health Status: unhealthy Age Group: 50 years (range: 30–78 years) Sex: F Sources: |
Dry skin | all grades, 10% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Insomnia | all grades, 10% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Back pain | all grades, 11% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Dyspepsia | all grades, 11% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Dyspnea | all grades, 12% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Pain in extremity | all grades, 12% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Stomatitis | all grades, 14% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Mucosal inflammation | all grades, 15% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Vomiting | all grades, 26% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Rash | all grades, 28% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Nausea | all grades, 44% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Palmar-plantar erythrodysesthesia syndrome | all grades, 53% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Diarrhea | all grades, 65% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
ALT increased | grade 1-2, 35% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Bilirubin total increased | grade 1-2, 41% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
AST increased | grade 1-2, 46% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Back pain | grade 3, 1% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Pain in extremity | grade 3, 1% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Palmar-plantar erythrodysesthesia syndrome | grade 3, 12% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Diarrhea | grade 3, 13% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
ALT increased | grade 3, 2% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
AST increased | grade 3, 2% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Nausea | grade 3, 2% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Rash | grade 3, 2% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Vomiting | grade 3, 2% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Dyspnea | grade 3, 3% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Bilirubin total increased | grade 3, 4% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Dermatitis acneiform | grade 3, <1% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Dyspepsia | grade 3, <1% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Insomnia | grade 3, <1% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Diarrhea | grade 4, 1% Disc. AE |
1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
AST increased | grade 4, <1% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Hepatotoxicity | severe|grade 5 | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: |
Lymphocyte count decreased | grade 1, 1 patient | 1800 mg 1 times / day steady, oral MTD Dose: 1800 mg, 1 times / day Route: oral Route: steady Dose: 1800 mg, 1 times / day Sources: |
unhealthy, 60 years (range: 37 – 73 years) Health Status: unhealthy Age Group: 60 years (range: 37 – 73 years) Sex: M+F Sources: |
Paronychia | grade 1, 1 patient | 1800 mg 1 times / day steady, oral MTD Dose: 1800 mg, 1 times / day Route: oral Route: steady Dose: 1800 mg, 1 times / day Sources: |
unhealthy, 60 years (range: 37 – 73 years) Health Status: unhealthy Age Group: 60 years (range: 37 – 73 years) Sex: M+F Sources: |
Seborrheic dermatitis | grade 1, 1 patient | 1800 mg 1 times / day steady, oral MTD Dose: 1800 mg, 1 times / day Route: oral Route: steady Dose: 1800 mg, 1 times / day Sources: |
unhealthy, 60 years (range: 37 – 73 years) Health Status: unhealthy Age Group: 60 years (range: 37 – 73 years) Sex: M+F Sources: |
Stomatitis | grade 1, 1 patient | 1800 mg 1 times / day steady, oral MTD Dose: 1800 mg, 1 times / day Route: oral Route: steady Dose: 1800 mg, 1 times / day Sources: |
unhealthy, 60 years (range: 37 – 73 years) Health Status: unhealthy Age Group: 60 years (range: 37 – 73 years) Sex: M+F Sources: |
Anorexia | grade 1, 3 patients | 1800 mg 1 times / day steady, oral MTD Dose: 1800 mg, 1 times / day Route: oral Route: steady Dose: 1800 mg, 1 times / day Sources: |
unhealthy, 60 years (range: 37 – 73 years) Health Status: unhealthy Age Group: 60 years (range: 37 – 73 years) Sex: M+F Sources: |
Rash | grade 2, 2 patients | 1800 mg 1 times / day steady, oral MTD Dose: 1800 mg, 1 times / day Route: oral Route: steady Dose: 1800 mg, 1 times / day Sources: |
unhealthy, 60 years (range: 37 – 73 years) Health Status: unhealthy Age Group: 60 years (range: 37 – 73 years) Sex: M+F Sources: |
Gamma GT increased | grade 3, 1 patient DLT |
1800 mg 1 times / day steady, oral MTD Dose: 1800 mg, 1 times / day Route: oral Route: steady Dose: 1800 mg, 1 times / day Sources: |
unhealthy, 60 years (range: 37 – 73 years) Health Status: unhealthy Age Group: 60 years (range: 37 – 73 years) Sex: M+F Sources: |
Diarrhea | grade 3, 2 patients DLT, Disc. AE |
1800 mg 1 times / day steady, oral MTD Dose: 1800 mg, 1 times / day Route: oral Route: steady Dose: 1800 mg, 1 times / day Sources: |
unhealthy, 60 years (range: 37 – 73 years) Health Status: unhealthy Age Group: 60 years (range: 37 – 73 years) Sex: M+F Sources: |
Bilirubin total increased | grade 1-2, 20% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 63 years Health Status: unhealthy Age Group: 63 years Sex: F Sources: |
ALT increased | grade 1-2, 40% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 63 years Health Status: unhealthy Age Group: 63 years Sex: F Sources: |
AST increased | grade 1-2, 47% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 63 years Health Status: unhealthy Age Group: 63 years Sex: F Sources: |
ALT increased | grade 3, 5% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 63 years Health Status: unhealthy Age Group: 63 years Sex: F Sources: |
AST increased | grade 3, 6% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 63 years Health Status: unhealthy Age Group: 63 years Sex: F Sources: |
Bilirubin total increased | grade 3, <1% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 63 years Health Status: unhealthy Age Group: 63 years Sex: F Sources: |
ALT increased | grade 4, <1% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 63 years Health Status: unhealthy Age Group: 63 years Sex: F Sources: |
Bilirubin total increased | grade 4, <1% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 63 years Health Status: unhealthy Age Group: 63 years Sex: F Sources: |
Hepatotoxicity | severe|grade 5 | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Sources: |
unhealthy, 63 years Health Status: unhealthy Age Group: 63 years Sex: F Sources: |
Overview
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Drug as victim
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
Targeting HER2 in brain metastases from breast cancer. | 2003 Nov 15 |
|
Gateways to clinical trials. | 2003 Oct |
|
Gateways to clinical trials. | 2004 Jan-Feb |
|
Early success of combined EGFR and Her2 receptor blockade as a clinical strategy in breast cancer. | 2004 Jun |
|
Gateways to clinical trials. | 2004 Nov |
|
A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells. | 2004 Sep 15 |
|
Study of the biologic effects of lapatinib, a reversible inhibitor of ErbB1 and ErbB2 tyrosine kinases, on tumor growth and survival pathways in patients with advanced malignancies. | 2005 Apr 10 |
|
The epidermal growth factor receptor as a target for colorectal cancer therapy. | 2005 Feb |
|
Phase I pharmacokinetic studies evaluating single and multiple doses of oral GW572016, a dual EGFR-ErbB2 inhibitor, in healthy subjects. | 2005 Jan |
|
The dual ErbB1/ErbB2 inhibitor, lapatinib (GW572016), cooperates with tamoxifen to inhibit both cell proliferation- and estrogen-dependent gene expression in antiestrogen-resistant breast cancer. | 2005 Jan 1 |
|
Gateways to clinical trials. | 2005 Jan-Feb |
|
Clinical trials of intracellular signal transductions inhibitors for breast cancer--a strategy to overcome endocrine resistance. | 2005 Jul |
|
Gateways to clinical trials. | 2005 Jun |
|
Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. | 2005 Mar |
|
EGFR inhibition in non-small cell lung cancer: resistance, once again, rears its ugly head. | 2005 Mar |
|
Combining lapatinib (GW572016), a small molecule inhibitor of ErbB1 and ErbB2 tyrosine kinases, with therapeutic anti-ErbB2 antibodies enhances apoptosis of ErbB2-overexpressing breast cancer cells. | 2005 Sep 15 |
|
Antitumor activity of HER-2 inhibitors. | 2005 Sep 8 |
|
Targeting the EGFR pathway for cancer therapy. | 2006 |
|
Dual/pan-HER tyrosine kinase inhibitors: focus in breast cancer. | 2006 |
|
Lessons from the drug discovery of lapatinib, a dual ErbB1/2 tyrosine kinase inhibitor. | 2006 |
|
Targeted therapy for metastatic breast cancer. | 2006 Dec 28 |
|
Lapatinib plus capecitabine for HER2-positive advanced breast cancer. | 2006 Dec 28 |
|
A novel mutation in the tyrosine kinase domain of ERBB2 in hepatocellular carcinoma. | 2006 Dec 6 |
|
Lapatinib: a novel dual tyrosine kinase inhibitor with activity in solid tumors. | 2006 Feb |
|
Regulation of survivin by ErbB2 signaling: therapeutic implications for ErbB2-overexpressing breast cancers. | 2006 Feb 1 |
|
Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells. | 2006 Feb 1 |
|
HER2 kinase domain mutation results in constitutive phosphorylation and activation of HER2 and EGFR and resistance to EGFR tyrosine kinase inhibitors. | 2006 Jul |
|
Old and new perspectives in the pharmacological treatment of advanced or recurrent endometrial cancer: Hormonal therapy, chemotherapy and molecularly targeted therapies. | 2006 Jun |
|
Gateways to clinical trials. | 2006 Mar |
|
Her-2 targeted therapy: beyond breast cancer and trastuzumab. | 2006 Mar |
|
A phase II study of vinflunine in bladder cancer patients progressing after first-line platinum-containing regimen. | 2006 May 22 |
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Closing in on a cure. | 2006 Oct 23 |
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Targeted therapy of breast cancer. | 2007 |
|
HER2 therapy. HER2 (ERBB2): functional diversity from structurally conserved building blocks. | 2007 |
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relocating job wise? A mathematical model separates quantitatively the cytostatic and cytotoxic effects of a HER2 tyrosine kinase inhibitor. | 2007 Apr 3 |
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Lapatinib plus capecitabine in breast cancer. | 2007 Apr 5 |
|
European Society for Medical Oncology 2006: meeting highlights on targeted therapies. Istanbul, Turkey, 29 September-3 October 2006. | 2007 Feb |
|
Lapatinib: a dual inhibitor of EGFR and HER2 tyrosine kinase activity. | 2007 Feb |
|
Dual inhibition of ErbB1 (EGFR/HER1) and ErbB2 (HER2/neu). | 2007 Feb |
|
The 17q12-q21 amplicon: Her2 and topoisomerase-IIalpha and their importance to the biology of solid tumours. | 2007 Feb |
|
The EGF receptor Hokey-Cokey. | 2007 Mar |
|
Vinorelbine plus 3-weekly trastuzumab in metastatic breast cancer: a single-centre phase 2 trial. | 2007 Mar 20 |
|
Combination treatment with Grb7 peptide and Doxorubicin or Trastuzumab (Herceptin) results in cooperative cell growth inhibition in breast cancer cells. | 2007 May 21 |
Patents
Sample Use Guides
The recommended dosage of TYKERB for advanced or metastatic breast cancer is 1,250 mg (5 tablets) given orally once daily on Days 1-21 continuously in combination with capecitabine 2,000 mg/m2 /day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle. The recommended dose of TYKERB for hormone receptor positive, HER2 positive metastatic breast cancer is 1500 mg (6 tablets) given orally once daily continuously in combination with letrozole. When TYKERB is coadministered with letrozole, the recommended dose of letrozole is 2.5 mg once daily. • TYKERB should be taken at least one hour before or one hour after a meal. However, capecitabine should be taken with food or within 30 minutes after food. • TYKERB should be taken once daily. Do not divide daily doses of TYKERB. • Modify dose for cardiac and other toxicities, severe hepatic impairment, and CYP3A4 drug interactions.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22964224
lapatinib-induced time- and dose-dependent phosphorylation dynamics in SKBR3 breast cancer cells. Among 4953 identified phosphopeptides from 1548 proteins, a small proportion (5-7%) was regulated at least twofold by 1-10 μm lapatinib.
Substance Class |
Chemical
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QL01XE07
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C155764
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NBK547971
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C2167
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C129825
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284209
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L01XE07
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Lapatinib
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Related Record | Type | Details | ||
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TRANSPORTER -> INHIBITOR | |||
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METABOLIC ENZYME -> INHIBITOR |
Lapatinib is a mechanism-based inactivator of CYP3A4, most likely via the formation and further oxidation of its O-dealkylated metabolite to a quinoneimine that covalently modifies the CYP3A4 apoprotein and/or heme moiety.
TIME-DEPENDENT INHIBITION
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BINDING
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SALT/SOLVATE -> PARENT |
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EXCRETED UNCHANGED |
AMOUNT EXCRETED
FECAL
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Related Record | Type | Details | ||
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METABOLITE -> PARENT | |||
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METABOLITE TOXIC -> PARENT |
Specifically, the structure of O-dealkylated lapatinib has the potential to generate a reactive quinoneimine similar to the model hepatotoxin acetaminophen. lapatinib is a mechanism-based inactivator of CYP3A4, most likely via the formation and further oxidation of its O-dealkylated metabolite to a quinoneimine that covalently modifies the CYP3A4 apoprotein and/or heme moiety.
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METABOLITE -> PARENT | |||
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METABOLITE -> PARENT | |||
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METABOLITE -> PARENT | |||
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METABOLITE -> PARENT | |||
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METABOLITE -> PARENT |
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METABOLITE -> PARENT |
MAJOR
FECAL
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METABOLITE -> PARENT |
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METABOLITE -> PARENT |
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METABOLITE -> PARENT | |||
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METABOLITE -> PARENT |
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ACTIVE MOIETY |
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Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Tmax | PHARMACOKINETIC |
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Biological Half-life | PHARMACOKINETIC |
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