Lapatinib
Therapeutic Class: Oncology (Cytotoxic Chemotherapy)
Indications:
Lapatinib, a kinase inhibitor, 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.
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. Lapatinib in combination with an aromatase inhibitor has not been compared to a trastuzumab-containing chemotherapy regimen for the treatment of metastatic breast cancer.
Lapatinib, a kinase inhibitor, 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.
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. Lapatinib in combination with an aromatase inhibitor has not been compared to a trastuzumab-containing chemotherapy regimen for the treatment of metastatic breast cancer.
Presentation:
Lapatinib 250: Each tablet contains Lapatinib ditosylate monohydrate INN equivalent to Lapatinib 250 mg
Description:
Lapatinib is a 4-anilinoquinazoline kinase inhibitor of the intracellular tyrosine kinase domains of both Epidermal Growth Factor Receptor (EGFR [ErbB1]) and of Human Epidermal Receptor Type 2 (HER2 [ErbB2]) receptors (estimated Kiapp values of 3nM and 13nM, respectively) with a dissociation half-life of ≥ 300 minutes. Lapatinib inhibits ErbB-driven tumor cell growth in vitro and in various animal models. Hormone receptor-positive breast cancer cells (with ER [Estrogen Receptor] and/or PgR[Progesterone Receptor]) that co-express the HER2 tend to be resistant to established endocrine therapies. Similarly, hormone receptor-positive breast cancer cells that initially lack EGFR or HER2, up-regulate these receptor proteins as the tumor becomes resistant to endocrine therapy.
Dosage & Administration:
The recommended dosage of Lapatinib 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 Lapatinib for hormone receptor-positive, HER2 positive metastatic breast cancer is 1500 mg (6 tablets) given orally once daily continuously in combination with letrozole. When Lapatinib is coadministered with letrozole, the recommended dose of letrozole is 2.5 mg once daily.
Lapatinib 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.
Lapatinib should be taken once daily. Do not divide daily doses of Lapatinib.
Modify dose for cardiac and other toxicities, severe hepatic impairment, and CYP3A4 drug interactions.
Administration
Should be taken on an empty stomach. Take at least 1 hr before or 1 hr after a meal. Do not eat/drink grapefruit products.
Interaction:
May increase the serum levels of CYP3A4, CYP2C8, and P-glycoprotein substrates. Increased exposure with CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, atazanavir, ritonavir). CYP3A4 inducers (e.g. carbamazepine, rifampicin) may reduce exposure to lapatinib. Increased risk of QT prolongation with drugs known to prolong QT intervals (e.g. antiarrhythmic agents, cumulative high-dose anthracycline therapy). May increase serum levels of digoxin.
Contraindications:
Contraindicated to hypersensitivity to any other ingredient of this product.
Side Effects:
GI disturbances, dermatological reactions (e.g. palmar-plantar erythrodysesthesia, rash), fatigue, decreases in LVEF, QT interval prolongation, stomatitis, mucosal inflammation, pain in extremities, back pain, dyspnoea, insomnia, epistaxis, alopecia, nail disorders (e.g. paronychia), interstitial lung disease, pneumonitis and hypersensitivity reactions including anaphylaxis.
Pregnancy & Lactation:
Pregnancy category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
Precautions & Warnings:
Patient with hypokalaemia or hypomagnesaemia, congenital QT prolongation. Severe hepatic impairment. Pregnancy and lactation.
Use in Special Populations:
Patient on potent CYP3A4 inhibitor-
HER2 overexpressing advanced or metastatic breast cancer: Increase gradually from 1.25 g daily up to 4.5 g daily.
HER2 overexpressing hormone receptor-positive metastatic breast cancer: Increase gradually from 1.5 g daily up to 5.5 g daily.Hepatic Impairment (Severe)-
HER2 overexpressing advanced or metastatic breast cancer: 750 mg once daily.
HER2 overexpressing hormone receptor positive metastatic breast cancer: 1 g once daily.
Storage:
Store between 15-30° C.
Description:
Lapatinib is a 4-anilinoquinazoline kinase inhibitor of the intracellular tyrosine kinase domains of both Epidermal Growth Factor Receptor (EGFR [ErbB1]) and of Human Epidermal Receptor Type 2 (HER2 [ErbB2]) receptors (estimated Kiapp values of 3nM and 13nM, respectively) with a dissociation half-life of ≥ 300 minutes. Lapatinib inhibits ErbB-driven tumor cell growth in vitro and in various animal models. Hormone receptor-positive breast cancer cells (with ER [Estrogen Receptor] and/or PgR[Progesterone Receptor]) that co-express the HER2 tend to be resistant to established endocrine therapies. Similarly, hormone receptor-positive breast cancer cells that initially lack EGFR or HER2, up-regulate these receptor proteins as the tumor becomes resistant to endocrine therapy.
Dosage & Administration:
The recommended dosage of Lapatinib 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 Lapatinib for hormone receptor-positive, HER2 positive metastatic breast cancer is 1500 mg (6 tablets) given orally once daily continuously in combination with letrozole. When Lapatinib is coadministered with letrozole, the recommended dose of letrozole is 2.5 mg once daily.
Lapatinib 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.
Lapatinib should be taken once daily. Do not divide daily doses of Lapatinib.
Modify dose for cardiac and other toxicities, severe hepatic impairment, and CYP3A4 drug interactions.
Administration
Should be taken on an empty stomach. Take at least 1 hr before or 1 hr after a meal. Do not eat/drink grapefruit products.
Interaction:
May increase the serum levels of CYP3A4, CYP2C8, and P-glycoprotein substrates. Increased exposure with CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, atazanavir, ritonavir). CYP3A4 inducers (e.g. carbamazepine, rifampicin) may reduce exposure to lapatinib. Increased risk of QT prolongation with drugs known to prolong QT intervals (e.g. antiarrhythmic agents, cumulative high-dose anthracycline therapy). May increase serum levels of digoxin.
Contraindications:
Contraindicated to hypersensitivity to any other ingredient of this product.
Side Effects:
GI disturbances, dermatological reactions (e.g. palmar-plantar erythrodysesthesia, rash), fatigue, decreases in LVEF, QT interval prolongation, stomatitis, mucosal inflammation, pain in extremities, back pain, dyspnoea, insomnia, epistaxis, alopecia, nail disorders (e.g. paronychia), interstitial lung disease, pneumonitis and hypersensitivity reactions including anaphylaxis.
Pregnancy & Lactation:
Pregnancy category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
Precautions & Warnings:
Patient with hypokalaemia or hypomagnesaemia, congenital QT prolongation. Severe hepatic impairment. Pregnancy and lactation.
Use in Special Populations:
Patient on potent CYP3A4 inhibitor-
HER2 overexpressing advanced or metastatic breast cancer: Increase gradually from 1.25 g daily up to 4.5 g daily.
HER2 overexpressing hormone receptor-positive metastatic breast cancer: Increase gradually from 1.5 g daily up to 5.5 g daily.Hepatic Impairment (Severe)-
HER2 overexpressing advanced or metastatic breast cancer: 750 mg once daily.
HER2 overexpressing hormone receptor positive metastatic breast cancer: 1 g once daily.
Storage:
Store between 15-30° C.