Lapatinib

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 is a 4-anilinoquinazoline tyrosine kinase inhibitor of both Epidermal Growth Factor Receptor (EGFR [ErbB1]) and Human Epidermal Receptor Type 2 (HER2 [ErbB2]) receptors. It blocks the phosphorylation and activation of downstream 2nd messengers (Erk1/2 and Akt) which regulate cellular proliferation and survival of ErbB- and ErbB2-expressing tumours.

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.

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. antiarrythmic agents, cumulative high-dose anthracycline therapy). May increase serum levels of digoxin.

Contraindicated to hypersensitivity to any other ingredient of this product.

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 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).

Patient with hypokalaemia or hypomagnesaemia, congenital QT prolongation. Severe hepatic impairment. Pregnancy and lactation.

Cytotoxic Chemotherapy

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.

Store between 15-30° C.