LAPATINIB

12.1 Mechanism of Action 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 Ki app values of 3nM and 13nM, respectively) with a dissociation half-life of greater than or equal to 300 minutes. Lapatinib inhibits ErbB-driven tumor cell growth in vitro and in various animal models. An additive effect was demonstrated in an in vitro study when lapatinib and 5-FU (the active metabolite of capecitabine) were used in combination in the 4-tumor cell lines tested. The growth inhibitory effects of lapatinib were evaluated in trastuzumab-conditioned cell lines. Lapatinib retained significant activity against breast cancer cell lines selected for long-term growth in trastuzumab-containing medium in vitro . These in vitro findings suggest non-cross-resistance between these two agents. Hormone receptor-positive breast cancer

Contraindications

• • 4 CONTRAINDICATIONS Lapatinib tablets are contraindicated in patients with known severe hypersensitivity (e.g.
• • anaphylaxis) to this product or any of its components. Known severe hypersensitivity (e.g.
• • anaphylaxis) to this product or any of its components. ( 4 )