Lapatinib

Indications

Lapatinib is used for: Breast cancer

Adult Dose

Oral Breast Cancer HER2-overexpressing metastatic breast cancer Indicated in combination with capecitabine for 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 1250 mg PO qDay on Days 1-21 continuously in combination with capecitabine (2000 mg/m²/day PO divided q12hr) on Days 1-14 in a repeating 21-day cycle Hormone-positive & HER2-positive advanced breast cancer Indicated in combination therapy with letrozole for treatment of postmenopausal women with hormone receptor-positive and HER2-positive breast cancer for whom hormonal therapy is indicated 1500 mg PO qDay administered continuously in combination with letrozole 2.5 mg PO qDay Hepatic Impairment Severe (Child-Pugh Class C) HER2 positive metastatic breast cancer: Reduce dose from 1250 mg/day to 750 mg/day Hormone receptor positive, HER2 positive breast cancer: Reduce dose from 1500 mg/day to 1000 mg/day

Child Dose

Safety and efficacy not established

Renal Dose

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.

Contra Indications

Hypersensitivity to lapatinib ditosylate

Precautions

Evaluate left ventricular ejection fraction (LVEF) prior to treatment. Moderate or severe hepatic impairment. Patients who have or may develop QTc prolongation, including those w/ hypokalaemia or hypomagnesemia. Monitor liver function & pulmonary symptoms indicative of interstitial lung disease/pneumonitis. Pregnancy & lactation. Lactation: Do not nurse

Pregnancy-Lactation

Pregnancy Category: D Lactation: Do not nurse

Interactions

Increased conc w/ CYP3A4 inhibitors (eg ketoconazole, itraconazole or grapefruit juice), midazolam, irinotecan & digoxin. Decreased conc w/ CYP3A4 inducers (eg rifampin, carbamazepine, phenytoin) & proton-pump inhibitors (eg esomeprazole). Altered pharmacokinetics w/ P-glycoprotein, breast cancer resistance protein (BCRP) inhibitors & inducers, topotecan & rosuvastation. Increased incidence & severity of adverse events w/ paclitaxel & docetaxel. CYP3A4 or CYP2C8 substrates.

Adverse Effects

Side effects of Lapatinib : >10% (lapatinib+capecitabine) Diarrhea (65%), Anemia (56%), Hand-foot synd (53%), Increased LFTs (37-49%), Nausea (44%), Rash (28%), Vomiting (26%), Pain (23%), Neutropenia (22%), Thrombocytopenia (18%), Mucositis (15%), Stomatitis (14%), Dyspnea (12%), Dyspepsia (11%), Insomnia (10%) 1-10% Insomnia

Mechanism of Action

Kinase inhibitor, blocks EGF-receptor HER2 kinase; tyrosing kinase inhibition possibly blocks angiogenesis and cellular proliferation.