Tykerb

Lapatinib ditosylate

In combination w/ capecitabine for patients w/ advanced or metastatic breast cancer, whose tumors overexpress HER2/neu (ErbB2) & who have progressed on prior trastuzumab therapy in the metastatic setting. In combination w/ trastuzumab for patients w/ hormone receptor -ve metastatic breast cancer whose tumors overexpress HER2/neu (ErbB2) & who have progressed on prior trastuzumab therapy in combination w/ chemotherapy in the metastatic setting. In combination w/ paclitaxel for the 1st line treatment of patients w/ metastatic breast cancer whose tumors overexpress HER2/neu (ErbB2) & for whom trastuzumab is not appropriate. In combination w/ an aromatase inhibitor for postmenopausal women w/ hormone receptor +ve, HER2/neu (ErbB2) overexpressing advanced or metastatic breast cancer, & for whom endocrine therapy is indicated.

Combination w/ capecitabine 1,250 mg once daily continuously + capecitabine 2,000 mg/m²/day in 2 doses 12 hr apart on days 1-14 in a 21-day cycle. Combination w/ trastuzumab 1,000 mg once daily continuously + trastuzumab 4 mg/kg as IV loading dose, followed by 2 mg/kg IV wkly. Combination w/ paclitaxel 1,500 mg once daily continuously + paclitaxel 80 mg/m² IV on days 1, 8, & 15 in a 28-day schedule. Alternatively, paclitaxel 175 mg/m² IV every 21 days. Combination w/ an aromatase inhibitor 1,500 mg once daily continuously + aromatase inhibitor (letrozole) 2.5 mg once daily. Patient w/ symptoms associated w/ decreased LVEF that are NCI CTCAE ≥3 or if LVEF drops below the institutional LLN Restart at a lower dose (reduced from 1,000 mg/day to 750 mg/day, from 1,250 mg to 1,000 mg/day or from 1,500 mg/day to 1,250 mg/day) after a min of 2 wk & if LVEF recovers to normal & the patient is asymptomatic. Patient w/ diarrhea which is NCI CTCAE grade 3 or grade 1 or 2 w/ complicating features Reintroduce at a lower dose (reduced from 1,000 mg/day to 750 mg/day, from 1,250 mg to 1,000 mg/day or from 1,500 mg/day to 1,250 mg/day) if diarrhea resolves to grade ≤1. Toxicity develops NCI CTCAE grade ≥2 Restart at standard dose of 1,000 mg/day, 1,250 mg/day, or 1,500 mg/day if the toxicity improves to grade ≤1. Toxicity recurs Restart at a lower dose (reduced from 1,000 mg/day to 750 mg/day, from 1,250 mg to 1,000 mg/day or from 1,500 mg/day to 1,250 mg/day). Severe hepatic impairment (Child-Pugh class C) Dose reduction from 1,250 mg/day to 750 mg/day or from 1,500 mg/day to 1,000 mg/day.

Should be taken on an empty stomach: Take at least 1 hr before or after a meal.

Hypersensitivity.

Patients w/ conditions that could impair left ventricular function, & those who have or may develop QTc interval prolongation (including hypokalemia or hypomagnesemia, congenital long QTc syndrome, & concomitant use w/ anti-arrhythmics or other medicinal products that cause QTc prolongation). Monitor for pulmonary symptoms indicative of ILD & pneumonitis. Monitor LFTs (transaminases, bilirubin, & alkaline phosphatase) before initiation, every 4-6 wk during treatment, & as clinically indicated. Discontinue permanently if severe hepatotoxicity develops during therapy. Diarrhea. Discontinue if erythema multiforme or life-threatening reactions eg, SJS or TEN are suspected. Concomitant use w/ CYP3A4 inhibitors or inducers. Severe hepatic impairment. Use of effective contraception in females of reproductive potential during therapy & for at least 5 days after the last dose. Pregnancy & lactation. Childn <18 yr. Elderly ≥65 yr.

Monotherapy: Anorexia; diarrhea leading to dehydration, nausea, vomiting; rash (including acneiform dermatitis); fatigue. Decreased LVEF; nail disorders including paronychia. Combination w/ capecitabine: Dyspepsia; dry skin; insomnia; stomatitis, constipation, abdominal pain; palmar-plantar erythrodysesthesia; pain in extremity, back pain; mucosal inflammation. Headache. Combination w/ paclitaxel: Neutropenia, leukopenia, anaemia; peripheral neuropathy; myalgia. Combination w/ letrozole: Epistaxis; alopecia; dry skin.

Increased systemic exposure w/ CYP3A4 inhibitors (eg, erythromycin, telithromycin, ketoconazole, itraconazole, posaconazole, voriconazole or grapefruit juice, ritonavir, saquinavir, cisapride, verapamil, pimozide, nefazodone, St. John's wort, cyclosporine). Decreased systemic exposure w/ CYP3A4 inducers (eg, rifampin, rifabutin, phenytoin, or carbamazepine). Decreased exposure w/ PPI pre-treatment (eg, esomeprazole). Increased oral midazolam AUC. Medications w/ narrow therapeutic index that are substrates of CYP3A4, CYP2C8 (eg, repaglinide), & P-gp (eg, quinidine). Increased exposure of paclitaxel. Increased occurrence of docetaxel-induced neutropenia. Increased AUC of SN-38 (active metabolite of irinotecan). Altered exposure &/or distribution w/ inhibitors & inducers of P-gp & BCRP. Increased AUC of digoxin. Affect pharmacokinetics of BCRP (eg, topotecan, quinidine) & OATP1B1 (eg, rosuvastatin) substrates. May increase bioavailability w/ grapefruit juice.

Targeted Cancer Therapy

L01EH01 - lapatinib ; Belongs to the class of human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitors. Used in the treatment of cancer.

Rx