Important Safety Information: WARNING: Hepatotoxicity has been observed in clinical trials and postmarketing experience. The hepatotoxicity may be severe and deaths have been reported. Causality of the deaths is uncertain. See More

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Indications

TYKERB 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.

Limitation of use:  Patients should have disease progression on trastuzumab prior to initiation of treatment with TYKERB in combination with capecitabine.

TYKERB is indicated in combination with 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.

TYKERB in combination with an aromatase inhibitor has not been compared to a trastuzumab-containing chemotherapy regimen for the treatment of metastatic breast cancer.

IMPORTANT SAFETY INFORMATION

WARNING: Hepatotoxicity has been observed in clinical trials and postmarketing experience. The hepatotoxicity may be severe and deaths have been reported. Causality of the deaths is uncertain.

Contraindication: TYKERB is contraindicated in patients with known severe hypersensitivity (eg, anaphylaxis) to this product or any of its components.

Decreased Left Ventricular Ejection Fraction (LVEF): TYKERB has been reported to decrease LVEF. In clinical trials, >57% of LVEF decreases occurred within the first 12 weeks of treatment. Use caution if administering to patients with conditions that could impair LVEF. Confirm normal LVEF before starting TYKERB, and continue evaluations during treatment.

Hepatotoxicity: Hepatotoxicity (alanine transaminase [ALT] or aspartate transaminase [AST] >3 times the upper limit of normal and total bilirubin >2 times the upper limit of normal) has been observed in clinical trials (<1% of patients) and postmarketing experience. The hepatotoxicity may be severe and deaths have been reported. Causality of the deaths is uncertain. The hepatotoxicity may occur days to several months after initiation of treatment. Liver function tests (transaminases, bilirubin, and alkaline phosphatase) should be monitored before initiation of treatment, every 4 to 6 weeks during treatment, and as clinically indicated. If changes in liver function are severe, therapy with TYKERB should be discontinued.

Patients With Severe Hepatic Impairment: If TYKERB is to be administered to patients with severe preexisting hepatic impairment, dose reduction should be considered.

Diarrhea: Diarrhea has been reported during treatment with TYKERB. The diarrhea may be severe, and deaths have been reported. Diarrhea generally occurs early during treatment with TYKERB, with almost half of those patients with diarrhea first experiencing it within 6 days. This usually lasts 4 to 5 days. Lapatinib-induced diarrhea is usually low-grade, with grade 3 and 4 diarrhea occurring in <10% and <1% of patients, respectively. Prompt treatment of diarrhea with antidiarrheal agents (such as loperamide) after the first unformed stool is recommended. Severe cases of diarrhea may require administration of oral or intravenous electrolytes and fluids, use of antibiotics such as fluoroquinolones (especially if diarrhea is persistent beyond 24 hours, there is fever, or grade 3 or 4 neutropenia), and interruption or discontinuation of therapy with TYKERB.

Interstitial Lung Disease/Pneumonitis: TYKERB has been associated with interstitial lung disease and pneumonitis. Patients should be monitored for pulmonary symptoms indicative of interstitial lung disease or pneumonitis. Discontinue TYKERB in patients who experience pulmonary symptoms indicative of greater than or equal to grade 3 interstitial lung disease/pneumonitis.

QT Prolongation: TYKERB prolongs the QT interval in some patients and should be administered with caution in patients who have or may develop QT prolongation, including patients with hypokalemia or hypomagnesemia, congenital long QT syndrome, patients taking cumulative high-dose anthracycline, antiarrhythmics, or other products that lead to QT prolongation. Hypokalemia and hypomagnesemia should be corrected prior to administration, and electrocardiogram and electrolyte monitoring should be considered.

Severe Cutaneous Reactions have been reported.  Discontinue TYKERB if life-threatening reactions (eg, erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis) are suspected.

Pregnancy: TYKERB can cause fetal harm when administered to a pregnant woman. Women should be advised not to become pregnant when taking TYKERB. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

Adverse Reactions in HER2+ Metastatic Breast Cancer: The most common adverse reactions (≥10%) during therapy with TYKERB plus capecitabine vs capecitabine were diarrhea (65%, 40%), palmar-plantar erythrodysesthesia (53%, 51%), nausea (44%, 43%), rash (28%, 14%), vomiting (26%, 21%), fatigue (23,%, 25%), mucosal inflammation (15%, 12%), stomatitis (14%, 11%), pain in extremity (12%, 7%), dyspnea (12%, 8%), back pain (11%, 6%), dyspepsia (11%, 3%), dry skin (10%, 6%), and insomnia (10%, 6%).The most common grade 3 and 4 adverse reactions with TYKERB plus capecitabine compared to capecitabine were diarrhea (14%, 10%) and palmar-plantar erythrodysesthesia (12%, 14%).

Adverse Reactions in HR+, HER2+ Metastatic Breast Cancer: The most common adverse reactions (≥10%) during therapy with TYKERB plus letrozole compared to letrozole were diarrhea (64%, 20%), rash (44%, 13%), nausea (31%, 21%), fatigue (20%, 17%), vomiting (17%, 11%), headache, (14%, 13%), dry skin (13%, 4%), alopecia (13%, 7%), pruritus (12%, 9%), asthenia (12%, 11%), nail disorder (11%, <1%), anorexia (11%, 9%) and epistaxis (11%, 2%). The most common grade 3 and 4 adverse reactions with TYKERB plus letrozole compared to letrozole alone were diarrhea (9%, <1%) and fatigue (2%, <1%).

Laboratory Abnormalities in HER2+ Metastatic Breast Cancer: Laboratory abnormalities during therapy with TYKERB plus capecitabine vs capecitabine included increased AST (49%, 43%), increased ALT (37%, 33%), and increased total bilirubin (45%, 30%).

Laboratory Abnormalities in HR+, HER2+ Metastatic Breast Cancer: Laboratory abnormalities during therapy with TYKERB plus letrozole compared to letrozole included increased AST (53%, 36%), increased ALT (46%, 35%), and increased total bilirubin (22%, 11%).