Tykerb(lapatinib) 250mg tablets

IMPORTANT SAFETY INFORMATION FOR TYKERB

BOXED WARNING: HEPATOTOXICITY
TYKERB has been associated with hepatotoxicity. Hepatotoxicity (ALT or 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 and patients should not be re-treated with TYKERB.

INDICATION

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.

DOSE MODIFICATION GUIDELINES

Modify dose for cardiac and other toxicities, severe hepatic impairment, and CYP3A4 drug interactions. The concomitant use of strong CYP3A4 inhibitors and inducers should be avoided. Please see complete Prescribing Information.

IMPORTANT SAFETY INFORMATION FOR TYKERB

BOXED WARNING: HEPATOTOXICITY
TYKERB has been associated with hepatotoxicity. Hepatotoxicity (ALT or 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 and patients should not be re-treated with TYKERB.

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 - 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.

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

Diarrhea - Diarrhea, including severe diarrhea, has been reported during treatment with TYKERB and was the most common adverse reaction resulting in discontinuation of TYKERB therapy. Proactive management of diarrhea with antidiarrheal agents is important, and severe cases of diarrhea may require administration of oral or intravenous electrolytes and fluids, 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 and if symptoms are ≥Grade 3 (NCI CTCAE), TYKERB should be discontinued.

QT Prolongation - TYKERB prolongs the QT interval in some patients and should be administered with caution in patients with hypokalemia or hypomagnesemia, congenital long-term 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 ECG and electrolyte monitoring should be considered.

Pregnancy - Pregnancy Category D: 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 - The most common adverse reactions (>20%) during therapy with TYKERB plus capecitabine versus capecitabine alone were diarrhea (65%, 40%), palmar-plantar erythrodysesthesia (53%, 51%), nausea (44%, 43%), rash (28%, 14%), vomiting (26%, 21%), and fatigue (23%, 25%).

The most common Grade 3 and 4 adverse reactions (NCI CTCAE v3) with TYKERB plus capecitabine compared to capecitabine alone were diarrhea (14%, 10%) and palmar-plantar erythrodysesthesia (12%, 14%).

Laboratory Abnormalities - Laboratory Abnormalities during therapy with TYKERB plus capecitabine versus capecitabine alone were increased AST (49%, 43%), increased ALT (37%, 33%), and increased total bilirubin (45%, 30%).

Please see complete Prescribing Information, including BOXED WARNING for TYKERB.