Lapatinib - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS Decreases in left ventricular ejection fraction (LVEF) have been reported.

Confirm normal LVEF before starting lapatinib and continue evaluations during treatment.

Lapatinib has been associated with hepatotoxicity.

Monitor liver function tests before initiation of treatment, every 4 to 6 weeks during treatment, and as clinically indicated.

Discontinue and do not restart lapatinib if patients experience severe changes in liver function tests.

Dose reduction in patients with severe hepatic impairment should be considered. ( 2.2 , 5.3 , 8.7 ) Diarrhea, including severe diarrhea, has been reported during treatment.

Manage with antidiarrheal agents, and replace fluids and electrolytes if severe.

Lapatinib has been associated with interstitial lung disease and pneumonitis.

Discontinue lapatinib if patients experience severe pulmonary symptoms.

Lapatinib may prolong the QT interval in some patients.

Consider electrocardiogram (ECG) and electrolyte monitoring. ( 5.6, 12.2 ) Severe cutaneous reactions have been reported.

Discontinue lapatinib if life-threatening reactions are suspected.

Lapatinib can cause fetal harm.

Advise patients of the potential risk to the fetus and to use effective contraception. ( 5.8 , 8.1 , 8.3 ) 5.1 Decreased Left Ventricular Ejection Fraction Lapatinib has been reported to decrease LVEF [see Adverse Reactions ] .

In clinical trials, the majority (greater than 57%) of LVEF decreases occurred within the first 12 weeks of treatment; however, data on long-term exposure are limited.

Caution should be taken if lapatinib is to be administered to patients with conditions that could impair left ventricular function.

LVEF should be evaluated in all patients prior to initiation of treatment with lapatinib to ensure that the patient has a baseline LVEF that is within the institution’s normal limits.

LVEF should continue to be evaluated during treatment with lapatinib to ensure that LVEF does not decline below the institution’s normal limits [see Dosage and Administration ] .

5.2 Hepatotoxicity Hepatotoxicity [alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 times the upper limit of normal (ULN) and total bilirubin greater than 2 times the ULN] has been observed in clinical trials (less than 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 lapatinib should be discontinued and patients should not be retreated with lapatinib [see Adverse Reactions ] .

5.3 Patients With Severe Hepatic Impairment If lapatinib is to be administered to patients with severe preexisting hepatic impairment, dose reduction should be considered [see Dosage and Administration and Use in Specific Populations ] .