Lani
10-09-2008, 09:05 PM
On July 7, the FDA approved class safety labeling revisions for lapatinib tablets (Tykerb; GlaxoSmithKline) to include a boxed warning regarding the risk for hepatotoxicity.
Cases of hepatotoxicity (defined as serum aminotransferase levels > 3 times the upper limit of normal and total bilirubin levels > 1.5 x upper limit of normal) have been reported in clinical trials (incidence, < 1%) and postmarketing experience. Some of these cases have been severe, and deaths have been reported, although their cause remains uncertain. According to the FDA, disease onset has ranged from days to several months after initiation of therapy.
Liver function tests (transaminases, bilirubin, and alkaline phosphatase levels) should be obtained before starting treatment with lapatinib, every 4 to 6 weeks during therapy, and as clinically indicated.
Data from a pharmacokinetic study suggest that systemic exposure (area under the curve) to lapatinib after a single 100-mg oral dose increased by approximately 14% and 63% in patients with moderate and severe preexisting hepatic impairment, respectively. Because of this increase in exposure, caution is advised and dose reductions should be considered for patients with severe preexisting hepatic impairment. Severe changes in liver function that develop during therapy warrant permanent discontinuation of lapatinib.
Lapatinib is a kinase inhibitor indicated in combination with capecitabine for the treatment of advanced or metastatic breast cancer in patients whose tumors overexpress human epidermal receptor type 2 and who have received previous therapy, including an anthracycline, a taxane, and trastuzumab (Herceptin; Genentech Inc).
Cases of hepatotoxicity (defined as serum aminotransferase levels > 3 times the upper limit of normal and total bilirubin levels > 1.5 x upper limit of normal) have been reported in clinical trials (incidence, < 1%) and postmarketing experience. Some of these cases have been severe, and deaths have been reported, although their cause remains uncertain. According to the FDA, disease onset has ranged from days to several months after initiation of therapy.
Liver function tests (transaminases, bilirubin, and alkaline phosphatase levels) should be obtained before starting treatment with lapatinib, every 4 to 6 weeks during therapy, and as clinically indicated.
Data from a pharmacokinetic study suggest that systemic exposure (area under the curve) to lapatinib after a single 100-mg oral dose increased by approximately 14% and 63% in patients with moderate and severe preexisting hepatic impairment, respectively. Because of this increase in exposure, caution is advised and dose reductions should be considered for patients with severe preexisting hepatic impairment. Severe changes in liver function that develop during therapy warrant permanent discontinuation of lapatinib.
Lapatinib is a kinase inhibitor indicated in combination with capecitabine for the treatment of advanced or metastatic breast cancer in patients whose tumors overexpress human epidermal receptor type 2 and who have received previous therapy, including an anthracycline, a taxane, and trastuzumab (Herceptin; Genentech Inc).