UpToDate Official reprint from UpToDate? www.uptodate.com ?2016 UpToDate? Wolters Kluwer HealthPrint | Back Lapatinib: Drug information Copyright 1978-2016 Lexicomp, Inc. All rights reserved. (For additional information see "Lapatinib: Patient drug information")
For abbreviations and symbols that may be used in Lexicomp (show table) ALERT: US Boxed Warning Hepatotoxicity: 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.
Brand Names: US Tykerb Brand Names: Canada Tykerb Pharmacologic Category Antineoplastic Agent, Anti-HER2; Antineoplastic Agent, Epidermal Growth Factor Receptor (EGFR) Inhibitor; Antineoplastic Agent, Tyrosine Kinase Inhibitor Dosing: Adult Breast cancer, metastatic, HER2+ (with prior anthracycline, taxane, and trastuzumab therapy): Oral: 1250 mg once daily (in combination with capecitabine) until disease progression or unacceptable toxicity (Geyer, 2006)
Breast cancer, metastatic, HER2+, hormonal therapy indicated: Oral: 1500 mg once daily (in combination with letrozole) until disease progression (Johnston, 2009)
Breast cancer, metastatic, HER2+ with brain metastases, first-line therapy (off-label use): Oral: 1250 mg once daily (in combination with capecitabine) until disease progression or unacceptable toxicity (Bachelot, 2013)
Breast cancer, metastatic, HER2+, with progression on prior trastuzumab therapy (off-label use): Oral: 1000 mg once daily (in combination with trastuzumab) (Blackwell, 2010; Blackwell, 2012)
Missed doses: If a dose is missed, resume with the next scheduled daily dose; do not double the dose the next day.
Dosage adjustment for concomitant CYP3A4 inhibitors/inducers:
CYP3A4 inhibitors: Avoid the use of concomitant strong CYP3A4 inhibitors. If concomitant use cannot be avoided, consider reducing lapatinib to 500 mg once daily with careful monitoring. When a strong CYP3A4 inhibitor is discontinued, allow ~1 week to elapse prior to adjusting the lapatinib dose upward.
CYP3A4 inducers: Avoid the use of concomitant strong CYP3A4 inducers.
U.S. labeling: If concomitant use cannot be avoided, consider gradually titrating lapatinib from 1250 mg once daily up to 4500 mg daily (in combination with capecitabine) or from 1500 mg once daily up to 5500 mg daily (in combination with letrozole), based on tolerability and with careful monitoring. If the strong CYP3A4 enzyme inducer is discontinued, reduce the lapatinib dose to the indicated dose.
Canadian labeling: If concomitant use cannot be avoided, titrate lapatinib dose gradually upward based on tolerability. If the strong CYP3A4 enzyme inducer is discontinued, reduce the lapatinib dose over 2 weeks.
Dosing: Geriatric Refer to adult dosing. Dosing: Renal Impairment There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); however, due to the minimal renal elimination (<2%), dosage adjustments may not be necessary. Dosing: Hepatic Impairment Mild or moderate preexisting impairment (Child-Pugh class A or B): There are no dosage adjustments provided in the manufacturer’s labeling.
Severe preexisting impairment (Child-Pugh class C):
US labeling: The following adjustments should be considered (and are predicted to normalize the AUC), however, there are no clinical data associated with the adjustments.
In combination with capecitabine: Reduce dose from 1250 mg once daily to 750 mg once daily.
In combination with letrozole: Reduce dose from 1500 mg once daily to 1000 mg once daily.
Canadian labeling: There are no specific dosage adjustments provided in the manufacturer’s labeling; however, a dosage reduction is recommended based on pharmacokinetic modeling (safety and efficacy of dose reduction has not been demonstrated).
Severe hepatotoxicity during treatment: Discontinue permanently (do not rechallenge).
Dosing: Adjustment for Toxicity Cardiac toxicity: Discontinue treatment for at least 2 weeks for LVEF < LLN or decreased LVEF ≥ grade 2 (U.S. labeling) or decreased LVEF ≥ grade 3 (Canadian labeling); may be restarted at 1000 mg once daily (in combination with capecitabine) or 1250 mg once daily (in combination with letrozole) if LVEF recovers to normal and patient is asymptomatic.
Dermatologic toxicity: Discontinue treatment for suspected erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis.
Diarrhea:
Grade 3 diarrhea or grade 1 or 2 diarrhea with complicating features (moderate-to-severe abdominal cramping, grade 2 or higher nausea/vomiting, decreased performance status, fever, sepsis, neutropenia, frank bleeding, or dehydration):
U.S. labeling: Interrupt treatment; may restart at a reduced dose (from 1500 mg once daily to 1250 mg once daily or from 1250 mg once daily to 1000 mg once daily) when diarrhea resolves to ≤ grade 1.
Canadian labeling: Interrupt treatment; may restart at a reduced dose (from 1500 mg once daily to 1250 mg once daily or from 1250 mg once daily to 1000 mg once daily or from 1000 mg once daily to 750 mg once daily) when diarrhea resolves to ≤ grade 1.
