Adult Dosing
Metastatic or advanced breast CA (HER2 overexpressing tumors)
- 1250 mg PO Daily on days 1-21 of a repeating 21 day cycle
- It should be administered in combination with capecitabine 2000 mg/m2/day divided bid on days 1-14 of a repeating 21 day cycle
Hormone Receptor Positive, HER2 Positive Metastatic Breast Cancer
- 1500 mg PO Daily, in combination with letrozole 2.5 mg PO Daily
Notes:
- Take lapatinib
1 hr before or 1 hr after meal - Dividing the lapatinib daily dose is not recommended
- Take capecitabine either with food or within 30 minutes after meal
- Continue therapy until disease progression or toxicity
Pediatric Dosing
- Safety and efficacy in pediatric patients have not been established
[Outline]
Renal Dose Adjustment
- Renal impairment: Dosage adjustments not defined
Hepatic Dose Adjustment
- Severe hepatic impairment (Child-Pugh Class C): 750 mg/day PO (HER2 positive metastatic breast cancer indication), 1,000 mg/day PO (hormone receptor positive, HER2 positive breast cancer indication)
Dose adjustments
Cardiac events
- Discontinue if decrease LVEF grade 2 or more
- Restart at a reduced dosage of 1,000 mg/day (HER2-positive metastatic breast cancer) or 1,250 mg/day (hormone receptor positive, HER2-positive breast cancer) after a minimum of 2 wks, if LVEF recovers to normal and the patient is asymptomatic
Diarrhea
- Interrupt therapy in patients with diarrhea of NCI CTCAE Grade 3 or Grade 1 or 2 with complicating features
- Restart at a reduced dosage of 1,000 mg/day (HER2-positive metastatic breast cancer) or 1,250 mg/day (hormone receptor positive, HER2-positive breast cancer) after diarrhea resolves to Grade 1 or less
- Discontinue therapy permanently in patients with diarrhea of NCI CTCAE Grade 4
Concomitant use of CYP3A4 inhibitors
- Avoid if possible (including grapefruit juice) if use is necessary, 500 mg/day PO; when the inhibitor is discontinued allow 1 wk to pass before titrating upwards
Concomitant use of CYP3A4 inducers
- Gradually increase to 4,500 -5,500 mg/day PO (based on tolerability, when the inducer is discontinued, reduce the dose to the indicated dose)
Other Toxicities
- Discontinue therapy if patients develop Grade 2 NCI CTCAE
- Restarted at 1,250 mg/day when the toxicity improves to Grade 1 or less
- Lapatinib can decrease left ventricular ejection fraction (LVEF). Confirm normal LVEF before starting therapy and monitor throughout therapy
- Severe hepatotoxicity leading to death has been reported with lapatinib treatment. Monitor LFTs before starting treatment, then q4-6 wks during treatment; discontinue and do not restart if severe changes in LFTs noted [US Black Box Warning]
- Lapatinib treatment can cause severe diarrhea, discontinue the therapy and manage diarrhea with anti-diarrheal agents and oral or intravenous electrolytes and fluids
- Interstitial lung disease and pneumonitis have been reported in patients taking lapatinib; discontinue if patients experience severe pulmonary symptoms, grade 3 or higher
- Lapatinib prolongs the QT interval, use cautiously in patients with hypokalemia or hypomagnesemia, with congenital long QT syndrome, patients taking anti-arrhythmic medicines. Monitor ECG and electrolytes
- Fetal harm can occur when administered to pregnant women. Women should be advised not to become pregnant when taking lapatinib
Cautions: Use cautiously in
- Sever hepatic impairment
- Cardiovascular disease
- Congenital QT syndrome
- History of QT prolongation
- Concomitant administration of QT prolonging agent
- Hypokalemia
- Hypomagnesemia
- Concomitant use of strong CYP3A4 inducers
- Concomitant use of strong CYP3A4 inhibitors
- Cumulative high dose anthracycline treatment
Pregnancy Category:D
Breastfeeding: Safety unknown; due to the potential for possible serious adverse reactions in nursing infants, manufacturer recommends discontinuation of breastfeeding, or discontinuation of the drug, taking into account the importance of the drug to the mother.
Drug Name: Tykerb 250 MG Oral Tablet
Ingredient(s): Lapatinib
Imprint: GS;XJG
Color(s): Orange
Shape: Oval
Size (mm): 20.00
Score: 1
Inactive Ingredient(s): magnesium stearate / cellulose, microcrystalline / povidone / sodium starch glycolate type a potato / fd&c yellow no. 6 / hypromellose / polyethylene glycol / polysorbate 80 / titanium dioxide
Drug Label Author:
GlaxoSmithKline LLC
DEA Schedule:
Non-Scheduled
