Generic
Lapatinib
Dosage Administration
HER2-Positive Metastatic Breast Cancer: The recommended dose of Lapatinib is 1,250 mg given orally once daily on Days 1-21 continuously in combination with Capecitabine 2,000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21-day cycle. Lapatinib should be taken at least one hour before or one hour after a meal. The dose of Lapatinib should be once daily (5 tablets administered all at once); dividing the daily dose is not recommended. Capecitabine should be taken with food or within 30 minutes after food. If a day’s dose is missed, the patient should not double the dose the next day. Treatment should be continued until disease progression or unacceptable toxicity occurs. Hormone Receptor-Positive, HER2-Positive Metastatic Breast Cancer: The recommended dose of Lapatinib is 1,500 mg given orally once daily continuously in combination with Letrozole. When coadministered with Lapatinib, the recommended dose of Letrozole is 2.5 mg once daily. Lapatinib should be taken at least one hour before or one hour after a meal. The dose of Lapatinib should be once daily (6 tablets administered all at once); dividing the daily dose is not recommended. Pediatric Use: The safety and effectiveness of Lapatinib in pediatric patients have not been established.
Contraindications
Lapatinib is contraindicated in patients with known severe hypersensitivity (e.g., anaphylaxis) to this product or any of its components.
Side Effects
Dose Modification Guidelines: Cardiac Events: Lapatinib should be discontinued in patients with a decreased left ventricular ejection fraction (LVEF) that is Grade 2 or greater by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v3.0), and in patients with an LVEF that drops below the institution’s lower limit of normal (LLN) and Adverse Reactions (6.1)]. Lapatinib in combination with Capecitabine may be restarted at a reduced dose (1,000 mg/day) and in combination with Letrozole may be restarted at a reduced dose of 1,250 mg/day after a minimum of 2 weeks if the LVEF recovers to normal and the patient is asymptomatic. Hepatic Impairment: Patients with severe hepatic impairment (Child-Pugh Class C) should have their dose of Lapatinib reduced. A dose reduction from 1,250 mg/day to 750 mg/day (HER2-positive metastatic breast cancer indication) or from 1,500 mg/day to 1,000 mg/day (hormone receptor-positive, HER2-positive breast cancer indication) in patients with severe hepatic impairment is predicted to adjust the area under the curve (AUC) to the normal range and should be considered. However, there are no clinical data with this dose adjustment in patients with severe hepatic impairment. Diarrhea: Lapatinib should be interrupted in patients with diarrhea which is NCI CTCAE Grade 3 or Grade 1 or 2 with complicating features (moderate to severe abdominal cramping, nausea or vomiting greater than or equal to NCI CTCAE Grade 2, decreased performance status, fever, sepsis, neutropenia, frank bleeding, or dehydration). Lapatinib may be reintroduced at a lower dose (reduced from 1,250 mg/day to 1,000 mg/day or from 1,500 mg/day to 1,250 mg/day) when diarrhea resolves to Grade 1 or less. TYKERB should be permanently discontinued in patients with diarrhea which is NCI CTCAE Grade 4. Concomitant Strong CYP3A4 Inhibitors: The concomitant use of strong CYP3A4 inhibitors should be avoided (e.g., Ketoconazole, Itraconazole, Clarithromycin, Atazanavir, Indinavir, Nefazodone, Nelfinavir, Ritonavir, Saquinavir, Telithromycin, Voriconazole). Grapefruit may also increase plasma concentrations of Lapatinib and should be avoided. If patients must be coadministered, a strong CYP3A4 inhibitor, based on pharmacokinetic studies, a dose reduction to 500 mg/day of Lapatinib is predicted to adjust the Lapatinib AUC to the range observed without inhibitors and should be considered. However, there are no clinical data with this dose adjustment in patients receiving strong CYP3A4 inhibitors. If the strong inhibitor is discontinued, a washout period of approximately 1 week should be allowed before the Lapatinib dose is adjusted upward to the indicated dose. Concomitant Strong CYP3A4 Inducers: The concomitant use of strong CYP3A4 inducers should be avoided (e.g., Dexamethasone, Phenytoin, Carbamazepine, Rifampin, Rifabutin, Rifapentin, Phenobarbital, St. John’s wort). If patients must be coadministered a strong CYP3A4 inducer, based on pharmacokinetic studies, the dose of Lapatinib should be titrated gradually from 1,250 mg/day up to 4,500 mg/day (HER2-positive metastatic breast cancer indication) or from 1,500 mg/day up to 5,500 mg/day (hormone receptor-positive, HER2-positive breast cancer indication) based on tolerability. This dose of Lapatinib is predicted to adjust the Lapatinib AUC to the range observed without inducers and should be considered. However, there are no clinical data with this dose adjustment in patients receiving strong CYP3A4 inducers. If the strong inducer is discontinued the Lapatinib dose should be reduced to the indicated dose. Other Toxicities: Discontinuation or interruption of dosing with Lapatinib may be considered when patients develop greater than or equal to Grade 2 NCI CTCAE toxicity, and can be restarted at the standard dose of 1,250 or 1,500 mg/day when the toxicity improves to Grade 1 or less. If the toxicity recurs, then Lapatinib in combination with Capecitabine should be restarted at a lower dose (1,000 mg/day) and in combination with Letrozole should be restarted at a lower dose of 1,250 mg/day. Or as directed by the registered physician.
Pregnancy And Lactation
Based on findings in animal studies and its mechanism of action, Lapatinib can cause fetal harm when administered to a pregnant woman. There are no available human data to inform of the drug-associated risks. Advise pregnant women and females of reproductive potential of the potential risk to the fetus. There are no data on the presence of Lapatinib in human milk, or its effects on the breastfed child, or milk production. Because of the potential for serious adverse reactions in a breastfed child from Lapatinib, advise lactating women not to breastfeed during treatment with Lapatinib and for 1 week after the last dose.
Therapeutic
Cytotoxic Chemotherapy
Storage Conditions
Store below 30°C in a dry place. Keep out of the reach of children.
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