DOSAGE AND ADMINISTRATION
The recommended dose of TYKERB is 1,250 mg (5 tablets) 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. TYKERB should be taken at least one hour before or one hour after a meal. The dose of TYKERB should be once daily; dividing the daily dose is not recommended [see Clinical Pharmacology] . 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.
Dose Modification Guidelines
TYKERB should be discontinued in patients with a decreased left ventricular ejection fraction (LVEF) that is Grade 2 or greater by NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) and in patients with an LVEF that drops below the institution’s lower limit of normal [see Warnings and Precautions and Adverse Reactions]. TYKERB may be restarted at a reduced dose (1,000 mg/day) after a minimum of 2 weeks if the LVEF recovers to normal and the patient is asymptomatic.
Patients with severe hepatic impairment (Child-Pugh Class C) should have their dose of TYKERB reduced. A dose reduction to 750 mg/day 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 is no clinical data with this dose adjustment in patients with severe hepatic impairment.
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. [See Drug Interactions (7.2).]
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 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. [See Drug Interactions (7.2).]
Discontinuation or interruption of dosing with TYKERB may be considered when patients develop ≥Grade 2 NCI CTC toxicity and can be restarted at 1,250 mg/day when the toxicity improves to Grade 1 or less. If the toxicity recurs, then TYKERB should be restarted at a lower dose (1,000 mg/day).
See manufacturer’s prescribing information for capecitabine dosage adjustment guidelines in the event of toxicity.
DOSAGE FORMS AND STRENGTHS
250 mg tablets — oval, biconvex, orange, film-coated with GS XJG debossed on one side.