Tykerb Dosage/Direction for Use

Dosage regimen and method of administration: Lapatinib (Tykerb) should only be initiated by a physician experienced in the administration of anti-cancer agents.
Prior to the initiation of treatment, left ventricular ejection fraction (LVEF) must be evaluated to ensure that baseline LVEF is within the institutional limits of normal (see PRECAUTIONS). LVEF must continue to be monitored during treatment with lapatinib (Tykerb) to ensure that it does not fall below the institutional lower limit of normal (LLN) (see Dose delay and dose reduction as follows).
Lapatinib (Tykerb) should be taken at least 1 hour before, or at least 1 hour after food (see INTERACTIONS and PHARMACOLOGY UNDER ACTIONS). The recommended daily Lapatinib (Tykerb) dose should not be divided.
Missed doses should not be replaced and dosing should resume with the next scheduled daily dose (see OVERDOSAGE).
The full prescribing information of the co-administered medicinal product should be consulted for details of its posology and safety information.
General target population: HER2 overexpressing metastatic breast cancer: Lapatinib (Tykerb) in combination with capecitabine: The recommended dose of lapatinib (Tykerb) is 1250 mg (e.g. 5 tablets) once daily continuously when taken in combination with capecitabine.
The recommended dose of capecitabine is 2000 mg/m²/day taken in 2 doses 12 hours apart on days 1 to 14 in a 21 day cycle (see PHARMACOLOGY: PHARMACODYNAMICS: CLINICAL STUDIES UNDER ACTIONS). Capecitabine should be taken with food or within 30 minutes after food.
Lapatinib (Tykerb) in combination with trastuzumab: The recommended dose of lapatinib (Tykerb) is 1000 mg (e.g. 4 tablets) once daily continuously when taken in combination with trastuzumab.
The recommended dose of trastuzumab is 4 mg/kg as an IV loading dose, followed by 2 mg/kg IV weekly (see PHARMACOLOGY: PHARMACODYNAMICS: CLINICAL STUDIES UNDER ACTIONS).
Lapatinib (Tykerb) in combination with paclitaxel: The recommended dose of lapatinib (Tykerb) is 1500 mg (e.g. 6 tablets) once daily continuously in combination with paclitaxel.
The recommended dose of paclitaxel is 80 mg/m² IV on days 1, 8, and 15 of a 28 day schedule. Alternatively, paclitaxel may be given at a dose of 175 mg/m² IV every 21 days (see PHARMACOLOGY: PHARMACODYNAMICS: CLINICAL STUDIES UNDER ACTIONS).
Lapatinib (Tykerb) in combination with an aromatase inhibitor: The recommended dose of lapatinib (Tykerb) is 1500 mg (e.g. 6 tablets) once daily continuously when taken in combination with an aromatase inhibitor.
When lapatinib (Tykerb) is co-administered with the aromatase inhibitor letrozole, the recommended dose of letrozole is 2.5 mg once daily. If lapatinib (Tykerb) is co-administered with an alternative aromatase inhibitor, refer to the full prescribing information of the medicinal product for dosing details.
Dose delay and dose reduction (all indications): Cardiac events (see PRECAUTIONS): Lapatinib (Tykerb) should be interrupted in patients with symptoms associated with decreased LVEF that are National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grade 3 or greater or if their LVEF drops below the institutionals lower limit of normal (LLN). Lapatinib (Tykerb) may be restarted at a lower dose (reduced from 1000 mg/day to 750 mg/day, from 1250 mg/day to 1000 mg/day or from 1500 mg/day to 1250 mg/day) after a minimum of 2 weeks and if LVEF recovers to normal and the patient is asymptomatic. Based on current data, the majority of LVEF decreases occur within the first 12 weeks of treatment however, there is limited data on long term exposure.
Interstitial lung disease/pneumonitis (see PRECAUTIONS and ADVERSE REACTIONS): Lapatinib (Tykerb) should be discontinued in patients who experience pulmonary symptoms indicative of interstitial lung disease/pneumonitis which are NCI CTCAE grade 3 or higher.
Diarrhea (see PRECAUTIONS and ADVERSE REACTIONS): Lapatinib (Tykerb) 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 (Tykerb) may be reintroduced at a lower dose (reduced from 1000 mg/day to 750 mg/day, from 1250 mg/day to 1000 mg/day or from 1500 mg/day to 1250 mg/day) if diarrhea resolves to grade 1 or less. Lapatinib (Tykerb) should be permanently discontinued in patients with NCI CTCAE grade 4 diarrhea.
Severe cutaneous reactions (see PRECAUTIONS): Lapatinib (Tykerb) should be discontinued in patients who experience severe progressive skin rash with blisters or mucosal lesions.
Other toxicities: Discontinuation or interruption with lapatinib (Tykerb) may be considered if a patient develops toxicity greater than or equal to NCI CTCAE grade 2. Dosing can be restarted at the standard dose of 1000 mg/day, 1250 mg/day, or 1500 mg/day, if the toxicity improves to grade 1 or lower. If the toxicity recurs, lapatinib (Tykerb) should be restarted at a lower dose (reduced from 1000 mg/day to 750 mg/day, from 1250 mg/day to 1000 mg/day or from 1500 mg/day to 1250 mg/day).
Special populations: Renal impairment: There is no experience of lapatinib (Tykerb) in patients with severe renal impairment. However, patients with renal impairment are unlikely to require dose modification of lapatinib (Tykerb) given that under 2% of an administered dose (lapatinib and metabolites) is eliminated renally (see PHARMACOLOGY UNDER ACTIONS).
Hepatic impairment: Lapatinib is metabolized in the liver. Moderate and severe hepatic impairment have been associated with 56% and 85% increases in systemic exposure, respectively. Administration of lapatinib (Tykerb) to patients with hepatic impairment requires caution due to increased exposure to the drug (see PRECAUTIONS and PHARMACOLOGY UNDER ACTIONS).
Patients with severe hepatic impairment (Child-Pugh Class C) should have their dose reduced. A dose reduction from 1250 mg/day to 750 mg/day or from 1500 mg/day to 1000 mg/day in patients with severe hepatic impairment is predicted to adjust the area under the curve (AUC) to the normal range. However, there are no clinical data with this dose adjustment in patients with severe hepatic impairment (see PRECAUTIONS and PHARMACOLOGY UNDER ACTIONS).
Pediatric patients (below 18 years): The safety and efficacy of lapatinib (Tykerb) in pediatric patients has not been established.
Geriatric patients (65 years or above): There are limited data on the use of lapatinib (Tykerb) in patients aged 65 years and older. (See Table 13.)

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No age-based differences in the safety or efficacy of these regimens were observed. Other reported clinical experience has not identified differences in responses between geriatric and younger patients. Greater sensitivity of geriatric patients cannot be ruled out.