Source: European Medicines Agency (EU) Revision Year: 2019 Publisher: Novartis Europharm Limited, Vista Building, Elm Park, Merrion Road, Dublin 4, Ireland
Tyverb is indicated for the treatment of adult patients with breast cancer, whose tumours overexpress HER2 (ErbB2):
Tyverb treatment should only be initiated by a physician experienced in the administration of anti-cancer medicinal products.
HER2 (ErbB2) overexpressing tumours are defined by IHC3+, or IHC2+ with gene amplification or gene amplification alone. HER2 status should be determined using accurate and validated methods.
The recommended dose of Tyverb is 1250 mg (i.e. five tablets) once daily continuously.
The recommended dose of capecitabine is 2000 mg/m²/day taken in 2 doses 12 hours apart on days 1-14 in a 21 day cycle (see section 5.1). Capecitabine should be taken with food or within 30 minutes after food. Please refer to the full prescribing information of capecitabine.
The recommended dose of Tyverb is 1000 mg (i.e. four tablets) once daily continuously.
The recommended dose of trastuzumab is 4 mg/kg administered as an intravenous loading dose, followed by 2 mg/kg intravenous weekly (see section 5.1). Please refer to the full prescribing information of trastuzumab.
The recommended dose of Tyverb is 1500 mg (i.e. six tablets) once daily continuously.
Please refer to the full prescribing information of the co-administered aromatase inhibitor for dosing details.
Tyverb should be discontinued in patients with symptoms associated with decreased left ventricular ejection fraction (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 institutions lower limit of normal (see section 4.4). Tyverb may be restarted at a reduced dose (750 mg/day when administered with trastuzumab, 1000 mg/day when administered with capecitabine or 1250 mg/day when administered with an aromatase inhibitor) after a minimum of 2 weeks and if the LVEF recovers to normal and the patient is asymptomatic.
Tyverb should be discontinued in patients who experience pulmonary symptoms which are NCI CTCAE grade 3 or greater (see section 4.4).
Tyverb dosing should be interrupted in patients with diarrhoea 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) (see sections 4.4 and 4.8). Tyverb 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) when diarrhoea resolves to grade 1 or less. Tyverb dosing should be permanently discontinued in patients with diarrhoea which is NCI CTCAE grade 4.
Discontinuation or interruption of dosing with Tyverb may be considered when a patient develops toxicity greater than or equal to grade 2 on the NCI CTCAE. Dosing can be restarted, when the toxicity improves to grade 1 or less, at 1000 mg/day when administered with trastuzumab, 1250 mg/day when administered with capecitabine or 1500 mg/day when administered with an aromatase inhibitor. If the toxicity recurs, then Tyverb should be restarted at a lower dose (750 mg/day when administered with trastuzumab, 1000 mg/day when administered with capecitabine or 1250 mg/day when administered with an aromatase inhibitor).
No dose adjustment is necessary in patients with mild to moderate renal impairment. Caution is advised in patients with severe renal impairment as there is no experience of Tyverb in this population (see section 5.2).
Tyverb should be discontinued if changes in liver function are severe and patients should not be retreated (see section 4.4).
Administration of Tyverb to patients with moderate to severe hepatic impairment should be undertaken with caution due to increased exposure to the medicinal product. Insufficient data are available in patients with hepatic impairment to provide a dose adjustment recommendation (see section 5.2).
There are limited data on the use of Tyverb/capecitabine and Tyverb/trastuzumab in patients aged ≥65 years.
In the phase III clinical study of Tyverb in combination with letrozole, of the total number of hormone receptor positive metastatic breast cancer patients (Intent to treat population N=642), 44% were ≥65 years of age. No overall differences in efficacy and safety of the combination of Tyverb and letrozole were observed between these patients and patients <65 years of age.
The safety and efficacy of Tyverb in children below the age of 18 years have not yet been established. No data are available.
Tyverb is for oral use.
The daily dose of Tyverb should not be divided. Tyverb should be taken either at least one hour before, or at least one hour after food. To minimise variability in the individual patient, administration of Tyverb should be standardised in relation to food intake, for example always to be taken one hour before a meal (see sections 4.5 and 5.2 for information on absorption).
Missed doses should not be replaced and the dosing should resume with the next scheduled daily dose (see section 4.9).
The full prescribing information of the co-administered medicinal product should be consulted for relevant details of their posology including any dose reductions, contraindications and safety information.
There is no specific antidote for the inhibition of EGFR (ErbB1) and/or HER2 (ErbB2) tyrosine phosphorylation. The maximum oral dose of lapatinib that has been administered in clinical studies is 1800 mg once daily.
Asymptomatic and symptomatic cases of overdose have been reported in patients being treated with Tyverb. In patients who took up to 5000 mg of lapatinib, symptoms observed include known lapatinib associated events (see section 4.8) and in some cases sore scalp and/or mucosal inflammation. In a single case of a patient who took 9000 mg of Tyverb, sinus tachycardia (with otherwise normal ECG) was also observed.
Lapatinib is not significantly renally excreted and is highly bound to plasma proteins, therefore haemodialysis would not be expected to be an effective method to enhance the elimination of lapatinib.
Further management should be as clinically indicated or as recommended by the national poisons centre, where available.
Blister packs: 2 years.
Bottles: 3 years.
Do not store above 30°C.
Tyverb is supplied in either blister packs or bottles.
Blister packs:
Tyverb/capecitabine combination posology: Each pack of Tyverb contains 70 film-coated tablets in foil blisters (polyamide/aluminium/polyvinyl chloride/aluminium) of 10 tablets each. Each foil has a perforation down the middle to allow the blisters to be separated into a daily dose of 5 tablets.
Multipacks contain 140 (2 packs of 70) film-coated tablets.
Tyverb/aromatase inhibitor combination posology: Each pack of Tyverb contains 84 film-coated tablets in foil blisters (polyamide/aluminium/polyvinyl chloride/aluminium) of 12 tablets each. Each foil has a perforation down the middle to allow the blisters to be separated into a daily dose of 6 tablets.
Bottles:
Tyverb is also supplied in high density polyethylene bottles (HDPE) with a child resistant polypropylene closure containing 70, 84, 105 or 140 film-coated tablets.
Not all pack sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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