Posology : מינונים

4.2    Posology and method of administration

Tykerb 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.



TYK API MAR22 V2                                                            EU SmPC Feb22 Posology

Tykerb / capecitabine combination posology

The recommended dose of Tykerb 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.

Tykerb / letrozole combination posology

The recommended dose of Tykerb is 1500 mg (i.e. six tablets) once daily continuously.
Please refer to the full prescribing information of the co-administered letrozole for dosing details.

Dose delay and dose reduction

Cardiac events
Tykerb 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). Tykerb may be restarted at a reduced dose (1000 mg/day when administered with capecitabine or 1250 mg/day when administered with letrozole) after a minimum of 2 weeks and if the LVEF recovers to normal and the patient is asymptomatic.

Interstitial lung disease / pneumonitis

Tykerb should be discontinued in patients who experience pulmonary symptoms which are NCI CTCAE grade 3 or greater (see section 4.4).

Diarrhoea

Tykerb 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). 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) when diarrhoea resolves to grade 1 or less. Tykerb dosing should be permanently discontinued in patients with diarrhoea which is NCI CTCAE grade 4.

Other toxicities

Discontinuation or interruption of dosing with Tykerb 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 either 1250 mg/day when administered with capecitabine or 1500 mg/day when administered with letrozole. If the toxicity recurs, then Tykerb should be restarted at a lower dose (1000 mg/day when administered with capecitabine or 1250 mg/day when administered with letrozole.


TYK API MAR22 V2                                                              EU SmPC Feb22 Renal impairment

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 Tykerb in this population (see section 5.2).

Hepatic impairment

Tykerb should be discontinued if changes in liver function are severe and patients should not be retreated (see section 4.4).

Administration of Tykerb 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).

Elderly

There are limited data on the use of Tykerb and capecitabine in patients aged ≥ 65 years.
In the phase III clinical study of Tykerb 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 Tykerb and letrozole were observed between these patients and patients < 65 years of age.

Paediatric population

Tykerb is not indicated to children and adolescents below 18 years old.
The safety and efficacy of Tykerb in children below the age of 18 years have not yet been established. No data are available.

Method of administration

Tykerb is for oral use.
The daily dose of Tykerb should not be divided. Tykerb 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 Tykerb 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.