Source: European Medicines Agency (EU) Revision Year: 2022 Publisher: Novartis Europharm Limited, Vista Building, Elm Park, Merrion Road, Dublin 4, Ireland
Tabrecta as monotherapy is indicated for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) harbouring alterations leading to mesenchymal-epithelial transition factor gene exon 14 (METex14) skipping, who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy.
Treatment with Tabrecta should be initiated by a physician experienced in the use of anticancer therapies.
Patients have to be selected for treatment with Tabrecta based on the presence of genetic alterations leading to a METex14 skipping mutation in tumour tissue or plasma specimens using a validated test. If a genetic alteration is not detected in a plasma specimen, tumour tissue should be tested (see sections 4.4 and 5.1).
The recommended dose of Tabrecta is 400 mg orally twice daily with or without food.
Treatment should be continued based on individual safety and tolerability and as long as the patient is deriving clinical benefit from therapy.
If a dose of Tabrecta is missed or vomiting occurs, the patient should not make up for the dose, but take the next dose at the scheduled time.
The recommended dose reduction schedule for the management of adverse reactions based on individual safety and tolerability is listed in Table 1.
Table 1. Tabrecta dose reduction schedule:
| Dose level | Dose and schedule | Number and strength of tablets |
|---|---|---|
| Starting dose | 400 mg twice daily | Two 200 mg tablets / twice daily |
| First dose reduction | 300 mg twice daily | Two 150 mg tablets / twice daily |
| Second dose reduction | 200 mg twice daily | One 200 mg tablet / twice daily |
Doses of Tabrecta below 200 mg twice daily have not been investigated in clinical studies.
Recommendations for dose modifications of Tabrecta for adverse reactions are provided in Table 2.
Table 2. Tabrecta dose modifications for the management of adverse reactions:
| Adverse reaction | Severity | Dose modification |
|---|---|---|
| Interstitial lung disease (ILD)/pneumonitis | Any grade treatment-related | Permanently discontinue Tabrecta. |
| Isolated ALT and/or AST elevations from baseline, without concurrent total bilirubin increase | Grade 3 (>5.0 to ≤20.0 x ULN) | Temporarily withhold Tabrecta until recovery to baseline ALT/AST grade. If recovered to baseline within 7 days, then resume Tabrecta at the same dose, otherwise resume Tabrecta at a reduced dose as per Table 1. |
| Grade 4 (>20.0 x ULN) | Permanently discontinue Tabrecta. | |
| Combined elevations in ALT and/or AST with concurrent total bilirubin increase, in the absence of cholestasis or haemolysis | If patient develops ALT and/or AST >3 x ULN along with total bilirubin >2 x ULN, irrespective of baseline grade | Permanently discontinue Tabrecta. |
| Isolated total bilirubin elevation from baseline, without concurrent ALT and/or AST increase | Grade 2 (>1.5 to ≤3.0 x ULN) | Temporarily withhold Tabrecta until recovery to baseline bilirubin grade. If recovered to baseline within 7 days, then resume Tabrecta at the same dose, otherwise resume Tabrecta at a reduced dose as per Table 1. |
| Grade 3 (>3.0 to ≤10.0 x ULN) | Temporarily withhold Tabrecta until recovery to baseline bilirubin grade. If recovered to baseline within 7 days, then resume Tabrecta at a reduced dose as per Table 1, otherwise permanently discontinue Tabrecta. | |
| Grade 4 (>10.0 x ULN) | Permanently discontinue Tabrecta. | |
| Serum creatinine increased | Grade 2 (>1.5 to ≤3.0 x ULN) | Temporarily withhold Tabrecta until recovery to baseline serum creatinine grade. If recovered to baseline, then resume Tabrecta at the same dose level. |
| Grade 3 (>3.0 to ≤6.0 x ULN) | Temporarily withhold Tabrecta until recovery to baseline serum creatinine grade. If recovered to baseline, then resume Tabrecta at a reduced dose as per Table 1. | |
| Grade 4 (>6.0 x ULN) | Permanently discontinue Tabrecta. | |
| Vomiting | Grade 2 | Temporarily withhold Tabrecta until resolved to grade ≤1. If resolved to grade ≤1 then resume Tabrecta the same dose level. |
| Grade 3 | Temporarily withhold Tabrecta until resolved to grade ≤2. If resolved to grade ≤2 then resume Tabrecta at a reduced dose as per Table 1. | |
| Grade 4 | Temporarily withhold Tabrecta until resolved to grade ≤2. If resolved to grade ≤2 then resume Tabrecta at a reduced dose as per Table 1. | |
| Other adverse reactions | Grade 2 | Maintain dose level. If intolerable, consider temporarily withholding Tabrecta until resolved, then resume Tabrecta at a reduced dose as per Table 1. |
| Grade 3 | Temporarily withhold Tabrecta until resolved, then resume Tabrecta at a reduced dose as per Table 1. | |
| Grade 4 | Permanently discontinue Tabrecta. |
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ULN, upper limit of normal.
Grading according to CTCAE Version 4.03 (CTCAE = Common Terminology Criteria for Adverse Events).
Baseline = at the time of treatment initiation.
No dose adjustment is necessary in patients 65 years of age or older (see section 5.2).
Caution should be exercised in patients with severe renal impairment as Tabrecta has not been studied in these patients. No dose adjustment is necessary in patients with mild or moderate renal impairment (see section 5.2).
No dose adjustment is necessary in patients with mild, moderate or severe hepatic impairment (see section 5.2).
The safety and efficacy of Tabrecta in children aged 0 to 18 years have not been established. No data are available.
Tabrecta should be taken orally twice daily with or without food. Patients with swallowing difficulties are recommended to take Tabrecta with food. The tablets should be swallowed whole to ensure that the full dose is administered.
There is limited experience with overdose in clinical studies with Tabrecta. Patients should be closely monitored for signs or symptoms of adverse reactions, and general supportive measures and symptomatic treatment should be initiated in cases of suspected overdose.
3 years.
This medicinal product does not require any special temperature storage conditions.
Store in the original package in order to protect from moisture.
PCTFE/PVC (polychlorotrifluoroethylene/polyvinyl chloride) blisters backed with an aluminium lidding foil.
Packs containing 60 or 120 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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