Source: European Medicines Agency (EU) Revision Year: 2022 Publisher: Seagen B.V., Evert van de Beekstraat 1-104, 1118CL Schiphol, The Netherlands
TUKYSA is indicated in combination with trastuzumab and capecitabine for the treatment of adult patients with HER2-positive locally advanced or metastatic breast cancer who have received at least 2 prior anti-HER2 treatment regimens.
Treatment with TUKYSA should be initiated and supervised by a physician experienced in the administration of anti–cancer medicinal products.
The recommended dose is 300 mg tucatinib (two 150 mg tablets) taken twice daily continuously in combination with trastuzumab and capecitabine, at doses described in table 1. Refer to the summary of product characteristics (SmPC) for co-administered trastuzumab and capecitabine for additional information. The treatment components can be administered in any order.
Table 1. Recommended dosing:
| Treatment | Dose | Treatment days | Timing relative to food intake |
|---|---|---|---|
| Tucatinib | 300 mg orally twice daily | Continuously | With or without a meal |
| Capecitabine | 1.000 mg/m² orally twice daily | Days 1 to 14 every 21 days | Within 30 minutes after a meal |
| Trastuzumab Intravenous dosing Initial dose Subsequent doses OR Subcutaneous dosing | 8 mg/kg intravenously 6 mg/kg intravenously 600 mg subcutaneously | Day 1 Every 21 days Every 21 days | Not applicable |
Treatment with TUKYSA should be continued until disease progression or unacceptable toxicity.
In the case of a missed dose, the patient should take their next dose at the regularly scheduled time.
The recommended tucatinib dose modifications for patients with adverse reactions (see section 4.8) are provided in Tables 2 and 3. Refer to the SmPC for co-administered trastuzumab and capecitabine for dose modifications for toxicities suspected to be caused by those therapies.
Table 2. Recommended tucatinib dose reductions for adverse reactions:
| Dose level | Tucatinib dose |
|---|---|
| Recommended starting dose | 300 mg twice daily |
| First dose reduction | 250 mg twice daily |
| Second dose reduction | 200 mg twice daily |
| Third dose reduction | 150 mg twice daily1 |
1 TUKYSA should be permanently discontinued in patients unable to tolerate 150 mg orally twice daily.
Table 3. Recommended tucatinib dose modifications for adverse reactions:
| Adverse Reaction | Severity1 | Tucatinib dosage modification |
|---|---|---|
| Diarrhoea | Grade 1 and 2 | No dose modification is required. |
| Grade 3 without anti-diarrheal treatment | Initiate or intensify appropriate medical therapy. Hold tucatinib until recovery to ≤ Grade 1, then resume tucatinib at the same dose level. | |
| Grade 3 with anti-diarrheal treatment | Initiate or intensify appropriate medical therapy. Hold tucatinib until recovery to ≤ Grade 1, then resume tucatinib at the next lower dose level. | |
| Grade 4 | Permanently discontinue tucatinib. | |
| Increased ALT, AST or bilirubin2 | Grade 1 bilirubin (> ULN to 1.5 x ULN) | No dose modification is required. |
| Grade 2 bilirubin (>1.5 to 3 × ULN) | Hold tucatinib until recovery to ≤ Grade 1, then resume tucatinib at the same dose level. | |
| Grade 3 ALT or AST (>5 to 20 × ULN) OR Grade 3 bilirubin (>3 to 10 × ULN) | Hold tucatinib until recovery to ≤ Grade 1, then resume tucatinib at the next lower dose level. | |
| Grade 4 ALT or AST (>20 × ULN) OR Grade 4 bilirubin (>10 × ULN) | Permanently discontinue tucatinib. | |
| ALT or AST >3 × ULN AND Bilirubin >2 × ULN | Permanently discontinue tucatinib. | |
| Other adverse reactions | Grade 1 and 2 | No dose modification is required. |
| Grade 3 | Hold tucatinib until recovery to ≤ Grade 1, then resume tucatinib at the next lower dose level. | |
| Grade 4 | Permanently discontinue tucatinib. |
1 Grades based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03
2 Abbreviations: ULN = upper limit of normal; ALT = alanine aminotransferase; AST = aspartate aminotransferase
Concomitant use with strong CYP2C8 inhibitors should be avoided. If coadministration with a strong CYP2C8 inhibitor cannot be avoided, the starting tucatinib dose should be reduced to 100 mg orally twice daily. After discontinuation of the strong CYP2C8 inhibitor for 3 elimination half-lives, the tucatinib dose that was taken prior to initiating the inhibitor should be resumed (see section 4.4 and section 4.5). Monitoring for TUKYSA toxicity should be increased when administered with moderate CYP2C8 inhibitors.
No dose adjustment is required in patients aged ≥65 years (see section 5.2). Tucatinib has not been investigated in patients above the age of 80 years.
No dose adjustment is required in patients with mild, moderate, or severe renal impairment (see section 5.2).
No dose adjustment is required in patients with mild or moderate hepatic impairment (see section 5.2). For patients with severe hepatic impairment (Child-Pugh C), a reduced starting dose of 200 mg orally twice daily is recommended.
The safety and efficacy of TUKYSA in paediatric patients have not been established. No data are available.
TUKYSA is for oral use. The tablets should be swallowed whole and should not be chewed, crushed, or split prior to swallowing (see section 5.2).
TUKYSA should be taken approximately 12 hours apart, at the same time every day, with or without a meal. TUKYSA may be taken at the same time with capecitabine.
There is no specific antidote, and the benefit of haemodialysis in the treatment of tucatinib overdose is unknown. In the event of an overdose, treatment with tucatinib should be withheld and general supportive measures should be applied.
2 years.
This medicinal product does not require any special storage conditions.
oPA/ALU/PVC blister sealed with aluminium foil.
TUKYSA 50 mg film-coated tablets: Each carton contains 88 film-coated tablets (11 blisters with 8 tablets each).
TUKYSA 150 mg film-coated tablets: Each carton contains 84 film-coated tablets (21 blisters with 4 tablets each).
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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