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Tukysa is a brand name for Tucatinib. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 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.
Verbatim from this product's EMA label. Tap a section to expand.
Treatment with TUKYSA should be initiated and supervised by a physician experienced in the administration of anti–cancer medicinal products. Posology 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 3 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 Not applicable Initial dose 8 mg/kg intravenously Day 1 Subsequent doses 6 mg/kg intravenously Every 21 days OR Subcutaneous dosing 600 mg subcutaneously Every 21 days Treatment with TUKYSA should be continued until disease progression or unacceptable toxicity.
Missed dose In the case of a missed dose, the patient should take their next dose at the regularly scheduled time. 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.
TUKYSA should be permanently discontinued in patients unable to tolerate 150 mg orally twice daily. 4 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 antidiarrheal treatment Initiate or intensify appropriate medical therapy. Interrupt tucatinib until recovery to ≤ Grade 1, then resume tucatinib at the same dose level. Grade 3 with antidiarrheal treatment Initiate or intensify appropriate medical therapy.
Interrupt tucatinib until recovery to ≤ Grade 1, then resume tucatinib at the next lower dose level. Grade 4 Permanently discontinue tucatinib. 5 × ULN) No dose modification is required. 5 to 3 × ULN) Interrupt 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) Interrupt 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.
Summary of the safety profile The most commonly reported Grade 3 and 4 adverse reactions (≥ 5%) during treatment are diarrhoea (13%), ALT increased (6%) and AST increased (5%). Serious adverse reactions occurred in 29% of patients treated with tucatinib, and include diarrhoea (4%), vomiting (3%), and nausea (2%).
Adverse reactions leading to discontinuation of TUKYSA occurred in 6% of patients; the most common adverse reactions leading to discontinuation were diarrhoea (1%) and ALT increased (1%). Adverse reactions leading to dose reduction of TUKYSA occurred in 23% of patients; the most common adverse reactions leading to dose reduction were diarrhoea (6%), ALT increased (5%), and AST increased (4%).
1). 6). The adverse reactions observed during treatment are listed in this section by frequency category. Frequency categories are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000); not known (cannot be estimated from the available data).
Blood bilirubin increased also includes hyperbilirubinemia Description of selected adverse reactions Increased ALT, AST, or bilirubin In HER2CLIMB, increased ALT, AST or bilirubin occurred in 41% of patients treated with tucatinib in combination with trastuzumab and capecitabine.
Grade 3 and above events occurred in 9% of patients. 5% of patients. The median time to onset of any grade increased ALT, AST, or bilirubin was 37 days; 84% of events resolved, with a median time to resolution of 22 days. 4). Diarrhoea In HER2CLIMB, diarrhoea occurred in 82% of patients treated with tucatinib in combination with trastuzumab and capecitabine.
Grade 3 and above diarrhoea events occurred in 13% of patients. Two patients who developed Grade 4 diarrhoea subsequently died, with diarrhoea as a contributor to death. Diarrhoea led to dose reduction in 6% of the patients and treatment discontinuation in 1% of the patients.
8). ALT, AST, and total bilirubin should be monitored every three weeks or as clinically indicated. 2). 8). Alternative markers such as BUN, cystatin C, or calculated glomerular filtration rate (GFR), which are not based on creatinine, may be considered to determine whether renal function is impaired.
8). If diarrhoea occurs, antidiarrheals should be administered as clinically indicated. 2). Prompt medical management should also be instituted in the event of persistence of concomitant Grade 2 diarrhoea with concomitant Grade ≥ 2 nausea and/or vomiting.
Diagnostic tests should be performed as clinically indicated to exclude infectious causes of Grade 3 or 4 diarrhoea or diarrhoea of any grade with complicating features (dehydration, fever, neutropenia). Embryo-foetal toxicity Based on findings from animal studies and its mechanism of action, tucatinib may cause harmful effects to the foetus when administered to a pregnant woman.
In animal reproduction studies, administration of tucatinib to pregnant rabbits during organogenesis caused foetal abnormalities in rabbits at maternal exposures similar to the clinical exposures at the recommended dose. Pregnant women should be advised of the potential risk to a foetus.
6). Male patients with female partners of childbearing potential should also be advised to use an effective method of contraception during and up to at least 1 week after the last dose of treatment. Sensitive CYP3A substrates Tucatinib is a strong CYP3A inhibitor.
5). When tucatinib is co-administered with other medicinal products, the SmPC for the other product should be consulted for the recommendations regarding co-administration with CYP3A inhibitors. Concomitant treatment of tucatinib with CYP3A substrates when minimal concentration changes may lead to serious or life–threatening adverse reactions should be avoided.
If concomitant use is unavoidable, the CYP3A substrate dosage should be reduced in accordance with the concomitant medicinal product SmPC. P-gp substrates Concomitant use of tucatinib with a P-gp substrate increased the plasma concentrations of P-gp substrate, which may increase the toxicity associated with a P-gp substrate.
1.
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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 Interrupt tucatinib until recovery to ≤ Grade 1, then resume tucatinib at the next lower dose level.
Grade 4 Permanently discontinue tucatinib.
Abbreviations:
ULN=upper limit of normal; ALT=alanine aminotransferase; AST=aspartate aminotransferase Co-administration with CYP2C8 inhibitors Concomitant use with strong CYP2C8 inhibitors should be avoided. If co-administration with a strong CYP2C8 inhibitor cannot be avoided, the starting tucatinib dose should be reduced to 100 mg orally 5 twice daily.
5). Monitoring for TUKYSA toxicity should be increased when administered with moderate CYP2C8 inhibitors. 2). Tucatinib has not been investigated in patients above the age of 80 years. 2). 2). For patients with severe hepatic impairment (Child-Pugh C), a reduced starting dose of 200 mg orally twice daily is recommended.
Paediatric population The safety and efficacy of TUKYSA in paediatric patients have not been established. No data are available. Method of administration TUKYSA is for oral use. 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.
The median time to onset of any grade diarrhoea was 12 days; 81% of diarrhoea events resolved, with a median time to resolution of 8 days. Prophylactic use of antidiarrheals was not required. Antidiarrheal medicinal products were used in less than half of the treatment cycles where diarrhoea events were reported.
4). Increased creatinine without impaired renal function Increase in serum creatinine has been observed in patients treated with tucatinib due to inhibition of renal tubular transport of creatinine without affecting glomerular function.
In clinical studies, increases in serum creatinine (30% mean increase) occurred within the first cycle of tucatinib, remained elevated but stable throughout treatment and were reversible upon treatment discontinuation. Special populations Elderly In the HER2CLIMB study, 82 patients who received tucatinib were ≥ 65 years, of whom 8 patients were ≥ 75 years.
The incidence of serious adverse reactions was 34% in patients ≥ 65 years compared to 28% in patients < 65 years. There were too few patients ≥ 75 years to assess differences in safety. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 11 professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
Dose reduction of P-gp substrates (including sensitive intestinal substrate such as dabigatran) should be considered in accordance with the concomitant medicine SmPC and P-gp substrates should be administered with caution when minimal concentration changes may lead to serious or life-threatening toxicities.
Strong CYP3A/moderate CYP2C8 inducers Concomitant use of tucatinib with a strong CYP3A or moderate CYP2C8 inducer decreased tucatinib concentrations, which may reduce tucatinib activity. Concomitant use with a strong CYP3A inducer or moderate CYP2C8 inducer should be avoided.
Strong/moderate CYP2C8 inhibitors Concomitant use of tucatinib with a strong CYP2C8 inhibitor increased tucatinib concentrations, which may increase the risk of tucatinib toxicity. 2). There are no clinical data on the impact of concomitant use of moderate CYP2C8 inhibitors on tucatinib concentrations.
Monitoring for tucatinib toxicity should be increased with moderate CYP2C8 inhibitors. 3 mg sodium per 300 mg dose. 75% of the recommended maximum daily dietary intake of sodium for an adult. 6 mg potassium per 300 mg dose. This should be taken into consideration for patients who have impaired kidney function or are on a controlled potassium diet (diet with low potassium content).