Tucaone Tablet

Tucatinib is a kinase inhibitor indicated: - in combination with trastuzumab and capecitabine for treatment of adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting. - in combination with trastuzumab for the treatment of adult patients with RAS wild-type HER2-positive unresectable or metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Metastatic Breast Cancer Tucatinib is indicated in combination with trastuzumab and capecitabine for treatment of adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting. Unresectable or Metastatic Colorectal Cancer Tucatinib is indicated in combination with trastuzumab for the treatment of adult patients with RAS wild-type, HER2-positive unresectable or metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

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Source: US FDA prescribing information, via openFDA. Provided for general information only — it is not a substitute for your doctor's or pharmacist's advice. Always follow your prescriber's instructions.

• Diarrhea: Severe diarrhea, including dehydration, acute kidney injury, and death, has been reported. Administer antidiarrheal treatment as clinically indicated. Interrupt dose, then dose reduce, or permanently discontinue Tucatinib based on severity. - Hepatotoxicity: Severe hepatotoxicity has been reported on Tucatinib. Monitor ALT, AST and bilirubin prior to starting Tucatinib, every 3 weeks during treatment and as clinically indicated. - Embryo-Fetal Toxicity: Tucatinib can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception. Also, refer to the Full Prescribing Information of trastuzumab and capecitabine for pregnancy and contraception information. Diarrhea Tucatinib can cause severe diarrhea including dehydration, hypotension, acute kidney injury, and death. If diarrhea occurs, administer antidiarrheal treatment as clinically indicated. Perform diagnostic tests as clinically indicated to exclude other causes of diarrhea. Based on the severity of the diarrhea, interrupt dose, then dose reduce or permanently discontinue Tucatinib. Tucatinib with trastuzumab and capecitabine In HER2CLIMB, 81% of patients who received Tucatinib experienced diarrhea, including 0.5% with Grade 4 diarrhea and 12% with Grade 3 diarrhea. Both patients who developed Grade 4 diarrhea subsequently died, with diarrhea as a contributor to death. The median time to onset of the first episode of diarrhea was 12 days and the median time to resolution was 8 days. Diarrhea led to dose reductions of Tucatinib in 6% of patients and discontinuation of Tucatinib in 1% of patients. Prophylactic use of antidiarrheal treatment was not required on HER2CLIMB. Tucatinib with trastuzumab In MOUNTAINEER, diarrhea occurred in 64% of patients, including Grade 3 (3.5%), Grade 2 (10%), and Grade 1 (50%). Hepatotoxicity Tucatinib can cause severe hepatotoxicity. Based on the severity of hepatotoxicity, interrupt dose, then dose reduce or permanently discontinue Tucatinib. Tucatinib with trastuzumab and capecitabine In HER2CLIMB, 8% of patients who received Tucatinib had an ALT increase > 5 × ULN, 6% had an AST increase > 5 × ULN, and 1.5% had a bilirubin increase > 3 × ULN (Grade ≥3). Hepatotoxicity led to dose reduction of Tucatinib in 8% of patients and discontinuation of Tucatinib in 1.5% of patients. Tucatinib with trastuzumab In MOUNTAINEER, 6% of patients had a bilirubin increase > 3 × ULN (Grade ≥3), 6% had an AST increase > 5 × ULN, and 4.7% had an ALT increase > 5 × ULN. Hepatotoxicity led to dose reduction of Tucatinib in 3.5% of patients and discontinuation of Tucatinib in 2.3% of patients. Embryo-Fetal Toxicity Based on findings from animal studies and its mechanism of action, Tucatinib can cause fetal harm when administered to a pregnant woman. Abridged from the full prescribing information.

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Source: US FDA prescribing information, via openFDA. Provided for general information only — it is not a substitute for your doctor's or pharmacist's advice. Always follow your prescriber's instructions.

The following clinically significant adverse reactions are described elsewhere in the labeling: - Diarrhea - Hepatotoxicity - The most common adverse reactions (≥20%) with Tucatinib in combination with trastuzumab and capecitabine in patients with metastatic breast cancer are diarrhea, palmar-plantar erythrodysesthesia, nausea, hepatotoxicity, vomiting, stomatitis, decreased appetite, anemia, and rash. - The most common adverse reactions (≥20%) with Tucatinib in combination with trastuzumab in patients with unresectable or metastatic colorectal cancer are diarrhea, fatigue, rash, nausea, abdominal pain, infusion related reactions, and pyrexia.. Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. HER2-Positive Metastatic Breast Cancer The safety of Tucatinib in combination with trastuzumab and capecitabine was evaluated in HER2CLIMB. Patients received either Tucatinib 300 mg twice daily plus trastuzumab or a non-US approved trastuzumab product, and capecitabine (n=404) or placebo plus trastuzumab or a non-US approved trastuzumab product and capecitabine (n=197). The median duration of treatment was 5.8 months (range: 3 days, 2.9 years) for the Tucatinib arm. Serious adverse reactions occurred in 26% of patients who received Tucatinib. Serious adverse reactions in ≥ 2% of patients who received Tucatinib were diarrhea (4%), vomiting (2.5%), nausea (2%), abdominal pain (2%), and seizure (2%). Fatal adverse reactions occurred in 2% of patients who received Tucatinib including sudden death, sepsis, dehydration, and cardiogenic shock. Adverse reactions leading to treatment discontinuation occurred in 6% of patients who received Tucatinib. Adverse reactions leading to treatment discontinuation of Tucatinib in ≥1% of patients were hepatotoxicity (1.5%) and diarrhea (1%). Adverse reactions leading to dose reduction occurred in 21% of patients who received Tucatinib. Adverse reactions leading to dose reduction of Tucatinib in ≥2% of patients were hepatotoxicity (8%) and diarrhea (6%). The most common adverse reactions in patients who received Tucatinib (≥20%) were diarrhea, palmar-plantar erythrodysesthesia, nausea, hepatotoxicity, vomiting, stomatitis, decreased appetite, anemia, and rash. Table 3 summarizes the adverse reactions in HER2CLIMB. Abridged from the full prescribing information.

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Source: US FDA prescribing information, via openFDA. Provided for general information only — it is not a substitute for your doctor's or pharmacist's advice. Always follow your prescriber's instructions.