tukysa

In patients with unresectable or metastatic colorectal cancer, confirm the presence of HER2 protein overexpression and RAS wild-type in tumor specimens prior to the initiation of TUKYSA ( 2.1 ) • Recommended dosage: 300 mg taken orally twice daily with or without food. ( 2.1 ) • For patients with severe hepatic impairment, the recommended dosage is 200 mg orally twice daily. ( 2.3 , 8.7 ) 2.1 Patient Selection Select patients for treatment of unresectable or metastatic colorectal cancer with TUKYSA based on the presence of: • HER2 overexpression or gene amplification [see Clinical Studies (14.2) ]. FDA-approved tests for the detection of HER2 overexpression and gene amplification in patients with unresectable or metastatic colorectal cancer are not currently available, and • RAS wild-type [see Clinical Studies (14.2) ]. Information on FDA-approved tests for the detection of RAS mutations in patients with unresectable or metastatic colorectal cancer is available at http://www.fda.gov/CompanionDiagnostics . 2.2 Recommended Dosage Metastatic Breast Cancer The recommended dosage of TUKYSA is 300 mg taken orally twice daily in combination with trastuzumab and capecitabine until disease progression or unacceptable toxicity [see Clinical Studies (14.1) ] . Unresectable or Metastatic Colorectal Cancer The recommended dosage of TUKYSA is 300 mg taken orally twice daily in combination…

The following clinically significant adverse reactions are described elsewhere in the labeling: • Diarrhea [see Warnings and Precautions (5.1) ] • Hepatotoxicity [see Warnings and Precautions (5.2) ] • The most common adverse reactions (≥20%) with TUKYSA 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. ( 6.1 ) • The most common adverse reactions (≥20%) with TUKYSA in combination with trastuzumab in patients with unresectable or metastatic colorectal cancer are diarrhea, fatigue, rash, nausea, abdominal pain, infusion related reactions, and pyrexia. To report SUSPECTED ADVERSE REACTIONS, contact Seagen at 1-855-4SEAGEN or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 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 TUKYSA in combination with trastuzumab and capecitabine was evaluated in HER2CLIMB [see Clinical Studies (14) ]. Patients received either TUKYSA 300 mg twice daily plus trastuzumab or a non-US…

None. None. ( 4 )

Strong CYP3A Inducers or Moderate CYP2C8 Inducers : Avoid concomitant use. ( 7.1 ) • Strong CYP2C8 Inhibitors : Avoid concomitant use; reduce TUKYSA dose if concomitant use cannot be avoided. ( 2.4 , 7.1 ) • CYP3A Substrates : Avoid concomitant use with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. ( 7.2 ) • P-gp Substrates : Consider reducing the dose of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. ( 7.2 ) 7.1 Effects of Other Drugs on TUKYSA Table 7 summarizes the effect of other drugs on TUKYSA. Table 7: Drug Interactions that Affect TUKYSA Strong CYP3A Inducers or Moderate CYP2C8 Inducers Clinical Impact Concomitant use of TUKYSA with a strong CYP3A or moderate CYP2C8 inducer decreased tucatinib plasma concentrations [see Clinical Pharmacology (12.3) ] , which may reduce TUKYSA activity. Management Avoid concomitant use of TUKYSA with a strong CYP3A inducer or a moderate CYP2C8 inducer. Strong or Moderate CYP2C8 Inhibitors Clinical Impact Concomitant use of TUKYSA with a strong CYP2C8 inhibitor increased tucatinib plasma concentrations [see Clinical Pharmacology (12.3) ] , which may increase the risk of TUKYSA toxicity. Management Avoid concomitant use of TUKYSA with a strong CYP2C8 inhibitor. Increase monitoring for TUKYSA toxicity with moderate CYP2C8 inhibitors. 7.2 Effects of TUKYSA on Other Drugs Table 8 summarizes the effect of TUKYSA on other drugs. Table 8: TUKYSA Drug Interactions that Affect Other Drugs CYP3A Substrates Clinical Impact Concomitant use of TUKYSA with a CYP3A substrate increased the plasma concentrations of CYP3A substrate [see Clinical Pharmacology (12.3) ] , which may increase the toxicity associated with a CYP3A substrate. Management Avoid concomitant use of TUKYSA with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If concomitant use is unavoidable, decrease the CYP3A substrate dosage in accordance with approved product labeling. P-glycoprotein (P-gp) Substrates Clinical Impact Concomitant use of TUKYSA with a P-gp substrate increased the plasma concentrations of P-gp substrate [see Clinical Pharmacology (12.3) ] , which may increase the toxicity associated with a P-gp substrate. Management Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.