투카티닙헤미에탄올레이트

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. ( 1.1 ) • 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. ( 1.2 ) This indication is approved under accelerated approval based on tumor response rate and durability of response [see Clinical Studies (14.2) ]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. 1.1 Metastatic Breast Cancer TUKYSA 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. 1.2 Unresectable or Metastatic Colorectal Cancer TUKYSA 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 …

None. None. ( 4 )

• 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 TUKYSA based on severity. ( 2.2 , 5.1 ) • Hepatotoxicity : Severe hepatotoxicity has been reported on TUKYSA. Monitor ALT, AST and bilirubin prior to starting TUKYSA, every 3 weeks during treatment and as clinically indicated. Interrupt dose, then dose reduce, or permanently discontinue TUKYSA based on severity. ( 2.2 , 5.2 ) • Embryo-Fetal Toxicity : TUKYSA can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception. ( 5.3 , 8.1 , 8.3 ) Also, refer to the Full Prescribing Information of trastuzumab and capecitabine for pregnancy and contraception information. 5.1 Diarrhea TUKYSA can cause severe diarrhea including dehydration, hypotension, acute kidney injury, and death [see Adverse Reactions (6.1) ] . 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 TUKYSA [see Dosage and Administration (2.2) ] . TUKYSA with trastuzumab and capecitabine In HER2CLIMB, 81% of patients who received TUKYSA experienced diarrhea, including 0.5% with Grade 4 diarrhea and 12% with Grade 3 diarrhea. Both patients who …

8.1 Pregnancy Risk Summary TUKYSA is used in combination with trastuzumab and capecitabine. Refer to the Full Prescribing Information of trastuzumab and capecitabine for pregnancy information. Based on findings in animals and its mechanism of action, TUKYSA can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available human data on TUKYSA use in pregnant women to inform a drug-associated risk. In animal reproduction studies, administration of tucatinib to pregnant rats and rabbits during organogenesis resulted in embryo-fetal mortality, reduced fetal weight and fetal abnormalities at maternal exposures ≥ 1.3 times the human exposure …