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 (AUC) at the recommended dose (see Data). Advise pregnant women and females of reproductive potential of the potential risk to the fetus.
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively.
Animal Data
In pilot embryo-fetal development studies, pregnant rats and rabbits received oral doses of tucatinib up to 150 mg/kg/day during the period of organogenesis.
In rats, oral administration of tucatinib resulted in maternal toxicity (body weight loss, reduced body weight gain, low food consumption) at doses ≥ 90 mg/kg/day. Fetal effects included reduced number of live fetuses, decreased fetal weight, and fetal abnormalities (increase in skeletal variations, incomplete ossification) at ≥ 90 mg/kg/day (approximately 3.5 times the human exposure at the recommended dose based on AUC).
In rabbits, oral administration of tucatinib resulted in increased resorptions, decreased percentages of live fetuses, and skeletal, visceral, and external malformations in fetuses at doses ≥ 90 mg/kg/day (1.3 times the human exposure at the recommended dose based on AUC). Fetal abnormalities included domed head, brain dilation, incomplete ossification of frontal and parietal bones, and a hole in the parietal bone.
Risk Summary
TUKYSA is used in combination with trastuzumab and capecitabine. Refer to the Full Prescribing Information of trastuzumab and capecitabine for lactation information.
There are no data on the presence of tucatinib or its metabolites in human or animal milk or its effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with TUKYSA and for 1 week after the last dose.
TUKYSA can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. TUKYSA is used in combination with trastuzumab and capecitabine. Refer to the Full Prescribing Information of trastuzumab and capecitabine for contraception and infertility information.
Pregnancy Testing
Verify the pregnancy status of females of reproductive potential prior to initiating treatment with TUKYSA.
Contraception
Females
Advise females of reproductive potential to use effective contraception during treatment with TUKYSA and for 1 week after the last dose.
Males
Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TUKYSA and for 1 week after the last dose.
Infertility
Based on findings from animal studies, TUKYSA may impair male and female fertility [see Nonclinical Toxicology (13.1)].
The safety and effectiveness of TUKYSA in pediatric patients have not been established.
In HER2CLIMB, 82 patients who received TUKYSA were ≥ 65 years, of whom 8 patients were ≥ 75 years. The incidence of serious adverse reactions in those receiving TUKYSA was 34% in patients ≥ 65 years compared to 24% in patients <65 years. The most frequent serious adverse reactions in patients ≥65 years who received TUKYSA were diarrhea (9%), vomiting (6%), and nausea (5%). There were no observed overall differences in the effectiveness of TUKYSA in patients ≥ 65 years compared to younger patients. There were too few patients ≥75 years to assess differences in effectiveness or safety.
In MOUNTAINEER, 12 patients were ≥65 years of age. There were too few patients ≥65 years to assess differences in effectiveness or safety.
The use of TUKYSA in combination with capecitabine and trastuzumab is not recommended in patients with severe renal impairment (creatinine clearance [CLcr]: < 30 mL/min estimated by Cockcroft-Gault Equation), because capecitabine is contraindicated in patients with severe renal impairment. Refer to the Full Prescribing Information of capecitabine for additional information in severe renal impairment.
No dose adjustment is recommended for patients with mild or moderate renal impairment (CLcr: 30 to 89 mL/min).
Tucatinib exposure is increased in patients with severe hepatic impairment (Child-Pugh C). Reduce the dose of TUKYSA for patients with severe (Child-Pugh C) hepatic impairment [see Dosage and Administration (2.3), Clinical Pharmacology (12.3)].
No dose adjustment for TUKYSA is required for patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment.
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 (AUC) at the recommended dose (see Data). Advise pregnant women and females of reproductive potential of the potential risk to the fetus.
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively.
Animal Data
In pilot embryo-fetal development studies, pregnant rats and rabbits received oral doses of tucatinib up to 150 mg/kg/day during the period of organogenesis.
In rats, oral administration of tucatinib resulted in maternal toxicity (body weight loss, reduced body weight gain, low food consumption) at doses ≥ 90 mg/kg/day. Fetal effects included reduced number of live fetuses, decreased fetal weight, and fetal abnormalities (increase in skeletal variations, incomplete ossification) at ≥ 90 mg/kg/day (approximately 3.5 times the human exposure at the recommended dose based on AUC).
In rabbits, oral administration of tucatinib resulted in increased resorptions, decreased percentages of live fetuses, and skeletal, visceral, and external malformations in fetuses at doses ≥ 90 mg/kg/day (1.3 times the human exposure at the recommended dose based on AUC). Fetal abnormalities included domed head, brain dilation, incomplete ossification of frontal and parietal bones, and a hole in the parietal bone.
Risk Summary
TUKYSA is used in combination with trastuzumab and capecitabine. Refer to the Full Prescribing Information of trastuzumab and capecitabine for lactation information.
There are no data on the presence of tucatinib or its metabolites in human or animal milk or its effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with TUKYSA and for 1 week after the last dose.
TUKYSA can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. TUKYSA is used in combination with trastuzumab and capecitabine. Refer to the Full Prescribing Information of trastuzumab and capecitabine for contraception and infertility information.
Pregnancy Testing
Verify the pregnancy status of females of reproductive potential prior to initiating treatment with TUKYSA.
Contraception
Females
Advise females of reproductive potential to use effective contraception during treatment with TUKYSA and for 1 week after the last dose.
Males
Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TUKYSA and for 1 week after the last dose.
Infertility
Based on findings from animal studies, TUKYSA may impair male and female fertility [see Nonclinical Toxicology (13.1)].
The safety and effectiveness of TUKYSA in pediatric patients have not been established.
In HER2CLIMB, 82 patients who received TUKYSA were ≥ 65 years, of whom 8 patients were ≥ 75 years. The incidence of serious adverse reactions in those receiving TUKYSA was 34% in patients ≥ 65 years compared to 24% in patients <65 years. The most frequent serious adverse reactions in patients ≥65 years who received TUKYSA were diarrhea (9%), vomiting (6%), and nausea (5%). There were no observed overall differences in the effectiveness of TUKYSA in patients ≥ 65 years compared to younger patients. There were too few patients ≥75 years to assess differences in effectiveness or safety.
In MOUNTAINEER, 12 patients were ≥65 years of age. There were too few patients ≥65 years to assess differences in effectiveness or safety.
The use of TUKYSA in combination with capecitabine and trastuzumab is not recommended in patients with severe renal impairment (creatinine clearance [CLcr]: < 30 mL/min estimated by Cockcroft-Gault Equation), because capecitabine is contraindicated in patients with severe renal impairment. Refer to the Full Prescribing Information of capecitabine for additional information in severe renal impairment.
No dose adjustment is recommended for patients with mild or moderate renal impairment (CLcr: 30 to 89 mL/min).
Tucatinib exposure is increased in patients with severe hepatic impairment (Child-Pugh C). Reduce the dose of TUKYSA for patients with severe (Child-Pugh C) hepatic impairment [see Dosage and Administration (2.3), Clinical Pharmacology (12.3)].
No dose adjustment for TUKYSA is required for patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment.
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