TUKYSA Film-coated tablet (2020)

Βιβλιογραφική αναφορά

Συγγραφείς

Seattle Genetics, Inc.

Λέξεις κλειδιά

51144-001 51144-002

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1. Indications and Usage

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 ...

2. Dosage and Administration

2.1 Recommended Dosage 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 ...

3. Dosage Forms and Strengths

Tablets: 50 mg: round, yellow, film-coated, debossed with TUC on one side and 50 on the other side. 150 mg: oval-shaped, yellow, film-coated, debossed with TUC on one side and 150 on the other side. ...

4. Contraindications

None.

5. Warnings and Precautions

5.1 Diarrhea TUKYSA can cause severe diarrhea including dehydration, hypotension, acute kidney injury, and death [see Adverse Reactions (6.1)]. In HER2CLIMB, 81% of patients who received TUKYSA ...

6. Adverse Reactions

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)] ...

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 ...

7. Drug Interactions

7.1 Effects of Other Drugs on TUKYSA Table 5 summarizes the effect of other drugs on TUKYSA. Table 5. Drug Interactions that Affect TUKYSA: Strong CYP3A Inducers or Moderate CYP2C8 Inducers ...

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 ...

8.2. Lactation

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 ...

8.3. Females and Males of Reproductive Potential

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 ...

8.4. Pediatric Use

The safety and effectiveness of TUKYSA in pediatric patients have not been established.

8.5. Geriatric Use

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 ...

8.6. Renal Impairment

The use of TUKYSA in combination with capecitabine and trastuzumab is not recommended in patients with severe renal impairment (CLcr <30 mL/min estimated by Cockcroft-Gault Equation), because capecitabine ...

8.7. Hepatic Impairment

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 ...

11. Description

Tucatinib is a kinase inhibitor. The chemical name is (N4-(4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)N6(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine. The molecular formula ...

12.1. Mechanism of Action

Tucatinib is a tyrosine kinase inhibitor of HER2. In vitro, tucatinib inhibits phosphorylation of HER2 and HER3, resulting in inhibition of downstream MAPK and AKT signaling and cell proliferation, and ...

12.2. Pharmacodynamics

Exposure Response Relationship Tucatinib exposure-response relationships and the time course of pharmacodynamics response have not been fully characterized. Cardiac Electrophysiology No large mean increase ...

12.3. Pharmacokinetics

Tucatinib AUC0-INF and Cmax increases proportionally over a dosage range from 50 mg to 300 mg (0.17 to 1 times the approved recommended dosage). Tucatinib exhibited 1.7-fold accumulation ...

13.1. Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity studies have not been conducted with tucatinib. Tucatinib was not mutagenic in an in vitro bacterial reverse mutation (Ames) assay. Tucatinib was not clastogenic in either an in vitro chromosome ...

14. Clinical Studies

14.1 HER2-Positive Metastatic Breast Cancer The efficacy of TUKYSA in combination with trastuzumab and capecitabine was evaluated in 612 patients in HER2CLIMB (NCT02614794), a randomized (2:1), double-blind, ...

16.1. How Supplied

TUKYSA 50 mg tablets are supplied as yellow, film-coated, round tablets containing 50 mg of tucatinib. Each tablet is debossed with TUC on one side and 50 on the other side, and is packaged as follows: ...

17. Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Patient Information). Diarrhea: Inform patients that TUKYSA has been associated with severe diarrhea. Instruct patients on how to manage ...