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Tukysa

tucatinib
HER2 TKI (Selective) FDA Approved 2020 Seagen/AstraZeneca
Route
Oral
Half-Life
8 hrs
FDA Approved
2020
Manufacturer
Seagen/AstraZeneca
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1. Indications and Usage

HER2+ Metastatic Breast Cancer: In combination with trastuzumab and capecitabine for adult patients with HER2-positive unresectable locally advanced or metastatic breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting.
HER2+ Metastatic Colorectal Cancer: In combination with trastuzumab for adult patients with RAS wild-type, HER2-positive unresectable or metastatic colorectal cancer that has progressed after fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

2. Dosage and Administration

Recommended dose: 300 mg orally twice daily, approximately 12 hours apart, in combination with trastuzumab and capecitabine (breast) or trastuzumab alone (CRC)
Administration: With or without food. Swallow tablets whole.
Dose reductions: First: 250 mg twice daily; Second: 200 mg twice daily; Third: 150 mg twice daily. Discontinue if unable to tolerate 150 mg.

3. Dosage Forms and Strengths

Tablets (film-coated): 50 mg, 150 mg

4. Contraindications

None listed in the prescribing information.

5. Warnings and Precautions
  • Diarrhea: Reported in 81% of patients. Grade ≥3 diarrhea in 13%. If not responsive to antidiarrheal treatment, withhold until resolution.
  • Hepatotoxicity: Monitor ALT, AST, and bilirubin before starting and every 3 weeks or as clinically indicated.
  • Embryo-Fetal Toxicity: Can cause fetal harm.
6. Adverse Reactions
Most Common Adverse Reactions

Diarrhea (81%), PPE Syndrome (63%), Nausea (58%), Fatigue (45%), Vomiting (36%), Stomatitis (32%), Decreased Appetite (24%), Abdominal Pain (20%), Headache (16%), Anemia (15%)

Diarrhea
81%
PPE Syndrome
63%
Nausea
58%
Fatigue
45%
Vomiting
36%
Stomatitis
32%
Decreased Appetite
24%
Abdominal Pain
20%
Headache
16%
Anemia
15%

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

7. Drug Interactions

Strong CYP3A Inducers: Avoid concurrent use as they decrease tucatinib exposure.
Strong CYP3A Inhibitors: Avoid concurrent use as they increase tucatinib exposure.
CYP3A Substrates: Tucatinib is a strong CYP3A inhibitor. The dose of sensitive CYP3A substrates with narrow therapeutic index may need to be reduced.
CYP2C8 Substrates: Tucatinib is a moderate CYP2C8 inhibitor. Monitor for increased adverse reactions of CYP2C8 substrates.
P-gp Substrates: Tucatinib is a P-gp inhibitor. Consider reducing the dose of P-gp substrates with narrow therapeutic index.

8. Use in Specific Populations
Pregnancy

Consult the full prescribing information for pregnancy-related considerations.

Lactation

Refer to prescribing information for lactation guidance.

Pediatric Use

Pediatric safety and efficacy information is detailed in the full label.

Hepatic/Renal Impairment

Dose modifications for organ impairment are specified in the complete prescribing information.

12. Clinical Pharmacology
Mechanism of Action

Tucatinib is a tyrosine kinase inhibitor that is highly selective for the kinase domain of HER2 with minimal inhibition of EGFR. In combination with trastuzumab, tucatinib demonstrated enhanced anti-tumor activity compared with either agent alone. Tucatinib has demonstrated activity in the CNS, supporting its use in patients with brain metastases.

Pharmacokinetics

Tmax: 2 hours. Bioavailability not characterized. Vd: 1670 L. Protein binding: 97%. Metabolized by CYP2C8 and CYP3A. Half-life: 8.5 hours. Steady state within 4 days. Elimination: feces 86%, urine 5%.

14. Clinical Studies

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

Pivotal Clinical Trials
Additional Resources
FDA-Approved Tumor Types

Tukysa has FDA-approved indications across the following cancer types covered on CancerDrugEvidence:

External Resources
Important Notice: This page is intended as a navigational reference to the FDA-approved prescribing information for Tukysa. It does not replace the full prescribing information. Healthcare professionals should consult the complete package insert available at DailyMed before making prescribing decisions. Patient-specific factors should always guide clinical decision-making.

Frequently Asked Questions

What is Tukysa (tucatinib) approved for?

Tukysa (tucatinib) is an FDA-approved oncology agent. Refer to the full prescribing information for complete indication details.

How is Tukysa (tucatinib) administered?

Refer to the full prescribing information for dosing schedules, administration instructions, and dose modifications.

How does Tukysa (tucatinib) work?

Tucatinib is a tyrosine kinase inhibitor that is highly selective for the kinase domain of HER2 with minimal inhibition of EGFR. In combination with trastuzumab, tucatinib demonstrated enhanced anti-tumor activity compared with either agent alone. Tucatinib has demonstrated activity in the CNS, supporting its use in patients with brain metastases.

What are the most common side effects?

Diarrhea (81%), PPE Syndrome (63%), Nausea (58%), Fatigue (45%), Vomiting (36%), Stomatitis (32%), Decreased Appetite (24%), Abdominal Pain (20%), Headache (16%), Anemia (15%) Diarrhea 81% PPE Syndrome 63% Nausea 58% Fatigue 45% Vomiting 36% Stomatitis 32% Decreased Appetite 24% Abdominal Pain 20% H