[Key Drug Information]

Generic Name: Tucatinib Tablets / Tucatinib

Brand Name: Tukysa / TUCAXEN

English Name: Tucatinib Tablets

Dosage Form: Film-coated tablets

Specification: 150 mg/tablet; 30 tablets/box

Manufacturer: Everest Pharma Ltd (Everest Pharma, Bangladesh)

[Indications and Mechanism of Action]

Mechanism of Action: A highly selective HER2 tyrosine kinase inhibitor with weak inhibitory activity against the epidermal growth factor receptor (EGFR), designed to enhance efficacy while minimizing side effects.

Indications:

1. Advanced HER2-Positive Breast Cancer: Used in combination with trastuzumab and capecitabine for the treatment of adult patients with advanced unresectable or metastatic HER2-positive breast cancer who have previously received at least one anti-HER2 regimen (including patients with brain metastases). Its use in earlier lines of therapy is currently under investigation.

2. Advanced HER2-Positive Colorectal Cancer: Used in combination with trastuzumab for the treatment of adult patients with RAS wild-type, HER2-positive, unresectable or metastatic colorectal cancer who have previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. This is an indication approved under the Accelerated Approval Program.

[Dosage and Administration]

Patient Selection:

Breast Cancer: HER2-positive status must be confirmed.

Colorectal Cancer: Use is indicated only after testing confirms that the tumor exhibits HER2 overexpression/amplification and is RAS wild-type.

Recommended Dosage: 300 mg orally, twice daily (approximately 12 hours apart), taken with or without food.

Dosage Adjustment: Adjustments should be made based on the severity of adverse reactions. The table below outlines common dosage adjustment regimens:

Adjustment Step | Dosage Regimen

Initial Dose | 300 mg, twice daily

First Dose Reduction | 250 mg, twice daily

Second Dose Reduction | 200 mg, twice daily

Third Dose Reduction | 150 mg, twice daily

Special Populations:

Hepatic Impairment: For patients with severe hepatic impairment, the recommended initial dose is 200 mg, twice daily.

Renal Impairment: No dosage adjustment is required for patients with mild to moderate renal impairment; data are limited for patients with severe renal impairment.

Missed Doses: Skip the missed dose and take the next dose at the regularly scheduled time; do not take an extra dose or double the dose.

[Important Warnings and Precautions]

1. Severe Diarrhea: Severe diarrhea may occur, including cases involving dehydration, acute kidney injury, or even death. Antidiarrheal treatment should be initiated immediately upon the onset of diarrhea; depending on the severity, treatment may require temporary interruption, dose reduction, or permanent discontinuation.

2. Hepatotoxicity: May cause severe liver injury. Monitor ALT, AST, and bilirubin levels prior to initiating treatment, every 3 weeks during treatment, and as clinically indicated.

3. Embryo-Fetal Toxicity: May cause harm to the fetus. Females and males of reproductive potential must use effective contraception during treatment and for at least 1 week following the last dose.

4. Combination Therapy: Tucatinib must be used in combination with trastuzumab and capecitabine (for breast cancer) or with trastuzumab alone (for colorectal cancer); please also follow the prescribing information for these concomitant medications.

[Adverse Reactions]

In clinical studies for breast cancer, the most common adverse reactions (incidence ≥20%) included: diarrhea, palmar-plantar erythrodysesthesia syndrome, nausea, hepatotoxicity, vomiting, stomatitis, decreased appetite, anemia, and rash.

The most common Grade 3 or 4 laboratory abnormalities (incidence ≥5%) included: decreased phosphate, increased ALT, decreased potassium, increased AST, increased bilirubin, and decreased hemoglobin. [Drug Interactions]

Tucatinib is a strong inhibitor of CYP3A and an inhibitor of P-gp. The table below summarizes the major interactions and recommended management strategies:

| Interacting Drug Category | Clinical Recommendation |

|---|---|

| Strong CYP3A Inducers (e.g., Rifampin) or Moderate CYP2C8 Inducers | Avoid co-administration, as this will decrease tucatinib plasma concentrations and compromise efficacy. |

| Strong CYP2C8 Inhibitors (e.g., Gemfibrozil) | Avoid co-administration, as this will increase tucatinib plasma concentrations and the risk of toxicity. |

| CYP3A Substrates with a Narrow Therapeutic Window | Avoid co-administration, as tucatinib will significantly increase their plasma concentrations, potentially leading to severe toxicity. |

| P-gp Substrates with a Narrow Therapeutic Window | Consider reducing the dosage of the co-administered drug and use with caution. |

[Use in Specific Populations]

Pregnant Women: Contraindicated. Based on its mechanism of action, the drug may cause harm to the fetus.

Lactating Women: Breastfeeding is not recommended during treatment and for at least 1 week after the last dose.

Children and Adolescents: Safety and efficacy have not been established.

Geriatric Patients: No significant differences in overall safety were observed compared to younger patients.

[Storage]

Store at room temperature (20–25°C) in the original packaging, protected from moisture.

Once opened, use within 3 months; any remaining tablets should be discarded thereafter.

[Important Notes]

Key Advantage: Clinical studies have confirmed that tucatinib-based combination regimens demonstrate significant efficacy in patients with HER2-positive breast cancer with brain metastases.

Pre-treatment Requirement: Before use, it is mandatory to confirm the HER2 status (for breast cancer) or the HER2 and RAS status (for colorectal cancer) via genetic testing.

This package insert integrates official drug information with data from various authoritative medical platforms; it is intended to serve as a comprehensive reference for you and does not substitute for the prescription and guidance of a professional physician. If you are interested in data regarding the use of Tucatinib in specific tumor types (such as those with brain metastases), or in how it differs from other HER2-targeted therapies (such as Lapatinib or Neratinib), you may also search for and review that information.

Product Specifications

Product Name: Tucatinib Tablets (Tucatinib) 150mg × 90 Tablets/Box | TUCAXEN Tucatinib Tablets

Common Name: Tucatinib Tablets

Active Ingredient: Tucatinib

Dosage Form: Oral Film-Coated Tablets

Specification: 150mg/tablet; 30 tablets/box

Manufacturer: Everest Pharma Ltd (Bangladesh)

Indications:

1. Advanced HER2-Positive Breast Cancer: Used in combination with Trastuzumab and Capecitabine for the treatment of adult patients with advanced, unresectable, or metastatic HER2-positive breast cancer (including those with brain metastases) who have previously received at least one anti-HER2 regimen. Its use in earlier lines of therapy is currently under investigation.

2. Advanced HER2-Positive Colorectal Cancer: Used in combination with Trastuzumab for the treatment of adult patients with RAS wild-type, HER2-positive, unresectable, or metastatic colorectal cancer who have previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. This is an indication approved under the Accelerated Approval Program.

Dosage and Administration:

Patient Selection:

Breast Cancer: HER2-positivity must be confirmed.

Colorectal Cancer: Prior to use, the tumor must be confirmed via testing to exhibit HER2 overexpression/amplification and to be RAS wild-type.

Standard Dosage: 300mg (two 150mg tablets) orally, twice daily (BID), approximately 12 hours apart. May be taken with or without food. Continue treatment until disease progression or until toxicity becomes intolerable.

Combination Regimen:

Breast Cancer: Tucatinib 300mg BID + Capecitabine 1000mg/m² BID (Days 1–14 of each cycle) + Trastuzumab 6mg/kg IV every 3 weeks (q3w) [with an initial loading dose of 8mg/kg]. Colorectal Cancer: Tucatinib 300 mg BID + Trastuzumab 6 mg/kg IV q3w (loading dose: 8 mg/kg).