Tuccatinn Tucatinib Tablet 150mg

I. Basic Drug Information

Generic Name: Tucatinib Tablets (Tucatinib)

Brand Names: Tukysa, Tuccatinn, Tuokesai

Dosage Form and Strength: Film-coated tablets; 150 mg/tablet; 60 tablets/box

Manufacturer: BDR PHARMACEUTICALS PVT LTD

Pharmacological Class: Highly selective HER2 tyrosine kinase inhibitor

Mechanism of Action: Selectively inhibits the ATP-binding sites of HER2 and HER3; blocks downstream PI3K/Akt and MAPK signaling pathways; inhibits the proliferation of HER2-positive tumor cells; capable of crossing the blood-brain barrier and is effective against brain metastases.

Storage Conditions: Store at 20–25°C (excursions permitted between 15–30°C); keep dry and protected from light; do not freeze. Shelf life: 24 months in the original container; use within 6 months after opening.

II. Indications

1. HER2-positive Metastatic Breast Cancer: In combination with trastuzumab and capecitabine, for the treatment of unresectable or metastatic HER2-positive breast cancer in adults (including those with brain metastases) who have previously received at least one anti-HER2 regimen.

2. HER2-Positive Metastatic Colorectal Cancer: In combination with trastuzumab, for the treatment of unresectable or metastatic HER2-positive colorectal cancer in adults with *RAS* wild-type tumors, whose disease has progressed following prior therapy with fluoropyrimidine, oxaliplatin, and irinotecan.

III. Dosage and Administration

Standard Dosage

Recommended Dose: 300 mg orally, twice daily (approximately 12 hours apart). Tablets should be swallowed whole; do not chew, crush, or split. May be taken with or without food.

Combination Regimens

Breast Cancer: + Trastuzumab (initial dose 8 mg/kg, followed by 6 mg/kg every 3 weeks) + Capecitabine (1000 mg/m² orally, twice daily, on Days 1–14 of a 21-day cycle).

Colorectal Cancer: + Trastuzumab (initial dose 8 mg/kg, followed by 6 mg/kg every 3 weeks).

Missed Dose: If more than 6 hours remain before the next scheduled dose, take the missed dose immediately; if 6 hours or less remain, skip the missed dose and do not take a double dose.

Dosage Adjustments

Hepatic Impairment: Mild (Child-Pugh A)—no adjustment required; Moderate (Child-Pugh B)—reduce dose to 200 mg orally, twice daily; Severe (Child-Pugh C)—contraindicated.

Renal Impairment: Mild to Moderate (CrCl ≥ 30 mL/min)—no adjustment required; Severe (CrCl < 30 mL/min)—combination with capecitabine is not recommended.

Adjustments for Adverse Reactions

Grade 3 Diarrhea: Withhold therapy until recovery to Grade ≤ 1; upon recovery, resume at a dose of 250 mg twice daily. Grade 4 Diarrhea: Permanently discontinue therapy.

Grade 3 ALT/AST Elevation (> 3 × ULN): Withhold therapy until recovery to Grade ≤ 1; upon recovery, resume at a dose of 250 mg. bid; Grade 4 hepatotoxicity requires permanent discontinuation.

IV. Adverse Reactions

Common Adverse Reactions (Incidence ≥ 20%)

Diarrhea (81%), fatigue (60%), nausea (57%), palmar-plantar erythrodysesthesia syndrome (Hand-Foot Syndrome, 63%), vomiting, decreased appetite, abdominal pain, headache, elevated AST/ALT (42%), anemia.

Serious Adverse Reactions (Require Immediate Medical Attention)

Severe diarrhea (Grade 3: 13%; Grade 4: 0.5%): dehydration, electrolyte disturbances.

Hepatotoxicity (Grade 3 elevated ALT/AST: 9.2%): jaundice, hepatic failure.

Interstitial lung disease/pneumonitis (< 1%): dyspnea, cough, fever.

Severe hemorrhage, arrhythmias, hypersensitivity reactions.

V. Precautions

Diarrhea Management

Prophylactic use of loperamide; for Grade 3 diarrhea, suspend treatment and administer fluids, then resume at a reduced dose once resolved; for Grade 4 diarrhea, permanently discontinue treatment.

Hepatotoxicity Monitoring

Monitor ALT/AST/bilirubin prior to treatment, every 3 weeks thereafter, and as clinically indicated; for Grade ≥ 3 elevations, suspend/reduce dose/discontinue treatment.

Embryo-Fetal Toxicity

Contraindicated in pregnant women; women of childbearing potential must use effective contraception during treatment and for 1 week after the last dose; men must use effective contraception during treatment and for 1 week after the last dose.

Other

Avoid administration of live vaccines; monitor for symptoms of interstitial lung disease; if symptoms occur, immediately discontinue treatment and seek medical attention.

VI. Contraindications

Patients with hypersensitivity to tucatinib or any of its excipients.

Patients with severe hepatic impairment (Child-Pugh Class C).

Pregnant and breastfeeding women (discontinue treatment or discontinue breastfeeding).

VII. Drug Interactions

Strong CYP3A4 Inducers (e.g., rifampin, carbamazepine): Avoid co-administration, as this may decrease plasma drug concentrations.

Strong CYP2C8 Inhibitors (e.g., gemfibrozil): Reduce the tucatinib dose to 150 mg. bid

Digoxin: When used concomitantly, reduce the digoxin dosage by 30%–50% and monitor serum drug concentrations.

Acid-suppressing agents: Administer at a separate time interval from proton pump inhibitors; administer at an interval of ≥2 hours from H2 receptor antagonists or antacids.

VIII. Use in Specific Populations

Children/Adolescents: Safety and efficacy have not been established; use is not recommended.

Elderly Patients (≥65 years): No dosage adjustment is required; closely monitor for diarrhea and hepatotoxicity.

Lactating Women: Discontinue the drug or discontinue breastfeeding; breastfeeding may be resumed 1 week after discontinuing the drug.

Product Specifications

Product Name: Tucatinib Tablets 150 mg (60 tablets/box) [Tuccatinn]

Generic Name: Tucatinib Tablets

Active Ingredient: Tucatinib

Dosage Form: Tablets

Specification: 150 mg/tablet; 60 tablets/box

Manufacturer: BDR PHARMACEUTICALS PVT LTD

Indications: 1. HER2-positive metastatic breast cancer: In combination with trastuzumab and capecitabine, for the treatment of unresectable or metastatic HER2-positive adult breast cancer (including cases with brain metastases) that has previously received ≥1 anti-HER2-based regimen.

2. HER2-positive metastatic colorectal cancer: In combination with trastuzumab, for the treatment of unresectable or metastatic HER2-positive adult colorectal cancer with RAS wild-type status that has progressed following prior treatment with fluorouracil, oxaliplatin, and irinotecan.

Dosage and Administration: Standard Dosage

Recommended Dosage: 300 mg per dose, taken orally, twice daily (approximately 12 hours apart). Swallow the tablet whole; do not chew, crush, or split it. May be taken with or without food.

Combination Regimens

Breast Cancer: + Trastuzumab (initial dose: 8 mg/kg; subsequent doses: 6 mg/kg, once every 3 weeks) + Capecitabine (1000 mg/m², twice daily, on Days 1–14; 21-day cycle).

Colorectal Cancer: + Trastuzumab (initial dose: 8 mg/kg; subsequent doses: 6 mg/kg, once every 3 weeks).

Missed Dose: If more than 6 hours remain before the next scheduled dose, take the missed dose immediately; if 6 hours or less remain, skip the missed dose and do not take a double dose.