Tucatinib (Tukysa) is a highly selective HER2 tyrosine kinase inhibitor. It is indicated for use in combination with trastuzumab and capecitabine for the treatment of advanced HER2-positive breast cancer, or in combination with trastuzumab for the treatment of RAS wild-type HER2-positive colorectal cancer. By blocking the HER2 signaling pathway, it inhibits tumor growth and exhibits particularly favorable efficacy in patients with brain metastases.

Precautions for Taking Tucatinib (Tukysa)

Eligible Populations and Contraindications

Used in combination with trastuzumab and capecitabine for the treatment of advanced HER2-positive breast cancer (including patients with brain metastases) in patients who have previously received anti-HER2 regimens.

Used in combination with trastuzumab for the treatment of RAS wild-type HER2-positive colorectal cancer that has progressed following fluorouracil-, oxaliplatin-, or irinotecan-based chemotherapy (under the accelerated approval pathway).

Contraindications: No absolute contraindications are listed in the current package insert, but patients with hypersensitivity to any component of the drug must be excluded.

Administration Method

Swallow the tablets whole; do not chew, crush, or split them.

If a tablet is broken, cracked, or incomplete, do not take it.

Management of missed doses: If vomiting occurs after administration or a dose is missed, do not make up for the missed dose—take the next dose directly as scheduled.

Adverse Reaction Warnings

Diarrhea: Diarrhea occurs in 81% of breast cancer patients, of which 12% experience Grade 3 diarrhea and 0.5% experience Grade 4 diarrhea (which can be fatal). Antidiarrheal medications should be prepared, and fluid replacement should be administered promptly.

Hepatotoxicity: 8% of patients experience alanine transaminase (ALT) elevation exceeding 5 times the upper limit of normal. Regular liver function monitoring is required during treatment.

Embryo-fetal toxicity: Animal studies have shown that tucatinib can cause fetal abnormalities. Patients of childbearing age must use effective contraceptive measures during treatment and for 1 week after the last dose.

Other common reactions: These include palmar-plantar erythrodysesthesia (63%), nausea (58%), vomiting (36%), stomatitis (32%), and anemia (21%).

Management in Special Populations

Hepatic impairment: No dosage adjustment is required for mild to moderate impairment; dosage reduction is necessary for severe impairment.

Renal impairment: No dosage adjustment is required for mild to moderate impairment, but caution is needed when used in combination with capecitabine, as capecitabine is contraindicated in patients with severe renal impairment.

Elderly patients: In clinical trials, the incidence of severe adverse reactions was higher in patients aged ≥ 65 years, so enhanced monitoring is required.

Medication Monitoring for Tucatinib (Tukysa)

Liver Function Monitoring

Frequency: Before treatment, once every 3 weeks, or as clinically needed.

Indicators: Alanine transaminase (ALT), aspartate transaminase (AST), and total bilirubin.

Renal Function Monitoring

Tucatinib may cause an increase in serum creatinine, but it does not affect the glomerular filtration rate.

If the increase persists, other renal function markers should be considered for assessment.

Drug Interaction Monitoring

Concomitant use with CYP3A substrates (e.g., certain antiarrhythmic drugs) should be avoided to prevent increased toxicity.

If concomitant use with P-gp substrates (e.g., digoxin) is necessary, dosage adjustment should be considered.