Tukysa (tucatinib) is an oral tyrosine kinase inhibitor primarily used for the treatment of HER2-positive advanced or metastatic breast cancer and colorectal cancer. While it demonstrates significant efficacy in inhibiting tumor growth, it may be accompanied by a series of side effects during use.

What Are the Side Effects of Tukysa (Tucatinib)?

When Combined with Trastuzumab and Capecitabine (for Breast Cancer)

Diarrhea (81%).

Palmar-plantar erythrodysesthesia syndrome (hand-foot redness and pain) (63%).

Nausea (58%).

Hepatotoxicity (42%).

Vomiting (36%).

When Combined with Trastuzumab (for Colorectal Cancer)

Diarrhea (64%).

Fatigue (44%).

Rash (37%).

Nausea (35%).

Abdominal pain (21%).

Severe Side Effects of Tukysa (Tucatinib)

Severe Diarrhea

Diarrhea caused by Tukysa can be extremely severe, potentially leading to dehydration, hypotension, acute kidney injury, or even death.

Management Recommendations: Once diarrhea occurs, initiate antidiarrheal treatment immediately.

If grade 3 diarrhea occurs, discontinue Tukysa temporarily; consider dose reduction upon recovery.

If grade 4 diarrhea occurs, permanently discontinue Tukysa.

Hepatotoxicity

Tukysa may cause severe liver damage, manifested as elevated transaminases or bilirubin.

Monitoring Requirements: Before starting treatment, every 3 weeks during treatment, and when symptoms appear, test alanine transaminase (ALT), aspartate transaminase (AST), and bilirubin levels.

Management Recommendations: If grade 2 bilirubin elevation occurs, temporarily discontinue Tukysa.

If grade 3 transaminase or bilirubin elevation occurs, temporarily discontinue Tukysa and consider dose reduction.

If grade 4 elevation occurs or Hy’s Law criteria are met, permanently discontinue Tukysa.

Embryofetal Toxicity

Tukysa may cause harm to the fetus; use in pregnant women may result in embryonic death or fetal malformations.

Recommendations: Women of childbearing potential should use effective contraceptive measures during treatment and for 1 week after the last dose.

Male patients with partners of childbearing potential should also use contraceptive measures during the same period.

Precautions for Tukysa (Tucatinib) Use

Drug Interactions

Avoid Concomitant Use: Strong CYP3A inducers or moderate CYP2C8 inducers (e.g., rifampicin).

Strong CYP2C8 Inhibitors (e.g., gemfibrozil): If concomitant use is unavoidable, reduce the Tukysa dose to 100 mg twice daily.

Use with Caution: CYP3A substrates (e.g., midazolam): Concomitant use may increase their plasma concentrations.

P-gp Substrates (e.g., digoxin): Dose reduction of the P-gp substrate is recommended.

Special Populations

Patients with Hepatic Impairment: No dose adjustment is required for mild to moderate hepatic impairment. For severe hepatic impairment (Child-Pugh Class C), reduce the dose to 200 mg twice daily.

Patients with Renal Impairment: No dose adjustment is required for mild to moderate renal impairment. If used concomitantly with capecitabine, it is contraindicated in patients with severe renal impairment.

Elderly Patients: The incidence of severe adverse reactions is higher in patients aged 65 years and above; enhanced monitoring is required.

Lactation: Breastfeeding is prohibited during treatment and for 1 week after the last dose.