Tucatinib

HER2 tyrosine kinase inhibitors
HER2 tyrosine kinase inhibitors
High alert
An error with this medicine can cause serious harm: double checks and protocols are used.
Pregnancy: avoid
Avoid in pregnancy. Can harm the fetus: a pregnancy test is done before starting, effective contraception is used during treatment and for a time afterwards (by women and by men…

A HER2-selective oral kinase inhibitor, with trastuzumab and capecitabine, for HER2-positive breast cancer, including brain metastases.

Updated Nov 1, 2026

Quick facts

Group: HER2 tyrosine kinase inhibitors
Target: HER2 (ERBB2) tyrosine kinase
Used for: HER2-positive unresectable · HER2-positive
Key effects: Diarrhoea · Redness · Nausea
Monitor: Liver tests before and during treatment
ATC: L01EH03

No doses: the clinician sets them by the current guideline.

Mechanism of action

HER2 (ERBB2) tyrosine kinaseTucatinib

The figure shows tucatinib in the ATP pocket of a human HER2 kinase domain carrying an exon 20 insertion mutation.

Target in 3D: HER2 (ERBB2) tyrosine kinase. PDB structure 8VB5 (RCSB PDB, public domain). View the structure at RCSB PDB

Tucatinib reversibly blocks the ATP site of the HER2 kinase with very little effect on EGFR. Added to trastuzumab, which binds the outside of HER2, it blocks the receptor from both sides and improved survival in heavily pretreated patients, including those with brain metastases. Sparing EGFR makes rash much less common than with other kinase inhibitors of this family.

Selectively blocks the HER2 kinase, sparing EGFR
With trastuzumab: HER2 blocked inside and outside
Active in brain metastases; little rash

Indications

HER2-positive unresectable or metastatic breast cancer, including brain metastases, after at least one anti-HER2 treatment, with trastuzumab and capecitabine. Breast cancer →
HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer after prior treatment, with trastuzumab (accelerated approval). Colorectal cancer →

Adverse effects

Common

Diarrhoea
Redness, pain or blisters of the hands and feet (with capecitabine)
Nausea, vomiting, abdominal pain, decreased appetite
Fatigue, mouth sores, nosebleeds

Contraindications

No absolute contraindications in the label apart from hypersensitivity; see the warnings

Key interactions

Strong inhibitors or inducers of CYP2C8 or CYP3A: Change tucatinib levels.
St John's wort: Can lower its levels; it is avoided.

What is monitored

HER2 status of the tumour before starting
Liver tests before and during treatment
Stool frequency and hydration

Administration and safety

Oral tablets swallowed whole; broken or damaged tablets are not taken.
Given together with trastuzumab and capecitabine in breast cancer: check that every drug of the regimen is on the order.

Pregnancy and breastfeeding

Avoid in pregnancy. Can harm the fetus: a pregnancy test is done before starting, effective contraception is used during treatment and for a time afterwards (by women and by men with partners who could conceive), and breastfeeding is avoided.

Nursing care

Teach to report diarrhoea early and how to recognise dehydration.
Review liver tests; teach to report jaundice, dark urine or right upper abdominal pain.
Inspect hands and feet for capecitabine-related skin changes.
Confirm a negative pregnancy test before the first dose and teach contraception during treatment and afterwards.

Pharmacokinetics

Absorption: Oral tablets, twice daily, with or without food.
Metabolism: Mainly CYP2C8, less CYP3A.
Half-life: About 8.5 hours.

Test yourself

Think of the answer, then tap the question to see it.

Which receptor does tucatinib spare, and what is the clinical consequence?

EGFR; skin rash is much less common.

Which two drugs accompany tucatinib in metastatic HER2-positive breast cancer?

Trastuzumab and capecitabine.

Which enzyme mainly metabolises tucatinib?

CYP2C8 (CYP3A to a lesser extent).

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Connections

← Back to the class: HER2 tyrosine kinase inhibitors

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Tucatinib: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2023); Tucatinib - NCI (National Cancer Institute, 2024); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.