Tucatinib

TUKYSA

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Pronunciation: too-KA-ti-nib (too-KYE-sa)

Tucatinib ballicule: receptor binding, kinetics and half-life diagram — Mechanism of action: Tucatinib ballicule

What it isHER2-selective tyrosine-kinase inhibitor; HER2-positive metastatic breast cancer (including brain metastases and post-induction maintenance) and HER2-positive colorectal cancer.

Why this oneHER2 selectivity spares EGFR, reducing the rash and diarrhea of less selective agents while preserving CNS activity.

What limits itDiarrhea and hepatotoxicity require monitoring. Strong CYP2C8 inhibitors raise exposure, and tucatinib strongly inhibits CYP3A4.

Tucatinib molecular structure (skeletal formula) — Molecular structure: Tucatinib

Tucatinib prescription history

Animated chart of estimated U.S. prescriptions per year, Tyrosine kinase inhibitors (2001–2026). Tucatinib enters in 2020 (estimated).

FDA-approved for

HER2-positive metastatic breast cancer (2020)
HER2-positive breast cancer maintenance (with trastuzumab + pertuzumab) (2026)
HER2-positive metastatic colorectal cancer (2023)

Principal riskDiarrhea and hepatotoxicity

Classes and tags

Clinical profile

Therapeutic safety burden3 / 4

Overdose danger2 / 4

Weight-gain liability0 / 4

Sedation liability0 / 4

QT / Torsades0 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk3 / 4

Legacy pregnancy categoryNot assigned — PLLR-era drug

Defining liabilityMyelosuppression and agent-specific hepatic, cardiac, pulmonary, neurologic or reproductive toxicity require oncology monitoring.

FDA label

Read the full label on DailyMed ↗

BOXED WARNING Hepatotoxicity: severe and fatal, particularly after rechallenge; obtain LFTs before and during treatment; withhold, reduce dose, or permanently discontinue by severity.

FDA dosing	Population	Start	Target	Max
HER2+ metastatic breast cancer (with trastuzumab + capecitabine)	Adults	300 mg BID	300 mg BID	300 mg BID
RAS wild-type, HER2+ unresectable/metastatic colorectal cancer (with trastuzumab)	Adults	300 mg BID	300 mg BID	300 mg BID

Renal No adjustment for mild–moderate (CLcr 30–89). With capecitabine: not recommended in severe (CLcr <30), as capecitabine is contraindicated

Hepatic Severe (Child-Pugh C): reduce to 200 mg BID. Mild–moderate: no adjustment

Instructions

Swallow tablets whole; do not chew, crush, or split
Do not take a broken/cracked tablet
Take ~12 h apart at the same time daily, with or without food
If a dose is missed or vomited, take the next dose at its usual time (do not replace)
Confirm HER2 overexpression and RAS wild-type before colorectal use

Available strengths

tab 50, 150 mg

Cautions

Severe diarrhea (dehydration, acute kidney injury, death) — give antidiarrheals; interrupt/reduce/discontinue by severity
Hepatotoxicity — monitor ALT/AST/bilirubin at baseline, every 3 weeks, and as indicated
Embryo-fetal toxicity — advise contraception

Adverse reactions

Diarrhea
Palmar-plantar erythrodysesthesia
Nausea, vomiting, stomatitis
Hepatotoxicity (transaminase/bilirubin increases)
Decreased appetite
Anemia
Rash
Increased serum creatinine (tubular; benign)

Pregnancy Can cause fetal harm (animal embryo-fetal mortality, reduced weight, malformations); advise contraception

Lactation Do not breastfeed during treatment and for 1 week after last dose

Cost

Tucatinib (TUKYSA)

Strength		#/mo	generic $/mo	CostPlus
50 mg	tab	60 BID		not offered
150 mg	tab	60 BID		not offered

NADAC is a voluntary CMS survey of what retail community pharmacies pay for the drugs they stock. Tucatinib is dispensed outside retail pharmacies, so it rarely appears on surveyed invoices.

Generic entry2038 est.

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Self-check

Which receptor does tucatinib selectivity spare?
EGFR.
Which CYP enzyme does tucatinib strongly inhibit?
CYP3A4.