(tucatinib)

Prescribing Information
Download Prescribing Information

5 WARNINGS AND PRECAUTIONS

5 WARNINGS AND PRECAUTIONS

     

5.1 Hepatotoxicity

TUKYSA can cause severe and fatal hepatotoxicity, particularly after rechallenge [see Adverse Reactions (6.1)].

Monitor ALT, AST, and bilirubin prior to starting TUKYSA, every 2 weeks for the first 2 months, then every 3 weeks during treatment, and as clinically indicated. For patients who experience AST/ALT >3 × ULN and bilirubin > ULN to ≤2 × ULN, repeat testing within 48-72 hours. For patients who experience AST/ALT >5 × ULN, withhold TUKYSA and repeat testing within 48-72 hours to determine if worsening. Based on the severity of hepatotoxicity, reduce dose or permanently discontinue TUKYSA [see Dosage and Administration (2.3)]. Institute weekly liver function monitoring if TUKYSA is resumed after resolution to Grade ≤1.

TUKYSA with trastuzumab and pertuzumab

In HER2CLIMB-05, 18% of patients who received TUKYSA had an ALT increase >5 × ULN, 10% had an AST increase >5 × ULN, and 1.2% had a bilirubin increase >3 × ULN (Grade ≥3). There were five confirmed Hy’s Law cases, including a fatal case. All occurred following rechallenge with TUKYSA. Hepatotoxicity led to dose reduction of TUKYSA in 16% of patients and discontinuation of TUKYSA in 8% of patients.

TUKYSA with trastuzumab and capecitabine

In HER2CLIMB, 8% of patients who received TUKYSA had an ALT increase >5 × ULN, 6% had an AST increase >5 × ULN, and 1.5% had a bilirubin increase >3 × ULN (Grade ≥3). Hepatotoxicity led to dose reduction of TUKYSA in 8% of patients and discontinuation of TUKYSA in 1.5% of patients.

TUKYSA with trastuzumab

In MOUNTAINEER, 6% of patients had a bilirubin increase >3 × ULN (Grade ≥3), 6% had an AST increase >5 × ULN, and 4.7% had an ALT increase >5 × ULN. Hepatotoxicity led to dose reduction of TUKYSA in 3.5% of patients and discontinuation of TUKYSA in 2.3% of patients.

5.2 Diarrhea

TUKYSA can cause severe diarrhea, including dehydration, hypotension, acute kidney injury, and death [see Adverse Reactions (6.1)].

If diarrhea occurs, administer antidiarrheal treatment as clinically indicated. Perform diagnostic tests as clinically indicated to exclude other causes of diarrhea. Based on the diarrhea severity, interrupt dose, reduce dose, or permanently discontinue TUKYSA [see Dosage and Administration (2.3)].

TUKYSA with trastuzumab and pertuzumab

In HER2CLIMB-05, 73% of patients who received TUKYSA experienced diarrhea, including 6% with Grade 3 events. The median time to onset of the first episode of diarrhea was 11 days and the median time to resolution was 2 days. Diarrhea led to dose reductions of TUKYSA in 6% of patients and discontinuation of TUKYSA in 1.5% of patients. Prophylactic use of antidiarrheal treatment was not required in HER2CLIMB-05.

TUKYSA with trastuzumab and capecitabine

In HER2CLIMB, 81% of patients who received TUKYSA experienced diarrhea, including 0.5% with Grade 4 diarrhea and 12% with Grade 3 diarrhea. Both patients who developed Grade 4 diarrhea subsequently died, with diarrhea as a contributor to death. The median time to onset of the first episode of diarrhea was 12 days and the median time to resolution was 8 days. Diarrhea led to dose reductions of TUKYSA in 6% of patients and discontinuation of TUKYSA in 1% of patients. Prophylactic use of antidiarrheal treatment was not required in HER2CLIMB.

TUKYSA with trastuzumab

In MOUNTAINEER, diarrhea occurred in 64% of patients, including Grade 3 (3.5%), Grade 2 (10%), and Grade 1 (50%).

5.3 Embryo-Fetal Toxicity

Based on findings from animal studies and its mechanism of action, TUKYSA can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of tucatinib to pregnant rats and rabbits during organogenesis caused embryo-fetal mortality, reduced fetal weight and fetal abnormalities at maternal exposures ≥1.3 times the human exposure (AUC) at the recommended dose.

Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TUKYSA and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TUKYSA and for 1 week after the last dose [see Use in Specific Populations (8.1, 8.3)].

TUKYSA is used in combination with other agents. Refer to the Prescribing Information of combination agents for pregnancy and contraception information.

5.4 Increased Serum Creatinine Without Affecting Renal Function

TUKYSA can increase serum creatinine. Across three clinical trials in 816 patients (HER2CLIMB-05, HER2CLIMB, and MOUNTAINEER), the mean increase in serum creatinine was 29%-32% within the first 21 days of treatment with TUKYSA. The serum creatinine increases persisted throughout treatment and were reversible upon treatment completion. These increases were not associated with changes in glomerular function [see Adverse Reactions (6.1)]. These increases in serum creatinine may be due to inhibition of renal tubular transport of creatinine. During TUKYSA treatment, use alternative measures that are not based on serum creatinine to assess renal function [see Clinical Pharmacology (12.3)].

Medication Guide

MEDICATION GUIDE

   

This Medication Guide has been approved by the U.S. Food and Drug Administration.  Revised: 10/2026

MEDICATION GUIDE

TUKYSA® (too-KYE-sah)

(tucatinib)

tablets

Important: If your healthcare provider prescribes TUKYSA in combination with capecitabine or pertuzumab, also read the Patient Information that comes with capecitabine or pertuzumab.

What is the most important information I should know about TUKYSA?

TUKYSA can cause serious side effects, including:

•
Liver Problems. TUKYSA can cause severe liver problems that can lead to death, especially if you restart TUKYSA after previously stopping treatment due to liver problems. Your healthcare provider will do blood tests to check your liver function before starting treatment with TUKYSA, every 2 weeks for the first 2 months, and then every 3 weeks during treatment with TUKYSA, or as needed. Tell your healthcare provider right away if you get any signs and symptoms of liver problems including:
o
itching
o
yellowing of your skin or eyes
o
dark or brown urine (tea-colored)
o
pain in the upper right side of your stomach-area (abdomen)
o
feeling very tired
o
decreased appetite
o
bleeding or bruising more easily than normal
•
Diarrhea. TUKYSA can cause severe diarrhea that can lead to loss of too much body fluids (dehydration), low blood pressure, kidney problems, and death. Tell your healthcare provider right away if you have a change in your bowel movements or severe diarrhea. Your healthcare provider may prescribe medicines to treat your diarrhea during treatment with TUKYSA.

See “What are the possible side effects of TUKYSA?” for more information about side effects.

What is TUKYSA?

TUKYSA is a prescription medicine used in adults:

•
in combination with the medicines trastuzumab and pertuzumab for maintenance treatment of a type of breast cancer called human epidermal growth factor receptor-2 (HER2)-positive breast cancer that has spread:
o
to nearby tissue or lymph nodes and cannot be removed by surgery (unresectable locally advanced) or
o
to other parts of the body (metastatic).
•
in combination with trastuzumab and capecitabine to treat HER2-positive breast cancer that has spread to other parts of the body (metastatic), or cannot be removed by surgery, who have received 1 or more anti-HER2 metastatic breast cancer treatments.
•
in combination with the medicine trastuzumab to treat a type of colorectal cancer called RAS wild-type HER2-positive colorectal cancer that has spread to other parts of the body (metastatic), or cannot be removed by surgery, who have received treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy and it did not work or is no longer working.

Your healthcare provider will perform a test to make sure TUKYSA is right for you.

It is not known if TUKYSA is safe and effective in children.

Before taking TUKYSA, tell your healthcare provider about all of your medical conditions, including if you:

•
have liver problems.
•
are pregnant or plan to become pregnant. TUKYSA can harm your unborn baby.
Females who are able to become pregnant:
o
Your healthcare provider will do a pregnancy test before you start treatment with TUKYSA.
o
Use effective birth control (contraception) during treatment with TUKYSA and for 1 week after the last dose of TUKYSA. Talk with your healthcare provider about forms of birth control that you can use during this time.
o
Your healthcare provider will tell you how long you should use birth control (contraception) after your treatment with trastuzumab, pertuzumab, or capecitabine.
o
Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with TUKYSA.
 
Males with female partner who are able to become pregnant:
o
Use effective birth control during treatment with TUKYSA and for 1 week after the last dose of TUKYSA.
•
are breastfeeding or plan to breastfeed. It is not known if TUKYSA passes into your breast milk. Do not breastfeed during treatment with TUKYSA and for 1 week after the last dose of TUKYSA. Your healthcare provider will tell you how long you should not breastfeed after your treatment with trastuzumab and pertuzumab.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. TUKYSA may affect the way your other medicines work, and other medicines may affect the way TUKYSA works.

Know the medicines you take. Keep a list of all the medicines you take and show it to your healthcare provider and pharmacist every time you get a new medicine.

How should I take TUKYSA?

•
Take TUKYSA exactly as your healthcare provider tells you.
•
Follow your healthcare provider’s instruction for taking TUKYSA with the medicines trastuzumab, trastuzumab and capecitabine, or trastuzumab and pertuzumab.
•
Take TUKYSA 2 times a day, with or without a meal.
•
Take TUKYSA about 12 hours apart and at the same times every day.
•
Swallow TUKYSA tablets whole. Do not chew, crush, or split TUKYSA tablets before swallowing. Do not take TUKYSA tablets if they are broken, cracked, or damaged.
•
If you vomit or miss a dose of TUKYSA, take your next dose at your regular time.

What are the possible side effects of TUKYSA?

TUKYSA can cause serious side effects, including:

•
See “What is the most important information I should know about TUKYSA?”

The most common side effects of TUKYSA in combination with trastuzumab and pertuzumab in adults with HER2-positive breast cancer include:

•
diarrhea
•
muscle and joint pain
•
liver problems
•
nausea
•
tiredness
•
rash
•
vomiting

The most common side effects of TUKYSA in combination with trastuzumab and capecitabine in adults with HER2-positive breast cancer include:

•
diarrhea
•
rash, redness, pain, swelling or blisters on the palms of your hands or soles of your feet
•
nausea
•
liver problems
•
vomiting
•
mouth sores (stomatitis)
•
decreased appetite
•
low red blood cell counts (anemia)
•
rash

The most common side effects of TUKYSA in combination with trastuzumab in adults with RAS wild-type HER2-positive colorectal cancer include:

•
diarrhea
•
tiredness
•
rash
•
nausea
•
stomach-area (abdomen) pain
•
infusion related reactions
•
fever

Your healthcare provider may change your dose of TUKYSA, temporarily stop, or permanently stop treatment with TUKYSA if you have certain side effects.

TUKYSA may cause fertility problems in males and females, which may affect the ability to have children. Talk to your healthcare provider if you have concerns about fertility.

These are not all of the possible side effects of TUKYSA.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store TUKYSA?

•
Store TUKYSA at room temperature between 68°F to 77°F (20ºC to 25ºC).
•
Keep TUKYSA in its original container. The TUKYSA bottle contains a desiccant packet to help keep your tablets dry (protect from moisture). Keep the desiccant in the bottle.
•
Tightly close the bottle of TUKYSA after you take your dose.
•
TUKYSA must be used within 3 months after opening the bottle. Throw away (discard) any unused tablets 3 months after opening the bottle.

Keep TUKYSA and all medicines out of the reach of children.

General information about the safe and effective use of TUKYSA.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use TUKYSA for a condition for which it was not prescribed. Do not give TUKYSA to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about TUKYSA that is written for health professionals.

What are the ingredients in TUKYSA?

Active ingredient: tucatinib

Inactive ingredients:

Tablet core: copovidone, crospovidone, sodium chloride, potassium chloride, sodium bicarbonate, colloidal silicon dioxide, magnesium stearate, and microcrystalline cellulose.

Tablet coating: yellow film coat: polyvinyl alcohol, titanium dioxide, macrogol/polyethylene glycol, talc, and yellow iron oxide non-irradiated.

This product’s labeling may have been updated. For the most recent prescribing information, please visit https://www.pfizer.com.

Manufactured for: Seagen Inc., Bothell, WA 98021
TUKYSA is a registered trademark owned by Seagen Inc.
©2026 Seagen Inc.
For more information, call 1-800-438-1985.
LAB-1594-1.0

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