Tukysa

Tukysa (tucatinib) is an oral targeted therapy (tyrosine kinase inhibitor) used to treat certain types of advanced HER2-positive breast cancer and colorectal cancer. Tukysa is always used together with trastuzumab. For breast cancer, it is also given with either capecitabine or pertuzumab depending on the stage of treatment.

Tukysa is an oral tablet taken twice daily with or without food.

Tukysa is a tyrosine kinase inhibitor.

Tukysa works by targeting HER2, a protein in the cell membrane that helps control how cells grow. Part of HER2 is on the cell surface, and part is inside the cell. In HER2-positive cancer, the cancer cells make too much HER2, which sends constant signals telling the cells to grow and divide. Tukysa attaches to the part of HER2 inside the cell and blocks these signals, which can help slow or stop the cancer's growth.

Tukysa is FDA-approved to treat adults with:

• HER2-positive breast cancer: that is advanced and cannot be removed by surgery (unresectable), or has spread to other parts of the body (metastatic), including to the brain, in people who have already had at least one anti-HER2 treatment for metastatic cancer. It is used together with trastuzumab (Herceptin) and capecitabine (Xeloda). as a maintenance treatment for unresectable locally advanced or metastatic HER2-positive breast cancer after induction therapy, used together with trastuzumab and pertuzumab.
• HER2-positive colorectal cancer that is: RAS wild-type and unresectable or metastatic, after prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. It is used together with trastuzumab. This use is approved under accelerated approval based on tumor response. Continued approval may depend on results from further studies.

Important information: Serious liver problems and severe diarrhea

Tukysa can cause severe liver problems that can lead to death. The risk is higher if you start taking Tukysa again after stopping it because of liver problems.

Your doctor will do blood tests to check your liver function before you start Tukysa and regularly during treatment. These tests are usually done every 2 weeks for the first 2 months, then every 3 weeks. If you have liver problems, your doctor may pause your treatment, lower your dose, or stop Tukysa permanently.

Call your doctor right away if you have signs of liver problems, such as:

• itching
• yellowing of your skin or the whites of your eyes (jaundice)
• dark or tea-colored urine
• pain in the upper right side of your stomach area
• feeling very tired
• loss of appetite
• bleeding or bruising more easily than normal

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.

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions and allergies.

Take Tukysa exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.

You may take Tukysa with or without food.

Swallow the tablet whole and do not crush, chew, or break it. Do not use a cracked or broken tablet.

Take the medicine at the same time each day, about every 12 hours.

If you vomit shortly after taking Tukysa, do not take another dose. Wait until your next scheduled dose time to take the medicine again.

Use all medications as directed and read all medication guides you receive. Do not change your dose or dosing schedule without your doctor's advice.

You will need frequent blood tests to check your liver function.

Store at room temperature away from moisture and heat. Keep the tablets in their original container, along with the packet or canister of moisture-absorbing preservative.

Throw away any unused Tukysa tablets 3 months after you first opened the bottle.

Both men and women using Tukysa should use effective birth control to prevent pregnancy. Tucatinib can harm an unborn baby if the mother or father is using this medicine. Keep using birth control for at least 1 week after your last dose.

Tell your doctor right away if a pregnancy occurs while either the mother or the father is using Tukysa.

This medicine may affect fertility (ability to have children) in both men and women. However, it is important to use birth control to prevent pregnancy because tucatinib can harm an unborn baby.

Do not breastfeed while using Tukysa, and for at least 1 week after your last dose.

You may need to prevent pregnancy or avoid breastfeeding for longer periods of time after you stop using capecitabine, pertuzumab, or trastuzumab. Read all medication guides you receive. Follow directions about pregnancy or breastfeeding after you stop combination chemotherapy.

Tell your doctor if you have ever had liver disease.

Get emergency medical help if you have signs of an allergic reaction to Tukysa: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• severe or ongoing diarrhea;
• pain, blisters, bleeding, or severe rash in the palms of your hands or the soles of your feet;
• blisters or ulcers in your mouth, red or swollen gums, trouble swallowing;
• liver problems: itching, yellowing of the skin or eyes (jaundice), dark or tea-colored urine, pain in the upper right stomach area, feeling very tired, loss of appetite, or bleeding or bruising more easily than normal; or
• low red blood cells (anemia) - pale skin, unusual tiredness, feeling light-headed or short of breath, cold hands and feet.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

Common Tukysa side effects when used in combination with trastuzumab and capecitabine in adults with HER2-positive breast cancer include:

• diarrhea;
• nausea, vomiting, stomach pain, loss of appetite;
• anemia;
• mouth sores;
• rash;
• headache, tiredness; or
• abnormal liver function tests.

Common Tukysa side effects when used in combination with trastuzumab and pertuzumab in adults with HER2-positive breast cancer include:

• diarrhea;
• muscle, bone, or joint pain;
• liver problems;
• nausea, vomiting;
• tiredness; or
• rash.

Common Tukysa side effects when used in combination with trastuzumab in adults with RAS wild-type HER2-positive colorectal cancer include:

• diarrhea;
• nausea, vomiting, stomach pain;
• rash;
• headache, tiredness;
• infusion-related reactions; or
• fever.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Dose may be modified due to side effects, medicine interactions or other health conditions.

Tukysa dosing information for previously treated HER2-positive breast cancer

Usual adult dose: 300 mg orally 2 times a day in combination with trastuzumab and capecitabine until disease progression or unacceptable toxicity.

When given in combination with this drug, the recommended dose of capecitabine is 1000 mg/m2 orally 2 times daily taken within 30 minutes after a meal.

Use: In combination with trastuzumab and capecitabine, is indicated for treatment of adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting.

Tukysa dosing information for maintenance treatment of HER2-positive breast cancer

Usual adult dose: 300 mg orally twice daily in combination with trastuzumab and pertuzumab, until disease progression or unacceptable toxicity.

Use: as maintenance treatment, with trastuzumab and pertuzumab, for adults with unresectable locally advanced or metastatic HER2-positive breast cancer following induction treatment.

Tukysa dosing information for colorectal cancer

Usual adult dose: 300 mg orally 2 times a day in combination with trastuzumab until disease progression or unacceptable toxicity.

Use: in combination with trastuzumab for the treatment of adult patients with RAS wild-type HER2-positive unresectable or metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

Skip the missed dose and use your next dose at the regular time. Do not use two doses at one time.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Sometimes it is not safe to use certain medications at the same time. Some drugs can affect your blood levels of other drugs you take, which may increase side effects or make the medications less effective.

Other drugs may interact with tucatinib, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.