Tucatinib (Tukysa)

Medicine at a glance

Tucatinib, also called Tukysa, is a targeted cancer tablet that blocks HER2-related growth signals. A usual dose is 300 mg twice daily, about 12 hours apart, with or without food. It is taken continuously unless your team tells you to pause. Lower doses are used when needed for side effects, liver impairment or a specific interaction.

It is prescribed with trastuzumab, and some treatment plans also include capecitabine. Each medicine has its own schedule and precautions. Tucatinib may continue during the week when capecitabine is not taken. A shared written calendar helps avoid taking the wrong tablets or applying one medicine's rules to another.

Some plans include pertuzumab. The October 2026 US label includes maintenance with trastuzumab and pertuzumab after initial treatment for adults with unresectable locally advanced or metastatic HER2-positive breast cancer.

Diarrhoea and liver problems are important tucatinib risks. Blood tests and early reporting of symptoms help the team manage these safely. Trastuzumab adds heart-monitoring and reaction precautions, while capecitabine adds chemotherapy-specific risks when it is part of your regimen.

What tucatinib is and how it works

HER2 is a protein involved in signals that tell cells to grow. Some cancers produce too much HER2 protein or have extra copies of its gene. Tucatinib is a tyrosine kinase inhibitor that acts on the HER2 signalling machinery inside cells. Blocking these signals can slow cancer growth.

Trastuzumab is an antibody that attaches to HER2 on the outside of cells. The medicines act in complementary ways. Capecitabine, when prescribed, is a chemotherapy tablet converted in the body into fluorouracil. It works differently from tucatinib.

Tucatinib is not an immune-checkpoint treatment. A targeted medicine can still cause serious side effects. Their intensity does not establish whether treatment is working.

How the team decides whether it is suitable

The team reviews HER2 testing, your diagnosis, previous medicines, organ function and overall health. HER2 testing can assess protein levels or gene amplification. Additional tumour tests may matter in particular settings: for example, the reviewed US colorectal treatment instructions also require RAS wild-type status, meaning the relevant RAS mutations are not found. This is not a rule for every person receiving tucatinib.

HER2 is the key target; an EGFR test is not a substitute. Ask your oncologist to explain which result supports this treatment and whether any result needs confirmation. A report about a different HER2-directed drug does not automatically establish the same treatment plan.

Tell the team about liver disease, kidney problems, persistent diarrhoea, difficulty swallowing, significant heart disease or a previous severe reaction to trastuzumab. Kidney function affects the safety of capecitabine particularly. The US tucatinib label does not recommend tucatinib with trastuzumab and capecitabine in severe kidney impairment. European information does not require a kidney-based tucatinib adjustment, but contraindicates capecitabine in severe impairment. The whole regimen needs review.

If you have severe liver impairment, the reviewed tucatinib labels recommend a starting dose of 200 mg twice daily. This does not make every partner suitable: European capecitabine information prohibits use in severe liver impairment. The specialist must assess the complete plan.

Before treatment starts

Blood tests assess liver enzymes, bilirubin, kidney function, blood counts and salts. The team also reviews your current medicines and checks pregnancy status where relevant. Trastuzumab requires heart-function assessment, usually with an echocardiogram or another heart scan, before treatment and periodically afterwards.

If capecitabine is prescribed

Ask about testing for DPD deficiency before the first dose. DPD is an enzyme needed to break down fluorouracil, the active chemotherapy produced from capecitabine. People with very low or absent activity can develop life-threatening toxicity. Genetic tests examine the DPYD gene; some testing approaches assess enzyme function indirectly.

Current US Xeloda instructions call for DPYD genetic testing before treatment unless immediate treatment is necessary. European guidance recommends testing for DPD deficiency before treatment. Complete deficiency means capecitabine should not be used; partial deficiency requires an individual prescribing plan. A reassuring test does not eliminate every risk, so unusually severe early diarrhoea, mouth sores, fever or neurological symptoms still need immediate attention.

Bring all medicine packets or an up-to-date list, including supplements. Ask for a written diarrhoea plan, the unit's fever threshold and instructions for contacting the team out of hours. Have a thermometer and know which anti-diarrhoea medicine, if any, has been prescribed for you. Routine preventive anti-diarrhoea treatment is not automatically required for everyone taking tucatinib.

How to take tucatinib

Dose, timing and swallowing

The usual dose is 300 mg twice daily, approximately 12 hours apart, at consistent times. A 300 mg dose commonly means two 150 mg tablets. Tablets also come in 50 mg strength, which may be used for dose adjustments. Check the milligrams and tablet count on each new prescription.

Swallow tablets whole with water. Do not chew, crush or split them, and do not take a tablet that is broken, cracked or otherwise damaged. If swallowing is difficult or you use a feeding tube, ask the oncology pharmacist for help; the reviewed labels do not provide a home dispersion or tube method.

Tucatinib can be taken with or without a meal. If you also take capecitabine, that medicine should be swallowed within 30 minutes after a meal. You can take both at the same time when scheduled, which may simplify your morning and evening routine.

Keeping the partner schedules separate

When capecitabine is prescribed, a common three-week combination cycle uses tucatinib every day, with capecitabine twice daily on days 1–14 followed by days 15–21 without capecitabine. Trastuzumab is given at the clinic according to its prescription, commonly every three weeks in this regimen. Do not stop tucatinib merely because capecitabine's planned break has begun.

The calendar may change if blood tests or symptoms require a pause. Ask exactly which medicine to hold, for how long and who will authorise restarting. A pause in one component does not mean you should automatically restart or stop every other component without advice.

Missed doses, vomiting and extra tablets

If you miss tucatinib, skip that dose and take the next one at the usual scheduled time. If you vomit after a dose, do not take extra tablets to replace it. Never double the next dose. Report repeated missed doses, vomiting or difficulty keeping fluids down so the team can help.

If you take more than prescribed, contact the treating team or nearest emergency department immediately, even if you feel well. Explain the strength, number of tablets and time taken. Keep the medicine packaging available and await instructions before taking another dose.

Dose changes and storage

For side effects, the usual prescribed reductions are 250 mg, then 200 mg, then 150 mg twice daily. Other circumstances can require a different plan. Do not split tablets or assemble a new dose yourself; the pharmacist will explain the correct strengths and count. Tucatinib is permanently stopped if 150 mg twice daily cannot be tolerated; some severe problems require stopping sooner.

Keep tablets in their original packaging, out of children's and pets' reach. US bottle instructions specify room-temperature storage, a tightly closed cap, retaining the drying packet and using the tablets within three months after opening. European packs may be blisters; follow your actual pack rather than applying a bottle-opening rule to every presentation. Return unwanted medicine through a pharmacy.

Monitoring and checking whether treatment is working

Liver tests include ALT, AST and bilirubin. The October 2026 US prescribing information recommends tests before treatment, every two weeks for the first two months, then every three weeks, with extra checks when needed. Your oncology team will confirm your schedule. European guidance also specifies three-weekly monitoring or checks as clinically indicated. A blood-test change can be important even when you feel normal.

Blood counts, kidney function and salts are monitored according to your complete regimen and symptoms. Diarrhoea or vomiting may require earlier tests because dehydration can affect the kidneys and blood salts. Trastuzumab requires repeated heart scans, commonly around every three months, with extra assessment if symptoms or results warrant it.

Tucatinib can raise blood creatinine by changing how the kidneys transport it, without necessarily reducing actual filtration. Your team may use another marker, such as cystatin C, to clarify the result. This does not mean every rise is harmless: dehydration, capecitabine toxicity and other causes of real kidney injury must still be considered.

Scans, examination and symptoms assess cancer control. Your oncologist may arrange imaging of particular sites when relevant to your disease. Keep appointments even if treatment feels easy to tolerate, and bring a brief record of doses, stool changes, appetite, skin symptoms and new medicines.

Common side effects and practical management

Diarrhoea

Loose or frequent stools are common and can become serious. Tell the team promptly when your bowel pattern changes. Record how many stools you pass compared with normal, whether diarrhoea wakes you at night and any increase in stoma output. Use the anti-diarrhoea medicine according to your personal plan.

Take regular fluids as advised, but ask for an individual target if you have heart or kidney problems. Contact the urgent service for persistent or worsening diarrhoea, especially with vomiting, fever, blood in stool, dizziness or reduced urine. Severe symptoms need advice before the next oral cancer dose, not another day of waiting to see whether they settle.

Sore palms and soles

Hand–foot syndrome is particularly important when capecitabine is included. Palms and soles may become tender, red or darker, swollen, tingly, blistered or cracked. Reduce rubbing and pressure, avoid excessive heat, use recommended moisturiser and wear comfortable shoes.

Report pain that affects walking or using your hands. Continuing through worsening symptoms can cause more damage. The team may interrupt or adjust capecitabine and will tell you separately what to do with tucatinib. Do not cut thickened skin or apply harsh treatments without advice.

Nausea, appetite and mouth soreness

Take prescribed anti-sickness medicine as directed. Small meals and snacks may be easier than large meals. Tell the team about persistent vomiting, weight loss or inability to eat enough; a dietitian may help. Remember that capecitabine still has a meal-related instruction even though tucatinib does not.

Use gentle mouth care and a soft toothbrush. Report painful ulcers, difficulty swallowing or signs of infection. Severe mouth soreness soon after starting capecitabine is an important warning, particularly if accompanied by diarrhoea or fever. Do not treat it as something you must simply endure.

Tiredness, rash and other symptoms

Fatigue may be helped by pacing, rest and activity within your ability. Persistent exhaustion can also reflect anaemia, dehydration, infection or a heart problem. Report a sudden change in stamina or breathlessness rather than assuming fatigue is inevitable.

Rash, dry skin, joint discomfort and mild nosebleeds can occur. Use gentle skin care and check suitable creams or pain relief with the team. A widespread blistering rash, mouth or eye involvement, uncontrolled bleeding or rash with breathing difficulty needs urgent assessment.

Important risks that need medical assessment

Severe diarrhoea, dehydration and kidney injury

Severe diarrhoea can cause low blood pressure, acute kidney injury and, in reported cases, death. Symptoms of dehydration include thirst, dry mouth, dizziness, faintness and reduced urine. Infection or another treatment may contribute, so the team may arrange stool and blood tests rather than attributing every episode to tucatinib.

Do not take further oral cancer doses while severe diarrhoea or dehydration is being urgently assessed unless the treating team specifically tells you to. Treatment may need fluids, a temporary hold, a lower dose or permanent discontinuation. Life-threatening diarrhoea requires permanent tucatinib discontinuation under the reviewed labels. Restart only with a clear plan.

Liver injury

The October 2026 US prescribing information has a boxed warning for severe liver injury that can be fatal, especially after tucatinib is restarted. Report yellow eyes or skin, dark urine, itching, right-sided upper abdominal pain, loss of appetite, unusual tiredness or easy bruising. A rise in liver enzymes may appear before symptoms, which is why regular blood testing matters.

The team reviews the pattern and severity, possible alternative causes and all medicines. Some abnormalities require a pause and later resumption, while very severe elevations or certain combined enzyme and bilirubin increases require permanent stopping. Do not restart because jaundice or nausea has improved without confirming the blood results and instructions. If your team restarts tucatinib after liver-test abnormalities have improved to no more than mild (grade 1 or below), the US label recommends weekly liver tests.

Early severe capecitabine toxicity

If capecitabine is part of your treatment, severe early diarrhoea, mouth ulcers, fever, profound weakness, confusion or balance problems can signal unusually high chemotherapy toxicity. Stop the oral cancer medicines and seek urgent advice. DPD testing reduces uncertainty but cannot predict every serious reaction. Early assessment is important; do not wait for the next cycle.

Capecitabine can also cause serious skin reactions, kidney injury, low blood counts and heart-related chest pain. These are partner risks, not evidence that tucatinib alone causes every complication in the combination. The team must decide which component is responsible and what can safely continue.

Heart, lung and infusion problems from trastuzumab

Trastuzumab can weaken heart pumping function and cause serious administration reactions or lung toxicity. Tell the team about increasing breathlessness, difficulty breathing when lying down, ankle swelling, rapid weight gain or palpitations. Chest pain, severe breathing difficulty or collapse requires emergency care.

At a trastuzumab visit, report chills, rash, dizziness, wheezing or chest discomfort immediately. Severe allergy can include swelling of the face or throat. Reactions can develop after leaving the unit. A new cough or increasing breathlessness also needs prompt assessment because infection, heart failure and lung inflammation may feel similar.

Other medicines, supplements and vaccines

Tucatinib has clinically important interactions. Some medicines lower its level, while others raise it or become more concentrated themselves. Have every new prescription, over-the-counter medicine and supplement checked before use, including medicines started by a dentist or another clinic.

Avoid combinations with strong CYP3A or moderate CYP2C8 inducers, such as rifampicin, carbamazepine, phenytoin and St John's wort. Gemfibrozil strongly inhibits CYP2C8 and is usually avoided. If a strong CYP2C8 inhibitor is unavoidable, the specialist may prescribe tucatinib 100 mg twice daily temporarily; this is not a change to make yourself.

Tucatinib can increase exposure to certain sedatives, statins, transplant medicines and other CYP3A substrates. It can also affect P-glycoprotein substrates such as digoxin or dabigatran. Alternatives, dose changes or extra monitoring may be needed. Give the pharmacist the exact drug names rather than relying on broad categories.

Omeprazole did not show a clinically meaningful interaction in the reviewed tucatinib studies. There is no blanket tucatinib prohibition on proton-pump inhibitors or a routine spacing rule copied from another cancer tablet. The full combination and reason for treatment still need review.

Capecitabine has additional interactions. Warfarin and similar vitamin K antagonists require close clotting-test monitoring because serious bleeding can occur. Allopurinol should be avoided with capecitabine. Do not take folic acid or folate supplements unless the team directs you: these can increase capecitabine toxicity. European information prohibits capecitabine with the antiviral brivudine, including recent use within four weeks. Always mention these medicines promptly.

Ask about vaccination in the context of your full regimen and immune status. Non-live vaccines may be appropriate; live vaccines need specialist assessment. Do not assume one fixed waiting period applies to everyone receiving tucatinib.

Everyday life during treatment

A simple medicine diary can distinguish continuous tucatinib from capecitabine treatment and rest days. Use reminders, but keep tablets in their supplied packaging unless the oncology pharmacist approves another arrangement. If eyesight, memory or hand discomfort makes administration difficult, ask for practical support.

Plan access to toilets, fluids and the urgent advice number when travelling or working away from home. Arrange medication supply and blood tests in advance. Do not extend a break or change the dose schedule to fit a trip without discussing it.

Maintain food intake and gentle activity as tolerated. Avoid driving when dizzy, weak, confused or otherwise unsafe. Discuss alcohol, supplements and restrictive diets with the team, particularly because liver tests and nutrition need attention. New symptoms should be assessed rather than hidden to avoid a treatment delay.

Ask for support with emotional strain, intimacy or treatment burden.

Fertility, contraception, pregnancy and breastfeeding

Tucatinib can harm a developing baby. Pregnancy status should be checked before starting where relevant. Tucatinib-specific instructions require effective contraception during treatment and for at least one week after the final dose, both for patients who can become pregnant and male patients with partners who can become pregnant.

That one-week interval is not enough for the whole combination. Trastuzumab requires female pregnancy precautions for seven months after its last dose. Capecitabine instructions require female contraception for six months and relevant male contraception for three months after its last dose. Obtain written advice based on every component and its own last-dose date.

Do not breastfeed during treatment. Tucatinib and US capecitabine instructions extend this for one week after their last doses, whereas European capecitabine advice specifies two weeks. European trastuzumab information says seven months after the last dose; US trastuzumab information requires an individual benefit–risk discussion that considers its seven-month washout. Do not restart breastfeeding after only one week without explicit whole-regimen advice.

Fertility may be affected. Tucatinib's animal findings indicate possible risk, while the effects in people remain uncertain; partner chemotherapy adds concerns. Discuss preservation before treatment if future parenthood matters. Tell the team promptly if pregnancy is possible during a precaution period.

After a pause or when treatment finishes

Confirm which medicines have stopped, which continue and the exact restart date and dose if a pause is temporary. After liver injury, follow the team's blood-test and restart plan described under Liver injury. Blood tests may also be needed before restarting after severe diarrhoea. Feeling better alone is not sufficient clearance.

Continue partner heart monitoring and the relevant contraception and breastfeeding precautions after treatment ends. Keep the last-dose dates for each medicine. Report new severe symptoms during a break or after stopping, and return unused tablets safely through a pharmacy.

Ask when the next scan and review are due and who will manage any continuing diarrhoea, fatigue, skin discomfort or nutritional difficulty. Finishing tablets does not mean support or monitoring ends immediately.

Frequently asked questions