Entrectinib (Rozlytrek)

Entrectinib at a glance

Rozlytrek is the verified brand for entrectinib. It is a tyrosine kinase inhibitor that blocks particular growth-signalling proteins, including TRK and ROS1. A relevant gene-fusion result and specialist assessment are needed before treatment.

The usual adult dose is 600 mg once daily, with or without food. Children need an individual dose based on age and body size. Capsules contain 100 mg or 200 mg. Oral pellets, called film-coated granules in European information, contain 50 mg per packet or sachet. Capsules can also be prepared as an authorised suspension.

Important possible effects include dizziness, altered thinking or mood, weight gain, fluid swelling, bowel changes, heart problems, liver changes, raised uric acid, visual problems and fractures. Tests help detect effects that may not yet be causing symptoms.

How entrectinib works

A gene fusion occurs when parts of different genes join together. Some fusions involving NTRK genes or ROS1 produce abnormal proteins that continually send growth signals. Entrectinib interferes with the activity of these proteins. It is targeted therapy, rather than conventional chemotherapy or checkpoint immunotherapy.

NTRK genes make TRK proteins, which normally contribute to nervous-system functions. Blocking related signals helps explain why treatment can affect sensation, balance, appetite or thinking as well as cancer growth. Targeted treatment still needs careful monitoring; it does not act only on cancer cells.

In some circumstances, a fusion can guide treatment across different tumour types. This is sometimes called tumour-agnostic treatment. It does not mean that every tumour with any NTRK change will respond. The exact fusion, other cancer features and previous treatments remain important.

Entrectinib can reach the central nervous system, but this does not guarantee control of brain disease. Scans and clinical assessment establish benefit.

How the team decides whether it is suitable

The team checks the diagnosis, the specific NTRK fusion or ROS1 rearrangement, prior treatment and current prescribing information. A fusion is different from a general increase in protein expression or an unrelated gene mutation. Ask the clinician to explain the result in your report and why it supports this choice.

Testing usually uses tumour material. US guidance allows blood-based testing in specified settings when tumour tissue is unavailable. The oncologist decides whether the sample and test are adequate.

Tell the team about heart failure, irregular rhythms, fainting, liver or kidney disease, gout, previous fractures, visual problems, depression or memory difficulties. Previous brain radiotherapy and medicines that cause sleepiness are also relevant when assessing dizziness or cognitive symptoms.

Tell the team about allergies. European capsules are unsuitable with certain rare inherited sugar-processing disorders because they contain lactose; the 200 mg capsule also contains E110 colouring, which can cause allergy.

Severe kidney impairment has not been well studied. Liver guidance differs: European information does not recommend an initial adjustment for hepatic impairment but requires close monitoring in severe impairment; US information emphasises an individual risk–benefit decision for moderate or severe impairment. Your clinician must interpret these differences for your situation.

Before treatment starts

Blood tests assess liver and kidney function, blood counts, blood salts and uric acid. Uric acid is a waste substance that can rise during treatment and cause joint or kidney problems. Pregnancy status is checked if pregnancy is possible.

An ECG records the heart's electrical activity and checks the QT interval, a measure of electrical recovery between beats. Potassium, magnesium and other relevant salts should be assessed. A heart scan measures pumping strength. The US label recommends this before treatment for all patients; European guidance specifically calls for it when heart-failure symptoms or risk factors are present.

Bring a complete list of medicines, vitamins and herbal products. Ask for a written plan for missed doses and vomiting: entrectinib's immediate-vomiting instruction differs from many other oral cancer medicines, and European instructions also distinguish whole capsules from suspension or granules.

If you will prepare a liquid dose, have the pharmacist demonstrate the capsule strength, liquid volume, syringe markings and tube method if relevant. Check both milligram and millilitre doses.

How to take entrectinib

Daily dose and whole capsules

Take it once daily at a consistent time, with or without food. An adult 600 mg dose is three 200 mg capsules; other prescriptions may differ. Swallow whole capsules with water; do not chew or crush them.

Treatment is generally taken every day without a routine weekly break. The team may temporarily interrupt treatment or reduce the dose because of side effects. Do not restart a medically directed pause without confirming the dose and timing.

Capsules prepared as a suspension

If swallowing is difficult or a feeding tube is needed, the prescribed capsules can be opened and prepared as a suspension using room-temperature drinking water or milk. This is a specific measured method, not permission to mix capsule powder into any food or drink. The prescribed quantity of capsules, liquid and dose to withdraw must follow the product's instructions.

The mixture is allowed to stand for 15 minutes during preparation. Take or give the prepared suspension promptly; discard it if not used within two hours. Keep it below 30°C (86°F).

Measure only the prescribed volume, which may be less than the prepared amount. Use the demonstrated oral-syringe and rinsing method. Supported gastric or nasogastric tube administration exists for capsule suspension, with requirements for tube size, dividing larger volumes and flushing. Have the pharmacy confirm these details for the actual tube. Do not improvise if the tube blocks or the full dose cannot be delivered.

Pellets or film-coated granules

These come in 50 mg packets or sachets for doses in multiples of 50 mg. Sprinkle the prescribed whole packets onto one or more spoonfuls of soft food, such as apple sauce, yoghurt or pudding, and take within 20 minutes. Do not chew or crush the pellets. Drink water afterwards to help swallow the full amount.

Do not divide a packet by eye to create a smaller dose. Pellets must not be used to make a suspension or given through a feeding tube because they may block it. Very small dose increments require the capsule-suspension method selected by the prescriber. Switching preparation needs pharmacy guidance.

Missed doses and vomiting

If you forget a dose, take it when remembered unless the next dose is due within 12 hours. If 12 hours or less remain, skip it and resume the usual schedule. Do not take a double dose to catch up.

For whole capsules, the US and European labels allow repeating a dose if vomiting happens immediately after it. This is different from the advice for many other oral cancer medicines. If vomiting occurs later, the timing is uncertain or vomiting repeats, contact the treating team before taking more. Do not keep giving replacement doses.

European instructions for capsule suspension and granules say to contact the clinician or pharmacist if some or all of the dose is vomited or spat out immediately. The US label gives a general instruction to repeat an immediately vomited dose. Agree the exact plan for your formulation beforehand; do not automatically repeat a child's partly swallowed dose.

If you take too much, contact the treating service or seek hospital advice immediately and bring the packaging. Repeated vomiting or inability to keep fluids down needs urgent advice because it can affect hydration and blood salts.

Storage and disposal

Keep the medicine in its original packaging, protected from moisture, with capsule bottles tightly closed. US storage is 20–25°C (68–77°F), with permitted brief excursions to 15–30°C (59–86°F). European granules should not be stored above 30°C (86°F). Follow the actual pack instructions, including the short limits for prepared doses. Keep medicines out of children's reach and return unused supplies to the pharmacy.

Monitoring and checking whether treatment is working

Liver tests are particularly important early in treatment. US guidance specifies testing every two weeks during the first month, then monthly and whenever clinically needed. Blood counts, kidney function and blood salts are monitored according to your treatment plan. Uric acid is checked before treatment and periodically afterwards.

ECGs and blood salts are reassessed during treatment. European guidance recommends a check after one month, then as clinically indicated; US guidance adjusts the interval to individual risk. Report fainting or palpitations between tests. A normal initial ECG does not remove the need to report new symptoms.

Report changes in breathing, swelling, vision, thinking, mood, sleep and mobility. Heart scans are repeated when symptoms or the clinical plan require them. New limb pain or a change in walking, especially in a child, may need examination and imaging for a fracture.

Scans, symptoms and clinical review assess cancer control. A treatment break can be necessary to manage toxicity and does not by itself mean the medicine has failed.

Common side effects and practical management

Dizziness, tiredness and altered sensation

Dizziness, sleepiness and fatigue can make driving, stairs or getting up quickly more difficult. Sit down if you feel lightheaded, rise slowly and ask for help if your balance is affected. Review other sedating medicines with the team. Do not drive, cycle in traffic or operate machinery while impaired.

Tingling, burning or altered sensitivity to touch can occur. Take care with hot water, cooking and sharp objects if sensation is reduced. Tell the team if symptoms interfere with walking, sleep or usual activities. New severe weakness or sudden neurological changes need urgent assessment.

Taste, appetite and weight

Food may taste different and appetite can change. Experiment with small meals and foods you can tolerate, and discuss persistent poor intake with a dietitian. Weight gain is also possible, so monitoring weight is useful even when you are eating normally.

Swelling from retained fluid can look like weight gain. Report rapid weight increase, swollen legs or worsening breathlessness rather than assuming this is only a dietary issue.

Bowel changes, nausea and discomfort

Constipation, diarrhoea, nausea and vomiting can occur. Keep track of your usual bowel pattern and use the medicines chosen for you. Fluids and suitable food changes may help, but the plan should account for any heart or kidney condition. Persistent vomiting, diarrhoea or very little urine needs prompt advice.

Report constipation with significant pain, a swollen abdomen or vomiting urgently. Muscle and joint aches may also occur; ask which pain relief is safe. A new focal pain, limp or difficulty bearing weight should not be treated as an ordinary ache without assessment.

Important side effects

Heart failure and heart-muscle inflammation

Entrectinib can weaken heart pumping, sometimes in people with no previous heart disease. Warning symptoms include new breathlessness, difficulty breathing when lying flat, increasing leg swelling, rapid weight gain or unusual exhaustion. Myocarditis, inflammation of heart muscle, has also been reported.

Contact the team immediately for these symptoms. Severe breathing difficulty, chest pain or collapse is an emergency. Treatment is withheld when new or worsening heart failure is suspected or identified, with reassessment and appropriate treatment before a decision about restarting.

Heart-rhythm changes

QT prolongation can increase the risk of an abnormal heartbeat. Risk is greater with certain heart conditions, low blood salts or interacting medicines. Palpitations, severe dizziness, fainting or a blackout requires urgent assessment; collapse should be treated as an emergency.

Do not assume a fainting episode is simply dehydration or a usual dizziness side effect. The team may correct blood salts, review medicines and pause or change treatment.

Thinking, mood and sleep changes

Memory, attention, thinking or speech can change. Some people become confused, agitated, anxious or unusually sleepy; hallucinations or significant mood changes can occur. Tell the team promptly and ask a trusted person to mention changes they notice, particularly during the early months.

Sudden severe confusion, a seizure, weakness on one side or difficulty waking needs emergency care. If you develop thoughts of harming yourself, seek immediate help from the treating team or emergency services and stay with someone who can support you. These symptoms should not be dismissed as a normal emotional response to cancer.

Fractures

Fractures have occurred in adults and children, with a greater proportion reported in children. Some paediatric fractures occurred without an obvious fall or injury. New limb or hip pain, limping, difficulty walking, refusal to bear weight or a visible deformity needs prompt assessment.

Do not encourage a child to walk through pain. The team will decide whether imaging, treatment interruption or other support is needed. Evidence about healing and future fracture risk during entrectinib treatment is limited, so follow the individual mobility and follow-up plan.

Liver injury, raised uric acid and tumour lysis

Liver injury may first appear on blood tests. Report yellow skin or eyes, dark urine, persistent nausea, reduced appetite or pain on the upper right side of the abdomen. Do not start herbal remedies intended to “protect the liver” without checking them.

Raised uric acid can cause a painful, swollen joint or kidney problems. Report joint redness, severe pain, flank pain or changes in urine. The team may give uric-acid-lowering treatment and temporarily withhold entrectinib when symptomatic.

Tumour lysis syndrome occurs when rapid cancer-cell breakdown releases substances into the blood, affecting salts, kidneys and sometimes heart rhythm. Severe weakness, cramps, confusion, palpitations or very little urine needs urgent assessment. Higher-risk patients may require closer blood tests and a preventive plan.

Vision changes and blood-count effects

Blurred or double vision, flashes, new floaters or sensitivity to light should be reported immediately. US guidance calls for withholding treatment for new visual changes or changes affecting daily activities until improvement or stability, with eye assessment as appropriate. Withhold the next dose and contact the team immediately; restart only on their advice. Sudden loss of vision needs emergency care.

Blood counts can fall. Low red cells may contribute to tiredness and breathlessness; low white cells can increase infection risk. Fever, shaking chills or feeling suddenly unwell needs prompt advice, even if there is no obvious source of infection.

Other medicines, supplements and vaccinations

Entrectinib is processed by an enzyme called CYP3A. Certain antifungals, antibiotics, HIV medicines, seizure medicines and other drugs can markedly raise or lower its level. Avoid strong or moderate CYP3A inhibitors and inducers. If an inhibitor is unavoidable, certain patients may receive a specialist-adjusted dose for up to 14 days; young children have stricter restrictions. Entrectinib can also change levels of other medicines. Dose changes require the oncology pharmacist.

Avoid combining it with medicines that prolong QT unless the specialist has explicitly assessed and managed the risk. This includes some anti-sickness drugs, so use the prescription selected for you rather than leftover treatment from another illness. Bring a complete list of prescription, over-the-counter, herbal and Ayurvedic products to every medication review. Avoid St John's wort.

Avoid grapefruit, grapefruit juice and Seville oranges. Ordinary meal timing does not need to change. European information states that proton-pump inhibitors, H2 blockers and antacids do not require an entrectinib dose adjustment, but include heartburn remedies in the full interaction check.

Discuss vaccines with the oncology team, including live and travel vaccines. Timing depends on immune function, blood counts and other treatment. Do not assume that every vaccine is prohibited or that everyone needs the same waiting period after treatment.

Everyday life during treatment

Agree who will prepare and check liquid doses. Store the latest written instructions with the medicine and update them after any dose change; an old syringe-volume instruction may no longer be correct.

Adapt work, school and physical activity to energy, balance and mobility. Ask for support if falls, driving or caring for children becomes difficult. Tell dentists and other clinicians about treatment before new medicines or procedures. Emotional and practical support can be arranged through your oncology service.

Before travel, plan supply, storage and access to urgent care. Keep the original labelled packaging. Prepared suspension has a short usable period, so discuss how to prepare doses safely away from home. Avoid driving or hazardous activities whenever dizziness, visual problems, sleepiness or cognitive changes are present.

Fertility, contraception, pregnancy and breastfeeding

Entrectinib may harm an unborn baby. Pregnancy testing is required before treatment if pregnancy is possible. Contact the team immediately if pregnancy occurs or is suspected. Human fertility effects are uncertain; discuss fertility preservation before treatment if future parenthood is important.

Women who could become pregnant should use effective contraception during treatment and for at least five weeks after the last dose. Men with partners who could become pregnant should use effective contraception during treatment and for three months afterwards. European guidance uses the term highly effective and advises adding a barrier method when systemic hormonal contraception is used, because its reliability with entrectinib is uncertain.

Do not breastfeed during treatment. US guidance continues this restriction for seven days after the last dose. European information advises stopping breastfeeding during treatment without specifying the same post-treatment interval. Confirm when feeding can safely resume for your product and any other medicines. A child receiving suspension prepared in milk is a different situation from a mother taking entrectinib and breastfeeding.

After treatment finishes

Keep follow-up appointments for cancer assessment and unresolved side effects. Dizziness, swelling, visual changes or bone pain should still be reported after treatment stops.

Continue the contraception and breastfeeding precautions for their full intervals. Tell other prescribers when treatment stops, so interaction-related changes can be reassessed. Return unused medicine and clarify whether a pause is temporary or permanent before deciding what to do with the remaining supply.

Frequently asked questions