Rozlytrek (Entrectinib)
Targeted cancer therapy for NTRK fusion-positive solid tumors and ROS1-positive non-small cell lung cancer
Rozlytrek (entrectinib) is a prescription targeted cancer medicine that works by blocking the action of abnormal enzymes produced by NTRK gene fusions and ROS1 gene rearrangements. It is used in adults, adolescents, and children older than 1 month with NTRK fusion-positive solid tumors, and in adults with ROS1-positive non-small cell lung cancer (NSCLC). Entrectinib is notable for its ability to cross the blood-brain barrier, making it effective against central nervous system metastases.
Quick Facts
Key Takeaways
- Rozlytrek targets NTRK gene fusions and ROS1 rearrangements — genetic testing is required before starting treatment to confirm eligibility.
- The standard adult dose is 600 mg once daily; pediatric dosing is based on body surface area (height and weight).
- It crosses the blood-brain barrier, offering therapeutic benefit for patients with brain metastases from NTRK or ROS1-positive cancers.
- Common side effects include fatigue, altered taste, dizziness, swelling, and gastrointestinal symptoms — most are manageable with dose adjustments.
- Grapefruit and Seville oranges must be avoided during treatment, and effective contraception is required for both men and women.
What Is Rozlytrek and What Is It Used For?
Quick Answer: Rozlytrek (entrectinib) is a targeted cancer medicine that blocks abnormal enzymes caused by NTRK gene fusions and ROS1 gene rearrangements. It is used to treat certain solid tumors and a specific type of lung cancer driven by these genetic changes.
Rozlytrek belongs to a class of medications known as tyrosine kinase inhibitors (TKIs). It contains the active substance entrectinib, which was developed to selectively inhibit the tropomyosin receptor kinases (TRKA, TRKB, and TRKC) encoded by the NTRK1, NTRK2, and NTRK3 genes, as well as the ROS1 kinase. When these genes undergo fusions or rearrangements, they produce abnormal proteins that drive uncontrolled cancer cell growth. By blocking these proteins, entrectinib can slow or stop tumor growth and may cause tumors to shrink.
NTRK Fusion-Positive Solid Tumors
Rozlytrek is approved for the treatment of adults, adolescents, and children older than 1 month who have solid tumors caused by an NTRK gene fusion. NTRK fusions are relatively rare but can occur across many different cancer types, including lung cancer, thyroid cancer, salivary gland tumors, soft tissue sarcomas, colorectal cancer, and various pediatric cancers. For a patient to be eligible for Rozlytrek treatment, several criteria must be met: the cancer must have been confirmed to harbor an NTRK gene fusion through validated testing; the tumor must have spread within the affected organ or to other organs, or surgical removal would cause severe complications; no prior treatment with an NTRK inhibitor has been given; and other treatment options have been unsuccessful or are not suitable.
The tumor-agnostic nature of Rozlytrek's approval is significant — it means the drug is indicated based on the presence of the NTRK gene fusion regardless of where in the body the cancer originated. This represents a shift toward precision medicine, where treatment decisions are guided by the molecular characteristics of the tumor rather than its anatomical location alone.
ROS1-Positive Non-Small Cell Lung Cancer
Rozlytrek is also indicated for adults with advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC). ROS1 rearrangements occur in approximately 1–2% of all NSCLC cases and are more common in younger patients, never-smokers, and those with adenocarcinoma histology. For this indication, patients must have confirmed ROS1-positive disease and must not have been previously treated with a ROS1 inhibitor.
How Rozlytrek Works
Entrectinib works by binding to the adenosine triphosphate (ATP) binding site of the target kinases (TRKA, TRKB, TRKC, ROS1, and ALK), preventing them from activating the downstream signaling pathways that promote cancer cell survival, proliferation, and invasion. A key advantage of entrectinib over some other targeted therapies is its ability to effectively cross the blood-brain barrier. This property makes it particularly useful for patients whose cancer has spread to the brain or central nervous system (CNS), a common occurrence in both NTRK fusion-positive cancers and ROS1-positive NSCLC. Clinical trial data have demonstrated meaningful intracranial responses in patients with CNS metastases treated with entrectinib.
Rozlytrek has received conditional marketing authorization in the European Union. This means that additional evidence about the medicine is expected. The European Medicines Agency (EMA) reviews new information at least annually and updates the product information as needed.
What Should You Know Before Taking Rozlytrek?
Quick Answer: Before taking Rozlytrek, inform your doctor about any history of heart problems, bone fractures, liver or kidney disease, and all medications you are taking. Rozlytrek is contraindicated in patients with known hypersensitivity to entrectinib. Women and men of reproductive potential must use effective contraception.
Contraindications
You must not take Rozlytrek if you are allergic to entrectinib or any of the other ingredients in the formulation. The inactive ingredients include microcrystalline cellulose, tartaric acid, colloidal silicon dioxide, croscarmellose sodium, sodium stearyl fumarate, mannitol, and magnesium stearate, among others. If you are uncertain whether you have an allergy to any of these components, consult your doctor or pharmacist before starting treatment.
Warnings and Precautions
Talk to your doctor, pharmacist, or nurse before taking Rozlytrek if any of the following apply to you:
- Cognitive effects: You have recently experienced memory loss, confusion, hallucinations, or changes in mental status. Entrectinib can affect the central nervous system and may worsen these symptoms.
- Bone fractures: You have had bone fractures or have conditions that increase your risk of breaking bones, such as osteoporosis or osteopenia. Clinical trials have shown an increased fracture risk with entrectinib use.
- Hyperuricemia: You are taking medications to lower uric acid levels in your blood. Entrectinib may increase uric acid levels, potentially worsening gout or causing kidney problems.
- Heart failure: You have congestive heart failure or have experienced signs such as cough, shortness of breath, or swelling of the legs and arms. Entrectinib can cause new or worsening heart failure.
- QTc prolongation: You have a history of heart rhythm disorders or prolonged QTc interval on electrocardiogram (ECG), or low electrolyte levels. Entrectinib may prolong the QTc interval, increasing the risk of potentially life-threatening cardiac arrhythmias.
- Lactose intolerance: You have hereditary galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption.
Rozlytrek can cause serious side effects including congestive heart failure, CNS effects (confusion, hallucinations, mood changes), bone fractures, hyperuricemia, and QTc prolongation. Report any new or worsening symptoms to your doctor immediately. Your doctor may need to reduce your dose, temporarily stop treatment, or discontinue Rozlytrek permanently.
Pregnancy and Breastfeeding
Rozlytrek may cause harm to an unborn baby. Women who are pregnant or may become pregnant should not take this medicine. If you are a woman of childbearing potential, you must use highly effective contraception during treatment and for at least 5 weeks after the last dose. It is not known whether Rozlytrek affects the efficacy of hormonal contraceptives (birth control pills or implants), so an additional barrier method (such as a condom) should be used concurrently.
Men with female partners of childbearing potential should also use highly effective contraception during treatment and for at least 3 months after the last dose, as entrectinib may impair male fertility.
Do not breastfeed while taking Rozlytrek. It is not known whether entrectinib passes into breast milk, and a risk to the nursing infant cannot be excluded. Your doctor will help you weigh the benefits of breastfeeding against the risks.
Driving and Operating Machinery
Rozlytrek can affect your ability to drive, cycle, or operate machinery. The medicine may cause blurred vision, fatigue, dizziness, fainting, confusion, or hallucinations. If you experience any of these effects, do not drive or operate heavy machinery until you feel well again. Discuss with your doctor whether it is safe for you to perform these activities during treatment.
How Does Rozlytrek Interact with Other Drugs?
Quick Answer: Rozlytrek interacts with many medications, particularly strong CYP3A4 inhibitors and inducers. Grapefruit and Seville oranges must be avoided. Always inform your doctor about all medications you are taking, including over-the-counter products and herbal supplements.
Entrectinib is primarily metabolized by the CYP3A4 enzyme system in the liver. Drugs that inhibit or induce this enzyme can significantly alter entrectinib blood levels, potentially increasing toxicity or reducing efficacy. Additionally, entrectinib itself can affect the metabolism and transport of other drugs, altering their concentrations and effects.
Major Interactions
The following medications can significantly increase entrectinib levels in your blood, potentially causing dangerous side effects. Your doctor may need to adjust your Rozlytrek dose or choose alternative medications:
| Medication Category | Examples | Interaction Effect |
|---|---|---|
| Antifungals (azoles) | Ketoconazole, itraconazole, voriconazole, posaconazole | Increased entrectinib levels (strong CYP3A4 inhibitors) |
| HIV antivirals | Ritonavir, saquinavir | Increased entrectinib levels (strong CYP3A4 inhibitors) |
| Anti-epileptics | Phenytoin, carbamazepine, phenobarbital | Decreased entrectinib levels (strong CYP3A4 inducers) |
| Anti-tuberculosis | Rifampicin, rifabutin | Decreased entrectinib levels (strong CYP3A4 inducers) |
| Herbal products | St. John’s wort (Hypericum perforatum) | Decreased entrectinib levels (CYP3A4 inducer) |
| Antipsychotics | Pimozide | Risk of QTc prolongation and cardiac arrhythmia |
| Antiarrhythmics | Quinidine | Risk of QTc prolongation and cardiac arrhythmia |
Other Notable Interactions
The following medications may also interact with Rozlytrek. While these interactions may be less severe, they are still clinically significant and should be discussed with your healthcare provider:
| Medication | Used For | Interaction Note |
|---|---|---|
| Warfarin, dabigatran | Blood clot prevention | Altered anticoagulant levels; monitor INR closely |
| Paroxetine, fluvoxamine | Depression | CYP enzyme inhibition; dose adjustment may be needed |
| Topotecan, lapatinib, mitoxantrone, methotrexate | Cancer treatment | Altered levels of co-administered anticancer drugs |
| Fentanyl, ergotamine | Severe pain, migraine | Increased risk of adverse effects |
| Atorvastatin, pravastatin, rosuvastatin | High cholesterol | Altered statin levels; monitor for muscle symptoms |
| Sirolimus, tacrolimus, ciclosporin | Immunosuppression | Altered immunosuppressant levels; monitor trough levels |
| Omeprazole | Acid reflux (heartburn) | Altered omeprazole metabolism |
| Bosentan, felodipine, nifedipine, verapamil | High blood pressure | Altered antihypertensive levels |
| Dexamethasone | Inflammation, nausea | Can reduce entrectinib levels (CYP3A4 inducer) |
| Repaglinide, tolbutamide | Diabetes (high blood sugar) | Altered blood sugar-lowering effect |
| Apalutamide | Prostate cancer | Strong CYP3A4 inducer; may decrease entrectinib levels |
Do not drink grapefruit juice or eat grapefruit or Seville oranges during treatment with Rozlytrek. These can increase the amount of entrectinib in your blood to potentially harmful levels. This applies to all grapefruit-containing products, including marmalades and supplements.
What Is the Correct Dosage of Rozlytrek?
Quick Answer: The recommended dose for adults is 600 mg once daily, taken orally. For children and adolescents, the dose is calculated based on body surface area. Always take Rozlytrek exactly as prescribed by your doctor.
Rozlytrek is available as hard capsules (100 mg and 200 mg) for patients who can swallow capsules whole, and as film-coated granules in 50 mg sachets for patients who cannot swallow capsules or who require a flexible dosing regimen. The capsules can also be prepared as an oral suspension. Your doctor will select the most appropriate formulation for your needs.
Adults
Standard Adult Dosage
Recommended dose: 600 mg once daily, taken orally.
This can be achieved with three 200 mg capsules, six 100 mg capsules, or twelve 50 mg sachets of film-coated granules sprinkled over soft food. Your doctor may reduce your dose, interrupt treatment temporarily, or discontinue treatment entirely if you experience side effects that are difficult to tolerate.
Children and Adolescents
Pediatric Dosage (children older than 1 month)
Dose calculation: Based on the child’s body surface area (BSA), derived from height and weight.
The child’s doctor will calculate the appropriate dose and adjust it as needed during treatment. The dose may be changed as the child grows. For the film-coated granules, each sachet must be used whole — do not split the contents of a sachet to prepare a smaller dose.
How to Take Rozlytrek
When using the film-coated granules formulation:
- Sprinkle the granules on one or more spoonfuls of soft food (e.g., applesauce, yogurt, or porridge).
- Consume the mixture within 20 minutes of preparation.
- Do not crush or chew the granules — they have a bitter taste.
- Drink water after taking the medication to ensure all granules are swallowed.
- Do not administer the granules via a feeding tube, as they may clog the tube.
- Do not split the contents of a sachet to create a smaller dose.
When using the hard capsules, swallow them whole with water. They may be taken with or without food.
Missed Dose
If you miss a dose and your next scheduled dose is more than 12 hours away, take the missed dose as soon as you remember. If it is less than 12 hours until your next dose, skip the missed dose and take your next dose at the usual time. Do not take a double dose to make up for a missed one.
Overdose
If you take more Rozlytrek than prescribed, contact your doctor immediately or go to a hospital emergency department. Bring the medication packaging and this information with you. There is no specific antidote for entrectinib overdose. Treatment is supportive and symptomatic.
Do not stop taking Rozlytrek without first talking to your doctor. It is important to take this medicine every day for as long as your doctor has prescribed it. Stopping treatment prematurely may allow the cancer to progress.
Vomiting After Taking Rozlytrek
If you or the patient vomits partially or completely after taking a dose, contact your doctor or pharmacist for guidance on whether to take another dose or wait for the next scheduled dose.
What Are the Side Effects of Rozlytrek?
Quick Answer: Like all medicines, Rozlytrek can cause side effects. The most common include fatigue, taste changes, dizziness, swelling, constipation, diarrhea, and nausea. Serious side effects include heart failure, cognitive changes, and bone fractures. Most side effects can be managed with dose adjustments.
Not everyone who takes Rozlytrek will experience side effects, and many side effects are manageable with appropriate medical intervention. Your doctor may reduce your dose, temporarily pause treatment, or discontinue the drug if side effects become severe. It is important to report any new or worsening symptoms to your healthcare team promptly.
Serious Side Effects
Contact your doctor immediately if you experience any of the following:
- Heart failure: Cough, shortness of breath, or swelling in the legs and arms (fluid retention).
- Cognitive effects: Confusion, mood changes, memory problems, or hallucinations (seeing things that are not there).
- Cardiac arrhythmia: Dizziness, lightheadedness, or the sensation that your heart is beating irregularly or rapidly — this may indicate QTc prolongation.
- Bone fractures: Joint pain, bone pain, deformities, or reduced ability to move.
- Hyperuricemia: Kidney problems or joint inflammation (arthritis) — you may have elevated uric acid levels.
Side Effects by Frequency
Very Common
May affect more than 1 in 10 people
- Fatigue
- Altered taste (dysgeusia)
- Dizziness or unsteadiness
- Blurred vision
- Swelling (edema)
- Diarrhea or constipation
- Nausea and vomiting
- Difficulty swallowing (dysphagia)
- Tingling, prickling, or burning sensations (paresthesia)
- Skin rash
- Shortness of breath (dyspnea)
- Cough or fever
- Headache
- Weight gain
- Muscle pain or weakness (myalgia)
- Pain (back, neck, musculoskeletal, limb)
- Abdominal pain
- Joint pain (arthralgia)
- Abnormal sensation in arms or legs
- Loss of muscle coordination, unsteady gait (ataxia)
- Sleep disturbances
- Lung infection (pneumonia)
- Urinary tract infection
- Inability to fully empty the bladder (urinary retention)
- Loss of appetite
- Low blood pressure (hypotension)
- Decreased neutrophils (neutropenia)
- Anemia (low red blood cells)
- Elevated liver enzymes (AST/ALT)
- Elevated blood creatinine
Common
May affect up to 1 in 10 people
- Mood changes
- Dehydration
- Fluid around the lungs (pleural effusion)
- Fainting (syncope)
- Increased skin sensitivity to sunlight (photosensitivity)
Uncommon
May affect up to 1 in 100 people
- Tumor lysis syndrome — changes in blood chemistry caused by rapid breakdown of tumor cells, which can damage kidneys, heart, and liver
- Myocarditis (inflammation of the heart muscle)
It is important to report suspected side effects after the medicine has been authorized. This helps in the continuous monitoring of the medicine’s benefit-risk balance. Healthcare professionals and patients are encouraged to report adverse reactions to their national pharmacovigilance authority (e.g., FDA MedWatch in the US, Yellow Card Scheme in the UK, or EMA EudraVigilance in the EU).
How Should You Store Rozlytrek?
Quick Answer: Store Rozlytrek below 30°C (86°F) in the original packaging to protect from moisture. Keep out of the sight and reach of children. Once sprinkled on soft food, consume within 20 minutes.
Proper storage of Rozlytrek is essential to ensure the medication remains effective and safe to use. Follow these guidelines carefully:
- Temperature: Store below 30°C (86°F). Discard the medication if it has been exposed to temperatures above this threshold.
- Packaging: Keep the film-coated granules in their original sachets and the hard capsules in their original bottles or blister packs. The formulations are moisture-sensitive.
- After preparation: Once the granules are sprinkled on soft food, the mixture must be consumed within 20 minutes. If not consumed within this time, discard the preparation and make a new dose.
- Expiration: Do not use after the expiration date (EXP) printed on the carton and sachet. The expiration date refers to the last day of that month.
- Children: Keep out of the sight and reach of children at all times.
- Disposal: Do not dispose of medications via the drain or in household waste. Ask your pharmacist how to dispose of medicines that are no longer needed. These measures help protect the environment.
What Does Rozlytrek Contain?
Quick Answer: Each Rozlytrek 50 mg sachet contains entrectinib as the active ingredient, along with inactive ingredients including microcrystalline cellulose, tartaric acid, and various excipients. The medicine contains less than 1 mmol (23 mg) sodium per 600 mg dose, making it essentially sodium-free.
The active substance in Rozlytrek is entrectinib. Each sachet of film-coated granules contains 50 mg of entrectinib.
Inactive Ingredients
The other components of the formulation include:
- Granule core: Microcrystalline cellulose (E460), tartaric acid (E334), colloidal anhydrous silica (E551), croscarmellose sodium (E468), sodium stearyl fumarate, mannitol (E421), magnesium stearate (E470b).
- Film coating: Titanium dioxide (E171), talc, yellow iron oxide (E172), red iron oxide (E172), black iron oxide (E172), polyethylene glycol 3350, polyvinyl alcohol (partially hydrolyzed).
Appearance
Rozlytrek 50 mg film-coated granules are brownish-orange or grayish-orange in color, packaged in individual sachets. Each carton contains 42 sachets. The hard capsules are available in 100 mg (yellow, size 2) and 200 mg (orange, size 0) strengths.
Sodium Content
Rozlytrek contains less than 1 mmol (23 mg) sodium per 600 mg dose. It is therefore considered essentially sodium-free, which is relevant for patients on a controlled sodium diet.
Marketing Authorization Holder
Rozlytrek is manufactured by Roche Pharma AG (Grenzach-Wyhlen, Germany) and marketed by Roche Registration GmbH. The medicine has received conditional marketing authorization from the European Medicines Agency (EMA) and has been approved by the US Food and Drug Administration (FDA) and regulatory authorities in multiple other countries worldwide.
Frequently Asked Questions About Rozlytrek
Rozlytrek (entrectinib) is used to treat two types of cancer: (1) Solid tumors in adults, adolescents, and children older than 1 month that harbor NTRK gene fusions — this includes cancers in various organs when the cancer has spread or cannot be safely removed by surgery, other treatments have not worked, and no prior NTRK inhibitor has been given. (2) Advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC) in adults who have not previously received a ROS1 inhibitor. Genetic testing must confirm the presence of an NTRK fusion or ROS1 rearrangement before treatment can begin.
The most common side effects (occurring in more than 1 in 10 patients) include fatigue, altered taste, dizziness, blurred vision, swelling, constipation or diarrhea, nausea, vomiting, shortness of breath, cough, headache, weight gain, muscle and joint pain, anemia, low neutrophil count, elevated liver enzymes, and elevated blood creatinine. These side effects are typically manageable and your doctor may adjust your dose if needed. Serious but less common side effects include heart failure, cognitive changes, bone fractures, and QTc prolongation.
Yes, Rozlytrek can be taken with or without food. The hard capsules should be swallowed whole with water. The film-coated granules are designed to be sprinkled on soft food such as applesauce, yogurt, or porridge and consumed within 20 minutes of preparation. However, grapefruit juice, grapefruit, and Seville oranges must be strictly avoided during treatment, as they inhibit CYP3A4 and can increase entrectinib blood levels to potentially toxic concentrations.
Yes, one of the key advantages of entrectinib (Rozlytrek) is its ability to cross the blood-brain barrier effectively. This means it can reach and treat cancer that has spread to the brain or central nervous system (CNS metastases). Clinical trials have demonstrated clinically meaningful intracranial responses in patients with CNS disease. This property distinguishes Rozlytrek from some other kinase inhibitors that have limited CNS penetration.
Before starting Rozlytrek, your tumor tissue must be tested to confirm the presence of an NTRK gene fusion or ROS1 rearrangement. This is typically performed using molecular diagnostic methods such as next-generation sequencing (NGS), fluorescence in situ hybridization (FISH), or immunohistochemistry (IHC). Only patients whose tumors test positive for these specific genetic alterations are eligible for treatment. Your oncologist will arrange the appropriate testing.
Rozlytrek should be stored below 30°C (86°F) in the original packaging to protect from moisture. Do not use the medication after the expiration date printed on the carton. Once the film-coated granules are sprinkled on soft food, the preparation must be consumed within 20 minutes — if not consumed in time, discard it and prepare a new dose. Always keep Rozlytrek out of the reach and sight of children.
References
This article is based on the following peer-reviewed sources and regulatory documents:
- European Medicines Agency (EMA). Rozlytrek (entrectinib) – Summary of Product Characteristics (SmPC). Last updated March 2025. Available from: EMA – Rozlytrek EPAR.
- U.S. Food and Drug Administration (FDA). ROZLYTREK (entrectinib) Prescribing Information. Revised 2024. Available from: FDA – Rozlytrek Label.
- Doebele RC, Drilon A, Paz-Ares L, et al. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1–2 trials. Lancet Oncol. 2020;21(2):271–282. doi:10.1016/S1470-2045(19)30691-6.
- Drilon A, Siena S, Dziadziuszko R, et al. Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1–2 trials. Lancet Oncol. 2020;21(2):261–270. doi:10.1016/S1470-2045(19)30690-4.
- National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. Version 4.2025.
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd List (2023). Geneva: WHO; 2023.
- Demetri GD, Paz-Ares L, Farago AF, et al. Efficacy and safety of entrectinib in patients with NTRK fusion-positive tumours: pooled analysis of STARTRK-2, STARTRK-1 and ALKA-372-001. Ann Oncol. 2022;33(suppl_7):S808–S869.
Editorial Team
Written by the iMedic Medical Editorial Team — specialists in oncology and clinical pharmacology with documented academic background and clinical experience.
Reviewed by the iMedic Medical Review Board, an independent panel of medical experts who verify all content according to international guidelines (EMA, FDA, NCCN, WHO).
Evidence Standard: All medical claims in this article are based on Level 1A evidence (systematic reviews and clinical trials) following the GRADE framework. We maintain strict editorial independence with no commercial funding or pharmaceutical sponsorship.