InfoCons Consumer Protection informs you – Rozlytrek – Package Leaflet

Before anything else

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.
• This leaflet has been written as though the person taking the medicine is reading it. If you are giving this medicine to your child, please replace ‘ you’ with ‘your child ’ throughout.

ℹ️ 1. What Rozlytrek is and what it is used for

What Rozlytrek is Rozlytrek is a cancer medicine that contains the active substance ‘ entrectinib ’.

What Rozlytrek is used for

Rozlytrek is used to treat either :

• adults , adolescents , and children older than 1 month with solid tumour s (cancer ) in various parts of the body that are caused by a change in a gene called ‘neurotrophic tyrosine receptor kinase ’ (NTRK ), or
• adults with a type of lung cancer called ‘non- small cell lung cancer’ (NSCLC) that is caused by a change in a gene called ‘ROS1 ’.

This medicine is used for solid tumour cancers when :

• a test has shown that your cancer cells have a change in genes called ‘ NTRK ’ (see ‘How Rozlytrek works’ below), and
• your cancer has spread within the affected organ or to other organs in your body or if surgery to remove the cancer is likely to cause severe complications, and
• you have not previously been given medicines called ‘ NTRK inhibitors ’
• other treatments have not worked or are not suitable for you.

96 This medicine is used if your lung cancer (NSCLC) :

• is ‘ROS1 -positive’ – this means that your cancer cells have a change in a gene called ‘ ROS1 ’ (see ‘How Rozlytrek works’ below), and
• is advanced – for example, has spread to other parts of your body (metastatic), and
• you have not previously been given medicines called ‘ ROS1 inhibitors ’.

How Rozlytrek works

Rozlytrek works by blocking the action of faulty enzymes. These faulty enzymes are caused by a change in the NTRK or ROS1 genes that make them. The faulty enzymes make the cancer cells grow.

Rozlytrek may slow down or stop the growth of the cancer. It may also help to shrink your cancer.

⚠️ 2. What you need to know before you take Rozlytrek

Do not take Rozlytrek

• if you are allergic to entrectinib or any of the other ingredients of this medicine (listed in section 6).

If you are not sure, talk to your doctor, pharmacist or nurse before taking Rozlytrek.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before taking Rozlytrek if:

• you have recently had memory loss, confusion, hallucinations, or mental status changes
• you have had fractured bones, or conditions which may increase your risk of breaking bones, called ‘osteoporosis’ or ‘osteopaenia’
• you take medicine to lower the uric acid in your blood
• you have heart failure ( when your heart struggles to pump blood to supply oxygen to the body )
• signs can include cough, feeling short of breath, or swelling in your legs or arms
• you have ever had heart problems or a heart conduction problem called ‘prolonged QT c interval’ – this is shown on an ‘electro -cardiogram’ (ECG), or by low levels of electrolytes in your blood
• you have an inherited problem called ‘galactose intolerance’, ‘congenital lactase deficiency’ or ‘glucose -galactose malabsorption’ .

If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or nurse before taking Rozlytrek.

Other medicines and Rozlytrek

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This is because Rozlytrek can affect the way some other medicines work. Also, some other medicines can affect the way Rozlytrek works.

In particular, tell your doctor or pharmacist if you are taking any of the following medicines for:

• fungal infections (anti -fungals) – such as ketoconazole, itraconazole, voriconazole, posaconazole
• AIDS/HIV infection – such as ritonavir or saquinavir
• depression – such as paroxetine, fluvoxamine, or a herbal medicine for depression – St. John’s Wort
• stopping seizures or fits – such as phenytoin, carbamazepine, or phenobarbital
• tuberculosis – such as rifampicin or rifabutin 97 • solid cancers and blood cancer – topotecan, lapatinib, mitoxantrone, apalutamide, or methotrexate
• inflam ed joints or joint autoimmune disease (rheumatoid arthritis) – methotrexate
• migraines – ergotamine
• severe pain – fentanyl
• mental illness (psychoses) or Tourette Syndrome – pimozide
• irregular heart rate – quinidine
• stopping the formation of blood clots – warfarin or dabigatran etexilate
• gastric reflux (heartburn) – cisapride or omeprazole
• lowering blood cholesterol – atorvastatin, pravastatin, or rosuvastatin
• suppressing your body’s immune system, or stopping your body from rejecting an organ transplant – sirolimus, tacrolimus, or cyclosporin
• lowering blood sugar levels – repaglinide or tolbutamide
• high blood pressure – bosentan, felodipine, nifedipine, or verapamil
• inflammation or nausea – dexamethasone If any of the above apply to you (or you are not sure), talk to your doctor or pharmacist before taking Rozlytrek.

Rozlytrek with food and drink Do not drink grapefruit juice or eat grapefruit or Seville oranges during your treatment with this medicine . It may increase the amount of the medicine in your blood to a harmful level.

Women and contraception You must avoid becoming pregnant while taking this medicine because it could harm the baby. If you are able to become pregnant, you must use highly effective contraception:

• while on treatment , and
• for at least 5 weeks after stopping treatment.

It is not known if Rozlytrek can reduce the effect of birth control medicines ( contraceptive pills or implanted hormonal contraceptives). You should use another reliable method of birth control such as a barrier method ( such as a condom).

Talk to your doctor about the right methods of contraception for you and your partner.

Men and contraception Your female partner must avoid becoming pregnant while you are taking this medicine because it could harm the baby. If your female partner is able to become pregnant, you must use highly effective contraception :

• while on treatment , and
• for at least 3 months after stopping treatment.

Talk to your doctor about the right methods of contraception for you and your partner.

Pregnancy

• Do not take Rozlytrek if you are pregnant. This is because it may harm your baby.
• If you become pregnant when taking the medicine or during the 5 weeks after taking your last dose, tell your doctor straight away.

98 Breast -feeding Do not breast -feed while taking this medicine. This is because it is not known if Rozlytrek can pass over into breast milk and could therefore harm your baby.

Driving , cycling and using machines Rozlytrek may affect your ability to drive , ride a bicycle, or use machines. Rozlytrek may cause you to:

• have blurred vision
• feel tired, dizzy , or pass out
• have changes in your mental status, feel confused or see things that are not there (hallucinations).

If this happens, you should not drive, ride a bicycle, or operate heavy machines until you feel better .

Talk to your doctor or pharmacist about whether it is okay for you to drive , ride a bicycle, or use machines.

Rozlytrek contains sodium

This medicinal product contains less than 1mmol sodium (23 mg) per 600 mg dose, that is to say essentially ‘sodium -free’. See section 6.

💊 3. How to take Rozlytrek

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

How much to take For adults:

• The recommended dose is 12 sachets once a day (total amount 600 mg). Each individual sachet is 50 mg.
• If you feel unwell, your doctor may lower your dose, stop treatment for a short time or stop treatment completely.

For adolescents and children older than 1 month :

• Your child’s doctor will work out the correct dose to use – based on the height and weight of the child.
• Your child’s doctor will review the dose and change it as needed.

Rozlytrek is also available as hard capsules for patients who are able to swallow capsules whole.

Capsules may also be prepared as an oral suspension for patients who are unable to swallow soft food or need to use a feeding tube.

How to take Take Rozlytrek film-coated granules by mouth – sprinkled on soft food.

• Do not divide the content of a sachet of film-coated granules to prepare a smaller dose.
• Film -coated g ranules should be sprinkled on one or more spoonfuls of a soft food (such as applesauce, yogurt , or pudding ) and taken within 20 minutes of mixing.

99 • Do not crush or chew film-coated granules to avoid a bitter taste.

• Drink water after taking the medicine.
• Film -coated granules are not to be used with a feeding tube – they could block the tubing .

Read the ‘Instructions for Use’ at the end of this leaflet Read and follow the ‘ Instructions for Use’ at the end of this leaflet carefully on how to take or give Rozlytrek. It shows you details on how to prepare a dose using film-coated granules and soft food .

If you vomit after taking Rozlytrek If partial or total vomiting or spitting occurs immediately after giving an administered dose to the patient , consult the patient’s doctor or pharmacist for the next steps.

If you take more Rozlytrek than you should

If you take more Rozlytrek than you should, talk to a doctor or go to hospital straight away. Take the medicine pack and this leaflet with you.

If you forget to take Rozlytrek

• If your next dose is more than 12 hours later, take the missed dose as soon as you remember.
• If there are less than 12 hours until your next dose, do not take the missed dose. Take your next dose at the usual time.
• Do not take a double dose to make up for a missed dose.

If you stop taking Rozlytrek

Do not stop taking this medicine without talking to your doctor first. It is important to take this medicine every day for as long as your doctor prescribes it for you.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

❗ 4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The following side effects may happen with this medicine.

Serious side effects

Tell your doctor straight away if you notice any of the following serious side effects . Your doctor may lower your dose, stop your treatment for a short time or stop your treatment completely if:

• you have cough, feel short of breath, or swelling in your legs or arms (fluid retention) – these can be signs of heart problems (congestive heart failure )
• you feel confused, have mood changes , memory problems or see things that are not there (hallucinations)
• you feel dizzy or light -headed, or feel your heart beating irregularly or fast – this may be a sign of an abnormal heart beat
• you notice any joint pain, bone pain, deformities or changes in your ability to move , as this may be a sign of fractures
• you have kidney problems or arthritis – you may have high uric acid levels in your blood Tell your doctor straight away if you notice any of the side effects above.

100 Other side effects Tell your doctor, pharmacist or nurse if you notice any of the following side effects:

Very common: may affect more than 1 in 10 people

• feeling tired
• changes in taste
• feeling unsteady or dizzy
• blurred vision
• swelling
• diarrhoea or constipation
• being or feeling sick
• difficulty swallowing
• abnormal sense of touch which feels like itching, tingling or burning sensation
• rash
• feeling short of breath
• cough or fever
• headache
• weight gain
• vomiting
• muscle pain or weakness
• pain including back pain, neck pain, musculoskeletal pain, pain in limbs
• stomach pain
• joint pain
• abnormal unpleasant sensation in your arms or legs
• loss of muscle coordination, being unsteady when walking
• disturbance in normal sleep patterns
• lung infection
• urinary tract infection
• cannot empty your bladder completely
• loss of appetite
• low blood pressure
• decreased number of a type of white blood cell called neutrophils
• lack of enough red blood cells (anaemia)
• increased blood levels of certain liver enzymes (AST/ALT)
• increased blood level of creatinine ( something normally removed by the kidneys into the urine)

Common: may affect up to 1 in 10 people

• mood disorders
• dehydration
• fluid around your lungs
• fainting
• skin being more sensitive to sunlight

Uncommon : may affect less than 1 in 100 people

• changes in certain chemicals in your blood caused by fast breakdown of tumour cells – this may cause damage to organs, including the kidneys, heart, and liver.
• inflammation of the heart muscle Tell your doctor, pharmacist or nurse if you notice any of the side effects above.

101 Reporting of side effects If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V . By reporting side effects you can help provide more information on the safety of this medicine.

🌡️ 5. How to store Rozlytrek

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the carton and the sachet after EXP. The expiry date refers to the last day of that month.
• Store the film -coated granules in the original package in order to protect from moisture.
• After addition to soft food, use within 20 minutes of preparation.
• Do not throw away any medicines via wastewater. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

📦 6. Contents of the pack and other information

What Rozlytrek contains

The active substance is entrectinib. Each sachet contains 50 mg of entrectinib.

The other ingredients are:

• Granule core: microcrystalline cellulose (E460) , tartaric acid (E334) , silica, colloidal anhydrous (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 hydrolysed) .

What Rozlytrek looks like and contents of the pack

Rozlytrek 50 mg film-coated granules are brownish orange or greyish orange granules and contained in a sachet. Each carton contains 42 sachets .

Marketing Authorisation Holder

Roche Registration GmbH Emil -Barell -Strasse 1 79639 Grenzach -Wyhlen Germany

Manufacturer

Roche Pharma AG Emil -Barell -Strasse 1 79639 Grenzach -Wyhlen Germany 102 For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien , Luxembourg/Luxemburg N.V. Roche S.A.

België/Belgique/Belgien Tél/Tel: +32 (0) 2 525 82 11 Latvija Roche Latvija SIA Tel: +371 – 6 7039831 България Рош България ЕООД Тел: +359 2 474 5444 Lietuva UAB “Roche Lietuva” Tel: +370 5 2546799 Česká republika Roche s. r. O.

Tel: +420 – 2 20382111 Magyarország Roche (Magyarország) Kft.

Tel: +36 – 1 279 4500 Danmark Roche Pharmaceuticals A/S Tlf.: +45 – 36 39 99 99 Nederland Roche Nederland B.V.

Tel: +31 (0) 348 438050 Deutschland Roche Pharma AG Tel: +49 (0) 7624 140 Norge Roche Norge AS Tlf: +47 – 22 78 90 00 Eesti Roche Eesti OÜ Tel: + 372 – 6 177 380 Österreich Roche Austria GmbH Tel: +43 (0) 1 27739 Ελλάδα , Κύπρος Roche (Hellas) A.E.

Ελλάδα Τηλ: +30 210 61 66 100 Polska Roche Polska Sp.z o.o.

Tel: +48 – 22 345 18 88 España Roche Farma S.A.

Tel: +34 – 91 324 81 00 Portugal Roche Farmacêutica Química, Lda Tel: +351 – 21 425 70 00 France Roche Tél: +33 (0) 1 47 61 40 00 România Roche România S.R.L.

Tel: +40 21 206 47 01 Hrvatska Roche d.o.o.

Tel: +385 1 4722 333 Ireland , Malta Roche Products (Ireland) Ltd.

Ireland/L -Irlanda Tel: +353 (0) 1 469 0700 Slovenija Roche farmacevtska družba d.o.o.

Tel: +386 – 1 360 26 00 Slovenská republika Roche Slovensko, s.r.o.

Tel: +421 – 2 52638201 Ísland Roche Pharmaceuticals A/S c/o Icepharma hf Sími: +354 540 8000 Suomi/Finland Roche Oy Puh/Tel: +358 (0) 10 554 500 Italia Roche S.p.A.

Tel: +39 – 039 2471 Sverige Roche AB Tel: +46 (0) 8 726 1200

This leaflet was last revised in

This medicine has been given ‘conditional approval’. This means that there is more evidence to come about this medicine.

The European Medicines Agency will review new information on this medicine at least every year and this leaflet will be updated as necessary.

Other sources of information Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu 104 7. Instructions for use Rozlytrek (entrectinib) Film -coated granules for oral use These Instructions for Use contain information on how to prepare , take and give Rozlytrek film-coated granules.

Before starting

• Read these Instructions for Use before taking or giving Rozlytrek film-coated granules.
• Ask your healthcare professional to show you how to use Rozlytrek before treatment is started.
• If you have any further questions on the use of Rozlytrek, ask your healthcare professional.

Important Information You Need to Know Before Preparing and Taking or Giving Rozlytrek

• Your healthcare professional should show you how to correctly prepare and take or give a daily dose of Rozlytrek film-coated granules . Always take or give Rozlytrek film-coated granules exactly as your healthcare professional tells you.
• Do not take or give Rozlytrek to someone else until you have been shown how to properly prepare and take or give Rozlytrek.
• Wash your hands before and after using Rozlytrek .
• Check the expir y date and the product for damage before use. Do not use if expired or damaged.
• If partial or to tal vomiting or spitting occurs immediately after giving an administered dose to the patient , consult the patient’s doctor or pharmacist for the next steps.
• Give within 20 minutes of preparation .

Dosing Rozlytrek film-coated granules Your healthcare professional will decide the right dose of Rozlytrek for you or your child.

• Each sachet contains 50 mg of Rozlytrek.
• Do not divide the content of a sachet of film-coated granules to prepare a smaller dose.
• Take Rozlytrek film-coated granules by mouth – sprinkled on soft food. The film -coated g ranules should be sprinkled on one or more spoonfuls of a soft food (such as applesauce, yogurt, or pudding) and taken within 20 minutes of preparation .
• Do not crush or chew the film -coated granules to avoid a bitter taste.
• Drink water after taking the medicine.
• Film -coated granules must not be used with a feeding tube – they could block the tubing.

105 Preparing to give Rozlytrek Step 1. Wash your hands.

Step 2. To give a dose, you will need:

• the number of sachets needed for your prescribed dose
• a paper towel or clean plate
• a clean spoon
• soft food (for example, applesauce, yoghurt, or pudding) Step 3. Count the number of sachets (50 mg each) you will need to give the prescribed dose (Figure A).

Figure A Step 4. Tap the sachet to ensure the film-coated granules are on one side of the sachet.

Hold the side of the sachet where the film-coated granules are tapped and open the sachet by hand or with scissors ( Figure B).

Note: Take care not to cut the film-coated granules with scissors.

Figure B Step 5. Get a spoonful of the soft food and hold the spoonful above a paper towel or clean plate.

Sprinkle the prescribed number of sachets on the spoonful of soft food ( Figure C).

Tap the sachets to make sure all film -coated granules are sprinkled on the food.

Note : You may need to use more than 1 spoonful of soft food to give the prescribed dose.

Figure C 106 Step 6. Take or give the spoonful of food with the film-coated granules sprinkled on it right away (Figure D).

Take or give the spoonful of soft food within 20 minutes after sprinkling the film-coated granules on it if you cannot take or give it right way.

Note: Do not crush or chew to avoid a bitter taste.

If you l eave the film-coated granules in the soft food for too long it may dissolve the coating and cause a bitter taste.

If not taken within 20 minutes , throw away the soft food with the film-coated granules sprinkled on it and prepare a new dose (start at Step 2 ).

Figure D Step 7. Give patients some water after giving Rozlytrek to make sure all the film-coated granules are swallowed ( Figure E).

Patients can be given any meal or drink of their choice after giving Rozlytrek to improve the taste.

Figure E Step 8. Check the mouth to make sure that all of the film-coated granules were swallowed properly (Figure F).

If not all of the film -coated granules were swallowed, give some water.

Figure F Step 9. Wash your hands and the items used to give Rozlytrek. Throw away the disposable items according to your local requirements.

Storing Rozlytrek

• Store below 30°C and keep film-coated granules in the original package to protect from moisture.
• Throw away Rozlytrek if exposed to temperatures higher than 30°C and see section 5 of the leaflet .
• Always keep Rozlytrek out of sight and reach of children.

📄 Package Leaflet – official source

This article reproduces the information in the official package leaflet, as authorised in the European Union. You can consult the original document here: Product information Rozlytrek (PDF, ec.europa.eu).

You can check this medicine at any time in the Union Register of medicinal products (EU number EU/1/20/1460).

⚠️ Important: This article is for information purposes only and does not replace medical advice or the package leaflet inside the medicine box. Read the leaflet carefully before use. For any questions about your treatment, talk to your doctor or pharmacist. If you experience side effects, tell your doctor or pharmacist and report them through your national reporting system.