ROZLYTREK 100 mg HARD CAPSULES

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, changes in mental status
• you have had bone fractures or conditions that may increase the risk of bone fractures, called 'osteoporosis' or 'osteopenia'
• you are taking medication to lower uric acid in the blood
• you have heart failure (when your heart has difficulty pumping blood to supply oxygen to the rest of your body) - signs may include cough, difficulty breathing, and swelling in legs and arms.
• you have had heart problems or electrical conduction problems in the heart called 'prolonged QTc interval' - this is shown on an electrocardiogram (ECG) or by low levels of electrolytes in the blood.
• you have a hereditary problem called "galactose intolerance", "congenital lactase deficiency", or "glucose-galactose malabsorption"

If you have any of the above conditions (or are not sure), talk to your doctor or pharmacist 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 may affect the way other medicines work. Similarly, other medicines may affect the way Rozlytrek works.

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

• for fungal infections (antifungals) - such as ketoconazole, itraconazole, voriconazole, posaconazole
• for HIV/AIDS infection - such as ritonavir or saquinavir
• for depression - such as paroxetine, fluvoxamine, or herbal medicine for depression - St. John's Wort
• to stop seizures or fits - such as phenytoin, carbamazepine, or phenobarbital
• for tuberculosis - such as rifampicin, rifabutin
• for solid tumors and blood cancers - topotecan, lapatinib, mitoxantrone, apalutamide, or methotrexate
• for joint inflammation or autoimmune joint diseases (rheumatoid arthritis) - methotrexate
• for migraines - ergotamine
• for severe pain - fentanyl
• for mental illnesses (psychosis) or Tourette's syndrome - pimozide
• for irregular heart rhythm - quinidine
• to prevent blood clots - warfarin or dabigatran etexilate
• for acid reflux (heartburn) - cisapride or omeprazole
• to lower cholesterol in the blood - atorvastatin, pravastatin, or rosuvastatin
• to suppress your body's immune system or prevent your body from rejecting a transplanted organ - sirolimus, tacrolimus, or cyclosporin
• to lower blood sugar levels - repaglinide or tolbutamide
• for high blood pressure - bosentan, felodipine, nifedipine, or verapamil
• for inflammation or nausea - dexamethasone

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

Using Rozlytrek with food or drinks

Do not drink grapefruit juice or eat grapefruit or bitter oranges while taking this medicine. This can increase the amount of the medicine in your blood to harmful levels.

Pregnancy, breastfeeding, and fertility

Women and contraceptive measures

You must avoid becoming pregnant while taking this medicine, because it may harm your unborn baby. If you can become pregnant, you must use a highly effective method of contraception:

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

Rozlytrek may reduce the effect of contraceptive medicines (birth control pills or hormonal contraceptives). You should use another reliable method of contraception, such as a barrier method (e.g., condoms).

Talk to your doctor about the contraceptive methods that are suitable for you and your partner.

Men and contraceptive measures

Your partner must avoid becoming pregnant while you are taking this medicine, because it may harm your unborn baby. If your partner can become pregnant, you must use a highly effective method of contraception:

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

Talk to your doctor about the contraceptive methods that are suitable for you and your partner.

Pregnancy

• Do not take Rozlytrek if you are pregnant, because it may harm your unborn baby.
• If you become pregnant while taking this medicine or in the 5 weeks following your last dose, tell your doctor immediately.

Breastfeeding

Do not breastfeed while taking this medicine. It is not known whether Rozlytrek passes into breast milk and may harm your baby.

Driving and using machines

Rozlytrek may affect your ability to drive, ride a bike, or use machines. The following side effects may occur while taking Rozlytrek:

• blurred vision
• feeling tired, dizzy, or faint
• changes in mental status, confusion, or seeing things that are not there (hallucinations).

If this happens, do not drive, ride a bike, or use heavy machinery until you feel better. Ask your doctor or pharmacist if you can drive, ride a bike, or use machines.

Rozlytrek contains:

• Lactose- a type of sugar. If your doctor has told you that you have an intolerance to some sugars, talk to them before taking this medicine.
• Orange Yellow FCF (E-110) only in 200 mg hard capsules.It is a coloring agent that may cause allergic reactions.

3. How to take Rozlytrek

Follow exactly the instructions of your doctor or pharmacist. If you are not sure, talk to your doctor or pharmacist again.

How much to take

Adults

• The recommended dose is 3 capsules of 200 mg once a day (this is equivalent to a total dose of 600 mg).
• If you feel unwell, your doctor may reduce your dose, interrupt your treatment for a short period, or stop your treatment completely.

Adolescents and children over 1 month of age:

Your doctor will calculate the correct dose for you - based on the child's height and weight.

Your doctor will review the dose and change it as necessary.

Rozlytrek is also available as a film-coated granule in a sachet for patients who cannot swallow capsules but can eat soft foods.

How to take it

Rozlytrek can be taken with or without food.

There are two ways your doctor may tell you to take Rozlytrek capsules:

• Swallow each capsule whole. Do not crush or chew the capsules.
• Take it prepared as an oral suspension (using a syringe) or, if necessary, through a feeding tube.

Read the 'Instructions for Use' at the end of the package leaflet.

Read and follow carefully the 'Instructions for Use' at the end of the package leaflet on how to take and administer Rozlytrek. It provides detailed information on how to prepare, measure, take, or administer Rozlytrek prepared as an oral suspension:

• by mouth, or
• through a feeding tube (such as a gastric or nasogastric tube).

If you vomit after taking Rozlytrek

Capsules

If you vomit immediately after taking a dose of Rozlytrek, take another dose.

Capsules administered as an oral suspension

If you vomit or have total or partial regurgitation immediately after taking the dose, talk to your doctor or pharmacist about what to do.

If you take more Rozlytrek than you should

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

If you forget to take Rozlytrek

• If it is more than 12 hours until your next dose, take the missed dose as soon as you remember.
• If it is 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 that you take this medicine every day for the time your doctor has prescribed.

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 occur with this medicine.

Serious side effects

Tell your doctor immediately if you experience any of the following serious side effects. Your doctor may reduce your dose, interrupt your treatment for a short period, or stop your treatment completely if:

• you have a cough, difficulty breathing, or swelling in your legs or arms (fluid retention) - these may be signs of heart problems (congestive heart failure)
• you feel confused, changes in mood, memory problems, or see things that are not there (hallucinations)
• you feel dizzy or faint or feel that your heart is beating irregularly and quickly - this may be a symptom of an abnormal heart rhythm
• 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 levels of uric acid in your blood

Tell your doctor immediately if you notice any of the above side effects.

Other side effectsTell your doctor, pharmacist, or nurse if you experience any of the following side effects:Very common:may affect more than 1 in 10 people:

• fatigue
• altered taste
• feeling unsteady or dizzy
• blurred vision
• swelling
• diarrhea or constipation
• feeling or being sick
• difficulty swallowing
• abnormal sensation, numbness, tingling, pricking, or burning
• skin rash
• difficulty breathing
• 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
• unpleasant abnormal sensation in arms or legs
• loss of muscle control, unsteadiness when walking
• changes in normal sleep patterns
• lung infection
• urinary tract infection
• inability to empty the bladder completely
• loss of appetite
• low blood pressure
• decrease in the number of a type of white blood cell called neutrophils
• decrease in the number of red blood cells (anemia)
• increase in the levels of certain liver enzymes (AST/ALT) in the blood
• increase in the levels of creatinine in the blood (a substance that is normally eliminated in the urine through the kidneys)

Common:may affect up to 1 in 10 people:

• mood changes
• dehydration
• fluid in the lungs
• fainting
• skin sensitivity to sunlight

Uncommon:may affect up to 1 in 100 people:

Changes in certain chemicals in your blood, due to the rapid breakdown of tumor cells - this may cause damage to organs, including kidneys, heart, and liver.

• inflammation of the heart muscle.

Tell your doctor, pharmacist, or nurse if you experience any of the above side effects.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report side effects directly through 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. Storage of 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 blister after EXP. The expiry date refers to the last day of the month shown.
• Store the capsules in the original package and keep the bottle tightly closed to protect from moisture.
• After preparation of the oral suspension, store below 30°C and use within 2 hours of preparation.
• Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Contents and Additional Information

Composition of Rozlytrek

The active ingredient is entrectinib.

Rozlytrek 100 mg: each capsule contains 100 mg of entrectinib. Rozlytrek 200 mg: each capsule contains 200 mg of entrectinib.

The other ingredients are:

• Capsule content:tartaric acid (E334), lactose (see section 2 "Rozlytrek contains lactose"), hypromellose (E464), crospovidone (E1202), microcrystalline cellulose (E460), anhydrous colloidal silica (E551), magnesium stearate (E470b).
• Capsule shell:hypromellose (E464), titanium dioxide (E-171), yellow iron oxide (E172; for Rozlytrek 100 mg capsule), orange yellow FCF (E-110; for Rozlytrek 200 mg capsule. See section 2 "Rozlytrek contains orange yellow FCF (E110)").
• Printing ink:shellac, propylene glycol, aluminum lake indigo carmine (E-132).

Appearance of Rozlytrek and Container ContentsRozlytrek 100 mg hard opaque yellow capsules with ENT 100 printed in blue ink on the body.

Rozlytrek 200 mg hard opaque orange capsules with ENT 200 printed in blue ink on the body.

The capsules are presented in bottles containing:

• 30 hard capsules of Rozlytrek 100 mg, or
• 90 hard capsules of Rozlytrek 200 mg.

Marketing Authorization Holder

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

Manufacturer

Roche Pharma AG

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet

This medicine has been authorized with a "conditional approval". This type of approval means that more information is expected to be obtained about this medicine.

The European Medicines Agency will review the new information about this medicine at least once a year and this leaflet will be updated as necessary.

Other Sources of Information

Detailed information about this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu,

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1. Instructions for Use

Rozlytrek

(entrectinib)

Oral capsules

(administered as a whole capsule or as an oral suspension)

These instructions for use contain information on how to prepare, take, and administer Rozlytrek capsules.

Rozlytrek capsules can be swallowed whole or prepared as a suspension (in water or milk) and administered orally or through a gastric or nasogastric tube.

Before Starting

• Read these Instructions for Usebefore taking or administering Rozlytrek capsules.

• Ask your doctor to show you how to use Rozlytrek before starting treatment.
• If you have any questions about using Rozlytrek, ask your doctor.

Important Information You Need to Know Before Preparing, Taking, or Administering Rozlytrek

• Your doctor should teach you how to prepare and take or administer Rozlytrek capsules correctly. Follow your doctor's instructions for administering Rozlytrek exactly.

• Do not take oradminister Rozlytrek to another person until you have been shown how to prepare and take or administer Rozlytrek correctly.
• Wash your hands before and after using Rozlytrek. Do nottouch your eyes, nose, or mouth during the preparation of the oral suspension.
• Check the expiration date and for any damage to the product before using it. Do notuse it if it has expired or is damaged.
• For whole capsules, if you vomit immediately after taking the dose of Rozlytrek, take another dose.
• For capsules administered as an oral suspension, if you vomit or have partial or total regurgitation immediately after administering a dose, consult your doctor or pharmacist for further instructions.
• The oral suspension should be administered within 2 hours of preparation.

Administration of Rozlytrek Capsules Orally

Your doctor will decide the correct daily dose of Rozlytrek for you or your child.

• Swallow the capsules whole, with or without food, with a little water, as directed by your doctor.
• Do not crush or chew the capsules.

Administration of Rozlytrek as a Liquid Suspension – Orally or Through a Gastric/Nasogastric Tube

If you or your child cannot swallow whole capsules, Rozlytrek capsules can be prepared as a suspension (in water or milk) and administered orally or through a feeding tube.

Your doctor will tell you the number of capsules to use, the exact amount of liquid (water or milk) to mix with the contents of the capsule(s) to prepare the suspension, and the exact amount (ml) of suspension to extract to achieve the prescribed dose of Rozlytrek to take or administer.

In Table 1, the prescribed dose, the number and concentration of capsules needed, the amount of water or milk to mix with the contents of the capsule(s) to prepare the suspension, and the amount of suspension to extract to achieve the prescribed dose are shown.

It is possible that you will need to measure a smaller amount of suspension than you prepared to take or administer the correct prescribed dose of Rozlytrek.

To prepare the suspension, you will need:

• The number of capsules indicated by your doctor
• A clean, empty glass (not included in the packaging)
• A glass of drinking water or milk at room temperature (below 30°C)
• An oral syringe (provided by your pharmacist) with 0.5 ml gradations
• A paper towel

Preparation of Rozlytrek Suspension

Oral Administration

Administration Through a Gastric or Nasogastric Tube

Storage of Rozlytrek

• Keep below 30°C in the original packaging and keep the bottle tightly closed to protect it from moisture.
• Discard Rozlytrek if it is exposed to temperatures above 30°C and follow the instructions for disposal indicated in Step C1 and in Section 5 of the package insert.
• After preparing the oral suspension, keep below 30°C and use within 2 hours of preparation.
• Always keep Rozlytrek out of sight and reach of children.