• 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.

1. What Rozlytrek is and what it is used for
2. What you need to know before you take Rozlytrek
3. How to take Rozlytrek
4. Possible side effects
5. How to store Rozlytrek
6. Contents of the pack and other information

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

Rozlytrek is used to treat either:

• adults and children 12 years of age and older with solid tumour (cancer) in various parts of the body that is caused by a change in the neurotrophic tyrosine receptor kinase (NTRK) gene, or
• adults with a type of lung cancer called ‘non-small cell lung cancer’ (NSCLC) that is caused by a change in the ROS1 gene.

NTRK gene fusion-positive solid tumour cancer

It is used when:

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

ROS1-positive non -small cell lung cancer (NSCLC)

It is used if your lung cancer:

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

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

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

• 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.

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

• you have recently experienced memory loss, confusion, hallucinations, or mental status changes
• you have a history of fractured bones, or conditions which may increase your risk of breaking bones, called ‘osteoporosis’ or ‘osteopaenia’
• you take medication to lower the levels of uric acid in your blood
• you have heart failure (an inability for your heart to adequately pump blood to supply oxygen to the body) – signs can include cough, shortness of breath, and swelling in your legs or arms
• you have or had heart disorders or a heart conduction problem called ‘prolonged QTc interval’ – this is shown on an ‘electro-cardiogram’ (ECG), or low levels of electrolytes (potassium, magnesium, calcium or phosphorus) in your blood
• you have an inherited problem called ‘galactose intolerance’, ‘congenital lactase deficiency’ or ‘glucose-galactose malabsorption’.

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:

• medicines for fungal infections (anti-fungals) – such as ketoconazole, itraconazole, voriconazole, posaconazole
• medicines to treat Acquired Immune Deficiency Syndrome (AIDS)/Human immunodeficiency virus (HIV) infection – such as ritonavir or saquinavir
• a herbal medicine for depression – St. John’s Wort
• medicines to stop seizures or fits (anti-epileptics) – such as phenytoin, carbamazepine, or phenobarbital
• medicines for tuberculosis – such as rifampicin, rifabutin
• medicines to treat solid cancers and blood cancer – topotecan, lapatinib, mitoxantrone, apalutamide, methotrexate
• a medicine for inflammation of joints or joint autoimmune disease (rheumatoid arthritis) – methotrexate
• a medicine for migraine-type headaches – ergotamine
• a medicine for relief of severe pain – fentanyl
• a medicine for mental illness (psychoses) or involuntary movements and sounds, also called Tourette Syndrome – pimozide
• a medicine for irregular heart rate –quinidine
• medicines to prevent formation of blood clots – warfarin, dabigatran etexilate
• medicines for gastric reflux (heartburn) – cisapride, omeprazole
• medicines to reduce blood cholesterol – atorvastatin, pravastatin, rosuvastatin
• medicines to suppress your body’s immune system, or prevent the body from rejecting an organ transplant – sirolimus, tacrolimus, cyclosporin,
• medicines for depression – paroxetine, fluvoxamine
• medicines to reduce blood sugar levels – repaglinide, tolbutamide
• medicines for high blood pressure – bosentan, felodipine, nifedipine, verapamil.

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

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

Women and contraception

You should not become 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 (pills or implanted hormonal contraceptives). You should use another reliable method of birth control such as a barrier method (e.g. condom) so you do not become pregnant while you are taking Rozlytrek and for 5 weeks after you stop treatment.

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

Men and contraception

Your female partner should not become 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.

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.

Rozlytrek may affect your ability to drive or use machines. Rozlytrek may cause you to:

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

If this happens, you should not drive, use a bicycle, or operate heavy machinery until your symptoms resolve. Talk to your doctor or pharmacist about whether it is okay for you to drive or use machines.

• lactose (a type of sugar). If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
• sunset yellow FCF (E110) in 200 mg hard capsules only. This is a colouring agent, which may cause allergic reactions.

Adults

• The recommended dose is 3 capsules of 200 mg once a day (total amount 600 mg).
• If you feel unwell, sometimes your doctor may lower your dose, stop treatment for a short time or stop treatment completely.

Children

• Rozlytrek can be used in children 12 years of age and older.
• Your doctor will work out the correct dose to use – this will depend on the height and weight of the child.

Take Rozlytrek by mouth – with or without food. Swallow each capsule whole. Do not open or dissolve the capsules since the contents of the capsule are very bitter.

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

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 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. Then take your next dose at the usual time.
• Do not take a double dose to make up for a missed dose.

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

Tell your doctor straight away if you notice any of the following after having taken Rozlytrek. Your doctor may lower your dose, stop your treatment for a short time or stop your treatment completely:

• you have cough, shortness of breath, and swelling in your legs or arms (fluid retention). These can be signs of heart problems
• you feel confused, have changes in mood, memory problems or hallucinations (see things that are not there)
• you feel dizzy or light-headed, or feel your heart beating irregularly or fast, as this may be a sign of an abnormal heart rhythm
• you notice any joint pain, bone pain, deformities or changes in your ability to move
• you have kidney problems or arthritis, as this may be the result of high uric acid levels in your blood.

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
• constipation
• changes in taste
• feeling unsteady or dizzy
• swelling
• diarrhoea
• feeling sick
• abnormal sense of touch which feels like itching, tingling or burning sensation
• lack of enough red blood cells (anaemia)
• shortness of breath
• weight gain
• increased blood level of creatinine (a substance normally eliminated by the kidneys into the urine)
• pain including back pain, neck pain, musculoskeletal pain, pain in limbs
• vomiting
• cough
• fever
• muscle pain
• joint pain
• headache
• low blood pressure
• increased blood levels of certain liver enzymes (AST/ALT)
• 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
• muscle weakness
• decreased appetite
• blurred vision
• rash
• decreased number of a type of white blood cell called neutrophils
• stomach pain
• inability to empty your bladder completely
• difficulty swallowing.

Common: may affect up to 1 in 10 people:

• mood disorders
• dehydration
• fluid in your lungs
• fainting
• increased sensitivity of the skin to sunlight

Uncommon: may affect less than 1 in 100 people:

• changes in certain chemicals in your blood caused by rapid breakdown of tumour cells, which may cause damage to organs, including the kidneys, heart, and liver.

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

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 (see details below). By reporting side effects you can help provide more information on the safety of this medicine.

United Kingdom

or search for MHRA Yellow Card in the Google Play or Apple App Store

The active substance is entrectinib.

Rozlytrek 100 mg: each capsule contains 100 mg entrectinib

Rozlytrek 200 mg: each capsule contains 200 mg entrectinib

The other ingredients are:

• Capsule content: tartaric acid, lactose (see section 2 ‘Rozlytrek contains lactose’), hypromellose, crospovidone, microcrystalline cellulose, colloidal anhydrous silica, magnesium stearate.
• Capsule shell: hypromellose, titanium dioxide (E171), yellow iron oxide (E172; for Rozlytrek 100 mg capsule), sunset yellow FCF (E110; for Rozlytrek 200 mg capsule). See section 2 ‘Rozlytrek contains sunset yellow FCF (E110)’.
• Printing ink: shellac, propylene glycol, indigo carmine aluminium lake (E132).

Rozlytrek 100 mg hard capsules are opaque yellow with ENT 100 imprinted in blue on the body.

Rozlytrek 200 mg hard capsules are opaque orange with ENT 200 imprinted in blue on the body.

The capsules are provided in bottles containing either:

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

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder: