Prospect: information for the patient

VITRAKVI 20 mg/ml oral solution

larotrectinib

This medicine is subject to additional monitoring, which will expedite the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report these adverse effects.

Read this prospect thoroughly before starting to take this medicine, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed only to you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience adverse effects, consult your doctor, pharmacist, or nurse, even if they do not appear in this prospect. See section 4.
• This prospect has been written as if you were reading it yourself. If you are administering this medicine to your child, replace “your” with “your child” in the entire text.

What VITRAKVI is used for

VITRAKVI contains the active ingredient larotrectinib.

It is used in adults, adolescents, and children to treat solid tumors (cancer) in various parts of the body caused by a change in the neurotrophic tyrosine kinase receptor (NTRK) gene.

VITRAKVI is only used when

• these cancers are advanced or have spread to other parts of the body or when surgery to remove them would cause severe complicationsand
• there are no satisfactory treatment options.

Before VITRAKVI is started, your doctor will perform a test to determine if you have the NTRK gene change.

How VITRAKVI works

In patients with cancer caused by an NTRK gene alteration, the change in the gene causes the body to produce an abnormal protein called TRK fusion protein, which can cause uncontrolled cell growth and cancer. VITRAKVI blocks the action of TRK fusion proteins and can therefore slow down or stop cancer growth. It may also help reduce its size.

If you have any doubts about how VITRAKVI works or why you have been prescribed it, consult your doctor, pharmacist, or nurse.

Do not take VITRAKVI

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

Analysis and checks

VITRAKVI may increase the levels of liver enzymes ALT and AST and bilirubin in the blood. Your doctor will perform blood tests before treatment and during treatment to check the levels of ALT, AST, and bilirubin and evaluate liver function.

Other medicines and VITRAKVI

Inform your doctor, pharmacist, or nurse if you are taking, have taken recently, or may need to take any other medicine. This is because some medicines may affect the way VITRAKVI works or VITRAKVI may affect their action.

Inform your doctor, pharmacist, or nurse in particular if you are taking any of the following medicines:

• some medicines used to treat fungal or bacterial infections, called itraconazole, voriconazole, clarithromycin, telithromycin, and troleandomycin
• a medicine used to treat Cushing's syndrome, called ketoconazole
• some medicines used to treat HIV infection, called atazanavir, indinavir, nelfinavir, ritonavir, saquinavir, rifabutin, and efavirenz
• a medicine used to treat depression, called nefazodone
• some medicines used to treat epilepsy, called phenytoin, carbamazepine, and phenobarbital
• a herbal medicine used to treat depression, called St. John's Wort or hypericum
• a medicine used to treat tuberculosis, called rifampicin
• a medicine used to relieve intense pain, called alfentanil
• some medicines used to prevent rejection after organ transplantation, called cyclosporin, sirolimus, and tacrolimus
• a medicine used to treat abnormal heart rhythms, called quinidine
• some medicines used to treat migraines, called dihydroergotamine and ergotamine
• a medicine used to treat long-lasting pain, called fentanyl
• a medicine used to control involuntary movements or sounds, called pimozide
• a medicine to help you stop smoking, called bupropion
• some medicines to reduce blood sugar levels, called repaglinide and tolbutamide
• a medicine that prevents blood clots, called warfarin
• a medicine used to reduce stomach acid production, called omeprazole
• a medicine used to help control high blood pressure, called valsartan
• a group of medicines used to lower cholesterol, called statins
• hormonal medicines used for contraception, see the section "contraception - for men and women" below.

If any of these apply to you (or you are unsure), speak with your doctor, pharmacist, or nurse.

Taking VITRAKVI with food and drink

Do not eat grapefruit or drink grapefruit juice during treatment with VITRAKVI, as this may increase the amount of VITRAKVI in your body.

Pregnancy and breastfeeding

Pregnancy

If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine. You should not use VITRAKVI while pregnant, as its effect on the fetus is unknown.

Breastfeeding

Do not breastfeed while taking this medicine or for 3 days after the last dose, as it is unknown whether VITRAKVI passes into breast milk.

Contraception - for men and women

You must avoid becoming pregnant while taking this medicine.

If you are of childbearing age, your doctor will perform a pregnancy test before starting treatment.

You must use effective contraceptive methods while taking VITRAKVI and for at least one month after the last dose if:

• you are of childbearing age. If you use hormonal contraceptives, you must also use a barrier method, such as a condom.
• you have sexual intercourse with a woman of childbearing age.

Ask your doctor about the best contraceptive method for you.

Driving, cycling, and using machines

VITRAKVI may cause dizziness or fatigue. If this occurs, do not drive, cycle, or use any type of tools or machines.

VITRAKVI contains:

• 2 mg of sodium benzoate per 1 mL.
• less than 1 mmol (or 23 mg) of sodium per 5 mL; this is essentially "sodium-free".

Follow exactly the administration instructions of this medication as indicated by your doctor or pharmacist. In case of doubt, consult again with your doctor, pharmacist, or nurse.

How much to take

Adults (18 years and older)

• The recommended dose of VITRAKVI is 100 mg (5 ml), twice a day.
• Your doctor will review the dose and modify it as necessary.

Use in children and adolescents

• Your child's doctor will determine the appropriate dose based on their weight and height.
• The maximum recommended dose is 100 mg (5 ml), twice a day.
• Your child's doctor will review the dose and modify it as necessary.

How to take this medication

• VITRAKVI can be taken with or without food.
• Do not eat grapefruit or drink grapefruit juice while taking this medication.
• You will need a 28 mm diameter adapter for the bottle and a syringe that can be used to administer the medication orally. Use a 1 ml syringe with 0.1 ml markings for doses less than 1 ml. Use a 5 ml syringe with 0.2 ml markings for doses of 1 ml or more.
• • Press the cap of the bottle and turn it counterclockwise to open the bottle.
  • Place the adapter for the bottle on the neck of the bottle and ensure it is securely attached.
  • Pull the plunger back on the syringe and then place the syringe in the opening of the adapter. Invert the bottle downwards.
  • Fill the syringe with a small amount of solution by pulling the plunger down; then push the plunger up to expel any large bubbles that may be in the syringe.
  • Pull the plunger down to the mark corresponding to the prescribed dose in ml.
  • Invert the bottle upwards and remove the syringe from the adapter.
  • Insert the syringe into the mouth pointing towards the inner cheek; this will help you swallow the medication naturally. Push the plunger slowly.
  • Replace the cap of the bottle and close it tightly; leave the adapter on the bottle.

If necessary, VITRAKVI can be administered through a nasogastric feeding tube. For detailed information on how to do this, ask your doctor, pharmacist, or nurse.

If you take more VITRAKVI than you should

Inform your doctor, pharmacist, or nurse or go immediately to the hospital. Bring the medication packaging and this leaflet with you.

If you forget to take VITRAKVI

Do not take a double dose to make up for the missed doses or if you vomit after taking the medication. Take the next dose at the usual time.

If you interrupt treatment with VITRAKVI

Do not stop taking this medication without consulting your doctor first. It is essential that you take VITRAKVI for as long as your doctor tells you to.

If you cannot take the medication as prescribed by your doctor, speak immediately with your doctor.

If you have any other questions about the use of this medication, ask your doctor, pharmacist, or nurse.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

You shouldcontact your doctor immediatelyif you experience any of the followingserious side effects:

• dizziness (very common, may affect more than 1 in 10 people), tingling, numbness, or burning sensation in the hands and feet, difficulty walking normally (common, may affect up to 1 in 10 people). These may be symptoms ofnerve problems.

Your doctor may decide to reduce the dose or stop or interrupt treatment.

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

Very common(may affect more than 1 in 10 people):

• you may look pale and feel the heartbeat, which may be symptoms ofanemia
• symptoms similar to the flu, including fever, which may be symptoms ofneutropenia and leucopenia
• feeling or being sick (nausea or vomiting)
• diarrhea
• constipation
• muscle pain (myalgia)
• feeling tired (fatigue)
• increased liver enzymes in blood tests
• weight gain

Common(may affect up to 1 in 10 people)

• you may bleed or bruise more easily, which may be symptoms oftrombocytopenia
• changes in taste (dysgeusia)
• muscle weakness
• increased "alkaline phosphatase" in blood tests (very common in children)

Unknown frequency(does not know how often they occur)

• you may experience a combination of fatigue, pain in the upper right abdomen, loss of appetite, nausea or vomiting, yellowing of the skin or eyes, bruising or bleeding more easily, and dark urine. These may be symptoms ofliver problems

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through thenational notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information about the safety of this medicine.

• Keep this medication out of the sight and reach of children.

• Do not use this medication after the expiration date that appears on the box and on the bottle after CAD. The expiration date is the last day of the month indicated.
• Store in refrigerator (between 2 °C and 8 °C).
• Do not freeze.
• Once the bottle is opened, use the medication within 10 days after opening.
• Do not take the medication if the bottle or the bottle cap shows damage or appears to have leaks.
• Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of VITRAKVI

The active ingredient is larotrectinib.

Each milliliter of oral solution contains 20mg of larotrectinib (in the form of sulfate).

The other components are:

• Purified water
• Hidroxipropil betadex0.69
• Sucralose (E955)
• Sodium citrate (E331)
• Sodium benzoate (E211)
• Strawberry flavor
• Citric acid (E330)

For more information, see “VITRAKVI contains:” in section2.

Appearance of the product and contents of the pack

VITRAKVI is an colorless oral solution, yellow, orange, red, or brown.

Each box contains 2glass bottles with child-resistant caps containing 50ml of oral solution each.

Marketing Authorization Holder

Bayer AG

51368 Leverkusen

Germany

Responsible for manufacturing

Bayer AG

Kaiser-Wilhelm-Allee

51368 Leverkusen

Germany

For more information about this medicine, please contact the local representative of the marketing authorization holder:

Last update of this leaflet:

This medicine has been authorized under 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.

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