VITRAKVI 20 mg/ml ORAL SOLUTION, 2 bottles of 50 ml

Introduction

Package Leaflet: Information for the Patient

VITRAKVI 20 mg/ml Oral Solution

larotrectinib

This medicinal product is subject to additional monitoring, which will allow for quick identification of new safety information. You can help by reporting any side effects you may get. The last section of the leaflet contains information on how to report side effects.

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 in a way that assumes the person taking the medicine is you. If you are giving this medicine to your child, please replace “you” with “your child” throughout this leaflet.

Contents of the pack:

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

1. What is VITRAKVI and what is it used for

What VITRAKVI is used for

VITRAKVI contains the active substance larotrectinib.

It is used in adults, adolescents, and children to treat solid tumors (cancer) in various parts of the body that are caused by a change in the neurotrophic receptor tyrosine kinase (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 is likely to cause serious complications and
• there are no satisfactory treatment options.

Before you start taking VITRAKVI, your doctor will perform a test to determine if you have the change in the NTRK gene.

How VITRAKVI works

In patients with cancer due to an alteration of the NTRK gene, 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 the growth of cancer. It may also help reduce its size.

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

2. What you need to know before you take VITRAKVI

Do not take VITRAKVI

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

Tests 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 to assess liver function.

Other medicines and VITRAKVI

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

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

• 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
• medicines used to treat HIV infection, called atazanavir, indinavir, nelfinavir, ritonavir, saquinavir, rifabutin, and efavirenz
• a medicine used to treat depression, called nefazodone
• medicines used to treat epilepsy, called phenytoin, carbamazepine, and phenobarbital
• a herbal medicine used to treat depression, called St. John's Wort
• a medicine used to treat tuberculosis, called rifampicin
• a medicine used to relieve severe pain, called alfentanil
• medicines used to prevent organ rejection after transplantation, called cyclosporine, sirolimus, and tacrolimus
• a medicine used to treat heart rhythm disorders, called quinidine
• medicines used to treat migraines, called dihydroergotamine and ergotamine
• a medicine used to treat long-term pain, called fentanyl
• a medicine used to control involuntary movements or sounds, called pimozide
• a medicine to help you stop smoking, called bupropion
• medicines to reduce blood sugar levels, called repaglinide and tolbutamide
• a medicine that prevents blood clots, called warfarin
• a medicine used to reduce the amount of acid produced in the stomach, 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), talk to your doctor, pharmacist, or nurse.

Taking VITRAKVI with food and drinks

Do not eat grapefruit or drink grapefruit juice while taking VITRAKVI, as they may increase the amount of VITRAKVI in your body.

Pregnancy and breast-feeding

Pregnancy

If you are pregnant, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. You should not take VITRAKVI while you are pregnant, as its effects on the fetus are unknown.

Breast-feeding

Do not breast-feed while taking this medicine and 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 should also use a barrier method, such as a condom.
• you have sex with a woman of childbearing age.

Ask your doctor about the best contraceptive method for you.

Driving, cycling, and using machines

VITRAKVI may cause you to feel dizzy or tired. If this happens, do not drive, cycle, or use any tools or machines.

VITRAKVI contains:

• 2 mg of sodium benzoate in 1 ml.
• less than 1 mmol (or 23 mg) of sodium per 5 ml; this is essentially “sodium-free”.

3. How to take VITRAKVI

Follow exactly the instructions given to you by your doctor or pharmacist. If you are unsure, ask your doctor, pharmacist, or nurse.

How much to take

Adults (from 18 years)

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

Use in children and adolescents

• Your child's doctor will determine the correct dose for them 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 adjust it as necessary.

How to take this medicine

• VITRAKVI can be taken with or without food.
• Do not eat grapefruit or drink grapefruit juice while taking this medicine.
• You will need a bottle adapter (28 mm diameter) and an oral syringe to take this medicine. 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 and turn the bottle in an anti-clockwise direction to open it.
  • Place the bottle adapter on the neck of the bottle and make sure it is securely attached.
  • Push the plunger completely into the syringe and then place the syringe into the adapter opening. Turn the bottle upside down.
  • 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 inside the syringe.
  • Pull the plunger down to the mark corresponding to the prescribed dose in ml.
  • Turn the bottle right side up and remove the syringe from the adapter.
  • Put the syringe into your mouth, pointing towards the inside of your cheek; this will help you swallow the medicine naturally. Push the plunger slowly.
  • Replace the cap and tighten it; leave the adapter on the bottle.

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

If you take more VITRAKVI than you should

Tell your doctor, pharmacist, or nurse or go to the hospital immediately. Take the medicine pack and this leaflet with you.

If you forget to take VITRAKVI

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

If you stop taking VITRAKVI

Do not stop taking this medicine without talking to your doctor first. It is important that you take VITRAKVI for as long as your doctor tells you to.

If you cannot take the medicine as prescribed by your doctor, talk to your doctor immediately.

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.

You must contact your doctor immediatelyif you experience any of the following serious side effects:

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

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

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):

• you may look pale and feel your heart beating, which may be symptoms of low red blood cell count (anemia)
• flu-like symptoms, including fever, which may be symptoms of low white blood cell count (neutropenia 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 of low platelet count (thrombocytopenia)
• changes in taste (dysgeusia)
• muscle weakness
• increased “alkaline phosphatase” in blood tests (very common in children)

Frequency not known(frequency cannot be estimated from the available data)

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

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. Storage of VITRAKVI

• 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 bottle after EXP. The expiry date is the last day of the month shown.
• Store in a refrigerator (2°C to 8°C).
• Do not freeze.
• Once the bottle is opened, the medicine must be used within 10 days.
• Do not take the medicine if the bottle or cap appears to be damaged or leaking.
• 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

VITRAKVI composition

The active ingredient is larotrectinib.

Each ml of oral solution contains 20 mg of larotrectinib (as sulfate).

The other components are:

• Purified water
• Hydroxypropyl betadex 0.69
• Sucralose (E 955)
• Sodium citrate (E 331)
• Sodium benzoate (E 211)
• Strawberry flavor
• Citric acid (E 330)

For more information, see "VITRAKVI contains:" in section 2.

Product appearance and container contents

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

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

Marketing authorization holder

Bayer AG

51368 Leverkusen

Germany

Manufacturer

Bayer AG

Kaiser-Wilhelm-Allee

51368 Leverkusen

Germany

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

Date of last revision of this prospectus:

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

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

Detailed information about this medication is available on the European Medicines Agency website: https://www.ema.europa.eu.