Vitrakvi 20 mg/ml oral solution, 2 bottles of 50 ml

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

VITRAKVI 20 mg/ml oral solution

larotrectinib

This medicinal product is subject to additional monitoring, which will enable rapid identification of new information on its safety. You can help by reporting any adverse reactions you may experience. Information on how to report adverse reactions is included at the end of section 4.

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

• Keep this leaflet as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you, because it could harm them.
• If you experience any adverse reactions, consult your doctor, pharmacist, or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.
• This leaflet has been written as if the person taking the medicine is reading it. If you are administering this medicine to your child, replace “your” with “your child’s” throughout the text.

Contents of the leaflet:

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

1. What VITRAKVI is and what it is used for

What VITRAKVI is used for

VITRAKVI contains the active substance larotrectinib.

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

VITRAKVI is used only 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 available.

Before you are started on VITRAKVI, your doctor will perform a test to determine whether you have the NTRK gene alteration.

How VITRAKVI works

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

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

2. What you need to know before starting VITRAKVI

Do not take VITRAKVI

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

Tests and monitoring

VITRAKVI may increase blood levels of the liver enzymes ALT and AST, as well as bilirubin. Your doctor will perform blood tests before and during treatment to monitor ALT, AST, and bilirubin levels and assess liver function.

Other medicines and VITRAKVI

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

In particular, inform your doctor, pharmacist, or nurse 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
• an herbal medicine used to treat depression, called St. John’s wort (hypericum)
• a medicine used to treat tuberculosis, called rifampicin
• a medicine used to relieve severe pain, called alfentanil
• medicines used to prevent organ transplant rejection, 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 used to lower blood sugar levels, called repaglinide and tolbutamide
• a medicine used to prevent 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 contraceptives; see the section “Contraception – for men and women” below.

If any of these apply to you (or if you have any doubts), speak with your doctor, pharmacist, or nurse.

Taking VITRAKVI with food and drinks

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

Pregnancy and breastfeeding

Pregnancy

If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine. You should not use VITRAKVI during pregnancy, as its effects on the unborn baby are 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 potential, your doctor should perform a pregnancy test before starting treatment.

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

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

Ask your doctor about the most suitable contraceptive method for you.

Driving, cycling, and using machines

VITRAKVI may cause dizziness or fatigue. If this occurs, do not drive, cycle, or operate any tools or machinery.

VITRAKVI contains:

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

3. How to take VITRAKVI

Follow exactly the administration instructions for this medicine given by your doctor or pharmacist. If in doubt, consult your doctor, pharmacist, or nurse again.

How much to take

Adults (from 18 years of age)

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

Use in children and adolescents

• Your child’s doctor will determine the appropriate dose for them based on their weight and height.
• The maximum recommended dose is 100 mg (5 ml), twice daily.
• Your child’s doctor will review the dose and adjust it as necessary.

How to take this medicine

• VITRAKVI may be taken with or without food.
• Do not eat grapefruit or drink grapefruit juice while taking this medicine.
• This medicine requires a bottle adapter (28 mm diameter) and an oral dosing syringe. 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 down on the bottle cap and turn it counterclockwise to open the bottle.
  • Place the bottle adapter onto the neck of the bottle and make sure it is securely attached.
  • Push the syringe plunger fully in, then attach the syringe to the opening of the adapter. Invert the bottle upside down.
  • Draw a small amount of solution into the syringe by pulling down the plunger; then push the plunger up to expel any large air bubbles inside the syringe.
  • Pull down the plunger to the mark corresponding to the dose in ml prescribed by your doctor.
  • Turn the bottle upright and remove the syringe from the adapter.
  • Insert the syringe into the mouth, directing it towards the inside of the cheek; this will help you swallow the medicine naturally. Slowly push the plunger.
  • Replace the bottle cap and close it tightly; leave the adapter on the bottle.

If necessary, VITRAKVI may be administered via 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 a hospital. Take the medicine packaging and this leaflet with you.

If you forget to take VITRAKVI

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

If you stop taking VITRAKVI

Do not stop treatment with this medicine without first consulting your doctor. It is important that you take VITRAKVI for as long as your doctor instructs.

If you are unable to take the medicine as prescribed by your doctor, speak to your doctor immediately.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

You should contact your doctor immediately if you experience any of the following serious adverse effects:

• dizziness (very common adverse effect, may affect more than 1 in 10 people), tingling, numbness, or burning sensation in the hands and feet, difficulty walking normally (common adverse effect, 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.

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

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

• you may look pale and feel your heart pounding, which may be symptoms of low red blood cells (anaemia)
• flu-like symptoms, including fever, which may be symptoms of low white blood cells (neutropenia and leucopenia)
• feeling sick or being sick (nausea or vomiting)
• diarrhoea
• 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 a reduced number of platelets (thrombocytopenia)
• changes in taste sensation (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 adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting adverse 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 on the bottle after EXP. The expiry date refers to the last day of the month indicated.

• Store in a refrigerator (between 2 °C and 8 °C).

• Do not freeze.

• After opening the bottle, the medicine should be used within 10 days of opening.

• Do not take the medicine if the bottle or the bottle's screw cap is damaged or appears to be leaking.

• Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to properly dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of VITRAKVI

The active substance 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 flavour
• Citric acid (E 330)

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

Appearance of the product and contents of the pack

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

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

Marketing Authorisation Holder

Bayer AG

51368 Leverkusen

Germany

Manufacturer

Bayer AG

Kaiser-Wilhelm-Allee

51368 Leverkusen

Germany

More information on this medicine is available upon request from the local representative of the Marketing Authorisation Holder:

Date of the most recent review of this leaflet:

This medicinal product has been authorised under a "conditional approval". This type of approval means that further information on this medicinal product is expected.

The European Medicines Agency will review the new information on this medicinal product at least once a year, and this leaflet will be updated as necessary.

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