VITRAKVI 20 mg/ml ORAL SOLUTION, 1 bottle of 100 ml

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 a transplant, called cyclosporine, sirolimus, and tacrolimus
• a medicine used to treat irregular heartbeats, 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 lower 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 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 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 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 dizziness or fatigue. If this happens, do not drive, cycle, or use any tools or machines.

VITRAKVI contains:

• sucrose: may be harmful to teeth. If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.
• 22 mg of sorbitolin 1 ml. Sorbitol is a source of fructose. If your doctor has told you that you or your child have an intolerance to some sugars, or have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which the patient cannot break down fructose, consult your doctor before taking this medicine.
• less than 1 mmol (or 23 mg) of sodiumper 5 ml; this is, essentially “sodium-free”.
• 1.2 mg of propylene glycolin 1 ml. If the baby is less than 4 weeks old, consult your doctor or pharmacist before giving this medicine, especially if the baby has been given other medicines that contain propylene glycol or alcohol.
• parahydroxybenzoate: may cause allergic reactions (possibly delayed)

3. How to take VITRAKVI

Follow exactly the instructions for administration of this medicine given by your doctor or pharmacist. If you are unsure, consult 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 appropriate 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 in diameter) and an oral syringe that can be used to administer medicines by mouth. 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 bottle cap and turn it counterclockwise to open the bottle.
  • Place the bottle adapter on the bottle neck and make sure it is securely attached.
  • Push the plunger completely into the syringe and then place the syringe into the adapter opening. Invert the bottle.
  • 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.
  • Invert the bottle and remove the syringe from the adapter.
  • Place the syringe in your mouth, pointing towards the inside of your 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 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

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 consulting your doctor first. It is important that you take VITRAKVI for as long as your doctor tells you.

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:

• dizziness (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 fatigue, 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 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 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 stated.
• Store in a refrigerator (between 2 °C and 8 °C).
• Do not freeze.
• Once the bottle is opened, the medicine must be used within 30 days.
• Do not take the medicine if the bottle or the 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 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
• Sucrose
• Hydroxypropyl betadex 0.69
• Glycerol (E 422)
• Sorbitol (E 420)
• Sodium citrate (E 331)
• Sodium dihydrogen phosphate dihydrate (E 339)
• Citric acid (E 330)
• Propylene glycol (E 1520)
• Potassium sorbate (E 202)
• Methylparaben (E 218)
• Citrus fruit flavor
• Natural flavor

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

Product appearance and container contents

VITRAKVI is a clear, yellow to orange oral solution.

Each box contains 1 child-resistant glass bottle containing 100 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 medicinal product by contacting the local representative of the marketing authorization holder:

Date of last revision of this prospectus:

This medicinal product has been authorized under a "conditional approval" regime. This approval regime means that further information on this medicinal product is awaited.

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

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