VITRAKVI 100 mg HARD CAPSULES

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 do 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 how VITRAKVI works or VITRAKVI may affect how 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, such as itraconazole, voriconazole, clarithromycin, telithromycin, and troleandomycin
• a medicine used to treat Cushing's syndrome, called ketoconazole
• medicines used to treat HIV infection, such as atazanavir, indinavir, nelfinavir, ritonavir, saquinavir, rifabutin, and efavirenz
• a medicine used to treat depression, called nefazodone
• medicines used to treat epilepsy, such as 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, such as cyclosporin, sirolimus, and tacrolimus
• a medicine used to treat irregular heart rhythms, called quinidine
• medicines used to treat migraines, such as 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, such as 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 section “Contraception – for men and women” below.

If any of these apply to you (or you are not sure), talk to your doctor, pharmacist, or nurse.

Taking VITRAKVI with food and drink

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 unborn baby are not known.

Breast-feeding

Do not breast-feed while taking this medicine and for 3 days after the last dose, as it is not known if 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 do a pregnancy test before you start treatment.

You must use effective contraception while taking VITRAKVI and for at least 1 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.

3. How to take VITRAKVI

Take this medicine exactly as your doctor or pharmacist has told you. If you are not sure, ask your doctor, pharmacist, or nurse.

How much to take

Adults (18 years and over)

• The recommended dose of VITRAKVI is 100 mg (1 x 100 mg capsule or 4 x 25 mg capsules), twice a day.
• Your doctor will check your dose and change it if necessary.

Use in children and adolescents

• Your child's doctor will decide the right dose for them based on their weight and height.
• The maximum recommended dose is 100 mg (1 x 100 mg capsule or 4 x 25 mg capsules), twice a day.
• Your child's doctor will check their dose and change it if necessary.

An oral solution of VITRAKVI is available for patients who cannot swallow the capsules.

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.
• Swallow the VITRAKVI capsules whole with a glass of water. Do not open, chew, or crush the capsule, as it has a very bitter taste.

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 a forgotten dose 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 your doctor has prescribed, 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 the 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 the blood
• 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 the blood (very common in children)

Frequency not known(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 blister after EXP. The expiry date refers to the last day of that month.
• This medicine does not require any special storage conditions.
• Do not use this medicine if you notice that the capsules are damaged.
• Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What VITRAKVI contains

The active substance is larotrectinib.

Each VITRAKVI 25 mg capsule contains 25 mg of larotrectinib (as sulfate).

Each VITRAKVI 100 mg capsule contains 100 mg of larotrectinib (as sulfate).

The other ingredients are:

Capsule shell:

• Gelatin
• Titanium dioxide (E 171)

Printing ink:

• Shellac, bleached and de-waxed
• Indigo carmine aluminum lake (E 132)
• Titanium dioxide (E 171)
• Propylene glycol (E 1520)
• Dimeticone 1000

Appearance and pack contents

• VITRAKVI 25 mg is a white, opaque hard gelatin capsule (18 mm long x 6 mm wide), with blue printing of the Bayer cross and "25 mg" on the body of the capsule
• VITRAKVI 100 mg is a white, opaque hard gelatin capsule (22 mm long x 7 mm wide), with blue printing of the Bayer cross and "100 mg" on the body of the capsule

Each carton contains 1 child-resistant plastic bottle containing 56 hard gelatin capsules.

Marketing authorization holder

Bayer AG

51368 Leverkusen

Germany

Manufacturer

Bayer AG

Kaiser-Wilhelm-Allee

51368 Leverkusen

Germany

You can get more information about this medicine from your local representative of the marketing authorization holder:

Date of last revision of this leaflet:

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

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

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