Patient leaflet - Vitrakvi

B. PACKAGE LEAFLET

Package leaflet: Information for the patient

VITRAKVI 25 mg hard capsules

VITRAKVI 100 mg hard capsules larotrectinib

This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for 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 as though the person taking the medicine is reading it. If you are giving this medicine to your child, please replace “you” with “your child” throughout.

What is in this leaflet:

1. What VITRAKVI is and what it is used for
2. What you need to know before you take VITRAKVI
3. How to take VITRAKVI
4. Possible side effects
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 NTRK gene (neurotrophic tyrosine receptor kinase).

VITRAKVI is only used when

– these cancers are advanced or have spread to other parts of the body or if a surgery to remove the cancer is likely to cause severe complications and
– there are no satisfactory treatment options.

Before you are given VITRAKVI, your doctor will do a test to check if you have the change in the NTRK gene.

How VITRAKVI works

In patients whose cancer is due to an altered NTRK gene, the change in the gene causes the body to make 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 so may slow or stop the growth of the cancer. It may also help to shrink the cancer.

If you have any questions on how VITRAKVI works or why it has been prescribed for you, 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 can increase the amount of the liver enzymes ALT and AST in your blood. Your doctor will do blood tests before and during treatment to check the level of ALT and AST and check how well your liver is working.

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 how other medicines work.

In particular, tell 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, troleandomycin
– a medicine used to treat Cushing’s syndrome called ketoconazole
– medicines used to treat HIV infection called atazanavir, indinavir, nelfinavir, ritonavir, saquinavir, rifabutin, efavirenz
– a medicine used to treat depression called nefazodone
– medicines used to treat epilepsy called phenytoin, carbamazepine, phenobarbital
– a herbal medicine used to treat depression called St. John’s wort
– a medicine used to treat tuberculosis called rifampicin
– a medicine used for strong pain relief called alfentanil
– medicines used to prevent organ rejection after an organ transplant called ciclosporin, sirolimus,

tacrolimus

– a medicine used to treat an abnormal heart rhythm called quinidine
– medicines used to treat migraines called dihydroergotamine, 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, 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 help lower cholesterol called statins
– hormonal medicines used for contraception, see section “contraception – for men and women” below.

If any of the above 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. This is because it 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 use VITRAKVI during pregnancy since the effect of VITRAKVI on the unborn is not known.

Breast-feeding

Do not breast-feed while taking this medicine and for 3 days after the last dose. This is because it is not known if VITRAKVI passes into breast milk.

Contraception – for men and women

You should avoid getting pregnant while taking this medicine.

If you are able to become pregnant, your doctor should do a pregnancy test before you start treatment.

You must use effective methods of contraception while taking VITRAKVI and for at least 1 month after the last dose, if

– you are able to become pregnant. If you use hormonal contraceptives, you should also use a barrier method, such as a condom.
– you have sex with a woman able to become pregnant.

Ask your doctor about the best method of contraception for you.

Driving, cycling and using machines

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

3. How to take VITRAKVI

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor, pharmacist or nurse if you are not sure.

How much to take

Adults (from 18 years)

– The recommended dose of VITRAKVI is 100 mg (1 capsule of 100 mg or 4 capsules of 25 mg), two times a day.
– Your doctor will review your dose and change it as needed.

Children and adolescents

– Your child’s doctor will work out the right dose for your child based on their height and weight.
– The maximum recommended dose is 100 mg (1 capsule of 100 mg or 4 capsules of 25 mg), two

times a day.

– Your child’s doctor will review the dose and change it as needed.

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

Talk to your doctor, pharmacist or nurse or go to a hospital straight away. Take the medicine pack and this leaflet with you.

If you miss a dose of VITRAKVI

Do not take a double dose to make up for a forgotten dose or if you vomit after taking this medicine. Take your 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 to take VITRAKVI for as long as your doctor tells you.

If you are not able to take the medicine as your doctor prescribed talk to your doctor straight away.

If you have 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 should immediately contact your doctor if you experience any of the following serious side effects:

– feeling dizzy (very common side effect, may affect more than 1 in 10 people), tingling, feeling numb, or a burning feeling in your hands and feet, difficulty walking normally (common side effect, may affect up to 1 in 10 people). This could be symptoms of nervous system problems.

Your doctor may decide to lower the dose, or pause or stop the 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 pumping, which could be symptoms of low red blood cells (anaemia)
– flu like symptoms including fever, which could be symptoms of low white blood cells (neutropenia, leukopenia)
– feeling or being sick (nausea or vomiting)
– constipation
– muscle pain (myalgia)
– feeling tired (fatigue)
– increased amount of liver enzymes in blood tests
– weight increase.

Common (may affect up to 1 in 10 people):

– change in how things taste (dysgeusia)
– muscle weakness
– increased amount of “alkaline phosphatase” in blood tests (very common in children).

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 inBy reporting side effects you can help provide more information on the safety of this medicine.

5. How to store 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 the bottle label 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 capsules look damaged.
– Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to 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
– Indigo carmine aluminium lake (E 132)
– Titanium dioxide (E 171)
– Propylene glycol (E 1520)
– Dimeticone

What VITRAKVI looks like and the contents of the bottle

– VITRAKVI 25 mg is supplied as white opaque hard gelatine capsule, (18 mm long x 6 mm wide), with blue printing of BAYER-cross and “25 mg” on the body of the capsule
– VITRAKVI 100 mg is supplied as white opaque hard gelatine capsule, (22 mm long x 7 mm wide), with blue printing of BAYER-cross and “100 mg” on the body of the capsule

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

Marketing Authorisation Holder

Bayer AG

51368 Leverkusen

Germany

Manufacturer

Bayer AG

Kaiser-Wilhelm-Allee

51368 Leverkusen

Germany

For any information about this medicine, please contact the local representative of the Marketing

Authorisation Holder:

Belgie/Belgique/Belgien	Lietuva
Bayer SA-NV	UAB Bayer
Tél/Tel: +32-(0)2–535 63 11	Tel. +37 05 23 36 868
Efc^rapufl	Luxembourg/Luxemburg
Eaňep Etnrapua EOOfl	Bayer SA-NV
Tea.: +359 02 4247280	Tél/Tel: +32-(0)2–535 63 11
Česká republika	Magyarország
Bayer s.r.o.	Bayer Hungária KFT
Tel: +420 266 101 111	Tel:+36 14 87–41 00
Danmark	Malta
Bayer A/S	Alfred Gera and Sons Ltd.
Tlf: +45 45 23 50 00	Tel: +35 621 44 62 05
Deutschland	Nederland
Bayer Vital GmbH	Bayer B.V.
Tel: +49 (0)214–30 513 48	Tel: +31-(0)297–28 06 66
Eesti	Norge
Bayer OÜ	Bayer AS
Tel: +372 655 8565	Tlf: +47 23 13 05 00
EXXáSa	Österreich
Bayer EXXág ABEE	Bayer Austria Ges.m.b.H.
Tql: +30–210–61 87 500	Tel: +43-(0)1–711 46–0
España	Polska
Bayer Hispania S.L.	Bayer Sp. z o.o.
Tel: +34–93–495 65 00	Tel: +48 22 572 35 00
France	Portugal
Bayer HealthCare	Bayer Portugal, Lda.
Tél (N° vert): +33-(0)800 87 54 54	Tel: +351 21 416 42 00
Hrvatska	Romania
Bayer d.o.o.	SC Bayer SRL
Tel: +385-(0)1–6599 900	Tel: +40 21 529 59 00
Ireland	Slovenija
Bayer Limited	Bayer d. o. o.
Tel: +353 1 216 3300	Tel: +386 (0)1 58 14 400
Ísland	Slovenská republika
Icepharma hf.	Bayer spol. s r.o.
Sími: +354 540 8000	Tel. +421 2 59 21 31 11
Italia	Suomi/Finland
Bayer S.p.A.	Bayer Oy
Tel: +39 02 397 8 1	Puh/Tel: +358– 20 785 21
Kúnpog	Sverige
NOVAGEM Limited	Bayer AB
Tql: +357 22 48 38 58	Tel: +46 (0) 8 580 223 00
Latvija	United Kingdom
SIA Bayer	Bayer plc
Tel: +371 67 84 55 63	Tel: +44-(0)118 206 3000
This leaflet was last revised in

This medicine has been given ‘conditional approval’. This means that there is more evidence to come about this medicine.

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

Detailed information on this medicine is available on the European Medicines Agency web site:

Package leaflet: Information for the patient

VITRAKVI 20 mg/mL oral solution larotrectinib

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 as though the person taking the medicine is reading it. If you are giving this medicine to your child, please replace “you” with “your child” throughout.

What is in this leaflet:

1. What VITRAKVI is and what it is used for
2. What you need to know before you take VITRAKVI
3. How to take VITRAKVI
4. Possible side effects
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 NTRK gene (neurotrophic tyrosine receptor kinase).

VITRAKVI is only used when

– these cancers are advanced or have spread to other parts of the body or if a surgery to remove the cancer is likely to cause severe complications and
– there are no satisfactory treatment options.

Before you are given VITRAKVI, your doctor will do a test to check if you have the change in the NTRK gene.

How VITRAKVI works

If you have any questions on how VITRAKVI works or why it has been prescribed for you, 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

Other medicines and VITRAKVI

In particular, tell 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, troleandomycin
– a medicine used to treat Cushing’s syndrome called ketoconazole
– medicines used to treat HIV infection called atazanavir, indinavir, nelfinavir, ritonavir, saquinavir, rifabutin, efavirenz
– a medicine used to treat depression called nefazodone
– medicines used to treat epilepsy called phenytoin, carbamazepine, phenobarbital
– a herbal medicine used to treat depression called St. John’s wort
– a medicine used to treat tuberculosis called rifampicin
– a medicine used for strong pain relief called alfentanil
– medicines used to prevent organ rejection after an organ transplant called ciclosporin, sirolimus, tacrolimus
– a medicine used to treat an abnormal heart rhythm called quinidine
– medicines used to treat migraines called dihydroergotamine, 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, 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 help lower cholesterol called statins
– hormonal medicines used for contraception, see section “contraception – for men and women” below.

If any of the above 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. This is because it 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 use VITRAKVI during pregnancy since the effect of VITRAKVI on the unborn is not known.

Breast-feeding

Do not breast-feed while taking this medicine and for 3 days after the last dose. This is because it is not known if VITRAKVI passes into breast milk.

Contraception – for men and women

You should avoid getting pregnant while taking this medicine.

If you are able to become pregnant, your doctor should do a pregnancy test before you start treatment. You must use effective methods of contraception while taking VITRAKVI and for at least 1 month after the last dose, if

– you are able to become pregnant. If you use hormonal contraceptives, you should also use a barrier method, such as a condom.
– you have sex with a woman able to become pregnant.

Ask your doctor about the best method of contraception for you.

Driving, cycling and using machines

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

VITRAKVI contains:

- sucrose : it may be harmful to the teeth. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
– 22 mg sorbitol in 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 if you have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which a person cannot break down fructose, talk to your doctor before you or your child take or receive this medicine.

– less than 1 mmol (or 23 mg) of sodium per 5 mL, that is to say essentially ‘sodium free’.
– 1.2 mg propylene glycol in 1 mL. If your baby is less than 4 weeks old, talk to your doctor or

pharmacist before giving them this medicine, in particular if the baby is given other medicines that contain propylene glycol or alcohol.

- parahydroxybenzoate : it may cause allergic reactions (possibly delayed).

3. How to take VITRAKVI

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor, pharmacist or nurse if you are not sure.

How much to take

Adults (from 18 years)

– The recommended dose of VITRAKVI is 100 mg (5 mL), two times a day.
– Your doctor will review your dose and change it as needed.

Children and adolescents

– Your child’s doctor will work out the right dose for your child based on their height and weight.
– The maximum recommended dose is 100 mg (5 mL), two times a day.
– Your child’s doctor will review the dose and change it as needed.

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.
– Along with this medicine you need a bottle adapter (28 mm diameter) and a syringe that can be used to give medicines by mouth. Use a 1 mL syringe with 0.1 mL marks for doses less than 1 mL. Use a 5 mL syringe with 0.2 mL marks for doses of 1 mL or more.

– Press the bottle cap and turn it anti-clockwise to open the bottle.
– Put the bottle adapter into the bottle neck and make sure it is well fixed.
– Push the plunger fully into the syringe and then put the syringe in 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 upwards to remove any large bubbles that are in the syringe.
– Pull the plunger down to the mark equal to the dose in mL prescribed by your doctor.
– Turn the bottle the right way up and take the syringe out of the adapter.
– Put the syringe in the mouth, pointing towards the inside of the cheek – this will help you

swallow the medicine naturally. Slowly press the plunger in.

– Put the bottle cap on and tightly close the bottle – leave the adapter in the bottle. If necessary, VITRAKVI may be administered via a nasogastric feeding tube. For details how to do so, please ask your doctor, pharmacist or nurse.

If you take more VITRAKVI than you should

Talk to your doctor, pharmacist or nurse or go to a hospital straight away. Take the medicine pack and this leaflet with you.

If you miss a dose of VITRAKVI

Do not take a double dose to make up for a forgotten dose or if you vomit after taking this medicine. Take your 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 to take VITRAKVI for as long as your doctor tells you.

If you are not able to take the medicine as your doctor prescribed talk to your doctor straight away.

If you have 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 should immediately contact your doctor if you experience any of the following serious side effects:

– feeling dizzy (very common side effect, may affect more than 1 in 10 people), tingling, feeling

numb, or a burning feeling in your hands and feet, difficulty walking normally (common side effect, may affect up to 1 in 10 people). This could be symptoms of nervous system problems.

Your doctor may decide to lower the dose, or pause or stop the 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 pumping, which could be symptoms of low red blood cells (anaemia)
– flu like symptoms including fever, which could be symptoms of low white blood cells (neutropenia, leukopenia)
– feeling or being sick (nausea or vomiting)
– constipation
– muscle pain (myalgia)
– feeling tired (fatigue)
– increased amount of liver enzymes in blood tests
– weight increase.

Common (may affect up to 1 in 10 people):

– change in how things taste (dysgeusia)
– muscle weakness
– increased amount of “alkaline phosphatase” in blood tests (very common in children).

Reporting of side effects

5. How to store 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 the bottle label after EXP. The expiry date refers to the last day of that month.
– Store in a refrigerator (2 °C – 8 °C).
– Do not freeze.
– Once the bottle is open, you must use your medicine within 30 days of opening.
– Do not take the medicine if the bottle or bottle cap looks damaged or like it has leaked.
– Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.

6. Contents of the pack and other information

What VITRAKVI contains

The active substance is larotrectinib.

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

The other ingredients are:

– Purified water
– Sucrose
– Hydroxypropylbetadex
– 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)
– Methyl parahydroxybenzoate (E 218)
– Citrus fruit flavour
– Natural flavour

See “VITRAKVI contains” in section 2 for more information.

What VITRAKVI looks like and the contents of the bottle

VITRAKVI is a clear yellow to orange oral solution.

Each carton contains 1 child-resistant glass bottle containing 100 mL oral solution.

Marketing Authorisation Holder

Bayer AG

51368 Leverkusen

Germany

Manufacturer

Bayer AG

Kaiser-Wilhelm-Allee

51368 Leverkusen

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Belgie/Belgique/Belgien	Lietuva
Bayer SA-NV	UAB Bayer
Tél/Tel: +32-(0)2–535 63 11	Tel. +37 05 23 36 868
Efcnrapua	Luxembourg/Luxemburg
Eaňep Etnrapua EOOfl	Bayer SA-NV
Ten.: +359 02 4247280	Tél/Tel: +32-(0)2–535 63 11
Česká republika	Magyarország
Bayer s.r.o.	Bayer Hungária KFT
Tel: +420 266 101 111	Tel:+36 14 87–41 00
Danmark	Malta
Bayer A/S	Alfred Gera and Sons Ltd.
Tlf: +45 45 23 50 00	Tel: +35 621 44 62 05
Deutschland	Nederland
Bayer Vital GmbH	Bayer B.V.
Tel: +49 (0)214–30 513 48	Tel: +31-(0)297–28 06 66
Eesti	Norge
Bayer OÜ	Bayer AS
Tel: +372 655 8565	Tlf: +47 23 13 05 00
EXXáSa	Österreich
Bayer EXXág ABEE	Bayer Austria Ges.m.b.H.
Tql: +30–210–61 87 500	Tel: +43-(0)1–711 46–0
España	Polska
Bayer Hispania S.L.	Bayer Sp. z o.o.
Tel: +34–93–495 65 00	Tel: +48 22 572 35 00
France	Portugal
Bayer HealthCare	Bayer Portugal, Lda.
Tél (N° vert): +33-(0)800 87 54 54	Tel: +351 21 416 42 00
Hrvatska	Romania
Bayer d.o.o.	SC Bayer SRL
Tel: +385-(0)1–6599 900	Tel: +40 21 529 59 00
Ireland	Slovenija
Bayer Limited	Bayer d. o. o.
Tel: +353 1 216 3300	Tel: +386 (0)1 58 14 400
Ísland	Slovenská republika
Icepharma hf.	Bayer spol. s r.o.
Sími: +354 540 8000	Tel. +421 2 59 21 31 11
Italia	Suomi/Finland
Bayer S.p.A.	Bayer Oy
Tel: +39 02 397 8 1	Puh/Tel: +358– 20 785 21
Kúnpog	Sverige
NOVAGEM Limited	Bayer AB
Tql: +357 22 48 38 58	Tel: +46 (0) 8 580 223 00
Latvija	United Kingdom
SIA Bayer	Bayer plc
Tel: +371 67 84 55 63	Tel: +44-(0)118 206 3000
This leaflet was last revised in

This medicine has been given ‘conditional approval’. This means that there is more evidence to come about this medicine.

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

Detailed information on this medicine is available on the European Medicines Agency web site:.

Package leaflet: Information for the patient

VITRAKVI 20 mg/mL oral solution larotrectinib

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 as though the person taking the medicine is reading it. If you are

giving this medicine to your child, please replace “you” with “your child” throughout.

What is in this leaflet:

1. What VITRAKVI is and what it is used for
2. What you need to know before you take VITRAKVI
3. How to take VITRAKVI
4. Possible side effects
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 NTRK gene (neurotrophic tyrosine receptor kinase).

VITRAKVI is only used when

– these cancers are advanced or have spread to other parts of the body or if a surgery to remove the cancer is likely to cause severe complications and
– there are no satisfactory treatment options.

Before you are given VITRAKVI, your doctor will do a test to check if you have the change in the NTRK gene.

How VITRAKVI works

If you have any questions on how VITRAKVI works or why it has been prescribed for you, 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

Other medicines and VITRAKVI

In particular, tell 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, troleandomycin
– a medicine used to treat Cushing’s syndrome called ketoconazole
– medicines used to treat HIV infection called atazanavir, indinavir, nelfinavir, ritonavir, saquinavir, rifabutin, efavirenz
– a medicine used to treat depression called nefazodone
– medicines used to treat epilepsy called phenytoin, carbamazepine, phenobarbital
– a herbal medicine used to treat depression called St. John’s wort
– a medicine used to treat tuberculosis called rifampicin
– a medicine used for strong pain relief called alfentanil
– medicines used to prevent organ rejection after an organ transplant called ciclosporin, sirolimus, tacrolimus
– a medicine used to treat an abnormal heart rhythm called quinidine
– medicines used to treat migraines called dihydroergotamine, 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, 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 help lower cholesterol called statins
– hormonal medicines used for contraception, see section “contraception – for men and women” below.

If any of the above 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. This is because it 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 use VITRAKVI during pregnancy since the effect of VITRAKVI on the unborn is not known.

Breast-feeding

Do not breast-feed while taking this medicine and for 3 days after the last dose. This is because it is not known if VITRAKVI passes into breast milk.

Contraception – for men and women

You should avoid getting pregnant while taking this medicine.

If you are able to become pregnant, your doctor should do a pregnancy test before you start treatment.

You must use effective methods of contraception while taking VITRAKVI and for at least 1 month after the last dose, if

– you are able to become pregnant. If you use hormonal contraceptives, you should also use a barrier method, such as a condom.
– you have sex with a woman able to become pregnant.

Ask your doctor about the best method of contraception for you.

Driving, cycling and using machines

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

VITRAKVI contains:

– 2 mg sodium benzoate in 1 mL.
– less than 1 mmol (or 23 mg) of sodium per 5 mL, that is to say essentially ‘sodium free’.

3. How to take VITRAKVI

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor, pharmacist or nurse if you are not sure.

How much to take

Adults (from 18 years)

– The recommended dose of VITRAKVI is 100 mg (5 mL), two times a day.
– Your doctor will review your dose and change it as needed.

Children and adolescents

– Your child’s doctor will work out the right dose for your child based on their height and weight.
– The maximum recommended dose is 100 mg (5 mL), two times a day.
– Your child’s doctor will review the dose and change it as needed.

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.
– Along with this medicine you need a bottle adapter (28 mm diameter) and a syringe that can be used to give medicines by mouth. Use a 1 mL syringe with 0.1 mL marks for doses less than 1 mL. Use a 5 mL syringe with 0.2 mL marks for doses of 1 mL or more.

– Press the bottle cap and turn it anti-clockwise to open the bottle.
– Put the bottle adapter into the bottle neck and make sure it is well fixed.
– Push the plunger fully into the syringe and then put the syringe in 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 upwards to remove any large bubbles that are in the syringe.

– Pull the plunger down to the mark equal to the dose in mL prescribed by your doctor.
– Turn the bottle the right way up and take the syringe out of the adapter.
– Put the syringe in the mouth, pointing towards the inside of the cheek – this will help you

swallow the medicine naturally. Slowly press the plunger in.

– Put the bottle cap on and tightly close the bottle – leave the adapter in the bottle.

If necessary, VITRAKVI may be administered via a nasogastric feeding tube. For details how to do so, please ask your doctor, pharmacist or nurse.

If you take more VITRAKVI than you should

Talk to your doctor, pharmacist or nurse or go to a hospital straight away. Take the medicine pack and this leaflet with you.

If you miss a dose of VITRAKVI

Do not take a double dose to make up for a forgotten dose or if you vomit after taking this medicine. Take your 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 to take VITRAKVI for as long as your doctor tells you.

If you are not able to take the medicine as your doctor prescribed talk to your doctor straight away.

If you have 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 should immediately contact your doctor if you experience any of the following serious side effects:

– feeling dizzy (very common side effect, may affect more than 1 in 10 people), tingling, feeling numb, or a burning feeling in your hands and feet, difficulty walking normally (common side effect, may affect up to 1 in 10 people). This could be symptoms of nervous system problems.

Your doctor may decide to lower the dose, or pause or stop the 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 pumping, which could be symptoms of low red blood cells (anaemia)
– flu like symptoms including fever, which could be symptoms of low white blood cells (neutropenia, leukopenia)
– feeling or being sick (nausea or vomiting)
– constipation
– muscle pain (myalgia)
– feeling tired (fatigue)
– increased amount of liver enzymes in blood tests
– weight increase.

Common (may affect up to 1 in 10 people):

– change in how things taste (dysgeusia)
– muscle weakness
– increased amount of “alkaline phosphatase” in blood tests (very common in children).

Reporting of side effects

5. How to store 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 the bottle label after EXP. The expiry date refers to the last day of that month.

Store in a refrigerator (2 °C – 8 °C).

Do not freeze.

Once the bottle is open, you must use your medicine within 10 days of opening.

Do not take the medicine if the bottle or bottle screw cap looks damaged or like it has leaked. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to 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
– Indigo carmine aluminium lake (E 132)
– Titanium dioxide (E 171)
– Propylene glycol (E 1520)
– Dimeticone

What VITRAKVI looks like and the contents of the bottle

– VITRAKVI 25 mg is supplied as white opaque hard gelatine capsule, (18 mm long x 6 mm wide), with blue printing of BAYER-cross and “25 mg” on the body of the capsule
– VITRAKVI 100 mg is supplied as white opaque hard gelatine capsule, (22 mm long x 7 mm wide), with blue printing of BAYER-cross and “100 mg” on the body of the capsule

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

Marketing Authorisation Holder

Bayer AG

51368 Leverkusen

Germany

Manufacturer

Bayer AG

Kaiser-Wilhelm-Allee

51368 Leverkusen

Germany

For any information about this medicine, please contact the local representative of the Marketing

Authorisation Holder:

Belgie/Belgique/Belgien	Lietuva
Bayer SA-NV	UAB Bayer
Tél/Tel: +32-(0)2–535 63 11	Tel. +37 05 23 36 868
Efc^rapufl	Luxembourg/Luxemburg
Eaňep Etnrapua EOOfl	Bayer SA-NV
Tea.: +359 02 4247280	Tél/Tel: +32-(0)2–535 63 11
Česká republika	Magyarország
Bayer s.r.o.	Bayer Hungária KFT
Tel: +420 266 101 111	Tel:+36 14 87–41 00
Danmark	Malta
Bayer A/S	Alfred Gera and Sons Ltd.
Tlf: +45 45 23 50 00	Tel: +35 621 44 62 05
Deutschland	Nederland
Bayer Vital GmbH	Bayer B.V.
Tel: +49 (0)214–30 513 48	Tel: +31-(0)297–28 06 66
Eesti	Norge
Bayer OÜ	Bayer AS
Tel: +372 655 8565	Tlf: +47 23 13 05 00
EXXáSa	Österreich
Bayer EXXág ABEE	Bayer Austria Ges.m.b.H.
Tql: +30–210–61 87 500	Tel: +43-(0)1–711 46–0
España	Polska
Bayer Hispania S.L.	Bayer Sp. z o.o.
Tel: +34–93–495 65 00	Tel: +48 22 572 35 00
France	Portugal
Bayer HealthCare	Bayer Portugal, Lda.
Tél (N° vert): +33-(0)800 87 54 54	Tel: +351 21 416 42 00
Hrvatska	Romania
Bayer d.o.o.	SC Bayer SRL
Tel: +385-(0)1–6599 900	Tel: +40 21 529 59 00
Ireland	Slovenija
Bayer Limited	Bayer d. o. o.
Tel: +353 1 216 3300	Tel: +386 (0)1 58 14 400
Ísland	Slovenská republika
Icepharma hf.	Bayer spol. s r.o.
Sími: +354 540 8000	Tel. +421 2 59 21 31 11
Italia	Suomi/Finland
Bayer S.p.A.	Bayer Oy
Tel: +39 02 397 8 1	Puh/Tel: +358– 20 785 21
Kúnpog	Sverige
NOVAGEM Limited	Bayer AB
Tql: +357 22 48 38 58	Tel: +46 (0) 8 580 223 00
Latvija	United Kingdom
SIA Bayer	Bayer plc
Tel: +371 67 84 55 63	Tel: +44-(0)118 206 3000
This leaflet was last revised in

This medicine has been given ‘conditional approval’. This means that there is more evidence to come about this medicine.

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

Detailed information on this medicine is available on the European Medicines Agency web site:

Package leaflet: Information for the patient

VITRAKVI 20 mg/mL oral solution larotrectinib

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 as though the person taking the medicine is reading it. If you are giving this medicine to your child, please replace “you” with “your child” throughout.

What is in this leaflet:

1. What VITRAKVI is and what it is used for
2. What you need to know before you take VITRAKVI
3. How to take VITRAKVI
4. Possible side effects
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 NTRK gene (neurotrophic tyrosine receptor kinase).

VITRAKVI is only used when

– these cancers are advanced or have spread to other parts of the body or if a surgery to remove the cancer is likely to cause severe complications and
– there are no satisfactory treatment options.

Before you are given VITRAKVI, your doctor will do a test to check if you have the change in the NTRK gene.

How VITRAKVI works

If you have any questions on how VITRAKVI works or why it has been prescribed for you, 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

Other medicines and VITRAKVI

In particular, tell 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, troleandomycin
– a medicine used to treat Cushing’s syndrome called ketoconazole
– medicines used to treat HIV infection called atazanavir, indinavir, nelfinavir, ritonavir, saquinavir, rifabutin, efavirenz
– a medicine used to treat depression called nefazodone
– medicines used to treat epilepsy called phenytoin, carbamazepine, phenobarbital
– a herbal medicine used to treat depression called St. John’s wort
– a medicine used to treat tuberculosis called rifampicin
– a medicine used for strong pain relief called alfentanil
– medicines used to prevent organ rejection after an organ transplant called ciclosporin, sirolimus, tacrolimus
– a medicine used to treat an abnormal heart rhythm called quinidine
– medicines used to treat migraines called dihydroergotamine, 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, 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 help lower cholesterol called statins
– hormonal medicines used for contraception, see section “contraception – for men and women” below.

If any of the above 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. This is because it 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 use VITRAKVI during pregnancy since the effect of VITRAKVI on the unborn is not known.

Breast-feeding

Do not breast-feed while taking this medicine and for 3 days after the last dose. This is because it is not known if VITRAKVI passes into breast milk.

Contraception – for men and women

You should avoid getting pregnant while taking this medicine.

– you are able to become pregnant. If you use hormonal contraceptives, you should also use a barrier method, such as a condom.
– you have sex with a woman able to become pregnant.

Ask your doctor about the best method of contraception for you.

Driving, cycling and using machines

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

VITRAKVI contains:

- sucrose : it may be harmful to the teeth. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
– 22 mg sorbitol in 1 mL. Sorbitol is a source of fructose. If your doctor has told you that you or

– less than 1 mmol (or 23 mg) of sodium per 5 mL, that is to say essentially ‘sodium free’.
– 1.2 mg propylene glycol in 1 mL. If your baby is less than 4 weeks old, talk to your doctor or

pharmacist before giving them this medicine, in particular if the baby is given other medicines that contain propylene glycol or alcohol.

- parahydroxybenzoate : it may cause allergic reactions (possibly delayed).

3. How to take VITRAKVI

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor, pharmacist or nurse if you are not sure.

How much to take

Adults (from 18 years)

– The recommended dose of VITRAKVI is 100 mg (5 mL), two times a day.
– Your doctor will review your dose and change it as needed.

Children and adolescents

– Your child’s doctor will work out the right dose for your child based on their height and weight.
– The maximum recommended dose is 100 mg (5 mL), two times a day.
– Your child’s doctor will review the dose and change it as needed.

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.
– Along with this medicine you need a bottle adapter (28 mm diameter) and a syringe that can be used to give medicines by mouth. Use a 1 mL syringe with 0.1 mL marks for doses less than 1 mL. Use a 5 mL syringe with 0.2 mL marks for doses of 1 mL or more.

– Press the bottle cap and turn it anti-clockwise to open the bottle.
– Put the bottle adapter into the bottle neck and make sure it is well fixed.
– Push the plunger fully into the syringe and then put the syringe in 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 upwards to remove any large bubbles that are in the syringe.
– Pull the plunger down to the mark equal to the dose in mL prescribed by your doctor.
– Turn the bottle the right way up and take the syringe out of the adapter.
– Put the syringe in the mouth, pointing towards the inside of the cheek – this will help you

swallow the medicine naturally. Slowly press the plunger in.

– Put the bottle cap on and tightly close the bottle – leave the adapter in the bottle. If necessary, VITRAKVI may be administered via a nasogastric feeding tube. For details how to do so, please ask your doctor, pharmacist or nurse.

If you take more VITRAKVI than you should

Talk to your doctor, pharmacist or nurse or go to a hospital straight away. Take the medicine pack and this leaflet with you.

If you miss a dose of VITRAKVI

Do not take a double dose to make up for a forgotten dose or if you vomit after taking this medicine. Take your 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 to take VITRAKVI for as long as your doctor tells you.

If you are not able to take the medicine as your doctor prescribed talk to your doctor straight away.

If you have 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 should immediately contact your doctor if you experience any of the following serious side effects:

– feeling dizzy (very common side effect, may affect more than 1 in 10 people), tingling, feeling

numb, or a burning feeling in your hands and feet, difficulty walking normally (common side effect, may affect up to 1 in 10 people). This could be symptoms of nervous system problems.

Your doctor may decide to lower the dose, or pause or stop the 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 pumping, which could be symptoms of low red blood cells (anaemia)
– flu like symptoms including fever, which could be symptoms of low white blood cells (neutropenia, leukopenia)
– feeling or being sick (nausea or vomiting)
– constipation
– muscle pain (myalgia)
– feeling tired (fatigue)
– increased amount of liver enzymes in blood tests
– weight increase.

Common (may affect up to 1 in 10 people):

– change in how things taste (dysgeusia)
– muscle weakness
– increased amount of “alkaline phosphatase” in blood tests (very common in children).

Reporting of side effects

5. How to store 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 the bottle label after EXP. The expiry date refers to the last day of that month.
– Store in a refrigerator (2 °C – 8 °C).
– Do not freeze.
– Once the bottle is open, you must use your medicine within 30 days of opening.
– Do not take the medicine if the bottle or bottle cap looks damaged or like it has leaked.
– Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.

6. Contents of the pack and other information

What VITRAKVI contains

The active substance is larotrectinib.

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

The other ingredients are:

– Purified water
– Sucrose
– Hydroxypropylbetadex
– 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)
– Methyl parahydroxybenzoate (E 218)
– Citrus fruit flavour
– Natural flavour

See “VITRAKVI contains” in section 2 for more information.

What VITRAKVI looks like and the contents of the bottle

VITRAKVI is a clear yellow to orange oral solution.

Each carton contains 1 child-resistant glass bottle containing 100 mL oral solution.

Marketing Authorisation Holder

Bayer AG

51368 Leverkusen

Germany

Manufacturer

Bayer AG

Kaiser-Wilhelm-Allee

51368 Leverkusen

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Belgie/Belgique/Belgien	Lietuva
Bayer SA-NV	UAB Bayer
Tél/Tel: +32-(0)2–535 63 11	Tel. +37 05 23 36 868
Efcnrapua	Luxembourg/Luxemburg
Eaňep Etnrapua EOOfl	Bayer SA-NV
Ten.: +359 02 4247280	Tél/Tel: +32-(0)2–535 63 11
Česká republika	Magyarország
Bayer s.r.o.	Bayer Hungária KFT
Tel: +420 266 101 111	Tel:+36 14 87–41 00
Danmark	Malta
Bayer A/S	Alfred Gera and Sons Ltd.
Tlf: +45 45 23 50 00	Tel: +35 621 44 62 05
Deutschland	Nederland
Bayer Vital GmbH	Bayer B.V.
Tel: +49 (0)214–30 513 48	Tel: +31-(0)297–28 06 66
Eesti	Norge
Bayer OÜ	Bayer AS
Tel: +372 655 8565	Tlf: +47 23 13 05 00
EXXáSa	Österreich
Bayer EXXág ABEE	Bayer Austria Ges.m.b.H.
Tql: +30–210–61 87 500	Tel: +43-(0)1–711 46–0
España	Polska
Bayer Hispania S.L.	Bayer Sp. z o.o.
Tel: +34–93–495 65 00	Tel: +48 22 572 35 00
France	Portugal
Bayer HealthCare	Bayer Portugal, Lda.
Tél (N° vert): +33-(0)800 87 54 54	Tel: +351 21 416 42 00
Hrvatska	Romania
Bayer d.o.o.	SC Bayer SRL
Tel: +385-(0)1–6599 900	Tel: +40 21 529 59 00
Ireland	Slovenija
Bayer Limited	Bayer d. o. o.
Tel: +353 1 216 3300	Tel: +386 (0)1 58 14 400
Ísland	Slovenská republika
Icepharma hf.	Bayer spol. s r.o.
Sími: +354 540 8000	Tel. +421 2 59 21 31 11
Italia	Suomi/Finland
Bayer S.p.A.	Bayer Oy
Tel: +39 02 397 8 1	Puh/Tel: +358– 20 785 21
Kúnpog	Sverige
NOVAGEM Limited	Bayer AB
Tql: +357 22 48 38 58	Tel: +46 (0) 8 580 223 00
Latvija	United Kingdom
SIA Bayer	Bayer plc
Tel: +371 67 84 55 63	Tel: +44-(0)118 206 3000
This leaflet was last revised in

This medicine has been given ‘conditional approval’. This means that there is more evidence to come about this medicine.

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

Detailed information on this medicine is available on the European Medicines Agency web site:.

Package leaflet: Information for the patient

VITRAKVI 20 mg/mL oral solution larotrectinib

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 as though the person taking the medicine is reading it. If you are

giving this medicine to your child, please replace “you” with “your child” throughout.

What is in this leaflet:

1. What VITRAKVI is and what it is used for
2. What you need to know before you take VITRAKVI
3. How to take VITRAKVI
4. Possible side effects
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 NTRK gene (neurotrophic tyrosine receptor kinase).

VITRAKVI is only used when

– these cancers are advanced or have spread to other parts of the body or if a surgery to remove the cancer is likely to cause severe complications and
– there are no satisfactory treatment options.

Before you are given VITRAKVI, your doctor will do a test to check if you have the change in the NTRK gene.

How VITRAKVI works

If you have any questions on how VITRAKVI works or why it has been prescribed for you, 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

Other medicines and VITRAKVI

In particular, tell 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, troleandomycin
– a medicine used to treat Cushing’s syndrome called ketoconazole
– medicines used to treat HIV infection called atazanavir, indinavir, nelfinavir, ritonavir, saquinavir, rifabutin, efavirenz
– a medicine used to treat depression called nefazodone
– medicines used to treat epilepsy called phenytoin, carbamazepine, phenobarbital
– a herbal medicine used to treat depression called St. John’s wort
– a medicine used to treat tuberculosis called rifampicin
– a medicine used for strong pain relief called alfentanil
– medicines used to prevent organ rejection after an organ transplant called ciclosporin, sirolimus, tacrolimus
– a medicine used to treat an abnormal heart rhythm called quinidine
– medicines used to treat migraines called dihydroergotamine, 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, 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 help lower cholesterol called statins
– hormonal medicines used for contraception, see section “contraception – for men and women” below.

If any of the above 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. This is because it 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 use VITRAKVI during pregnancy since the effect of VITRAKVI on the unborn is not known.

Breast-feeding

Do not breast-feed while taking this medicine and for 3 days after the last dose. This is because it is not known if VITRAKVI passes into breast milk.

Contraception – for men and women

You should avoid getting pregnant while taking this medicine.

If you are able to become pregnant, your doctor should do a pregnancy test before you start treatment.

You must use effective methods of contraception while taking VITRAKVI and for at least 1 month after the last dose, if

– you are able to become pregnant. If you use hormonal contraceptives, you should also use a barrier method, such as a condom.
– you have sex with a woman able to become pregnant.

Ask your doctor about the best method of contraception for you.

Driving, cycling and using machines

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

VITRAKVI contains:

– 2 mg sodium benzoate in 1 mL.
– less than 1 mmol (or 23 mg) of sodium per 5 mL, that is to say essentially ‘sodium free’.

3. How to take VITRAKVI

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor, pharmacist or nurse if you are not sure.

How much to take

Adults (from 18 years)

– The recommended dose of VITRAKVI is 100 mg (5 mL), two times a day.
– Your doctor will review your dose and change it as needed.

Children and adolescents

– Your child’s doctor will work out the right dose for your child based on their height and weight.
– The maximum recommended dose is 100 mg (5 mL), two times a day.
– Your child’s doctor will review the dose and change it as needed.

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.
– Along with this medicine you need a bottle adapter (28 mm diameter) and a syringe that can be used to give medicines by mouth. Use a 1 mL syringe with 0.1 mL marks for doses less than 1 mL. Use a 5 mL syringe with 0.2 mL marks for doses of 1 mL or more.

– Press the bottle cap and turn it anti-clockwise to open the bottle.
– Put the bottle adapter into the bottle neck and make sure it is well fixed.
– Push the plunger fully into the syringe and then put the syringe in 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 upwards to remove any large bubbles that are in the syringe.

– Pull the plunger down to the mark equal to the dose in mL prescribed by your doctor.
– Turn the bottle the right way up and take the syringe out of the adapter.
– Put the syringe in the mouth, pointing towards the inside of the cheek – this will help you

swallow the medicine naturally. Slowly press the plunger in.

– Put the bottle cap on and tightly close the bottle – leave the adapter in the bottle.

If necessary, VITRAKVI may be administered via a nasogastric feeding tube. For details how to do so, please ask your doctor, pharmacist or nurse.

If you take more VITRAKVI than you should

Talk to your doctor, pharmacist or nurse or go to a hospital straight away. Take the medicine pack and this leaflet with you.

If you miss a dose of VITRAKVI

Do not take a double dose to make up for a forgotten dose or if you vomit after taking this medicine. Take your 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 to take VITRAKVI for as long as your doctor tells you.

If you are not able to take the medicine as your doctor prescribed talk to your doctor straight away.

If you have 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 should immediately contact your doctor if you experience any of the following serious side effects:

– feeling dizzy (very common side effect, may affect more than 1 in 10 people), tingling, feeling numb, or a burning feeling in your hands and feet, difficulty walking normally (common side effect, may affect up to 1 in 10 people). This could be symptoms of nervous system problems.

Your doctor may decide to lower the dose, or pause or stop the 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 pumping, which could be symptoms of low red blood cells (anaemia)
– flu like symptoms including fever, which could be symptoms of low white blood cells (neutropenia, leukopenia)
– feeling or being sick (nausea or vomiting)
– constipation
– muscle pain (myalgia)
– feeling tired (fatigue)
– increased amount of liver enzymes in blood tests
– weight increase.

Common (may affect up to 1 in 10 people):

– change in how things taste (dysgeusia)
– muscle weakness
– increased amount of “alkaline phosphatase” in blood tests (very common in children).

Reporting of side effects

5. How to store 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 the bottle label after EXP. The expiry date refers to the last day of that month.

Store in a refrigerator (2 °C – 8 °C).

Do not freeze.

Once the bottle is open, you must use your medicine within 10 days of opening.

6. Contents of the pack and other information

What VITRAKVI contains

The active substance is larotrectinib.

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

The other ingredients are:

– Purified water
– Hydroxypropylbetadex
– Sucralose (E 955)
– Sodium citrate (E 331)
– Sodium benzoate (E 211)
– Strawberry flavour
– Citric acid (E 330)

Vitrakvi - patient leaflet, side effects, dosage

Table of contents

Patient leaflet - Vitrakvi

1. What VITRAKVI is and what it is used for

2. What you need to know before you take VITRAKVI

3. How to take VITRAKVI

4. Possible side effects

5. How to store VITRAKVI

6. Contents of the pack and other information

1. What VITRAKVI is and what it is used for

2. What you need to know before you take VITRAKVI

3. How to take VITRAKVI

4. Possible side effects

5. How to store VITRAKVI

6. Contents of the pack and other information

1. What VITRAKVI is and what it is used for

2. What you need to know before you take VITRAKVI

3. How to take VITRAKVI

4. Possible side effects

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

2. What you need to know before you take VITRAKVI

3. How to take VITRAKVI

How to take this medicine

4. Possible side effects

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

2. What you need to know before you take VITRAKVI

3. How to take VITRAKVI

How to take this medicine

4. Possible side effects

5. How to store VITRAKVI

6. Contents of the pack and other information