VITRAKVI 25 мг Капсулы

Содержание инструкции

1. VITRAKVI 25 mg hard capsules, 100 mg hard capsules
   1. What is VITRAKVI and what is it used for
   2. What you need to know before you take VITRAKVI
   3. How to take VITRAKVI
   4. Possible side effects
   5. How to store VITRAKVI
   6. Contents of the pack and other information
2. VITRAKVI 20 mg/mL oral solution
   1. What is VITRAKVI and what is it used for
   2. What you need to know before you take VITRAKVI
   3. How to take VITRAKVI
   4. Possible side effects
   5. How to store VITRAKVI
   6. Package Contents and Other Information
3. VITRAKVI 20 mg/mL oral solution
   1. What is VITRAKVI and what is it used for
   2. What you need to know before you take VITRAKVI
   3. How to take VITRAKVI
   4. Possible side effects
   5. How to store VITRAKVI
   6. Contents of the pack and other information

VITRAKVI 25 mg hard capsules, 100 mg hard capsules

larotrectinib

Medicinal product subject to additional monitoring. This will allow the rapid identification of
new safety information. You can contribute by reporting any adverse effects
experienced during the use of this medicinal product. See the end of section 4 for
information on how to report adverse effects.

Read this leaflet carefully before taking this medicine as it contains
important information for you.

• Keep this leaflet. 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. Do not pass it on to others, even if they have the same symptoms as you, as it may be harmful.
• If any side effects occur, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

medicinal product. If you give this medicine to your child, replace “you” with “your child”.

Contents of 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 is VITRAKVI and what is it used for

What is VITRAKVI used for
VITRAKVI contains the active substance larotrectinib.
It is used in adults, adolescents and children to treat solid tumors (cancer) in various
parts of the body that are caused by an alteration in the NTRK gene ( Neurotrophic Tyrosine Receptor

Kinase, neurotrophic tyrosine kinase receptor).
VITRAKVI is used only if

• these tumors are in an advanced stage of disease or have spread to other parts of the body, or when surgical removal of the tumor could cause serious complications and
• there are no satisfactory therapeutic options.

Before administering VITRAKVI, your doctor will perform a test to check for this
alteration of the NTRK gene.

How does VITRAKVI work
In patients with cancer due to an alteration in the NTRK gene, this alteration causes the body to produce
an abnormal protein called a TRK fusion protein, which can lead to
uncontrolled cell growth and tumor development.
VITRAKVI blocks the action of TRK fusion proteins and can therefore reduce or stop the growth
of the tumor. It may also help to reduce the tumor.
If you have questions about 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 may increase the level of liver enzymes ALT, AST and bilirubin in the blood. Your doctor
will perform blood tests before and during treatment to measure the levels of ALT, AST and
bilirubin and check the function of your liver.

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 change the action of
VITRAKVI or because VITRAKVI may change the action of other medicines.
In particular, tell your doctor, pharmacist or nurse if you are taking any of the
following medicines:

• medicines used for the treatment of fungal or bacterial infections, such as itraconazole, voriconazole, clarithromycin, telithromycin, troleandomycin
• a medicine used for the treatment of Cushing's syndrome, ketoconazole
• medicines used for the treatment of HIV infection, such as atazanavir, indinavir, nelfinavir, ritonavir, saquinavir, rifabutin, efavirenz
• a medicine used for the treatment of depression, nefazodone
• medicines used for the treatment of epilepsy, such as phenytoin, carbamazepine, phenobarbital
• a herbal medicine used for the treatment of depression, known as St John's Wort
• a medicine used for the treatment of tuberculosis, rifampicin
• a medicine used to relieve severe pain, alfentanil
• medicines used to prevent rejection after an organ transplant, such as cyclosporine, sirolimus, tacrolimus
• a medicine used for the treatment of irregular heart rhythms, quinidine
• medicines used for the treatment of migraine, such as dihydroergotamine, ergotamine
• a medicine used for the long-term treatment of pain, fentanyl
• a medicine used to control involuntary movements or sounds, pimozide
• a medicine that helps you to stop smoking, bupropion
• medicines to reduce blood sugar levels, such as repaglinide, tolbutamide
• a medicine that prevents blood clots from forming, warfarin
• a medicine used to reduce the amount of acid produced by the stomach, omeprazole
• a medicine that helps to control high blood pressure, valsartan
• a group of medicines that helps to lower cholesterol, statins
• medicines containing hormones used for contraception, see section “contraception - for men and women” below. If any of these apply to you (or if you are unsure), talk to your doctor, pharmacist or nurse.

VITRAKVI with food and drink
Do not eat grapefruit or drink grapefruit juice during treatment with VITRAKVI. This
is because grapefruit can increase the amount of VITRAKVI in the body.

Pregnancy and breastfeeding
Pregnancy
If you are pregnant, or suspect you might be pregnant, or are planning to become pregnant, ask your doctor
or pharmacist for advice before taking this medicine.
You should not take VITRAKVI during pregnancy as the effect of VITRAKVI on the
foetus is unknown.
Breastfeeding
Do not breastfeed while taking this medicine and for 3 days after the last dose. This is because
it is not known 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 will perform a pregnancy test before starting treatment.
You must use effective contraceptive methods while taking VITRAKVI and for at least 1 month after
the last dose, if

• you are of childbearing potential. If you are using 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 which contraceptive method is most suitable for you.

Driving and using machines
VITRAKVI can cause dizziness or tiredness. If you experience these effects, do not drive, ride a bicycle and do not
use any tools or machinery.

3. How to take VITRAKVI

Take this medicine following exactly the instructions of your doctor or pharmacist. If you
have any doubts, consult your doctor, pharmacist or nurse.

What dose to take
Adults (from 18 years of age)

• The recommended dose of VITRAKVI is 100 mg (1 capsule of 100 mg or 4 capsules of 25 mg), twice a day.
• The doctor will check the dose and modify it as needed.

Children and adolescents

• The pediatrician will determine the appropriate dose for your child based on height and weight.
• The maximum recommended dose is 100 mg (1 capsule of 100 mg or 4 capsules of 25 mg), twice a day.
• The pediatrician will check the dose and modify it as needed.

For patients who are unable to swallow the capsules, an oral solution of
VITRAKVI is available.

How to take this medicine

• VITRAKVI can be taken independently of meals.
• Do not eat grapefruit or drink grapefruit juice during treatment with this medicine.
• Swallow 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
Contact your doctor, pharmacist or nurse or go to the hospital immediately. Bring with you the

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

If you stop taking VITRAKVI
Do not stop treatment with this medicine without consulting your doctor. It is important
that you take VITRAKVI for the entire time prescribed by your doctor.
If you are unable to take the medicine as prescribed by your doctor, contact your doctor immediately.
If you have any doubts about the use of this medicine, contact your doctor, pharmacist or
nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will get them.

Contact your doctor immediatelyif you experience any of the following serious side effects:

• feeling dizzy (a very common side effect that can affect more than 1 in 10 people), tingling, numbness or burning sensation in the hands and feet, difficulty walking normally (a common side effect that can affect up to 1 in 10 people). These side effects may be symptoms of problems with the nervous system. Your doctor may decide to reduce the dose or to stop or discontinue treatment permanently.

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):

• pale skin and feeling your heartbeat, which may be symptoms of a low number of red blood cells (anaemia)
• flu-like symptoms, including fever, which may be symptoms of a low number of white blood cells (neutropenia, leucopenia)
• feeling or being unwell (nausea or vomiting)
• diarrhoea
• constipation
• muscle pain (myalgia)
• feeling tired (fatigue)
• increased levels of liver enzymes in blood tests
• weight gain.

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

• increased tendency to bruising and bleeding, which may be a symptom of a reduced number of platelets (thrombocytopenia)
• altered sense of taste (dysgeusia)
• muscle weakness
• increased level of “alkaline phosphatase” in blood tests (very common in children).

Not known(frequency not known):

• fatigue, pain in the upper right part of the abdomen, loss of appetite, nausea or vomiting, yellowing of the skin or eyes, increased tendency to bruising and bleeding and dark urine may occur. 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
through the national reporting system listed in Annex V. By 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 package and on the bottle label after “Scad.” / “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 appear damaged.
• Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What VITRAKVI contains
The active ingredient 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 dewaxed
• Aluminium lake containing indigo carmine (E 132)
• Titanium dioxide (E 171)
• Propylene glycol (E 1520)
• Dimethicone 1000

Description of the appearance of VITRAKVI and contents of the pack

• VITRAKVI 25 mg is supplied as an opaque white hard gelatin capsule, (18 mm in length x 6 mm in width), with the BAYER cross and “25 mg” printed in blue on the capsule body.
• VITRAKVI 100 mg is supplied as an opaque white hard gelatin capsule, (22 mm in length x 7 mm in width), with the BAYER cross and “100 mg” printed in blue on the capsule body.

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

Marketing Authorisation Holder
Bayer AG
51368 Leverkusen
Germany

Manufacturer
Bayer AG
Kaiser-Wilhelm-Allee
51368 Leverkusen
Germany
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
Bayer SA-NV
Tél/Tel: +32-(0)2-535 63 11

Lietuva
UAB Bayer
Tel. +37 05 23 36 868

България
Байер България ЕООД
Tел.: +359 (0)2 4247280

Luxembourg/Luxemburg
Bayer SA-NV
Tél/Tel: +32-(0)2-535 63 11

Česká republika
Bayer s.r.o.
Tel: +420 266 101 111

Magyarország
Bayer Hungária KFT
Tel:+36 14 87-41 00

Danmark
Bayer A/S
Tlf: +45 45 23 50 00

Malta
Alfred Gera and Sons Ltd.
Tel: +35 621 44 62 05

Deutschland
Bayer Vital GmbH
Tel: +49 (0)214-30 513 48

Nederland
Bayer B.V.
Tel: +31-23-799 1000

Eesti
Bayer OÜ
Tel: +372 655 8565

Norge
Bayer AS
Tlf: +47 23 13 05 00

Ελλάδα
Bayer Ελλάς ΑΒΕΕ
Τηλ: +30-210-61 87 500

Österreich
Bayer Austria Ges.m.b.H.
Tel: +43-(0)1-711 46-0

España
Bayer Hispania S.L.
Tel: +34-93-495 65 00

Polska
Bayer Sp. z o.o.
Tel: +48 22 572 35 00

France
Bayer HealthCare
Tél (N° vert): +33-(0)800 87 54 54

Portugal
Bayer Portugal, Lda.
Tel: +351 21 416 42 00

Hrvatska
Bayer d.o.o.
Tel: +385-(0)1-6599 900

România
SC Bayer SRL
Tel: +40 21 529 59 00

Ireland
Bayer Limited
Tel: +353 1 216 3300

Slovenija
Bayer d. o. o.
Tel: +386 (0)1 58 14 400

Ísland
Icepharma hf.
Sími: +354 540 8000

Slovenská republika
Bayer spol. s r.o.
Tel. +421 2 59 21 31 11

Italia
Bayer S.p.A.
Tel: +39 02 397 8 1

Suomi/Finland
Bayer Oy
Puh/Tel: +358- 20 785 21

Κύπρος
NOVAGEM Limited
Τηλ: +357 22 48 38 58

Sverige
Bayer AB
Tel: +46 (0) 8 580 223 00

Latvija
SIA Bayer
Tel: +371 67 84 55 63
An authorisation “subject to conditions” has been granted for this medicinal product. This means that
further data must be provided on this medicinal product.
The European Medicines Agency will review the new information at least annually.
More detailed information on this medicinal product is available on the website of the European
Medicines Agency: https://www.ema.europa.eu.

VITRAKVI 20 mg/mL oral solution

larotrectinib

Medicinal product subject to additional monitoring. This will allow the rapid identification of
new safety information. You can contribute by reporting any adverse effects
experienced during the use of this medicinal product. See the end of section 4 for
information on how to report adverse effects.

Read this leaflet carefully before you start to take this medicine as it contains
important information for you.

• Keep this leaflet. 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. Do not pass it on to others, even if they have the same symptoms as you, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

medicinal product. If you are giving this medicine to your child, replace “you” with “your child”.

Contents of 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 is VITRAKVI and what is it used for

What is VITRAKVI used for
VITRAKVI contains the active substance larotrectinib.
It is used in adults, adolescents and children to treat solid tumors (cancer) in various
parts of the body that are caused by an alteration in the NTRK gene ( Neurotrophic Tyrosine Receptor

Kinase, neurotrophic tyrosine receptor kinase).
VITRAKVI is used only if

• these tumors are in an advanced stage of disease or have spread to other parts of the body, or when surgical removal of the tumor could cause serious complications and
• there are no satisfactory treatment options.

Before administering VITRAKVI, the doctor will perform a test to verify the presence of this
alteration of the NTRK gene.

How does VITRAKVI work
In patients with tumors due to an alteration of the NTRK gene, this alteration causes the body to produce
an abnormal protein called a TRK fusion protein, which can lead to
uncontrolled cell growth and tumor development.
VITRAKVI blocks the action of TRK fusion proteins and can therefore reduce or stop the growth
of the tumor. It may also help to reduce the tumor.
If you have questions about how VITRAKVI works or why it has been prescribed for you, please ask your
doctor, pharmacist or nurse.

2. What you need to know before you take VITRAKVI

Do not take VITRAKVI if

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

Tests and checks
VITRAKVI may increase the levels of liver enzymes ALT, AST and bilirubin in the blood. Your doctor
will perform blood tests before and during treatment to measure levels of ALT, AST and
bilirubin and check 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 can change the action of
VITRAKVI or because VITRAKVI can change the action of other medicines.
In particular, tell your doctor, pharmacist or nurse if you are taking any of the
following medicines:

• medicines used for the treatment of fungal or bacterial infections, such as itraconazole, voriconazole, clarithromycin, telithromycin, troleandomycin
• a medicine used for the treatment of Cushing's syndrome, ketoconazole
• medicines used for the treatment of HIV infection, such as atazanavir, indinavir, nelfinavir, ritonavir, saquinavir, rifabutin, efavirenz
• a medicine used for the treatment of depression, nefazodone
• medicines used for the treatment of epilepsy, such as phenytoin, carbamazepine, phenobarbital
• a herbal medicine used for the treatment of depression, known as St John's Wort
• a medicine used for the treatment of tuberculosis, rifampicin
• a medicine used to relieve severe pain, alfentanil
• medicines used to prevent rejection after an organ transplant, such as cyclosporine, sirolimus, tacrolimus
• a medicine used for the treatment of irregular heart rhythms, quinidine
• medicines used for the treatment of migraine, such as dihydroergotamine, ergotamine
• a medicine used for the long-term treatment of pain, fentanyl
• a medicine used to control involuntary movements or sounds, pimozide
• a medicine that helps you to stop smoking, bupropion
• medicines to reduce blood sugar levels, such as repaglinide, tolbutamide
• a medicine that prevents blood clots, warfarin
• a medicine used to reduce the amount of acid produced by the stomach, omeprazole
• a medicine that helps to control high blood pressure, valsartan
• a group of medicines that help to lower cholesterol, statins
• medicines containing hormones used for contraception, see section “contraception – for men and women” below. If any of these apply to you (or if you are unsure), speak to your doctor, pharmacist or nurse.

VITRAKVI with food and drink
Do not eat grapefruit or drink grapefruit juice during treatment with VITRAKVI. This
is because grapefruit can increase the amount of VITRAKVI in the body.

Pregnancy and breastfeeding
Pregnancy
If you are pregnant, suspect you are pregnant or are planning to become pregnant, ask your doctor
or pharmacist for advice before taking this medicine.
You should not take VITRAKVI during pregnancy as the effect of VITRAKVI on the
fetus is unknown.
Breastfeeding
Do not breastfeed while taking this medicine and for 3 days after the last dose. This is because
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 will need to perform a pregnancy test before starting treatment.
You must use effective contraceptive methods while taking VITRAKVI and for at least 1 month after
the last dose, if

• you are of childbearing potential. If you are using 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 which contraceptive method is most suitable for you.

Driving and using machines
VITRAKVI can cause dizziness or fatigue. If this happens, do not drive, cycle or
use any tools or machinery.

VITRAKVI contains:

• sucrose:may be harmful to teeth. If your doctor has told you that you have an intolerance to some sugars, contact your doctor 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 is intolerant to some sugars, or if you have a diagnosis of hereditary fructose intolerance, a rare genetic illness where patients are unable to process fructose, talk to your doctor before you or your child takes this medicine.
• less than 1 mmol (23 mg) of sodiumper 5 mL, that is to say essentially ‘sodium-free’.
• 1.2 mg of propylene glycolin 1 mL. If the child is less than 4 weeks old, talk to your doctor or pharmacist before giving this medicine, especially if the child is taking other medicines containing propylene glycol or alcohol.
• parahydroxybenzoate: may cause allergic reactions (including delayed reactions)

3. How to take VITRAKVI

Take this medicine following exactly the instructions of your doctor or pharmacist. If you
have any doubts, consult your doctor, pharmacist or nurse.

What dose to take
Adults (from 18 years of age)

• The recommended dose of VITRAKVI is 100 mg (5 mL), twice a day.
• The doctor will check the dose and adjust it as needed.

Children and adolescents

• The pediatrician will determine the appropriate dose for your child based on height and weight.
• The maximum recommended dose is 100 mg (5 mL), twice a day.
• The pediatrician will check the dose and adjust it as needed.

How to take this medicine

• VITRAKVI can be taken independently of meals.
• Do not eat grapefruit or drink grapefruit juice during treatment with this medicine.
• To take this medicine you need an adapter for the bottle (28 mm in diameter) and a syringe that can be used to administer medicines by mouth. Use a 1 ml syringe with 0.1 ml increments for doses less than 1 ml. Use a 5 ml syringe with 0.2 ml increments for doses equal to or greater than 1 ml.
• Press on the closing cap of the bottle and rotate it counterclockwise to open the bottle.
• Insert the adapter into the neck of the bottle and make sure it is securely attached.
• Press the plunger of the syringe completely into the syringe, then insert the syringe into the opening of the adapter. Turn the bottle upside down.
• Fill the syringe with a small amount of solution by pulling the plunger down, then push the plunger up to remove any large air bubbles present in the syringe.
• Pull the plunger down to the mark corresponding to the dose in mL prescribed by the doctor.
• Straighten the bottle and remove the syringe from the adapter.
• Place the syringe in your mouth, holding it towards the inside of your cheek - this will help you swallow the medicine naturally. Press the plunger slowly.
• Close the bottle tightly with the closing cap - leave the adapter in the bottle. If necessary, VITRAKVI can be administered with a nasogastric tube. For detailed information, consult your doctor, pharmacist or nurse.

If you take more VITRAKVI than you should
Contact your doctor, pharmacist or nurse or go to the hospital immediately. Bring with you the

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

If you stop taking VITRAKVI
Do not stop treatment with this medicine without consulting your doctor. It is important
that you take VITRAKVI for the entire time prescribed by your doctor.
If you are unable to take the medicine as prescribed by your doctor, contact your doctor immediately.
If you have any questions about the use of this medicine, consult your doctor, pharmacist or
nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Contact your doctor immediatelyif you experience any of the following serious side effects:

• feeling of dizziness (a very common side effect that can affect more than 1 in 10 people), tingling, numbness or burning sensation in the hands and feet, difficulty walking normally (a common side effect that can affect up to 1 in 10 people). These side effects may be symptoms of problems with the nervous system. Your doctor may decide to reduce the dose or to stop or discontinue treatment permanently.

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):

• pale skin and feeling of heartbeat, which may be symptoms of a low number of red blood cells (anemia)
• flu-like symptoms, including fever, which may be symptoms of a low number of white blood cells (neutropenia, leucopenia)
• feeling or state of unwellness (nausea or vomiting)
• diarrhea
• constipation
• muscle pain (myalgia)
• feeling of tiredness (fatigue)
• increased level of liver enzymes in blood tests
• weight gain.

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

• increased tendency to bruise and bleed, which may be a symptom of a reduced number of platelets (thrombocytopenia)
• altered taste perception (dysgeusia)
• muscle weakness
• increased level of “alkaline phosphatase” in blood tests (very common in children).

Not known(frequency not known):

• fatigue, pain in the upper right part of the stomach, loss of appetite, nausea or vomiting, yellowing of the skin or eyes, increased tendency to bruise and bleed, and dark urine may occur. 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
through the national reporting system listed in Annex V. By 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 pack and on the bottle label after “Scad.” / “EXP”. The expiry date refers to the last day of that month.
• Store in a refrigerator (2 °C - 8 °C).
• Do not freeze.
• After opening the vial, you must use the medicine within 30 days of opening.
• Do not take the medicine if the vial or its screw cap appears damaged or if there seems to be any leakage.
• Do not dispose of any medicine in waste water or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package Contents and Other Information

What VITRAKVI contains
The active ingredient is larotrectinib.
Each mL of oral solution contains 20 mg of larotrectinib (as larotrectinib sulfate).
The other ingredients are:

• Purified water
• Sucrose
• Hydropropyl betadex 0.69
• Glycerol (E 422)
• Sorbitol (E 420)
• Sodium citrate (E 331)
• Disodium hydrogen phosphate dihydrate (E 339)
• Citric acid (E 330)
• Propylene glycol (E 1520)
• Potassium sorbate (E 202)
• Methyl parahydroxybenzoate (E 218)
• Citrus aroma
• Natural aroma

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

Description of the appearance of VITRAKVI and contents of the pack
VITRAKVI is a clear oral solution, from yellow to orange in color.
Each pack contains 1 child-resistant glass bottle containing 100 mL of oral solution.

Marketing Authorisation Holder
Bayer AG
51368 Leverkusen
Germany

Manufacturer
Bayer AG
Kaiser-Wilhelm-Allee
51368 Leverkusen
Germany
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
Bayer SA-NV
Tél/Tel: +32-(0)2-535 63 11

Lietuva
UAB Bayer
Tel. +37 05 23 36 868

България
Байер България ЕООД
Tел.: +359 (0)2 4247280

Luxembourg/Luxemburg
Bayer SA-NV
Tél/Tel: +32-(0)2-535 63 11

Česká republika
Bayer s.r.o.
Tel: +420 266 101 111

Magyarország
Bayer Hungária KFT
Tel:+36 14 87-41 00

Danmark
Bayer A/S
Tlf: +45 45 23 50 00

Malta
Alfred Gera and Sons Ltd.
Tel: +35 621 44 62 05

Deutschland
Bayer Vital GmbH
Tel: +49 (0)214-30 513 48

Nederland
Bayer B.V.
Tel: +31-23-799 1000

Eesti
Bayer OÜ
Tel: +372 655 8565

Norge
Bayer AS
Tlf: +47 23 13 05 00

Ελλάδα
Bayer Ελλάς ΑΒΕΕ
Τηλ: +30-210-61 87 500

Österreich
Bayer Austria Ges.m.b.H.
Tel: +43-(0)1-711 46-0

España
Bayer Hispania S.L.
Tel: +34-93-495 65 00

Polska
Bayer Sp. z o.o.
Tel: +48 22 572 35 00

France
Bayer HealthCare
Tél (N° vert): +33-(0)800 87 54 54

Portugal
Bayer Portugal, Lda.
Tel: +351 21 416 42 00

Hrvatska
Bayer d.o.o.
Tel: +385-(0)1-6599 900

România
SC Bayer SRL
Tel: +40 21 529 59 00

Ireland
Bayer Limited
Tel: +353 1 216 3300

Slovenija
Bayer d. o. o.
Tel: +386 (0)1 58 14 400

Ísland
Icepharma hf.
Sími: +354 540 8000

Slovenská republika
Bayer spol. s r.o.
Tel. +421 2 59 21 31 11

Italia
Bayer S.p.A.
Tel: +39 02 397 8 1

Suomi/Finland
Bayer Oy
Puh/Tel: +358- 20 785 21

Κύπρος
NOVAGEM Limited
Τηλ: +357 22 48 38 58

Sverige
Bayer AB
Tel: +46 (0) 8 580 223 00

Latvija
SIA Bayer
Tel: +371 67 84 55 63
An authorisation has been granted for this medicinal product under Article 57(k) of Regulation (EC) No 726/2004.
This means that the medicinal product is subject to additional monitoring.
The European Medicines Agency will review the new information on this medicinal product at least annually.
More detailed information on this medicinal product is available on the website of the European Medicines
Agency: https://www.ema.europa.eu .

VITRAKVI 20 mg/mL oral solution

larotrectinib

Medicinal product subject to additional monitoring. This will allow the rapid identification of
new safety information. You can contribute by reporting any adverse effects
experienced during the use of this medicinal product. See the end of section 4 for
information on how to report adverse effects.

Read this leaflet carefully before you start to take this medicine as it contains
important information for you.

• Keep this leaflet. 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. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

medicinal product. If you are giving this medicine to your child, replace “you” with “your child”.

Contents of 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 is VITRAKVI and what is it used for

What is VITRAKVI used for
VITRAKVI contains the active substance larotrectinib.
It is used in adults, adolescents and children to treat solid tumors (cancer) in various
parts of the body that are caused by an alteration in the NTRK gene ( Neurotrophic Tyrosine Receptor

Kinase, neurotrophic tyrosine kinase receptor).
VITRAKVI is used only if

• these tumors are in an advanced stage of disease or have spread to other parts of the body, or when surgical removal of the tumor could cause serious complications and
• there are no satisfactory treatment options.

Before administering VITRAKVI, your doctor will perform a test to check for this
alteration of the NTRK gene.

How does VITRAKVI work
In patients with cancer due to an alteration of the NTRK gene, this alteration causes the body to produce
an abnormal protein called a TRK fusion protein, which can lead to
uncontrolled cell growth and tumor development.
VITRAKVI blocks the action of TRK fusion proteins and can therefore reduce or stop the growth
of the tumor. It may also help to reduce the tumor.
If you have any questions about how VITRAKVI works or why it has been prescribed to 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 monitoring
VITRAKVI may increase the levels of liver enzymes ALT, AST and bilirubin in the blood. Your doctor
will perform blood tests before and during treatment to measure the levels of ALT, AST and
bilirubin and check 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 can affect the action of
VITRAKVI or because VITRAKVI can affect the action of other medicines.
In particular, tell your doctor, pharmacist or nurse if you are taking any of the
following medicines:

• medicines used for the treatment of fungal or bacterial infections, such as itraconazole, voriconazole, clarithromycin, telithromycin, troleandomycin
• a medicine used for the treatment of Cushing's syndrome, ketoconazole
• medicines used for the treatment of HIV infection, such as atazanavir, indinavir, nelfinavir, ritonavir, saquinavir, rifabutin, efavirenz
• a medicine used for the treatment of depression, nefazodone
• medicines used for the treatment of epilepsy, such as phenytoin, carbamazepine, phenobarbital
• a herbal medicine used for the treatment of depression, known as St John's Wort
• a medicine used for the treatment of tuberculosis, rifampicin
• a medicine used to relieve severe pain, alfentanil
• medicines used to prevent rejection after an organ transplant, such as cyclosporine, sirolimus, tacrolimus
• a medicine used for the treatment of irregular heartbeats, quinidine
• medicines used for the treatment of migraine, such as dihydroergotamine, ergotamine
• a medicine used for the long-term treatment of pain, fentanyl
• a medicine used to control involuntary movements or sounds, pimozide
• a medicine that helps you to stop smoking, bupropion
• medicines to reduce blood sugar levels, such as repaglinide, tolbutamide
• a medicine that prevents blood clots, warfarin
• a medicine used to reduce the amount of acid produced by the stomach, omeprazole
• a medicine that helps to control high blood pressure, valsartan
• a group of medicines that help to lower cholesterol, statins
• medicines containing hormones used for contraception, see section “contraception – for men and women” below. If any of these apply to you (or if you are unsure), talk to your doctor, pharmacist or nurse.

VITRAKVI with food and drink
Do not eat grapefruit or drink grapefruit juice while taking VITRAKVI. This
is because grapefruit can increase the amount of VITRAKVI in the body.

Pregnancy and breastfeeding
Pregnancy
If you are pregnant, suspect you are pregnant or are planning to become pregnant, ask your doctor
or pharmacist for advice before taking this medicine.
You should not take VITRAKVI during pregnancy as the effect of VITRAKVI on the
foetus is unknown.
Breastfeeding
Do not breastfeed while taking this medicine and for 3 days after the last dose. This is because
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 will perform a pregnancy test before starting treatment.
You must use effective contraceptive methods while taking VITRAKVI and for at least 1 month after
the last dose, if

• you are of childbearing potential. If you are using hormonal contraceptives, you should also use a barrier method, such as a condom.
• you have sexual relations with a man of childbearing potential. Ask your doctor which contraceptive method is most suitable for you.

Driving and using machines
VITRAKVI can cause dizziness or fatigue. If this happens, do not drive, cycle or
use any tools or machinery.

VITRAKVI contains:

• 2 mg of sodium benzoatein 1 mL
• less than 1 mmol (23 mg) of sodiumper 5 mL, that is to say essentially ‘sodium-free’.

3. How to take VITRAKVI

Take this medicine following exactly the instructions of your doctor or pharmacist. If you
have any doubts, ask your doctor, pharmacist or nurse.

What dose to take
Adults (from 18 years of age)

• The recommended dose of VITRAKVI is 100 mg (5 mL), twice a day.
• The doctor will check the dose and adjust it as needed.

Children and adolescents

• The pediatrician will determine the appropriate dose for your child based on height and weight.
• The maximum recommended dose is 100 mg (5 mL), twice a day.
• The pediatrician will check the dose and adjust it as needed.

How to take this medicine

• VITRAKVI can be taken independently of meals.
• Do not eat grapefruit or drink grapefruit juice during treatment with this medicine.
• To take this medicine you need an adapter for the bottle (28 mm in diameter) and a syringe that can be used to administer medicines by mouth. Use a 1 ml syringe with 0.1 ml increments for doses less than 1 ml. Use a 5 ml syringe with 0.2 ml increments for doses equal to or greater than 1 ml.
• Press on the closing cap of the bottle and rotate it counterclockwise to open the bottle.
• Insert the adapter into the neck of the bottle and make sure it is firmly attached.
• Press the plunger of the syringe completely, then insert the syringe into the opening of the adapter. Turn the bottle upside down.
• Fill the syringe with a small amount of solution by pulling the plunger down, then push the plunger up to remove any large air bubbles present in the syringe.
• Pull the plunger down to the mark corresponding to the dose in mL prescribed by the doctor.
• Straighten the bottle and remove the syringe from the adapter.
• Place the syringe in your mouth, holding it towards the inside of your cheek - this will help you swallow the medicine naturally. Press the plunger slowly.
• Close the bottle tightly with the closing cap - leave the adapter in the bottle. If necessary, VITRAKVI can be administered with a nasogastric tube. For detailed information, please contact your doctor, pharmacist or nurse.

If you take more VITRAKVI than you should
Contact your doctor, pharmacist or nurse or go to the hospital immediately. Bring with you the

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

If you stop taking VITRAKVI
Do not stop treatment with this medicine without consulting your doctor. It is important
that you take VITRAKVI for the entire time prescribed by your doctor.
If you are unable to take the medicine as prescribed by your doctor, contact your doctor immediately.
If you have any doubts about 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.

Contact your doctor immediatelyif you experience any of the following serious side effects:

• feeling of dizziness (a very common side effect that can affect more than 1 in 10 people), tingling, numbness or burning sensation in the hands and feet, difficulty walking normally (a common side effect that can affect up to 1 in 10 people). These side effects may be symptoms of problems with the nervous system. Your doctor may decide to reduce the dose or stop or discontinue treatment permanently.

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):

• pale skin and feeling of heartbeat, which may be symptoms of a low number of red blood cells (anemia)
• flu-like symptoms, including fever, which may be symptoms of a low number of white blood cells (neutropenia, leukopenia)
• feeling or state of unwellness (nausea or vomiting)
• diarrhea
• constipation
• muscle pain (myalgia)
• feeling tired (fatigue)
• increased levels of liver enzymes in blood tests
• weight gain.

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

• increased tendency to bruising and bleeding, which may be a symptom of a reduced number of platelets (thrombocytopenia)
• altered sense of taste (dysgeusia)
• muscle weakness
• increased level of “alkaline phosphatase” in blood tests (very common in children).

Not known(frequency not known):

• fatigue, pain in the upper right part of the stomach, loss of appetite, nausea or vomiting, yellowing of the skin or eyes, increased tendency to bruising and bleeding and dark urine may occur. 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 through the national reporting system listed in Annex V. By 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 package and on the bottle label after “Scad.” / “EXP”. The expiry date refers to the last day of that month.
• Store in a refrigerator (2 °C - 8 °C).
• Do not freeze.
• After opening the vial, you must use the medicine within 10 days of opening.
• Do not take the medicine if the vial or its screw cap appears damaged or if there seems to be any leakage.
• Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What VITRAKVI contains
The active ingredient is larotrectinib.
Each mL of oral solution contains 20 mg of larotrectinib (as sulfate).
The other ingredients are:

• purified water
• hydroxypropyl betadex 0.69
• sucralose (E 955)
• sodium citrate (E 331)
• sodium benzoate (E 211)
• strawberry flavour
• citric acid (E 330)

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

Description of the appearance of VITRAKVI and contents of the pack
VITRAKVI is an oral solution from colourless to yellow or orange or red or brownish.
Each pack contains 2 child-resistant glass bottles containing 50 mL of oral solution
each.

Marketing Authorisation Holder
Bayer AG
51368 Leverkusen
Germany

Manufacturer
Bayer AG
Kaiser-Wilhelm-Allee
51368 Leverkusen
Germany
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
Bayer SA-NV
Tél/Tel: +32-(0)2-535 63 11

Lietuva
UAB Bayer
Tel. +37 05 23 36 868

България
Байер България ЕООД
Tел.: +359 (0)2 4247280

Luxembourg/Luxemburg
Bayer SA-NV
Tél/Tel: +32-(0)2-535 63 11

Česká republika
Bayer s.r.o.
Tel: +420 266 101 111

Magyarország
Bayer Hungária KFT
Tel:+36 14 87-41 00

Danmark
Bayer A/S
Tlf: +45 45 23 50 00

Malta
Alfred Gera and Sons Ltd.
Tel: +35 621 44 62 05

Deutschland
Bayer Vital GmbH
Tel: +49 (0)214-30 513 48

Nederland
Bayer B.V.
Tel: +31-23-799 1000

Eesti
Bayer OÜ
Tel: +372 655 8565

Norge
Bayer AS
Tlf: +47 23 13 05 00

Ελλάδα
Bayer Ελλάς ΑΒΕΕ
Τηλ: +30-210-61 87 500

Österreich
Bayer Austria Ges.m.b.H.
Tel: +43-(0)1-711 46-0

España
Bayer Hispania S.L.
Tel: +34-93-495 65 00

Polska
Bayer Sp. z o.o.
Tel: +48 22 572 35 00

France
Bayer HealthCare
Tél (N° vert): +33-(0)800 87 54 54

Portugal
Bayer Portugal, Lda.
Tel: +351 21 416 42 00

Hrvatska
Bayer d.o.o.
Tel: +385-(0)1-6599 900

România
SC Bayer SRL
Tel: +40 21 529 59 00

Ireland
Bayer Limited
Tel: +353 1 216 3300

Slovenija
Bayer d. o. o.
Tel: +386 (0)1 58 14 400

Ísland
Icepharma hf.
Sími: +354 540 8000

Slovenská republika
Bayer spol. s r.o.
Tel. +421 2 59 21 31 11

Italia
Bayer S.p.A.
Tel: +39 02 397 8 1

Suomi/Finland
Bayer Oy
Puh/Tel: +358- 20 785 21

Κύπρος
NOVAGEM Limited
Τηλ: +357 22 48 38 58

Sverige
Bayer AB
Tel: +46 (0) 8 580 223 00

Latvija
SIA Bayer
Tel: +371 67 84 55 63
This medicinal product is subject to additional monitoring. This means that further information may be
required.
The European Medicines Agency will review the new information at least annually.
More detailed information on this medicinal product is available on the website of the European
Medicines Agency: https://www.ema.europa.eu.