ENTYVIO 300 mg Порошок Для Раствора Для Внутривенного Введения

Содержание инструкции

1. Entyvio 300 mg powder for concentrate for solution for infusion
   1. What is Entyvio and what it is used for
   2. What you need to know before you are given Entyvio
   3. How Entyvio will be administered
   4. Possible side effects
   5. How to store Entyvio
   6. Package contents and other information
2. Entyvio 108 mg solution for injection in pre-filled syringe
   1. What is Entyvio and what is it used for
   2. What you need to know before you use Entyvio
   3. How to use Entyvio
   4. Possible side effects
   5. How to store Entyvio
   6. Content of the pack and other information
3. Entyvio 108 mg injectable solution in a pre-filled pen
   1. What is Entyvio and what is it used for
   2. What you need to know before you use Entyvio
   3. How to use Entyvio
   4. Possible side effects
   5. How to store Entyvio
   6. Contents of the pack and other information

Entyvio 300 mg powder for concentrate for solution for infusion

vedolizumab

Read this leaflet carefully before you start using 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 or nurse.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet

• 1. What Entyvio is and what it is used for
• 2. What you need to know before Entyvio is administered to you
• 3. How Entyvio will be administered to you
• 4. Possible side effects
• 5. How to store Entyvio
• 6. Contents of the pack and other information

1. What is Entyvio and what it is used for

What is Entyvio
Entyvio contains the active substance ‘vedolizumab’. Vedolizumab belongs to a group of biological medicines
called monoclonal antibodies (MAb, from Monoclonal Antibodies).

How Entyvio works
Entyvio works by blocking a protein present on the surface of white blood cells that causes
inflammation in ulcerative colitis, Crohn's disease and pouchitis. This reduces the extent
of the inflammation.

What Entyvio is used for
Entyvio is used to treat signs and symptoms in adults with:

• active moderate to severe ulcerative colitis
• active moderate to severe Crohn's disease
• active moderate to severe chronic pouchitis.

Ulcerative colitis
Ulcerative colitis is a disease that causes inflammation of the large intestine. If you have ulcerative
colitis, you will first be prescribed other medicines. If you do not respond adequately or are unable to
tolerate these medicines, your doctor may prescribe Entyvio to reduce signs and symptoms of the
disease.
Crohn's disease
Crohn's disease is a disease that causes inflammation of the digestive system. If you have Crohn's
disease, you will first be given other medicines. If you do not respond adequately or
are unable to tolerate these medicines, your doctor may prescribe Entyvio to reduce signs and
symptoms of the disease.
Pouchitis
Pouchitis is a disease that causes inflammation of the inner lining of the pouch
created during surgery to treat ulcerative colitis. If you have pouchitis, you may
first be prescribed antibiotics. If you do not respond adequately to antibiotics, your
doctor may prescribe Entyvio to reduce signs and symptoms of the disease.

2. What you need to know before you are given Entyvio

Do not use Entyvio

• if you are allergic to vedolizumab or any of the other ingredients of this medicine (listed in section 6).
• if you have a serious active infection, such as TB (tuberculosis), blood infection (sepsis), severe diarrhoea and vomiting (gastroenteritis), or infection of the nervous system.

Warnings and precautions
Talk to your doctor or nurse before you are given Entyvio.

Tell your doctor or nurse immediatelywhen you receive this medicine for the first
time, during treatment, and between doses:

• if you experience blurred vision, loss of vision, or double vision, difficulty speaking, weakness in an arm or leg, changes in the way you walk, or problems with balance, persistent numbness, reduced or loss of sensation, memory loss, or confusion. These could all be symptoms of a serious brain disease that can be fatalcalled progressive multifocal leukoencephalopathy (PML, from the English Progressive Multifocal Leukoencephalopathy).
• if you have, or think you have, an infection: signs of infection include chills, tremors, persistent cough, or high fever. Some infections can become serious and can be fatal if not treated.
• if you experience signs of an allergic reaction or another reaction to the infusion, such as wheezing, difficulty breathing, hives, itching, swelling, or dizziness. These symptoms may occur during or after the infusion. For more details, see infusion and allergic reactions in section 4.
• if you are about to have a vaccinationor have recently had a vaccination. Entyvio may affect your response to the vaccination.
• if you have cancer, tell your doctor. The doctor will decide if you can still receive Entyvio.
• if you do not feel better, as in patients with very active Crohn's disease, the effect of vedolizumab may take up to 14 weeks to appear.

Children and adolescents
The use of Entyvio is not recommended in children or adolescents (under 18 years of age), due to the lack of data on the use of this medicine in this age group.

Other medicines and Entyvio
Tell your doctor or nurse if you are taking, have recently taken, or might take
any other medicines.

• Entyvio should not be given with other biological medicines that suppress the immune system, as the effects of this combination are unknown.

Tell your doctor if you have previously taken:

• natalizumab (a medicine for multiple sclerosis) or
• rituximab (a medicine for some types of cancer and rheumatoid arthritis). The doctor will decide if you can still receive Entyvio.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding with
breast milk, ask your doctor for advice before taking this medicine.
Pregnancy
The effects of Entyvio on pregnant women are unknown. This medicine is therefore not
recommended during pregnancy. You and your doctor must decide if the benefit to you
clearly outweighs the potential risk to you and your baby.
If you are a woman of childbearing potential, it is recommended to avoid pregnancy while using Entyvio. You should
use adequate contraception during treatment and for at least 4.5 months after
the last treatment.
Breastfeeding
Tell your doctor if you are breastfeeding or intend to do so. Entyvio passes into breast milk. Information regarding the possible effects on the baby and milk production is insufficient.
A decision must be made whether to discontinue breastfeeding or discontinue therapy with Entyvio
taking into account the benefit of breastfeeding for your baby and the benefit of
therapy for you.

Driving and using machines
This medicine slightly impairs the ability to drive or operate tools or machines. A
small number of patients have experienced dizziness after receiving Entyvio. If this happens,
do not drive or operate tools or machines.

3. How Entyvio will be administered

How much Entyvio you will receive
Treatment with Entyvio is the same for ulcerative colitis, Crohn's disease and pouchitis.
The recommended dose is 300 mg of Entyvio administered as follows (see the table
below):
Treatment number (infusion) Timing of treatment (infusion)
Treatment 1 0 weeks
Treatment 2 2 weeks after treatment 1
Treatment 3 6 weeks after treatment 1
Further treatments Every 8 weeks
The doctor may decide to modify this treatment schedule based on the effectiveness
that Entyvio has on you.

• The infusion will be administered to you by a doctor or nurse, via intravenous drip into a vein in your arm (intravenous infusion) over 30 minutes.
• For the first 2 infusions, the doctor or nurse will monitor you carefully during the infusion and for approximately 2 hours after it is completed. For all subsequent infusions (after the first 2), you will be monitored during the infusion and for approximately 1 hour after it is completed.

If you forget or miss your Entyvio infusion
If you forget or miss an appointment for the infusion, schedule another
appointment as soon as possible.

If you stop taking Entyvio
Do not stop taking Entyvio without first consulting your doctor.
If you have any questions about the use of this medicine, ask your doctor or nurse.

4. Possible side effects

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

Serious side effects
Tell your doctor immediatelyif you notice any of the following symptoms:

• allergic reactions (may affect up to 1 in 100 people). Signs of an allergic reaction include: wheezing or difficulty breathing, hives, itchy skin, swelling, feeling unwell, pain at the infusion site, skin redness;
• infections (may affect up to 1 in 10 people). Signs of infection include: chills or tremors, high fever or skin rash.

Other side effects
Tell your doctor as soon as possibleif you notice any of the following symptoms:

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

• cold
• joint pain
• headache

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

• lung infection
• infection of the large intestine due to the bacterium Clostridium difficile
• fever
• chest infection
• changes in liver function, increased liver enzymes (indicated by blood tests)
• fatigue
• cough
• flu
• back pain
• sore throat
• sinusitis
• itching
• skin rash and redness
• pain in legs and/or arms
• muscle cramps
• muscle weakness
• throat infection
• gastrointestinal flu
• anal infection
• anal fissures
• hard stools
• bloated stomach
• intestinal gas
• high blood pressure
• tingling or prickling
• heartburn
• hemorrhoids
• stuffy nose
• eczema
• night sweats
• acne (pimples)
• rectal bleeding
• chest discomfort
• shingles (herpes zoster)

Uncommon side effects(may affect up to 1 in 100 people):

• redness and tenderness of hair follicles
• yeast infection of the throat and mouth
• vaginal infection
• blurred vision (loss of sharpness of vision)

Very rare side effects(may affect up to 1 in 10,000 people):

• sudden severe allergic reaction that can cause difficulty breathing, swelling, rapid heartbeat, sweating, drop in blood pressure, feeling dizzy, loss of consciousness and collapse (anaphylactic reaction and anaphylactic shock)
• inflammation of the liver (hepatitis). Signs and symptoms of hepatitis may include abnormal liver function tests, yellowing of the skin or whites of the eyes (jaundice), pain on the right side of the area corresponding to the stomach, bruising.

Not known(frequency cannot be estimated from available data):

• lung disease that causes shortness of breath (interstitial lung disease)

Reporting of side effects
If you get any side effects, talk to your doctor 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 detailed in Annex V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Entyvio

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 box and the label after
“Exp.”. The expiry date refers to the last day of that month.
Entyvio is generally administered by a doctor or nurse and patients should not
store or handle Entyvio.
Entyvio is for single use only.

Unopened vial:Store in a refrigerator (2 °C – 8 °C). Keep the vial in the
original packaging to protect the medicine from light.

Reconstituted and diluted solutions:Use immediately. If this is not possible, the solution
reconstituted in the vial can be stored for up to 8 hours at 2 °C-8 °C. The diluted solution in
sodium chloride 9 mg/mL (0.9%) solution for injection can be stored for up to 12 hours at
room temperature not exceeding 25 °C or up to 24 hours in a refrigerator (2 °C-8 °C), or up to 12 hours
at room temperature and in a refrigerator (2 °C-8 °C) for a total period of 24 hours. The period of
24 hours may include up to 8 hours at 2 °C-8 °C for the reconstituted solution in the vial and up to 12 hours
at 20 °C-25 °C for the diluted solution in the infusion bag, provided that the infusion bag is stored in a refrigerator (2 °C-8 °C) for the remaining part of the 24-hour period. The time
the reconstituted solution remains inside the vial must be subtracted from the allowed time for the solution inside the infusion bag.
Do not freeze.
Do not use this medicine if you notice the presence of particles in the liquid or a change in color (the
solution must be clear or opalescent, from colorless to yellowish) before
administration.
Do not dispose of any medicine in drains 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 Entyvio contains

• The active substanceis vedolizumab. Each vial contains 300 mg of vedolizumab.
• The other ingredientsare L-histidine, L-histidine monohydrochloride, L-arginine hydrochloride, sucrose and polysorbate 80.

Description of Entyvio and package contents

• Entyvio is a powder for concentrate for solution for infusion, of a colour from white to off-white, contained in glass vials with a rubber stopper and plastic cap.
• Each pack of Entyvio contains a single vial.

Marketing Authorisation Holder
Takeda Pharma A/S
Delta Park 45
2665 Vallensbaek Strand
Denmark

Manufacturer
Takeda Austria GmbH
St. Peter-Straβe 25
4020 Linz
Austria
For further information on this medicine, contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
Takeda Belgium NV
Tél/Tel: + 32 2 464 06 11
[email protected]

Lietuva
Takeda, UAB
Tel: +370 521 09 070
[email protected]

България
Такеда България ЕООД
Тел.: + 359 2 958 27 36
[email protected]

Luxembourg/Luxemburg
Takeda Belgium NV
Tél/Tel: + 32 2 464 06 11
[email protected]

Česká republika
Takeda Pharmaceuticals Czech Republic s.r.o.
Tel: +420 234 722 722
[email protected]

Magyarország
Takeda Pharma Kft.
Tel.: + 361 270 7030
[email protected]

Danmark
Takeda Pharma A/S
Tlf.: +45 46 77 10 10
[email protected]

Malta
Drugsales Ltd.
Tel.: + 356 2141 9070
[email protected]

Deutschland
Takeda GmbH
Tel.: + 49 (0) 800 825 3325
[email protected]

Nederland
Takeda Nederland B.V.
Tel.: + 31 20 203 5492
[email protected]

Eesti
Takeda Pharma OÜ
Tel.: + 372 6177 669
[email protected]

Norge
Takeda AS
Tlf: +47 800 800 30
[email protected]

Ελλάδα
TAKEDA ΕΛΛΑΣ Α.Ε.
Τηλ.: + 30 210 6387800
[email protected]

Österreich
Takeda Pharma Ges.m.b.H.
Tel.: + 43 (0) 800-20 80 50
[email protected]

España
Takeda Farmacéutica España, S.A.
Tel.: + 34 917 90 42 22
[email protected]

Polska
Takeda Pharma Sp. z o.o.
Tel.: +48223062447
[email protected]

France
Takeda France SAS
Tel.: + 33 1 40 67 33 00
[email protected]

Portugal
Takeda Farmacêuticos Portugal, Lda.
Tel.: + 351 21 120 1457
[email protected]

Hrvatska
Takeda Pharmaceuticals Croatia d.o.o.
Tel: + 385 1 377 88 96
[email protected]

România
Takeda Pharmaceuticals SRL
Tel.: +40 21 335 03 91
[email protected]

Slovenija
Takeda Pharmaceuticals farmacevtska družba
d.o.o.
Tel.: + 386 (0) 59 082 480
[email protected]

Ísland
Vistor hf.
Sími: + 354 535 7000
[email protected]

Ireland
Takeda Products Ireland Ltd.
Tel.: 1800 937 970
[email protected]

Slovenská republika
Takeda Pharmaceuticals Slovakia s.r.o.
Tel: + 421 (2) 20 602 600
[email protected]

Italia
Takeda Italia S.p.A.
Tel.: + 39 06 502601
[email protected]

Suomi/Finland
Takeda Oy
Puh/Tel: 0800 774 051
[email protected]

Κύπρος
A.POTAMITIS MEDICARE LTD
Τηλ: +357 22583333
[email protected]

Sverige
Takeda Pharma AB
Tel: 020 795 079
[email protected]

United Kingdom (Northern Ireland)
Takeda UK Ltd
Tel.: +44 (0) 3333 000 181
[email protected]

Other sources of information
This leaflet is available in formats suitable for blind or partially sighted patients, which can be requested from the local representative of the Marketing Authorisation Holder.
More detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu .
---------------------------------------------------------------------------------------------------------------------------

Latvija
Takeda Latvia SIA
Tel: +371 67840082
[email protected]
The following information is intended exclusively for healthcare professionals:
Traceability
In order to improve the traceability of biological medicines, the name and batch number of the medicine administered must be clearly recorded.
Instructions for reconstitution and infusion

• 1. Use aseptic technique to prepare Entyvio solution for intravenous infusion.
• 2. Remove the tear-off cap (flip-off) from the vial and wipe with an alcohol swab. Reconstitute vedolizumab with 4.8 mL of sterile water for injections, at room temperature (20 °C-25 °C), using a syringe with a 21-25 G needle.
• 3. Insert the needle into the vial through the center of the stopper and direct the liquid flow towards the wall of the vial to avoid excessive foaming.
• 4. Gently rotate the vial for at least 15 seconds. Do not shake vigorously, or invert.
• 5. Allow the vial to stand for 20 minutes at room temperature (20 °C-25 °C), to allow reconstitution and the dissipation of any foam; during this time the vial may be rotated and inspected to check for dissolution. If, after 20 minutes, dissolution is not complete, continue for another 10 minutes.
• 6. Visually inspect the reconstituted solution before dilution to exclude the presence of particulate matter and signs of colour change. The solution should appear clear or opalescent, from colourless to yellowish and free from visible particulate matter. If the reconstituted solution has an unusual colour or contains particulate matter, it should not be administered.
• 7. Once dissolved, gently invert the vial 3 times.
• 8. Immediately withdraw 5 mL (300 mg) of reconstituted Entyvio, using a syringe with a 21-25 G needle.
• 9. Add the 5 mL (300 mg) of reconstituted Entyvio to 250 mL of sterile sodium chloride 9 mg/mL (0.9%) solution for injection and gently swirl the infusion bag (do not withdraw 5 mL of sodium chloride 9 mg/mL (0.9%) solution for injection from the infusion bag before adding Entyvio). Do not add other medicines to the prepared infusion solution or to the intravenous infusion set. Administer the infusion solution within 30 minutes.

Once reconstituted, the infusion solution must be used as soon as possible.

Storage conditions
Refrigerator (2 °C-8 °C) 20 °C-25 °C
Reconstituted solution in the vial 8 hours Do not store
Diluted solution in sodium chloride 9 mg/mL (0.9%) solution
24 hours 12 hours
Do not freeze. Do not store unused portions of the reconstituted solution or the infusion solution for subsequent use.
Each vial is for single use only.
Unused medicine and waste derived from such medicine must be disposed of in accordance with local regulations.

Entyvio 108 mg solution for injection in pre-filled syringe

vedolizumab

Read this leaflet carefully before you use 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.

Contents of this leaflet

• 1. What Entyvio is and what it is used for
• 2. What you need to know before you use Entyvio
• 3. How to use Entyvio
• 4. Possible side effects
• 5. How to store Entyvio
• 6. Contents of the pack and other information

1. What is Entyvio and what is it used for

What is Entyvio
Entyvio contains the active substance ‘vedolizumab’. Vedolizumab belongs to a group of biological medicines
called monoclonal antibodies (MAb).

How Entyvio works
Entyvio works by blocking a protein present on the surface of white blood cells that causes
inflammation in ulcerative colitis and Crohn's disease. This reduces the extent of inflammation.

What Entyvio is used for
Entyvio is used to treat signs and symptoms in adults with:

• active moderate to severe ulcerative colitis
• active moderate to severe Crohn's disease.

Ulcerative colitis
Ulcerative colitis is a disease that causes inflammation of the large intestine. If you have ulcerative
colitis, you will first be prescribed other medicines. If you do not respond adequately or are unable to
tolerate these medicines, your doctor may prescribe Entyvio to reduce signs and symptoms of the
disease.
Crohn's disease
Crohn's disease is a disease that causes inflammation of the digestive system. If you have Crohn's
disease, you will first be given other medicines. If you do not respond adequately or
are unable to tolerate these medicines, your doctor may prescribe Entyvio to reduce signs and
symptoms of the disease.

2. What you need to know before you use Entyvio

Do not use Entyvio

• if you are allergic to vedolizumab or any of the other ingredients of this medicine (listed in section 6).
• if you have a serious active infection, such as TB (tuberculosis), blood infection (sepsis), severe diarrhoea and vomiting (gastroenteritis), or infection of the nervous system.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Entyvio.

Tell your doctor, pharmacist or nurse immediatelywhen you use this medicine for
the first time, during therapy and between doses:

• if you experience blurred vision, loss of vision or double vision, difficulty speaking, weakness in an arm or leg, changes in your way of walking or problems with balance, persistent numbness, reduced or loss of sensation, memory loss or confusion. These could all be symptoms of a serious brain disease that canbe fatalcalled progressive multifocal leukoencephalopathy (PML, from the English Progressive Multifocal Leukoencephalopathy).
• if you have, or think you have, an infection: signs of infection are chills, tremors, persistent cough or high fever. Some infections can become serious and can be fatal if not treated.
• if you experience signs of an allergic reaction, such as wheezing, difficulty breathing, hives, itching, swelling or dizziness. For more detailed information, see allergic reactions in section 4.
• if you are about to have a vaccinationor have recently had a vaccination. Entyvio may affect your response to the vaccination.
• if you have cancer, tell your doctor. The doctor will decide if you can still receive Entyvio.
• if you do not feel better, as in patients with very active Crohn's disease, the effect of vedolizumab may take up to 14 weeks to appear.

Children and adolescents
The use of Entyvio is not recommended in children or adolescents (under 18 years of age), in
view of the lack of data on the use of this medicine in this age group.

Other medicines and Entyvio
Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might
take any other medicines.

• Entyvio must not be given with other biological medicines that suppress the immune system, as the effects of this combination are not known.

Tell your doctor if you have previously taken:

• natalizumab (a medicine for multiple sclerosis) or
• rituximab (a medicine for some types of cancer and rheumatoid arthritis). The doctor will decide if you can still receive Entyvio.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant or are planning to become pregnant, or if you are
breastfeeding, ask your doctor for advice before taking this medicine.
Pregnancy
The effects of Entyvio on pregnant women are not known. This medicine is therefore not
recommended during pregnancy. You and your doctor must decide whether the benefit for you
clearly outweighs the potential risk to you and your baby.
If you are a woman of childbearing potential, it is recommended to avoid pregnancy while using Entyvio. You should
use adequate contraception during treatment and for at least 4.5 months after
the last treatment.
Breastfeeding
Tell your doctor if you are breastfeeding or intend to do so. Entyvio passes into breast milk. Information regarding the possible effects on the baby and milk production is insufficient.
A decision must be made whether to discontinue breastfeeding or discontinue therapy with Entyvio
considering the benefit of breastfeeding for your baby and the benefit of
therapy for you.

Driving and using machines
This medicine slightly impairs the ability to drive or operate tools or machines. A
small number of patients have experienced dizziness after receiving Entyvio. If this happens,
do not drive or operate tools or machines.

Entyvio 108 mg solution for injection contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, that is to say it is essentially ‘sodium-free’.

3. How to use Entyvio

Use this medicine following the instructions of your doctor or pharmacist exactly. If you have any
doubts, consult your doctor or pharmacist.
You or your caregiver will receive adequate training on how to administer the subcutaneous injections of
Entyvio (subcutaneous injections).

How much Entyvio you will receive
The treatment with Entyvio is the same for ulcerative colitis and Crohn's disease.
The recommended dose is 108 mg of Entyvio administered by subcutaneous injection once
every 2 weeks.

• At the beginning of treatment, your doctor will administer the initial doses of Entyvio by intravenous infusion into a vein in your arm (intravenous infusion) over approximately 30 minutes.
• After at least 2 intravenous infusions, you may start receiving Entyvio by subcutaneous injection. The first subcutaneous injection will be administered on the day your next intravenous infusion was scheduled and, subsequently, every 2 weeks.

How to inject Entyvio
Subcutaneous injections can be performed by yourself or by your caregiver, after
training on how to do so. Instructions are available at the end of this leaflet.

If you forget or miss an Entyvio injection
If you forget or miss a dose, administer the next dose as soon as possible and,
thereafter, every 2 weeks.

If you stop taking Entyvio
Do not stop treatment with Entyvio without first consulting your doctor.
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.

Serious side effects
Tell your doctor immediatelyif you notice any of the following symptoms:

• allergic reactions (may affect up to 1 in 100 people). Signs of an allergic reaction include wheezing or difficulty breathing, hives, itchy skin, swelling, feeling unwell, skin redness;
• infections (may affect up to 1 in 10 people). Signs of infection include chills or tremors, high fever or skin rash.

Other side effects
Tell your doctor as soon as possibleif you notice any of the following symptoms:

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

• cold
• joint pain
• headache

Common side effects(may affect up to 1 in 10 people)

• lung infection
• thick bowel infection caused by the bacterium Clostridium difficile
• fever
• chest infection
• changes in liver function, increased liver enzymes (indicated by blood tests)
• fatigue
• cough
• flu
• back pain
• sore throat
• sinusitis
• itching
• skin rash and redness
• pain in legs and/or arms
• muscle cramps
• muscle weakness
• throat infection
• gastrointestinal flu
• anal infection
• anal fissures
• hard stools
• bloated stomach
• intestinal gas
• high blood pressure
• tingling or prickling sensation
• heartburn
• hemorrhoids
• stuffy nose
• eczema
• night sweats
• acne (pimples)
• reactions at the injection site (including pain, swelling, redness or itching)
• shingles (herpes zoster)

Uncommon side effects(may affect up to 1 in 100 people):

• redness and tenderness of hair follicles
• yeast infection of the throat and mouth
• vaginal infection
• blurred vision (loss of sharpness of vision)

Very rare side effects(may affect up to 1 in 10,000 people):

• sudden severe allergic reaction that can cause difficulty breathing, swelling, rapid heartbeat, sweating, low blood pressure, feeling dizzy, loss of consciousness and collapse (anaphylactic reaction and anaphylactic shock)
• inflammation of the liver (hepatitis). Signs and symptoms of hepatitis may include abnormal liver function tests, yellowing of the skin or whites of the eyes (jaundice), pain on the right side of the area corresponding to the stomach, bruising.

Not known(frequency cannot be estimated from the available data):

• lung disease causing shortness of breath (interstitial lung disease)

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 Entyvio

• 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 label after “Exp”. The expiry date refers to the last day of that month.
• Entyvio is for single use only.
• Store in a refrigerator (2 °C - 8 °C). Store the pre-filled syringe(s) in the original package to protect the medicine from light. If necessary, a pre-filled syringe can be kept out of the refrigerator protected from light at room temperature (up to 25 °C) for a maximum of 7 days. Do not use the pre-filled syringe if it has been out of the refrigerator for more than 7 days.
• Do not freeze. Do not expose to direct sunlight.
• Do not use this medicine if you notice the presence of particles in the liquid or a change in color (the medicine should be from colorless to yellow) before administration.
• 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. Content of the pack and other information

What Entyvio contains

• The active substanceis vedolizumab. Each pre-filled syringe contains 108 mg of vedolizumab.
• The other ingredientsare citric acid monohydrate, sodium citrate dihydrate, L-histidine, L-histidine monohydrochloride, L-arginine hydrochloride, polysorbate 80 and water for injections.

Description of Entyvio and content of the pack

• Entyvio is a solution for injection from colourless to yellow, contained in a pre-filled glass syringe with a safety device that is activated by extension and locks the needle inside the protection once the injection is complete. The syringe is equipped with a rubber needle cap enclosed in a plastic wrapper and a rubber stopper.
• Entyvio is available in boxes containing 1 or 2 pre-filled syringes and in multiple packs of 6 (6x1) pre-filled syringes. Not all packs may be marketed.

Marketing Authorisation Holder
Takeda Pharma A/S
Delta Park 45
2665 Vallensbaek Strand
Denmark

Manufacturer
Takeda Austria GmbH
St. Peter-Straβe 25
4020 Linz
Austria
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder:

Lietuva
Takeda, UAB
Tel.: +370 521 09 070
[email protected]

България
Такеда България ЕООД
Тел.: + 359 2 958 27 36
[email protected]

België/Belgique/Belgien
Takeda Belgium NV
Tél./Tel.: + 32 2 464 06 11
[email protected]

Luxembourg/Luxemburg
Takeda Belgium NV
Tél/Tel: + 32 2 464 06 11
[email protected]

Česká republika
Takeda Pharmaceuticals Czech Republic s.r.o.
Tel: +420 234 722 722
[email protected]

Magyarország
Takeda Pharma Kft.
Tel.: + 361 270 7030
[email protected]

Danmark
Takeda Pharma A/S
Tlf.: +45 46 77 10 10
[email protected]

Malta
Drugsales Ltd
Tel.: + 356 21419070
[email protected]

Deutschland
Takeda GmbH
Tel.: + 49 (0) 800 825 3325
[email protected]

Nederland
Takeda Nederland B.V.
Tel.: + 31 20 203 5492
[email protected]

Eesti
Takeda Pharma OÜ
Tel.: + 372 6177 669
[email protected]

Norge
Takeda AS
Tlf.: +47 800 800 30
[email protected]

Ελλάδα
TAKEDA ΕΛΛΑΣ Α.Ε.
Τηλ.: + 30 210 6387800
[email protected]

Österreich
Takeda Pharma Ges.m.b.H.
Tel: + 43 (0) 800-20 80 50
[email protected]

España
Takeda Farmacéutica España, S.A.
Tel: + 34 917 90 42 22
[email protected]

Polska
Takeda Pharma Sp. z o.o.
Tel.: +48223062447
[email protected]

France
Takeda France SAS
Tel: + 33 1 40 67 33 00
[email protected]

Portugal
Takeda Farmacêuticos Portugal, Lda.
Tel.: + 351 21 120 1457
[email protected]

Hrvatska
Takeda Pharmaceuticals Croatia d.o.o.
Tel: + 385 1 377 88 96
[email protected]

România
Takeda Pharmaceuticals SRL
Tel.: + 40 21 335 03 91
[email protected]

Ireland
Takeda Products Ireland Ltd.
Tel.: 1800 937 970
[email protected]

Slovenija
Takeda Pharmaceuticals farmacevtska družba
d.o.o.
Tel: +386 (0) 59 082 480
[email protected]

Ísland
Vistor hf.
Sími: +354 535 7000
[email protected]

Slovenská republika
Takeda Pharmaceuticals Slovakia s.r.o.
Tel.: + 421 (2) 20 602 600
[email protected]

Italia
Takeda Italia S.p.A.
Tel.: + 39 06 502601
[email protected]

Suomi/Finland
Takeda Oy
Puh./Tel.: 0800 774 051
[email protected]

Κύπρος
A.POTAMITIS MEDICARE LTD
Τηλ: +357 22583333
[email protected]

Sverige
Takeda Pharma AB
Tel: 020 795 079
[email protected]

Latvija
Takeda Latvia SIA
Tel.: + 371 67840082
[email protected]

United Kingdom (Northern Ireland)
Takeda UK Ltd
Tel.: +44 (0) 3333 000 181
[email protected]

Other sources of information
This leaflet is available in formats suitable for blind or visually impaired patients, which
can be requested from the local representative of the marketing authorisation holder.
More detailed information on this medicinal product is available on the website of the European
Medicines Agency: http://www.ema.europa.eu .
---------------------------------------------------------------------------------------------------------------------------
The following information is intended exclusively for healthcare professionals:
Traceability
In order to improve the traceability of biological medicinal products, the name and batch number of the
medicinal product administered must be clearly recorded.
Instructions for use:
Read and follow these instructions before proceeding with the injection. The doctor, pharmacist or nurse
will show you how to use the Entyvio pre-filled syringe before you use it for the first time.

Your Entyvio single-dose pre-filled syringe
Before use
Needle protection Medicinal Needle

Purple plunger Finger grip
base
Spring Needle cap

After use
Needle protection

Needle covered
Each pre-filled syringe is equipped with a needle protection, which covers the needle automatically
after the plunger is pushed all the way in and then released.

• 1)Place all the necessary items for the injection on aflat and clean surface
• Take the pre-filled syringe box from the refrigerator.
• If you are opening the box for the first time, check it to make sure it is sealed. Do notuse the pre-filled syringe(s) if any of the seals on the box are broken or missing.
• Check the expiry date (Exp.) on the box. Do notuse after the expiry date stated on the box.
• Take a pre-filled syringe from the box. Keep any remaining pre-filled syringes in the box in the refrigerator.
• Wait 30 minutesfor the pre-filled syringe to reach room temperature.
• Do notheat the pre-filled syringe in other ways.
• Do notexpose the medicinal product to direct sunlight.
• Do notremove the syringe from the tray before you are ready to proceed with the injection.
• You will also need:
• Alcohol swab
• Cotton wool or gauze
• Sharps container Wait 30 minutes

• 2)Open and check the pre-filled syringe
• Wash your hands.
• Remove the paper backing from the tray and take the pre-filled syringe by holding it in the middle.
• Do nottouch or pull the purple plunger.
• Do notremove the needle cap until you are ready to proceed with the injection.
• Inspect the pre-filled syringe for any damage.
• Do notuse the pre-filled syringe if any component is damaged.
• Check the expiry date on the pre-filled syringe.
• Do notuse the pre-filled syringe after the expiry date stated on it.
• Check the medicinal product. It should be from colourless to yellow.
• Do notuse the pre-filled syringe if the medicinal product appears cloudy or if there are particles in suspension.
• You may see air bubbles in the syringe. This is normal.
• Do nottry to remove the air bubbles from the pre-filled syringe.
• Do notshake the pre-filled syringe.

• 3)Prepare the injection site
• Choose an injection siteon bare skin from 1 of the following options:
• Front of the thigh, or
• Abdominal area (stomach), except for the area extending 5 cm around the navel, or
• Back of the arm (only if the injection will be administered by someone who cares for you).
• Use a new injection site for each injection or a different area within the same injection site.
• Do notinject into moles, scars, bruises or areas where the skin is painful, hard, red or damaged.
• Clean the chosen site with an alcohol swab. Allow the skin to dry.
• Do nottouch this area again before proceeding with the injection.

• 4) Inject Entyvio

• Remove the needle cap with a straight motion.
• Do nottouch or pull back the purple plunger.
• You may see a drop of liquid on the tip of the needle. This is normal.
• Do nottouch the needle and do not put the cap back on the needle.
• Do notuse the pre-filled syringe if it has fallen.
• Do notuse a pre-filled syringe whose needle is bent or broken.
• Throw away the cap.
• Hold the pre-filled syringe with 1 hand and pinch a fold of skin at the injection site with the other hand.

• Keep the skin fold until the injection is complete.
• Insert the needle at an angle of approximately 45 degreesby pushing it all the way into the skin.
• Push the plunger all the way into inject all of the medicine.

• Withdraw the needle from the skin while keeping the plunger pressed down.
• Release your thumb from the plungerto allow the protection device to cover the needle.
• You may see a small amount of blood at the injection site. If so, press cotton wool or gauze on the skin.

• 5) Dispose of used materials
• Place the used pre-filled syringe in a puncture-resistant container, such as a sharps container, immediately after use.
• Dispose of the sharps container according to local regulations.
• The rest of the material can be thrown away with household waste.

Entyvio 108 mg injectable solution in a pre-filled pen

vedolizumab

Read this leaflet carefully before you start using 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.

Contents of this leaflet

• 1. What Entyvio is and what it is used for
• 2. What you need to know before you use Entyvio
• 3. How to use Entyvio
• 4. Possible side effects
• 5. How to store Entyvio
• 6. Contents of the pack and other information

1. What is Entyvio and what is it used for

What is Entyvio
Entyvio contains the active substance ‘vedolizumab’. Vedolizumab belongs to a group of biological medicines
called monoclonal antibodies (MAb).

How Entyvio works
Entyvio works by blocking a protein present on the surface of white blood cells that causes
inflammation in ulcerative colitis and Crohn's disease. This reduces the extent of inflammation.

What Entyvio is used for
Entyvio is used to treat signs and symptoms in adults with:

• active moderate to severe ulcerative colitis
• active moderate to severe Crohn's disease.

Ulcerative colitis
Ulcerative colitis is a disease that causes inflammation of the large intestine. If you have ulcerative
colitis, you will first be prescribed other medicines. If you do not respond adequately or are unable to
tolerate these medicines, your doctor may prescribe Entyvio to reduce signs and symptoms of the
disease.
Crohn's disease
Crohn's disease is a disease that causes inflammation of the digestive system. If you have Crohn's
disease, you will first be given other medicines. If you do not respond adequately or
are unable to tolerate these medicines, your doctor may prescribe Entyvio to reduce signs and
symptoms of the disease.

2. What you need to know before you use Entyvio

Do not use Entyvio

• if you are allergic to vedolizumab or any of the other ingredients of this medicine (listed in section 6).
• if you have a serious active infection, such as TB (tuberculosis), blood infection (sepsis), severe diarrhoea and vomiting (gastroenteritis), or an infection of the nervous system.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Entyvio.

Tell your doctor, pharmacist or nurse immediatelywhen you use this medicine for
the first time, during therapy and between doses:

• if you experience blurred vision, loss of vision or double vision, difficulty speaking, weakness in an arm or leg, changes in the way you walk or problems with balance, persistent numbness, reduced or loss of sensation, memory loss or confusion. These could all be symptoms of a serious brain disease that canbe fatalcalled progressive multifocal leukoencephalopathy (PML, from the English Progressive Multifocal Leukoencephalopathy).
• if you have, or think you have, an infection: signs of infection include chills, tremors, persistent cough or high fever. Some infections can become serious and can be fatal if not treated.
• if you experience signs of an allergic reaction, such as wheezing, difficulty breathing, hives, itching, swelling or dizziness. For more detailed information, see allergic reactions in section 4.
• if you are about to have a vaccinationor have recently had a vaccination. Entyvio may affect your response to the vaccination.
• if you have cancer, tell your doctor. The doctor will decide if you can still receive Entyvio.
• if you do not feel better, as in patients with very active Crohn's disease, the effect of vedolizumab may take up to 14 weeks to appear.

Children and adolescents
The use of Entyvio is not recommended in children or adolescents (under 18 years of age), in
consideration of the lack of data on the use of this medicine in this age group.

Other medicines and Entyvio
Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might
take any other medicines.

• Entyvio should not be given with other biological medicines that suppress the immune system, as the effects of this combination are not known.

Tell your doctor if you have previously taken:

• natalizumab (a medicine for multiple sclerosis) or
• rituximab (a medicine for some types of cancer and rheumatoid arthritis). The doctor will decide if you can still receive Entyvio.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, are planning a pregnancy or are breastfeeding with
breast milk, ask your doctor for advice before taking this medicine.
Pregnancy
The effects of Entyvio on pregnant women are not known. This medicine is therefore not
recommended during pregnancy. You and your doctor must decide whether the benefit for you
clearly outweighs the potential risk to you and the baby.
If you are a woman of childbearing potential, it is recommended to avoid pregnancy while using Entyvio. You should
use adequate contraception during treatment and for at least 4.5 months after
the last treatment.
Breastfeeding
Tell your doctor if you are breastfeeding or intend to do so. Entyvio passes into breast milk. Information regarding the possible effects on the baby and milk production is insufficient.
A decision must be made whether to discontinue breastfeeding or discontinue therapy with Entyvio
considering the benefit of breastfeeding for your baby and the benefit of
therapy for you.

Driving and using machines
This medicine slightly impairs the ability to drive or operate tools or machines. A
small number of patients have experienced dizziness after receiving Entyvio. If this happens,
do not drive or operate tools or machines.

Entyvio 108 mg solution for injection contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Entyvio

Use this medicine following exactly the instructions of your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
You or your caregiver will receive adequate training on how to perform the injections under the skin
of Entyvio (subcutaneous injections).

How much Entyvio you will receive
The treatment with Entyvio is the same for ulcerative colitis and for Crohn's disease.
The recommended dose is 108 mg of Entyvio administered by subcutaneous injection once
every 2 weeks.

• At the beginning of treatment, your doctor will administer the initial doses of Entyvio by infusion into a vein in your arm (intravenous infusion) over approximately 30 minutes.
• After at least 2 intravenous infusions, you may start receiving Entyvio by subcutaneous injection. The first subcutaneous injection will be administered on the day your next intravenous infusion was scheduled and, subsequently, every 2 weeks.

How to inject Entyvio
Subcutaneous injections can be performed by yourself or by your caregiver, after
training on how to do so. Instructions are available at the end of this leaflet.

If you forget or miss an Entyvio injection
If you forget or miss a dose, administer the next dose as soon as possible and,
subsequently, every 2 weeks.

If you stop taking Entyvio
Do not stop taking Entyvio without first consulting your doctor.
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.

Serious side effects
Tell your doctor immediatelyif you notice any of the following symptoms:

• allergic reactions (may affect up to 1 in 100 people). Signs of an allergic reaction include: wheezing or difficulty breathing, hives, itchy skin, swelling, feeling unwell, skin redness;
• infections (may affect up to 1 in 10 people). Signs of infection include: chills or tremors, high fever or skin rash.

Other side effects
Tell your doctor as soon as possibleif you notice any of the following symptoms:

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

• cold
• joint pain
• headache

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

• lung infection
• thick bowel infection due to the bacterium Clostridium difficile
• fever
• chest infection
• changes in liver function, increased liver enzymes (indicated by blood tests)
• fatigue
• cough
• flu
• back pain
• sore throat
• sinusitis
• itching
• skin rash and redness
• pain in legs and/or arms
• muscle cramps
• muscle weakness
• throat infection
• gastrointestinal flu
• anal infection
• anal fissures
• hard stools
• swollen stomach
• intestinal gas
• high blood pressure
• tingling or prickling
• heartburn
• hemorrhoids
• blocked nose
• eczema
• night sweats
• acne (pimples)
• reactions at the injection site (including pain, swelling, redness or itching)
• shingles (herpes zoster)

Uncommon side effects(may affect up to 1 in 100 people):

• redness and tenderness of hair follicles
• yeast infection of the throat and mouth
• vaginal infection
• blurred vision (loss of sharpness of vision)

Very rare side effects(may affect up to 1 in 10,000 people):

• sudden severe allergic reaction that can cause difficulty breathing, swelling, rapid heartbeat, sweating, drop in blood pressure, feeling dizzy, loss of consciousness and collapse (anaphylactic reaction and anaphylactic shock)
• inflammation of the liver (hepatitis). Signs and symptoms of hepatitis may include abnormal liver function tests, yellowing of the skin or whites of the eyes (jaundice), pain on the right side of the area corresponding to the stomach, bruising.

Not known(frequency cannot be estimated from available data):

• lung disease that causes shortness of breath (interstitial lung disease)

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 Entyvio

• 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 label after “Exp.”. The expiry date refers to the last day of that month.
• Entyvio is for single use only.
• Store in a refrigerator (2 °C - 8 °C). Store the/the pre-filled pen/pre-filled pens in the original packaging to protect the medicine from light. If necessary, a pre-filled pen can be kept out of the refrigerator protected from light at room temperature (up to 25 °C) for a maximum of 7 days. Do not use the pre-filled pen if it has been out of the refrigerator for more than 7 days.
• Do not freeze. Do not expose to direct sunlight.
• Do not use this medicine if you notice the presence of particles in the liquid or a change in color (the medicine should be from colorless to yellow) before administration.
• 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 Entyvio contains

• The active substanceis vedolizumab. Each pre-filled pen contains 108 mg of vedolizumab.
• The other ingredientsare citric acid monohydrate, sodium citrate dihydrate, L-histidine, L-histidine monohydrochloride, L-arginine hydrochloride, polysorbate 80 and water for injections.

Description of Entyvio and contents of the pack

• Entyvio is a solution for injection, from colourless to yellow, contained in a glass pre-filled pen with an automatic needle protection that extends and covers the needle once the device is removed from the injection site.
• Entyvio is available in packs containing 1 or 2 pre-filled pens and in multipacks of 6 (6x1) pre-filled pens. Not all pack sizes may be marketed.

Marketing Authorisation Holder
Takeda Pharma A/S
Delta Park 45
2665 Vallensbaek Strand
Denmark

Manufacturer
Takeda Austria GmbH
St. Peter-Straβe 25
4020 Linz
Austria
For further information on this medicinal product, contact the local representative of the marketing authorisation holder:

Lietuva
Takeda, UAB
Tel.: +370 521 09 070
[email protected]

България
Такеда България ЕООД
Тел.: + 359 2 958 27 36
[email protected]

België/Belgique/Belgien
Takeda Belgium NV
Tél./Tel.: + 32 2 464 06 11
[email protected]

Luxembourg/Luxemburg
Takeda Belgium NV
Tél/Tel: + 32 2 464 06 11
[email protected]

Česká republika
Takeda Pharmaceuticals Czech Republic s.r.o.
Tel: +420 234 722 722
[email protected]

Magyarország
Takeda Pharma Kft.
Tel.: + 361 270 7030
[email protected]

Danmark
Takeda Pharma A/S
Tlf.: +45 46 77 10 10
[email protected]

Malta
Drugsales Ltd
Tel.: + 356 21 419070
[email protected]

Deutschland
Takeda GmbH
Tel.: + 49 (0) 800 825 3325
[email protected]

Nederland
Takeda Nederland B.V.
Tel.: + 31 20 203 5492
[email protected]

Eesti
Takeda Pharma OÜ
Tel.: +372 6177 669
[email protected]

Norge
Takeda AS
Tlf: +47 800 800 30
[email protected]

Ελλάδα
TAKEDA ΕΛΛΑΣ Α.Ε.
Τηλ.: + 30 210 6387800
[email protected]

Österreich
Takeda Pharma Ges.m.b.H.
Tel.: + 43 (0) 800-20 80 50
[email protected]

España
Takeda Farmacéutica España, S.A.
Tel.: + 34 917 90 42 22
[email protected]

Polska
Takeda Pharma Sp. z o.o.
Tel.:+48223062447
[email protected]

France
Takeda France SAS
Tel.: + 33 1 40 67 33 00
[email protected]

Portugal
Takeda Farmacêuticos Portugal, Lda.
Tel.: + 351 21 120 1457
[email protected]

Hrvatska
Takeda Pharmaceuticals Croatia d.o.o.
Tel: + 385 1 377 88 96
[email protected]

România
Takeda Pharmaceuticals SRL
Tel.: + 40 21 335 03 91
[email protected]

Ireland
Takeda Products Ireland Ltd.
Tel.: 1800 937 970
[email protected]

Slovenija
Takeda Pharmaceuticals farmacevtska družba
d.o.o.
Tel.: + 386 (0) 59 082 480
[email protected]

Ísland
Vistor hf.
Sími: +354 535 7000
[email protected]

Slovenská republika
Takeda Pharmaceuticals Slovakia s.r.o.
Tel.: + 421 (2) 20 602 600
[email protected]

Italia
Takeda Italia S.p.A.
Tel.: + 39 06 502601
[email protected]

Suomi/Finland
Takeda Oy
Puh./Tel.: 0800 774 051
[email protected]

Κύπρος
A.POTAMITIS MEDICARE LTD
Τηλ: +357 22583333
[email protected]

Sverige
Takeda Pharma AB
Tel.: 020 795 079
[email protected]

Latvija
Takeda Latvia SIA
Tel.: +371 67840082
[email protected]

United Kingdom (Northern Ireland)
Takeda UK Ltd
Tel.: +44 (0) 3333 000 181
[email protected]

Other sources of information
This leaflet is available in formats suitable for patients with visual impairment, which
can be requested from the local representative of the marketing authorisation holder.
More detailed information on this medicinal product is available on the website of the European
Medicines Agency: http://www.ema.europa.eu .
---------------------------------------------------------------------------------------------------------------------------
The following information is intended for healthcare professionals only:
Traceability
In order to improve the traceability of biological medicinal products, the name and batch number of the
medicinal product administered must be clearly recorded.
Instructions for use:
Read and follow these instructions before proceeding with the injection. The doctor, pharmacist or nurse
will show you how to use the Entyvio pre-filled pen before you use it for the first time.

Your single-dose Entyvio pre-filled pen
Before use
Purple cap Observation window

After use
Yellow needle protection
Observation window
(injection completed)

• 1)Place everything you need for the injection on aflat and clean surface
• Take the pre-filled pen pack out of the refrigerator.
• If you are opening the pack for the first time, check that it is sealed. Do notuse the pre-filled pen(s) if any of the seals on the pack are broken or missing.
• Check the expiry date (Exp.) on the pack. Do notuse after the expiry date stated on the pack.
• Take a pre-filled pen out of the pack. Keep any remaining pre-filled pens in the pack in the refrigerator.
• Wait 30 minutesfor the pre-filled pen to reach room temperature.
• Do notheat the pre-filled pen in any other way.
• Do notexpose the medicine to direct sunlight.
• Do notremove the pre-filled pen from the tray before you are ready to proceed with the injection.
• You will also need:
• Alcohol swab
• Cotton wool or gauze
• Sharps container Wait 30 minutes

• 2)Open and check the pre-filled pen
• Wash your hands.
• Remove the paper backing from the tray and take out the pre-filled pen.
• Inspect the pre-filled pen for any damage.
• Do notuse the pre-filled pen if any of the components are damaged.
• Check the expiry date on the pre-filled pen.
• Do notuse the pre-filled pen after the expiry date stated on it.
• Check the medicine. It should be from colourless to yellow.
• Do notuse the pre-filled pen if the medicine appears cloudy or if there are particles in it.
• You may see air bubbles in the pre-filled pen. This is normal.
• Do notshake the pre-filled pen.

• 3)Prepare the injection site
• Choose an injection siteon bare skin from one of the following options:
• Front of the thigh, or
• Abdominal area (stomach), except for the area extending 5 cm around the navel, or
• Back of the arm (only if the injection will be given by someone who cares for you).
• Use a new injection site for each injection or a different area within the same injection site.
• Do notinject into moles, scars, bruises or areas where the skin is sore, hard, red or damaged.
• Clean the chosen site with an alcohol swab. Allow the skin to dry.
• Do nottouch this area again before proceeding with the injection.

• Remove the purple cap and discard it.
• Do nottouch or press with your thumb, other fingers or your hand on the yellow needle protection.
• Do notput the cap back on the pre-filled pen.
• Do notuse the pre-filled pen if it has been dropped.

• 4) Inject Entyvio
• Hold the pre-filled pen so that you can see the observation window.
• Position the pre-filled pen at a 90-degree angleto the injection site. PRESS

• Make sure that the yellow end is facing the injection site.
• Do notpress until you are ready to proceed with the injection.
• Push the pre-filled pen all the way into start the injection.
• Keep pressing and count to 10while continuing to press with steady pressure. This will inject all of the medicine. KEEP PRESSING (count to 10)

• You may hear 2 clicks, one at the beginning and one at the end of the injection.
• Check that the observation window is filled with purple colourbefore stopping pressing.
• You will see a small grey portion in the observation window. This is normal.
• Detach the pre-filled pen from the injection site. CONFIRM

• The yellow needle protection will descend to cover the needle.
• If the observation window is not completely filled with purple, call your doctor, pharmacist or nurse. You may not have received the full dose of the medicine.
• You may see a small amount of blood at the injection site. If so, press cotton wool or gauze on the skin.
• 5) Dispose of used materials
• Place the used pre-filled pen in a puncture-resistant container, such as a sharps container, immediately after use.
• Dispose of the sharps container according to local regulations.

• The rest of the material can be disposed of in household waste.

APPENDIX IV

SCIENTIFIC CONCLUSIONS AND JUSTIFICATION FOR VARIATION OF THE TERMS OF MARKETING AUTHORISATIONS
Scientific conclusions
Taking into account the assessment of the Pharmacovigilance and Risk Assessment Committee (PRAC) of the Periodic Safety Update Report (PSUR) for vedolizumab, the scientific conclusions of the PRAC are as follows:
In light of the available data on liver injury emerging from clinical studies, the literature, and spontaneous reports including cases with a close temporal relationship, a dechallengeand/or a positive rechallenge, the PRAC considers that a causal relationship between vedolizumab and increased liver enzymes and hepatitis should be considered at least a reasonable possibility.
Hypersensitivity reactions have occurred after switching from subcutaneous administration to intravenous administration in 8 spontaneous cases reported during the period of this PSUR and 4 relevant publications were identified within the scope of a national investigation on vedolizumab conducted in France by a regional pharmacovigilance centre. These cases reported the onset of adverse events related to immediate hypersensitivity reactions when intravenous vedolizumab was reintroduced after subcutaneous treatment. Six of these cases were serious, with one case of anaphylactic reaction, and 2 were non-serious. The PRAC believes that the existing warning on hypersensitivity in section 4.4 of the SmPC for the intravenous formulation should mention the cases that occurred during this switch, in order to reiterate the existing warning about the need to keep patients under observation for any signs of hypersensitivity reactions.
The PRAC concluded that the product information containing vedolizumab should be amended accordingly.
Having examined the PRAC recommendation, the Committee for Human Medicinal Products (CHMP) agrees with the general conclusions and with the justification for the recommendation.

Justification for variation of the terms of marketing authorisations
Based on the scientific conclusions on vedolizumab, the CHMP considers that the benefit/risk ratio of the medicinal products containing vedolizumab is unchanged, subject to the proposed changes to the product information.
The CHMP recommends the variation of the terms of the marketing authorisations.