Entyvio - patient leaflet, side effects, dosage

B. PACKAGE LEAFLET

Package leaflet: Information for the patient

Entyvio 300 mg powder for concentrate for solution for infusion vedolizumab

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.
• Your doctor will also give you a Patient Alert Card for you to keep with you at all times.

What is in this leaflet

• 1. What Entyvio is and what it is used for

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

• 3. How Entyvio will be given

• 4. Possible side effects

• 5. How to store Entyvio

• 6. Contents of the pack and other information

1. What Entyvio is and what it is used for

What Entyvio is

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

How Entyvio works

Entyvio works by blocking a protein on the surface of white blood cells that cause the inflammation in ulcerative colitis, Crohn’s disease and pouchitis. This reduces the amount of inflammation.

What Entyvio is used for

Entyvio is used to treat the signs and symptoms in adults of:

• moderately to severely active ulcerative colitis
• moderately to severely active Crohn’s disease
• moderately to severely active chronic pouchitis.

Ulcerative colitis

Ulcerative colitis is a disease that causes inflammation of the large bowel. If you have ulcerative colitis, you will first be given other medicines. If you do not respond well enough or cannot tolerate these medicines, your doctor may give you Entyvio to reduce the signs and symptoms of your 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 well enough or cannot tolerate these medicines, your doctor may give you Entyvio to reduce the signs and symptoms of your disease.

Pouchitis

Pouchitis is a disease that causes inflammation of the lining of the pouch, which was created during surgery to treat ulcerative colitis. If you have pouchitis, you may first be given antibiotics. If you do not respond well enough to antibiotics, your doctor may give you Entyvio to reduce the signs and symptoms of your 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 an active severe infection – such as TB (tuberculosis), blood poisoning, severe diarrhoea and vomiting (gastroenteritis), nervous system infection.

Warnings and precautions

Talk to your doctor or nurse before being given Entyvio.

Tell your doctor or nurse immediately when you first receive this medicine, during treatment, and between doses:

• if you experience blurred, loss of or double vision, difficulty speaking, weakness in an arm or a leg, a change in the way you walk or problems with your balance, persistent numbness, decreased sensation or loss of sensation, memory loss or confusion. These may all be symptoms of a serious and potentially fatal brain condition known as progressive multifocal leukoencephalo­pathy (PML).
• if you have an infection, or think you have an infection – signs include chills, shivering, persistent cough or a high fever. Some infections may become serious and possibly even life-threatening if left untreated.
• if you experience signs of an allergic reaction or other reaction to the infusion such as wheezing, difficulty breathing, hives, itching, swelling or dizziness. These could occur during or after the infusion. For more detailed information, see infusion and allergic reactions in section 4.
• if you are going to receive any vaccination or have recently had a vaccination. Entyvio may affect the way you respond to a vaccination.
• if you have cancer, tell your doctor. Your doctor will have to decide if you can still be given Entyvio.
• if you are not feeling any better as vedolizumab may take up to 14 weeks to work in some patients with very active Crohn’s disease.

Children and adolescents

Entyvio is not recommended for use in children or adolescents (under 18 years of age) due to the lack of information regarding 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 biologic medicines that suppress your immune system as the effect of this is not known.

Tell your doctor if you have previously taken:

• natalizumab (a medicine for multiple sclerosis) or
• rituximab (a medicine for certain types of cancer and rheumatoid arthritis).

Your doctor will decide if you can be given Entyvio.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

Pregnancy

The effects of Entyvio in pregnant women are not known. Therefore, this medicine is not recommended for use during pregnancy. You and your doctor should decide if the benefit to you clearly outweighs the potential risk to yourself and your baby.

If you are a woman of childbearing potential, you are advised to avoid becoming pregnant while using Entyvio. You should use adequate contraception during treatment and for at least 4.5 months after the last treatment.

Breast-feeding

Tell your doctor if you are breast-feeding or planning to breast-feed. Entyvio passes into breast milk. There is not enough information on what effect this may have on your baby and on milk production. A decision must be made whether to stop breast-feeding or to stop using Entyvio therapy taking into account the benefit of breast-feeding for your child and the benefit of therapy for you.

Driving and using machines

This medicine has a minor effect on your ability to drive or use tools or machines. A small number of patients have felt dizzy after receiving Entyvio. If you feel dizzy, do not drive or use tools or machines.

• 3. How Entyvio will be given

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 given as follows (see table below):

Your doctor may decide to alter this treatment schedule depending on how well Entyvio works for you.

• The infusion will be given to you, by your doctor or nurse, through a drip in 1 of the veins in your arm (intravenous infusion) over about 30 minutes.
• For your first 2 infusions, your doctor or nurse will monitor you closely during the infusion and for approximately 2 hours after you have completed the infusion. For all subsequent infusions (after the first 2), you will be monitored during the infusion and for approximately 1 hour after you have completed the infusion.

If you forget or miss your Entyvio infusion

If you forget or miss an appointment to receive the infusion, make another appointment as soon as possible.

If you stop using Entyvio

Do not stop using Entyvio without talking with your doctor first.

If you have any further questions on 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 immediately if you notice any of the following:

• allergic reactions (may affect up to 1 in 100 people) – the signs may include: wheezing or difficulty breathing, hives, itching of the skin, swelling, feeling sick, pain at the infusion site, redness of skin and
• infections (may affect up to 1 in 10 people) – the signs may include: chills or shivering, high fever or rash

Other side effects

Tell your doctor as soon as possible if you notice any of the following:

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

• common cold
• joint pain
• headache

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

• fever
• chest infection
• tiredness
• cough
• flu (influenza)
• back pain
• throat pain
• sinus infection
• itching / itchiness
• rash and redness
• pain in the limb
• muscle cramps
• muscle weakness
• throat infection
• stomach flu
• anal infection
• anal sore
• hard faeces
• bloated stomach
• passing gas
• high blood pressure
• prickling or tingling
• heart burn
• haemorrhoids
• blocked nose
• eczema
• night sweats
• acne (pimples)
• rectal bleeding
• chest discomfort

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

• redness and tenderness of hair follicle
• throat and mouth yeast infection
• vaginal infection
• shingles (herpes zoster)

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

• pneumonia
• blurred vision (loss of sharpness of eyesight)
• sudden, severe allergic reaction which can cause breathing difficulty, swelling, fast heartbeat, sweating, drop in blood pressure, light-headedness, loss of consciousness and collapse (anaphylactic reaction and anaphylactic shock)

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 or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in 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 carton after “EXP”. The expiry date refers to the last day of that month.

Entyvio is given by a doctor or nurse and patients should not need to 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 carton in order to protect from light.

Reconstituted and diluted solutions: Use immediately. If this is not possible, reconstituted solution in the vial can be stored for up to 8 hours at 2 °C-8 °C. Diluted solution in sodium chloride 9 mg/mL (0.9%) solution for injection can be stored up to 12 hours at a room temperature of not above 25 °C, or up to 24 hours in a refrigerator (2 °C-8 °C), or for up to 12 hours at room temperature and in a refrigerator (2 °C-8 °C), up to a combined total of 24 hours. A 24 hour period may include up to 8 hours at 2 °C-8 °C for reconstituted solution in the vial and up to 12 hours at 20 °C-25 °C for diluted solution in the infusion bag but the infusion bag must be stored in the refrigerator (2 °C-8 °C) for the rest of the 24 hour period Any time that the reconstituted solution was held in the vial should be subtracted from the time the solution may be held in the infusion bag.

Do not freeze.

Do not use this medicine if you notice any particles in the liquid or discolouration (solution should be clear or opalescent, colourless to light yellow) prior to administration.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Entyvio contains

• The active substance is vedolizumab. Each vial contains 300 mg of vedolizumab.
• The other ingredients are L-histidine, L-histidine monohydrochloride, L-arginine

hydrochloride, sucrose, and polysorbate 80.

What Entyvio looks like and contents of the pack

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in 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 Entyvio is and what it is used for

What Entyvio is

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

How Entyvio works

Entyvio works by blocking a protein on the surface of white blood cells that cause the inflammation in ulcerative colitis and Crohn’s disease. This reduces the amount of inflammation.

What Entyvio is used for

Entyvio is used to treat the signs and symptoms in adults of:

• moderately to severely active ulcerative colitis
• moderately to severely active Crohn’s disease.

Ulcerative colitis

Ulcerative colitis is a disease that causes inflammation of the large bowel. If you have ulcerative colitis, you will first be given other medicines. If you do not respond well enough or cannot tolerate these medicines, your doctor may give you Entyvio to reduce the signs and symptoms of your 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 well enough or cannot tolerate these medicines, your doctor may give you Entyvio to reduce the signs and symptoms of your 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 an active severe infection – such as TB (tuberculosis), blood poisoning, severe diarrhoea and vomiting (gastroenteritis), nervous system infection.

Warnings and precautions

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

Tell your doctor, pharmacist or nurse immediately when you first use this medicine, during treatment, and between doses:

• if you experience blurred, loss of or double vision, difficulty speaking, weakness in an arm or a leg, a change in the way you walk or problems with your balance, persistent numbness, decreased sensation or loss of sensation, memory loss or confusion. These may all be symptoms of a serious and potentially fatal brain condition known as progressive multifocal leukoencephalo­pathy (PML).
• if you have an infection, or think you have an infection -signs include chills, shivering, persistent cough or a high fever. Some infections may become serious and possibly even life-threatening if left untreated.
• 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 going to receive any vaccination or have recently had a vaccination. Entyvio may affect the way you respond to a vaccination.
• if you have cancer, tell your doctor. Your doctor will have to decide if you can still be given Entyvio.
• if you are not feeling any better as vedolizumab may take up to 14 weeks to work in some patients with very active Crohn’s disease.

Children and adolescents

Entyvio is not recommended for use in children or adolescents (under 18 years of age) due to the lack of information regarding 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 biologic medicines that suppress your immune system as the effect of this is not known.

Tell your doctor if you have previously taken:

• natalizumab (a medicine for multiple sclerosis) or
• rituximab (a medicine for certain types of cancer and rheumatoid arthritis).

Your doctor will decide if you can be given Entyvio.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

Pregnancy

The effects of Entyvio in pregnant women are not known. Therefore, this medicine is not recommended for use during pregnancy. You and your doctor should decide if the benefit to you clearly outweighs the potential risk to yourself and your baby.

If you are a woman of childbearing potential, you are advised to avoid becoming pregnant while using Entyvio. You should use adequate contraception during treatment and for at least 4.5 months after the last treatment.

Breast-feeding

Tell your doctor if you are breast-feeding or planning to breast-feed. Entyvio passes into breast milk. There is not enough information on what effect this may have on your baby and on milk production. A decision must be made whether to stop breast-feeding or to stop using Entyvio therapy taking into account the benefit of breast-feeding for your child and the benefit of therapy for you.

Driving and using machines

This medicine has a minor effect on your ability to drive or use tools or machines. A small number of patients have felt dizzy after receiving Entyvio. If you feel dizzy, do not drive or use tools or machines.

Entyvio 108 mg solution for injection contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.

3. How to use Entyvio

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

You or your caregiver will be given training on how to use Entyvio injections under the skin (subcutaneous injections).

How much Entyvio you will receive

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 start of treatment, the doctor will give initial doses of Entyvio through a drip into a vein in your arm (intravenous infusion) over about 30 minutes.
• After at least 2 intravenous infusions, you can start receiving Entyvio by a subcutaneous injection. The first subcutaneous injection is given at the time of the next scheduled intravenous infusion, and every 2 weeks thereafter.

Injecting Entyvio

The subcutaneous injections can be given by yourself or a caregiver, after training on how to do it. Instructions are provided at the end of this leaflet.

If you forget to take or miss your Entyvio injection

If you forget or miss a dose, inject the next dose as soon as possible and then every 2 weeks thereafter.

If you stop using Entyvio

Do not stop using Entyvio without talking with your doctor first.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

4. Possible side effects

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

Serious side effects

Tell your doctor immediately if you notice any of the following:

• allergic reactions (may affect up to 1 in 100 people) – the signs may include: wheezing or difficulty breathing, hives, itching of the skin, swelling, feeling sick, redness of skin
• infections (may affect up to 1 in 10 people) – the signs may include: chills or shivering, high fever or rash

Other side effects

Tell your doctor as soon as possible if you notice any of the following:

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

• common cold
• joint pain
• headache

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

• fever
• chest infection
• tiredness
• cough
• flu (influenza)
• back pain
• throat pain
• sinus infection
• itching / itchiness
• rash and redness
• pain in the limb
• muscle cramps
• muscle weakness
• throat infection
• stomach flu
• anal infection
• anal sore
• hard faeces
• bloated stomach
• passing gas
• high blood pressure
• prickling or tingling
• heart burn
• haemorrhoids
• blocked nose
• eczema
• night sweats
• acne (pimples)
• injection site reactions (including pain, swelling, redness or itching)

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

• redness and tenderness of hair follicle
• throat and mouth yeast infection
• vaginal infection
• shingles (herpes zoster)

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

• pneumonia
• blurred vision (loss of sharpness of eyesight)
• sudden, severe allergic reaction which can cause breathing difficulty, swelling, fast heartbeat, sweating, drop in blood pressure, light-headedness, loss of consciousness and collapse (anaphylactic reaction and anaphylactic shock)

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 via the national reporting system listed in 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 carton 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). Keep the pre-filled syringe in the original carton in order to protect from light. If needed, the pre-filled syringe can be left out of the refrigerator in its original carton at room temperature (up to 25 °C) for up to 7 days. Do not use if left out of the refrigerator for more than 7 days.
• Do not freeze. Do not leave in direct sunlight.
• Do not use this medicine if you notice any particles in the liquid or discolouration (should be colourless to yellow) prior to administration.
• Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Entyvio contains

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

What Entyvio looks like and contents of the pack

• Entyvio is a colourless to yellow solution for injection provided in a glass pre-filled syringe with a needle safety device that activates to extend and lock a guard over the needle once the injection is completed. The syringe has a rubber needle cover encased in a plastic shell and rubber stopper.
• Entyvio is available in a carton containing 1 pre-filled syringe and multipacks containing

2 (2×1 pre-filled syringes), or 6 (6×1 pre-filled syringes). 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-Straße 25

4020 Linz

Austria

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

This leaflet was last revised in

Other sources of information

This leaflet is available in formats suitable for the blind or partially sighted patient and can be requested from respective local representative of the Marketing Authorisation Holder.

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

-----------------------------------------------------------------------------------------------------------------------

The following information is intended for healthcare professionals only:

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded

Instructions for use:

Read and follow these instructions before you inject. Your doctor, nurse or pharmacist should 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 guard Medicine Needle

Purple plunger Finger Grip Spring Needle cap

After Use

Needle guard

Covered needle

Each pre-filled syringe has a needle guard. It will automatically cover the needle after the plunger is pushed down as far as it will go and then released.

• 2) Open and check the pre-filled syringe

• ■ Wash your hands

• ■ Peel back the paper on the tray and lift the pre-filled syringe out by the body.

• Do not touch or lift from the purple plunger.
• Do not remove the needle cap until ready to inject.

■ Inspect the pre-filled syringe for damage.

• Do not use the pre-filled syringe if any part of it is damaged.

■ Check the expiry date on the pre-filled syringe.

• Do not use if the expiry date on the pre-filled syringe has passed.

■ Check the medicine. It should be colourless to yellow.

• Do not use the pre-filled syringe if the medicine is cloudy or has particles floating in it.

■ You may see air bubbles in the syringe. This is normal.

• Do not attempt to remove air bubbles from the pre-filled syringe.
• Do not shake

• 3) Prepare the injection site

• ■ Choose an injection site on your bare skin from 1 of the following.

• Front of the thighs, or
• Stomach area (abdomen) except for the area 5 cm around the belly button (navel), or
• Back of the upper arm (only if a caregiver gives the injection).

■ Use a new injection site or a different area within the same injection site for each injection.

• Do not inject into moles, scars, bruises, or skin that is tender, hard, red, or damaged.

■ Wipe the chosen site with an alcohol pad. Let your skin dry.

• Do not touch this area again before you inject.

• 4) Inject Entyvio

• ■ Pull the needle cap straight off.

• Do not touch or pull back the purple plunger.
• You may see a drop of liquid at the end of the needle.

This is normal.

• Do not touch or re-cap the needle.
• Do not use a dropped pre-filled syringe.
• Do not use a pre-filled syringe with a bent or broken needle.

• ■ Throw away the cap.

• ■ Hold the pre-filled syringe with 1 hand and pinch the skin around the injection site with your other hand.

• Hold the pinch until the injection is completed.

• ■ Insert the needle at about a 45-degree angle all the way into the pinched skin.

• ■ Push down on the plunger as far as it will go to inject all the

medicine.

• Keep pressure on the plunger and take the needle out of the skin.

• ■ Take your thumb off the plunger to allow the needle guard to cover the needle.

• ■ You may see a small amount of blood at the injection site. If you do, press on your skin with a cotton ball or gauze.

• 5) Throw away used material

• ■ Put the used pre-filled syringe in a puncture-resistant container, like a sharps container, immediately after use.

• Dispose of your sharps container according to your local regulations.

■ The rest of the material can be thrown in your household rubbish.

Package leaflet: Information for the patient

Entyvio 108 mg solution for injection in pre-filled pen

vedolizumab

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in 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 Entyvio is and what it is used for

What Entyvio is

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

How Entyvio works

Entyvio works by blocking a protein on the surface of white blood cells that cause the inflammation in ulcerative colitis and Crohn’s disease. This reduces the amount of inflammation.

What Entyvio is used for

Entyvio is used to treat the signs and symptoms in adults of:

• moderately to severely active ulcerative colitis
• moderately to severely active Crohn’s disease.

Ulcerative colitis

Ulcerative colitis is a disease that causes inflammation of the large bowel. If you have ulcerative colitis, you will first be given other medicines. If you do not respond well enough or cannot tolerate these medicines, your doctor may give you Entyvio to reduce the signs and symptoms of your 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 well enough or cannot tolerate these medicines, your doctor may give you Entyvio to reduce the signs and symptoms of your 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 an active severe infection – such as TB (tuberculosis), blood poisoning, severe diarrhoea and vomiting (gastroenteritis), nervous system infection.

Warnings and precautions

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

Tell your doctor, pharmacist or nurse immediately when you first use this medicine, during treatment, and between doses:

• if you experience blurred, loss of or double vision, difficulty speaking, weakness in an arm or a leg, a change in the way you walk or problems with your balance, persistent numbness, decreased sensation or loss of sensation, memory loss or confusion. These may all be symptoms of a serious and potentially fatal brain condition known as progressive multifocal leukoencephalo­pathy (PML).
• if you have an infection, or think you have an infection – signs include chills, shivering,

persistent cough or a high fever. Some infections may become serious and possibly even life-threatening if left untreated.

• 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 going to receive any vaccination or have recently had a vaccination. Entyvio may affect the way you respond to a vaccination.
• if you have cancer, tell your doctor. Your doctor will have to decide if you can still be given Entyvio.
• if you are not feeling any better as vedolizumab may take up to 14 weeks to work in some patients with very active Crohn’s disease.

Children and adolescents

Entyvio is not recommended for use in children or adolescents (under 18 years of age) due to the lack of information regarding 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 biologic medicines that suppress your immune system as the effect of this is not known.

Tell your doctor if you have previously taken:

• natalizumab (a medicine for multiple sclerosis) or
• rituximab (a medicine for certain types of cancer and rheumatoid arthritis).

Your doctor will decide if you can be given Entyvio.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

Pregnancy

The effects of Entyvio in pregnant women are not known. Therefore, this medicine is not recommended for use during pregnancy. You and your doctor should decide if the benefit to you clearly outweighs the potential risk to yourself and your baby.

If you are a woman of childbearing potential, you are advised to avoid becoming pregnant while using Entyvio. You should use adequate contraception during treatment and for at least 4.5 months after the last treatment.

Breast-feeding

Tell your doctor if you are breast-feeding or planning to breast-feed. Entyvio passes into breast milk. There is not enough information on what effect this may have on your baby and on milk production. A decision must be made whether to stop breast-feeding or to stop using Entyvio therapy taking into account the benefit of breast-feeding for your child and the benefit of therapy for you.

Driving and using machines

This medicine has a minor effect on your ability to drive or use tools or machines. A small number of patients have felt dizzy after receiving Entyvio. If you feel dizzy, do not drive or use tools or machines.

Entyvio 108 mg solution for injection contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.

3. How to use Entyvio

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

You or your caregiver will be given training on how to use Entyvio injections under the skin (subcutaneous injections).

How much Entyvio you will receive

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 start of treatment, the doctor will give initial doses of Entyvio through a drip into a vein in your arm (intravenous infusion) over about 30 minutes.
• After at least 2 intravenous infusions, you can start receiving Entyvio by a subcutaneous injection. The first subcutaneous injection is given at the time of the next scheduled intravenous infusion, and every 2 weeks thereafter.

Injecting Entyvio

The subcutaneous injections can be given by yourself or a caregiver, after training on how to do it. Instructions are provided at the end of this leaflet.

If you forget to take or miss your Entyvio injection

If you forget or miss a dose, inject the next dose as soon as possible and then every 2 weeks thereafter.

If you stop using Entyvio

Do not stop using Entyvio without talking with your doctor first.

If you have any further questions on the use of this medicine, ask your doctor pharmacist or nurse.

4. Possible side effects

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

Serious side effects

Tell your doctor immediately if you notice any of the following:

• allergic reactions (may affect up to 1 in 100 people) – the signs may include: wheezing or difficulty breathing, hives, itching of the skin, swelling, feeling sick, redness of skin and
• infections (may affect up to 1 in 10 people) – the signs may include: chills or shivering, high fever or rash

Other side effects

Tell your doctor as soon as possible if you notice any of the following:

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

• common cold
• joint pain
• headache

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

• fever
• chest infection
• tiredness
• cough
• flu (influenza)
• back pain
• throat pain
• sinus infection
• itching / itchiness
• rash and redness
• pain in the limb
• muscle cramps
• muscle weakness
• throat infection
• stomach flu
• anal infection
• anal sore
• hard faeces
• bloated stomach
• passing gas
• high blood pressure
• prickling or tingling
• heart burn
• haemorrhoids
• blocked nose
• eczema
• night sweats
• acne (pimples)
• injection site reactions (including pain, swelling, redness or itching)

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

• redness and tenderness of hair follicle
• throat and mouth yeast infection
• vaginal infection
• shingles (herpes zoster)

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

• pneumonia
• blurred vision (loss of sharpness of eyesight)
• sudden, severe allergic reaction which can cause breathing difficulty, swelling, fast heartbeat, sweating, drop in blood pressure, light-headedness, loss of consciousness and collapse (anaphylactic reaction and anaphylactic shock)

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 via the national reporting system listed in 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 carton 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). Keep the pre-filled pen in the original carton in order to protect from light. If needed the pre-filled pen can be left out of the refrigerator in its original carton at room temperature (up to 25 oC) for up to 7 days. Do not use if left out of the refrigerator for more than 7 days.
• Do not freeze. Do not leave in direct sunlight.
• Do not use this medicine if you notice any particles in the liquid or discolouration (should be colourless to yellow) prior to administration.
• Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Entyvio contains

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

What Entyvio looks like and contents of the pack

• Entyvio is a colourless to yellow solution for injection provided in a glass pre-filled pen equipped with an automated needle shield to extend and lock over the needle once the device is removed from the injection site.
• Entyvio is available in a carton containing 1 pre-filled pen and multipacks containing

2 (2×1 pre-filled pens), or 6 (6×1 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-Straße 25

4020 Linz

Austria

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

This leaflet was last revised in

Other sources of information

This leaflet is available in formats suitable for the blind or partially sighted patient and can be requested from respective local representative of the Marketing Authorisation Holder.

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

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The following information is intended for healthcare professionals only:

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded

Instructions for use:

Read and follow these instructions before you inject. Your doctor, nurse or pharmacist should show you how to use the Entyvio pre-filled pen before you use it for the first time.

Your Entyvio single-dose pre-filled pen

Before Use

Purple Cap Viewing window

After Use

Viewing window

Yellow needle shield (Completed Injection)

I I

• 2) Open and check the pre-filled pen

• ■ Wash your hands.

• ■ Peel back the paper on the tray and lift the pre-filled pen out.

• ■ Inspect the pre-filled pen for damage.

• Do not use the pre-filled pen if any part of it is damaged.

■ Check the expiry date on the pre-filled pen.

• Do not use if the expiry date on the pre-filled pen has passed.

■ Check the medicine. It should be colourless to yellow.

• Do not use the pre-filled pen if the medicine is cloudy or has particles floating in it.

■ You may see air bubbles in the pre-filled pen. This is normal.

• Do not shake

• 3) Prepare the injection site

• ■ Choose an injection site on your bare skin from 1 of the following.

• Front of the thighs, or
• Stomach area (abdomen) except for the area 5 cm around the belly button (navel), or
• Back of the upper arm (only if a caregiver gives the injection).

■ Use a new injection site or a different area within the same injection site for each injection.

• Do not inject into moles, scars, bruises, or skin that is tender, hard, red, or damaged.

■ Wipe the chosen site with an alcohol pad. Let your skin dry.

• Do not touch this area again before you inject.

■ Pull the purple cap straight off and throw it away.

• Do not put or press thumb, fingers or hand over the yellow needle shield.
• Do not re-cap the pre-filled pen.
• Do not use a dropped pre-filled pen.

• 4) Inject Entyvio

• ■ Hold the pre-filled pen so you can see the viewing window.

• ■ Place the pre-filled pen at 90 degrees to the injection site.

• Be sure the yellow end is toward the injection site.
• Do not push down until you are ready to inject.

• ■ Push down on the pre-filled pen as far as it will go to begin the injection.

• ■ Hold and count to 10 while pushing down with constant pressure. This will allow all of the medicine to be injected.

• You may hear 2 clicks, one at the start and one near the end of the injection.

■ Confirm that the viewing window is filled with purple before you stop pushing.

• You will see a small amount of grey in the window. This is normal.

■ Lift the pre-filled pen from the injection site.

• The yellow needle shield will drop down and lock over the needle.
• If the viewing window did not fill completely, call your doctor,

nurse or pharmacist. You may not have received your full dose of medicine.

• ■ You may see a small amount of blood at the injection site.

If you do, press on your skin with a cotton ball or gauze.

• 5) Throw away used material

• ■ Put the used pre-filled pen in a puncture-resistant container, like a sharps container, immediately after use.

• Dispose of your sharps container according to your local regulations.

■ The rest of the material can be thrown away in your household rubbish.

ANNEX IV

CONCLUSIONS ON THE REQUEST FOR ONE-YEAR MARKETING PROTECTION PRESENTED BY THE EUROPEAN MEDICINES AGENCY

Conclusions presented by the European Medicines Agency on:

• one-year marketing protection

The CHMP reviewed the data submitted by the marketing authorisation holder, taking into account the provisions of Article 14(11) of Regulation (EC) No 726/2004, and considers that the new therapeutic indication brings significant clinical benefit in comparison with existing therapies as further explained in the European Public Assessment Report.

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