Entyvio 300 mg powder for concentrate for solution for infusion

Package Leaflet: Information for the User

Introduction

Package Leaflet: Information for the Patient

Entyvio 300mg powder for concentrate for solution for infusion

vedolizumab

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet as you may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If you experience any adverse reactions, consult your doctor or nurse, even if they are not listed in this leaflet. See section 4.

Leaflet Contents

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 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 known as monoclonal antibodies (MAb).

How Entyvio works

Entyvio blocks a protein on the surface of white blood cells (leukocytes) that causes inflammation in ulcerative colitis, Crohn's disease, and pouchitis, thereby reducing inflammation.

What Entyvio is indicated for

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

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

Ulcerative colitis

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

Crohn's disease

Crohn's disease is a condition that causes inflammation of the digestive tract. If you have Crohn's disease, you will first be given other medications. If you do not respond adequately or cannot tolerate these medications, your doctor may prescribe Entyvio to reduce the signs and symptoms of the disease.

Pouchitis

Pouchitis is a disease that causes inflammation of the lining of the pouch created during surgery to treat ulcerative colitis. If you have pouchitis, you may first be given antibiotics. If you do not respond sufficiently to antibiotics, your doctor may prescribe Entyvio to reduce the signs and symptoms of the disease.

2. What you need to know before Entyvio is administered to you

Do not use Entyvio:

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

Warnings and precautions

Talk to your doctor or nurse before receiving Entyvio.

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

• if you experience double vision, blurred vision, or loss of vision, difficulty speaking, weakness in an arm or leg, a change in the way you walk, balance problems, persistent numbness, reduced or loss of sensation, confusion, or memory loss. All of these symptoms could indicate a serious and potentially life-threatening brain condition known as progressive multifocal leukoencephalopathy (PML).

• if you have an infection, or think you may have an infection — signs may include chills, persistent cough, or high fever. Some infections may be serious and even potentially life-threatening if not treated.

• if you experience signs of an allergic reaction or another infusion-related reaction, such as wheezing, difficulty breathing, hives, itching, swelling, or dizziness. These may occur during or after the infusion. For more detailed information, see the section on infusion and allergic reactions in section 4.

• if you are due to receive any vaccination or have recently received one. Entyvio may affect how you respond to a vaccine.

• if you have cancer, tell your doctor. Your doctor will need to decide whether it is safe to give you Entyvio.

• if you do not feel 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 and adolescents (under 18 years of age) due to lack of information 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 need to take any other medicines.

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

Tell your doctor if you have previously been treated with:

• natalizumab (a medicine used to treat multiple sclerosis), or
• rituximab (a medicine used to treat certain types of cancer and rheumatoid arthritis).

Your doctor will need to decide whether it is safe to give you Entyvio.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor before using this medicine.

Pregnancy

The effects of Entyvio in pregnant women are unknown. Therefore, the use of this medicine during pregnancy is not recommended. You and your doctor must decide whether 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 that you avoid becoming pregnant during treatment with Entyvio. You should use effective contraception during treatment and for at least 4.5 months after receiving the last dose.

Breastfeeding

Tell your doctor if you are breastfeeding or plan to breastfeed. Entyvio passes into breast milk. There is insufficient information on the effects this may have on your baby and on milk production. A decision must be made whether to discontinue breastfeeding or Entyvio therapy, taking into account the benefits of breastfeeding for your baby and the benefits of treatment for you.

Driving and using machines

The effects of this medicine on the ability to drive and use machines or tools are minor. A small number of patients have felt dizzy after receiving Entyvio. If you feel dizzy, do not drive or operate tools or machinery.

Entyvio contains polysorbate 80

This medicine contains 3.31 mg of polysorbate 80 in each 300 mg Entyvio vial. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergies.

3. How to administer Entyvio

How much Entyvio will be given to you

The treatment with Entyvio is the same for ulcerative colitis, Crohn's disease, and pouchitis.

The recommended dose is 300 mg of Entyvio, which will be administered as outlined below (see table):

Your doctor may decide to modify this treatment schedule depending on how you respond to treatment with Entyvio.

• Your doctor or nurse will administer the medicine through an intravenous infusion system, delivered slowly into one of the veins in your arm (intravenous infusion) over approximately 30 minutes.
• During the first 2 infusions, your doctor or nurse will carefully monitor you during the infusion and for approximately 2 hours after completion. For subsequent infusions (after the first 2), you will be monitored during the infusion and for approximately 1 hour after completion.

If you forget or miss an appointment for an Entyvio infusion

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

If you interrupt treatment with Entyvio

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

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Serious adverse effects

Inform your doctor immediately if you notice any of the following symptoms:

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

Other adverse effects

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

Very common adverse effects (may affect more than 1 in 10 patients)

• common cold
• joint pain
• headache

Common adverse effects (may affect up to 1 in 10 patients)

• pneumonia
• bacterial infection of the large intestine due to Clostridium difficile
• fever
• respiratory infection
• changes in liver function, increase in liver enzymes (shown in blood tests)
• fatigue
• cough
• flu
• back pain
• sore throat
• sinusitis
• itching/pruritus
• rash and redness
• pain in limbs
• muscle cramps
• muscle weakness
• throat infection
• stomach flu
• anal infection
• anal pain
• hard stools
• bloated stomach
• flatulence
• high blood pressure
• numbness or tingling
• heartburn
• haemorrhoids
• stuffy nose
• eczema
• night sweats
• acne (spots)
• rectal bleeding
• chest discomfort
• shingles

Uncommon adverse effects (may affect up to 1 in 100 patients)

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

Very rare adverse effects (may affect up to 1 in 10,000 patients)

• sudden and severe allergic reaction which may cause difficulty breathing, swelling, rapid heartbeat, sweating, low blood pressure, dizziness, loss of consciousness and fainting (anaphylactic reaction and anaphylactic shock)
• inflammation of the liver (hepatitis). Signs and symptoms of hepatitis may include abnormal liver function tests, yellowing of the eyes or skin (jaundice), pain in the right side of the stomach area, or bruising

Frequency not known (frequency cannot be estimated from available data)

• lung disease causing difficulty in breathing (interstitial lung disease)

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Entyvio

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the carton and label, following "EXP". The expiry date refers to the last day of the month indicated.

Entyvio is administered by a doctor or nurse. Patients must not store or handle it.

Entyvio is for single use only.

Closed vial: Store in a refrigerator (between 2 °C and 8 °C). Keep the vial in the original carton to protect it from light.

Reconstituted and diluted solutions: Use immediately. If this is not possible, the reconstituted solution in the vial may be stored for up to 8 hours between 2 °C and 8 °C. The diluted solution in 9 mg/ml (0.9 %) sodium chloride solution for injection may be stored for up to 12 hours at room temperature not exceeding 25 °C, up to 24 hours in a refrigerator (between 2 °C and 8 °C), or up to 12 hours at room temperature and in the refrigerator (between 2 °C and 8 °C), for a total combined storage time of 24 hours. The 24-hour period may include up to 8 hours for the reconstituted solution in the vial stored between 2 °C and 8 °C and up to 12 hours for the diluted solution in the infusion bag stored at a temperature between 20 °C and 25 °C. However, the infusion bag should be stored in the refrigerator (between 2 °C and 8 °C) for the remainder of the 24-hour period. The time the reconstituted solution remains in the vial should be subtracted from the time the solution remains in the infusion bag.

Do not freeze.

Do not use this medicine if particles are visible in the liquid or if discoloration occurs prior to administration (the solution should be clear or opalescent, colourless or with a yellowish tint).

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Entyvio

• The active substance is vedolizumab. Each vial contains 300 mg of vedolizumab.
• The other components are L-histidine, L-histidine monohydrochloride, L-arginine hydrochloride, sucrose and polysorbate 80 (E 433). See section 2 “Entyvio contains polysorbate 80”.

Appearance of the product and contents of the pack

• Entyvio is a white or almost white powder for concentrate for solution for infusion supplied in a glass vial with a rubber stopper and a plastic cap.
• Each pack of Entyvio contains one vial.

Marketing Authorisation Holder

Takeda Pharma A/S

Delta Park 45

2665 Vallensbaek Strand

Denmark

Manufacturer

Takeda Austria GmbH

St. Peter-Straße 25

A-4020 Linz

Austria

More information about this medicinal product is available upon request by contacting the local representative of the Marketing Authorisation Holder:

Date of the most recent review of this leaflet:

Other sources of information

This leaflet is available in a format suitable for blind or visually impaired patients and can be requested from the local representative of the marketing authorization holder.

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

This information is intended for healthcare professionals only:

Traceability

In order to improve the traceability of biological medicines, the name and batch number of the administered medicine should be clearly documented.

Instructions for reconstitution and infusion

1. Use an aseptic technique to prepare the Entyvio solution for intravenous infusion.

2. Remove the easy-open cap from the vial and clean the top with an alcohol-impregnated cotton swab. Reconstitute vedolizumab with 4.8 ml of sterile water for injection at room temperature between 20 °C and 25 °C, using a syringe with a 21–25 gauge needle.

3. Insert the needle into the vial through the center of the rubber stopper and direct the liquid onto the vial wall to avoid excessive foaming.

4. Gently swirl the vial in circles for at least 15 seconds. Do not shake vigorously or invert it.

5. Let the vial stand for approximately 20 minutes at room temperature between 20 °C and 25 °C to allow reconstitution and dissipation of any foam; during this time, gently swirl the vial and check for dissolution. If not completely dissolved after 20 minutes, allow it to stand for an additional 10 minutes.

6. Before dilution, inspect the reconstituted solution for particles and discoloration. The solution should be clear or opalescent, colorless to pale yellow, and free of visible particles. Do not administer any reconstituted solution that shows atypical discoloration or contains particles.

7. Once dissolved, gently invert the vial three times.

8. Immediately withdraw 5 ml (300 mg) of reconstituted Entyvio using a syringe with a 21–25 gauge needle.

9. Add the 5 ml (300 mg) of reconstituted Entyvio to 250 ml of sterile 9 mg/ml (0.9 %) sodium chloride solution for injection and gently mix in the infusion bag (do not remove 5 ml of 9 mg/ml (0.9 %) sodium chloride solution for injection from the infusion bag before adding Entyvio). Do not add other medications to the prepared infusion solution or to the intravenous infusion set. Administer the infusion solution over 30 minutes.

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

1 In the case of reconstitution, up to 30 minutes are permitted.

2 This time assumes that the reconstituted solution is immediately diluted in sodium chloride 9 mg/ml (0.9%) solution for injection and stored only in the infusion bag. The time the reconstituted solution is stored in the vial must be subtracted from the time the solution may be stored in the infusion bag.

3 This time period may include up to 12 hours at 20°C and 25°C.

Do not freeze. Do not store unused portions of the reconstituted solution or the infusion solution for reuse.

Each vial is for single use only.

Disposal of unused medicine and all materials that have come into contact with it must be carried out in accordance with local regulations.