YESINTEK 130 mg CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the Patient

Yesintek 130 mg Concentrate for Solution for Infusion

Ustekinumab

This medicinal product is subject to additional monitoring, which will allow for quick identification of new safety information. You can help by reporting any side effects you may get. The last section of the leaflet includes information on how to report side effects.

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

This leaflet has been written for patients who are taking the medicine.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• If you get any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Yesintek and what is it used for

What is Yesintek

Yesintek contains the active substance “ustekinumab”, a monoclonal antibody. Monoclonal antibodies are proteins that identify and bind to specific proteins in the body.

Yesintek belongs to a group of medicines called “immunosuppressants”. These medicines work by weakening part of the immune system.

What is Yesintek used for

Yesintek is used to treat moderate to severe Crohn's disease in adults.

Crohn's disease is an inflammatory disease of the intestine. If you have Crohn's disease, you will first be given other medicines. If you do not respond well to these medicines or cannot tolerate them, you may be given Yesintek to reduce the signs and symptoms of your disease.

2. What you need to know before you use Yesintek

Do not use Yesintek

• If you are allergic to ustekinumabor any of the other ingredients of this medicine (listed in section 6).
• If you have an active infectionthat your doctor thinks is important.

If you are not sure if any of the above applies to you, talk to your doctor or pharmacist before using Yesintek.

Warnings and precautions

Talk to your doctor or pharmacist before starting Yesintek. Your doctor will check how you are before treatment. Make sure you tell your doctor about any illness you have before treatment. Also, tell your doctor if you have recently been near someone who might have tuberculosis. Your doctor will examine you and do a test to check for tuberculosis before you use Yesintek. If your doctor thinks you are at risk of tuberculosis, they may give you medicines to treat it.

Watch for serious side effects

Yesintek can cause serious side effects, including allergic reactions and infections. You should be aware of certain signs of illness while you are using Yesintek. See the complete list of these side effects in “Serious side effects” in section 4.

Before using Yesintek, tell your doctor:

• If you have ever had an allergic reaction to Yesintek.Check with your doctor if you are not sure.
• If you have ever had any type of cancer– this is because immunosuppressants like Yesintek weaken part of the immune system. This may increase the risk of getting cancer.
• If you have received treatment for psoriasis with other biologics (a medicine made from a biological source and usually given by injection)– the risk of getting cancer may be higher.
• If you have had a recent infection or have any open sores on your skin (fistula).
• If you have any new or changing lesionswithin the area of psoriasis or on intact skin.
• If you are taking any other treatment for psoriasis and/or psoriatic arthritis– such as any other immunosuppressant or phototherapy (when your body is treated with a type of ultraviolet light (UV)). These treatments may also weaken part of the immune system. It has not been studied whether these treatments can be used together with Yesintek. However, it is possible that it may increase the likelihood of getting illnesses related to a weakened immune system.
• If you are receiving or have ever received allergy shots– it is not known if Yesintek can affect these treatments.
• If you are 65 years of age or older– you are more likely to get infections.

If you are not sure if you have any of these conditions, talk to your doctor or pharmacist before using Yesintek.

Some patients have experienced lupus-like reactions during treatment with ustekinumab, including cutaneous lupus or lupus-like syndrome. Talk to your doctor right away if you experience a red, raised, and scaly skin rash, sometimes with a darker border, in areas of the skin exposed to the sun, or if they are accompanied by joint pains.

Heart attacks and strokes

In a study of patients with psoriasis treated with Yesintek, heart attacks and strokes have been observed. Your doctor will check your risk factors for heart disease and stroke regularly to make sure they are being treated properly. Seek medical attention right away if you experience chest pain, weakness, or an unusual feeling on one side of your body, facial paralysis, or abnormalities in speech or vision.

Children and adolescents

Yesintek is not recommended for use in children under 18 years of age with Crohn's disease, as it has not been studied in this age group.

Using Yesintek with other medicines, vaccines

Tell your doctor or pharmacist:

• If you are using, have recently used, or might use other medicines.
• If you have been vaccinated recently or are going to have a vaccine. Certain types of vaccines (live vaccines) should not be given while you are using Yesintek.
• If you received Yesintek during pregnancy, inform your baby's doctor about your treatment with Yesintek before your baby receives any vaccine, including live vaccines, such as the BCG vaccine (used to prevent tuberculosis). Live vaccines are not recommended for your baby in the first 12 months after birth if you received Yesintek during pregnancy, unless your baby's doctor recommends otherwise.

Pregnancy and breastfeeding

• If you are pregnant, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine.
• No increased risk of birth defects has been seen in babies exposed to Yesintek in the womb. However, there is limited experience with Yesintek in pregnant women. Therefore, it is preferable to avoid using Yesintek during pregnancy.
• If you are a woman of childbearing age, you are advised to avoid becoming pregnant and to use adequate contraception while using Yesintek and for at least 15 weeks after the last treatment with Yesintek.
• Yesintek may pass into the placenta to the fetus. If you received Yesintek during pregnancy, your baby may have a higher risk of getting an infection.
• It is important that you inform your baby's doctors and other healthcare professionals if you received Yesintek during your pregnancy before your baby receives any vaccine. Live vaccines, such as the BCG vaccine (used to prevent tuberculosis), are not recommended for your baby in the first 12 months after birth if you received Yesintek during pregnancy, unless your baby's doctor recommends otherwise.
• Ustekinumab may be excreted in breast milk in very small amounts. If you are breastfeeding or plan to breastfeed, talk to your doctor. You and your doctor will decide whether you should breastfeed or use Yesintek. Do not do both.

Driving and using machines

Yesintek has no or negligible influence on the ability to drive and use machines.

Yesintek contains sodium

Yesintek contains less than 1 mmol of sodium (23 mg) per dose; this is essentially “sodium-free”. However, before you are given Yesintek, it is mixed with a solution that contains sodium. Talk to your doctor if you are on a low-salt diet.

Yesintek contains polysorbate 80

This medicine contains 10.4 mg of polysorbate 80 (E 433) in each 130 mg/26 ml vial, equivalent to 0.4 mg/ml (0.6 mg/kg per day). Polysorbates may cause allergic reactions. Inform your doctor if you have any allergies.

3. How to use Yesintek

Yesintek should be used under the guidance and supervision of a doctor with experience in the diagnosis and treatment of Crohn's disease.

Your doctor will give you Yesintek 130 mg concentrate for solution for infusion by drip into a vein in your arm (intravenous infusion) over at least one hour. Ask your doctor when you should have the injections and about follow-up appointments.

How much Yesintek is given

Your doctor will decide how much Yesintek you need to receive and how long your treatment will last.

Adults aged 18 years and over

• Your doctor will calculate the recommended infusion dose for you based on your body weight.

• After the initial intravenous dose, you will receive the next dose of 90 mg of Yesintek by injection under the skin (subcutaneous injection) 8 weeks later and then every 12 weeks.

How Yesintek is given

• The first dose of Yesintek for the treatment of Crohn's disease is given by a doctor by drip into a vein in your arm (intravenous infusion).

Talk to your doctor if you have any questions about your treatment with Yesintek.

If you miss a dose of Yesintek

If you miss a dose or do not attend an appointment to have it given to you, talk to your doctor to schedule another appointment.

If you stop using Yesintek

Stopping Yesintek is not dangerous. However, if you stop using it, your symptoms may come back.

If you have any other questions about using this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

Serious side effects

Some patients may have serious side effects that may need urgent treatment.

Allergic reactions – these may need urgent treatment. Contact your doctor or get urgent medical help immediately if you notice any of the following signs.

• Severe allergic reactions (“anaphylaxis”) are rare in people using Yesintek (may affect up to 1 in 1,000 people). Signs include:

• difficulty breathing and swallowing
• low blood pressure, which can cause dizziness or mild headaches
• swelling of the face, lips, mouth, or throat

• Common signs of an allergic reaction include skin rash and hives (these may affect up to 1 in 100 people).

Infusion-related reactions – If you are being treated for Crohn's disease, the first dose of Yesintek is given by drip into a vein (intravenous infusion). Some patients have had severe allergic reactions during the infusion.

In rare cases, allergic reactions in the lungs and inflammation of the lungs have been reported in patients treated with ustekinumab. Tell your doctor immediately if you have symptoms such as cough, difficulty breathing, and fever.

If you have a severe allergic reaction, your doctor may decide that you should not use Yesintek again.

Infections – these may need urgent treatment. Contact your doctor immediately if you notice any of these signs.

• Nose or throat infections and the common cold are common (may affect up to 1 in 10 people).
• Chest infections are uncommon (may affect up to 1 in 100 people).
• Inflammation of the tissues under the skin (“cellulitis”) is uncommon (may affect up to 1 in 100 people).
• Herpes (a type of painful rash with blisters) is uncommon (may affect up to 1 in 100 people).

Yesintek can affect your ability to fight infections. Some of these may be serious and be caused by viruses, fungi, bacteria (including tuberculosis), or parasites, and include infections that mainly occur in people with a weakened immune system (opportunistic infections). Opportunistic infections of the brain (encephalitis, meningitis), lungs, and eyes have been reported in patients receiving treatment with ustekinumab.

You should watch for signs of infection while you are using Yesintek. These include:

• fever, flu-like symptoms, night sweats, weight loss
• feeling tired or having trouble breathing; cough that does not go away
• having hot, red, and painful skin or a painful skin rash with blisters
• burning when urinating
• diarrhea
• vision problems or loss of vision
• headache, stiff neck, sensitivity to light, nausea, or confusion.

Tell your doctor immediately if you notice any of these signs of infection, as they may be signs of infections such as chest infections, skin infections, herpes, or opportunistic infections that may have serious complications. You should also tell your doctor if you have any type of infection that does not go away or comes back. Your doctor may decide that you should not use Yesintek until the infection goes away. Also, talk to your doctor if you have any open cuts or sores that may become infected.

Shedding of the skin – increased redness and shedding of the skin over a large area of the body may be symptoms of erythrodermic psoriasis or exfoliative dermatitis, which are serious skin disorders. If you notice any of these symptoms, you should tell your doctor immediately.

Other side effects

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

• Diarrhea
• Nausea
• Vomiting
• Feeling tired
• Feeling dizzy
• Headache
• Itching (“pruritus”)
• Back, muscle, or joint pain
• Sore throat
• Redness and pain at the injection site
• Sinusitis

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

• Dental infections
• Vaginal yeast infections
• Depression
• Nasal congestion or stuffiness
• Bleeding, bruising, hardening, swelling, and itching at the injection site
• Feeling weak
• Drooping eyelid and sinking of the muscles on one side of the face (“facial paralysis” or “Bell's palsy”), which is usually temporary
• A change in psoriasis with redness and new small, yellow, or white bumps on the skin, sometimes accompanied by fever (pustular psoriasis)
• Shedding of the skin (exfoliation of the skin)
• Acne

Rare side effects(may affect up to 1 in 1,000 people):

• Redness and shedding of the skin over a large area of the body, which may be itchy or painful (exfoliative dermatitis). Similar symptoms may develop, such as a change in the natural symptoms of psoriasis (erythrodermic psoriasis)
• Inflammation of small blood vessels, which may cause a skin rash with small red or purple bumps, fever, or joint pain (vasculitis)

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

• Blisters on the skin, which may be red, itchy, and painful (bullous pemphigoid).
• Cutaneous lupus or lupus-like syndrome (red, raised, and scaly skin rash in areas of the skin exposed to the sun, possibly accompanied by joint pains).

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Yesintek

• Yesintek 130 mg concentrate for solution for infusion is administered in a hospital or medical center and it is not necessary for patients to store or handle it.
• Keep this medicine out of the sight and reach of children.
• Store in a refrigerator (2 °C – 8 °C). Do not freeze.
• Keep the vial in the outer packaging to protect it from light.
• Do not shake Yesintek vials. Prolonged vigorous shaking can damage the product.

Do not use this medicine:

• After the expiry date which is stated on the label and carton after “EXP”. The expiry date is the last day of the month shown.
• If the liquid changes color, is cloudy or has foreign particles floating in it (see section 6 “Appearance and package contents”).
• If you know or think it has been exposed to extreme temperatures (such as accidental heating or freezing).
• If the product has been vigorously shaken.
• If the seal is broken.

Yesintek is for single use. You should dispose of any unused diluted infusion solution left in the vial or syringe in accordance with local regulations.

6. Package contents and additional information

Composition of Yesintek

• The active substance is ustekinumab. Each vial contains 130 mg of ustekinumab in 26 ml.
• The other ingredients are disodium dihydrate EDTA, L-histidine, L-histidine monohydrochloride monohydrate, L-methionine, polysorbate 80 (E 433), sucrose, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment), and water for injections.
• This medicine contains 10.4 mg of polysorbate 80 (E 433) in each 130 mg/26 ml vial, equivalent to 0.4 mg/ml (0.6 mg/kg per day). Polysorbates may cause allergic reactions. Inform your doctor if you have allergies.

Appearance and package contents

Yesintek is a clear, pale yellow to colorless concentrate for solution for infusion. It is presented in a pack containing 1 single-dose vial of 30 ml glass. Each vial contains 130 mg of ustekinumab in 26 ml of concentrate for solution for infusion.

Marketing Authorisation Holder

Biosimilar Collaborations Ireland Limited

Unit 35/36 Grange Parade,

Baldoyle Industrial Estate,

Dublin 13, DUBLIN

Ireland, D13 R20R

Manufacturer

Biosimilar Collaborations Ireland Limited

Block B, The Crescent Building, Santry Demesne

Dublin

D09 C6X8

Ireland

You can request more information about this medicine by contacting the local representative of the marketing authorisation holder:

Date of last revision of this leaflet

Other sources of information

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

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

This information is intended only for healthcare professionals:

Traceability:

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

Instructions for dilution:

Yesintek concentrate for solution for infusion must be diluted, prepared, and infused by a healthcare professional using aseptic technique.

1. Calculate the dose and number of Yesintek vials needed based on the patient's weight (see section 3, Table 1). Each 26 ml vial of Yesintek contains 130 mg of ustekinumab.
2. Withdraw and then discard a volume of 9 mg/ml (0.9%) sodium chloride solution from the 250 ml infusion bag equivalent to the volume of Yesintek to be added (discard 26 ml of sodium chloride for each vial of Yesintek needed: for 2 vials, discard 52 ml; for 3 vials, discard 78 ml; for 4 vials, discard 104 ml).
3. Withdraw 26 ml of Yesintek from each required vial and add it to the 250 ml infusion bag. The final volume of the infusion bag should be 250 ml. Mix gently.
4. Perform a visual inspection of the diluted solution before infusion. Do not use if opaque particles, color changes, or foreign particles are detected.
5. Infuse the diluted solution over a minimum period of one hour. Once diluted, the infusion must be completed within 8 hours of dilution in the infusion bag.
6. Use only an infusion system with an in-line filter, sterile, apyrogenic, and low protein-binding (pore size of 0.2 micrometers).
7. Each vial is for single use and unused medicine should be discarded in accordance with local regulations.

Storage

If necessary, the diluted infusion solution can be stored at room temperature. The infusion must be completed within 12 hours of dilution in the infusion bag. Do not freeze. Do not refrigerate after dilution.