WEZENLA 130 mg CONCENTRATE FOR INFUSION SOLUTION

2. What you need to know before you use WEZENLA

Do not use WEZENLA

• 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 WEZENLA.

Warnings and precautions

Talk to your doctor or pharmacist before starting WEZENLA. 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 WEZENLA. If your doctor thinks you are at risk of tuberculosis, they may give you medicines to treat it.

Watch for serious side effects

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

Before using WEZENLA, tell your doctor:

• If you have ever had an allergic reaction to WEZENLA.Check with your doctor if you are not sure.
• If you have ever had any type of cancer– this is because immunosuppressants like WEZENLA weaken part of the immune system. This may increase the risk of having 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 having cancer may be higher.
• If you have had a recent infection or have any open sores (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 WEZENLA. However, it is possible that it may increase the likelihood of suffering from diseases related to a weaker immune system.
• If you are receiving or have ever received allergy shots– it is not known if WEZENLA 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 WEZENLA.

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

Heart attacks and strokes

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

Children and adolescents

WEZENLA 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 WEZENLA 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 receive a vaccine.Certain types of vaccines (live vaccines) should not be given while you are using WEZENLA.
• If you received WEZENLA during pregnancy, inform your baby's doctor about your treatment with WEZENLA 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 WEZENLA during pregnancy, unless your baby's doctor recommends otherwise.

Pregnancy and breastfeeding

• If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.
• No increased risk of birth defects has been seen in babies exposed to WEZENLA in the womb.However, there is limited experience with WEZENLA in pregnant women. Therefore, it is preferable to avoid using WEZENLA during pregnancy.
• If you are a woman of childbearing age, you are advised to avoid becoming pregnant and to use adequate contraceptive measures while you are using WEZENLA and for at least 15 weeks after the last treatment with WEZENLA.
• WEZENLA may pass through the placenta to the fetus.If you received WEZENLA 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 WEZENLA 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 WEZENLA 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, inform your doctor. You and your doctor will decide whether you should breastfeed or use WEZENLA. Do not do both.

Driving and using machines

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

WEZENLA contains sodium

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

WEZENLA contains polysorbate 80

WEZENLA contains 10.4 mg of polysorbate 80 (E 433) per single dose, equivalent to 0.40 mg/ml. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergy.

3. How to use WEZENLA

WEZENLA 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 WEZENLA 130 mg concentrate for solution for infusion by dripping it 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 WEZENLA is given

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

Adults aged 18 and over

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

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

How WEZENLA is given

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

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

If you miss a dose of WEZENLA

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

If you stop using WEZENLA

Stopping WEZENLA 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 emergency medical help immediately if you notice any of the following signs.

• Severe allergic reactions (“anaphylaxis”) are rare in people using WEZENLA (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 WEZENLA is given by dripping it into a vein (intravenous infusion).Some patients have had severe allergic reactions during the infusion.

In rare cases, allergic reactions in the lungs and lung inflammation 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 WEZENLA 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)

WEZENLA may 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 occur mainly 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 WEZENLA. 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 having a painful skin rash with blisters
• pain when urinating
• diarrhea
• vision problems or loss of vision
• headache, stiff neck, sensitivity to light, nausea, or confusion.

Talk to 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 WEZENLA until the infection goes away. Also, talk to your doctor if you have any open sores or ulcers 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 weakness 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)
• skin peeling (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 natural change in the symptoms of psoriasis (erythrodermic psoriasis)

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

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

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 WEZENLA

• WEZENLA 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 (between 2 °C and 8 °C). Do not freeze.
• Keep the vial in the outer packaging to protect it from light.
• Do not shake WEZENLA vials. Prolonged vigorous shaking can damage the product.

Do not use this medicine:

• After the expiration date shown on the label and carton after "CAD" or "EXP". The expiration date is the last day of the month indicated.
• If the liquid changes color, is turbid, or has foreign particles floating in it (see section 6 "Appearance of WEZENLA and package contents").
• If you know or believe 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.

WEZENLA is for single use. You should discard any unused diluted solution for infusion that remains in the vial or syringe in accordance with local regulations.

6. Package contents and additional information

Composition of WEZENLA

• 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 hydrochloride monohydrate, L-methionine, polysorbate 80, sucrose, sodium hydroxide (for pH adjustment), and water for injectable preparations.

Appearance of WEZENLA and package contents

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

Marketing authorization holder and manufacturer

Amgen Technology (Ireland) UC,

Pottery Road,

Dun Laoghaire,

Co Dublin,

Ireland

Marketing authorization holder

Amgen Technology (Ireland) UC,

Pottery Road,

Dun Laoghaire,

Co Dublin,

Ireland

Manufacturer

Amgen NV

Telecomlaan 5-7

1831 Diegem

Belgium

You can request more information about this medicine by contacting the local representative of the marketing authorization 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: http://www.ema.europa.eu.

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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 administered product must be clearly recorded.

Instructions for dilution:

WEZENLA 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 WEZENLA vials needed based on the patient's weight (see section 3, table 1). Each 26 ml vial of WEZENLA 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 WEZENLA to be added (discard 26 ml of sodium chloride per vial of WEZENLA needed: for 2 vials, discard 52 ml; for 3 vials, discard 78 ml; for 4 vials, discard 104 ml).
3. Withdraw 26 ml of WEZENLA 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.
6. Use only an infusion system with an in-line filter, sterile, non-pyrogenic, and low protein-binding (pore size 0.2 microns).
7. Each vial is for single use and unused medicine should be discarded in accordance with local regulations.

Storage

If necessary, the diluted solution for infusion can be stored at room temperature.

The chemical and physical stability of the product has been demonstrated for 24 hours at a temperature between 15 °C and 25 °C once diluted between 0.86 mg/ml and 2.60 mg/ml. Do not refrigerate again. Do not freeze.