PYZCHIVA 130 MG CONCENTRATE FOR INFUSION SOLUTION

2. What you need to know before you use Pyzchiva

Do not use Pyzchiva

• If you are allergic to ustekinumabor to 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 Pyzchiva.

Warnings and precautions

Talk to your doctor or pharmacist before starting Pyzchiva. 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 may have tuberculosis. Your doctor will examine you and do a test to check for tuberculosis before you use Pyzchiva. If your doctor thinks you are at risk of tuberculosis, they may give you medicines to treat it.

Observe serious side effects

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

Before using Pyzchiva, tell your doctor:

• If you have ever had an allergic reaction to ustekinumab.Talk to your doctor if you are not sure.
• If you have ever had any type of cancer– this is because immunosuppressants like ustekinumab 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 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 ustekinumab. 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 ustekinumab 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 Pyzchiva.

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 the skin exposed to the sun or if they are accompanied by joint pain.

Heart attacks and strokes

In a study in 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

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

Using Pyzchiva 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 Pyzchiva.
• If you received Pyzchiva during pregnancy, inform your baby's doctor about your treatment with Pyzchiva 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 six months after birth if you received Pyzchiva during pregnancy, unless your baby's doctor recommends otherwise.

Pregnancy and breastfeeding

• It is preferable to avoid the use of Pyzchiva during pregnancy. The effects of ustekinumab in pregnant women are not known. 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 ustekinumab and for at least 15 weeks after the last treatment with ustekinumab.
• Tell your doctor if you are pregnant, think you may be pregnant, or plan to become pregnant.
• Ustekinumab may pass through the placenta to the fetus. If you received Pyzchiva 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 Pyzchiva 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 six months after birth if you received Pyzchiva during pregnancy, unless your baby's doctor recommends otherwise.
• Ustekinumab may be excreted in breast milk in very small amounts. Tell your doctor if you are breastfeeding or plan to breastfeed. You and your doctor will decide whether you should breastfeed or use ustekinumab. Do not do both.

Driving and using machines

The influence of ustekinumab on the ability to drive and use machines is negligible.

Pyzchiva contains sodium

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

Pyzchiva contains polysorbate 80 (E433)

This medicine contains 10.4 mg of polysorbate 80 (E433) in each vial (30 ml) equivalent to 10.4 mg/26 ml. Polysorbates may cause allergic reactions. Tell your doctor if you have any known allergy.

3. How to use Pyzchiva

Pyzchiva 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 Pyzchiva 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 Pyzchiva is given

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

Adults aged 18 years 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 Pyzchiva by injection under the skin (subcutaneous injection) 8 weeks later and then every 12 weeks.

How Pyzchiva is given

The first dose of Pyzchiva 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 Pyzchiva.

If you miss a dose of Pyzchiva

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 Pyzchiva

Stopping ustekinumab 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 ustekinumab (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 receiving treatment for Crohn's disease, the first dose of ustekinumab is given by drip into a vein (intravenous infusion). Some patients have experienced 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 Pyzchiva 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).

Ustekinumab 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 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 be aware of signs of infection while you are using ustekinumab. 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 ustekinumab 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 natural change in the 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 and 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 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 Pyzchiva

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

Do not use this medicine:

• After the expiration date stated on the label and carton after "EXP". The expiration date is the last day of the month indicated.
• If the liquid changes color, is cloudy, or has foreign particles floating in it (see section 6 "Appearance of Pyzchiva 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.

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

6. Package contents and additional information

Composition of Pyzchiva

• The active substance is ustekinumab. Each vial contains 130 mg of ustekinumab in 26 ml.
• The other ingredients are histidine, histidine hydrochloride monohydrate, methionine, disodium edetate, sucrose, polysorbate 80 (E 433), water for injections.

Appearance of Pyzchiva and package contents

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

Marketing Authorization Holder and manufacturer

Samsung Bioepis NL. B.V.

Olof Palmestraat 10

2616 LR Delft

Netherlands

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: MM/AAAA

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: https://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:

Pyzchiva 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 Pyzchiva vials needed based on the patient's weight (see section 3, Table 1). Each 26 ml vial of Pyzchiva 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 Pyzchiva to be added (discard 26 ml of sodium chloride for each vial of Pyzchiva needed: for 2 vials, discard 52 ml; for 3 vials, discard 78 ml; for 4 vials, discard 104 ml). Alternatively, a 250 ml infusion bag containing 0.45% sodium chloride injection, USP, can be used.
3. Withdraw 26 ml of Pyzchiva from each vial needed and add 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 72 hours of dilution in the infusion bag. If necessary, the diluted infusion solution can be stored between 2 °C and 8 °C for a maximum of 1 month and at room temperature up to 30 °C for 72 hours after removal from refrigeration, including the infusion period.
6. Use only an infusion system with an in-line filter, sterile, non-pyrogenic, low protein-binding (0.2 micrometer pore size).
7. Each vial is for single use and unused medicine should be discarded in accordance with local regulations.

Storage

The diluted infusion solution can be stored at room temperature up to 30 °C for a maximum of 72 hours, including the infusion period. If necessary, the diluted infusion solution can be stored between 2 °C and 8 °C for a maximum of 1 month and at room temperature up to 30 °C for 72 hours after removal from refrigeration, including the infusion period. Do not freeze.