UZPRUVO 130 MG CONCENTRATE FOR INFUSION SOLUTION

2. What you need to know before you use Uzpruvo

Do not use Uzpruvo

• 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 Uzpruvo.

Warnings and precautions

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

Watch for serious side effects

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

Before using Uzpruvo, tell your doctor

• If you have ever had an allergic reaction to Uzpruvo.Check with your doctor if you are not sure.
• If you have ever had any type of cancer– this is because immunosuppressants like Uzpruvo 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 getting cancer may be higher.
• If you have had a recent infectionor 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 Uzpruvo. 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 Uzpruvo 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 Uzpruvo.

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 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

Uzpruvo 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 Uzpruvo 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 vaccination.Certain types of vaccines (live vaccines) should not be given while you are using Uzpruvo.
• If you received Uzpruvo during pregnancy, inform your baby's doctor about your treatment with Uzpruvo before your baby receives any vaccination, 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 Uzpruvo 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 ustekinumab in the womb.However, there is limited experience with ustekinumab in pregnant women. Therefore, it is preferable to avoid the use of Uzpruvo during pregnancy.
• If you are a woman of childbearing age, you are advised to avoid becoming pregnant and to use adequate contraception while using Uzpruvo and for at least 15 weeks after the last treatment with Uzpruvo.
• Uzpruvo may pass through the placenta to the fetus.If you received Uzpruvo 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 Uzpruvo during your pregnancy before your baby receives any vaccination.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 Uzpruvo 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 Uzpruvo. Do not do both.

Driving and using machines

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

Uzpruvo contains sodium and polysorbate 80

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

This medicine contains 0.4 mg of polysorbate 80 in each ml. Polysorbates may cause allergic reactions. Tell your doctor if you have any known allergy.

3. How to use Uzpruvo

Uzpruvo 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 Uzpruvo 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 Uzpruvo is given

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

Adults from 18 years of age

• 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 Uzpruvo by injection under the skin (subcutaneous injection) 8 weeks later and then every 12 weeks.

How Uzpruvo is given

• The first dose of Uzpruvo 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 Uzpruvo.

If you miss a dose of Uzpruvo

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 Uzpruvo

Stopping Uzpruvo 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 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 being treated for Crohn's disease, the first dose of Uzpruvo is given by drip into a vein (intravenous infusion). Some patients have had serious 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 serious allergic reaction, your doctor may decide that you should not use Uzpruvo 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).

Uzpruvo 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 Uzpruvo. These include:

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

Tell your doctor immediately if you notice any of these signs of infection, as they can be signs of infections such as chest infections, skin infections, herpes, or opportunistic infections that can 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 Uzpruvo until the infection goes away. Also, talk to your doctor if you have any open cuts or sores that could become infected.

Shedding of the skin – increased redness and shedding of the skin over a large area of the body can 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, pus-filled bumps on the skin, sometimes accompanied by fever (pustular psoriasis)
• Scaling 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 can be itchy or painful (exfoliative dermatitis). Similar symptoms can develop, such as a natural change in the symptoms of psoriasis (erythrodermic psoriasis)
• Inflammation of small blood vessels, which can 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 can 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 it is possible that 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 Uzpruvo

• Uzpruvo 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.
• If necessary, the unopened vial can also be stored at room temperature up to 30 °C for a maximum single period of up to 7 days in its original carton to protect it from light. Once the vial has been stored at room temperature (up to a maximum of 30 °C), it must not be stored in the refrigerator again. Discard the vial if it is not used within 7 days of storage at room temperature or from the original expiry date, whichever occurs first.
• Do not shake Uzpruvo vials. Prolonged vigorous shaking can damage the product.

Do not use this medicine

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

Uzpruvo 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 Uzpruvo

• The active substance is ustekinumab. Each vial contains 130 mg of ustekinumab in 26 ml.
• The other ingredients are disodium dihydrate EDTA, histidine, histidine hydrochloride monohydrate, methionine, polysorbate 80 (E433), sucrose, and water for injections.

Appearance of Uzpruvo and package contents

Uzpruvo is a clear, colorless to pale yellow, practically particle-free solution for infusion concentrate (sterile concentrate). 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 solution for infusion concentrate (sterile concentrate).

Marketing Authorisation Holder

STADA Arzneimittel AG

Stadastrasse 2–18

61118 Bad Vilbel

Germany

Manufacturers

Alvotech Hf

Sæmundargata 15-19

Reykjavik, 102

Iceland

STADA Arzneimittel AG

Stadastrasse 2–18

61118 Bad Vilbel

Germany

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

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

The following information is intended for healthcare professionals only:

Traceability:

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

Dilution instructions:

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

1. Calculate the dose and the number of Uzpruvo vials needed based on the patient's weight (see section 3, Table 1). Each 26 ml vial of Uzpruvo contains 130 mg of ustekinumab.
2. Withdraw and then discard a volume of the 9 mg/ml (0.9%) sodium chloride solution from the 250 ml infusion bag equivalent to the volume of Uzpruvo to be added (discard 26 ml of sodium chloride for each vial of Uzpruvo needed: for 2 vials, discard 52 ml; for 3 vials, discard 78 ml; for 4 vials, discard 104 ml).
3. Withdraw 26 ml of Uzpruvo 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, with 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 infusion must be completed within 8 hours of dilution in the infusion bag. Do not freeze.