Prospect: information for the patient

Pyzchiva45mg injectable solution in pre-filled syringe

ustekinumab

This medicine is subject to additional monitoring, which will speed up the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report these adverse effects.

Read this prospect carefully before starting to use this medicine, because it contains important information for you.

This prospect has been written for the person using the medicine. If you are the parent or caregiver of a child to whom you will administer Pyzchiva, please read this information carefully.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed only to you, and you must not give it to other people even if they present the same symptoms as you, as it may harm them.
• If you experience adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this prospect. See section4.

1. What Pyzchiva is and for what it is used

2. What you need to know before starting to use Pyzchiva

3. How to use Pyzchiva

4. Possible adverse effects

5. Storage of Pyzchiva

6. Contents of the package and additional information

What is Pyzchiva

Pyzchiva contains the active ingredient “ustekinumab”, a monoclonal antibody. Monoclonal antibodies are proteins that specifically identify and bind to certain proteins in the body.

Pyzchiva belongs to a group of medications called “immunosuppressants”. These medications act by weakening part of the immune system.

What is Pyzchiva used for

Pyzchiva is used to treat the following inflammatory diseases:

• Plaque psoriasis - in adults and children 6 years of age and older
• Psoriatic arthritis - in adults
• Moderate to severe Crohn's disease - in adults

Plaque psoriasis

Plaque psoriasis is a skin disease that causes inflammation affecting the skin and nails. Pyzchiva reduces inflammation and other symptoms of the disease.

Pyzchiva is used in adults with plaque psoriasis of moderate to severe severity who cannot use ciclosporin, methotrexate, or phototherapy, or where these treatments are not effective.

Pyzchiva is used in children and adolescents 6 years of age and older with plaque psoriasis of moderate to severe severity who are unable to tolerate phototherapy or other systemic therapies, or where these treatments are not effective.

Psoriatic arthritis

Psiatic arthritis is an inflammatory joint disease, which is usually accompanied by psoriasis. If you have active psoriatic arthritis, you will first receive other medications. If you do not respond well to these medications, you may be treated with Pyzchiva to:

• Reduce the signs and symptoms of your disease.
• Improve your physical function.
• Reduce damage to your joints.

Crohn's disease

Crohn's disease is an inflammatory bowel disease. If you have Crohn's disease, you will first be given other medications. If you do not respond adequately or cannot tolerate these medications, you may be given Pyzchiva to reduce the signs and symptoms of your disease.

No use Pyzchiva

• If you are allergic to ustekinumabor to any of the other components of this medication (listed in section6).
• If you have an active infectionthat your doctor thinks is important.

If you are not sure ifanyof the above points concern you, talk to your doctor or pharmacist before using Pyzchiva.

Warnings and precautions

Consult your doctor or pharmacist before starting to use Pyzchiva. Your doctor will check how you arebefore each treatment. Make sure to inform your doctor about any illness you suffer from before each treatment. Your doctor will also ask if you have recently been near someone who may have tuberculosis. Your doctor will examine you and perform a test for tuberculosis detection before using Pyzchiva. If your doctor thinks you are at risk of tuberculosis, they may give you medication to treat it.

Observe severe side effects

Pyzchiva may cause severe side effects, including allergic reactions and infections. You must pay attention to certain signs of illness while using Pyzchiva. See the complete list of these side effects in “Severe side effects” of section4.

Tell your doctor:

• If you have ever had an allergic reaction to ustekinumab.Consult your doctor if you are unsure.
• If you have ever had any type of cancer– this is becauseimmunosuppressants like ustekinumab weaken part of the immune system. This may increase the risk of cancer.
• If you have received treatment for psoriasis with other biologics (a medication produced from a biological source and usually administered by injection)–the risk of cancer may be higher.
• If you have or have had a recent infection.
• If you have any new lesions or changes to existing lesionswithin the psoriasis area 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 (UV) light). These treatments may also weaken part of the immune system. Although it has not been studied, it is possible that using these treatments together with ustekinumab may increase the likelihood of developing immune-related diseases.
• If you are receiving or have ever received injections to treat allergies– it is unknown if ustekinumab may affect these treatments.
• If you are 65years or older– you are more likely to acquire infections.

If you are unsure about not having any of these conditions, talk to your doctor or pharmacist before using Pyzchiva.

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

Heart attacks and strokes

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

Children and adolescents

Ustekinumab is not recommended for use in children under 6years of age with psoriasis or in children under 18years of age with psoriatic arthritis or Crohn's disease, as it has not been studied in this age group.

Using Pyzchiva with other medications, vaccines

Inform your doctor or pharmacist:

• If you are using, have used recently, or may use other medications.
• If you have been vaccinated recently or are to receive a vaccine. Certain types of vaccines (live vaccines) should not be administered while 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 using Pyzchiva during pregnancy.Ustekinumab's effects on pregnant women are unknown. If you are a fertile woman, it is recommended that you avoid becoming pregnant and use suitable contraceptive measures while using ustekinumab and for at least 15weeks after the last treatment with ustekinumab.
• Inform your doctor if you are pregnant, think you may be pregnant, or intend to become pregnant.
• Pyzchiva may pass through the placenta to the fetus. If you received Pyzchiva during pregnancy, your baby may be at a higher risk of contracting an infection.
• It is essential to inform your baby's doctors and other healthcare professionals if you received Pyzchiva during 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.Inform your doctor if you are breastfeeding or plan to do so. You and your doctor will decide whether to breastfeed or use ustekinumab. Do not do both at the same time.

Driving and operating machinery

The influence of ustekinumab on the ability to drive and operate machinery is negligible or insignificant.

Pyzchiva contains polisorbate 80 (E433)

This medication contains 0.02 mg of polisorbate 80 (E433) in each pre-filled syringe (1 ml) equivalent to 0.02 mg/0.5 ml. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergies.

Pyzchiva should be used under the guidance and supervision of a doctor with experience in treating the conditions for which Pyzchiva is indicated.

Always follow exactly the administration instructions for this medication as indicated by your doctor. If in doubt, ask your doctor. Ask your doctor when to administer the injections and about follow-up consultations.

What amount of Pyzchiva is administered

Your doctor will decide the amount of Pyzchiva you need to use and the duration of treatment.

Adults 18 years of age and older

Psoriasis or psoriatic arthritis

• The recommended starting dose is 45 mg of Pyzchiva. Patients weighing more than 100 kg may start with a dose of 90 mg instead of 45 mg.
• After the initial dose, you will take the next dose 4 weeks later and then every 12 weeks. The subsequent doses are usually the same as the starting dose.

Crohn's disease

• During treatment, your doctor will administer the first dose of approximately 6 mg/kg of Pyzchiva through a vein in your arm (intravenous infusion). After the initial dose, you will receive the next dose of 90 mg of Pyzchiva 8 weeks later and then every 12 weeks through a subcutaneous injection.
• In some patients, after the first subcutaneous injection, 90 mg of Pyzchiva will be administered every 8 weeks. Your doctor will decide when you should receive the next dose.

Children and adolescents 6 years of age and older

Psoriasis

• Pyzchiva is not indicated for pediatric patients with plaque psoriasis weighing less than 60 kg, as Pyzchiva is only available in pre-filled syringes of 45 mg and 90 mg for subcutaneous injection. Therefore, it is not possible to administer Pyzchiva to patients who require less than a full dose of 45 mg. If another dose is required, another format of ustekinumab 45 mg injectable solution in vials should be used that allows for weight-based administration.
• Your doctor will indicate the correct dose for you, including the amount (volume) of Pyzchiva to inject to give the correct dose. The appropriate dose for you will depend on your body weight at the time each dose is given.
• If you weigh between 60 kg and 100 kg, the recommended dose is 45 mg of Pyzchiva.
• If you weigh more than 100 kg, the recommended dose is 90 mg of Pyzchiva.
• After the initial dose, you will receive the next dose 4 weeks later, and then every 12 weeks.

How Pyzchiva is administered

• Pyzchiva is administered through a subcutaneous injection. Initially, medical or nursing staff may administer Pyzchiva to you.

• However, you and your doctor may decide that you should inject Pyzchiva yourself. In that case, you will be trained on how to inject Pyzchiva yourself.

• For instructions on how to administer Pyzchiva, see "Administration Instructions" at the end of this leaflet.

Consult your doctor if you have any questions about self-injecting.

If you use more Pyzchiva than you should

If you have used or have been given too much Pyzchiva, speak immediately with your doctor or pharmacist. Always carry the medication box with you, even if it is empty.

If you forget to use Pyzchiva

If you forget a dose, speak with your doctor or pharmacist. Do not take a double dose to make up for the missed doses.

If you interrupt treatment with Pyzchiva

Stopping ustekinumab is not hazardous. However, if you stop, your symptoms may return.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Severe side effects

Some patients may experience severe side effects that may require urgent treatment.

Allergic reactions– these may require urgent treatment. Contact your doctor or seek immediate medical help if you notice any of the following signs.

• Severe allergic reactions (“anaphylaxis”) are rare in the population using ustekinumab (they can affect up to 1 in 10,000 people). The 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 urticaria (these can affect up to 1 in 100 people).

In rare cases, pulmonary allergic reactions and lung inflammation have been reported in patients treated with ustekinumab. Inform your doctor immediately if you have symptoms such as coughing, 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 require urgent treatment. Contact your doctor immediately if you notice any of these signs.

• Common colds and sore throats are frequent (they can affect up to 1 in 10 people).
• Chest infections are rare (they can affect up to 1 in 100 people).
• Cellulitis, an inflammation of the tissues under the skin, is rare (it can affect up to 1 in 100 people).
• Herpes, a painful rash with blisters, is rare (it can affect up to 1 in 100 people).

Ustekinumab may affect your ability to fight infections. Some of them may be severe and caused by viruses, fungi, bacteria (including tuberculosis) or parasites, and include opportunistic infections that occur mainly in people with weakened immune systems (opportunistic infections).Cases of opportunistic infections of the brain (encephalitis, meningitis), lungs, and eyes have been reported in patients receiving ustekinumab treatment.

You should monitor signs of infection while using ustekinumab. These include:

• Fever, flu-like symptoms, night sweats, weight loss,
• Feeling tired or difficulty breathing; persistent cough,
• Having hot, red, and painful skin or having a painful skin rash with blisters,
• Urinary burning,
• Diarrhea,

• Visual deterioration or loss of vision,
• Headache, neck stiffness, photosensitivity, nausea, or confusion.

Notify your doctor immediately if you notice any of these signs of infection, as they may be signs of infections such as pneumonia, skin infections, herpes, or opportunistic infections that could have serious complications. You should also inform your doctor if you have any type of infection that does not disappear or reappear. Your doctor may decide that you should not use ustekinumab until the infection has cleared up. You should also contact your doctor if you have any open wounds or ulcers that may become infected.

Skin peeling – increased redness and skin peeling on a large area of the body may be symptoms of psoriasis erythroderma or dermatitis exfoliativa, which are severe skin disorders. If you notice any of these symptoms, you should inform your doctor immediately.

Other side effects

Frequent side effects(they can affect up to 1 in 10 people):

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

Rare side effects(they can affect up to 1 in 100 people):

• Dental infections
• Vaginal yeast infections
• Depression
• Stuffy or congested nose
• Bleeding, petechiae, hardening, swelling, and itching at the injection site
• Feeling weak
• Drooping eyelid and facial muscle weakness (“facial paralysis” or “Bell's palsy”), which is usually temporary
• A change in psoriasis with redness and new small skin blisters, sometimes accompanied by fever (psoriasis pustular)
• Skin peeling (exfoliation of the skin)
• Acne

Rare side effects(they can affect up to 1 in 10,000 people):

• Redness and skin peeling on a large area of the body, which can cause itching or pain (dermatitis exfoliativa). Similar symptoms may develop as a natural change in psoriasis symptoms (psoriasis erythroderma)
• 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(they can affect up to 1 in 10,000 people)

• Blisters on the skin, which can be red andcause itching and pain(pemphigoid bullous).
• Cutaneous lupus or lupus-like syndrome (red, elevated, and scaly skin rash in sun-exposed areas, possibly accompanied by joint pain).

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet.You can also report them directly through the national notification system included in theAppendixV. By reporting side effects, you can contribute to providing more information about the safety of this medicine.

• Maintain this medication out of the sight and reach of children.
• Store in the refrigerator (2°C and 8°C). Do not freeze.
• Store the pre-filled syringe in the outer packaging to protect it from light.
• If necessary, individual pre-filled Pyzchiva syringes can also be stored at room temperature up to 30°C for a maximum period of up to 1 month in their original packaging to protect them from light. Write the date when the pre-filled syringe is first removed from the refrigerator in the designated space on the outer packaging. At the end of this period, it can be stored in the refrigerator again. Discard the syringe if it is not used within a period of 1 month of storage at room temperature or beyond the original expiration date, whichever occurs first.
• Do not shake the pre-filled Pyzchiva syringes. Prolonged vigorous shaking may damage the product.

Do not use this medication:

• After the expiration date appearing on the label and packaging after “CAD/EXP”. The expiration date is the last day of the month indicated.
• If the liquid changes color, becomes cloudy, or presents unusual particles floating in it (see section 6 “Appearance of Pyzchiva and contents of the packaging”).
• If you know or suspect you have been exposed to extreme temperatures (such as accidental overheating or freezing).
• If the product has been shaken vigorously.

Pyzchiva is for single use only. Dispose of the unused product remaining in the syringe. Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of empty packaging and unused medications. This will help protect the environment.

Composition of Pyzchiva

• The active ingredient is ustekinumab. Each pre-filled syringe contains45mg of ustekinumab in 0.5ml.
• The other components are histidine, histidine hydrochloride monohydrate, polisorbate 80 (E433), sucrose, water for injection.

Appearance of Pyzchiva and contents of the package

Pyzchiva is a transparent, colourless to light yellow solution. The solution may contain a few translucent or white protein particles. It is presented in a package containing 1pre-filled syringe of1ml of glass single-dose vial. Each pre-filled syringe contains 45mg of ustekinumab in 0.5ml of injectable solution.

Marketing Authorization Holder andResponsible for Manufacturing

Samsung Bioepis NL. B.V.

Olof Palmestraat 10

2616 LR Delft

Netherlands

For more information about this medicine, please contact the local representative of the marketing authorization holder:

Traceability

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

Last update of this leaflet: MM/YYYY

Other sources of information

More detailed information about this medicine is available on the website of the European Medicines Agency:https://www.ema.europa.eu/.

Administration instructions

At the beginning of treatment, the healthcare professional will help you with your first injection. However, it is possible that you and your doctor may decide that you can administer Pyzchiva yourself. In that case, they will teach you how to administer Pyzchiva. Talk to your doctor if you have any doubts about administering the injections.

• Do not mix Pyzchiva with other injectable liquids.
• Do not shake the pre-filled syringes of Pyzchiva. The medicine may deteriorate if it is shaken vigorously. Do not use the medicine if it has been shaken vigorously.

The Figure1 shows how the pre-filled syringe looks.

Figure1

1. Check the number of pre-filled syringes and prepare the materials:

Preparing to use the pre-filled syringe

• Take the pre-filled syringe(s) out of the refrigerator. Leave the pre-filled syringe out of the box for 30minutes. This will allow the liquid to reach a comfortable temperature for administration (room temperature). Do not heat the pre-filled syringe in any other way (e.g. do not heat it in the microwave or in hot water). Do not remove the needle cap while waiting for the temperature to reach room temperature.
• Hold the pre-filled syringe by the body with the needle cap on pointing upwards.
• Do not hold the pre-filled syringe by the plunger, the plunger, the wings of the needle shield or the needle cap.
• Do not remove the plunger at any time.
• Do not remove the needle cap from the pre-filled syringe until instructed to do so.

Check the pre-filled syringe(s) to ensure that

• The number of pre-filled syringes and the concentration are correct
• • If your dose is 45mg, you will have a pre-filled syringe of 45mg of Pyzchiva.
  • If your dose is 90mg, you will have two pre-filled syringes of 45mg of Pyzchiva and you will need to administer two injections. Choose two different places for these injections (e.g. one in the right thigh and one in the left thigh), and inject one after the other.
• It is the correct medicine.
• The expiration date has not expired.
• The pre-filled syringe is not damaged.
• The solution in the pre-filled syringe is transparent and colourless to light yellow.
• The solution in the pre-filled syringe does not have an abnormal colour, is turbid or contains foreign particles.
• The solution in the pre-filled syringe is not frozen.

Prepare all the materials you need and place them on a clean surface. Including antiseptic wipes, cotton or gauze and a container for sharp objects.

2. Choose and prepare the injection site:

Choose the injection site (see Figure2).

• Pyzchiva is administered by subcutaneous injection.
• Some suitable places for injection are the upper thigh or the abdominal area (the abdomen) at least 5cm from the navel.
• As far as possible, do not use skin areas that show signs of psoriasis.
• If someone else is administering the injection, they can also choose the upper arm as the injection site.

*In grey, the recommended injection sites are indicated.

Figure2

Prepare the injection site

• Wash your hands very well with soap and warm water.
• Clean the skin at the injection site with an antiseptic wipe.
• Do nottouch this area again before putting the injection.
• Do notfan or blow on the clean area

3. Remove the needle cap (see Figure3):

• The needle capmust notbe removed until you are ready to inject.
• Hold the pre-filled syringe, and hold the body of the pre-filled syringe with one hand.
• Remove the needle cap and dispose of it. Do not touch the plunger while doing this.

Figure3

• You may observe a bubble of air in the pre-filled syringe or a drop of liquid at the end of the needle. Both are normal and do not need to be removed.
• Do not touch the needle or allow it to touch any surface.
• Do not use the pre-filled syringe if it has fallen without the needle cap. If this happens, tell your doctor or pharmacist.
• Inject the dose immediately after removing the needle cap.

4. Inject the dose:

• Hold the pre-filled syringe with one hand between your index and middle fingers, place your thumb on the plunger, and with the other hand carefully pinch a disinfected piece of skin with your thumb and index finger. Do not squeeze.
• Do not remove the plunger at any time.
• With a single quick movement, insert the needle through the skin until it can go no further (see Figure4).

Figure4

• Inject all the medicine by pushing the plunger until the head of the plunger is completely between the wings of the needle shield (see Figure5).

Figure5

• When you have pushed the plunger as far as it will go, keep the pressure on the plunger, remove the needle, and release the skin (see Figure6).

Figure6

• Slowly remove your thumb from the plunger to allow the empty syringe to advance until the needle is completely covered by the needle shield, as shown in Figure7:

Figure7

5. After the injection:

• Press the injection site with an antiseptic wipe for a few seconds after the injection.
• You may see a small amount of blood or liquid at the injection site. This is normal.
• You can press a cotton ball or gauze on the injection site and hold it for 10seconds.
• Do not rub the skin at the injection site. You can cover the injection site with a bandage, if necessary.

6. Disposal:

• The used syringes must be deposited in a puncture-resistant container, similar to a container for sharp objects (see Figure8). For your safety and health and for the safety of others, never reuse the syringe. Dispose of your sharp object container according to local regulations.
• Antiseptic wipes and other materials can be disposed of in the trash.

Figure8