Pyzchiva 130 mg concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Pyzchiva 130 mg concentrate for solution for infusion

ustekinumab

This medicinal product is subject to additional monitoring, which will allow for faster detection of new safety information. You can help by reporting any adverse reactions you may experience. Information on how to report adverse reactions is included at the end of section 4.

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 the person using the medicine.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• If you experience any adverse reactions, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Contents of this leaflet

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

1. What Pyzchiva is and what it is used for

What Pyzchiva is

Pyzchiva contains the active substance “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 medicines called “immunosuppressants”. These medicines work by weakening part of the immune system.

What Pyzchiva is used for

Pyzchiva is used to treat the following inflammatory diseases:

• Moderately to severely active Crohn’s disease – in adults and children weighing at least 40 kg.

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, Pyzchiva may be given to reduce the signs and symptoms of your disease.

2. What you need to know before using Pyzchiva

Do not use Pyzchiva

• If you are allergic to ustekinumab or any of the other ingredients of this medicine (listed in section 6).
• If you have an active infection that your doctor considers significant.

If you are unsure whether any of the above apply to you, speak with your doctor or pharmacist before using Pyzchiva.

Warnings and precautions

Talk to your doctor or pharmacist before starting to use Pyzchiva. Your doctor will assess your overall health before treatment. Make sure to inform your doctor about any medical conditions you have before treatment. Also, inform your doctor if you have recently been in close contact with someone who may have tuberculosis. Your doctor will examine you and perform a test to detect tuberculosis before you start using Pyzchiva. If your doctor believes you are at risk for tuberculosis, you may be given medication to treat it.

Watch for serious adverse reactions

Pyzchiva may cause serious adverse reactions, including allergic reactions and infections. You should be alert for certain signs of illness while using Pyzchiva. See the complete list of these adverse reactions in the section “Serious adverse reactions” in section 4.

Before using Pyzchiva, 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 – because immunosuppressants like ustekinumab weaken part of the immune system, which may increase the risk of developing cancer.
• If you have been treated for psoriasis with other biologics (a medicine produced from a biological source and usually administered by injection) – the risk of developing cancer may be higher.
• If you currently have or have recently had an infection or have any skin openings (fistula).
• If you have any new skin lesions or changes in existing lesions within the psoriasis area or on intact skin.
• If you are taking any other treatments for psoriasis and/or psoriatic arthritis – such as other immunosuppressants or phototherapy (when your body is treated with a type of ultraviolet (UV) light). These treatments may also weaken part of the immune system. The use of these treatments together with ustekinumab has not been studied, but it may increase the likelihood of developing illnesses related to a weaker immune system.
• If you are receiving or have ever received allergy shots (immunotherapy) – it is unknown whether ustekinumab may affect these treatments.
• If you are 65 years of age or older – you may be more likely to develop infections.

If you are unsure whether any of these conditions apply to you, speak with 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. Contact your doctor immediately if you develop a red, raised, scaly rash, sometimes with a darker border, on areas of skin exposed to sunlight, or if accompanied by joint pain.

Heart attacks and strokes

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

Children and adolescents

The use of ustekinumab is not recommended in children weighing less than 40 kg with Crohn’s disease, as it has not been studied in this age group.

Use of Pyzchiva with other medicines and vaccines

Inform your doctor or pharmacist:

• If you are currently using, have recently used, or might use any other medicines.
• If you have recently been vaccinated or are scheduled 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 infant’s doctor about your treatment with Pyzchiva before the infant receives any vaccine, including live vaccines such as the BCG vaccine (used to prevent tuberculosis). Live vaccines are not recommended for your infant within the first six months after birth if you received Pyzchiva during pregnancy, unless otherwise recommended by your infant’s doctor.

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 observed in babies exposed to ustekinumab in the womb. However, experience with ustekinumab in pregnant women is limited. Therefore, it is preferable to avoid using ustekinumab during pregnancy.
• If you are a woman of childbearing potential, you are advised to avoid becoming pregnant and to use adequate contraception while using ustekinumab and for at least 15 weeks after the last dose.
• Ustekinumab can cross the placenta to the fetus. If you received Pyzchiva during pregnancy, your infant may have an increased risk of developing infections.
• It is important to inform your infant’s doctors and other healthcare professionals if you received Pyzchiva during pregnancy before the infant receives any vaccine. Live vaccines, such as the BCG vaccine (used to prevent tuberculosis), are not recommended for your infant within the first twelve months after birth if you received Pyzchiva during pregnancy, unless otherwise recommended by your infant’s doctor.
• Ustekinumab may be excreted in breast milk in very small amounts. Inform your doctor if you are breastfeeding or plan to breastfeed. You and your doctor will decide whether to breastfeed or use ustekinumab. Do not do both simultaneously.

Driving and using machines

The effect of ustekinumab on the ability to drive and use machines is negligible or none.

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, it is mixed with a solution containing sodium. Consult 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) per vial (30 ml), equivalent to 10.4 mg/26 ml. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergies.

3. How to use Pyzchiva

Pyzchiva should be used under the guidance and supervision of a physician experienced in the diagnosis and treatment of Crohn's disease.

Your doctor will administer Pyzchiva 130 mg concentrate for solution for infusion as a drip into a vein in your arm (intravenous infusion) for at least one hour. Ask your doctor when your injections should be given and about follow-up appointments.

How much Pyzchiva is given

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

Adults from 18 years of age

• 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 as an injection under the skin (subcutaneous injection) 8 weeks later, and subsequently every 12 weeks.

Children with Crohn's disease weighing at least 40 kg

• 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 as an injection under the skin (subcutaneous injection) 8 weeks later, and subsequently every 12 weeks.

How Pyzchiva is administered

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

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

If you forget to use Pyzchiva

If you miss a dose or fail to attend your appointment for administration, speak with your doctor to schedule another appointment.

If you stop treatment with Pyzchiva

Stopping ustekinumab is not dangerous. However, if you discontinue treatment, your symptoms may return.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Serious adverse effects

Some patients may experience serious adverse 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 (may affect up to 1 in 1,000 people). Signs include:

• difficulty breathing and swallowing,

• low blood pressure, which may cause dizziness or mild headaches,

• swelling of the face, lips, mouth or throat.

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

Infusion-related reactions – If you are being treated for Crohn's disease, the first dose of ustekinumab is administered via intravenous infusion. Some patients have experienced severe allergic reactions during infusion.

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

• Nasal 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 tissues beneath the skin ("cellulitis") is uncommon (may affect up to 1 in 100 people).
• Herpes (a type of painful blistering rash) is uncommon (may affect up to 1 in 100 people).

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

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

• fever, flu-like symptoms, night sweats, weight loss,
• feeling tired or short of breath; persistent cough,
• skin that feels warm, red and painful, or a painful skin rash with blisters,
• burning sensation when urinating,
• diarrhoea,
• visual deterioration or loss of vision,
• headache, neck stiffness, photosensitivity, nausea or confusion.

Contact your doctor immediately if you notice any of these signs of infection, as they may indicate infections such as chest infections, skin infections, herpes or opportunistic infections, which could lead to serious complications. You should also inform your doctor if you have any infection that does not go away or keeps recurring. Your doctor may decide that you should not use ustekinumab until the infection resolves. Also contact your doctor if you have any open cuts or ulcers that could become infected.

Skin peeling – increased redness and peeling 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 must inform your doctor immediately.

Other adverse effects

Frequent adverse effects (may affect up to 1 in 10 people):

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

Uncommon adverse 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 facial muscle weakness 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 blisters, sometimes accompanied by fever (pustular psoriasis)
• Skin peeling (skin exfoliation)
• Acne

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

• Redness and peeling of the skin over a large area of the body, which may cause itching or pain (exfoliative dermatitis). Similar symptoms may develop as a natural change in psoriasis symptoms (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 adverse effects (may affect up to 1 in 10,000 people):

• Blisters on the skin, which may be red and cause itching and pain (bullous pemphigoid).
• Cutaneous lupus or lupus-like syndrome (a red, raised, scaly rash on areas of skin exposed to sunlight, possibly accompanied by joint pain).

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system detailed in Appendix V. By reporting adverse 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 centre and patients do not need to store or handle it.
• Keep this medicine out of the sight and reach of children.
• Store in a refrigerator (2 °C to 8 °C). Do not freeze.
• Keep the vial in the outer packaging to protect it from light.
• If necessary, individual vials of Pyzchiva may also be stored at room temperature up to 30 °C for a single period of up to 35 days in their original carton to protect them from light. Write the date when the vial is first removed from the refrigerator in the designated space on the outer packaging. At any time before the end of this period, the vial may be returned to the refrigerator once and stored there until the original expiry date. Discard the vial if not used within the maximum 35-day period at room temperature or after the original expiry date, whichever occurs first.
• Do not shake Pyzchiva vials. Prolonged vigorous shaking may damage the product.

Do not use this medicine:

• After the expiry date stated on the label and packaging after “CAD/EXP”. The expiry date refers to the last day of the month indicated.
• If the liquid changes colour, becomes cloudy, or contains floating particles (see section 6, “Appearance of Pyzchiva and contents of the container”).
• If you know or suspect it has been exposed to extreme temperatures (such as accidental overheating or freezing).
• If the product has been vigorously shaken.
• If the seal is broken.

Pyzchiva is for single use only. Any unused diluted solution for infusion remaining in the vial or syringe must be discarded according to local regulations.

6. Pack contents and other information

Composition of Pyzchiva

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

Appearance of Pyzchiva and contents of the pack

Pyzchiva is a concentrate for infusion solution, a clear, colourless to pale yellow liquid. It is supplied in a pack containing one single-use 30 ml glass vial. Each vial contains 130 mg of ustekinumab in 26 ml of concentrate for infusion solution.

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Samsung Bioepis NL. B.V.

Olof Palmestraat 10

2616 LR Delft

The Netherlands

Further information on this medicinal product is available from the local representative of the Marketing Authorization Holder:

Date of the most recent review of this leaflet: MM/YYYY

Other sources of information

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

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 medicinal product should be clearly documented.

Dilution instructions:

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

1. Calculate the dose and number of Pyzchiva vials required based on the patient's body weight (see section 3, Table 1, Table 2). 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 equal to the volume of Pyzchiva to be added (discard 26 ml of sodium chloride per vial of Pyzchiva required: 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 for injection, USP, may be used.
3. Withdraw 26 ml of Pyzchiva from each required vial and add it to the 250 ml infusion bag. The final volume of the infusion bag must be 250 ml. Mix gently.
4. Visually inspect the diluted solution prior to infusion. Do not use if particulate matter, discoloration, or foreign particles are observed.
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 may be stored between 2 °C and 8 °C for up to 1 month and at room temperature up to 30 °C for an additional 72 hours after removal from refrigeration, including the infusion period.
6. Use only an infusion system with an in-line, sterile, pyrogen-free, low protein-binding filter (pore size 0.2 micrometres).
7. Each vial is for single use only, and any unused medicinal product should be discarded in accordance with local regulations.

Storage

If necessary, individual vials of Pyzchiva may also be stored at room temperature up to 30 °C for a single period of up to 35 days in their original carton to protect from light. Write the date when the vial is first removed from the refrigerator in the designated space on the outer packaging. At any time before the end of this period, the vial may be returned to the refrigerator once and stored there until the original expiry date. Discard the vial if not used within the maximum 35-day period at room temperature or after the original expiry date, whichever occurs first.

The diluted infusion solution may 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 may be stored between 2 °C and 8 °C for up to 1 month and at room temperature up to 30 °C for an additional 72 hours after removal from refrigeration, including the infusion period. Do not freeze.