Usymro 130 mg concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Usymro 130 mg concentrate for solution for infusion

ustekinumab

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

Read the entire leaflet carefully before you start using this medicine, as it contains important information for you.

This leaflet has been written for the person taking 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.

Leaflet contents

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

1. What Usymro is and what it is used for

What Usymro is

Usymro contains the active substance "ustekinumab", a monoclonal antibody. Monoclonal antibodies are proteins that specifically recognize and bind to certain proteins in the body.

Usymro belongs to a group of medicines called "immunosuppressants". These medicines work by weakening part of the immune system.

What Usymro is used for

Usymro 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 medicines. If you do not respond adequately or cannot tolerate those medicines, Usymro may be given to reduce the signs and symptoms of your disease.

2. What you need to know before using Usymro

Do not use Usymro

• If you are allergic to ustekinumab or to 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 Usymro.

Warnings and precautions

Talk to your doctor or pharmacist before starting to use Usymro. Your doctor will assess your condition before treatment begins. Make sure to inform your doctor about any medical conditions you currently have before starting 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 for tuberculosis before you start using Usymro. If your doctor believes you are at risk of developing tuberculosis, they may prescribe medication to treat it.

Be aware of serious adverse effects

Usymro may cause serious adverse effects, including allergic reactions and infections. You should be alert for certain signs of illness while taking Usymro. See “Serious adverse effects” in section 4 for a complete list of these side effects.

Before using Usymro, tell your doctor:

• If you have ever had an allergic reaction to Usymro. Consult your doctor if you are unsure.
• If you have ever had any type of cancer – this is because immunosuppressants like Usymro weaken part of the immune system, which may increase the risk of cancer.
• If you have been treated for psoriasis with other biological medicines (a medicine derived from a biological source and usually administered by injection) – the risk of cancer may be higher.
• If you have or have recently had an infection, or if you have any abnormal skin openings (fistulas).
• If you have any new or changing lesions within areas of psoriasis or on normal skin.
• If you are taking any other treatments for psoriasis and/or psoriatic arthritis – such as another 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. The use of these treatments together with Usymro has not been studied. However, combining them may increase the likelihood of illnesses related to a weaker immune system.
• If you are receiving or have ever received allergy shots (immunotherapy) – it is unknown whether Usymro may affect these.
• If you are 65 years of age or older – you may be more likely to develop infections.

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

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 you experience joint pain.

Heart attack and stroke

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 drooping, or speech or vision problems.

Children and adolescents

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

Other medicines, vaccines, and Usymro

Inform your doctor or pharmacist:

• If you are taking, have recently taken, or might need to take any other medicines.
• If you have recently been vaccinated or are planning to be vaccinated. Certain types of vaccines (live vaccines) must not be given while you are using Usymro.
• If you received Usymro during pregnancy, inform your infant’s doctor about your treatment with Usymro before your infant receives any vaccines, including live vaccines such as the BCG vaccine (used to prevent tuberculosis). Live vaccines are not recommended for your infant during the first twelve months after birth if you received Usymro during pregnancy, unless your infant’s doctor advises 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 congenital malformations 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 Usymro during pregnancy.
• Women of childbearing potential are advised to avoid becoming pregnant and to use adequate contraception while using Usymro and for at least 15 weeks after the last dose of Usymro.
• Usymro can cross the placenta and reach the fetus. If you received Usymro during pregnancy, your infant may have an increased risk of infection.
• It is important to inform your infant’s doctors and other healthcare professionals if you received Usymro during pregnancy before your infant receives any vaccines. Live vaccines, such as the BCG vaccine (used to prevent tuberculosis), are not recommended for your infant during the first twelve months after birth if you received Usymro during pregnancy, unless your infant’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 breastfeed. You and your doctor should decide whether to breastfeed or use Usymro – do not do both.

Driving and using machines

Usymro has no or negligible influence on the ability to drive or operate machinery.

Usymro contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose unit; hence, it is essentially “sodium-free.” However, before Usymro is administered, it is mixed with a solution containing sodium. Speak with your doctor if you are on a low-salt diet.

Usymro contains polysorbate 80

This medicine contains 10.4 mg of polysorbate 80 (E433) in each 130 mg/26 ml vial, equivalent to 0.40 mg/ml. Polysorbates may cause allergic reactions. Inform your doctor if you or your child has any known allergies.

3. How to use Usymro

Usymro is indicated for use under the guidance and supervision of a physician experienced in the diagnosis and treatment of Crohn's disease.

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

Dosage of Usymro

Your doctor will decide the dose of Usymro you need to receive and for how long.

Adults aged 18 years and older

• 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 90 mg dose of Usymro via 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 90 mg dose of Usymro as an injection under the skin (subcutaneous injection) 8 weeks later, and subsequently every 12 weeks.

How Usymro is administered

• The first dose of Usymro for the treatment of Crohn's disease is given by a doctor through a drip into a vein in the arm (intravenous infusion).

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

If you forget to use Usymro

If you forget or miss your appointment for the dose, speak with your doctor to schedule another appointment.

If you stop treatment with Usymro

Stopping treatment with Usymro 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 will experience 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 Usymro (may affect up to 1 in 1,000 people). Signs include:

• difficulty breathing or 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, your first dose of Usymro is administered as an intravenous infusion (into a vein). Some patients have experienced severe allergic reactions during infusion.

In rare cases, pulmonary allergic reactions and lung inflammation have been reported in patients treated with ustekinumab. Inform your doctor immediately if you develop symptoms such as cough, difficulty breathing, or fever.

If you have a severe allergic reaction, your doctor may decide that you should not use Usymro again.

Infections – these may require urgent treatment. Contact your doctor immediately if you notice any of these signs.

• Infections of the nose or throat 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 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)

Usymro may reduce your ability to fight infections. Some infections may worsen and may include those caused by viruses, fungi, bacteria (including tuberculosis), or parasites, including infections that primarily 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 ustekinumab treatment.

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

• fever, flu-like symptoms, night sweats, weight loss
• feeling tired or shortness of breath; persistent cough
• skin that is warm, red, and painful, or a painful blistering skin rash
• burning sensation when urinating
• diarrhea
• visual deterioration or loss of vision
• headache, neck stiffness, light sensitivity, nausea, or confusion.

Contact your doctor immediately if you notice any of these signs of infection, as they may indicate serious infections such as chest infections, skin infections, herpes, or opportunistic infections that could lead to serious complications. Consult your doctor if you have any infection that does not go away or keeps recurring. Your doctor may decide that you should not use Usymro until the infection resolves. Also contact your doctor if you have an open wound or ulcer 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

Common adverse effects (may 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

Uncommon adverse effects (may affect up to 1 in 100 people):

• Dental infections
• Vaginal candidiasis
• 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 tiny yellow or white blisters on the skin, sometimes accompanied by fever (pustular psoriasis)
• Skin peeling (exfoliation)
• Acne

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

• Redness and peeling of the skin over a larger area of the body, which may cause itching or pain (exfoliative dermatitis). Sometimes, similar symptoms develop as a natural change in the type of 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 that may be red, itchy, and painful (bullous pemphigoid).
• Cutaneous lupus or lupus-like syndrome (a red, raised, scaly rash on sun-exposed areas of skin, 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 listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Usymro

• Usymro 130 mg concentrate for solution for infusion is administered in a hospital or clinic setting, 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 (between 2 °C and 8 °C). Do not freeze.
• Keep the vial in the outer packaging to protect it from light.
• Do not shake Usymro vials. Prolonged vigorous shaking may damage the medicine.

Do not use this medicine:

• After the expiry date stated on the label and container following “EXP”. The expiry date refers to the last day of the month indicated.
• If the liquid has changed colour, is cloudy, or contains foreign particles floating in it (see section 6, “Appearance of Usymro and contents of the container”).
• If you know or suspect 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.

Usymro is for single use only. Any diluted perfusion solution remaining unused, or any unused product left in the vial or syringe, must be discarded according to local regulations.

6. Package contents and other information

Composition of Usymro

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

Appearance of the product and contents of the pack

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

Marketing Authorisation Holder and Manufacturer

Gedeon Richter Plc.
Gyömroi út 19-21.
1103 Budapest, Hungary

Date of the most recent revision of this summary:

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

This 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 should be clearly recorded.

Instructions for dilution:

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

1. Calculate the dose and the number of Usymro vials required based on the patient's body weight (see section 3, Table 1, Table 2). Each 26 ml vial of Usymro contains 130 mg of ustekinumab.
2. Withdraw and discard a volume of 0.9% sodium chloride solution from the 250 ml infusion bag equal to the volume of Usymro to be added (discard 26 ml of sodium chloride per vial of Usymro required: for 2 vials, discard 52 ml; for 3 vials, discard 78 ml; for 4 vials, discard 104 ml).
3. Withdraw 26 ml of Usymro from each required vial and add it to the 250 ml infusion bag. The final volume in the infusion bag must be 250 ml. Mix gently.
4. Visually inspect the diluted solution before infusion. Do not use if visible opalescent particles, discolouration, 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 eight hours of dilution in the infusion bag.
6. Each vial is for single use only. Any unused medicinal product and all materials that have come into contact with it must be disposed of in accordance with local requirements.

Storage after dilution:

Chemical and physical in-use stability has been demonstrated for diluted concentrations between 1.04 mg/ml and 2.08 mg/ml for up to 48 hours when stored at 2 °C to 8 °C, and for up to 8 hours when stored at 15 °C to 25 °C.