Usymro 45 mg solution for injection in pre-filled syringe

Package Leaflet: Information for the User

Introduction

Package leaflet: information for the user

Usymro 45 mg injectable solution in pre-filled syringe

ustekinumab

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

Read this 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. If you are a parent, guardian, or caregiver administering Usymro to a child, please read this information carefully.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only and must not be given to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse reactions, consult your doctor or pharmacist, even if they are adverse reactions 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 effects
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:

• Plaque psoriasis – in adults and children from 6 years of age
• Psoriatic arthritis – in adults
• Moderate to severe Crohn's disease – in adults and children weighing at least 40 kg

Plaque psoriasis

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

Usymro is used in adults with moderate to severe plaque psoriasis who cannot use cyclosporine, methotrexate, or phototherapy, or when these treatments are not effective.

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

Psoriatic arthritis

Psoriatic arthritis is an inflammatory joint disease, which usually occurs together with psoriasis. If you have active psoriatic arthritis, you will first be given other medicines. If you do not respond adequately to these medicines, you may be given Usymro 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 medicines. If you do not respond adequately or cannot tolerate those medicines, you may be given Usymro 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 health condition before treatment. Make sure to inform your doctor about any medical conditions you have before starting treatment. Also inform your doctor if you have recently been in 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.

Watch for serious adverse effects

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

Before using Usymro, inform 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 produced from a biological source and usually administered by injection) – the risk of cancer may be higher.
• If you currently have or have recently had an infection.
• If you have any new or changing lesions within areas of psoriasis or on normal skin.
• If you have ever had an allergic reaction to latex or to the Usymro injection – the packaging of this medicine contains latex rubber, which may cause severe allergic reactions in people sensitive to latex. See “Watch for serious adverse effects” in section 4 for signs of an allergic reaction.
• 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 light [UV]). These treatments may also weaken part of the immune system. The use of these treatments together with Usymro has not been studied. However, it may increase the likelihood of diseases related to a weakened 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 prone to 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 sun-exposed areas of skin, or if you experience joint pain.

Heart attack and stroke

In a study of patients with psoriasis treated with ustekinumab, heart attacks and strokes were observed. 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 problems.

Children and adolescents

The use of Usymro is not recommended in children under 6 years of age with psoriasis, children with Crohn’s disease weighing less than 40 kg, or children under 18 years of age with psoriatic arthritis, as it has not been studied in these age groups.

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) should 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 recommends 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.
• If you are a woman of childbearing potential, you 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

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

Usymro contains polysorbate 80

This medicine contains 0.05 mg of polysorbate 80 (E433) in each 45 mg/0.5 ml pre-filled syringe, equivalent to 0.10 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 intended for use under the guidance and supervision of a physician experienced in the treatment of the conditions for which Usymro is indicated.

Always use this medicine exactly as your doctor has told you. If you are unsure, ask your doctor. Ask your doctor about when you will receive your injections and follow-up appointments.

How much Usymro is administered

Your doctor will decide how much Usymro you need to receive and for how long.

Adults aged 18 years and older

Psoriasis or psoriatic arthritis

• The recommended starting dose is 45 mg of Usymro. Patients weighing more than 100 kilograms (kg) may start with a dose of 90 mg instead of 45 mg.
• After the initial dose, you will receive the next dose 4 weeks later, and subsequently every 12 weeks. The following 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 Usymro as an intravenous infusion (a drip into a vein in your arm). After the initial dose, you will receive the next dose of 90 mg of Usymro 8 weeks later, and then every 12 weeks thereafter, by injection under the skin ("subcutaneously").
• In some patients, after the first subcutaneous injection, 90 mg of Usymro will be administered every 8 weeks. Your doctor will decide when you should receive the next dose.

Children and adolescents aged 6 years and older

Psoriasis

• Your doctor will determine the correct dose for you, including the amount (volume) of Usymro to inject to deliver the correct dose. The appropriate dose for you will depend on your body weight at the time each dose is administered.
• For pediatric patients who require a dose lower than the full 45 mg dose, a 45 mg vial is available.
• If you weigh less than 60 kg, the recommended dose is 0.75 mg of Usymro per kg of body weight.
• If you weigh between 60 kg and 100 kg, the recommended dose is 45 mg of Usymro.
• If you weigh more than 100 kg, the recommended dose is 90 mg of Usymro.
• After the initial dose, you will receive the next dose 4 weeks later, and subsequently every 12 weeks.

Children weighing at least 40 kg

Crohn's disease

• During treatment, your doctor will administer the first dose of approximately 6 mg/kg of Usymro as an intravenous infusion (a drip into a vein in your arm). After the initial dose, you will receive the next dose of 90 mg of Usymro 8 weeks later, and then every 12 weeks thereafter, by injection under the skin ("subcutaneously").
• In some patients, after the first subcutaneous injection, 90 mg of Usymro will be administered every 8 weeks. Your doctor will decide when you should receive the next dose.

How Usymro is administered

• Usymro is administered by injection under the skin ("subcutaneously"). At the beginning of your treatment, medical or nursing staff may administer Usymro to you.
• However, you and your doctor may decide that you will self-inject Usymro. In that case, you will be trained on how to self-inject Usymro.
• For instructions on how to inject Usymro, see "Instructions for administration" at the end of this leaflet.

Talk to your doctor if you have any questions about how to self-inject.

If you use more Usymro than you should

If you have used or have been given too much Usymro, contact your doctor or pharmacist immediately. Always carry the medicine carton with you, even if it is empty.

If you forget to use Usymro

If you miss a dose, contact your doctor or pharmacist. Do not take a double dose to make up for a missed dose.

If you stop using Usymro

Stopping 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).

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, and 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.

• 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 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 treatment with ustekinumab.

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

• fever, flu-like symptoms, night sweats, weight loss
• feeling tired or short of breath; persistent cough
• skin that is hot, red, and painful or a painful blistering skin rash
• burning sensation when urinating
• diarrhea
• worsening vision or vision loss
• 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 infections such as chest infections, skin infections, herpes, or opportunistic infections that could lead to serious complications. Consult your doctor if you have any type of infection that does not go away or recurs. Your doctor may decide that you should not use Usymro 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

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 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 tiny yellow or white blisters, sometimes accompanied by fever (pustular psoriasis)
• Skin peeling (exfoliative dermatitis)
• 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 result in 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 in areas of skin exposed to sunlight, possibly accompanied by joint pains).

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 included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Usymro

• 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 pre-filled syringe in the outer packaging to protect it from light.
• If necessary, individual pre-filled syringes of Usymro may also be stored at room temperature up to 30 °C for a maximum period of 40 days in their original packaging to protect them from light. Record the date when the pre-filled syringe is first removed from the refrigerator and the date when it must be discarded in the space provided on the outer packaging. The discard date must not exceed the original expiry date printed on the carton. Once a syringe has been stored at room temperature (up to 30 °C), it must not be returned to the refrigerator. Discard the syringe if it is not used within 40 days of storage at room temperature or after the original expiry date, whichever comes first.
• Do not shake the pre-filled syringes of Usymro. Prolonged vigorous shaking may damage the medicine.

Do not use this medicine:

• After the expiry date stated on the label and packaging 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 “What Usymro looks like and contents of the pack”).
• If you know or suspect it has been exposed to extreme temperatures (such as accidental overheating or freezing).
• If the product has been shaken vigorously.

Usymro is for single use only. Any unused portion remaining in the syringe must be discarded. Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Usymro

• The active substance is ustekinumab. Each pre-filled syringe contains 45 mg of ustekinumab in 0.5 ml.
• The other components are L-histidine, L-histidine monohydrochloride monohydrate, polysorbate 80 (E433), sucrose, and water for injections.

Appearance of the product and contents of the pack

Usymro is a transparent or slightly opalescent (with a pearly sheen), colourless to pale yellow injectable solution. The solution may contain a few translucent or white protein particles. It is supplied in a cardboard pack containing 1 single-dose glass pre-filled syringe of 1 ml. Each pre-filled syringe contains 45 mg of ustekinumab in 0.5 ml of injectable solution.

Marketing Authorisation Holder and Manufacturer

Gedeon Richter Plc.

Gyömroi út 19-21.

1103 Budapest

Hungary

Date of the most recent revision of this leaflet:

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

Instructions for administration

At the beginning of treatment, your healthcare professional will assist you with the first injection. However, you and your doctor may decide that you will self-inject Usymro. In such a case, you will be trained on how to administer Usymro injections. Speak with your doctor if you have any questions about administering an injection to yourself.

Do not mix Usymro with other injectable liquids.

Do not shake the pre-filled syringes of Usymro. The medicine may deteriorate if shaken vigorously. Do not use the medicine if it has been shaken vigorously.

Figure 1 shows what the pre-filled syringe looks like.

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

Preparation for using the pre-filled syringe

• Remove the pre-filled syringe(s) from the refrigerator. Leave the pre-filled syringe outside the carton for half an hour. This will allow the liquid to reach a comfortable temperature for injection (room temperature). Do not remove the needle cap from the syringe while waiting for it to reach room temperature.
• Hold the pre-filled syringe by the barrel with the covered needle pointing upwards.
• Do not hold it by the plunger rod, plunger, needle shield wings, or needle cap.
• Do not pull back 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 concentration are correct.

• If your dose is 45 mg, you will receive one 45 mg pre-filled syringe of Usymro.

• If your dose is 90 mg, you will receive two 45 mg pre-filled syringes of Usymro and must administer two injections. Choose two different injection sites (for example, one injection in the right thigh and the other in the left thigh), and administer the injections one immediately after the other.

• it is the correct medicine.

• the expiry date has not passed.

• the pre-filled syringe is not damaged.

• the solution in the pre-filled syringe is transparent or slightly opalescent and colourless to pale yellow.

• the solution in the pre-filled syringe has not changed colour or become cloudy, and contains no foreign particles.

• the solution in the pre-filled syringe has not been frozen.

Gather all the items you need and place them on a clean surface. This includes antiseptic wipes, a cotton ball or gauze, and a sharps container.

2. Choose and prepare the injection site:

Choose the injection site (see Figure 2).

• Usymro is administered by injection under the skin ("subcutaneously").
• Suitable injection sites include the upper thigh or around the belly (abdomen), at least 5 cm away from the navel.
• As far as possible, avoid areas of skin showing signs of psoriasis.
• If someone else is administering the injection, they may also choose the upper arm as an injection site.

Prepare the injection site.

• Wash your hands thoroughly with warm water and soap.
• Clean the skin at the injection site with an antiseptic wipe.
• Do not touch this area again before administering the injection.

3. Remove the needle cap (see Figure 3):

• The needle cap should not be removed until you are ready to administer the dose.
• Hold the pre-filled syringe and grasp the barrel with one hand.
• Remove the needle cap and discard it. Do not touch the plunger while doing this.

• You may see an air bubble in the pre-filled syringe or a drop of liquid at the tip 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 been dropped without the needle cap. If this happens, consult your doctor or pharmacist.
• Administer the dose immediately after removing the needle cap.

4. Administer the dose:

• Hold the pre-filled syringe with one hand between the index and middle fingers, place your thumb on the plunger rod, and with the other hand gently pinch the disinfected skin with your thumb and index finger. Do not squeeze tightly.
• Do not pull back the plunger at any time.
• With a quick, single motion, insert the needle through the skin until fully inserted (see Figure 4).

• Inject the entire medicine by pushing the plunger until the plunger rod is completely between the needle shield wings (see Figure 5).

• After pushing the plunger fully down, continue applying pressure on the plunger rod, withdraw the needle, and release the skin (see Figure 6).

• Slowly release your thumb from the plunger rod so that the empty syringe moves upward until the needle is completely covered by the needle shield, as shown in Figure 7:

Figure 7

5. After the injection:

• Press the injection site with an antiseptic wipe for a few seconds after the injection.
• A small amount of blood or fluid may appear at the injection site. This is normal.
• You may press a cotton ball or gauze on the injection site and hold it for 10 seconds.
• Do not rub the skin at the injection site. If needed, you may cover the injection site with a plaster.

6. Disposal:

• Used syringes must be placed in a puncture-resistant container, such as a sharps container (see Figure 8). For your safety and health, and for the safety of others, never reuse the syringe. Dispose of your sharps container according to local regulations.
• Antiseptic wipes and other supplies can be thrown in the trash.