Usymro

Package leaflet: Information for the user

Usymro 130 mg concentrate for solution for infusion

ustekinumab
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please 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 people who take this medicine.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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 side 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 recognise and bind to specific target proteins in the body.
Usymro belongs to a group of medicines called "immunosuppressants". These medicines
reduce the activity of the immune system to some extent.
What Usymro is used for
Usymro is used to treat the following inflammatory diseases:

• Moderate to severe 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
treated with other medicines. If you do not respond adequately or are intolerant to these
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 important.

If you are unsure whether any of the conditions listed above apply to you, speak with your doctor or
pharmacist before using Usymro.
Warnings and precautions
Talk to your doctor or pharmacist before using Usymro. Your doctor will check your health status
before starting 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 contact with people who might have
had tuberculosis. Your doctor will examine you and perform tests for tuberculosis before administering
Usymro. If your doctor believes you are at risk for tuberculosis, you may be given medicines to treat
tuberculosis.
Be aware of serious side effects
Usymro can cause serious side effects, including allergic reactions and infections. You should pay
attention to certain signs of illness while taking Usymro. See “Serious side effects” in section 4 for a
complete list of these side effects.
Before using Usymro, contact your doctor

• If you have ever had an allergic reaction to Usymro. Ask your doctor if you are unsure.
• If you have ever had any type of cancer – this is because immunosuppressants like Usymro partially weaken the immune system. This may increase the risk of cancer.
• If you have been treated for psoriasis with other biological medicines (a medicinal product derived 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 or if you have abnormal openings on the skin (fistulas).
• If you have ever had any new or changed skin lesions within the area of psoriasis or on normal skin.
• If you are currently receiving any other treatment for psoriasis and/or psoriatic arthritis – such as another immunosuppressant or phototherapy (when the body is treated with a type of ultraviolet (UV) light). These treatments may also partially reduce immune system activity. The concomitant use of these therapies with Usymro has not been studied. However, it may increase the likelihood of conditions related to a weakened immune system.
• If you are using or have ever used injections for the treatment of allergies – it is not known whether Usymro may affect them.
• If you are aged 65 years or older – you may have a higher risk of developing infections.

If you are unsure whether any of the above conditions apply to you, talk to your doctor or pharmacist
before starting treatment with Usymro.
During treatment with ustekinumab, some patients have developed lupus-like reactions, including
cutaneous lupus or lupus-like syndrome (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
In a study of patients with psoriasis treated with ustekinumab, heart attack and stroke were observed.
Your doctor will regularly monitor risk factors for heart disease and stroke to ensure they are
appropriately managed. Seek immediate medical attention if you develop chest pain, weakness or
unusual sensations on one side of the body, facial drooping, or speech or vision problems.
Children and adolescents
Usymro is not recommended for the treatment of 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 take any other medicines
• If you have recently been vaccinated or are about to be vaccinated. Some types of vaccines (live vaccines) should not be administered while you are using Usymro.
• If you received Usymro during pregnancy, inform your child’s paediatrician about the Usymro treatment before your child receives any vaccine, including live vaccines such as the BCG vaccine (used to prevent tuberculosis). If you received Usymro during pregnancy, live vaccines are not recommended for your child during the first twelve months after birth, unless otherwise recommended by your child’s paediatrician.

Pregnancy and breastfeeding

• If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor before taking this medicine.
• In newborns exposed to ustekinumab in the womb, no increased risk of congenital malformations has been observed. However, experience with ustekinumab in pregnant women is limited. Therefore, it is preferable to avoid using Usymro during pregnancy.
• If you are of childbearing potential, it is advisable to avoid becoming pregnant; you should use an effective method of contraception during treatment with Usymro and for at least 15 weeks after stopping treatment with Usymro.
• Usymro can pass to the unborn child through the placenta. If you received Usymro during pregnancy, your child may have an increased risk of developing an infection.
• If you received Usymro during pregnancy, it is important to inform your child’s paediatrician and other healthcare providers before your child receives any vaccine. If you received Usymro during pregnancy, live vaccines such as the BCG vaccine (used to prevent tuberculosis) are not recommended for your child during the first twelve months after birth, unless otherwise recommended by the paediatrician.
• Ustekinumab may be excreted in breast milk in very small amounts. If you are breastfeeding or plan to breastfeed, consult your doctor. You and your doctor will decide whether you should breastfeed or use Usymro. You cannot do both.

Driving and using machines
Usymro has no effect or a negligible effect on the ability to drive vehicles and use machines.
Usymro contains sodium
Usymro contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is essentially "sodium-free".
However, before Usymro is administered, it is mixed with a solution that contains sodium. Talk to your
doctor if you are on a low-salt diet.
Usymro contains polysorbate 80
This medicine contains 10.4 mg of polysorbate 80 (E433) per 130 mg/26 mL vial, equivalent to 0.40 mg/mL. Polysorbates may cause allergic reactions. Inform your doctor if you or your child have known allergies.

3. How to use Usymro

Usymro is intended for use under the guidance and supervision of a physician experienced in the diagnosis and treatment of Crohn's disease.
Usymro 130 mg concentrate for solution for infusion will be administered by your doctor through an intravenous infusion (IV infusion) into a vein in your arm for at least one hour. Discuss with your doctor when you should have your infusions and follow-up visits.
How much Usymro is given
Your doctor will decide how much Usymro you need and for how long.
Adults from 18 years of age

• Your doctor will calculate the recommended intravenous infusion dose based on your body weight.

• 8 weeks after the initial intravenous dose, you will receive the next 90 mg dose of Usymro as an injection under the skin (subcutaneous injection), followed by subsequent doses every 12 weeks.

Children with Crohn’s disease weighing at least 40 kg

• Your doctor will calculate the recommended intravenous infusion dose based on body weight.

• 8 weeks after the initial intravenous dose, you will receive the next dose of 90 mg of Usymro as an injection under the skin (subcutaneous injection), then continue every 12 weeks.

How Usymro is administered

• The first dose of Usymro for the treatment of Crohn's disease is given by your doctor as an intravenous infusion into a vein in your arm. Inform your doctor if you have any questions about the use of Usymro.

If you forget to use Usymro
If you forget or miss your scheduled dose appointment, contact your doctor to arrange a new appointment.

If you stop using Usymro
Stopping treatment with Usymro is not dangerous. However, if you stop treatment, your symptoms may return.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
Serious side effects
Some patients may experience serious side effects that may require urgent treatment.
Allergic reactions – these may require urgent treatment, so contact your doctor or seek immediate medical help if you notice any of the following signs.

• Severe allergic reactions ("anaphylaxis") are rare in patients taking Usymro (affecting up to 1 in 1,000 patients). Signs include:
  o difficulty breathing or swallowing, or low blood pressure, which may cause dizziness or a feeling of lightheadedness, or
  o swelling of the face, lips, mouth, or throat.
• Common signs of an allergic reaction include rash and hives (affecting up to 1 in 100 patients).

Infusion-related reactions – If you are being treated for Crohn’s disease, your first dose of Usymro is given by intravenous infusion (drip). Some patients have experienced severe allergic reactions during the infusion.
Allergic lung reactions and lung inflammation have been reported rarely in patients receiving ustekinumab. Inform your doctor immediately if you develop symptoms such as cough, shortness of breath, and fever.
If you experience a severe allergic reaction, your doctor may decide that you should not use Usymro again.
Infections – these may require urgent treatment, so contact your doctor immediately if you notice any of the following signs.

• Nasal, throat infections, and common cold are common (affecting up to 1 in 10 patients).
• Chest infections are uncommon (may affect up to 1 in 100 patients).
• Inflammation of the skin and underlying tissue ('cellulitis') is uncommon (affects up to 1 in 100 patients).
• Herpes zoster (a painful blistering rash) is uncommon (affects up to 1 in 100 patients).

Usymro may reduce your ability to fight infections. Some infections may become serious and may include those caused by viruses, fungi, bacteria (including tuberculosis) or parasites, including 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 treated with ustekinumab.
You should be aware of the signs of infection while taking Usymro. These include:

• fever, flu-like symptoms, night sweats, weight loss
• feeling tired or short of breath, persistent cough
• warmth, redness, and pain in the skin, or a painful blistering rash
• burning when urinating
• diarrhoea
• vision problems or loss of vision
• headache, neck stiffness, light sensitivity, nausea, or confusion

Inform your doctor immediately if you notice any of these signs of infection. These may be symptoms of infections such as chest infections, skin infections, herpes zoster, or opportunistic infections, which can have serious complications. Consult your doctor if you have any infection that persists or keeps recurring. Your doctor may decide to stop Usymro until the infection resolves. Also inform your doctor if you have any cuts or open wounds 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 conditions. If you notice any of these signs, inform your doctor immediately.
Other side effects
Common side effects (affect up to 1 in 10 patients)

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

Uncommon side effects (affect up to 1 in 100 patients)

• Dental infections
• Vaginal fungal infection
• Depression
• Stuffy or runny nose
• Bleeding, bruising, stiffness, swelling, and itching at the injection site
• Feeling weak
• Drooping eyelid and 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 (exfoliation of the skin)
• Acne

Rare side effects (affect up to 1 in 1,000 patients)

• Redness and peeling of the skin over a large area of the body, which may be itchy or painful (exfoliative dermatitis). Similar symptoms sometimes develop as a natural progression of psoriasis symptoms (erythrodermic psoriasis)
• Inflammation of small blood vessels, which may cause a rash with small red or purple bumps, fever, or joint pain (vasculitis)

Very rare side effects (affect up to 1 in 10,000 patients)

• Blistering skin rash, possibly with redness, itching, and pain (bullous pemphigoid)
• Cutaneous lupus or lupus-like syndrome (red, raised, scaly rash on sun-exposed skin areas, sometimes with joint pain)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Usymro

• Usymro 130 mg concentrate for solution for infusion is administered in a hospital or clinic setting, and patients do not need to handle or store it.
• Keep this medicine out of the sight and reach of children.
• Store in a refrigerator (2 °C–8 °C). Do not freeze.
• Keep the vial in the outer packaging to protect the medicine from light.
• Do not shake the Usymro vials. Prolonged vigorous shaking may damage the medicine.

Do not use this medicine

• After the expiry date stated on the label and carton after “Exp.”. The expiry date refers to the last day of that month.
• If the liquid has changed colour, is cloudy, or if you see foreign particles floating in it (see section 6 “Description of the appearance of Usymro and contents of the pack”).
• If you know or suspect the medicine has been exposed to extreme temperatures (e.g. accidentally frozen or heated).
• If the product has been shaken vigorously.
• If the seal is broken.

Usymro is for single use only. Any unused diluted solution for infusion remaining in the vial and syringe must be discarded in accordance with local regulations.

6. Package contents and other information

What Usymro contains

• 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, water for injections.

Description of the appearance of Usymro and contents of the pack
Usymro is a concentrate for infusion solution, clear, colourless to pale yellow. It is supplied in a
carton pack containing one single dose in a 30 mL glass vial. Each vial contains 130 mg of ustekinumab in 26 mL of concentrate for infusion solution.
Marketing Authorisation Holder
Gedeon Richter Plc.
Gyömrői út 19-21.
1103 Budapest
Hungary
Manufacturer
Cilatus Manufacturing Services Limited
Pembroke House, 28-32.
Upper Pembroke Street
Dublin 2, D02 EK84
Ireland
More detailed information on this medicinal product is available on the website of the European Medicines Agency, 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 must be clearly recorded.
Dilution instructions
Usymro concentrate for infusion solution must be diluted, prepared and administered by a healthcare professional using 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. Remove and discard a volume of 9 mg/mL (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 for each required Usymro vial; 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. Gently mix.
4. Visually inspect the diluted solution before infusion. Do not use if visible opaque particles, discolouration or foreign particles are observed.
5. Infuse the diluted solution over a period of at least 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 and any unused medicinal product must be disposed of in accordance with local regulations.

Storage
After dilution, chemical and physical in-use stability has been demonstrated between 1.04 mg/mL and 2.08 mg/mL for 48 hours at 2 °C–8 °C and for 8 hours at 15 °C–25 °C.

Patient Information Leaflet: Information for the User

Usymro 45 mg injectable solution

ustekinumab
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before using this medicine because it contains important information for you.
This leaflet has been written for people taking this medicine. If you are the parent or caregiver of a child who is to be given Usymro, please read these instructions carefully.

• Keep this leaflet. 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. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

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 side 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 recognize and bind to specific proteins in the body.
Usymro belongs to a group of medicines called "immunosuppressants". These medicines reduce the activity of the immune system to some extent.

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 condition causing inflammation of the skin and nails.
Usymro will reduce 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 in whom these treatments are ineffective.
Usymro is used in children and adolescents from 6 years of age with moderate to severe plaque psoriasis who cannot tolerate phototherapy or other systemic therapies, or when these treatments have not worked.

Psoriatic arthritis
Psoriatic arthritis is an inflammatory joint disease, usually associated with psoriasis. If you have active psoriatic arthritis, you will first be treated with other medicines. If you do not respond adequately to these medicines, you may be given Usymro to:

• reduce the signs and symptoms of the disease
• improve physical function
• slow down joint damage.

Crohn’s disease
Crohn’s disease is an inflammatory bowel disease. If you have Crohn’s disease, you will first be treated with other medications. If you do not respond adequately or are intolerant to these medicines, Usymro may be given to reduce the signs and symptoms of your disease.

2. What you should 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 important.

If you are unsure whether any of the conditions listed above apply to you, talk to your doctor or pharmacist before using Usymro.
Warnings and precautions
Talk to your doctor or pharmacist before using Usymro. Your doctor will check your health status before each treatment. Make sure to inform your doctor about any medical conditions you have before each treatment. Also, inform your doctor if you have recently been in contact with people who may have had tuberculosis. Your doctor will examine you and perform tests for tuberculosis before administering Usymro. If your doctor believes you are at risk for tuberculosis, you may be given medications to treat tuberculosis.
Be aware of serious side effects
Usymro can cause serious side effects, including allergic reactions and infections. You should pay attention to certain signs of illness while taking Usymro. See “Serious side effects” in section 4 for a complete list of these side effects.
Before using Usymro, contact your doctor:

• If you have ever had an allergic reaction to Usymro. Ask your doctor if you are unsure.

• If you have ever had any type of cancer – because immunosuppressants like Usymro partially weaken the immune system. This may increase the risk of cancer.

• If you have been treated for psoriasis with other biological medicines (a medicinal product derived 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 ever had any new or changed skin lesions within the area of psoriasis or on normal skin.

• If you are receiving any other type of treatment for psoriasis and/or psoriatic arthritis – such as another immunosuppressant or phototherapy (when the body is treated with a type of ultraviolet (UV) light). These treatments may also partially reduce immune system activity. The concomitant use of these therapies with Usymro has not been studied. However, it could potentially increase the likelihood of conditions related to a weakened immune system.

• If you are using or have ever used allergy injections – it is not known whether Usymro could affect them.

• If you are aged 65 years or older – you may have a higher risk of developing infections.

If you are unsure whether any of the conditions listed above apply to you, talk to your doctor or pharmacist before starting treatment with Usymro.
During treatment with ustekinumab, some patients have developed lupus-like reactions, including cutaneous lupus or lupus-like syndrome (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
In a study of psoriasis patients treated with ustekinumab, heart attack and stroke were observed. Your doctor will regularly monitor risk factors for heart disease and stroke to ensure they are appropriately managed. Seek immediate medical attention if you develop chest pain, weakness or unusual sensations on one side of the body, facial drooping, or speech or vision problems.
Children and adolescents
Usymro is not recommended for the treatment of 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 take any other medicines.
• If you have recently been vaccinated or are about to be vaccinated. Some types of vaccines (live vaccines) should not be given while you are using Usymro.
• If you received Usymro during pregnancy, inform your child’s paediatrician about the Usymro treatment before your child receives any vaccine, including live vaccines such as the BCG vaccine (used to prevent tuberculosis). If you received Usymro during pregnancy, live vaccines are not recommended for your child during the first twelve months of life, unless otherwise advised by your child’s paediatrician.

Pregnancy and breastfeeding

• If you are pregnant, think you might be pregnant, or are planning to become pregnant, consult your doctor before taking this medicine.

• In newborns exposed to ustekinumab in the womb, no increased risk of congenital malformations has been observed. However, experience with ustekinumab in pregnant women is limited. Therefore, it is preferable to avoid using Usymro during pregnancy.

• If you are of childbearing potential, it is advisable to avoid becoming pregnant; you should use an effective method of contraception during treatment with Usymro and for at least 15 weeks after stopping treatment with Usymro.

• Usymro can pass to the unborn child through the placenta. If you received Usymro during pregnancy, your baby may have an increased risk of developing an infection.

• If you received Usymro during pregnancy, it is important to inform your child’s paediatrician and other healthcare providers before your child receives any vaccine. If you received Usymro during pregnancy, live vaccines such as the BCG vaccine (used to prevent tuberculosis) are not recommended for your child during the first twelve months after birth, unless otherwise recommended by the paediatrician.

• Ustekinumab may be excreted in breast milk in very small amounts. If you are breastfeeding or planning to breastfeed, consult your doctor. You and your doctor will decide whether you should breastfeed or use Usymro. You cannot do both.

Driving and using machines
Usymro has no effect or has a negligible effect on the ability to drive and use machines.
Usymro contains polysorbate 80
This medicine contains 0.05 mg of polysorbate 80 (E433) per 45 mg/0.5 mL vial, equivalent to 0.10 mg/mL. Polysorbates may cause allergic reactions. Inform your doctor if you or your child have 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.
Use this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor. Discuss with your doctor when you should receive your injections and follow-up visits.

How much Usymro is administered
Your doctor will decide how much Usymro you need and for how long.

Adults from 18 years of age
Psoriasis and psoriatic arthritis

• The recommended initial 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.
• Four weeks after the initial dose, you will receive the next dose, followed by subsequent doses every 12 weeks. Subsequent doses are usually the same as the initial dose.

Crohn’s disease

• During treatment, the first dose of approximately 6 mg/kg of Usymro is administered by your doctor via an intravenous infusion (IV infusion) into a vein in the arm. Eight weeks after the initial dose, you will receive the next dose of 90 mg of Usymro, followed by subcutaneous injections (under the skin) every 12 weeks.
• In some patients, after the first subcutaneous injection, the 90 mg dose of Usymro may be administered every 8 weeks. Your doctor will decide when the next dose should be given.

Children and adolescents from 6 years of age
Psoriasis

• Your doctor will calculate the correct dose, including the amount (volume) of Usymro to be injected to ensure the correct dose is administered. The correct dose will depend on the child’s body weight at the time each dose is given.
• If body weight is less than 60 kg, the recommended dose is 0.75 mg of Usymro per kg of body weight.
• If body weight is between 60 kg and 100 kg, the recommended dose is 45 mg of Usymro.
• If body weight exceeds 100 kg, the recommended dose is 90 mg of Usymro.
• Four weeks after the initial dose, the next dose should be administered, followed by subsequent doses every 12 weeks.

Children weighing at least 40 kg
Crohn’s disease

• During treatment, the first dose of approximately 6 mg/kg of Usymro is administered by your doctor via an intravenous infusion (IV infusion) into a vein in the arm. Eight weeks after the initial dose, you will receive the next dose of 90 mg of Usymro, followed by subcutaneous injections (under the skin) every 12 weeks.
• In some patients, after the first subcutaneous injection, the 90 mg dose of Usymro may be administered every 8 weeks. Your doctor will decide when the next dose should be given.

How Usymro is administered

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

Inform your doctor if you have any questions about self-injection.

If you use more Usymro than you should
If you have used or received too much Usymro, inform your doctor or pharmacist immediately. Always bring the outer packaging of the medicine 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 the missed dose.

If you stop using Usymro
It is not dangerous to stop using Usymro. However, if you stop treatment, symptoms may return.

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
Serious side effects
Some patients may experience serious side effects that may require urgent treatment.
Allergic reactions – these may require urgent treatment, so contact your doctor or seek emergency
medical help if you notice any of the following signs.

• Severe allergic reactions ("anaphylaxis") are rare in patients taking Usymro (affecting up to 1 in 1,000 patients). Signs include:
  o difficulty breathing or swallowing, or low blood pressure, which may cause dizziness or a feeling of lightheadedness, or swelling of the face, lips, mouth or throat.
• Common signs of an allergic reaction include rash and hives (affecting up to 1 in 100 patients).

In rare cases, allergic lung reactions and lung inflammation have been reported in patients receiving ustekinumab. Inform your doctor immediately if you develop symptoms such as cough, shortness of breath, and fever.
If you experience a severe allergic reaction, your doctor may decide that you should not use Usymro again.
Infections – these may require urgent treatment, so contact your doctor immediately if you notice any of the following signs.

• Infections of the nose and throat and the common cold are common (affecting up to 1 in 10 patients).
• Chest infections are uncommon (may affect up to 1 in 100 patients).
• Inflammation of the tissue beneath the skin ("cellulitis") is uncommon (affects up to 1 in 100 patients).
• Herpes zoster (a type of painful blistering rash) is uncommon (affects up to 1 in 100 patients).

Usymro may reduce your ability to fight infections. Some infections may become serious and may include infections caused by viruses, fungi, bacteria (including tuberculosis) or parasites, including infections that mainly occur in people with weakened immune systems (opportunistic infections). Opportunistic infections of the brain (encephalitis, meningitis), lungs and eyes have been reported in patients treated with ustekinumab.
You should be aware of signs of infection while using Usymro. These include:

• fever, flu-like symptoms, night sweats, weight loss
• feeling tired or short of breath, persistent cough
• warmth, redness and pain in the skin, or a painful blistering rash
• burning sensation when urinating
• diarrhoea
• vision problems or loss of vision
• headache, neck stiffness, sensitivity to light, nausea or confusion

Inform your doctor immediately if you notice any of these signs of infection. These may be signs of infections such as chest infections, skin infections, herpes zoster or opportunistic infections, which may have serious complications. Consult your doctor if you have any type of infection that persists or keeps recurring. Your doctor may decide to stop Usymro until the infection resolves. Also inform your doctor if you have any cuts or open wounds 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 conditions. If you notice any of these signs, inform your doctor immediately.
Other side effects
Common side effects (affect up to 1 in 10 patients)

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

Uncommon side effects (affect up to 1 in 100 patients)

• Dental infections
• Vaginal fungal infection
• Depression
• Blocked or runny nose
• Bleeding, bruising, stiffness, swelling and itching at the injection site
• Feeling weak
• Drooping eyelid and 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 (exfoliation of the skin)
• Acne

Rare side effects (affect up to 1 in 1,000 patients)

• Redness and peeling of the skin over a large area of the body, which may be itchy or painful (exfoliative dermatitis). Similar symptoms sometimes develop as a natural progression in the type of psoriasis symptoms (erythrodermic psoriasis)
• Inflammation of small blood vessels, which may lead to a rash with small red or purple bumps, fever or joint pain (vasculitis)

Very rare side effects (affect up to 1 in 10,000 patients)

• Formation of skin blisters, possibly with redness, itching and pain (bullous pemphigoid).
• Cutaneous lupus or lupus-like syndrome (red, raised, scaly rash on areas of skin exposed to sunlight, sometimes accompanied by joint pain).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Usymro

• Keep this medicine out of the sight and reach of children.
• Store in the refrigerator (2 °C–8 °C). Do not freeze.
• Keep the vial in the outer packaging to protect the medicine from light.
• Do not shake the Usymro vials. Prolonged vigorous shaking may damage the medicine.

Do not use this medicine

• After the expiry date stated on the label and carton after “Exp.”. The expiry date refers to the last day of that month.
• If the liquid has changed colour, is cloudy, or if you see foreign particles floating in it (see section 6 “Description of the appearance of Usymro and contents of the pack”).
• If you know or suspect the medicine has been exposed to extreme temperatures (e.g. accidentally frozen or heated).
• If the product has been shaken vigorously.
• If the seal is broken.

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

6. Package contents and other information

What Usymro contains

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

Description of the appearance of Usymro and contents of the pack
Usymro is an injectable solution ranging from clear to slightly opalescent (pearl-like appearance), colourless to pale yellow. The solution may contain a few small translucent or white protein particles. It is supplied in a cardboard pack containing one single dose in a 2 mL glass vial. Each vial contains one dose of ustekinumab 45 mg in 0.5 mL of injectable solution.

Marketing Authorization Holder
Gedeon Richter Plc.
Gyömrői út 19-21.
1103 Budapest
Hungary

Manufacturer
Cilatus Manufacturing Services Limited
Pembroke House, 28-32
Upper Pembroke Street
Dublin 2, D02 EK84
Ireland

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

Instructions for administration
At the beginning of treatment, your doctor will assist you with the first injection. However, you and your doctor may decide whether you can self-inject Usymro. In this case, you will be trained on how to self-administer Usymro. Inform your doctor if you have any questions regarding self-injection.

• Do not mix Usymro with other injectable liquids.
• Do not shake the Usymro vials, as vigorous shaking may damage the medicine. Do not use the medicine if it has been shaken vigorously.

1. Check the number of vials and prepare materials:

Take out the vial or vials from the refrigerator. Leave the vial outside the refrigerator for
about half an hour. This will allow the liquid to reach a comfortable temperature for
injection (room temperature).
Check the vials to make sure that:

• the number of vials and the dose are correct; if your dose is 45 mg or less, you will take one 45 mg Usyma vial; if your dose is 90 mg, you will take two 45 mg Usyma vials and will need to perform two injections. Choose two different body sites for these injections (e.g., one injection in the right thigh and the other injection in the left thigh), and proceed with the injections one after the other. Use a new needle and a new syringe for each injection
• the medicine is the correct one
• the medicine has not expired
• the vial is not damaged and the cap is not broken
• the solution in the vial is clear or slightly opalescent (pearl-like appearance) and colorless or pale yellow
• the liquid does not have a changed color or appear cloudy, and contains no foreign particles
• it has not been frozen.

Children with pediatric psoriasis and body weight below 60 kg require a dose lower
than 45 mg. Ensure the appropriate amount (volume) to be withdrawn from the vial and the type of syringe needed for dosing. If you do not know the amount of medicine or the type of syringe to use, contact your doctor for further instructions.
Gather all necessary supplies and place them on a clean surface. You should have a syringe, needle, antiseptic swabs, a cotton ball or gauze, and a sharps container (see
Figure 1).

Figure 1

2. Choose and prepare the injection site

Choose an injection site (see Figure 2).

• Usymro is administered by injection under the skin (subcutaneously).
• A suitable injection site is the upper thigh or around the abdomen (abdominal area), at least 5 cm away from the navel.
• If possible, avoid areas of skin affected by psoriasis.
• If someone is assisting you with the injection, the upper arm may also be used as an injection site.

*The grey areas indicate the recommended injection sites.
Figure 2
Preparing the injection site

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

3. Prepare the dose:

• Remove the cap from the top of the vial (see Figure 3).

Figure 3

• Do not remove the stopper.
• Clean the stopper with an antiseptic swab.
• Place the vial on a flat surface.
• Take the syringe and remove the protective needle cap.
• Do not touch the needle, and do not let the needle touch anything.
• Insert the needle through the rubber stopper.
• Turn the vial and syringe upside down.
• Pull back the plunger of the syringe to draw up the prescribed amount of liquid.
• It is important that the needle tip remains immersed in the liquid at all times to prevent air bubbles from entering the syringe (see Figure 4).

Figure 4

• Remove the needle from the vial.
• Hold the syringe with the needle pointing upwards to check for the presence of air bubbles.
• If there are air bubbles, gently tap the side of the syringe until the air bubbles rise to the top (see Figure 5).

Figure 5

• Then push the plunger until all air is expelled (but not the liquid).
• Do not place the syringe down, and avoid letting the needle touch anything.

4. Inject the dose

• Gently pinch the clean area of skin, holding it between your thumb and index finger. Do not squeeze too forcefully.
• Insert the needle into the pinched skin.
• Push the plunger with your thumb until all the liquid is injected. Press slowly and steadily, keeping the skin gently pinched.
• When the plunger reaches the end of the syringe, withdraw the needle and release the skin.

5. After the injection

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

6. Disposal

• Used syringes and needles must be placed in a puncture-resistant container, such as a sharps disposal container. For your safety and the safety of others, never reuse needles or syringes. Dispose of the sharps container according to local regulations.
• Empty vials, antiseptic swabs, and other devices may be discarded in regular waste.

Package leaflet: Information for the user

Usymro 45 mg solution for injection in pre-filled syringe

ustekinumab
This medicinal product is subject to additional monitoring. This will allow any new safety information to be identified quickly. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read all of this leaflet carefully before using this medicine, as it contains important information for you.
This leaflet has been written for people who are taking this medicine. If you are a parent or caregiver of a child who is to be given Usymro, please read this information carefully.

• Keep this leaflet. 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. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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 side 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 recognise and bind to specific proteins in the body.
Usymro belongs to a group of medicines called “immunosuppressants”. These medicines reduce the activity 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)
• moderately to severely active Crohn’s disease in adults and children weighing at least 40 kg

Plaque psoriasis
Plaque psoriasis is a skin condition causing inflammation of the skin and nails. Usymro will reduce inflammation and other signs of the disease.
Usymro is used in adults with moderate to severe plaque psoriasis who cannot use ciclosporin, methotrexate, or phototherapy, or in whom these treatments are ineffective.
Usymro is used in children and adolescents from 6 years of age with moderate to severe plaque psoriasis who cannot tolerate phototherapy or other systemic therapies, or when these treatments have not worked.

Psoriatic arthritis
Psoriatic arthritis is an inflammatory joint disease, usually associated with psoriasis. If you have active psoriatic arthritis, you will first be treated with other medicines. If you do not respond adequately to these medicines, you may be given Usymro to:

• reduce the signs and symptoms of the disease
• improve physical function
• slow down joint damage

Crohn’s disease
Crohn’s disease is an inflammatory bowel disease. If you have Crohn’s disease, you will first be treated with other medicines. If you do not respond adequately or are intolerant to these 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 important.

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

Warnings and precautions

Talk to your doctor or pharmacist before using Usymro. Your doctor will check your health status before each treatment. Make sure you inform your doctor about any medical conditions you have before each treatment. Also, inform your doctor if you have recently been in contact with people who may have had tuberculosis. Your doctor will examine you and perform tests for tuberculosis before administering Usymro. If your doctor believes you are at risk of tuberculosis, you may be given medicines to treat tuberculosis.

Be aware of serious side effects

Usymro can cause serious side effects, including allergic reactions and infections. You should pay attention to certain signs of illness while taking Usymro. See "Serious side effects" in section 4 for a complete list of these side effects.

Before using Usymro, contact your doctor

• If you have ever had an allergic reaction to Usymro. Ask your doctor if you are unsure.
• If you have ever had any type of cancer – because immunosuppressants such as Usymro partially weaken the immune system, which may increase the risk of cancer.
• If you have been treated for psoriasis with other biological medicines (a medicinal product derived from a biological source, usually administered by injection) – the risk of cancer may be higher.
• If you currently have or have recently had an infection.
• If you have ever had any new or changed skin lesions within the psoriasis area or on normal skin.
• If you have ever had an allergic reaction to latex or to the injection of Usymro – the container of this medicinal product contains latex, which may cause serious allergic reactions in people who are sensitive to latex. See "Be aware of serious side effects" in section 4 for signs of an allergic reaction.
• If you are receiving any other treatment for psoriasis and/or psoriatic arthritis – such as another immunosuppressant or phototherapy (when the body is treated with a type of ultraviolet (UV) light). These treatments may also partially reduce immune system activity. The concomitant use of these therapies with Usymro has not been studied. However, it could increase the risk of conditions related to a weakened immune system.
• If you are using or have ever used injections for the treatment of allergies – it is not known whether Usymro could affect them.
• If you are aged 65 years or older – you may have a higher risk of developing infections.

If you are unsure whether any of the conditions listed above apply to you, talk to your doctor or pharmacist before starting treatment with Usymro.

During treatment with ustekinumab, some patients have developed lupus-like reactions, including cutaneous lupus or lupus-like syndrome (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

In a study of patients with psoriasis treated with ustekinumab, heart attack and stroke were observed. Your doctor will regularly monitor risk factors for heart disease and stroke to ensure they are appropriately managed. Seek immediate medical attention if you develop chest pain, weakness or unusual sensations on one side of the body, facial drooping, or speech or vision problems.

Children and adolescents

Usymro is not recommended for the treatment of 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 take any other medicines.
• If you have recently been vaccinated or are due to be vaccinated. Some types of vaccines (live vaccines) should not be given while you are using Usymro.
• If you received Usymro during pregnancy, inform your child’s paediatrician about the treatment with Usymro before your child receives any vaccine, including live vaccines such as the BCG vaccine (used to prevent tuberculosis). If you received Usymro during pregnancy, live vaccines are not recommended for your child during the first twelve months after birth, unless otherwise recommended by your child’s paediatrician.

Pregnancy and breastfeeding

• If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor before taking this medicine.
• No increased risk of congenital malformations has been observed in newborns exposed to ustekinumab in utero. However, experience with ustekinumab in pregnant women is limited. Therefore, it is preferable to avoid using Usymro during pregnancy.
• If you are of childbearing age, it is advisable to avoid becoming pregnant. You should use an effective method of contraception during treatment with Usymro and for at least 15 weeks after stopping treatment with Usymro.
• Usymro can cross the placenta and reach the unborn child. If you received Usymro during pregnancy, your baby may have an increased risk of developing an infection.
• If you received Usymro during pregnancy, it is important to inform your child’s paediatrician and other healthcare providers before your child receives any vaccine. If you received Usymro during pregnancy, live vaccines such as the BCG vaccine (used to prevent tuberculosis) are not recommended for your child during the first twelve months after birth, unless otherwise recommended by the paediatrician.
• Ustekinumab may be excreted in breast milk in very small amounts. If you are breastfeeding or planning to breastfeed, consult your doctor. You and your doctor will decide whether you should breastfeed or use Usymro. You cannot do both.

Driving and using machines

Usymro has no effect or has a negligible effect on the ability to drive vehicles and operate machinery.

Usymro contains polysorbate 80

This medicine contains 0.05 mg of polysorbate 80 (E433) per pre-filled syringe (PFS) of 45 mg/0.5 mL, equivalent to 0.10 mg/mL. Polysorbates may cause allergic reactions. Inform your doctor if you or your child have 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.
Use this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor. Discuss with your doctor when you should receive your injections and follow-up visits.

How much Usymro is administered

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

Adults from 18 years of age

Psoriasis and psoriatic arthritis

• The recommended initial 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.
• Four weeks after the initial dose, you will receive the next dose, followed by subsequent doses every 12 weeks. Subsequent doses are usually the same as the initial dose.

Crohn’s disease

• During treatment, the first dose of approximately 6 mg/kg of Usymro is administered by your doctor as an intravenous infusion (IV infusion) into the arm. Eight weeks after the initial dose, you will receive the next dose of 90 mg of Usymro, followed by subcutaneous injections (under the skin) every 12 weeks.
• In some patients, after the first subcutaneous injection, the 90 mg dose of Usymro may be administered every 8 weeks. Your doctor will decide when the next dose should be given.

Children and adolescents from 6 years of age

Psoriasis

• Your doctor will calculate the correct dose, including the amount (volume) of Usymro to be injected, to ensure the correct dose is administered. The correct dose will depend on the child’s body weight at the time of each administration.
• A 45 mg vial is available if a lower dose than 45 mg is required.
• If body weight is less than 60 kg, the recommended dose is 0.75 mg of Usymro per kg of body weight.
• If body weight is between 60 kg and 100 kg, the recommended dose is 45 mg of Usymro.
• If body weight exceeds 100 kg, the recommended dose is 90 mg of Usymro.
• Four weeks after the initial dose, the next dose should be administered, followed by doses every 12 weeks.

Children weighing at least 40 kg

Crohn’s disease

• During treatment, the first dose of approximately 6 mg/kg of Usymro is administered by your doctor as an intravenous infusion (IV infusion) into the arm. Eight weeks after the initial dose, you will receive the next dose of 90 mg of Usymro, followed by subcutaneous injections (under the skin) every 12 weeks.
• In some patients, after the first subcutaneous injection, the 90 mg dose of Usymro may be administered every 8 weeks. Your doctor will decide when the next dose should be given.

How Usymro is administered

• Usymro is administered by subcutaneous injection (“subcutaneously”). At the beginning of treatment, medical or nursing staff may administer Usymro to you.
• However, you and your doctor may decide whether you can self-inject Usymro. In this 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. Inform your doctor if you have any questions about self-injection.

If you use more Usymro than you should

If you have used or received too much Usymro, inform your doctor or pharmacist immediately. Always bring the outer packaging of the medicine 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 the missed dose.

If you stop using Usymro

It is not dangerous to stop using Usymro. However, if you stop treatment, symptoms may return.

If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious side effects

Some patients may experience serious side effects that may require treatment.

Allergic reactions – these may require urgent treatment, so contact your doctor or seek emergency medical help if you notice any of the following signs.

• Severe allergic reactions ("anaphylaxis") are rare in patients taking Usymro (affecting up to 1 in 1,000 patients). Signs include:

  o difficulty breathing or swallowing
  o low blood pressure, which may cause dizziness or lightheadedness
  o swelling of the face, lips, mouth or throat.

• Common signs of an allergic reaction include rash and hives (affecting up to 1 in 100 patients).

In rare cases, allergic lung reactions and lung inflammation have been reported in patients receiving ustekinumab. Inform your doctor immediately if you develop symptoms such as cough, shortness of breath, and fever.

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

Infections – these may require urgent treatment, so contact your doctor immediately if you notice any of the following signs.

• Nasal, throat infections and common cold are common (affecting up to 1 in 10 patients).
• Chest infections are uncommon (may affect up to 1 in 100 patients).
• Inflammation of the tissue under the skin ("cellulitis") is uncommon (affects up to 1 in 100 patients).
• Herpes zoster (a type of painful rash with blisters) is uncommon (affects up to 1 in 100 patients).

Usymro may reduce your ability to fight infections. Some infections may become serious and may include those caused by viruses, fungi, bacteria (including those causing tuberculosis) or parasites, including infections that mainly occur in people with weakened immune systems (opportunistic infections). Opportunistic infections of the brain (encephalitis, meningitis), lungs and eyes have been reported in patients treated with ustekinumab.

You should be alert 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
• warmth, redness and pain in the skin, or a painful blistering rash
• burning when urinating
• diarrhoea
• vision disturbance or loss of vision
• headache, neck stiffness, sensitivity to light, nausea or confusion

Inform your doctor immediately if you notice any of these signs of infection. These may be signs of infections such as chest infections, skin infections, herpes zoster or opportunistic infections, which may have serious complications. Contact your doctor if you have any type of infection that persists or keeps recurring. Your doctor may decide to stop Usymro until the infection resolves. Also inform your doctor if you have any cuts or open wounds 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 conditions. If you notice any of these signs, you must inform your doctor immediately.

Other side effects

Common side effects (affect up to 1 in 10 patients)

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

Uncommon side effects (affect up to 1 in 100 patients)

• Dental infections
• Vaginal fungal infection
• Depression
• Stuffy or runny nose
• Bleeding, bruising, stiffness, swelling and itching at the injection site
• Feeling weak
• Drooping eyelid and 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 (exfoliation of the skin)
• Acne

Rare side effects (affect up to 1 in 1,000 patients)

• Redness and peeling of the skin over a large area of the body, which may be itchy or painful (exfoliative dermatitis). Similar symptoms sometimes develop as a natural progression in the type of psoriasis symptoms (erythrodermic psoriasis)
• Inflammation of small blood vessels, which may lead to a rash with small red or purple bumps, fever or joint pain (vasculitis)

Very rare side effects (affect up to 1 in 10,000 patients)

• Formation of skin blisters with possible redness, itching and pain (bullous pemphigoid).
• Cutaneous lupus or lupus-like syndrome (red, raised, scaly rash on areas of skin exposed to sunlight, sometimes with joint pain).

Reporting of side effects

If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Usymro

• Keep this medicine out of the sight and reach of children.

• Store in a refrigerator (2 °C–8 °C). Do not freeze.

• Keep the pre-filled syringe in the outer packaging to protect the medicine from light.

• If necessary, individual pre-filled syringes of Usymro may also be stored at room temperature up to 30 °C for a single period of maximum 40 days, while remaining in the outer 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 should be discarded in the designated space on the outer packaging. The discard date must not exceed the original expiry date printed on the packaging. 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 not used within 40 days at room temperature or by 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 carton following "Exp". The expiry date refers to the last day of that month.
• If the solution has changed colour, appears cloudy, or if foreign particles are visible floating in it (see section 6 "Description of the appearance of Usymro and contents of the pack").
• If you know or suspect that the medicine has been exposed to extreme temperatures (e.g. accidentally frozen or overheated).
• If the product has been shaken vigorously.

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

6. Package contents and other information

What Usymro contains

• 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, water for injections.

Description of the appearance of Usymro and contents of the pack
Usymro is an injectable solution ranging from clear to slightly opalescent (pearl-like appearance), colourless to pale yellow. The solution may contain a few small translucent or white protein particles. It is supplied in a cardboard pack containing one single dose in a 1 mL glass pre-filled syringe. Each pre-filled syringe contains one dose of ustekinumab 45 mg in 0.5 mL of injectable solution.

Marketing Authorisation Holder
Gedeon Richter Plc.
Gyömrői út 19-21.
1103 Budapest
Hungary

Manufacturer
Cilatus Manufacturing Services Limited
Pembroke House, 28-32
Upper Pembroke Street
Dublin 2, D02 EK84
Ireland

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

Instructions for administration
At the beginning of treatment, your doctor will assist you with the first injection. However, you and your doctor may decide whether you can self-inject Usymro. If so, you will be taught how to self-inject Usymro. Inform your doctor if you have any questions about self-injection.

• Do not mix Usymro with other injectable liquids.
• Do not shake the pre-filled syringes of Usymro, as vigorous shaking may damage the medicine. Do not use the medicine if it has been shaken vigorously.

Figure 1 shows the appearance of the pre-filled syringe

Figure 1

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

Prepare for using the pre-filled syringes.

• Remove the pre-filled syringe or multiple pre-filled syringes from the refrigerator. Leave the pre-filled syringe outside the carton for about half an hour. This will allow the liquid to reach a comfortable injection temperature (room temperature). Do not remove the needle protective cap while waiting for the syringe to reach room temperature.
• Hold the pre-filled syringe by its barrel with the covered needle pointing upwards.
• Do not hold it by the plunger head, plunger rod, needle guard wings, or needle protective cap.
• Under no circumstances should the plunger be pulled back.
• Do not remove the needle cap from the pre-filled syringe until ready to use.

Inspect the pre-filled syringe to ensure the following:

• The number of pre-filled syringes and the dose are correct; if your dose is 45 mg, you will use one 45 mg pre-filled syringe of Usymro; if your dose is 90 mg, you will use two 45 mg pre-filled syringes of Usymro and will need to administer two injections. Choose two different body sites for these injections (e.g., one injection in the right thigh and the other in the left thigh), and proceed with the injections one after the other.
• The medicine is the correct one.
• The medicine has not expired.
• The pre-filled syringe is not damaged.
• The solution in the pre-filled syringe is clear or slightly opalescent (pearl-like appearance) and colorless to pale yellow.
• The liquid in the pre-filled syringe does not have a changed or cloudy color and does not contain foreign particles.
• The solution in the pre-filled syringe is not frozen.

Gather all necessary supplies and place them on a clean surface. You will need antiseptic wipes, a cotton ball or gauze, and a sharps container.

2. Choose and prepare the injection site

Choose an injection site (see Figure 2).

• Usymro is administered by injection under the skin (subcutaneously).
• A suitable place for the injection is the upper part of the thigh or around the abdomen (abdomen), at least 5 cm away from the navel.
• If possible, avoid areas of skin with signs of psoriasis.
• If someone is assisting you during the injection, the upper arm may also be used as an injection site.

*The grey areas indicate recommended injection sites
Figure 2
Prepare the injection site

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

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

• The needle protective cap must not be removed until you are ready to inject the dose.
• Hold the prefilled syringe by its body with one hand.
• Remove and discard the needle protective cap. Do not touch the plunger during this procedure.

Figure 3

• If you notice an air bubble in the prefilled syringe or a drop of liquid at the needle tip, this is normal. Do not remove them.
• Do not touch the needle and avoid contact between the needle and any surface.
• Do not use the prefilled syringe if it is removed without the needle protective cap in place. If this happens, consult your doctor or pharmacist.
• Inject the contents immediately after removing the needle protective cap.

4. Inject the dose

• Hold the pre-filled syringe with one hand between the middle finger and index finger, placing the thumb on the plunger head. Use the other hand to gently pinch the cleaned area of skin between the thumb and index finger. Do not pinch the skin too tightly.
• Do not pull back the plunger in any way.
• With one quick motion, insert the needle into the skin as deeply as possible (see Figure 4).

Figure 4

• Inject all the liquid by pushing the plunger until the plunger head is completely inside the needle guard wings (see Figure 5).

Figure 5

• Push the plunger until it reaches the end of its travel, and continue to press on the plunger head while withdrawing the needle and gently releasing the skin (see Figure 6).

Figure 6

• Slowly remove your thumb from the plunger head to allow the empty syringe to move upward, so that the needle is completely covered by the needle guard wings, as shown in Figure 7.

Figure 7

5. After the injection

• Press an antiseptic swab on the injection site for a few seconds after the injection.
• There may be a small amount of blood or fluid 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: you may cover the injection site with a small plaster, if needed.

6. Disposal

• Used syringes must be placed in a puncture-resistant container, such as a sharps container (see Figure 8). For your health and safety and for the safety of others, never reuse the syringe. Dispose of the sharps container according to local regulations.
• Antiseptic swabs and other devices may be disposed of in regular waste.

Figure 8

Package leaflet: information for the user

Usymro 90 mg solution for injection in pre-filled syringe

ustekinumab
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read all of this leaflet carefully before using this medicine because it contains important information for you.
This leaflet has been written for people who are taking this medicine. If you are the parent or caregiver of a child who needs to be given Usymro, please read this information carefully.

• Keep this leaflet. 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. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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 side 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 recognise and bind to specific proteins in the body.
Usymro belongs to a group of medicines called "immunosuppressants". These medicines partially reduce the activity 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)
• moderately to severely active Crohn’s disease in adults and children weighing at least 40 kg

Plaque psoriasis
Plaque psoriasis is a skin condition causing inflammation of the skin and nails.
Usymro will reduce inflammation and other signs of the disease.
Usymro is used in adults with moderate to severe plaque psoriasis who cannot use ciclosporin, methotrexate or phototherapy, or in whom these treatments are ineffective.
Usymro is used in children and adolescents from 6 years of age with moderate to severe plaque psoriasis who cannot tolerate phototherapy or other systemic therapies, or when these treatments have not worked.

Psoriatic arthritis
Psoriatic arthritis is an inflammatory joint disease, usually associated with psoriasis. If you have active psoriatic arthritis, you will first be treated with other medicines. If you do not respond adequately to these medicines, you may be given Usymro to:

• reduce the signs and symptoms of the disease
• improve physical function
• slow down joint damage.

Crohn’s disease
Crohn’s disease is an inflammatory bowel disease. If you have Crohn’s disease, you will first be treated with other medicines. If you do not respond adequately or are intolerant to these 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 important.

If you are unsure whether any of the conditions listed above apply to you, talk to your doctor or pharmacist before using Usymro.
Warnings and precautions
Talk to your doctor or pharmacist before using Usymro. Your doctor will check your health status before each treatment. Make sure to inform your doctor about any medical conditions you have before each treatment. Also, inform your doctor if you have recently been in contact with people who may have had tuberculosis. Your doctor will examine you and perform tests for tuberculosis before administering Usymro. If your doctor believes you are at risk of tuberculosis, you may be given medicines to treat tuberculosis.
Be aware of serious side effects
Usymro can cause serious side effects, including allergic reactions and infections. You should pay attention to certain signs of illness while taking Usymro. See “Serious side effects” in section 4 for a complete list of these side effects.
Before using Usymro, contact your doctor

• If you have ever had an allergic reaction to Usymro. Ask your doctor if you are unsure.

• If you have ever had any type of cancer – because immunosuppressants like Usymro partially weaken the immune system. This may increase the risk of cancer.

• If you have been treated for psoriasis with other biological medicines (a medicinal product 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.

• If you have ever had any new or changed skin lesions within the area of psoriasis or on normal skin.

• If you have ever had an allergic reaction to latex or to the injection of Usymro – the container of this medicinal product contains latex, which may cause severe allergic reactions in people who are sensitive to latex. See “Be aware of serious side effects” in section 4 for signs of an allergic reaction.

• If you are taking any other treatment for psoriasis and/or psoriatic arthritis – such as another immunosuppressant or phototherapy (when the body is treated with a type of ultraviolet (UV) light). These treatments may also partially reduce the activity of the immune system. The concomitant use of these therapies with Usymro has not been studied. However, it may increase the likelihood of conditions related to a weakened immune system.

• If you are using or have ever used injections for the treatment of allergies – it is not known whether Usymro may affect them.

• If you are aged 65 years or older – you may have a higher risk of developing infections.

If you are unsure whether any of the conditions listed above apply to you, talk to your doctor or pharmacist before starting treatment with Usymro.
During treatment with ustekinumab, some patients have developed lupus-like reactions, including cutaneous lupus or lupus-like syndrome (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
In a study of patients with psoriasis treated with ustekinumab, heart attacks and strokes were observed. Your doctor will regularly monitor risk factors for heart disease and stroke to ensure they are appropriately managed. Seek immediate medical attention if you develop chest pain, weakness or unusual sensations on one side of the body, facial drooping, or speech or vision problems.
Children and adolescents
Usymro is not recommended for the treatment of 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 take any other medicines
• if you have recently been vaccinated or are about to be vaccinated. Some types of vaccines (live vaccines) should not be given while you are using Usymro.
• if you received Usymro during pregnancy, inform your child’s paediatrician about the treatment with Usymro before your child receives any vaccine, including live vaccines such as the BCG vaccine (used to prevent tuberculosis). If you received Usymro during pregnancy, live vaccines are not recommended for your child during the first twelve months after birth, unless otherwise recommended by your child’s paediatrician.

Pregnancy and breastfeeding

• If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor before taking this medicine.
• In newborns exposed to ustekinumab in the womb, no increased risk of congenital malformations has been observed. However, experience with ustekinumab in pregnant women is limited. Therefore, it is preferable to avoid using Usymro during pregnancy.
• If you are of childbearing potential, it is advisable to avoid becoming pregnant; you should use an adequate method of contraception during treatment with Usymro and for at least 15 weeks after stopping treatment with Usymro.
• Usymro can pass to the unborn child through the placenta. If you received Usymro during pregnancy, your child may have an increased risk of developing an infection.
• If you received Usymro during pregnancy, it is important to inform your child’s paediatrician and other healthcare providers before your child receives any vaccine. If you received Usymro during pregnancy, live vaccines such as the BCG vaccine (used to prevent tuberculosis) are not recommended for your child during the first twelve months after birth, unless otherwise recommended by the paediatrician.
• Ustekinumab may be excreted in breast milk in very small amounts. If you are breastfeeding or plan to breastfeed, consult your doctor. You and your doctor will decide whether you should breastfeed or use Usymro. You cannot do both.

Driving and using machines
Usymro has no effect or a negligible effect on the ability to drive vehicles and use machines.
Usymro contains polysorbate 80
This medicine contains 0.10 mg of polysorbate 80 (E433) per pre-filled syringe (PFS) of 90 mg/mL, equivalent to 0.10 mg/mL. Polysorbates may cause allergic reactions. Inform your doctor if you or your child have 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.
Use this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor. Discuss with your doctor when you should receive your injections and follow-up appointments.

How much Usymro is administered

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

Adults from 18 years of age

Psoriasis and psoriatic arthritis

• The recommended initial dose is 45 mg of Usymro. Patients with a body weight greater than 100 kilograms (kg) may start with a dose of 90 mg instead of 45 mg.
• Four weeks after the initial dose, you will receive the next dose, followed by subsequent doses every 12 weeks. The following doses are usually the same as the initial dose.

Crohn’s disease

• During treatment, the first dose of approximately 6 mg/kg of Usymro is administered by your doctor through an intravenous infusion (IV infusion) into the arm. Eight weeks after the initial dose, you will receive the next dose of 90 mg of Usymro, followed by subcutaneous injections (under the skin) every 12 weeks.
• In some patients, after the first subcutaneous injection, the 90 mg dose of Usymro may be administered every 8 weeks. Your doctor will decide when the next dose should be given.

Children and adolescents from 6 years of age

Psoriasis

• Your doctor will calculate the correct dose, including the amount (volume) of Usymro to be injected to ensure the correct dose is administered. The correct dose will depend on the child's body weight at the time each dose is given.
• A 45 mg vial is available if a lower dose than 45 mg is required.
• If body weight is less than 60 kg, the recommended dose is 0.75 mg of Usymro per kg of body weight.
• If body weight is between 60 kg and 100 kg, the recommended dose is 45 mg of Usymro.
• If body weight exceeds 100 kg, the recommended dose is 90 mg of Usymro.
• Four weeks after the initial dose, you will receive the next dose, followed by doses every 12 weeks.

Children weighing at least 40 kg

Crohn’s disease

• During treatment, the first dose of approximately 6 mg/kg of Usymro is administered by your doctor through an intravenous infusion (IV infusion) into the arm. Eight weeks after the initial dose, you will receive the next dose of 90 mg of Usymro, followed by subcutaneous injections (under the skin) every 12 weeks.
• In some patients, after the first subcutaneous injection, the 90 mg dose of Usymro may be administered every 8 weeks. Your doctor will decide when the next dose should be given.

How Usymro is administered

• Usymro is administered by subcutaneous injection ("subcutaneously"). At the beginning of treatment, medical or nursing staff may administer Usymro to you.
• However, you and your doctor may decide whether you can self-inject Usymro. In this 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.

Inform your doctor if you have any questions about self-injection.
If you use more Usymro than you should
If you have used or received too much Usymro, inform your doctor or pharmacist immediately. Always bring the outer packaging of the medicine 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 the missed dose.
If you stop using Usymro
Stopping treatment with Usymro is not dangerous. However, if you discontinue treatment, symptoms may return.
If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious side effects

Some patients may experience serious side effects that may require treatment.

Allergic reactions – these may require urgent treatment, so contact your doctor or seek emergency medical help if you notice any of the following signs.

• Severe allergic reactions ("anaphylaxis") are rare in patients taking Usymro (affecting up to 1 in 1,000 patients). Signs include:

  o difficulty breathing or swallowing
  o low blood pressure, which may cause dizziness or a feeling of lightheadedness
  o swelling of the face, lips, mouth or throat.

• Common signs of an allergic reaction include rash and hives (affecting up to 1 in 100 patients).

In rare cases, allergic lung reactions and lung inflammation have been reported in patients receiving ustekinumab. Inform your doctor immediately if you develop symptoms such as cough, shortness of breath, and fever.

If you experience a severe allergic reaction, your doctor may decide that you should no longer use Usymro.

Infections – these may require urgent treatment, so contact your doctor immediately if you notice any of the following signs.

• Nasal, throat infections and common cold are common (affecting up to 1 in 10 patients).
• Chest infections are uncommon (may affect up to 1 in 100 patients).
• Inflammation of the tissue under the skin ("cellulitis") is uncommon (affects up to 1 in 100 patients).
• Herpes zoster (a type of painful blistering rash) is uncommon (affects up to 1 in 100 patients).

Usymro may reduce your ability to fight infections. Some infections may become serious and may include those caused by viruses, fungi, bacteria (including tuberculosis) or parasites, including infections that mainly occur in people with weakened immune systems (opportunistic infections). Opportunistic infections of the brain (encephalitis, meningitis), lungs and eyes have been reported in patients treated with ustekinumab.

You should be aware of signs of infection while using Usymro. These include:

• fever, flu-like symptoms, night sweats, weight loss
• feeling tired or short of breath, persistent cough
• warmth, redness, pain, or a painful blistering rash on the skin
• burning sensation when urinating
• diarrhoea
• vision problems or loss of vision
• headache, neck stiffness, sensitivity to light, nausea or confusion

Inform your doctor immediately if you notice any of these signs of infection. These may be symptoms of infections such as chest infections, skin infections, herpes zoster or opportunistic infections, which can have serious complications. Consult your doctor if you have any infection that persists or keeps recurring. Your doctor may decide to stop Usymro until the infection resolves. Also inform your doctor if you have any cuts or open wounds 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 conditions. If you notice any of these signs, inform your doctor immediately.

Other side effects

Common side effects (may affect up to 1 in 10 people)

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

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

• Dental infections
• Vaginal fungal infection
• Depression
• Stuffy or runny nose
• Bleeding, bruising, stiffness, swelling and itching at the injection site
• Feeling weak
• Drooping eyelid and 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 (exfoliation of the skin)
• Acne

Rare side 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 be itchy or painful (exfoliative dermatitis). Similar symptoms sometimes develop as a natural progression in the type of psoriasis symptoms (erythrodermic psoriasis)
• Inflammation of small blood vessels, which may lead to a rash with small red or purple spots, fever or joint pain (vasculitis)

Very rare side effects (may affect up to 1 in 10,000 people)

• Formation of skin blisters, possibly with redness, itching and pain (bullous pemphigoid)
• Cutaneous lupus or lupus-like syndrome (red, raised, scaly rash on areas of skin exposed to sunlight, sometimes with joint pain)

Reporting of side effects

If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Usymro

• Keep this medicine out of the sight and reach of children.
• Store in the refrigerator (2 °C–8 °C). Do not freeze.
• Keep the pre-filled syringe in the outer packaging to protect the medicine from light.
• If necessary, individual pre-filled syringes of Usymro may also be stored at room temperature up to 30 °C for a single period of up to 40 days, while remaining in the outer packaging to protect them from light. Record the date when the pre-filled syringe is first removed from the refrigerator and the date by which it must be discarded in the designated space on the outer packaging. The discard date must not exceed the original expiry date printed on the packaging.

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 not used within 40 days at room temperature or by 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 carton after "Exp". The expiry date refers to the last day of that month.
• If the solution has changed colour, is cloudy, or if you see foreign particles floating in it (see section 6 "Description of the appearance of Usymro and contents of the pack").
• If you know or suspect that the medicine has been exposed to extreme temperatures (e.g. accidentally frozen or overheated).
• If the product has been shaken vigorously.

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

6. Package contents and other information

What Usymro contains

• The active substance is ustekinumab. Each pre-filled syringe contains 90 mg of ustekinumab in 1 mL.
• The other components are: L-histidine, L-histidine monohydrochloride monohydrate, polysorbate 80 (E433), sucrose, water for injections.

Description of the appearance of Usymro and contents of the pack
Usymro is an injectable solution from clear to slightly opalescent (pearl-like appearance), colourless to pale yellow. The solution may contain a few small translucent or white protein particles. It is supplied in a cardboard pack containing one single dose in a 1 mL glass pre-filled syringe. Each pre-filled syringe contains one dose of ustekinumab 90 mg in 1 mL of injectable solution.

Marketing Authorization Holder
Gedeon Richter Plc.
Gyömrői út 19-21.
1103 Budapest
Hungary

Manufacturer
Cilatus Manufacturing Services Limited
Pembroke House, 28-32
Upper Pembroke Street
Dublin 2, D02 EK84
Ireland

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

Instructions for administration
At the beginning of treatment, your doctor will assist you with the first injection. However, you and your doctor may decide whether you can self-inject Usymro. In this case, you will be taught how to self-inject Usymro. Inform your doctor if you have any questions regarding self-injection.

• Do not mix Usymro with other injectable liquids.
• Do not shake the pre-filled syringes of Usymro, as vigorous shaking may damage the medicine. Do not use the medicine if it has been shaken vigorously.

Figure 1 shows the appearance of the pre-filled syringe.

Figure 1

1. Check the number of prefilled syringes and prepare materials

Prepare for the use of prefilled syringes.

• Remove the prefilled syringe or prefilled syringes from the refrigerator. Leave the prefilled syringe outside the carton for about 30 minutes. This will allow the liquid to reach a comfortable temperature for injection (room temperature). Do not remove the needle protective cap while waiting for the syringe to reach room temperature.
• Hold the prefilled syringe by its barrel with the covered needle pointing upwards.
• Do not hold it by the plunger rod, plunger, needle safety shield, or needle protective cap.
• Under no circumstances should the plunger be pulled back.
• Do not remove the needle cap from the prefilled syringe until ready for use.

Inspect the prefilled syringe to ensure that:

• the number of prefilled syringes and the dose are correct; if your dose is 90 mg, you will take one 90 mg prefilled syringe of Usymro
• the medicine is the correct one
• the medicine has not expired
• the prefilled syringe is not damaged
• the solution in the prefilled syringe is clear or slightly opalescent (pearl-like appearance) and colorless to pale yellow
• the liquid in the prefilled syringe does not have an altered or cloudy color and contains no foreign particles
• the solution in the prefilled syringe has not been frozen.

Gather all necessary supplies and place them on a clean surface. You will need antiseptic wipes, a cotton ball or gauze, and a sharps container.

2. Choose and prepare the injection site

Choose an injection site (see Figure 2).

• Usymro is administered by injection under the skin (subcutaneously).
• A suitable injection site is the upper part of the thigh or around the abdomen (abdomen), at least 5 cm away from the navel.
• If possible, avoid areas of skin with signs of psoriasis.
• If someone is assisting you during the injection, the upper arms may also be used as an injection site.

*The grey areas indicate the recommended injection sites
Figure 2
Prepare the injection site.

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

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

• The needle protective cap must not be removed until you are ready to inject the dose.
• Hold the pre-filled syringe by its body with one hand.
• Remove and discard the needle protective cap. Do not touch the plunger during this operation.

Figure 3

• If you notice an air bubble in the pre-filled syringe or a drop of liquid at the tip of the needle, this is normal. Do not remove them.
• Do not touch the needle and avoid contact between the needle and any surface.
• Do not use the pre-filled syringe if it is removed without the needle protective cap in place. If this happens, consult your doctor or pharmacist.
• Inject the contents immediately after removing the needle protective cap.

4. Inject the dose

• Hold the prefilled syringe in one hand between the middle finger and index finger, with the thumb placed on top of the plunger head. Use the other hand to gently pinch the cleaned area of skin between the thumb and index finger. Do not squeeze too tightly.
• Under no circumstances pull back on the plunger.
• With one quick, swift motion, insert the needle into the skin as far as possible (see Figure 4).

Figure 4

• Inject all the liquid by pushing the plunger until the plunger head is completely within the needle guard wings (see Figure 5).

Figure 5

• Push the plunger until it reaches the end of its travel and continue to keep pressure on the plunger head while removing the needle and gently releasing the skin (see Figure 6).

Figure 6

• Slowly remove your thumb from the plunger head, allowing the empty syringe to rise upward so that the needle is completely covered by the needle guard wings, as shown in Figure 7.

Figure 7

5. After the injection

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

6. Disposal

• Used syringes must be placed in a puncture-resistant container, such as a sharps container (see Figure 8). For your safety and the safety of others, never reuse the syringe. Dispose of the sharps container according to local regulations.
• Antiseptic swabs and other devices may be discarded in regular waste.

Figure 8