Otulfi

Package leaflet: Information for the user

Otulfi 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 are taking 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, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Otulfi is and what it is used for

What Otulfi is
Otulfi contains the active substance "ustekinumab", a monoclonal antibody.
Monoclonal antibodies are proteins that recognise and bind to specific proteins in the body.
Otulfi belongs to a group of medicines called "immunosuppressants". These medicines reduce the activity of the immune system to some extent.

What Otulfi is used for
Otulfi is used to treat the following inflammatory disease:

• 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 sufficiently or are intolerant to these medicines, Otulfi may be given to reduce the signs and symptoms of your disease.

2. What you need to know before using Otulfi

Do not use Otulfi

• If you are allergic to ustekinumab or to any of the other ingredients of this medicine (listed in section 6 below)
• 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 Otulfi.
Warnings and precautions
Talk to your doctor or pharmacist before using Otulfi. 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 carry out tests for tuberculosis before administering Otulfi. If your doctor believes you are at risk of tuberculosis, you may be given medicines to treat it.
Be aware of serious side effects
Otulfi can cause serious side effects, including allergic reactions and infections. You should pay attention to certain signs of illness while taking Otulfi. See “Serious side effects” in section 4 for a complete list of these side effects.
Before using Otulfi, contact your doctor

• If you have ever had an allergic reaction to ustekinumab. Ask your doctor if you are unsure.
• If you have ever had any type of cancer – because immunosuppressants like Otulfi 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 and usually administered by injection) – the risk of cancer may be higher.
• If you currently have or have recently had an infection or have abnormal openings in the skin (fistulas).
• If you have ever had any new or changing 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 Otulfi has not been studied. However, it could potentially increase the risk of conditions related to a weakened immune system.
• If you are using or have ever used allergy injections – it is not known whether Otulfi 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, speak with your doctor or pharmacist before starting treatment with Otulfi.

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, in 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 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 a strange sensation on one side of the body, facial drooping, or speech or vision problems.
Children and adolescents
Otulfi 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 Otulfi
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 scheduled to be vaccinated. Some types of vaccines (live vaccines) should not be administered while you are using Otulfi.
• if you received Otulfi during pregnancy, inform your child’s paediatrician about the Otulfi treatment before your child receives any vaccines, including live vaccines such as the BCG vaccine (used to prevent tuberculosis). If you received Otulfi during pregnancy, live vaccines are not recommended for your child during the first twelve months after birth, unless otherwise advised by your child’s paediatrician. Pregnancy and breastfeeding
• If you are pregnant, think you may be pregnant, or are planning to become pregnant, ask your doctor for advice 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 Otulfi 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 Otulfi and for at least 15 weeks after stopping treatment with Otulfi.
• Ustekinumab can pass to the unborn child through the placenta. If you received Otulfi during pregnancy, your child may have an increased risk of developing an infection.
• If you received Otulfi during pregnancy, it is important to inform your child’s paediatrician and other healthcare providers before your child receives any vaccines. If you received Otulfi 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 advised 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 Otulfi. You cannot do both. Driving and using machines Otulfi has no or negligible effect on the ability to drive vehicles and use machines.

Otulfi contains sodium
Otulfi contains less than 1 mmol of sodium (23 mg) per dose, i.e., it is essentially "sodium-free".
However, before Otulfi is administered, it is mixed with a solution containing sodium.
Talk to your doctor if you are on a low-salt diet.
Otulfi contains polysorbate 80 (E 433)
This medicine contains 10.4 mg of polysorbate 80 per 26 ml vial, equivalent to 0.4 mg/ml. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How Otulfi will be used

Otulfi is intended for use under the guidance and supervision of a physician experienced in the diagnosis and treatment of Crohn's disease.
Your doctor will administer Otulfi 130 mg concentrate for solution for infusion to you via an intravenous drip into a vein in your arm (intravenous infusion) for at least one hour. Discuss with your doctor when you should have your injections and follow-up visits.

How much Otulfi will be administered
Your doctor will decide how much Otulfi 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.
  Body weight       Dose
  ≤ 55 kg           260 mg

55 kg to ≤ 85 kg    390 mg
85 kg            520 mg

• After the initial intravenous dose, you will receive the next dose of 90 mg Otulfi as an injection under the skin (subcutaneous injection) 8 weeks later, and then every 12 weeks thereafter.

Children with Crohn's disease weighing at least 40 kg

• Your doctor will calculate the recommended intravenous infusion dose based on body weight.
  Body weight       Dose
  ≥ 40 to ≤ 55 kg     260 mg

55 kg to ≤ 85 kg    390 mg
85 kg            520 mg

• 8 weeks after the initial intravenous dose, you will receive the next dose of 90 mg Otulfi as a subcutaneous injection, followed by doses every 12 weeks thereafter.

How Otulfi is administered
The first dose of Otulfi for the treatment of Crohn's disease is administered by your doctor through an intravenous drip into your arm (intravenous infusion). Inform your doctor if you have any questions about the use of Otulfi.

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

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

4. Possible 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 urgent treatment.

Allergic reactions – these may require urgent treatment; therefore, 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 ustekinumab (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).

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

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

Infections – these may require urgent treatment; therefore, 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).

Otulfi may reduce your body’s 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 typically 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 the signs of infection while using Otulfi. 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
• visual 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 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 Otulfi 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 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)

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

• Otulfi 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 its outer packaging to protect the medicine from light.
• Do not shake the vials of Otulfi. 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 the month.
• If the solution has changed colour, is cloudy, or if foreign particles are visible floating in it (see section 6 “Description of the appearance of Otulfi and contents of the container”).
• 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.

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

6. Package contents and other information

What Otulfi contains

• The active substance is ustekinumab. Each vial contains 130 mg of ustekinumab in 26 mL.
• The excipients are: disodium EDTA dihydrate (E385), L-histidine, L-histidine monohydrochloride monohydrate, L-methionine, polysorbate 80 (E433), sucrose, water for injections. Description of the appearance of Otulfi and contents of the pack Otulfi is a clear concentrate for infusion solution, colourless to slightly brownish-yellow. It is supplied in a cardboard 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
Fresenius Kabi Deutschland GmbH
Else-Kroener-Strasse 1
61352 Bad Homburg v.d.Hoehe
Germany
Manufacturer
Fresenius Kabi Austria GmbH
Hafnerstraße 36
8055 Graz Austria
More detailed information on this medicine is available on the European Medicines Agency website: https://www.ema.europa.eu/
The following information is intended for healthcare professionals only.
Traceability
In order to improve the traceability of biological medicinal products, the trade name and batch number of the administered product must be clearly recorded.
Instructions for dilution.
Otulfi concentrate for infusion solution must be diluted, prepared and infused by a healthcare professional using aseptic technique.

1. Calculate the dose and the number of Otulfi vials required based on the patient's body weight (see section 3, Table 1, Table 2). Each 26 mL vial of Otulfi 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 Otulfi to be added (discard 26 mL of sodium chloride for each required Otulfi vial: for 2 vials discard 52 mL, for 3 vials discard 78 mL, for 4 vials discard 104 mL).
3. Withdraw 26 mL of Otulfi from each required vial and add it to the 250 mL infusion bag. The final volume in the infusion bag must be 250 mL. Mix gently.
4. Visually inspect the diluted solution before infusion. Do not use if visible 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 24 hours of dilution in the infusion bag.
6. Use a single infusion set with an in-line sterile, non-pyrogenic, low protein-binding filter (pore size 0.2 micrometres).
7. Each vial is for single use only and any unused medicine must be disposed of in accordance with local regulations.

Storage
If necessary, the diluted infusion solution should be stored at room temperature.
The infusion must be completed within 24 hours of dilution in the infusion bag. Do not freeze.

Package leaflet: Information for the user

Otulfi 45 mg solution for injection

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 taking this medicine. If you are the parent or caregiver of a child who is to be given Otulfi, please read these instructions carefully before administration.

• 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 they have the same symptoms as you, because it may 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 Otulfi is and what it is used for
2. What you need to know before using Otulfi
3. How to use Otulfi
4. Possible side effects
5. How to store Otulfi
6. Contents of the pack and other information

1. What Otulfi is and what it is used for

What Otulfi is
Otulfi contains the active substance "ustekinumab", a monoclonal antibody. Monoclonal antibodies are proteins that recognise and bind to specific proteins in the body.
Otulfi belongs to a group of medicines called "immunosuppressants". These medicines reduce the activity of the immune system to some extent.

What Otulfi is used for
Otulfi 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. Otulfi will reduce inflammation and other signs of the disease.
Otulfi is used in adults with moderate to severe plaque psoriasis who cannot use ciclosporin, methotrexate, or phototherapy, or in whom these treatments are ineffective.
Otulfi 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 Otulfi 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 sufficiently or are intolerant to these medicines, Otulfi may be given to reduce the signs and symptoms of your disease.

2. What you need to know before using Otulfi

Do not use Otulfi

• If you are allergic to ustekinumab or to any of the other ingredients of this medicine (listed in section 6 below).
• 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 Otulfi.
Warnings and precautions
Talk to your doctor or pharmacist before using Otulfi. 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. Additionally, 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 Otulfi. If your doctor believes you are at risk for tuberculosis, you may be given medications to treat tuberculosis. Be aware of serious side effects
Otulfi may cause serious side effects, including allergic reactions and infections. You should pay attention to certain signs of illness while taking Otulfi. See "Serious side effects" in section 4 for a complete list of these side effects.
Before using Otulfi, contact your doctor:

• If you have ever had an allergic reaction to ustekinumab. Ask your doctor if you are unsure.
• If you have ever had any type of cancer – because immunosuppressants like Otulfi 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 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 affected by 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 exposed to a type of ultraviolet (UV) light). These treatments may also partially reduce immune system activity. The concomitant use of these therapies with Otulfi has not been studied. However, it could potentially increase the risk of conditions related to a weakened immune system.
• If you are using or have ever used allergy injections for the treatment of allergies – it is not known whether Otulfi may affect them.
• If you are aged 65 years or older – you may have an increased risk of developing infections.

If you are unsure whether any of the conditions listed above apply to you, discuss them with your doctor or pharmacist before starting treatment with Otulfi.
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, in sun-exposed areas of skin or if you experience joint pain.
Heart attack and stroke
In a study of patients with psoriasis treated with Otulfi, 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 a strange sensation on one side of the body, facial drooping, or speech or vision problems.
Children and adolescents
Otulfi 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 Otulfi
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 scheduled to be vaccinated. Some types of vaccines (live vaccines) should not be administered while you are using Otulfi.
• if you received Otulfi during pregnancy, inform your child’s paediatrician about the Otulfi treatment before your child receives any vaccine, including live vaccines such as the BCG vaccine (used to prevent tuberculosis). If you received Otulfi 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, suspect 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 infants exposed to ustekinumab in utero. However, experience with ustekinumab in pregnant women is limited. Therefore, it is preferable to avoid using Otulfi 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 Otulfi and for at least 15 weeks after stopping treatment with Otulfi.
• Ustekinumab can cross the placenta and reach the unborn child. If you received Otulfi during pregnancy, your child may have an increased risk of developing infections.
• If you received Otulfi during pregnancy, it is important to inform your child’s paediatrician and other healthcare providers before your child receives any vaccine. If you received Otulfi 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 Otulfi. You cannot do both.

Driving and using machines
Otulfi has no effect or has a negligible effect on the ability to drive vehicles or use machinery.
Otulfi contains polysorbate 80 (E 433)
This medicine contains 0.02 mg of polysorbate 80 per 0.5 mL vial, equivalent to 0.04 mg/mL. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergies.

3. How to use Otulfi

Otulfi is intended for use under the guidance and supervision of a physician experienced in the treatment of the conditions for which Otulfi 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 Otulfi is administered

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

Adults from 18 years of age

Psoriasis and psoriatic arthritis

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

Children and adolescents from 6 years of age

Psoriasis

• Your doctor will calculate the correct dose, including the amount (volume) of Otulfi 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.
• If body weight is less than 60 kg, the recommended dose is 0.75 mg of Otulfi per kg of body weight.
• If body weight is between 60 kg and 100 kg, the recommended dose is 45 mg of Otulfi.
• If body weight exceeds 100 kg, the recommended dose is 90 mg of Otulfi.
• After the initial dose, the next dose should be administered 4 weeks later, and then every 12 weeks.

Children weighing at least 40 kg

Crohn’s disease

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

How Otulfi is administered

• Otulfi is administered via subcutaneous injection (“subcutaneously”). At the beginning of treatment, medical or nursing staff may administer Otulfi to you.
• However, you and your doctor may decide whether you can self-inject Otulfi. In this case, you will be trained on how to self-inject Otulfi.
• For instructions on how to inject Otulfi, 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 Otulfi than you should

If you have used or received too much Otulfi, 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 Otulfi

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 Otulfi

Stopping treatment with Otulfi is not dangerous. However, if you stop treatment, your symptoms may return.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets 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 ustekinumab (affecting up to 1 in 1,000 patients). Signs include:

  • Difficulty breathing or swallowing, or low blood pressure, which may cause dizziness or a feeling of lightheadedness
  • 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)

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, or fever.

If you have a severe allergic reaction, your doctor may decide that you should not use Otulfi 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 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)

Otulfi 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 Otulfi. These include:

• Fever, flu-like symptoms, night sweats, weight loss
• Feeling tired or short of breath, persistent cough
• Warm, red, painful 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 symptoms of infections such as chest infections, skin infections, herpes zoster or opportunistic infections, which can have serious complications. Contact your doctor if you have any infection that persists or keeps recurring. Your doctor may decide to stop Otulfi 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
• Feeling dizzy
• 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 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)

• 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 get 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 Otulfi

• 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 Otulfi 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 the 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 Otulfi 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 vigorously shaken.
• If the seal is broken.

Otulfi 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 Otulfi contains

• The active substance is ustekinumab. Each vial contains 45 mg of ustekinumab in 0.5 mL.
• The excipients are: L-histidine, polysorbate 80 (E433), sucrose, water for injections, and hydrochloric acid (used to adjust pH).

Description of the appearance of Otulfi and contents of the pack
Otulfi is a clear solution for injection, colourless to slightly yellowish-brown. It is supplied in a
cardboard pack containing 1 single dose in a 3 mL glass vial. Each vial contains a single dose of
ustekinumab 45 mg in 0.5 mL of solution for injection.
Marketing Authorisation Holder
Fresenius Kabi Deutschland GmbH
Else-Kroener-Strasse 1
61352 Bad Homburg v.d.Hoehe
Germany
Manufacturer
Fresenius Kabi Austria GmbH Hafnerstraße 36
8055 Graz
Austria
More detailed information on this medicine is available on the European Medicines Agency website:
https://www.ema.europa.eu.
Instructions for administration
At the beginning of treatment, your doctor will assist you during the first injection. However, you and your doctor may decide whether you can self-inject Otulfi. If so, you will be taught how to self-inject Otulfi. Inform your doctor if you have any questions about self-injection.

• Do not mix Otulfi with other injectable liquids.
• Do not shake the vials of Otulfi, 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
thirty minutes. This will allow the liquid to reach a comfortable temperature for injection
(room temperature).
Check the following:

• the number of vials and the dose are correct; if your dose is 45 mg or less, you will take one 45 mg vial of Otulfi; if your dose is 90 mg, you will take two 45 mg vials of Otulfi and will need to perform two injections. Choose two different body sites for these injections (for example, one injection in the right thigh and the other injection in the left thigh), and carry out 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, from colourless to slightly yellowish-brown
• the liquid does not have a changed or cloudy colour and does not contain foreign particles
• it has not been frozen.

Children with paediatric psoriasis weighing less than 60 kg require a dose lower than 45 mg. Be certain of the appropriate amount (volume) to withdraw from the vial and of 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. The supplies should include a syringe, needle, antiseptic wipes, 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).

• Otulfi 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 with the injection, the upper arm may also be used as an injection site.

*The grey areas indicate 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.
• Push the needle through the rubber stopper.
• Invert the vial and syringe.
• Pull back the plunger of the syringe to draw up the prescribed amount of liquid.
• It is important that the needle tip remains inside 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 upward to check for any air bubbles.
• If there are air bubbles, gently tap the side of the syringe until the air bubbles rise to the top of the syringe (see Figure 5).

Figure 5

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

4. Inject the dose

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

5. After the injection

• Press a 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 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 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 disposed of in the waste.

Package leaflet: Information for the user

Otulfi 45 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 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 a parent or caregiver of a child who is to be given Otulfi, please read these instructions carefully before administration.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult 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, consult your doctor or pharmacist. See section 4. Contents of this leaflet
  1. What Otulfi is and what it is used for
  2. What you need to know before using Otulfi
  3. How to use Otulfi
  4. Possible side effects
  5. How to store Otulfi
  6. Contents of the pack and other information

1. What Otulfi is and what it is used for

What Otulfi is
Otulfi contains the active substance "ustekinumab", a monoclonal antibody.
Monoclonal antibodies are proteins that recognise and bind to specific proteins in the body.
Otulfi belongs to a group of medicines called "immunosuppressants". These medicines reduce the activity of the immune system to some extent.

What Otulfi is used for
Otulfi 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.
Otulfi will reduce inflammation and other signs of the disease.
Otulfi is used in adults with moderate to severe plaque psoriasis who cannot use cyclosporine, methotrexate or phototherapy, or in whom these treatments have not worked.
Otulfi 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 been effective.

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 Otulfi 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 sufficiently or are intolerant to these medicines, Otulfi may be given to reduce the signs and symptoms of your disease.

2. What you need to know before using Otulfi

Do not use Otulfi

• If you are allergic to ustekinumab or to any of the other ingredients of this medicine (listed in section 6 below).
• 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 Otulfi.
Warnings and precautions
Talk to your doctor or pharmacist before using Otulfi. Your doctor will check your health status
before each treatment. Make sure to inform your doctor, before each treatment, about any medical
conditions you have. In addition, 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 Otulfi to you. If your doctor believes you are at risk of tuberculosis, you may be
given medicines to treat tuberculosis.
Be aware of serious side effects
Otulfi can cause serious side effects, including allergic reactions and infections. You should be alert to
certain signs of illness while taking Otulfi. See “Serious side effects” in section 4 for a complete list of
these side effects.
Before using Otulfi, contact your doctor

• If you have ever had an allergic reaction to ustekinumab – Ask your doctor if you are unsure.
• If you have ever had any type of cancer – This is because immunosuppressants such as Otulfi 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 changing skin lesions within the area of psoriasis or on normal skin.
• If you have ever had an allergic reaction to an injection of Otulfi – See “Be aware of serious side effects” in section 4 for signs of an allergic reaction.
• 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 use of these therapies together with Otulfi 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 allergy injections for the treatment of allergies – It is not known whether Otulfi 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, speak with your doctor or
pharmacist before starting treatment with Otulfi.
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 a
strange sensation on one side of the body, facial drooping, or speech or vision problems.
Children and adolescents
Otulfi is not recommended for the treatment of children with psoriasis under 6 years of age, children
with Crohn’s disease weighing less than 40 kg, or for the treatment of children under 18 years of age
with psoriatic arthritis, as it has not been studied in these age groups.
Other medicines, vaccines and Otulfi
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) must not be given while you are using Otulfi.

• if you received Otulfi during pregnancy, inform your child’s paediatrician about the treatment with Otulfi before your child receives any vaccine, including live vaccines such as the BCG vaccine (used to prevent tuberculosis). If you received Otulfi 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, ask your doctor for advice 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 Otulfi 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 Otulfi and for at least 15 weeks after stopping treatment with Otulfi.

• Ustekinumab can cross the placenta and reach the unborn child. If you received Otulfi during pregnancy, your child may have an increased risk of developing infections.

• If you received Otulfi during pregnancy, it is important that you inform your child’s paediatrician and other healthcare providers before your child receives any vaccine. If you received Otulfi 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 your child’s 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 Otulfi. You cannot do both. Driving and using machines Otulfi does not affect or has a negligible effect on the ability to drive and use machines.

Otulfi contains polysorbate 80 (E 433)
This medicine contains 0.02 mg of polysorbate 80 per 0.5 ml pre-filled syringe, equivalent to 0.04 mg/ml.
Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How to use Otulfi

Otulfi is intended for use under the guidance and supervision of a physician experienced in the treatment of the conditions for which Otulfi 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 Otulfi is administered

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

Adults from 18 years of age

Psoriasis and psoriatic arthritis

• The recommended initial dose is 45 mg of Otulfi. Patients weighing more than 100 kilograms (kg) may start with a dose of 90 mg instead of 45 mg.
• After the initial dose, you will receive the next dose 4 weeks later, and then 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 Otulfi is administered by your doctor as an intravenous infusion into your arm. After the initial dose, you will receive the next dose of 90 mg of Otulfi after 8 weeks, followed by doses every 12 weeks via subcutaneous injection (subcutaneous route).
• In some patients, after the first subcutaneous injection, the 90 mg dose of Otulfi may be administered every 8 weeks. Your doctor will decide when you should receive the next dose.

Children and adolescents from 6 years of age

Psoriasis

• Your doctor will calculate the correct dose, including the amount (volume) of Otulfi 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 between 60 kg and 100 kg, the recommended dose is 45 mg of Otulfi.
• If body weight exceeds 100 kg, the recommended dose is 90 mg of Otulfi.
• After the initial dose, the next dose should be administered 4 weeks later, and then every 12 weeks.

Children weighing at least 40 kg

Crohn’s disease

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

How Otulfi is administered

Otulfi is administered by subcutaneous injection ("subcutaneous route"). At the beginning of treatment, medical or nursing staff may administer Otulfi to you.

• However, you and your doctor may decide whether you can self-inject Otulfi. In this case, you will be taught how to self-inject Otulfi. In children from 6 years of age, it is recommended that Otulfi be administered by a healthcare professional or by the person caring for the child, after adequate training.
• For instructions on how to inject Otulfi, 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 Otulfi than you should

If you have used or received too much Otulfi, 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 Otulfi

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 Otulfi

Stopping treatment with Otulfi is not dangerous. However, if you stop treatment, symptoms may return. If you have further questions about the use of this medicine, ask 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 urgent medical assistance if you notice any of the following signs.

• Severe allergic reactions ("anaphylaxis") are rare in patients taking ustekinumab (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 no longer use Otulfi.
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 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).

Otulfi may reduce the 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 signs of infection while using Otulfi. 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 infection that persists or keeps recurring. Your doctor may decide to stop Otulfi 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 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 and scaly rash on areas of skin exposed to sunlight, sometimes accompanied by 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 detailed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Otulfi

• 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 Otulfi may also be stored at room temperature up to 30 °C for a single period of up to 30 days, 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 spaces 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 30 days at room temperature or by the original expiry date, whichever comes first.
• Do not shake the pre-filled syringes of Otulfi. Prolonged vigorous shaking may damage the medicine. Do not use this medicine
• After the expiry date stated on the label and carton after EXP or Exp.
• 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 Otulfi and contents of the pack”).
• If you know or suspect the medicine has been exposed to extreme temperatures (e.g. accidentally frozen or overheated).
• If the product has been shaken vigorously. Otulfi is for single use only. Any unused product remaining in the syringe must be discarded.

Do not dispose of any 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. OTHER INFORMATION

What Otulfi contains

• The active substance is ustekinumab. Each pre-filled syringe contains 45 mg of ustekinumab in 0.5 mL.
• The excipients are: L-histidine, polysorbate 80 (E433), sucrose, water for injections, and hydrochloric acid (for pH adjustment).

Description of the appearance of Otulfi and contents of the pack
Otulfi is a clear solution for injection, colourless to slightly brownish-yellow. It is supplied in a
cardboard pack containing 1 single dose in a 1 mL glass pre-filled syringe. Each pre-filled syringe
contains a dose of ustekinumab 45 mg in 0.5 mL of solution for injection.
Marketing Authorisation Holder
Fresenius Kabi Deutschland GmbH
Else-Kroener-Strasse 1
61352 Bad Homburg v.d.Hoehe
Germany
Manufacturer
Fresenius Kabi Austria GmbH
Hafnerstraße 36
8055 Graz Austria
More detailed information on this medicinal product is available on the European Medicines Agency
website: 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 Otulfi. In this case, you will be taught how to self-inject Otulfi. Inform your doctor if you have any questions about self-injection. In children from 6 years of age, it is recommended that Otulfi be administered by a healthcare professional or by the person caring for the child, after appropriate training.

• Do not mix Otulfi with other injectable liquids.
• Do not shake the pre-filled syringes of Otulfi, 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 the use of 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, the plunger, the needle safety wing, or the needle protective cap.
• Under no circumstances should you pull back the plunger.
• Do not remove the needle cap from the pre-filled syringe until it is needed.
• Do not touch the activation clip for needle protection (as indicated by the asterisk * in Figure 1) to prevent premature covering of the needle by the needle safety wing.
• Do not use the pre-filled syringe if it has fallen onto a hard surface.

Inspect the pre-filled syringe to ensure that:

• 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 Otulfi; if your dose is 90 mg, you will use two 45 mg pre-filled syringes of Otulfi and will need to perform two injections. Choose two different injection sites for these injections (e.g., one injection in the right thigh and the other injection in the left thigh), and administer 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, colorless to slightly brown-yellow
• the liquid in the pre-filled syringe shows no discoloration or cloudiness and contains no foreign particles
• the solution in the pre-filled syringe has not been frozen

Gather all necessary supplies and place them on a clean surface. The supplies should include 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).

• Otulfi is administered by injection under the skin (subcutaneously).
• A suitable place for the injection is the upper thigh or around the abdomen (abdominal area), 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.

Figure 2: The grey areas indicate recommended injection sites
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 giving 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.
• Take the prefilled syringe and hold it by the barrel with one hand.
• Remove and discard the needle protective cap. Do not touch the plunger during this step.

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 letting the needle touch 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 in one hand between the middle finger and index finger, placing the thumb on top of the plunger. Use the other hand to gently pinch the cleaned area of skin between the thumb and index finger. Do not pinch too tightly.
• Do not pull back on the plunger in any way.
• With one quick, smooth 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

• Continue pushing the plunger until it reaches the end of its travel, and keep pressing 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 rise upward, so that the needle is fully covered by the needle guard wings, as shown in Figure 7.

Figure 7

5. After the injection

• Press a 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 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

Package leaflet: Information for the user

Otulfi 90 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 because 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 Otulfi, please read these instructions carefully before administration.

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

1. What Otulfi is and what it is used for

What Otulfi is
Otulfi contains the active substance “ustekinumab”, a monoclonal antibody.
Monoclonal antibodies are proteins that recognise and bind to specific proteins in the body.
Otulfi belongs to a group of medicines called “immunosuppressants”. These medicines partially reduce the activity of the immune system.

What Otulfi is used for
Otulfi 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.
Otulfi will reduce inflammation and other signs of the disease.
Otulfi is used in adults with moderate to severe plaque psoriasis who cannot use ciclosporin, methotrexate or phototherapy, or in whom these treatments are ineffective.
Otulfi 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 Otulfi 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 sufficiently or are intolerant to these medicines, Otulfi may be given to reduce the signs and symptoms of your disease.

2. What you need to know before using Otulfi

Do not use Otulfi

• If you are allergic to ustekinumab or to any of the other ingredients of this medicine (listed in section 6 below).
• 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 Otulfi.
Warnings and precautions
Talk to your doctor or pharmacist before using Otulfi. Your doctor will check your health status
before each treatment. Make sure to inform your doctor, before each treatment, about any medical
conditions you have. Also, inform your doctor if you have recently been in contact with people
who might have had tuberculosis. Your doctor will examine you and carry out tests for
tuberculosis before administering Otulfi to you. If your doctor considers that you are at risk of tuberculosis, you may be given medicines to treat it.
Be aware of serious side effects
Otulfi can cause serious side effects, including allergic reactions and infections. You should pay
attention to certain signs of illness while taking Otulfi. See “Serious side effects” in section 4
for a complete list of these side effects.
Before using Otulfi, contact your doctor

• If you have ever had an allergic reaction to ustekinumab. Ask your doctor if you are unsure.
• If you have ever had any type of cancer – because immunosuppressants such as Otulfi 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 an Otulfi injection – see “Be aware of serious side effects” in section 4 for signs of an allergic reaction.
• 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 reduce immune system activity.

The concomitant use of these therapies with Otulfi 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 Otulfi may affect them.
• If you are aged 65 years or older – you may have an increased 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 Otulfi.
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. Contact a doctor immediately if you develop chest pain, weakness or a strange sensation on one side of the body, facial drooping, or speech or vision problems.
Children and adolescents
Otulfi 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 Otulfi
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) must not be given while you are using Otulfi.
• if you received Otulfi during pregnancy, inform your child’s paediatrician about the Otulfi treatment before your child receives any vaccine, including live vaccines such as the BCG vaccine (used to prevent tuberculosis). If you received Otulfi during pregnancy, live vaccines are not recommended for your child during the first twelve months after birth, unless otherwise advised by your child’s paediatrician. Pregnancy and breastfeeding
• If you are pregnant, think you may be pregnant, or are planning to become pregnant, ask your doctor for advice 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 Otulfi 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 Otulfi and for at least 15 weeks after stopping treatment with Otulfi.
• Ustekinumab can pass to the unborn child through the placenta. If you received Otulfi during pregnancy, your child may have an increased risk of developing an infection.
• If you received Otulfi during pregnancy, it is important to inform your child’s paediatrician and other healthcare providers before your child receives any vaccine. If you received Otulfi 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 Otulfi. You cannot do both.

Driving and using machines
Otulfi has no effect or has a negligible effect on the ability to drive and use machines.
Otulfi contains polysorbate 80 (E 433)
This medicine contains 0.04 mg of polysorbate 80 per 1 ml pre-filled syringe, equivalent to
0.04 mg/ml. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How to use Otulfi

Otulfi is intended for use under the guidance and supervision of a physician experienced in the treatment of the conditions for which Otulfi 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 Otulfi is administered

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

Adults from 18 years of age

Psoriasis and psoriatic arthritis

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

Children and adolescents from 6 years of age

Psoriasis

• Your doctor will calculate the correct dose, including the amount (volume) of Otulfi 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 dose.
• If body weight is between 60 kg and 100 kg, the recommended dose is 45 mg of Otulfi.
• If body weight exceeds 100 kg, the recommended dose is 90 mg of Otulfi.
• After the initial dose, the next dose should be given 4 weeks later, and then every 12 weeks.

Children weighing at least 40 kg

Crohn’s disease

• During treatment, the first dose of approximately 6 mg/kg of Otulfi 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 Otulfi, followed by doses every 12 weeks via subcutaneous injection (under the skin).
• In some patients, after the first subcutaneous injection, the 90 mg dose of Otulfi may be administered every 8 weeks. Your doctor will decide when the next dose should be administered.

How Otulfi is administered

Otulfi is administered by subcutaneous injection (“subcutaneously”). At the beginning of treatment, medical or nursing staff may administer Otulfi to you.

• However, you and your doctor may decide whether you can self-inject Otulfi. In this case, you will be taught how to self-administer the injection. In children from 6 years of age, it is recommended that Otulfi be administered by a healthcare professional or caregiver after appropriate training.
• For instructions on how to inject Otulfi, 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 Otulfi than you should

If you have used or received too much Otulfi, 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 Otulfi

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 Otulfi

It is not dangerous to stop using Otulfi. However, if you discontinue treatment, symptoms may return. If you have any further questions about the use of this medicine, ask 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 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 ustekinumab (affecting up to 1 in 1,000 patients). Signs include: difficulty breathing or swallowing, low blood pressure (which may cause dizziness or a feeling of light-headedness), 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 no longer use Otulfi.

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).

Otulfi 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 Otulfi. 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
• visual 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 can have serious complications. Consult your doctor if you have any infection that persists or keeps recurring. Your doctor may decide to stop Otulfi 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 associated 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 Otulfi

• 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 Otulfi may also be stored at room temperature up to 30 °C for a single period of up to 30 days, 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 spaces provided 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 30 days at room temperature or by the original expiry date, whichever comes first.
• Do not shake the pre-filled syringes of Otulfi. Prolonged vigorous shaking may damage the medicine. Do not use this medicine
• After the expiry date stated on the label and carton after EXP or Exp.
• 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 Otulfi and contents of the pack”).
• If you know or suspect the medicine has been exposed to extreme temperatures (e.g. accidentally frozen or overheated).
• If the product has been shaken vigorously. Otulfi 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 Otulfi contains

• The active substance is ustekinumab. Each pre-filled syringe contains 90 mg of ustekinumab in 1 mL.
• The excipients are: L-histidine, polysorbate 80 (E433), sucrose, water for injections, and hydrochloric acid (for pH adjustment).

Description of the appearance of Otulfi and contents of the pack
Otulfi is a clear solution for injection, colourless to slightly brownish-yellow. 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 solution for injection.
Marketing Authorisation Holder
Fresenius Kabi Deutschland GmbH
Else-Kroener-Strasse 1
61352 Bad Homburg v.d.Hoehe
Germany
Manufacturer
Fresenius Kabi Austria GmbH
Hafnerstraße 36
8055 Graz Austria
More detailed information on this medicinal product is available on the European Medicines Agency
website: 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 Otulfi. In this case, you will be taught how to self-inject Otulfi. Inform your doctor if you have any questions about self-injection. In children from 6 years of age, it is recommended that Otulfi be administered by a healthcare professional or by the person caring for the child, after appropriate training.

• Do not mix Otulfi with other injectable liquids.
• Do not shake the pre-filled syringes of Otulfi, 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 the 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 30 minutes. 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 the syringe by the plunger tip, plunger, needle shield wing, 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 necessary.
• Do not touch the safety activation clip (as indicated by the asterisk * in Figure 1) to prevent premature coverage of the needle by the needle safety shield.
• Do not use the pre-filled syringe if it has fallen on a hard surface.

Inspect the pre-filled syringe to ensure that:

• the number of pre-filled syringes and the dose are correct; if your dose is 90 mg, you will use one 90 mg Otulfi pre-filled syringe
• 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, from colorless to slightly brown-yellow
• the liquid in the pre-filled syringe does not show any discoloration or cloudiness and contains no foreign particles
• the solution in the pre-filled syringe is not frozen

Gather all necessary supplies and place them on a clean surface. The supplies should include 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).

• Otulfi is administered by injection under the skin (subcutaneously).
• A suitable place for the injection is the upper thigh or around the abdomen (abdominal area), 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.

Figure 2: The grey areas indicate recommended injection sites
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 giving 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.
• Take the prefilled syringe and hold it by the body of the syringe with one hand.
• Remove and discard the needle protective cap. Do not touch the plunger during this step.

Figure 3

• If you notice an air bubble in the prefilled 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 letting the needle touch any surface.
• Do not use the prefilled syringe if it is found 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 in one hand between the middle finger and index finger, placing the thumb on the plunger head, and use the other hand to gently pinch the cleaned area of skin between the thumb and index finger. Do not pinch too tightly.
• Do not pull back on the plunger in any way.
• With one quick 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 the thumb from the plunger head to allow 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 liquid 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 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 discarded in regular waste.

Figure 8