Otulfi 130 mg concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Otulfi 130mg concentrate for solution for infusion

ustekinumab

This medicinal product is subject to additional monitoring, which will allow quicker identification of new safety information. You can help by reporting any side effects you may experience. See the final part of section 4 for information on how to report side effects.

Read all of this leaflet carefully before starting to use this medicine, because it contains important information for you.

This leaflet has been written for the person using the medicine.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• If you experience any side effects, consult your doctor or pharmacist, even if they are side effects not listed in this leaflet. 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 specifically identify and bind to certain proteins in the body.

Otulfi belongs to a group of medicines called “immunosuppressants”. These medicines work by weakening part of the immune system.

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 given other medications. If you do not respond adequately or cannot tolerate those medications, 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 components of this medicine (listed in section 6).
• If you have an active infection that your doctor considers important.

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

Warnings and precautions

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

Watch for serious side effects

Otulfi may cause serious side effects, including allergic reactions and infections. You should be aware of certain signs of illness while using Otulfi. See the complete list of these side effects in section 4 under “Serious side effects”.

Before using Otulfi, tell your doctor:

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

If you are unsure whether any of these conditions apply to you, speak with your doctor or pharmacist before using Otulfi.

Some patients have experienced lupus-like reactions during treatment with ustekinumab, including cutaneous lupus or lupus-like syndrome. Contact your doctor immediately if you develop a red, raised, scaly rash, sometimes with a darker border, on sun-exposed skin areas, especially if accompanied by joint pain.

Heart attacks and strokes

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

Children and adolescents

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

Use of Otulfi with other medicines and vaccines

Inform your doctor or pharmacist:

• If you are currently using, have recently used, or might use any other medicines.
• If you have recently been vaccinated or are scheduled to receive a vaccine. Certain types of vaccines (live vaccines) should not be administered while you are using Otulfi.
• If you received Otulfi during pregnancy, inform your infant’s doctor about your treatment with Otulfi before the infant receives any vaccines, including live vaccines such as the BCG vaccine (used to prevent tuberculosis). Live vaccines are not recommended for your infant during the first twelve months after birth if you received Otulfi during pregnancy, unless the infant’s doctor advises otherwise.

Pregnancy and breastfeeding

• If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

• No increased risk of birth defects has been observed in babies exposed to ustekinumab in the womb. However, experience with ustekinumab in pregnant women is limited. Therefore, it is preferable to avoid using Otulfi during pregnancy.

• Women of childbearing potential are advised to avoid becoming pregnant and to use adequate contraception while using Otulfi and for at least 15 weeks after the last dose.

• Ustekinumab can cross the placenta to the fetus. If you received Otulfi during pregnancy, your infant may have an increased risk of developing infections.

• It is important to inform your infant’s doctors and other healthcare professionals if you received Otulfi during pregnancy before the infant receives any vaccines. Live vaccines, such as the BCG vaccine (used to prevent tuberculosis), are not recommended for your infant during the first twelve months after birth if you received Otulfi during pregnancy, unless the infant’s doctor recommends otherwise.

• Ustekinumab may be excreted in breast milk in very small amounts. Inform your doctor if you are breastfeeding or plan to breastfeed. You and your doctor will decide whether to breastfeed or use Otulfi. Do not do both at the same time.

Driving and using machines

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

Otulfi contains sodium

Otulfi contains less than 1 mmol of sodium (23 mg) per dose, meaning it is essentially “sodium-free”. However, before administration, Otulfi is mixed with a solution containing sodium. Speak with 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 in each 26 ml vial, equivalent to 0.4 mg/ml. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergies.

3. How to use Otulfi

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

Your doctor will administer Otulfi 130 mg concentrate for solution for infusion by intravenous infusion into a vein in your arm over a period of at least one hour. Ask your doctor when your infusions should be given and about follow-up appointments.

Dose of Otulfi administered

Your doctor will decide the dose of Otulfi you need and the duration of treatment.

Adults aged 18 years and older

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

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

Children with Crohn's disease weighing at least 40 kg

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

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

How Otulfi is administered

The first dose of Otulfi for the treatment of Crohn's disease is administered by a doctor through an infusion into a vein in the arm (intravenous infusion).

Please consult your doctor if you have any questions about treatment with Otulfi.

If you forget to use Otulfi

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

If you stop treatment with Otulfi

Stopping the use of 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 adverse effects

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

Serious adverse effects

Some patients may experience serious adverse effects that may require urgent treatment.

Allergic reactions – these may require urgent treatment. Contact your doctor or seek immediate medical help if you notice any of the following signs.

• Severe allergic reactions ("anaphylaxis") are rare in the population using ustekinumab (may affect up to 1 in 1,000 people). Signs include:

• difficulty breathing and swallowing

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

• swelling of the face, lips, mouth or throat

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

Infusion-related reactions – If you are being treated for Crohn's disease, your first dose of Otulfi is administered via intravenous infusion (drip into a vein). Some patients have experienced severe allergic reactions during ustekinumab infusion.

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

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

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

• Nasal or throat infections and the common cold are common (may affect up to 1 in 10 people).
• Chest infections are uncommon (may affect up to 1 in 100 people).
• Inflammation of the tissues beneath the skin ("cellulitis") is uncommon (may affect up to 1 in 100 people).
• Herpes (a type of painful blistering rash) is uncommon (may affect up to 1 in 100 people).

Otulfi may affect your ability to fight infections. Some of these infections may become serious and may be caused by viruses, fungi, bacteria (including tuberculosis), or parasites. They include 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 receiving ustekinumab treatment.

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

• fever, flu-like symptoms, night sweats, weight loss
• feeling tired or having difficulty breathing; persistent cough
• skin that feels hot, red, and painful, or a painful blistering skin rash
• burning sensation when urinating
• diarrhea
• worsening vision or vision loss
• headache, neck stiffness, light sensitivity, nausea, or confusion.

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

Skin peeling – increased redness and peeling of the skin over a large area of the body may be symptoms of erythrodermic psoriasis or exfoliative dermatitis, which are serious skin disorders. If you notice any of these symptoms, you must inform your doctor immediately.

Other adverse effects

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

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

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

• Dental infections
• Vaginal yeast infections
• Depression
• Nasal congestion or stuffiness
• Bleeding, bruising, hardening, swelling, and itching at the injection site
• Feeling weak
• Drooping eyelid and sinking of the muscles on one side of the face ("facial paralysis" or "Bell's palsy"), which is usually temporary
• A change in psoriasis with redness and new small yellow or white blisters on the skin, sometimes accompanied by fever (pustular psoriasis)
• Skin flaking (skin exfoliation)
• Acne

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

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

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

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

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Otulfi

• Otulfi 130 mg concentrate for solution for infusion is administered in a hospital or medical center and does not need to be stored or handled by patients.
• Keep this medicine out of the sight and reach of children.
• Store in a refrigerator (2 °C to 8 °C). Do not freeze.
• Keep the vial in the outer packaging to protect it from light.
• Do not shake Otulfi vials. Prolonged vigorous shaking may damage the product.

Do not use this medicine:

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

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

6. Contents of the container and other information

Composition of Otulfi

• The active substance is ustekinumab. Each vial contains 130 mg of ustekinumab in 26 ml.
• The other components are disodium edetate dihydrate (E385), L-histidine, monohydrochloride monohydrate of L-histidine, L-methionine, polysorbate 80 (E433), sucrose and water for injections.

Appearance of Otulfi and contents of the container

Otulfi is a concentrate for infusion solution, transparent, ranging from colourless to slightly brownish-yellow. It is supplied in a pack containing one single-dose 30 ml glass vial. Each vial contains 130 mg of ustekinumab in 26 ml of concentrate for infusion solution.

Marketing Authorisation Holder

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

Date of the most recent revision of this leaflet

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

The following information is intended exclusively for healthcare professionals:

Traceability:

In order to improve the traceability of biological medicinal products, the name and batch number of the administered medicine should be clearly recorded.

Instructions for dilution:

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

1. Calculate the dose and 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. Withdraw and discard a volume from the 250 ml sodium chloride 9 mg/ml (0.9%) infusion bag equivalent to the volume of Otulfi to be added (discard 26 ml of sodium chloride for each vial of Otulfi required: 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 to the 250 ml infusion bag. The final volume of the infusion bag must be 250 ml. Mix gently.
4. Visually inspect the diluted solution before infusion. Do not use if particulate matter, discolouration or foreign particles are observed.
5. Administer the diluted solution over a minimum period of one hour. Once diluted, the infusion must be completed within 24 hours of dilution in the infusion bag.
6. Use only an in-line, sterile, pyrogen-free, low protein-binding infusion set (pore size 0.2 micrometres).
7. Each vial is for single use only. Any unused medicinal product should be discarded in accordance with local regulations.

Storage

If necessary, the diluted infusion solution may be stored at room temperature. The infusion must be completed within 8 hours after dilution in the infusion bag.

Do not freeze.