OTULFI 130 MG CONCENTRATE FOR INFUSION SOLUTION

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 for quick identification of new safety information. You can help by reporting any side effects you may get. The last section of this leaflet includes information on how to report side effects.

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 the person taking the medicine.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• If you get any side effects, talk to your doctor or pharmacist, even if you think they are not serious. See section 4.

Contents of the pack

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

1. What is Otulfi and what is it used for

What is Otulfi

Otulfi contains the active substance “ustekinumab”, a monoclonal antibody. Monoclonal antibodies are proteins that identify and bind to specific 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

Crohn's disease

Crohn's disease is an inflammatory disease of the intestine. If you have Crohn's disease, you will first be given other medicines. If you do not respond well to these medicines or cannot tolerate them, you may be given Otulfi to reduce the signs and symptoms of your disease.

2. What you need to know before you use Otulfi

Do not use Otulfi

• If you are allergic to ustekinumabor any of the other ingredients of this medicine (listed in section 6).
• If you have an active infectionthat your doctor thinks is important.

If you are not sure if any of the above applies to you, talk to your doctor or pharmacist before using Otulfi.

Warnings and precautions

Talk to your doctor or pharmacist before starting Otulfi. Your doctor will check how you are before treatment. Make sure you tell your doctor about any illness you have before treatment. Also, tell your doctor if you have recently been near someone who may have tuberculosis. Your doctor will examine you and do a test to check for tuberculosis before you use Otulfi. If your doctor thinks you are at risk of tuberculosis, they may give you medicines 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 you are using Otulfi. See the complete list of these side effects in “Serious side effects” in section 4.

Before using Otulfi, tell your doctor:

• If you have ever had an allergic reaction to ustekinumab.Check with your doctor if you are not sure.
• If you have ever had any type of cancer– this is because immunosuppressants like Otulfi weaken part of the immune system. This may increase the risk of having cancer.
• If you have received treatment for psoriasis with other biologics (a medicine made from a biological source and usually given by injection)– the risk of having cancer may be higher.
• If you have had a recent infection or have any open sores (fistula).
• If you have any new or changing lesionswithin the area of psoriasis or on intact skin.
• If you are taking any other treatment for psoriasis and/or psoriatic arthritis– such as any other immunosuppressant or phototherapy (when your body is treated with a type of ultraviolet light (UV)). These treatments may also weaken part of the immune system. It has not been studied whether these treatments can be used together with Otulfi. However, it is possible that it may increase the likelihood of suffering from diseases related to a weaker immune system.
• If you are receiving or have ever received allergy shots– it is not known if Otulfi can affect these treatments.
• If you are 65 years of age or older– you are more likely to get infections.

If you are not sure if you have any of these conditions, talk to 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. Talk to your doctor right away if you experience a red, raised, and scaly skin rash, sometimes with a darker border, in areas of the skin exposed to the sun or if they are accompanied by joint pain.

Heart attacks and strokes

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

Children and adolescents

Otulfi is not recommended for use in children under 18 years of age with Crohn's disease, as it has not been studied in this age group.

Using Otulfi with other medicines, vaccines

Tell your doctor or pharmacist:

• If you are using, have recently used, or might use other medicines.
• If you have been vaccinated recently or are going to have a vaccination.Certain types of vaccines (live vaccines) should not be given while you are using Otulfi.
• If you received Otulfi during pregnancy, tell your baby's doctor about your treatment with Otulfi before your baby receives any vaccination, including live vaccines such as the BCG vaccine (used to prevent tuberculosis).Live vaccines are not recommended for your baby in the first 12 months after birth if you received Otulfi during pregnancy, unless your baby's doctor recommends otherwise.

Pregnancy and breastfeeding

• If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.
• No increased risk of birth defects has been seen in babies exposed to ustekinumab in the womb.However, there is limited experience with ustekinumab in pregnant women. Therefore, it is preferable to avoid using Otulfi during pregnancy.
• If you are a woman of childbearing age, you are advised to avoid becoming pregnant and to use adequate contraceptive measures while you are using Otulfi and for at least 15 weeks after the last treatment with Otulfi.

• Ustekinumab may pass through the placenta to the fetus.If you received Otulfi during pregnancy, your baby may have a higher risk of getting an infection.
• It is important that you inform your baby's doctors and other healthcare professionals if you received Otulfi during your pregnancy before your baby receives any vaccination.Live vaccines, such as the BCG vaccine (used to prevent tuberculosis), are not recommended for your baby in the first 12 months after birth if you received Otulfi during pregnancy, unless your baby's doctor recommends otherwise.

• Ustekinumab may be excreted in breast milk in very small amounts.If you are breastfeeding or plan to breastfeed, tell your doctor. You and your doctor will decide whether you should breastfeed or use Otulfi. Do not do both.

Driving and using machines

Otulfi has no influence on the ability to drive and use machines.

Otulfi contains sodium

Otulfi contains less than 1 mmol of sodium (23 mg) per dose; this is essentially “sodium-free”. However, before you are given Otulfi, it is mixed with a solution that contains sodium. Talk to your doctor if you are on a low-salt diet.

Otulfi contains polysorbates

This medicine contains 10.4 mg of polysorbate 80 in each 26 ml vial, which is equivalent to 0.4 mg/ml. Polysorbates may cause allergic reactions. Tell your doctor if you have any known allergy.

3. How to use Otulfi

Otulfi should be used under the guidance and supervision of a doctor with experience in the diagnosis and treatment of Crohn's disease.

Your doctor will give you Otulfi 130 mg concentrate for solution for infusion through a drip into a vein in your arm (intravenous infusion) over at least one hour. Ask your doctor when you should have the injections and about follow-up appointments.

How much Otulfi is given

Your doctor will decide how much Otulfi you need to receive and how long your treatment will last.

Adults from 18 years of age

• Your doctor will calculate the recommended dose of intravenous infusion 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 then every 12 weeks.

How Otulfi is given

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

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

If you miss a dose of Otulfi

If you miss a dose or do not attend an appointment to have it given to you, talk to your doctor to schedule another appointment.

If you stop using Otulfi

Stopping Otulfi is not dangerous. However, if you stop using it, your symptoms may come back.

If you have any other questions about using 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 have serious side effects that may need urgent treatment.

Allergic reactions – these may need urgent treatment. Contact your doctor or get urgent medical help immediately if you notice any of the following signs.

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

• difficulty breathing and swallowing
• low blood pressure, which can cause dizziness or mild headaches
• swelling of the face, lips, mouth, or throat

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

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

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

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

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

• Nose 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 under the skin (“cellulitis”) is uncommon (may affect up to 1 in 100 people).
• Herpes (a type of painful rash with blisters) is uncommon (may affect up to 1 in 100 people).

Otulfi may affect your ability to fight infections. Some of these may be serious and be caused by viruses, fungi, bacteria (including tuberculosis), or parasites, and include infections that occur mainly in people with a weakened immune system (opportunistic infections). Opportunistic infections of the brain (encephalitis, meningitis), lungs, and eyes have been reported in patients receiving treatment with ustekinumab.

You should watch for signs of infection while you are using Otulfi. These include:

• fever, flu-like symptoms, night sweats, weight loss
• feeling tired or having trouble breathing; cough that does not go away
• having hot, red, and painful skin or a painful skin rash with blisters
• pain when urinating
• diarrhea
• vision problems or loss of vision
• headache, stiff neck, sensitivity to light, nausea, or confusion

Tell your doctor immediately if you notice any of these signs of infection, as they may be signs of infections such as chest infections, skin infections, herpes, or opportunistic infections that may have serious complications. You should also tell your doctor if you have any type of infection that does not go away or comes back. Your doctor may decide that you should not use Otulfi until the infection goes away. Also, talk to your doctor if you have any open sores or ulcers that may become infected.

Shedding of the skin – increased redness and shedding 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 should tell your doctor immediately.

Other side effects

Common side 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 side 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 bumps on the skin, sometimes accompanied by fever (pustular psoriasis)
• Scaling of the skin (skin exfoliation)
• Acne

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

• Redness and shedding of the skin over a large area of the body, which may be itchy or painful (exfoliative dermatitis).Similar symptoms may develop, such as a natural change in the symptoms of psoriasis (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 side effects(may affect up to 1 in 10,000 people)

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

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if you think they are not serious. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side 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 it is not necessary for patients to store or handle it.
• Keep this medicine out of the sight and reach of children.
• Store in a refrigerator (2 °C and 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 can damage the product.

Do not use this medicine:

• After the expiration date stated on the label and carton after "EXP". The expiration date is the last day of the month indicated.
• If the liquid changes color, is cloudy, or has foreign particles floating in it (see section 6 "Appearance of Otulfi and package contents").
• If you know or believe it has been exposed to extreme temperatures (such as accidental heating or freezing).
• If the product has been vigorously shaken.
• If the seal is broken.

Otulfi is for single use. You should discard any unused diluted solution for infusion left in the vial or syringe in accordance with local regulations.

6. Package contents and additional information

Composition of Otulfi

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

Appearance of Otulfi and package contents

Otulfi is a clear, colorless to slightly brown-yellow solution for infusion concentrate. It comes in a pack containing 1 single-dose 30 ml glass vial. Each vial contains 130 mg of ustekinumab in 26 ml of solution for infusion concentrate.

Marketing Authorization 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 last revision of this leaflet

Detailed information on this medicine is available on the European Medicines Agency website: 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 product must be clearly recorded.

Instructions for dilution:

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

1. Calculate the dose and number of Otulfi vials needed based on the patient's weight (see section 3, Table 1). Each 26 ml vial of Otulfi contains 130 mg of ustekinumab.
2. Withdraw and then discard a volume of 9 mg/ml (0.9%) sodium chloride solution from the 250 ml infusion bag equivalent to the volume of Otulfi to be added (discard 26 ml of sodium chloride for each Otulfi vial needed: 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 necessary vial and add it to the 250 ml infusion bag. The final volume of the infusion bag should be 250 ml. Mix gently.
4. Perform a visual inspection of the diluted solution before infusion. Do not use if opaque particles, color changes, or foreign particles are detected.
5. Infuse 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 infusion system with an in-line filter, sterile, apyrogenic, and low protein-binding (pore size 0.2 micrometers).
7. Each vial is for single use and unused medicine must be discarded in accordance with local regulations.

Storage

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

Do not freeze.