Label: information for the patient

Otulfi 90mg injectable solution in pre-filled syringe

ustekinumab

This medicine is subject to additional monitoring, which will facilitate the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section4 includes information on how to report these adverse effects.

Read this label carefully before starting to use this medicine, as it contains important information for you.

This label has been written for the person using the medicine. If you are the parent or caregiver of a child to whom you will administer Otulfi, please read this information carefully.

• Keep this label, as you may need to refer to it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed only for you, and you should not give it to other people even if they present the same symptoms as you, as it may harm them.
• If you experience adverse effects, consult your doctor or pharmacist, even if they are not listed in this label. See section4.

1.What is Otulfi and what it is used for

2.What you need to know before starting to use Otulfi

3.How to use Otulfi

4.Possible adverse effects

5.Storage of Otulfi

6.Contents of the package and additional information

What is Otulfi

Otulfi contains the active ingredient “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 medications called “immunosuppressants”. These medications act by weakening part of the immune system.

What is Otulfi used for

Otulfi is used to treat the following inflammatory diseases:

• Plaque psoriasis - in adults and children 6 years of age and older
• Psoriatic arthritis - in adults
• Moderate to severe Crohn's disease - in adults

Plaque psoriasis

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

Otulfi is used in adults with moderate to severe plaque psoriasis who cannot use ciclosporin, methotrexate, or phototherapy, or where these treatments are not effective.

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

Psoriatic arthritis

Psiatic arthritis is an inflammatory joint disease, which is usually accompanied by psoriasis. If you have active psoriatic arthritis, you will first receive other medications. If you do not respond well to these medications, you may be treated with Otulfi to:

• Reduce the signs and symptoms of your disease.
• Improve your physical function.
• Reduce damage to your joints.

Crohn's disease

Crohn's disease is an inflammatory bowel disease. If you have Crohn's disease, you will first receive other medications. If you do not respond adequately or cannot tolerate those medications, you may be administered Otulfi to reduce the signs and symptoms of your disease.

No use Otulfi

• If you are allergic to ustekinumabor to any of the other ingredients of this medicine (listed in section6).
• If you have an active infectionthat your doctor thinks is important.

If you are unsure if any of the above points apply to you, talk to your doctor or pharmacist before using Otulfi.

Warnings and precautions

Consult your doctor or pharmacist before starting to use Otulfi. Your doctor will check how you are before each treatment. Make sure to inform your doctor about any illness you have before each treatment. Your doctor will also ask if you have recently been near someone who may have tuberculosis. Your doctor will examine you and perform a test for tuberculosis detection before using Otulfi. If your doctor thinks you are at risk of tuberculosis, they may give you medicine to treat it.

Be aware of serious side effects

Otulfi may cause serious side effects, including allergic reactions and infections. You must pay attention to certain signs of illness while using Otulfi. See the complete list of these side effects in “Serious side effects” of section4.

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– this is because the immunosuppressants of the type of 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 produced from a biological source and usually administered by injection)– the risk of having cancer may be higher.
• If you have any new lesions or changes to lesionswithin the psoriasis area or on intact skin.
• If you have or have had a recent infection.
• If you have ever had an allergic reaction to the Otulfi injection. See “Be aware of serious side effects” in section 4for signs of an allergic reaction.
• 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 (UV) light). These treatments may also weaken part of the immune system. The use of these treatments together with Otulfi has not been studied. However, it may increase the likelihood of having diseases related to a weaker immune system.
• If you are receiving or have received injections to treat allergies– it is unknown if Otulfi may affect these treatments.
• If you are 65years or older– you are more likely to acquire infections.

If you are unsure if you have any of these conditions, talk to your doctor or pharmacist before using Otulfi.

Some patients have experienced reactions similar to lupus during treatment with ustekinumab, including cutaneous lupus or lupus-like syndrome. Talk to your doctor immediately if you experience a red, raised, and scaly rash, sometimes with a darker border, in sun-exposed areas or accompanied by joint pain.

Heart attacks and strokes

In a study of 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 abnormal sensation in one side of the body, facial paralysis, or abnormalities in speech or vision.

Children and adolescents

Otulfi is not recommended for use in children under 6years of age with psoriasis or in children under 18years of age with psoriatic arthritis or Crohn's disease, as it has not been studied in this age group.

Using Otulfi with other medicines, vaccines

Inform your doctor or pharmacist:

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

Pregnancy and breastfeeding

• It is preferable to avoid using Otulfi during pregnancy. The effects of Otulfi on pregnant women are unknown. If you are fertile, it is recommended that you avoid becoming pregnant and use adequate contraceptive measures while using Otulfi and for at least 15weeks after the last treatment with Otulfi.
• Inform your doctor if you are pregnant, think you may be pregnant, or intend to become pregnant.
• Ustekinumab may pass through the placenta to the fetus. If you received Otulfi during pregnancy, your baby may be at increased risk of contracting an infection.
• It is essential to inform your baby's doctors and other healthcare professionals if you received Otulfi during pregnancy before your baby receives any vaccine. Live vaccines, such as the BCG vaccine (used to prevent tuberculosis), should not be administered to your baby in the first six 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. Inform your doctor if you are breastfeeding or plan to do so. You and your doctor will decide whether to breastfeed or use Otulfi. Do not do both at the same time.

Driving and operating machinery

The influence of Otulfi on the ability to drive and operate machinery is negligible or insignificant.

Otulfi should be used under the guidance and supervision of a doctor with experience in treating the conditions for which Otulfi is indicated.

Always follow exactly the administration instructions for this medication as indicated by your doctor. In case of doubt, ask your doctor. Ask your doctor when to administer the injections and about follow-up consultations.

What amount of Otulfi is administered

Your doctor will decide on the amount of Otulfi you need to use and the duration of treatment.

Adults 18 years of age and older

Psoriasis or psoriatic arthritis

• The recommended starting dose is 45 mg of Otulfi. Patients weighing more than 100 kg may start with a dose of 90 mg instead of 45 mg.
• After the initial dose, you will take the next dose 4 weeks later and then every 12 weeks. The subsequent doses are usually the same as the starting dose.

Crohn's disease

• During treatment, your doctor will administer the first dose of approximately 6 mg/kg of Otulfi through a vein in the arm (intravenous infusion). After the initial dose, you will receive the next dose of 90 mg of Otulfi 8 weeks later and then every 12 weeks through a subcutaneous injection.
• In some patients, after the first subcutaneous injection, 90 mg of Otulfi will be administered every 8 weeks. Your doctor will decide when you should receive the next dose.

Children and adolescents 6 years of age and older

Psoriasis

• Your doctor will indicate the correct dose for you, including the amount (volume) of Otulfi to inject to give the correct dose. The suitable dose for you will depend on your body weight at the time each dose is given.
• If you weigh less than 60 kg, there is no posological formulation of Otulfi for children with a body weight less than 60 kg, so other ustekinumab products must be used.
• If you weigh between 60 kg and 100 kg, the recommended dose is 45 mg of Otulfi.
• If you weigh more than 100 kg, the recommended dose is 90 mg of Otulfi.
• After the initial dose, you will receive the next dose 4 weeks later, and then every 12 weeks.

How Otulfi is administered

• Otulfi is administered through a subcutaneous injection. Initially, medical or nursing staff may administer Otulfi to you.
• However, you and your doctor may decide that Otulfi is injected by you. In that case, you will be trained on how to inject Otulfi yourself. In children 6 years of age and older, it is recommended that Otulfi administration be performed by a healthcare professional or caregiver after receiving proper training.
• For instructions on how to inject Otulfi, see "Administration Instructions" at the end of this prospectus.

Consult your doctor if you have any questions about self-injecting.

If you use more Otulfi than you should

If you have used or have been administered too much Otulfi, speak immediately with your doctor or pharmacist. Always carry the medication box with you, even if it is empty.

If you forget to use Otulfi

If you forget a dose, speak with your doctor or pharmacist. Do not take a double dose to compensate for the missed doses.

If you interrupt treatment with Otulfi

Stopping using Otulfi is not hazardous. However, if you stop, your symptoms may reappear. If you have any other doubts about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Severe side effects

Some patients may experience severe side 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 (they can affect up to 1 in 1,000 people). The 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 urticaria (these can affect up to 1 in 100 people).

In rare cases, pulmonary allergic reactions and lung inflammation have been reported in patients treated with ustekinumab. Inform your doctor immediately if you 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 require urgent treatment. Contact your doctor immediately if you notice any of these signs.

• Common colds, sore throats, and respiratory tract infections are frequent (they can affect up to 1 in 10 people).
• Chest infections are rare (they can affect up to 1 in 100 people).
• Cellulitis, an inflammation of the tissues under the skin, is rare (it can affect up to 1 in 100 people).
• Herpes, a painful rash with blisters, is rare (it can affect up to 1 in 100 people).

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

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

• Fever, flu-like symptoms, night sweats, weight loss
• Feeling tired or difficulty breathing; persistent cough
• Hot, red, and painful skin or a painful skin rash with blisters
• Urinary burning
• Diarrhea
• Visual deterioration or loss of vision
• Headache, neck stiffness, photosensitivity, nausea, or confusion.

Notify your doctor immediately if you notice any of these signs of infection, as they may be signs of infections such as pneumonia, skin infections, herpes, or opportunistic infections that could have serious complications. You should also inform your doctor if you have any type of infection that does not resolve or reappears. Your doctor may decide that you should not use Otulfi until the infection resolves. Also, contact your doctor if you have any open wounds or ulcers that may become infected.

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

Other side effects

Frequent side effects(they can affect up to 1 in 10 people):

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

Rare side effects(they can affect up to 1 in 100 people):

• Dental infections
• Vaginal yeast infections
• Depression
• Stuffy or congested nose
• Bleeding, petechiae, hardening, swelling, and itching at the injection site
• Feeling weak
• Drooping eyelid and facial muscle weakness (“facial paralysis” or “Bell's palsy”), which is usually temporary
• A change in psoriasis with redness and new small skin blisters, sometimes accompanied by fever (pustular psoriasis).
• Skin peeling (exfoliation)
• Acne

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

• Redness and skin peeling over a large area of the body, which may cause itching or pain (dermatitis exfoliativa). Similar symptoms may develop as a natural change in psoriasis symptoms (psoriasis erythroderma)
• 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(they can affect up to 1 in 10,000 people)

• Blisters on the skin, which may be red and cause itching and pain (pemphigoid bullous).
• Cutaneous lupus or lupus-like syndrome (red, elevated, and scaly skin rash in sun-exposed areas, possibly accompanied by joint pain).

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the national reporting system included in theAppendixV. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

• Maintain this medication out of the sight and reach of children.
• Store in the refrigerator (2°C and 8°C). Do not freeze.
• Store the pre-filled syringe in the outer packaging to protect it from light.
• If necessary, individual pre-filled Otulfi syringes can also be stored at room temperature up to 30°C for a maximum period of up to 30 days in their original box to protect them from light. Write 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 expiration date printed on the box. Once a syringe has been stored at room temperature (up to a maximum of 30°C), it must not be stored again in the refrigerator. Discard the syringe if it is not used within 30 days of storage at room temperature or from the original expiration date, whichever occurs first.
• Do not shake the pre-filled Otulfi syringes. Prolonged vigorous shaking may damage the product.

Do not use this medication:

• After the expiration date appearing on the label and packaging after “CAD”. The expiration date is the last day of the month indicated.
• If the liquid changes color, becomes cloudy, or presents unusual particles floating in it (see section 6 “Appearance of Otulfi and contents of the packaging”).
• If you know or suspect you have been exposed to extreme temperatures (such as accidental heating or freezing).
• If the product has been shaken vigorously.

Otulfi is for single use. Dispose of the unused product remaining in the syringe. Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of empty packaging and unused medications. This will help protect the environment.

Composition of Otulfi

• The active ingredient is ustekinumab. Each pre-filled syringe contains 90 mg of ustekinumab in 1 ml.
• The other components are L-histidine, polisorbate 80, sucrose, water for injection and hydrochloric acid (for pH adjustment).

Appearance of Otulfi and contents of the package

Otulfi is a transparent, colourless to slightly yellowish solution for injection.

It is presented in a package containing 1 pre-filled syringe of 1 ml of glass for single use. Each pre-filled syringe contains 90 mg of ustekinumab in 1 ml of solution for injection.

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

Last update of this leaflet

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

Administration instructions

At the beginning of treatment, the healthcare professional will help you with your first injection. However, it is possible that you and your doctor decide that you can administer Otulfi yourself. In this case, they will teach you how to administer Otulfi. Talk to your doctor if you have any doubts about administering the injections. In children aged 6 years and older, it is recommended that Otulfi be administered by a healthcare professional or a caregiver after receiving proper training.

• Do not mix Otulfi with other injectable liquids.
• Do not shake the pre-filled syringes of Otulfi. The medicine may deteriorate if shaken vigorously. Do not use the medicine if it has been shaken vigorously.

The Figure 1 shows how the pre-filled syringe looks like.

Figure 1

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

Preparation for using the pre-filled syringe

• Take the pre-filled syringe(s) out of the refrigerator. Leave the pre-filled syringe outside the box for 30 minutes. This will allow the liquid to reach a comfortable temperature for administration (room temperature). Do not remove the cap from the needle while waiting for the temperature to reach room temperature.
• Hold the pre-filled syringe by the body with the capped needle pointing upwards.
• Do not pick up the syringe by the plunger, the plunger, the wings of the needle shield or the cap of the needle.
• Do not remove the plunger at any time.
• Do not remove the cap from the pre-filled syringe until instructed to do so.

• Do not touch the activation clips of the needle shield (indicated by asterisks* in Figure 1) to avoid the needle shield covering the needle too early.
• Do not use the pre-filled syringe if it falls on a hard surface.

Check the pre-filled syringe(s) to ensure that

• The number of pre-filled syringes and the concentration are correct
• If your dose is 90 mg, you will have a pre-filled syringe of 90 mg of Otulfi.
• It is the correct medicine.
• The expiration date has not expired.
• The pre-filled syringe is not damaged.
• The solution in the pre-filled syringe is transparent and colourless to slightly yellowish.
• The solution in the pre-filled syringe does not have an abnormal colour, is turbid or contains foreign particles.
• The solution in the pre-filled syringe is not frozen.

Prepare all the materials you need and place them on a clean surface. Including antiseptic wipes, cotton or gauze and a sharps container.

2.Choose and prepare the injection site:

Choose the injection site (see Figure 2).

• Otulfi is administered by subcutaneous injection.
• Some suitable injection sites are the upper thigh or the abdominal area (the abdomen) at least 5 cm from the navel.
• As far as possible, do not use skin areas that show signs of psoriasis.
• If someone else is administering the injection, they can also choose the upper arm as the injection site.

Figure 2: in grey, the recommended injection sites are indicated

Prepare the injection site

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

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

• The needle capmust not be removeduntil you are ready to administer the injection.
• Hold the pre-filled syringe and hold the body of the pre-filled syringe with one hand.
• Remove the needle cap and dispose of it. Do not touch the plunger while doing this.

Figure 3

• You may observe a bubble of air in the pre-filled syringe or a drop of liquid at the end of the needle. Both are normal and do not need to be removed.
• Do not touch the needle or allow it to touch any surface.
• Do not use the pre-filled syringe if it has fallen without the needle cap. If this happens, inform your doctor or pharmacist.
• Administer the dose immediately after removing the needle cap.

4.Administer the dose:

• Hold the pre-filled syringe with one hand between the index and middle fingers, place the thumb on the plunger and with the other hand pinch a disinfected piece of skin with the thumb and index finger. Do not press.
• Do not remove the plunger at any time.
• With a single quick movement, insert the needle through the skin until it can go no further (see Figure 4).

Figure 4

• Administer the entire dose by pushing the plunger until the head of the plunger is completely between the wings of the needle shield (see Figure 5).

Figure 5

• When you have pushed the plunger as far as it will go, maintain the pressure on the plunger, remove the needle and release the skin (see Figure 6).

Figure 6

• Slowly remove the thumb from the plunger to allow the empty syringe to advance until the needle is completely covered by the needle shield, as shown in Figure 7:

Figure 7

5.After the injection:

• Press the injection site with an antiseptic wipe for a few seconds after the injection.
• A small amount of blood or liquid may appear at the injection site. This is normal.
• You can press with a cotton ball or gauze the injection site and hold it for 10 seconds.
• Do not rub the skin at the injection site. You can cover the injection site with a bandage, if necessary.

6.Disposal:

• The used syringes must be deposited in a puncture-resistant container, similar to a sharps container (see Figure 8). For your safety and health and for the safety of others, never reuse the syringe. Dispose of your sharps container according to local regulations.
• Antiseptic wipes and other materials can be disposed of in the trash.

Figure 8