OTULFI 45 mg INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the Patient

Otulfi 45mg solution for injection

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. See the end of section 4 for 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 patients, or for parents/guardians of children, who have been prescribed Otulfi. If you are a parent or guardian, please read this leaflet carefully before giving Otulfi to a child.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. 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 is Otulfi used for

Otulfi is used to treat the following inflammatory disease:

• Plaque psoriasis – in adults and children aged 6 years and over
• 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 signs 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 have not worked.

Otulfi is used in children and adolescents aged 6 years and over with moderate to severe plaque psoriasis who are unable to tolerate phototherapy or other systemic therapies or where these treatments have not worked.

Psoriatic arthritis

Psoriatic arthritis is an inflammatory disease of the joints, usually accompanied by psoriasis. If you have active psoriatic arthritis, you will first receive other medicines. If you do not respond well to these medicines, 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 disease of the intestine. If you have Crohn's disease, you will first be given other medicines. If you do not respond adequately or cannot tolerate these medicines, 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, you may be given 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 been treated 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 on your skin (fistula).
• If you have any new or changing lesionswithin the area of psoriasis or on unaffected 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 (UV) light). 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 may increase the likelihood of illnesses 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 any of the above applies to you, 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 skin exposed to the sun or if 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 regularly check your risk factors for heart disease and stroke to ensure they are being treated properly. Seek medical attention immediately if you experience chest pain, weakness, or unusual sensation on one side of your body, facial paralysis, or abnormalities in speech or vision.

Children and adolescents

Otulfi is not recommended for use in children under 6 years of age with psoriasis or in children under 18 years 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

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 or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking 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 the use of Otulfi during pregnancy.
• If you are a woman of childbearing potential, you are advised to use adequate contraceptive measures while 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 doctor 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 breast-feeding or plan to breast-feed, talk to your doctor before using Otulfi. You and your doctor will decide whether you should breast-feed or use Otulfi. You should not do both.

Driving and using machines

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

Otulfi contains polysorbates

This medicine contains 0.02 mg of polysorbate 80 in each 0.5 ml vial, which is equivalent to 0.04 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 treatment of the conditions for which Otulfi is indicated.

Always use this medicine exactly as your doctor has told you. If you are not sure, check with your doctor. Ask your doctor when you should have 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 aged 18 years and over

Psoriasis or psoriatic arthritis

• The recommended starting 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 take the next dose 4 weeks later and then every 12 weeks.The following doses are usually the same as the starting dose.

Crohn's disease

• During treatment, your doctor will give you the first dose of approximately 6 mg/kg of Otulfi through a drip in a vein in your 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, given as an injection under the skin (“subcutaneously”).
• In some patients, after the first injection under the skin, 90 mg of Otulfi will be given every 8 weeks.Your doctor will decide when you should receive the next dose.

Children and adolescents aged 6 years and over

Psoriasis

• Your doctor will tell you the correct dose for you, including the amount (volume) of Otulfi to inject to give the correct dose.The dose that is right for you will depend on your body weight at the time of each dose.
• If you weigh less than 60 kg, the recommended dose is 0.75 mg of Otulfi per kilogram of body weight.
• 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 take the next dose 4 weeks later, and then every 12 weeks.

How Otulfi is given

• Otulfi is given as an injection under the skin (“subcutaneously”).At the start of your treatment, a healthcare professional may give you the injection.
• However, you and your doctor may decide that you can inject Otulfi yourself.In this case, you will be trained on how to inject Otulfi yourself.
• For instructions on how to inject Otulfi, see “Administration instructions” at the end of this leaflet.

Talk to your doctor if you have any questions about how to inject yourself.

If you use more Otulfi than you should

If you have used or been given too much Otulfi, talk to your doctor or pharmacist immediately. Always carry the medicine box with you, even if it is empty.

If you forget to use Otulfi

If you miss a dose, talk to your doctor or pharmacist. Do not take a double dose to make up for forgotten doses.

If you stop using Otulfi

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

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Severe Adverse Effects

Some patients may have severe adverse effects that may require urgent treatment.

Allergic Reactions – these may require urgent treatment. Contact your doctor or get emergency medical help immediately 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). 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 hives (these may affect up to 1 in 100 people).

In rare cases, allergic reactions in the lungs 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.

• Nose or throat infections and the common cold are frequent (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 them could become 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 using Otulfi. These include:

• fever, flu-like symptoms, night sweats, weight loss
• feeling tired or having difficulty breathing; cough that does not go away
• having hot, red, and painful skin or having a painful skin rash with blisters
• pain when urinating
• diarrhea
• visual impairment or loss of vision
• headache, neck stiffness, photosensitivity, nausea, or confusion.

Communicate with 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 could have serious complications. You should also inform 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, contact your doctor if you have any open cuts or ulcers that could become infected.

Shedding of the Skin – increased redness and shedding of the skin on a large surface 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 inform your doctor immediately.

Other Adverse Effects

Frequent 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 skin blisters, sometimes accompanied by fever (pustular psoriasis)
• Shedding of the skin (skin exfoliation)
• Acne

Rare Adverse Effects(may affect up to 1 in 1,000 people):

• Redness and shedding of the skin on a large surface of the body, which may cause itching or pain (exfoliative dermatitis). Similar symptoms may develop, such 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 and cause itching and pain (bullous pemphigoid).
• Cutaneous lupus or lupus-like syndrome (red, raised, and scaly skin rash in sun-exposed areas, possibly accompanied by joint pain).

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is 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 contribute to providing more information on the safety of this medicine.

5. Storage of Otulfi

• 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 that 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 product left in the vial or syringe. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Otulfi

• The active substance is ustekinumab. Each vial contains 45 mg of ustekinumab in 0.5 ml.
• The other ingredients are L-histidine, polysorbate 80 (E 433), sucrose, water for injections, and hydrochloric acid (for pH adjustment).

Appearance of Otulfi and Package Contents

Otulfi is a clear, colorless to slightly brown-yellow injectable solution.

It comes in a package containing 1 vial of 3 ml of glass. Each vial contains 45 mg of ustekinumab in 0.5 ml of injectable solution.

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/

Administration Instructions

At the start of treatment, your healthcare professional will help you with your first injection. However, you and your doctor may decide that you can inject Otulfi yourself. In this case, they will teach you how to inject Otulfi. Talk to your doctor if you have any questions about administering the injections.

• Do not mix Otulfi with other injectable liquids.
• Do not shake Otulfi vials. The medicine may be damaged if shaken vigorously. Do not use the medicine if it has been shaken vigorously.

1. Check the number of vials and prepare the materials:

Take the vial(s) out of the refrigerator. Let the vial sit for half an hour. This will allow the liquid to reach a comfortable temperature for administration (room temperature).

Check the vial(s) to ensure that:

• The number of vials and concentration are correct
• • If the dose is 45 mg or less, you will be given a 45 mg Otulfi vial.
  • If the dose is 90 mg, you will be given two 45 mg Otulfi vials, and you will need to administer 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 immediately after the other. Use a new needle and syringe for each injection.
• It is the correct medicine.
• The expiration date has not passed.
• The vial is not damaged and the seal is not broken.
• The solution in the vial is clear, colorless to slightly brown-yellow.
• The solution has not changed color or is not cloudy and does not contain any foreign particles.
• The solution is not frozen.

Children who weigh less than 60 kg need a dose less than 45 mg. Make sure you know the correct amount (volume) to withdraw from the vial and the type of syringe you need for dosing. If you do not know the amount or type of syringe needed, contact your healthcare professional for further instructions.

Gather everything you need and place it on a clean surface, including the syringe, needle, antiseptic wipes, cotton or gauze, and a container for disposing of sharp objects (see Figure 1).

1. Choose and prepare the injection site:

Choose the injection site (see Figure 2).

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

Prepare the injection site

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

1. Prepare the dose:
   • Remove the cap that covers the top of the vial (see Figure 3).

• Do not remove the stopper.
• Clean the stopper with an alcohol swab.
• Place the vial on a flat surface.
• Take the syringe and remove the needle cap.
• Do not touch the needle or let it touch anything.
• Insert the needle through the rubber stopper.
• Turn the vial and syringe upside down.
• Pull the syringe plunger to fill it with the amount of liquid indicated by your doctor.
• It is essential that the needle remains in the liquid at all times. This prevents air bubbles from forming in the syringe (see Figure 4).

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

• Then, push the plunger until all the air is eliminated (but not the liquid).
• Do not rest the syringe on any surface, and prevent the needle from touching anything.

1. Inject the dose:
   • Gently pinch the disinfected skin with your thumb and index finger, without squeezing.
   • Insert the needle into the skin fold.
   • Push the plunger with your thumb until it reaches the stop to inject all the liquid. Do this slowly and evenly, keeping the skin fold gently pinched.
   • When you have pushed the plunger to the stop, remove the needle and release the skin fold.

1. 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 the injection site with a cotton ball or gauze and hold it for 10 seconds.
   • Do not rub the skin at the injection site. You can cover the injection site with a band-aid if necessary.

1. Disposal:
   • Used syringes and needles should be placed in a puncture-resistant container, such as a sharps container. For your safety and health and the safety of others, never reuse needles and syringes. Dispose of your sharps container according to local regulations.
   • Empty vials, antiseptic wipes, and other materials can be disposed of in the trash.