Prospect: information for the user

Tyenne 162 mg injectable solution in pre-filled pen

tocilizumab

This medicine is subject to additional monitoring, which will speed up the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report these adverse effects.

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

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist or nurse.
• This medicine has been prescribed only for you, and you must not give it to other people, even if they have the same symptoms as you, as it may harm them.
• If you experience adverse effects, consult your doctor, pharmacist or nurse, even if they are adverse effects that do not appear in this prospect. See section 4.

In addition to this prospect, you will be given aPatient Information Leaflet, which contains important safety information that you should know before receiving and during treatment with Tyenne.

Tyenne contains an active substance called tocilizumab, which is a protein obtained from specific immune cells (monoclonal antibody), that blocks the action of a specific type of protein (cytokine) called interleukin-6. This protein is involved in inflammatory processes in the body, and blocking it can reduce inflammation. Tyenne is indicated for the treatment of:

• adults with moderate to severe active rheumatoid arthritis (RA), which is an autoimmune disease, if previous treatments have not worked well.

• adults with active and progressive severe rheumatoid arthritis (RA), who have not been previously treated with methotrexate.

Tyenne helps to reduce the symptoms of RA such as pain and swelling in your joints and may also improve your performance in daily tasks. Tyenne has shown to decrease the progression of damage in the cartilage and bones of your joints caused by the disease and improve your ability to perform your daily activities.

Tyenne is usually used in combination with another RA medication called methotrexate. However, Tyenne can be administered alone if your doctor determines that methotrexate is not suitable.

• adults with a disease of the arteries called giant cell arteritis (GCA), caused by inflammation of the larger arteries in the body, especially those that supply blood to the head and neck. Symptoms may include headache, fatigue (tiredness) and jaw pain. Effects may include strokes and blindness.

Tyenne can reduce pain and swelling of the arteries and veins in the head, neck and arms.

GCA is often treated with medications called steroids. They are usually effective, but can have side effects if used at high doses for a long time. Reducing the dose of steroids can also lead to a flare-up of GCA. Adding Tyenne to treatment makes the time of use of steroids shorter, while still controlling the disease.

• children and adolescents, 12 years of age and older, with active systemic juvenile idiopathic arthritis (sJIA), an inflammatory disease that causes pain and swelling in one or more joints, as well as fever and skin rash.

Tyenne is used to improve the symptoms of sJIA. It can be administered in combination with methotrexate or alone.

• children and adolescents, 12 years of age and older, with active polyarticular juvenile idiopathic arthritis (pJIA). This is an inflammatory disease that causes pain and swelling in one or more joints.

Tyenne is used to improve the symptoms of pJIA. It can be administered in combination with methotrexate or alone.

No use Tyenne

• If you or the pediatric patient you care for is allergic to tocilizumab or any of the other components of this medication (listed in section 6).
• If you or the pediatric patient you care for has an active severe infection.

If this happens, consult your doctor. Do not use Tyenne.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to receive Tyenne.

• If you experienceallergic reactionssuch as chest tightness, wheezing, dizziness, or intense drowsiness, swelling of the lips, tongue, face, or skin rash, hives, or itching during or after the injection,inform your doctor immediately.

• If you have experienced any symptoms of an allergic reaction after the administration of Tyenne, do not take the next dose until you have informed your doctor and your doctor has instructed you to take the next dose.

• If you have any type ofinfection, whether short-term or long-term, or if you often contract infections.Inform your doctor immediatelyif you feel unwell. Tyenne may reduce your body's ability to respond to infections and may make an existing infection worse or increase the likelihood of acquiring a new infection.

• If you have hadtuberculosis, inform your doctor. Your doctor will check for signs and symptoms of tuberculosis before starting treatment with Tyenne. Inform your doctor immediately if symptoms of tuberculosis (persistent cough, weight loss, general malaise, fever), or any other infection appear during or after treatment.

• If you have hadulcerative colitis or diverticulitis, inform your doctor. Symptoms include abdominal pain and unexplained changes in bowel habits with fever.

• If you haveliver disease, inform your doctor. Before using Tyenne, your doctor will perform a blood test to measure your liver function.

• If any patient has recently been vaccinated, or is planning to be vaccinated, inform your doctor. All patients must be up to date with their vaccination schedule before starting treatment with Tyenne. Certain types of vaccines should not be administered while receiving Tyenne.

• If you havecancer, inform your doctor. Your doctor will decide if you can continue receiving treatment with Tyenne.

• If you havecardiovascular risk factors, such as high blood pressure, and high cholesterol levels, inform your doctor. These factors need to be controlled while receiving treatment with Tyenne.

• If you havemoderate to severe kidney problems, your doctor will monitor you.

• If you havepersistent headaches.

Your doctor will perform blood tests before you receive Tyenne to determine if you have a low white blood cell count, a low platelet count, or elevated liver enzymes.

Children and adolescents

It is not recommended to inject Tyenne pre-filled pen in children under 12 years old.

Tyenne should not be administered to children with JIA (juvenile idiopathic arthritis) weighing less than 10 kg.

If the child has a history ofmacrophage activation syndrome(uncontrolled activation and proliferation of a specific type of blood cells), inform your doctor. Your doctor will decide if you can continue receiving Tyenne.

Other medications and Tyenne

Inform your doctor if you are taking any other medication, or have taken it recently. This is because Tyenne may affect how some medications work, and a dose adjustment may be needed.Inform your doctorif you have recently used medications containing any of the following active substances:

• prednisolone, dexamethasone, used to reduce inflammation,
• simvastatin or atorvastatin, used to reduce cholesterol levels,
• calcium channel blockers such as amlodipine used to treat high blood pressure,
• theophylline, used to treat asthma,
• warfarin or phenprocoumon, used as anticoagulants,
• phenytoin, used to treat seizures,
• ciclosporin, used in organ transplants as an immunosuppressant,
• benzodiazepines, such as temazepam used to calm anxiety.

Regarding vaccines, see the previous warning section.

Due to lack of clinical experience, it is not recommended to use Tyenne with other biologic medications used to treat RA, JIA, JIAp, or ACG.

Pregnancy and breastfeeding

Tyenneshould not be used during pregnancy, unless clearly necessary. Talk to your doctor if you are pregnant, think you may be pregnant, or plan to become pregnant.

Women of childbearing age should use effective contraceptive methods during and for 3 months after completing treatment.

Stop breastfeeding if you start treatment with Tyenne, and consult your doctor. Before resuming breastfeeding, at least 3 months should have passed since your last treatment with Tyenne. It is unknown if Tyenne passes into breast milk.

Driving and operating machinery

This medication may cause dizziness. If you feel dizzy, do not drive or operate machinery.

Tyenne contains sodium

This medication contains less than 23 mg of sodium (1 mmol) per 0.9 ml dose, which is essentially "sodium-free".

Follow exactly the administration instructions of this medication as indicated by your doctor, pharmacist, or nurse. In case of doubt, consult your doctor, pharmacist, or nurse again.

The treatment should be initiated by a healthcare professional with experience in the diagnosis and treatment of RA, JIA, JIpa, or ACG.

Adults with RA or ACG

Recommended dosefor all adults with RA (rheumatoid arthritis) or ACG (giant cell arteritis) is 162 mg (the content of one preloaded pen) administered once a week.

Adolescents with JIA (12 years of age and older)

The usual dose of Tyenne depends on the patient's weight.

• If the patient weighsless than 30 kg: the dose is 162 mg (the content of 1 preloaded pen), once every 2 weeks.
• If the patientweighs 30 kg or more: the dose is 162 mg (the content of 1 preloaded pen), once a week.

Adolescents with JIpa (12 years of age and older)

The usual dose of Tyenne depends on the patient's weight.

• If the patient weighsless than 30 kg: the dose is 162 mg (the content of 1 preloaded pen), once every 3 weeks.
• If the patient weighs30 kg or more: the dose is 162 mg (the content of 1 preloaded pen), once every 2 weeks.

Tyenne is administered by subcutaneous injection. At the beginning, your doctor or nurse may inject Tyenne for you. However, your doctor may decide that you can administer Tyenne yourself. In this case, you will receive information on how to self-administer Tyenne. Parents and caregivers will be trained on how to inject Tyenne for patients who cannot inject themselves.

Speak with your doctor if you have any questions about how you or a teenager you care for can self-administer an injection. At the end of this prospectus, you will find “administration instructions” in detail.

If you use more Tyenne than you should

Since Tyenne is administered in a preloaded pen, it is unlikely that you will receive too much. However, if you are concerned, speak with your doctor, pharmacist, or nurse.

If an adult with RA or ACG or an adolescent with JIA has lost or forgotten a dose

It is very important to use Tyenne exactly as prescribed by your doctor. Keep a record of your next dose.

• If you forget your weekly dose within 7 days, take your dose on the next scheduled day.
• If you forget your dose every 2 weeks within 7 days, inject a dose as soon as you remember and take your next dose according to your original schedule.
• If youforget your weekly dose or every 2 weeks for more than 7 days or are unsure when to inject Tyenne, call your doctor or pharmacist.

If an adolescent with JIpa has lost or forgotten a dose

It is very important to use Tyenne exactly as prescribed by your doctor. Keep a record of the next dose.

• If you forget a dose within 7 days, inject a dose as soon as you remember and administer the next dose according to your original schedule.
• If you forget a dose for 7 days or more, or are unsure when to inject Tyenne, call your doctor or pharmacist.

If you interrupt treatment with Tyenne

Do not stop treatment with Tyenne without consulting your doctor beforehand.

If you have any other questions about the use of this medication, ask your doctor, pharmacist, or nurse.

Like all medicines, this medicine can cause side effects, although not everyone will experience them. Side effects can occur up to at least 3 months after your last dose of Tyenne.

Severe side effects: consult your doctor immediately.

These are common: They can affect up to 1 in 10 people

Allergic reactionsduring or after injection:

• difficulty breathing, chest tightness, or dizziness,
• skin rash, itching, hives, swelling of the lips, tongue, or face.

If you experience any of these symptoms, speak with your doctorimmediately.

Signs of severe infections:

• fever and chills,
• blistering in the mouth or skin,
• abdominal pain.

Signs and symptoms of liver toxicity:

They can affect up to 1 in 1,000 people

• fatigue,
• abdominal pain,
• jaundice (yellowing of the skin or eyes).

If you notice any of these symptoms, inform your doctorimmediately.

Very common side effects:

They can affect more than 1 in 10 people

• upper respiratory tract infections, with typical symptoms such as cough, nasal congestion, runny nose, sore throat, and headache,
• high levels of fat in the blood (cholesterol),
• reactions at the injection site.

Common side effects:

They can affect up to 1 in 10 people

• lung infection (pneumonia),
• herpes (herpes zoster),
• fever blisters (herpes simplex oral), blisters,
• skin infections (cellulitis), sometimes with fever and chills,
• skin rash and itching, urticaria,
• allergic reactions (hypersensitivity),
• eye infection (conjunctivitis),
• headache, dizziness, hypertension,
• mouth ulcers, abdominal pain,
• fluid retention (edema) in the lower legs, weight gain,
• cough, shortness of breath,
• low white blood cell count in blood tests (neutropenia, leucopenia),
• abnormal liver function tests (elevated transaminases),
• high bilirubin levels measured through blood tests,
• low fibrinogen levels in the blood (protein involved in blood clotting).

Rare side effects:

They can affect up to 1 in 100 people

• diverticulitis (fever, nausea, diarrhea, constipation, abdominal pain),
• swollen and red areas in the mouth,
• high levels of fat in the blood (triglycerides),
• stomach ulcers,
• kidney stones,
• hypothyroidism.

Rare side effects:

They can affect up to 1 in 1,000 people

• Stevens-Johnson syndrome (skin rash, which can lead to severe blistering and peeling of the skin),
• fatal allergic reactions (anaphylaxis),
• inflammation of the liver (hepatitis), jaundice.

Very rare side effects:

They can affect up to 1 in 10,000 people

• low white blood cell, red blood cell, and platelet counts in blood tests,
• liver failure.

Additional side effects in children and adolescents with AIJs or AIJp

The side effects in children and adolescents with AIJs or AIJp are generally similar to those of adults. Some side effects that are observed more frequently in children and adolescents include: nasal and throat inflammation, headache, nausea, and decreased white blood cell count.

Reporting side effects

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

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the pre-filled pen label and on the box after (CAD). The expiration date is the last day of the month indicated.

Store in refrigerator (between 2°C and 8°C). Do not freeze.

Keep pre-filled pens in the outer packaging to protect from light.

A single pre-filled pen can be stored at temperatures of up to a maximum of 25°C for a single period of up to 14 days. The pre-filled pen must be protected from light and discarded if not used within 14 days.

Do not use this medication if you observe that it is turbid or contains particles, is of any color other than colorless to pale yellow, or any part of the pre-filled pen appears damaged.

Do not shake the pen. After removing the cap from the needle, the injection must be initiated immediately to prevent the medication from drying and blocking the needle. If the pre-filled pen is not used immediately after removing the cap, it must be disposed of in a sharps container and a new pre-filled pen used.

If after pressing the dose activation button the orange plunger rod does not move, the pre-filled pen must be disposed of in a sharps container.Do notattempt to re-use the pre-filled pen. Do not repeat the injection with another pre-filled pen. If you have any questions or problems, consult with your healthcare professional.

Composition of Tyenne

• The active ingredient is tocilizumab.

Each pre-filled pen contains 162 mg of tocilizumab in 0.9 ml.

• The other components are L-arginine, L-histidine, L-lactic acid, sodium chloride, polysorbate 80, hydrochloric acid (E507) and/or sodium hydroxide (E524), and water for injection.

Appearance of the product and contents of the pack

Tyenne is a solution for injection. The solution is transparent and colourless to pale yellow.

Tyenne is supplied in pre-filled pens of 0.9 ml containing 162 mg of tocilizumab solution for injection.

Each pack contains 1 or 4 pre-filled pens. The multiple pack contains 12 (3 packs of 4) pre-filled pens.Only some pack sizes may be marketed.

Marketing authorisation holder and responsible person for manufacture

Fresenius Kabi Deutschland GmbH

Else-Kroener-Strasse 1

61352 Bad Homburg v.d.Hoehe

Germany

Responsible person for manufacture

Fresenius Kabi Austria GmbH

Hafnerstrasse 36

8055 Graz

Austria

Last update of this leaflet:

Other sources of information

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

1. Instructions for use

Read these instructions for use carefully before using the Tyenne pre-filled pen.

Read and follow the instructions for use that come with the Tyenne pre-filled pen before starting to use it and each time you obtain a replacement. There may be new information. This information does not replace a consultation with your doctor about your disease or treatment. If you have any questions about the use of the Tyenne pre-filled pen, call your doctor.

Important information

• Read the patient leaflet that comes with the Tyenne pre-filled pen to obtain

important information you need to know before using it.

• Before using the Tyenne pre-filled pen for the first time, make sure your doctor shows you the correct way to use it.
• Do notattempt to disassemble the Tyenne pre-filled pen at any time.
• Inject the Tyenne pre-filled pen in the way your doctor has shown you.

Use of the Tyenne pre-filled pen

• The pre-filled pen is for self-injection or administration with the help of a carer.
• The pre-filled pen is for use at home.
• When injecting Tyenne, children may self-inject if both the doctor and the carer consider it appropriate.
• Do notre-use the pre-filled pen. The pre-filled pen is for a single dose (a single use).
• Do notshare your pre-filled pen with another person. You may infect another person or contract an infection from them.
• Do notremove the transparent cap from the pre-filled pen until you are ready to inject.
• Do notuse the pre-filled pen if it shows signs of deterioration or if it has fallen.

Storage of the Tyenne pre-filled pen

• Store Tyenne in the refrigerator between 2°C and 8°C.
• Store unused pre-filled pens in the original pack to protect them from light.
• Do not freeze. If Tyenne freezes, dispose of it in a sharps container.
• Keep Tyenne away from heat or direct sunlight.
• Keep the pre-filled pen out of the reach and sight of children.
• Tyenne can be stored at room temperature between 20°C and 25°C in the carton pack in which it is presented for a maximum of 14 days.
• Dispose of Tyenne in a sharps container or puncture-resistant container if it has been out of the refrigerator for more than 14 days. Once stored at room temperature, do not return it to the refrigerator.

Traveling with Tyenne pre-filled pens

• When traveling by air, always consult your airline and doctor about the possibility of carrying injectable medicines. Always carry Tyenne in your hand luggage because the luggage area may be very cold and could freeze.

Parts of the Tyenne pre-filled pen

Before use

After use

STEP 1: Prepare your injection

Keep Tyenne out of the reach of children.

STEP 2: Check the pre-filled pen

STEP 3: Wash your hands

STEP 4: Choose the injection site

STEP 5: Clean the injection site

STEP 6: Administer your injection

STEP 7: Remove and check the pre-filled pen

STEP 8: Dispose of your pre-filled pen

STEP 9: Record your injection