TYENNE 162 mg INJECTABLE SOLUTION IN PRE-FILLED PEN

Introduction

Package Leaflet: Information for the User

Tyenne 162 mg solution for injection in pre-filled pen

tocilizumab

This medicine 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 section 4 will tell you how to report side effects.

Read all of this leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• 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, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

In addition to this leaflet, you will be given a Patient Information Card, which contains important safety information that you should know before you receive and during treatment with Tyenne.

Contents of the pack

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

1. What is Tyenne and what is it used for

Tyenne contains the active substance 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 severe, active, and progressive 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 the joints and can also improve performance in daily tasks. Tyenne has been shown to slow down the progression of damage to the cartilage and bones of the joints caused by the disease and improve the ability to perform daily activities.

Tyenne is normally used in combination with another medicine for RA called methotrexate. However, Tyenne may be given alone if your doctor decides that methotrexate is not suitable.

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

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

GCA is often treated with medicines called steroids. These 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 can make 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 rash.

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

2. What you need to know before you use Tyenne

Tyenne will not be given to you

• If you are allergicto tocilizumab or any of the other ingredients of this medicine (listed in section 6).
• If you have a severe active infection.

If any of these apply to you, talk to your doctor or nurse.

Warnings and precautions

Talk to your doctor or nurse before you start receiving Tyenne.

• If you experience allergic reactionssuch as chest tightness, wheezing, dizziness, or severe dizziness, swelling of the lips, or rash during or after the infusion, tell your doctor immediately.

• If you have any type of infection, either short-term or long-term, or if you get infections often tell your doctor immediatelyif you feel unwell. Tyenne may reduce the ability of your body to respond to infections and may make an existing infection worse or increase the likelihood of getting a new infection.

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

• If you have had intestinal ulcer or diverticulitis, tell your doctor. Symptoms would include abdominal pain and unexplained changes in bowel habits with fever.

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

• If a patient has been recently vaccinated(adult or child) or is scheduled to be vaccinated, tell your doctor. All patients, especially children, must be up to date with their vaccination schedule before starting treatment with Tyenne, unless urgent treatment is required. Certain types of vaccines must not be given while receiving Tyenne.

• If you have cancer, tell your doctor. Your doctor will have to decide if you can continue treatment with Tyenne.

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

If you have moderate to severe kidney problems, your doctor will monitor you.

• If you have persistent headaches.

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

Children and adolescents

Tyenne is not recommended for use in children under 2 years of age.

Tell your doctor if the child has a history of macrophage activation syndrome(uncontrolled activation and proliferation of specific blood cells). Your doctor will decide if the child can continue receiving Tyenne.

Other medicines and Tyenne

Tell your doctor if you are taking, have recently taken, or might take any other medicines (or if the patient you are caring for is taking them). This includes medicines obtained without a prescription. Tyenne may affect how some medicines work, and a dose adjustment may be needed. Tell your doctorif you are using medicines that contain any of these active substances:

• methylprednisolone, 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,
• cyclosporin, used in organ transplants as an immunosuppressant,
• benzodiazepines, such as temazepam, used to calm anxiety.

Regarding vaccines, see the previous warnings section.

Because there is no clinical experience, the use of Tyenne with other biologic medicines used to treat RA, sJIA, or pJIA is not recommended.

Pregnancy and breastfeeding

Tyenne must 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 must use effective contraceptive methods during and up to 3 months after finishing treatment.

Stop breastfeeding if you start treatment with Tyenne, and consult your doctor. Before restarting breastfeeding, at least 3 months must have passed since your last treatment with Tyenne. It is not known if Tyenne passes into breast milk.

Data available so far do not suggest that this treatment has any effect on fertility.

Driving and using machines

This medicine may cause dizziness, if you feel dizzy, do not drive or use machines.

Tyenne contains sodium

This medicine contains 0.24 mg of sodium (main component of cooking/table salt) per ml. This is equivalent to 0.012% of the maximum recommended daily intake of sodium for an adult. However, Tyenne is diluted in a solution for infusion of sodium chloride 9 mg/ml (0.9%) or 4.5 mg/ml (0.45%). This should be taken into account in patients on a controlled sodium diet.

3. How to use Tyenne

Follow exactly the administration instructions of this medicine given by your doctor, pharmacist, or nurse. If you are unsure, talk to your doctor, pharmacist, or nurse.

Treatment should be initiated by a healthcare professional experienced in the diagnosis and treatment of RA, sJIA, pJIA, or GCA.

Adults with RA or GCA

The recommended dosefor all adults with RA (rheumatoid arthritis) or GCA (giant cell arteritis) is 162 mg (the content of one pre-filled pen) administered once a week.

Adolescents with sJIA (12 years of age and older)

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

• If the patient weighs less than 30 kg: the dose is 162 mg (the content of 1 pre-filled pen), once every 2 weeks.
• If the patient weighs 30 kg or more: the dose is 162 mg (the content of 1 pre-filled pen), once a week.

Adolescents with pJIA (12 years of age and older)

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

• If the patient weighs less than 30 kg: the dose is 162 mg (the content of 1 pre-filled pen), once every 3 weeks.
• If the patient weighs 30 kg or more: the dose is 162 mg (the content of 1 pre-filled pen), once every 2 weeks.

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

Talk to your doctor if you have any questions about how you or an adolescent you care for can self-administer an injection. At the end of this leaflet, you will find detailed "administration instructions".

If you use more Tyenne than you should

Since Tyenne is administered in a pre-filled pen, it is unlikely that you will be given too much. However, if you are concerned, talk to your doctor, pharmacist, or nurse.

If an adult with RA or GCA or an adolescent with sJIA misses or forgets a dose

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

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

If an adolescent with pJIA misses or forgets a dose

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

• If you miss 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 miss a dose for 7 days or more, or are unsure when to inject Tyenne, call your doctor or pharmacist.

If you stop treatment with Tyenne

Do not stop treatment with Tyenne without talking to your doctor first.

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

4. Possible side effects

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

Serious side effects: talk to your doctor immediately.

These are common: May affect up to 1 in 10 people

Allergic reactionsduring or after the infusion:

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

If you experience any of these symptoms, talk to your doctor immediately.

Signs of serious infections:

• fever and chills,
• mouth or skin blisters,
• stomach pain.

Signs and symptoms of liver toxicity:

May 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, tell your doctor immediately.

Very common side effects:

May 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:

May affect up to 1 in 10 people

• lung infection (pneumonia),
• shingles (herpes zoster),
• fever (oral herpes), blisters,
• skin infections (cellulitis), sometimes with fever and chills,
• rash and itching, hives,
• allergic reactions (hypersensitivity),
• eye infection (conjunctivitis),
• headache, dizziness, high blood pressure,
• mouth ulcers, stomach 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),
• increased bilirubin measured by blood tests,
• low levels of fibrinogen in the blood (protein involved in blood clotting).

Uncommon side effects:

May affect up to 1 in 100 people

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

Rare side effects:

May affect up to 1 in 1,000 people

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

Very rare side effects:

May affect up to 1 in 10,000 people

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

Additional side effects in children and adolescents with sJIA or pJIA

Side effects in children and adolescents with sJIA or pJIA are generally similar to those in adults. Some side effects that are more common in children and adolescents are: inflammation of the nose and throat, headache, nausea, and low white blood cell count.

Reporting of side effects

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

5. Storage of Tyenne

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

Do not use this medicine after the expiry date which is stated on the carton.

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

Keep the vials in the outer packaging to protect them from light.

6. Container Contents and Additional Information

Tyenne Composition

• The active ingredient is tocilizumab.

Each pre-filled syringe 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), water for injectable preparations.

Product Appearance and Container Contents

Tyenne is an injection solution. The solution is clear and colorless to pale yellow.

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

Each container contains 1 or 4 pre-filled syringes. The multiple container contains 12 (3 containers of 4) pre-filled syringes. Only certain container sizes may be marketed.

Marketing Authorization Holder and Manufacturer

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:

Other Sources of Information

Detailed information on this medicinal product is available on the European Medicines Agency website http://www.ema.europa.eu/.

1. Instructions for Use

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

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

Important Information

• Read the patient leaflet that comes with the Tyenne pre-filled syringe for

important information you need to know before using it.

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

Using the Tyenne Pre-filled Syringe

• The pre-filled syringe is for self-injection or administration with the help of a caregiver.
• The pre-filled syringe is for home use.
• When injecting Tyenne, children may self-inject if both the doctor and the caregiver consider it appropriate.
• Do notreuse the pre-filled syringe. The pre-filled syringe is for a single dose (single use).
• Do notshare your pre-filled syringe with another person. You could infect another person or get an infection from them.
• Do notremove the transparent cap from the pre-filled syringe until you are ready to inject.
• Do notuse the pre-filled syringe if it appears damaged or has been dropped.

Storing the Tyenne Pre-filled Syringe

• Store Tyenne in the refrigerator between 2 °C and 8 °C.
• Keep unused pre-filled syringes in the original container to protect them from light.
• Do not freeze. If Tyenne freezes, discard it in a sharps container.
• Keep Tyenne away from heat or direct sunlight.
• Keep the pre-filled syringe out of the reach and sight of children.
• Tyenne can be stored at room temperature between 20 °C and 25 °C in the carton it comes in for up to 14 days.
• Discard (throw away) Tyenne in a sharps container if it has been out of the refrigerator for more than 14 days. Once stored at room temperature, do not put it back in the refrigerator.

Traveling with Tyenne Pre-filled Syringes

• When traveling by air, always check with your airline and doctor about carrying injectable medications with you. Always carry Tyenne in your carry-on baggage because the baggage area may be very cold and it could freeze.

Parts of the Tyenne Pre-filled Syringe

Before Use

After Use

STEP 1: Prepare Your Injection

STEP 2: Check the Pre-filled Syringe

STEP 3: Wash Your Hands

STEP 4: Choose the Injection Site

STEP 5: Clean the Injection Site

STEP 6: Give Yourself the Injection

STEP 7: Remove and Check the Pre-filled Syringe

STEP 8: Dispose of Your Pre-filled Syringe

STEP 9: Record Your Injection