TYENNE 20 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Tyenne 20 mg/ml concentrate for solution for infusion

tocilizumab

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 section 4 will tell you how to report side effects.

Read all of this leaflet carefully before you start taking 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 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.

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

Contents of the pack

1. What Tyenne is and what it is 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 Tyenne is and what it is used for

Tyenne contains the active substance tocilizumab, which is a protein obtained from specific immune cells (monoclonal antibody), which blocks the action of a specific type of protein (cytokine) called interleukin 6. This protein is involved in inflammatory processes in the body, and by blocking it, inflammation can be reduced. Tyenne helps reduce symptoms such as pain and swelling in your joints and can also improve your ability to perform daily tasks. Tyenne has been shown to decrease the progression of damage to the cartilage and bones of the joints caused by the disease and improve your ability to perform daily activities.

• Tyenne is used to treat adultswith active rheumatoid arthritis (RA)of moderate to severe intensity, which is an autoimmune disease, if previous treatments have not worked well. Tyenne is normally used in combination with methotrexate. However, Tyenne may be administered alone if your doctor determines that methotrexate is not suitable.

• Tyenne can also be used for the treatment of adults who have not been previously treated with methotrexate if they have severe, active, and progressive rheumatoid arthritis.

• Tyenne is used in the treatment of children with sJIA. Tyenne is used in children aged 2 years and older who have 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 and may be administered in combination with methotrexate or alone.

• Tyenne is used in the treatment of children with pJIA. Tyenne is used in children aged 2 years and older with active polyarticular juvenile idiopathic arthritis (pJIA), an inflammatory disease that causes pain and swelling in one or more joints. Tyenne is used to improve the symptoms of pJIA and may be administered in combination with methotrexate or alone.

• Tyenne is used in the treatment of adults and childrenaged 2 years and older with cytokine release syndrome (CRS)of severe or potentially life-threatening intensity, an adverse effect in patients treated with chimeric antigen receptor (CAR) T-cell therapy, used to treat certain types of cancer.

• Tyenne is used in the treatment of adults with coronavirus disease 2019 (COVID-19), who receive systemic corticosteroids and require oxygen supplementation or mechanical ventilation.

2. What you need to know before you use Tyenne

Tyenne will not be administered to you

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

If any of these apply to you, consult with the doctor or nurse who administers the infusion.

Warnings and precautions

Consult your doctor or nurse before starting to receive Tyenne.

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

• If you have any type of infection, either short-term or long-term, or if you get infections frequently inform 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 acquiring a new infection.

• If you have had tuberculosis, 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, low-grade fever), or any other infection appear during or after treatment.

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

• If you have liver disease, inform 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, inform 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 administered while receiving Tyenne.

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

• If you have cardiovascular risk factors, such as high blood pressure,

high cholesterol levels, inform 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 your treatment, to determine if you have a low white blood cell count, a low platelet count, or elevated liver enzymes.

Children and adolescents

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

Inform 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

Inform your doctor if you are taking, have recently taken, or might take any other medicines (or if your child is taking them, if they are the patient). This includes medicines obtained without a prescription. Tyenne may affect the way some medicines work, and a dose adjustment may be necessary. Inform your doctorif you are using medicines that contain any of the following 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 whether Tyenne passes into breast milk.

Available data 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

This medicine is subject to medical prescription and must be administered by a doctor or nurse.

Tyenne will be administered by intravenous infusion, by a doctor or nurse.They will dilute the solution, prepare the intravenous infusion, and monitor you during and after treatment.

Adult patients with RA

The usual dose of Tyenne is 8 milligrams (mg) per kilogram (kg) of body weight. Depending on the response, the doctor may decide to reduce the dose to 4 mg/kg and then increase it back to 8 mg/kg when appropriate.

Adults will receive Tyenne once every 4 weeks through intravenous infusion (over 1 hour).

Children with sJIA (aged 2 years and older)

The usual dose of Tyenne depends on body weight.

• If you weigh less than 30 kg: the dose is 12 mg per kilogram of body weight.
• If you weigh 30 kg or more: the dose is 8 mg per kilogram of body weight.

The dose is calculated based on body weight at each administration.

Children with sJIA will receive Tyenne once every 2 weeks through intravenous infusion (over 1 hour).

Children with pJIA (aged 2 years and older)

The usual dose of Tyenne is calculated based on body weight.

• If you weigh less than 30 kg: the dose is 10 mg per kilogram of body weight.
• If you weigh 30 kg or more: the dose is 8 mg per kilogram of body weight.

The dose is calculated based on body weight at each administration.

Children with pJIA will receive Tyenne once every 4 weeks through intravenous infusion (over 1 hour).

Patients with CRS

The usual dose of Tyenne is 8 mg per kilogram of body weight if you weigh 30 kg or more.

The dose is 12 mg per kilogram of body weight if you weigh less than 30 kg.

Tyenne may be administered alone or in combination with corticosteroids.

Patients with COVID-19

The usual dose of Tyenne is 8 mg per kilogram of body weight. A second dose may be necessary.

If you are given too much Tyenne

As Tyenne is administered by a doctor or nurse, it is unlikely that you will be given too much.

However, if you are concerned, talk to your doctor.

If you miss a dose of Tyenne

As Tyenne is administered by a doctor or nurse, it is unlikely that you will miss a dose. However, if you are concerned, talk to your doctor or nurse.

If you stop treatment with Tyenne

You must not stop treatment with Tyenne without consulting your doctor first.

If you have any other questions about the use of this medicine, ask your doctor 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: consult 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,
• skin rash, itching, hives, swelling of the lips, tongue or face.

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

Signs of serious infections

• fever and chills,
• blisters in the mouth or skin,
• 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, inform your doctor as soon as possible.

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).

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, urticaria,
• 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 (a 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 blisters and severe peeling of the skin),
• fatal allergic reactions (anaphylaxis),
• liver inflammation (hepatitis), jaundice.

Very rare side effects:

May affect up to 1 in 10,000 people

• low levels of white blood cells, red blood cells, and platelets,
• liver failure.

Children with sJIA

Generally, side effects in patients with sJIA were of a similar type to those in adults with RA. Some side effects were observed more frequently: nasal and throat inflammation, diarrhea, decrease in white blood cell count, and increase in liver enzymes.

Children with pJIA

Generally, side effects in patients with pJIA were of a similar type to those in adults with RA. Some side effects were observed more frequently: nasal and throat inflammation, headache, feeling unwell (nausea), and decrease in 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 that they are not listed in this leaflet. 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 and other information

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 4 ml vial contains 80 mg of tocilizumab (20 mg/ml).

Each 10 ml vial contains 200 mg of tocilizumab (20 mg/ml).

Each 20 ml vial contains 400 mg of tocilizumab (20 mg/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 injectable preparations.

Regarding sodium, see section 2 "Tyenne contains sodium" above.

Appearance of the product and container contents

Tyenne is a concentrate for solution for infusion. The concentrate is a clear, colorless to pale yellow liquid.

Tyenne is supplied in vials containing 4 ml, 10 ml, and 20 ml of concentrate for solution for infusion. Each container contains 1 vial and multiple containers contain 4 (4 containers of 1) vials. Not all pack 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/.

This information is intended only for healthcare professionals:

Instructions for dilution prior to administration

Parenteral drugs should be inspected visually for particles or color change before administration. Only solutions that are clear and colorless to pale yellow and free of visible particles should be diluted. Use a sterile needle and syringe to prepare Tyenne.

Adult patients with RA, COVID-19, and sJIA(≥ 30 kg)

Remove from a 100 ml infusion bag a volume of sterile and apyrogenic sodium chloride injection solution 9 mg/ml (0.9%) or 4.5 mg/ml (0.45%) equal to the volume of Tyenne concentrate needed for the patient's dose, under aseptic conditions. The required amount of Tyenne concentrate (0.4 ml/kg) should be withdrawn from the vial and added to the 100 ml infusion bag. The final volume should be 100 ml. To mix the solution, gently invert the infusion bag to avoid foam formation.

Use in pediatric population

Patients with sJIA, pJIA, and sJIA with weight ≥ 30 kg

Remove from a 100 ml infusion bag a volume of sterile and apyrogenic sodium chloride injection solution 9 mg/ml (0.9%) or 4.5 mg/ml (0.45%) equal to the volume of Tyenne concentrate needed for the patient's dose, under aseptic conditions. The required amount of Tyenne concentrate (0.4 ml/kg) should be withdrawn from the vial and added to the 100 ml infusion bag. The final volume should be 100 ml. To mix the solution, gently invert the infusion bag to avoid foam formation.

Patients with sJIA and sJIA with weight < 30 kg

Remove from a 50 ml infusion bag a volume of sterile and apyrogenic sodium chloride injection solution 9 mg/ml (0.9%) or 4.5 mg/ml (0.45%) equal to the volume of Tyenne concentrate needed for the patient's dose, under aseptic conditions. The required amount of Tyenne concentrate (0.6 ml/kg) should be withdrawn from the vial and added to the 50 ml infusion bag. The final volume should be 50 ml. To mix the solution, gently invert the infusion bag to avoid foam formation.

Patients with pJIA with weight < 30 kg

Remove from a 50 ml infusion bag a volume of sterile and apyrogenic sodium chloride injection solution 9 mg/ml (0.9%) or 4.5 mg/ml (0.45%) equal to the volume of Tyenne concentrate needed for the patient's dose, under aseptic conditions. The required amount of Tyenne concentrate (0.5 ml/kg) should be withdrawn from the vial and added to the 50 ml infusion bag. The final volume should be 50 ml. To mix the solution, gently invert the infusion bag to avoid foam formation.

Tyenne is for single use.

Any unused product or waste material should be disposed of in accordance with local requirements.