Tyenne 20 mg/ml concentrado para solucion para perfusion

Summary of Product Characteristics: Information for the User

Tyenne 20 mg/ml Concentrate for Solution for Infusion

tocilizumab

This medicine is subject to additional monitoring, which will expedite 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 leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or nurse.
• If you experience any adverse effects, consult your doctor or nurse, even if they are not listed in this leaflet. See section 4.

In addition to this leaflet, you will be given aPatient Information Leaflet, which contains important safety information that you should know before receiving Tyenne 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 helps to reduce symptoms such as pain and swelling in your joints and can also improve your performance in daily tasks. Tyenne has shown to decrease the progression of damage in the cartilage and bones of the joints caused by the disease and improve your ability to perform your daily activities.

• Tyenne is used to treat adultswithmoderate to severe active rheumatoid arthritis (RA)who have not responded well to previous treatments. Tyenne is usually used in combination with methotrexate. However, Tyenne can be administered alone if your doctor determines that methotrexate is not suitable.

• Tyenne can also be used to treat adults who have not been previously treated with methotrexate and have severe, active, and progressive rheumatoid arthritis.

• Tyenne is used in the treatment of children with JIA. Tyenne is used in children aged 2 years and older who haveactive systemic juvenile idiopathic arthritis (JIA), 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 JIA and can be administered with or without methotrexate.

• Tyenne is used in the treatment of children with JIP. Tyenne is used in children aged 2 years and older withactive polyarticular juvenile idiopathic arthritis (JIP), an inflammatory disease that causes pain and swelling in one or more joints. Tyenne is used to improve the symptoms of JIP and can be administered with or without methotrexate.

• Tyenne is used in the treatment of adults and childrenaged 2 years and older withcytokine release syndrome (CRS)severe or potentially fatal, a side effect in patients treated with chimeric antigen receptor (CAR) T-cell therapies, used to treat certain types of cancer.

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

You will not be administered Tyenne

• If you areallergicto tocilizumab or any of the other components of this medication (listed in section 6).
• If you have an active severe infection.

Consult your doctor or nurse administering the infusion if this happens.

Warnings and precautions

Consult your doctor or nurse before starting to receive Tyenne.

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

• If you have any type ofinfection, whether short-term or long-term, or if you frequently contract infectionsInform 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 tuberculosis symptoms (persistent cough, weight loss, general malaise, low-grade 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(adult or child) or is planning to be vaccinated, inform your doctor. All patients, especially children, must be up to date on their vaccination schedule before starting treatment with Tyenne, unless urgent treatment is required. 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, 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 children under 2 years old.

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

Other medications and Tyenne

Inform your doctor if you are taking, have recently taken, or may need to take any other medication (or if your child is the patient). This includes over-the-counter medications. Tyenne may affect how some medications work, and dosage adjustments may be needed.Inform your doctorif you are using medications containing any of the following active substances:

• prednisolone, dexamethasone, used to reduce inflammation,
• simvastatin or atorvastatin, used to lower 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, Tyenne is not recommended for use with other biologic medications used to treat AR, AIJs, or AIJp.

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 birth control 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 whether Tyenne passes into breast milk.

The available data do not suggest that this treatment has any effect on fertility.

Driving and operating machines

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

Tyenne contains sodium

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

This medication is subject to restricted medical prescription by your doctor.

Tyenne will be administeredby 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 AR

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

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

Children with AIJs (2 years of age and older)

The usual dose of Tyenne depends on your 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 your body weight at each administration.

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

Children with AIJp (2 years of age and older)

The usual dose of Tyenne is calculated based on your 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 your body weight at each administration.

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

Patients with SLC

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

The dose is 12 mg per kg 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 kg of body weight. A second dose may be necessary.

If you are given more Tyenne than you should

Since a doctor or nurse administers Tyenne, it is unlikely that you will be given too much.

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

If you forget a dose of Tyenne

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

If you interrupt treatment with Tyenne

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

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

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

Severe possible side effects: consult your doctor immediately.

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

Allergic reactionsduring or after 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 doctorimmediately.

Signs of severe infections

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

Signs and symptoms of liver toxicity

They 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, notify your doctoras soon as possible.

Very common side effects:

They 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:

They may 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 by blood test,
• low fibrinogen levels in the blood (protein involved in blood clotting).

Uncommon side effects:

They may 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 may affect up to 1 in 1,000 people

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

Very rare side effects:

They may affect up to 1 in 10,000 people

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

Children with AIJs

In general, the side effects in patients with AIJs were of a similar type to those in adults with AR. Some side effects were observed more frequently: nasal and throat inflammation, diarrhea, decreased white blood cell count in the blood, and increased liver enzymes.

Children with AIJp

In general, the side effects in patients with AIJp were of a similar type to those in adults with AR. Some side effects were observed more frequently: nasal and throat inflammation, headache, feeling unwell (nausea), and decreased white blood cell count in the blood.

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 leaflet. 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 container.

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

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

Composition of Tyenne

• The active principle is tocilizumab.

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

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

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

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

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

Appearance of the product and contents of the package

Tyenne is a concentrate for solution for infusion. The concentrate is a transparent, 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 package contains 1 vial, and multiple packages contain 4 (4 packages of 1) vials. It may not be marketed in all package sizes.

Marketing authorization holder and responsible manufacturer

Fresenius Kabi Deutschland GmbH

Else-Kroener-Strasse 1

61352 Bad Homburg v.d.Hoehe

Germany

Responsible manufacturer

Fresenius Kabi Austria GmbH

Hafnerstrasse 36

8055 Graz

Austria

Last review date of this leaflet:

Other sources of information

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

This information is intended solely for healthcare professionals:

Instructions for prior dilution before administration

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

Adult patients with AR, COVID-19, and SLC (≥ 30 kg)

Withdraw from a 100 ml infusion bag a volume of sterile and pyrogen-free sodium chloride 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, in aseptic conditions. The amount of Tyenne concentrate (0.4 ml/kg) must be removed from the vial and deposited in the 100 ml infusion bag. The final volume must be 100 ml. To mix the solution, gently invert the infusion bag to avoid foam formation.

Use in pediatric population

Patients with AIJs, with AIJp, and SLC with a weight of ≥ 30 kg

Withdraw from a 100 ml infusion bag a volume of sterile and pyrogen-free sodium chloride 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, in aseptic conditions. The amount of Tyenne concentrate (0.4 ml/kg) must be removed from the vial and deposited in the 100 ml infusion bag. The final volume must be 100 ml. To mix the solution, gently invert the infusion bag to avoid foam formation.

Patients with AIJs and SLC with a weight of <30 kg

Withdraw from a 50 ml infusion bag a volume of sterile and pyrogen-free sodium chloride 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, in aseptic conditions. The amount of Tyenne concentrate (0.6 ml/kg) must be removed from the vial and deposited in the 50 ml infusion bag. The final volume must be 50 ml. To mix the solution, gently invert the infusion bag to avoid foam formation.

Patients with AIJp with a weight of <30 kg

Withdraw from a 50 ml infusion bag a volume of sterile and pyrogen-free sodium chloride 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, in aseptic conditions. The amount of Tyenne concentrate (0.5 ml/kg) must be removed from the vial and deposited in the 50 ml infusion bag. The final volume must be 50 ml. To mix the solution, gently invert the infusion bag to avoid foam formation.

Tyenne is for single use.

All unused or waste product must be disposed of in accordance with local requirements.