Tyenne 162 mg solution for injection in pre-filled pen

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Tyenne 162 mg solution for injection in a pre-filled pen

tocilizumab

This medicinal product is subject to additional monitoring, which will allow rapid identification of new safety information. You can help by reporting any side effects you may experience. Section 4 includes information on 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, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are side effects not listed in this leaflet. See section 4.

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

Leaflet contents

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

1. What Tyenne is and what it is used for

Tyenne contains an active substance called tocilizumab, which is a protein derived 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 by blocking it, inflammation can be reduced. Tyenne is indicated for the treatment of:

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

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

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

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

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

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

GCA is often treated with medicines called steroids. These are usually effective, but they may cause side effects if used at high doses for long periods. Reducing the steroid dose may also lead to a flare-up of GCA. Adding Tyenne to treatment allows for a shorter duration of steroid use while still maintaining control of the disease.

• children and adolescents, 12 years of age and older, with active systemic juvenile idiopathic arthritis (sJIA), an inflammatory disease causing 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 causing 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.

2. What you need to know before using Tyenne

Do not use Tyenne

• If you or the pediatric patient you are caring for is allergic to tocilizumab or to any of the other components of this medicine (listed in section 6).
• If you or the pediatric patient you are caring for has a serious active infection.

If any of these apply to you, consult your doctor. Do not use Tyenne.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting treatment with Tyenne.

• If you experience allergic reactions such as chest tightness, wheezing, severe dizziness or lightheadedness, swelling of the lips, tongue, or face, 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 receiving Tyenne, do not take the next dose until you have informed your doctor and your doctor has instructed you to continue.

• If you have any type of infection, whether short-term or long-term, or if you frequently get infections, inform your doctor immediately if you feel unwell. Tyenne may reduce your body's ability to respond to infections and may worsen an existing infection or increase the risk 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 ulcers or diverticulitis, inform your doctor. Symptoms may 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 assess your liver function.

• If any patient has been recently vaccinated or plans to be vaccinated, inform your doctor. All patients should 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 have cancer, inform your doctor. Your doctor will need to decide whether you can continue treatment with Tyenne.

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

• 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 to determine whether you have low white blood cell count, low platelet count, or elevated liver enzymes.

Children and adolescents

The use of the prefilled Tyenne pen is not recommended in children under 12 years of age.

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

If the child has a history of macrophage activation syndrome (uncontrolled activation and proliferation of a specific type of blood cells), inform your doctor. Your doctor will decide whether Tyenne can continue to be administered.

Other medicines and Tyenne

Inform your doctor if you are taking any other medicines or have recently taken any. This is because Tyenne may affect how some medicines work, and a dose adjustment may be needed. Inform your doctor if you have recently used medicines containing 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 in the treatment of asthma,
• warfarin or fenprocoumon, used as anticoagulants,
• phenytoin, used to treat seizures,
• cyclosporine, used as an immunosuppressant in organ transplantation,
• benzodiazepines, such as temazepam, used to relieve anxiety.

Regarding vaccines, refer to the warning section above.

Because there is no clinical experience, the use of Tyenne with other biological medicines used to treat rheumatoid arthritis (RA), sJIA, polyarticular juvenile idiopathic arthritis (pJIA), or giant cell arteritis (GCA) is not recommended.

Pregnancy and breastfeeding

Tyenne must not be used during pregnancy unless clearly necessary. Speak with your doctor if you are pregnant, think you might be pregnant, or plan to become pregnant.

Women of childbearing potential should use effective contraception during treatment and for at least 3 months after stopping treatment.

Interrupt breastfeeding if you start treatment with Tyenne and consult your doctor. Breastfeeding should not be resumed until at least 3 months after your last dose of Tyenne. It is unknown whether Tyenne passes into breast milk.

Driving and using machines

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

Tyenne contains sodium

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

Tyenne contains polysorbate 80

This medicine contains 0.18 mg of polysorbate 80 in each 162 mg/0.9 ml pen, equivalent to 0.2 mg/ml. Polysorbates may cause allergic reactions. Inform your doctor if you or your child has any known allergies.

3. How to use Tyenne

Follow exactly the administration instructions for this medicine as given by your doctor, pharmacist, or nurse. If in doubt, consult your doctor, pharmacist, or nurse again.

Treatment should be initiated by a healthcare professional experienced in the diagnosis and treatment of RA, JIA-s, JIA-p, or GCA.

Adults with RA or GCA

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

Adolescents with JIA-s (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 weekly.

Adolescents with JIA-p (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). Initially, your doctor or nurse may administer Tyenne to you. However, your doctor may decide that you can self-inject Tyenne. In this case, you will receive information on how to self-inject Tyenne. Parents and caregivers will be trained on how to inject Tyenne for patients who cannot self-inject.

Speak with your doctor if you have any questions about how you or an adolescent you care for can self-administer an injection. Detailed “administration instructions” can be found at the end of this leaflet.

If you use more Tyenne than you should

Since Tyenne is administered in a pre-filled 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 GCA or an adolescent with JIA-s misses or forgets a dose

It is very important to use Tyenne exactly as prescribed by your doctor. Keep track 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 dose every two weeks 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 two weeks dose for more than 7 days, or if you are unsure when to inject Tyenne, contact your doctor or pharmacist.

If an adolescent with JIA-p misses or forgets a dose

It is very important to use Tyenne exactly as prescribed by the doctor. Keep track of the 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 longer, or if you are unsure when to inject Tyenne, contact your doctor or pharmacist.

If you stop treatment with Tyenne

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

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

4. Possible adverse effects

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

Possible serious adverse effects: consult your doctor immediately.

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

Allergic reactions during 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 to your doctor immediately.

Signs of serious infections:

• fever and chills,
• blisters in the mouth or on the 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 immediately.

Very common adverse 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 adverse effects:

May affect up to 1 in 10 people

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

Uncommon adverse effects:

May affect up to 1 in 100 people

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

Rare adverse effects:

May affect up to 1 in 1,000 people

• Stevens-Johnson syndrome (skin rash, which may lead to blistering and severe skin peeling),
• life-threatening allergic reactions (anaphylaxis [fatal]),
• liver inflammation (hepatitis), jaundice.

Very rare adverse effects:

May affect up to 1 in 10,000 people

• low counts of white blood cells, red blood cells, and platelets in blood tests,
• liver failure.

Additional adverse effects in children and adolescents with JIA or pJIA

Adverse effects in children and adolescents with JIA or pJIA are generally similar to those in adults. Some adverse effects observed more frequently in children and adolescents are: inflammation of the nose and throat, headache, nausea, and decreased white blood cell count.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system included in Appendix V. By reporting adverse 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 stated on the label of the prefilled pen and on the carton after (EXP). The expiry date refers to the last day of the month indicated.

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

Keep prefilled pens in their outer packaging to protect from light.

Prefilled pens may be stored at room temperature (up to 30 °C) for a single period of up to 14 days. During this time, prefilled pens must be protected from light and discarded if not used within 14 days at room temperature (up to 30 °C) or when the expiry date is reached, whichever occurs first.

Do not use this medicine if it appears cloudy or contains particles, if it is any colour other than colourless to pale yellow, or if any part of the prefilled pen appears damaged.

Do not shake the pen. After removing the needle cap, the injection should be administered immediately to prevent the medicine from drying and blocking the needle. If the prefilled pen is not used immediately after removing the needle cap, it must be disposed of in a sharps container and a new prefilled pen used.

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

6. Contents of the pack and other information

Composition of Tyenne

• The active substance 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 (E 433), hydrochloric acid (E507) and/or sodium hydroxide (E524), water for injections.

Regarding sodium and polysorbate 80, see section 2 "Tyenne contains sodium" and "Tyenne contains polysorbate 80" above.

Appearance of the product and contents of the pack

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

Tyenne is supplied in 0.9 ml pre-filled pens 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 certain pack sizes may be marketed.

Marketing Authorisation 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 the most recent 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 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 get a refill. There may be new information. This information does not replace talking with your doctor about your condition or treatment. If you have any questions about how to use the Tyenne pre-filled pen, call your doctor.

Important information

• Read the patient leaflet that comes with the Tyenne pre-filled pen to get 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 not attempt to disassemble the Tyenne pre-filled pen at any time.
• Always inject Tyenne as your doctor has instructed you.

Use of the Tyenne pre-filled pen

• The pre-filled pen is intended for self-injection or administration with the help of a caregiver.
• The pre-filled pen is for home use.
• When injecting Tyenne, children may self-inject if both the doctor and caregiver consider it appropriate.
• Do not reuse the pre-filled pen. The pre-filled pen is for single dose (single use) only.
• Do not share your pre-filled pen with another person. You could transmit an infection to another person or become infected yourself.
• Do not remove the transparent cap from the pre-filled pen until you are ready to inject.
• Do not use the pre-filled pen if it shows signs of damage or if it has been dropped.

Storage of the Tyenne pre-filled pen

• Store Tyenne in the refrigerator between 2 °C and 8 °C.
• Keep unused pre-filled pens in the original packaging to protect them from light.
• Do not freeze. If Tyenne freezes, discard it in a sharps container.
• Keep Tyenne away from heat and direct sunlight.
• Keep the pre-filled pen out of the reach and sight of children.
• Tyenne may be stored at room temperature (up to 30 °C) in the cardboard packaging in which it is presented for a maximum of 14 days.
• Dispose of Tyenne in a sharps or puncture-resistant container if it has been outside the refrigerator for more than 14 days. Once stored at room temperature, do not return it to the refrigerator.

Travelling with Tyenne pre-filled pens

• When travelling by air, always consult your airline and your doctor about carrying injectable medicines. Always carry Tyenne in your hand luggage because the cargo hold may be too cold and could cause freezing.

Parts of the Tyenne pre-filled pen

Before use

After use

STEP 1: Prepare your injection

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