TYENNE 20 mg /Ml Concentrate For Infusion Solution

Зміст інструкції

1. Tyenne 20 mg/mL concentrate for solution for infusion
   1. What is Tyenne and what is it used for
   2. What you need to know before you are given Tyenne
   3. How Tyenne is administered
   4. Possible side effects
   5. How to store Tyenne
   6. Contents of the pack and other information
2. Tyenne 162 mg injectable solution in pre-filled syringe
   1. What is Tyenne and what is it 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. Content of the pack and other information
3. Tyenne 162 mg injectable solution in pre-filled pen
   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. How to store Tyenne
   6. Contents of the pack and other information
   7. Instructions for Use

Tyenne 20 mg/mL concentrate for solution for infusion

Tocilizumab
▼This medicinal product is subject to additional monitoring. This will allow rapid
identification of new safety information. You can help by reporting any adverse effects.
See section 4 for how to report adverse effects.

Read this leaflet carefully before you are given this medicine as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or nurse. See section 4.

contains important safety information that you must know before Tyenne is
administered to you and during treatment with Tyenne.

Contents of this leaflet:

• 1. What Tyenne is and what it is used for
• 2. What you need to know before you are given Tyenne
• 3. How Tyenne is administered
• 4. Possible side effects
• 5. How to store 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, a protein produced by specific immune cells (monoclonal antibody), which blocks the action of a specific protein (cytokine) called interleukin-6. This protein is involved in the body's inflammatory processes and blocking it can reduce inflammation in your body. Tyenne helps to reduce symptoms such as pain and swelling of the joints and can also improve your performance in daily activities. Tyenne has been shown to slow down damage to the cartilage and bone of the joints caused by the disease and to improve your ability to perform normal daily activities.

• Tyenne is used to treat adultswith active moderate to severe rheumatoid arthritis (RA), an autoimmune disease, if previous therapies have not worked well enough. Tyenne is usually used in combination with methotrexate. Tyenne can also be used alone if your doctor believes that methotrexate is inappropriate.
• Tyenne can also be used to treat adult patients previously not treated with methotrexate if they suffer from severe, active and progressive rheumatoid arthritis.
• Tyenne is used to treat children with systemic JIA. Tyenne is used for children aged 2 years and older who have active systemic juvenile idiopathic arthritis (SJIA), an inflammatory disease that causes pain and swelling of one or more joints, accompanied by fever and rash. Tyenne is used to improve the symptoms of SJIA and can be given in combination with methotrexate or alone.
• Tyenne is used in children with polyarticular JIA. Tyenne is used for children aged 2 years and older with active polyarticular juvenile idiopathic arthritis (pJIA), an inflammatory disease that causes pain and swelling of one or more joints. Tyenne is

used to improve the symptoms of pJIA and can be given in combination with
methotrexate or alone.

• Tyenne is used to treat adults and childrenaged 2 years and older with severe or potentially life-threatening cytokine release syndrome(CRS), a side effect that affects patients undergoing CAR-T (chimeric antigen receptor T-cell) cell-based therapies used to treat certain malignant tumors.
• Tyenne is used to treat adults with coronavirus disease 2019 (COVID-19)on systemic corticosteroids and who require supplemental oxygen or mechanical ventilation.

2. What you need to know before you are given Tyenne

Tyenne must not be given

• if you are allergicto tocilizumab or to any of the excipients of this medicine (listed in section 6)
• if you have a serious active infection.

If any of these conditions apply to you, tell your doctor or the nursing staff administering
the infusion.

Warnings and precautions
Tell your doctor or nurse before you are given Tyenne.

• If you experience allergic reactions, such as chest tightness, wheezing, severe dizziness, a feeling of lightheadedness, swelling of the lips or skin rash during or immediately after the infusion, tell your doctor immediately.
• If you have an infectionof any kind, whether short-term or long-term, or if you have frequent infections. Tell your doctor immediatelyif you feel unwell. Tyenne may reduce the body's ability to fight infections and may worsen an existing infection or increase your chances of developing a new infection.
• If you have had tuberculosis,tell your doctor. The doctor will look for signs and symptoms of tuberculosis before starting treatment with Tyenne. If symptoms of tuberculosis (persistent cough, weight loss, fatigue, low-grade fever), or any other infection appear during or after treatment, tell your doctor immediately.
• If you have a history of intestinal ulcersor diverticulitis, tell your doctor. Symptoms may include abdominal pain and unexplained changes in your usual bowel habits accompanied by fever.
• If you have a liver disease, tell your doctor. Before using Tyenne, your doctor may want to do a blood test to check your liver function.
• If a patient has been recently vaccinated(whether an adult or a child), or plans to be vaccinated, tell your doctor. All patients, especially children, should be up to date with all vaccinations before starting treatment with Tyenne, unless it is necessary to start urgently. Some types of vaccines should not be used during treatment with Tyenne.
• If you have a tumor, tell your doctor. The doctor will need to decide whether you can still receive Tyenne.
• If you have risk factors for heart diseasesuch as high blood pressure or high cholesterol levels, tell your doctor. These factors should be monitored while you take Tyenne.
• If you have moderate to severe kidney problems, your doctor will monitor you closely.
• If you have persistent headache.

Your doctor will perform blood tests before giving you Tyenne and during treatment,
to determine if you have a low number of white blood cells or platelets, or a high
level of liver enzymes.

Children and adolescents
The use of Tyenne is not recommended in children under 2 years of age.
If a child has a history of macrophage activation syndrome(uncontrolled activation and proliferation
of specific blood cells), tell your doctor. They will need to decide whether the patient
can still receive Tyenne.

Other medicines and Tyenne
Tell your doctor if you are taking any other medicines (or if your child is
the patient) or if you have recently taken any, including over-the-counter
medicines. Tyenne can affect the way some medicines work and the dose of these may
need to be adjusted. Tell your doctorif you are using medicines that contain the following
active ingredients:

• 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, anticoagulants used to thin the blood
• phenytoin, used to treat seizures
• cyclosporine, used to suppress the immune system during organ transplantation
• benzodiazepines (such as temazepam), used to treat anxiety.

Regarding vaccinations, see the warnings section above.
Due to the lack of clinical experience, Tyenne is not indicated for use with other biological drugs
for the treatment of RA, systemic juvenile idiopathic arthritis or polyarticular juvenile idiopathic arthritis.

Pregnancy and breastfeeding
Tyenne should not be used during pregnancy unless strictly necessary.
Tell your doctor if you are pregnant, if you might become pregnant or if you are planning a pregnancy.
Women of childbearing potential should use effective contraception during and for up to 3 months after
treatment.
Stop breastfeeding if you are about to be given Tyenne and tell your doctor.
At least 3 months should pass after the last dose before breastfeeding is started. It is not known if
Tyenne passes into breast milk
Available data so far do not indicate an effect on fertility from this treatment.

Driving and operating machinery
This medicine can cause dizziness. If you feel dizzy, do not drive or use machines.

Tyenne contains sodium
Tyenne contains 0.24 mg of sodium (the main component of table salt) per mL. This
amount corresponds to 0.012% of the recommended maximum daily intake with the diet of
an adult. Since Tyenne is diluted in a solution
containing sodium chloride 9 mg/mL (0.9%) or 4.5 mg/mL (0.45%) before intravenous administration, the doctor will take this into account in patients
on a sodium-controlled diet.

3. How Tyenne is administered

This medicine is subject to limited medical prescription by the doctor.
Tyenne will be administered drop by drop into a vein by a doctor or a nurse.They will dilute the
solution, prepare the intravenous infusion and monitor it during and after
administration.

Adult patients with AR
The usual dose of Tyenne is 8 mg per kg of body weight. Depending on your response, the doctor
may reduce the dose to 4 mg/kg and increase it back to 8 mg/kg when appropriate.
Tyenne will be administered to adult patients every 4 weeks via a drop-by-drop injection
into a vein (intravenous infusion) for one hour.

Children with AIGs (aged 2 years or older)
The usual dose of Tyenne depends on body weight.

• If the body weight is less than 30 kg: the dose is 12 mg for each kilogram of body weight.
• If the body weight is 30 kg or more: the dose is 8 mg for each kilogram of body weight. The dose is calculated based on body weight with each administration.

Tyenne will be administered to children with AIGs every 2 weeks via a drop-by-drop injection
into a vein (intravenous infusion) for one hour.

Children with AIGp (aged 2 years or older)
The usual dose of Tyenne depends on body weight.

• If the body weight is less than 30 kg: the dose is 10 mg for each kilogram of body weight.
• If the body weight is 30 kg or more: the dose is 8 mg for each kilogram of body weight. The dose is calculated based on body weight with each administration

Tyenne will be administered to children with AIGp every 4 weeks via a drop-by-drop injection
into a vein (intravenous infusion) for one hour.

Patients with CRS
In patients weighing 30 kg or more, the usual dose of Tyenne is 8 mg for each
kilogram of body weight.
In patients weighing less than 30 kg, the dose is 12 mg for each kilogram of body weight.
Tyenne can be administered alone or in combination with corticosteroids.

Patients with COVID-19
The indicated dose of Tyenne is 8 mg for each kilogram of body weight. A second dose may be necessary.

If you are given too much Tyenne
Since Tyenne will be administered by a doctor or a nurse, it is unlikely that
you will be given too much. However, if you have any concerns, contact your doctor.

If you do not receive a dose of Tyenne
Since Tyenne will be administered by a doctor or a nurse, it is unlikely that
you will miss a dose. However, if you have any concerns, contact your doctor or nurse.

If you stop taking Tyenne
You should not stop treatment with Tyenne without first talking to your doctor.
If you have any questions about the use of this medicine, contact your doctor or nurse.

4. Possible side effects

Like all medicines, Tyenne can cause side effects, although not everybody gets them.
Side effects can occur up to 3 months after the last dose of
Tyenne.

Possible serious side effects:report to your doctor immediately.

These are common: they can affect 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 notice any of these symptoms, tell your immediatelydoctor.

Signs of serious infections

• fever and chills
• blisters in the mouth or on the skin
• stomach pain

Signs and symptoms of liver toxicity

These can affect up to 1 in 1000 people

• fatigue
• abdominal pain
• jaundice (yellowing of the skin and the white of the eyes)

If you notice any of these symptoms, tell your doctor as soon as possible.
Very common side effects:

These can affect more than 1 in 10 people

• upper respiratory tract infections with typical symptoms such as cough, stuffy nose, runny nose, sore throat and headache
• high levels of fats in the blood (cholesterol).

Common side effects:

These can affect up to 1 in 10 people

• lung infection (pneumonia)
• shingles (herpes zoster)
• cold sores (oral herpes simplex), blister formation
• skin infections (cellulitis) sometimes associated with fever and chills
• skin 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 number of white blood cells (neutropenia, leucopenia) detected by blood tests
• abnormalities in liver function tests (increased transaminases)
• increased bilirubin as shown in blood tests
• low levels of fibrinogen in the blood (a protein involved in blood clotting).

Uncommon side effects:

These can affect up to 1 in 100 people

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

Rare side effects:

These can affect up to 1 in 1000 people

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

Very rare side effects:

These can affect up to 1 in 10000 people

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

Children with AIGs
In general, side effects of a similar type to those
in adult patients with AR have been observed in patients with AIGs. Some side effects have been observed more frequently:
inflammation of the nose and throat, diarrhea, low white blood cells and increased liver transaminases.

Children with AIGp
In general, the side effects in AIGp patients were similar to those observed in adult patients
with AR. Some side effects have been observed more frequently: inflammation of
nose and throat, headache, feeling unwell (nausea) and low white blood cells.

Reporting of side effects
If you get any side effect, even if not listed in this leaflet, tell your
doctor, pharmacist or nurse. You can also report side effects directly
through the national reporting system listed in Annex V. By reporting side
effects you can help provide more information on the safety of this medicine

5. How to store Tyenne

Keep Tyenne out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack.
Store in a refrigerator (2 °C – 8 °C). Do not freeze.
Keep the vial in the outer packaging to protect the medicine from light.

6. Contents of the pack and other information

What Tyenne contains

• The active substance 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 excipients are L-arginine, L-histidine, L-lactic acid, sodium chloride, polysorbate 80, hydrochloric acid (E507) and/or sodium hydroxide (E524), water for injections. Regarding sodium, see paragraph 2 “Tyenne contains sodium” above.

Description of the appearance of Tyenne and contents of the pack
Tyenne is a concentrate for solution for infusion. The concentrate is a liquid of clear appearance and
from colourless to light yellow.
Tyenne is supplied in vials containing 4 mL, 10 mL and 20 mL of concentrate for solution for
infusion. Each pack contains 1 vial and the multiple packs contain 4 (4
packs of 1). Not all pack sizes may be marketed.

Marketing Authorisation Holder
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

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

The following information is intended exclusively for healthcare professionals:
Instructions for dilution before administration
Medicines for parenteral administration must be visually inspected before
administration to exclude the presence of particulate matter or signs of colour change. Only clear and
from colourless to light yellow solutions, free of
visible particles, should be diluted. Use a sterile needle and syringe to prepare Tyenne.

Adult patients with AR, COVID-19 and CRS (≥ 30 kg)
Under aseptic conditions, withdraw a volume of sterile, non-pyrogenic sodium
chloride 9 mg/mL (0.9%) or 4.5 mg/mL (0.45%) solution from a 100 mL infusion bag equal to the volume of
Tyenne concentrate required for the patient’s dose. The required amount of Tyenne concentrate
(0.4 mL/kg) must be withdrawn from the vial and added to 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 the paediatric population
Patients with AIGs, AIGp and CRS weighing ≥ 30 kg
Under aseptic conditions, withdraw a volume of sterile, non-pyrogenic sodium
chloride 9 mg/mL (0.9%) or 4.5 mg/mL (0.45%) solution from a 100 mL infusion bag equal to the volume of
Tyenne concentrate required for the patient’s dose. The required amount of Tyenne concentrate
( 0.4 mL/kg) must be withdrawn from the vial and added to 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 AIGs and CRS weighing < 30 kg
Under aseptic conditions, withdraw a volume of sterile, non-pyrogenic sodium
chloride 9 mg/mL (0.9%) or 4.5 mg/mL (0.45%) solution from a 50 mL infusion bag equal to the volume of
Tyenne concentrate required for the patient’s dose. The required amount of Tyenne concentrate
( 0.6 mL/kg) must be withdrawn from the vial and added to 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 AIGp weighing < 30 kg
Under aseptic conditions, withdraw a volume of sterile, non-pyrogenic sodium
chloride 9 mg/mL (0.9%) or 4.5 mg/mL (0.45%) solution from a 50 mL infusion bag equal to the volume of
Tyenne concentrate required for the patient’s dosage. The required amount of Tyenne concentrate
( 0.5 mL/kg) must be withdrawn from the vial and added to 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.
Any unused medicine and waste materials derived from such medicine should be disposed of in accordance
with local regulations.

Tyenne 162 mg injectable solution in pre-filled syringe

Tocilizumab
This medicine is subject to additional monitoring. This will allow rapid
identification of new safety information. You can help by reporting any adverse effects.
See section 4 for how to report adverse effects.

Read this leaflet carefully before you start this medicine, as it contains
important information for you.

• Keep this leaflet. 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. Do not pass it on to others, even if their symptoms are the same as yours, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

contains important safety information that you must know before Tyenne is
administered to you and during treatment with Tyenne.

Contents of this leaflet:

• 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. How to store 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, a protein produced by specific immune cells (monoclonal antibody) that blocks the action of a specific protein (cytokine) called interleukin-6. This protein is involved in the body's inflammatory processes and blocking it can reduce inflammation in your body. Tyenne is used to treat:

• adults with active moderate to severe rheumatoid arthritis (RA), an autoimmune disease, if previous therapies have not worked well enough.
• adults with severe, active and progressive rheumatoid arthritis (RA), previously not treated with methotrexate.

Tyenne helps to reduce the symptoms of RA, such as pain and swelling of the joints, and can also improve your ability to perform daily activities. Tyenne has been shown to slow down damage to the cartilage and bone of the joints caused by the disease and to improve your ability to carry out normal daily activities. Tyenne is usually used in combination with another medicine for RA called methotrexate. However, Tyenne can still be used alone if the doctor decides that treatment with methotrexate is inappropriate.

• adults with an artery disease called giant cell arteritis (GCA),caused by inflammation of the large arteries in the body, especially those that

carry blood to the head and neck. Symptoms include headache, fatigue (tiredness) and pain in the jaw/mandible. Effects can include stroke and blindness. Tyenne can reduce pain and swelling of arteries and veins in the head, neck and arms.
GCA is often treated with medicines called steroids, which are generally effective, but can cause unwanted effects if used at high doses for prolonged periods.
Also, reducing the dose of steroids can cause a flare-up of GCA.
Adding Tyenne to the treatment means being able to use steroids for a shorter period, while still keeping the disease under control.

• children and adolescents, aged 1 year and over, 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 determine an improvement in the symptoms of sJIA. It can be administered in combination with methotrexate or alone.

• children and adolescents, aged 2 years and over, with active polyarticular juvenile idiopathic arthritis (pJIA), an inflammatory disease that causes pain and swelling in one or more joints.

Tyenne is used to determine an improvement in 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 a pediatric patient under your care are allergic to tocilizumab or any of the excipients of this medicine (listed in section 6).
• if you or a pediatric patient under your care have a serious active infection.

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

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Tyenne.

• If you experience allergic reactions, such as chest tightness, wheezing, severe dizziness or a feeling of lightheadedness, swelling of the lips, tongue, skin itching or facial itching, hives or rash during the injection or immediately after, tell your doctor immediately.
• If you experience any symptoms indicative of an allergic reaction after receiving Tyenne, do not take the next dose until you have informed your doctor AND they have told you to take it.
• If you have an infectionof any type, short-term or long-term, or if you have frequent infections. Tell your doctor immediatelyif you feel unwell. Tyenne may reduce the body's ability to respond to infections and may worsen an existing infection or increase the chances of developing a new infection.
• If you have had tuberculosis, tell your doctor. The doctor will look for signs and symptoms of tuberculosis before starting therapy with Tyenne. If symptoms of tuberculosis (persistent cough, weight loss, malaise, mild fever) or any other infection appear during or after therapy, tell your doctor immediately.

persistent, weight loss, malaise, mild fever) or any other infection appear
during or after therapy, tell your doctor immediately.

• If you have had intestinal ulcersor diverticulitis, tell your doctor. Symptoms may include abdominal pain and unexplained changes in bowel habits associated with fever.
• If you have a liver disease, tell your doctor. Your doctor may want to have a blood test to check your liver function before using Tyenne.
• If a patient has been recently vaccinated or plans to be vaccinated, tell your doctor. All patients should be up to date on all vaccinations before starting treatment with Tyenne. Some types of vaccines should not be given during therapy with Tyenne.
• If you have cancer, tell your doctor. The doctor will need to decide whether you can still receive Tyenne.
• If you have risk factors for heart diseasesuch as high blood pressure or high cholesterol levels, tell your doctor. These factors should be monitored while you take Tyenne.
• If you have moderate to severe kidney problems, your doctor will monitor you.
• If you have persistent headaches.

The doctor will perform a blood test before giving you Tyenne, to determine if
you have a low number of white blood cells or platelets, or a high level of liver
enzymes.

Children and adolescents
The use of Tyenne in pre-filled syringe is not recommended in children under 1 year of age.
Tyenne should not be given to children with JIA (juvenile idiopathic arthritis
systemic) weighing less than 10 kg.
If a child has a history of macrophage activation syndrome(uncontrolled activation and
proliferation of specific blood cells), tell your doctor. The doctor will need to
decide whether the patient can still be treated with Tyenne.

Other medicines and Tyenne
Tell your doctor if you are taking any other medicines or if you have recently taken any.
Tyenne can affect the way some medicines work and the dose of these may need to be
adjusted. Tell your doctorif you are using medicines that contain the following active ingredients:

• 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, anticoagulants used to thin the blood
• phenytoin, used to treat seizures
• cyclosporine, used to suppress the immune system during organ transplantation
• benzodiazepines (such as temazepam), used to treat anxiety

Regarding vaccinations, see the warnings section above.
Due to the lack of clinical experience, Tyenne is not indicated for use with other biological drugs
for the treatment of RA, JIA, JIAS or ACG.

Pregnancy and breastfeeding
Tyenne should not be used during pregnancy unless strictly necessary. Tell your doctor if you are
pregnant, if you might become pregnant or if you are planning a pregnancy.
Women of childbearing potential should use effective contraception during and up to 3 months after
treatment.
Stop breastfeeding if you are about to be given Tyenne and tell your doctor. At least 3 months must pass
after the last dose of Tyenne before breastfeeding is started. It is not known whether Tyenne
passes into breast milk.

Driving and using machines
This medicine can cause dizziness. If you feel dizzy, do not drive or use machines.

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

3. How to use Tyenne

Always use this medicine exactly as your doctor, pharmacist or
nurse has instructed. If you are unsure, ask your doctor, pharmacist or nurse.
Treatment will be prescribed and initiated by healthcare professionals experienced in the diagnosis and treatment
of AR, JIA, systemic JIA or ACG.

Adultswith AR or ACG
The recommended dosefor adults with AR (rheumatoid arthritis) and ACG (giant cell arteritis) is 162 mg (the content of 1 pre-filled syringe) administered once a week.

Children and adolescents with JIA (aged 1 year or 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 syringe) once every 2 weeks.
• If the patient weighs 30 kg or more: the dose is 162 mg (the content of 1 pre-filled syringe) once a week.

Children and adolescents with systemic JIA (aged 2 years or 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 syringe) once every 3 weeks.
• If the patient weighs 30 kg or more: the dose is 162 mg (the content of 1 pre-filled syringe) once every 2 weeks.

Tyenne is administered by injection under the skin (subcutaneous). At first, Tyenne may be
administered by your doctor or nurse. However, your doctor may decide that you are
able to inject Tyenne yourself. In this case, you will be instructed on how to self-inject Tyenne. Parents and caregivers will be instructed on how to inject Tyenne into
patients who are unable to self-inject the medicine, such as children.
Talk to your doctor if you have any questions about self-administering an injection or about administering to a child.

If you use more Tyenne than you should
Since Tyenne will be administered using a pre-filled syringe, it is unlikely that
you will be given too much. However, if you have any concerns, contact your doctor, pharmacist or nurse.

If an adult with AR or ACG or a child or adolescent with JIA 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 have forgotten the weekly dose and less than 7 days have passed since the missed dose, administer the dose on the next scheduled day.
• If you have forgotten the alternate-week dose and less than 7 days have passed since the missed dose, inject the dose as soon as you remember and administer the next one regularly on the scheduled day and time.
• If you have forgotten the dose and more than 7 days have passed since the missed dose, or if you are unsure when to inject Tyenne, contact your doctor or pharmacist.

If a child or adolescent with systemic JIA misses or forgets a dose
It is very important to use Tyenne exactly as prescribed by your doctor. Keep track of the
next dose.

• If a dose has been forgotten and less than 7 days have passed since the missed dose, inject the dose as soon as you remember and administer the next one regularly on the scheduled day and time.
• If a dose has been forgotten and more than 7 days have passed since the missed dose, or if you are unsure when to inject Tyenne, contact your doctor or pharmacist.

If you stop using Tyenne
Do not stop using Tyenne without first talking to your doctor.
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or
nurse

4. Possible side effects

Like all medicines, Tyenne can cause side effects, although not everybody gets them.
Side effects may occur up to 3 months or more after the last dose of Tyenne.

Possible serious common side effects: tell your doctor immediately.

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

Allergic reactionsduring or after the injection:

• difficulty breathing, chest tightness or dizziness;
• skin rash, itching, hives, swelling of the lips, tongue or face. If you notice any of these symptoms, tell 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

These may affect up to 1 in 1,000 people

• fatigue
• abdominal pain
• jaundice (yellowing of the skin and the white of the eyes)

If you notice any of these symptoms, tell your doctor as soon as possible.

Very common side effects:

May affect 1 in 10 people or more

• upper respiratory tract infections with typical symptoms such as cough, stuffy nose, runny nose, sore throat and headache
• high levels of fats 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)
• cold sores (oral herpes simplex), blister formation
• skin infections (cellulitis) sometimes associated with fever and chills
• skin 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 number of white blood cells as shown by blood tests (neutropenia, leukopenia)
• abnormalities in liver function tests (increased transaminases)
• increased bilirubin as shown 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)
• red and swollen areas in the mouth
• high levels of fats in the blood (triglycerides)
• gastric ulcer
• kidney stones
• hypothyroidism.

Rare side effects:

These may affect up to 1 in 1,000 people

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

Very rare side effects:

May affect up to 1 in 10,000 people

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

Additional side effects in children and adolescents with AIGs or AIGp
Side effects observed in children and adolescents with AIGs or AIGp are generally
similar to those recorded in adults. Some side effects are found more often in
children and adolescents: inflammation of the nose and throat, headache, feeling unwell
(nausea) and low white blood cell counts.

Reporting of side effects
If you get any side effect, even if not listed in this leaflet, tell your doctor, pharmacist or nurse. You can also report side effects
directly through the national reporting system listed in Annex V. By reporting side effects you can help provide more information on the safety of
this medicine.

5. How to store Tyenne

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack and on the label of the
pre-filled syringe (Exp.). The expiry date refers to the last day of the month.
Store in a refrigerator (2 °C – 8 °C). Do not freeze.
Keep the pre-filled syringes in the outer packaging to protect them from light.
A single pre-filled syringe can be stored at temperatures up to a maximum of 25 °C for
a single period of up to 14 days. The pre-filled syringe must be protected from light and discarded if
not used within the 14-day period.
The medicine should not be used if the solution is cloudy or contains particles, if it is not colourless or
presents a colour different from pale yellow, or if any part of the pre-filled syringe appears
damaged.
The syringe must not be shaken.
After removing the cap, the injection must be started immediately to prevent the
medicine from drying out and blocking the needle. If the pre-filled syringe is not used immediately
after removing the cap, it must be disposed of in a puncture-resistant container and
use a new pre-filled syringe.
If, after inserting the needle, it is not possible to push the plunger, the pre-filled syringe must be disposed of in a puncture-
resistant container and use a new pre-filled syringe.

6. Content of the pack and other information

What Tyenne contains
The active ingredient is tocilizumab.

• Each pre-filled syringe of 0.9 mL contains 162 mg of tocilizumab.

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

Description of the appearance of Tyenne and contents of the pack
Tyenne is an injectable solution. The solution is clear and colourless to pale yellow.
Tyenne is supplied in a pre-filled syringe of 0.9 mL containing 162 mg of tocilizumab solution
for injection.
Each pack contains 1, 4 or 12 pre-filled syringes. Not all pack sizes may be
marketed.

Marketing Authorisation Holder
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

Other sources of information
More detailed information on this medicinal product is available on the website of the European
Medicines Agency: http://www.ema.europa.eu/ .

7Instructions for use
Read these instructions for use before using the pre-filled syringe of Tyenne and each time you
receive a new prescription.
Important information
important information before using it.

• For the first use of the pre-filled syringe of Tyenne, make sure your doctor shows you or your carer how to use it correctly. Note that the syringe is supplied in an open plastic tray.
• People who are blind or have poor eyesight should not use the pre-filled syringe of Tyenne without the help of a person trained in the use of the Tyenne pre-filled syringe.
• Talk to your doctor if you have any questions or concerns.

Storage of the Tyenne pre-filled syringes

• Store the pre-filled syringe in its original packaging in a refrigerator at a temperature between 2°C and 8°C.
• Keep the pre-filled syringe in its original packaging to protect it from light.
• Keep the pre-filled syringe out of the reach and sight of children.

Do not freezeTyenne.

Do not usethe Tyenne pre-filled syringe if it has been frozen or left in direct sunlight
as this may cause reactions.

Using the Tyenne pre-filled syringe

• Always inject Tyenne using the technique that your doctor has taught you.
• The Tyenne pre-filled syringe is for single use only (one time only).

Do not shareyour Tyenne pre-filled syringe with another person. You could transmit
an infection to another person or contract an infection from them.

• The Tyenne pre-filled syringe has a transparent needle shield that covers the needle after the injection has been completed.

Do not usethe pre-filled syringe if the packaging is open or damaged.

Do not usethe pre-filled syringe if it has been dropped onto a hard surface. The pre-filled syringe may
be broken even if you cannot see the break.

Do not removethe needle cap from the pre-filled syringe until you are ready for the injection.

Do not tryto reuse the pre-filled syringe as this may cause an infection.

Transporting the Tyenne pre-filled syringe

• If necessary, for example when travelling, the Tyenne pre-filled syringe can be stored at room temperature between 20 °C and 25 °C for a maximum of 14 days.
• Discard (dispose of) Tyenne that has been stored at room temperature between 20 °C and 25 °C and has not been used within 14 days.
• When travelling by plane, always consult with your airline and your doctor about the possibility of carrying injectable medicines with you. Always carry Tyenne in your hand luggage as the aircraft hold can be very cold and Tyenne may freeze.

Your Tyenne pre-filled syringe

Before use

After use

Do nottry to activate the transparent needle shield before the injection.

STEP 1: Prepare for the injection

• 1.1 Prepare a flat, clean surface, such as a table or worktop, in a well-lit area.
• 1.2 Items needed for administration ( Figure B):

• 1 alcohol swab to clean the site before the injection
• 1 sterile cotton ball or gauze to use after the injection
• 1 sharps disposal container for the safe disposal of the needle cap and used syringe (see Step 7 “Dispose of the used pre-filled syringe”).

• 1.3 Take the Tyenne box out of the refrigerator and

open it ( Figure C).

• 1.4 Remove the Tyenne plastic tray from the packaging:

Place the plastic tray with the pre-filled syringe on a flat and
clean surface.

• 1.5 Leave the pre-filled syringe in its plastic tray at room

temperature for at least 30 minutes before use to allow the medicine
to reach room temperature ( Figure D). Injecting cold medicine may cause discomfort during the injection and make
it difficult to push the plunger.

Do not speed upthe warming process in any way, for example in
a microwave oven, or by placing the syringe in hot water or in direct
sunlight.

Do not removethe needle cap while allowing the Tyenne pre-
filled syringe to reach room temperature.

min

• 1.6 Prepare your injection log and check the sites of previous injections. This will help you choose the appropriate injection site for this injection (see Step 8 “Record your injection”).

STEP 2: Wash your hands

• 2.1 Wash your hands thoroughly with soap and water and dry them with a clean towel ( Figure E).

STEP 3: Check the syringe

Remove the Tyenne pre-filled syringe from the plastic tray

• Place two fingers on either side of the centre of the transparent needle shield.
• Pull the pre-filled syringe upwards and out of the tray ( FigureF).

Do not holdthe pre-filled syringe by the plunger or the needle
cap. This could damage the pre-filled syringe or activate the
transparent needle shield.

Figure F

• 3.1 Check the pre-filled syringe to make sure that:
• The pre-filled syringe, the transparent needle shield and the needle cap are not cracked or damaged ( Figure G).

Figure G

• The needle cap is securely attached ( Figure H).

Figure H

• The spring of the needle shield is not extended ( Figure I)

Do not usethe syringe if it shows signs of damage. If damaged, call your doctor or
pharmacist immediately and dispose of the syringe in the sharps container (see Step 7 “Dispose of the pre-filled syringe”).

• 3.2 Check the liquid through the transparent window of the syringe to make sure that:
• The liquid is clear and colourless to pale yellow and free of particles ( Figure J). Do not usethe pre-filled syringe if the liquid is cloudy, discoloured, contains particles or shows any signs of damage. If the liquid is cloudy, discoloured, contains particles or flocculated, call your doctor or pharmacist immediately and dispose of the syringe in the sharps container (see Step 7 “Dispose of the pre-filled syringe”).

Figure J

Tyenne

• 3.3 Check the label on the pre-filled syringe to make sure that:
• The name on the pre-filled syringe

• The name on the pre-filled syringe is Tyenne.

Figure K

• The expiry date on the pre-filled syringe has not passed. If the label does not show Tyenne or the expiry date has passed, contact your doctor or pharmacist immediately and dispose of the pre-filled syringe in the sharps container (see Step 7 "Dispose of the pre-filled syringe").

STEP 4: Choose the injection site

• 4.1 Choose an injection site ( Figure L):
• The front of the thighs, or
• The abdominal area (stomach), except for 5 cm around the navel (belly button).
• If you are injecting someone else, you can use the back of the arm ( Figure M).

Do not attemptto use the upper arm area yourself.

Inject only into the indicated sites.

• 4.2 Choose a different injection site (at least 3 cm from the last area where you injected) for each new injection to reduce redness, irritation or other skin problems. Do notinject into an area that is sore (sensitive), inflamed, red, thickened, wounded or where you have stretch marks, moles or tattoos. If you have psoriasis, do notinject into lesions or red, thick, raised or scaly patches.

STEP 5: Clean the injection site

• 5.1 Rub the skin of the injection site with an alcohol swab in a circular motion to clean it ( Figure N). Allow the skin to dry before the injection. Do not blow or touch the injection site after cleaning.

STEP 6: Give the injection

• 6.1 Remove the needle cap
• Hold the pre-filled syringe in one hand by the transparent needle shield

Do not holdthe plunger while removing the needle cap.
If you are unable to remove the needle cap, you should ask
for help from the carer or contact your doctor.

• Dispose of the needle cap in the sharps container.

You may see drops of liquid on the tip of the needle. This is normal and Figure O
will not affect the dose.

Do not touchthe needle or let the needle touch any surface after
removing the needle cap, as this could cause an accidental needle
stick.

• 6.2 Pinch the skin
• With your free hand, gently pinch around the area where you intend to inject (without squeezing or touching the cleaned area) and hold it firmly to avoid injecting into the muscle ( Figure P). Injecting into the muscle may cause discomfort during the injection.

• 6.3 Insert the needle

90°
Hold the pre-filled syringe as if it were a pencil.

45°

• With a quick and brief movement, insert the needle completely into the pinched skin at an angle between 45° and 90° ( Figure Q). Give the injection with the angle your doctor has instructed you to use. It is important to use the correct angle to ensure that the medicine is injected under the skin (into the fatty tissue), otherwise the injection may be painful and the medicine may not work.

Figure Q

• 6.4 Inject
• Use your thumb to gently push the plunger all the way down ( Figure R).
• Continue to press the plunger to deliver the entire dose until you can no longer press it ( Figure S).

Figure R
Do not removethe needle from the skin while the plunger is completely
depressed.

• 6.5 Complete the injection
• Hold the syringe firmly without moving it, at the same angle it was inserted.

• Slowly release your thumb from the plunger. The plunger will move upwards. The safety system will remove the needle from the skin and cover the needle ( Figure T). Figure S

• Release the pinched skin Important:contact your doctor immediately if:
• The transparent needle shield does not cover the needle after the injection. Injecting the wrong amount of medicine could affect treatment.

Figure T
Do not reusea syringe even if not all of the
medicine has been injected.

Do not attemptto re-cap the needle as this may cause needle-stick injuries.

• 6.6 After the injection

If there is blood or fluid at the injection site, gently press with a

cotton ball or gauze on the skin ( Figure U). An adhesive bandage can be used if necessary.

Do not rubthe injection site.

STEP 7: Dispose of the used pre-filled syringe

• 7.1 Place the used syringe in a sharps disposal container immediately after use ( Figure V). If you do not have a sharps disposal container, you can use a household container that:
• Is made of durable plastic,
• Can be closed with a tight and puncture-resistant lid that will prevent sharps from leaking out,

Figure V

• Is upright and stable during use,
• Is leakproof and
• Is properly labeled to warn of the presence of hazardous waste inside the container. When your sharps disposal container is almost full, you will need to follow local guidelines for disposing of the sharps disposal container. Do notdiscard used syringes in household waste. Do notdispose of the used sharps disposal container in household trash unless local guidelines allow it. Do notrecycle the used sharps disposal container. Keep Tyenne pre-filled syringes and the disposal container out of the reach and sight of children.

STEP 8: Record the injection

• 8.1 To help you remember when and where to give your next injection, write down the date, time, and specific part of your body where you injected ( Figure W).

It may also be helpful to write down any questions or concerns
about the injection so you can ask your doctor.

If you have any questions or concerns about the Tyenne pre-filled syringe,
contact the doctor who is familiar with Tyenne.

Tyenne 162 mg injectable solution in pre-filled pen

tocilizumab

• This medicine is subject to additional monitoring. This will allow rapid identification of new safety information. You can help by reporting any side effects. See section 4 for how to report side effects.

Read this leaflet carefully before you start to use this medicine as it contains
important information for you.

• Keep this leaflet. 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. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

contains important safety information that you must know before you are
given Tyenne and during treatment with Tyenne.

Contents of this leaflet:

• 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. How to store Tyenne
• 6. Contents of the pack and other information

1. What is Tyenne and what is it used for

Tyenne contains the active ingredient tocilizumab, a protein produced by specific immune cells (monoclonal antibody) that blocks the action of a specific protein (cytokine) called interleukin-6. This protein is involved in the inflammatory processes of the body and blocking it can reduce inflammation in your body. Tyenne is used to treat:

• adults with active moderate to severe rheumatoid arthritis (RA), an autoimmune disease, if previous therapies have not worked well enough.
• adults with severe, active and progressive rheumatoid arthritis (RA),previously not treated with methotrexate.

Tyenne helps to reduce the symptoms of RA, such as pain and swelling of the joints, and can also improve your ability to perform daily activities. Tyenne has been shown to slow down damage to the cartilage and bone of the joints caused by the disease and to improve your ability to carry out normal daily activities. Tyenne is usually used in combination with another medicine for RA called methotrexate. Tyenne can still be used alone if the doctor decides that treatment with methotrexate is inappropriate.

• adults with an artery disease called giant cell arteritis (GCA),caused by inflammation of the large arteries in the body, especially those that carry blood to the head and neck. Symptoms include headache, fatigue (tiredness) and pain in the jaw/jawbone. Effects can include stroke and blindness.

Tyenne can reduce the pain and swelling of arteries and veins in the head, neck and arms.
GCA is often treated with medicines called steroids, which are generally effective, but can cause unwanted effects if used at high doses for prolonged periods. In addition, reducing the dose of steroids can cause a flare-up of GCA. Adding Tyenne to the treatment means being able to use steroids for a shorter period, while still keeping the disease under control.

• children and adolescents, 12 years of age and older, with activejuvenile idiopathic arthritissystemic(JIS), an inflammatory disease that causes pain and swelling in one or more joints, as well as fever and rash.

Tyenne is used to determine an improvement in the symptoms of JIS. It can be administered in combination with methotrexate or alone.

• children and adolescents, 12 years of age and older, with activejuvenile idiopathic arthritispolyarticular(JIP), an inflammatory disease that causes pain and swelling in one or more joints.

Tyenne is used to determine an improvement in the symptoms of JIP. It can be administered in combination with methotrexate or alone.

2. What you need to know before you use Tyenne

Do not use Tyenne

• if you or a pediatric patient under your care are allergic to tocilizumab or any of the other ingredients of this medicine (listed in section 6).
• if you or a pediatric patient under your care have a serious active infection.

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

Warnings and precautions
Talk to your doctor, pharmacist or nurse before you use Tyenne.

• If you experience allergic reactions, such as chest tightness, wheezing, severe dizziness or a feeling of lightheadedness, swelling of the lips, tongue, skin itching or facial itching, hives or rash during the injection or immediately after, tell your doctor immediately.
• If you experience any symptoms indicative of an allergic reaction after receiving Tyenne, do not take the next dose until you have informed your doctor and they have told you to take it.
• If you have an infectionof any type, short-term or long-term, or if you have frequent infections. Tell your doctor immediatelyif you feel unwell. Tyenne may reduce the body's ability to respond to infections and may worsen an existing infection or increase the chances of developing a new infection.
• If you have had tuberculosis, tell your doctor. The doctor will look for signs and symptoms of tuberculosis before starting therapy with Tyenne. If symptoms of tuberculosis (persistent cough, weight loss, fatigue, mild fever) or any other infection appear during or after therapy, tell your doctor immediately.
• If you have had intestinal ulcersor diverticulitis, tell your doctor. Symptoms may include abdominal pain and unexplained changes in bowel habits accompanied by fever.
• If you have a liver disease, tell your doctor. Your doctor may want to do a blood test to check your liver function before you use Tyenne.
• If a patient has been recently vaccinatedor plans to be vaccinated, they should tell their doctor. All patients should be up to date with all vaccinations before starting treatment with Tyenne. Some types of vaccines should not be given during therapy with Tyenne.
• If you have cancer, tell your doctor. The doctor will need to decide if you can still receive Tyenne.
• If you have risk factors for heart diseasesuch as high blood pressure or high cholesterol levels, tell your doctor. These factors should be monitored while you take Tyenne.
• If you have moderate to severe kidney problems, your doctor will monitor you.
• If you have persistent headache.

Your doctor will perform blood tests before giving you Tyenne, to determine if you have
a low number of white blood cells or platelets, or a high level of liver enzymes.

Children and adolescents
The use of Tyenne in a pre-filled pen is not recommended in children under 12 years of age.
Tyenne should not be given to children with JIA (juvenile idiopathic arthritis) who weigh less than 10 kg.
If a child has a history of macrophage activation syndrome(uncontrolled activation and
proliferation of specific blood cells), tell your doctor. The doctor will need to
decide if the patient can still be treated with Tyenne.

Other medicines and Tyenne
Tell your doctor if you are taking or have recently taken any other medicines. Tyenne can
affect the way some medicines work and the dose of these may need to be
adjusted. Tell your doctorif you are using medicines that contain the following active ingredients:

• methylprednisolone, 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, anticoagulants used to thin the blood
• phenytoin, used to treat seizures
• cyclosporine, used to suppress the immune system during organ transplantation
• benzodiazepines (such as temazepam), used to treat anxiety.

Regarding vaccinations, see the warnings section above.
Due to the lack of clinical experience, Tyenne is not indicated for use with other biological drugs
for the treatment of RA, JIA, JIAS or ACG.

Pregnancy and breastfeeding
Tyenne should not be used during pregnancy unless strictly necessary. Tell your doctor if you are
pregnant, might become pregnant or are planning a pregnancy.
Women of childbearing potential should use effective contraception during and up to 3 months after
treatment.
Stop breastfeeding if you are about to be given Tyenne and tell your doctor. At least 3 months must pass
after the last dose of Tyenne before breastfeeding is started. It is not known whether Tyenne
passes into breast milk.

Driving and using machines
This medicine can cause dizziness. If you feel dizzy, do not drive or use machines.

Tyenne contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose of 0.9 mL, i.e.
essentially “sodium-free”.

3. How to use Tyenne

Use this medicine following exactly the instructions of your doctor, pharmacist or
nurse. If you have any doubts, ask your doctor, pharmacist or nurse.
Treatment will be prescribed and initiated by healthcare professionals experienced in the diagnosis and treatment
of RA, JIA, systemic JIA or ACG.

Adults with RA or ACG
The recommended dosefor adults with RA (rheumatoid arthritis) or ACG (giant cell arteritis) is 162 mg (the content of 1 pre-filled pen) administered once a week.

Adolescents with JIA (aged 12 years or 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 systemic JIA (aged 12 years or 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 beginning, Tyenne may be
administered to you by your doctor or nurse. However, your doctor may decide that you are able to inject Tyenne yourself. In this case, you will be instructed on how to self-inject Tyenne. Parents and those who care for patients will be instructed on how to inject Tyenne in
patients who are unable to self-inject the medicine.
Talk to your doctor if you have any questions about self-administering an injection or administering an injection in an adolescent patient you are caring for. At the end of this

If you use more Tyenne than you should
Since Tyenne will be administered to you using a pre-filled pen, it is unlikely that
you will be given too much. However, if you have any concerns, contact your doctor, pharmacist or nurse.

If an adult with RA or ACG or an adolescent with JIA misses or forgets a dose
It is very important that you use Tyenne exactly as prescribed by your doctor. Keep track of your
next dose.

• If you miss your weekly injection within 7 days, take your next scheduled dose.
• If you miss your every-other-week injection within 7 days, take the missed dose as soon as you remember and subsequent doses as scheduled.
• If you miss your weekly or every-other-week injection for more than 7 days or are unsure when to inject Tyenne, call your doctor or pharmacist.

If an adolescent with systemic JIA misses or forgets a dose
It is very important to use Tyenne exactly as prescribed by your doctor. Keep track of the
next dose.

• If a dose has been missed and less than 7 days have passed since the missed dose, inject a dose as soon as you remember and administer the next one regularly on the scheduled day and time.
• If a dose has been missed and more than 7 days have passed since the missed dose, or you are unsure when to inject Tyenne, contact your doctor or pharmacist.

If you stop taking Tyenne
You should not stop taking Tyenne without first talking to your doctor.
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or
nurse.

4. Possible side effects

Like all medicines, Tyenne can cause side effects, although not everybody gets them.
Side effects can occur up to 3 months or more after stopping Tyenne.

Serious possible side effects: tell your doctor immediately.

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

Allergic reactionsduring or after the injection:

• difficulty breathing, chest tightness or dizziness;
• skin rash, itching, hives, swelling of the lips, tongue or face. If you notice any of these symptoms, tell 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

These can affect up to 1 in 1000 people

• fatigue
• abdominal pain
• jaundice (yellowing of the skin and the white of the eyes)

If you notice any of these symptoms, tell your doctor as soon as possible.

Very common side effects:

May affect 1 in 10 people or more

• upper respiratory tract infections with typical symptoms such as cough, stuffy nose, runny nose, sore throat and headache
• high levels of fats in the blood (cholesterol)
• reactions related to the injection site.

Common side effects:

May affect up to 1 in 10 people

• lung infection (pneumonia)
• shingles (herpes zoster)
• cold sores (oral herpes simplex), blister formation
• skin infections (cellulitis) sometimes associated with fever and chills
• skin 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 number of white blood cells as shown by blood tests (neutropenia, leukopenia)
• abnormalities in liver function tests (increased transaminases)
• increased bilirubin as shown 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)
• red and swollen areas in the mouth
• high levels of fats in the blood (triglycerides)
• gastric ulcer
• kidney stones
• hypothyroidism.

Rare side effects:

These can affect up to 1 in 1,000 people

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

Very rare side effects:

May affect up to 1 in 10,000 people

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

Additional side effects in children and adolescents with AIGs or AIGp
The side effects observed in children and adolescents with AIGs or AIGp are generally
similar to those recorded in adults. Some side effects are found more often in
children and adolescents: inflammation of the nose and throat, headache, feeling unwell
(nausea) and lower counts of white blood cells.

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. You can also report side effects directly
through the national reporting system detailed in Annex V. By reporting side effects you can help provide more
information on the safety of this medicine.

5. How to store 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 and on the label of the
pre-filled pen (EXP.). The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C-8 °C). Do not freeze.
Keep the pre-filled pens in the outer packaging to protect them from light.
A single or pre-filled pen can be stored at temperatures 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 the 14-day period.
The medicine should not be used if the solution is cloudy or contains particles, if it is not colourless or
presents a colour different from pale yellow, or if any part of the pre-filled syringe appears
damaged.
The pen must not be shaken. After removing the cap, the injection must be started
immediately to prevent the medicine from drying out and blocking the needle. If the pre-filled pen is not
used immediately after removing the cap, it must be disposed of in a
puncture-resistant container and a new pre-filled pen used.
If after pressing the activation button the orange piston indicator does not move, it is
necessary to discard the pre-filled pen in a puncture-resistant container. Do notattempt to
reuse the pre-filled pen. Do not repeat the injection with another pre-filled pen. Contact
your healthcare professional for assistance.

6. Contents of the pack and other information

What Tyenne contains

• The active substance is tocilizumab. Each pre-filled pen contains 162 mg of tocilizumab in 0.9 mL.
• The excipients are L-arginine, L-histidine, L-lactic acid, sodium chloride, polysorbate 80, hydrochloric acid (E507) and/or sodium hydroxide (E524), water for injections.

Description of the appearance of Tyenne and contents of the pack
Tyenne is an injectable solution. The solution is clear and from colourless to pale yellow.
Tyenne is supplied in a pre-filled pen of 0.9 mL containing 162 mg of tocilizumab solution
for injection.
Each pack contains 1 or 4 pre-filled pens with multiple packs containing 12
(3 packs of 4) pre-filled pens. Not all pack sizes may be marketed.
Marketing Authorisation Holder
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

Other sources of information
More detailed information on this medicine is available on the website of the European
Medicines Agency, http://www.ema.europa.eu/ .

7. Instructions for Use

Read these instructions carefully before using the Tyenne pre-filled pen.
Read and follow the instructions for use provided with the Tyenne pre-filled pen before starting
to use it and each time you receive a new prescription. There may be new information.
This information does not replace consultation with your doctor regarding your
medical condition or treatment.
If you have any questions about using the Tyenne pre-filled pen, contact your doctor.

Important information
that you need to know before using it.
Before using the pre-filled pen for the first time, make sure your doctor shows you the
correct way to use it.

Nevertry to disassemble the Tyenne pre-filled pen.
Always inject Tyenne as your doctor has taught you.

Using the Tyenne pre-filled pen
The pre-filled pen is for self-injection or administration with the help of an assistant.
The pre-filled pen is for home use.

When injecting Tyenne, children can self-inject if both the doctor and the assistant
consider it appropriate.

Do not reusethe pre-filled pen. The pre-filled pen is for single-dose use only (1 time).

Do not shareyour pre-filled pen with another person. It could give another person an infection
or contract an infection from them.

Do not removethe transparent cap of the pre-filled pen until you are ready for
the injection.

Do not usethe pre-filled pen if it shows signs of damage or if it has been dropped.

Storing Tyenne pre-filled pens
Store Tyenne in a refrigerator between 2 °C and 8 °C.
Store unused pre-filled pens in the original packaging to protect them from
light.

Do not freeze.If Tyenne freezes, discard it in a sharps disposal container.
Keep Tyenne away from exposure to 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 packaging it
comes in for a maximum of 14 days.
Discard (dispose of) Tyenne in a sharps disposal container 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.
Transport the Tyenne pre-filled pen

• When traveling by plane, always check with your airline and your doctor about the possibility of carrying injectable medications with you. Always carry Tyenne in your hand luggage because the plane's hold could be very cold and Tyenne could freeze.

Your Tyenne pre-filled pen
Before use
After use

Cap

WindowBody

Medicinal product

Needle protection

WindowBody

Plunger rod
STEP 1: Prepare for the injectionfor injection

• 1.1Prepare a flat, clean surface, such as a table or worktop, in a well-lit area.
• 1.2 Gather the following materials (not included) (see Figure A):
• A sterile cotton ball or gauze
• An alcohol swab
• A sharps disposal container (see Step 8, “Dispose of your pre-filled pen”).

• 1.3 Remove the package containing the pre-filled pen from the refrigerator. Do notkeep the pre-filled pen out of the refrigerator for more than 14 days without using it.

• 1.4 Check the expiration date on the package to make sure it has not passed (see Figure B).

Do not usethe pre-filled pen if the expiration date has passed.

• 1.5 Remove the sealed tray from the package. Check the sealed tray for any signs of damage and make sure the expiration date on the tray has not passed.

Do not usethe pre-filled pen if the expiration date has passed, as it could
be unsafe.

Do not usethe pre-filled pen if the tray appears damagedor open.

• 1.6 Leave the sealed tray on the prepared surface for 45 minutes before use to allow the medicine in the pre-filled pen to reach room temperature (see Figure C). Note:otherwise, the injection may be uncomfortable and the injection

may take longer.

Do not heatin any other way, such as in a microwave, hot water or direct sunlight.

Keep Tyenne out of the reach of children.

• 1.7 Peel off the seal from the tray (see Figure D) and turn the tray over to remove the single-use pre-filled pen (see Figure E).

Do not removethe transparent cap of the pre-filled pen until you are
ready for the injection to avoid injury.

Step 2: Check the pre-filled pen

• 2.1 Check the pre-filled pen to make sure it is not cracked or damaged (see Figure F).

Do not useif the pre-filled pen shows signs of damage or if it has
been dropped.

• 2.2 Check the label on the pre-filled pen to make sure that:

• The name on the pre-filled pen is Tyenne
• The expiration date (EXP) on the pre-filled pen has not passed (see Figure G).

Do not usethe pre-filled pen if the name on the label is not
Tyenne or if the expiration date on the label has passed.

• 2.3 Look at the medicine through the viewing window. Make sure it is clear and colorless to pale yellowand does not contain flocculate or particles (see Figure H).

Note:air bubbles in the medicine are normal .

Do not injectif the liquid is cloudy, discolored, or contains clumps or particles

because it may not be safe to use.

STEP 3: Wash your hands

• 3.1 Wash your hands thoroughly with soap and water, then dry them with a clean towel (see Figure I).

STEP 4: Choose the injection site

• 4.1 If you are self-injecting, you can use:
• The front of the upper thigh
• The abdomen, except within 5 cm around the navel (belly button)
• If an assistant is giving the injection, they can use the outer area of the upper arm (see Figure J). Note:choose a different site for each injection to reduce redness, irritation, or other skin problems.

Do notinject into sore (sensitive), inflamed, reddened, thickened,
scaly or damaged skin, or moles, scars or stretch marks or tattoos.

Do notuse the pre-filled pen through clothing .STEP 5: Clean the injection site

• 5.1 Rub the skin at the point where you want to make the injection with an

alcohol swab to clean it (see Figure K). Let the skin dry.
Do notblow or touch the site after cleaning.

STEP 6: Give the injection

• 6.1 When you are ready for the injection, hold the pre-filled pen in one hand with the transparent cap pointing upwards. Using your other hand, firmly pull off the transparent cap without twisting it (see Figure L).

Note:use the pre-filled pen immediatelyafter removing the cap
to avoid contamination.

Do not tryto re-cap the needle, even after the injection.

Do not touchthe needle cap (the orange part located at the tip of the
pre-filled pen) as this could cause an accidental needle stick.

• 6.2 Throw away the transparent cap.
• 6.3 Rotate the pre-filled pen so that the orange needle protection is pointing downwards.
• 6.4 Position your hand on the pre-filled pen so that you can see the window.

• 6.5 Position the pre-filled pen on the skin at a 90-degree angle (straight) (see Figure M).

Note:to make sure you are injecting under the skin (into the fatty tissue), do not hold
the pre-filled pen at an angle.

Note:you do not needto pinch the skin.

To make sure you inject the full dose, read all steps from 6.6 to 6.9 before starting:

• 6.6 With one smooth motion, press the pre-filled pen firmly against the skin until you feel a first click. The orange plunger rod will move through the window during the injection (this means the injection has started) (see Figure N).

• 6.7 WAIT and hold the pre-filled pen in place until you feel a second click. This may take up to 10 seconds. Continue to PRESS (see Figure O).

• 6.8 WAIT and slowly count to 5 after hearing the second click. Continue to HOLD the pre-filled pen in place to make sure you inject a full dose (see Figure P). Do not liftthe pre-filled pen until you are sure 5 seconds have passed and the injection is complete.

• 6.9 While holding the pre-filled pen in place, check the window to make sure the orange plunger rod has completely appeared in the viewing window and has stopped moving (see Figure Q).

Note:if the orange plunger rod has not gone all the way down or if you think you
have not received a full injection, contact your doctor. Do nottry to repeat
the injection with a new pre-filled pen.

STEP 7: Remove and check the pre-filled pen

• 7.1 When the injection is complete, immediately lift the pre-filled pen from the skin (see Figure R).

Note:the needle protection will slide down and cover the needle.

Do not reclosethe pre-filled pen.

• 7.2 Check the window to ensure that the orange plunger rod is fully depressed (see Figure S).

Note: if the orange plunger rod has not descended completely or if you believe you did not receive a complete injection, contact your doctor. Do not attemptto repeat the injection with a new pre-filled pen.

• 7.3 If you see blood at the injection site, press a gauze pad or cotton ball against the skin until the bleeding stops (see Figure T).

Do not rubthe injection site.

STEP 8: Dispose of the pre-filled pen

• 8.1 Place the used pre-filled pen in a sharps disposal container immediately after use (see Figure U). Do notput the transparent cap back on the pre-filled pen. Do notthrow away (dispose of) the pre-filled pen in household waste. Do notreuse the pre-filled pen. If you do not havea sharps disposal container, you may use a household container that:
• is made of sturdy plastic,
• can be closed with a tight-fitting, puncture-resistant lid, without any sharp objects protruding,
• is upright and stable during use,
• is leak-proof and
• is adequately labeled to warn of the presence of hazardous waste inside the container. When the sharps disposal container is almost full, you will need to follow local guidelines for the proper way to dispose of the sharps container. Do notthrow away (dispose of) the used sharps disposal container in household waste unless local guidelines allow it.

Do not recyclethe used sharps disposal container.

Always keep the sharps disposal container out of
reach of children.
STEP 9:Record the injection

• 9.1 Record the date and injection site (see Figure V). Note:this will help you remember when and where to give your next injection.