RoActemra

Package leaflet: Information for the user

RoActemra 20 mg/mL concentrate for solution for infusion

tocilizumab
Please read all of this leaflet carefully before you are given this medicine because 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, including any not listed in this leaflet, tell your doctor or nurse. See section 4.

In addition to this package leaflet, you will be given a Patient Alert Card containing important safety information that you must know before being administered RoActemra and during treatment with RoActemra.

Contents of this leaflet:

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

1. What RoActemra is and what it is used for

RoActemra 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 inflammatory processes in the body, and blocking it may reduce inflammation. RoActemra helps reduce symptoms such as joint pain and swelling, and may also improve your ability to carry out daily activities. RoActemra has been shown to slow down joint cartilage and bone damage caused by the disease and to improve your ability to perform normal daily activities.

• RoActemra is used to treat adults with moderate to severe active rheumatoid arthritis (RA), an autoimmune disease, when previous treatments have not worked well enough. RoActemra is usually used in combination with methotrexate. RoActemra may also be used alone if your doctor considers methotrexate to be inappropriate.
• RoActemra may also be used to treat adult patients who have not previously been treated with methotrexate, if they have severe, active and progressive rheumatoid arthritis.
• RoActemra is used to treat children with sJIA. RoActemra is used in children aged 2 years and older who have active systemic juvenile idiopathic arthritis (sJIA), an inflammatory disease causing pain and swelling in one or more joints, accompanied by fever and rash. RoActemra is used to improve sJIA symptoms and may be given in combination with methotrexate or alone.
• RoActemra is used in children with pJIA. RoActemra is used in children aged 2 years and older with active polyarticular juvenile idiopathic arthritis (pJIA), an inflammatory disease causing pain and swelling in one or more joints. RoActemra is used to improve pJIA symptoms and may be given in combination with methotrexate or alone.
• RoActemra is used to treat adults and children aged 2 years and older with severe or potentially life-threatening cytokine release syndrome (CRS), an adverse reaction affecting patients receiving CAR-T cell (chimeric antigen receptor T-cell) therapies used to treat certain malignant tumours.
• RoActemra is used to treat adults with coronavirus disease 2019 (COVID-19) who are receiving systemic corticosteroids and require supplemental oxygen or mechanical ventilation.

2. What you should know before being given RoActemra

You will not be given RoActemra

• if you are allergic to tocilizumab or to any of the excipients of this medicine (listed in section 6)
• if you have an active severe infection (except for COVID-19)

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

Warnings and precautions

Inform your doctor or nurse before you are given RoActemra:

• If you experience allergic reactions, such as chest tightness, wheezing, severe dizziness, a feeling of fainting, swelling of the lips, or skin rash during or immediately after the infusion, inform your doctor immediately.
• If you have any type of short- or long-term infection, or if you frequently get infections. Inform your doctor immediately if you feel unwell. RoActemra may reduce your body’s ability to respond to infections and could worsen an existing infection or increase the risk of developing 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 RoActemra. If symptoms of tuberculosis (persistent cough, weight loss, fatigue, low-grade fever) or any other infection appear during or after treatment, inform your doctor immediately.
• If you have a history of intestinal ulcers or diverticulitis, inform your doctor. Symptoms may include abdominal pain and unexplained changes in bowel habits associated with fever.
• If you have liver disease, inform your doctor. Before using RoActemra, your doctor may want to perform a blood test to assess your liver function.
• If you or your child have recently been vaccinated or plan to receive a vaccination, inform your doctor. All patients, especially children, should be up to date with all vaccinations before starting treatment with RoActemra, unless urgent initiation is required. Some types of vaccines should not be used during treatment with RoActemra.
• If you have a tumor, inform your doctor. Your doctor will need to decide whether you can still receive RoActemra.
• If you have cardiovascular risk factors such as high blood pressure or elevated cholesterol levels, inform your doctor. These factors should be monitored while you are taking RoActemra.
• If you have moderate to severe kidney function problems, your doctor will monitor you.
• If you have persistent headaches, your doctor will perform blood tests before administering RoActemra and during treatment to determine whether you have low white blood cell or platelet counts, or elevated liver enzymes.

Children and adolescents

The use of RoActemra 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), inform the doctor. The doctor will need to decide whether the patient can still receive RoActemra.

Other medicines and RoActemra

Inform your doctor if you are taking any other medicines (or if your child is the patient, if they are taking any medicines) or if you have recently taken any, including medicines obtained without a prescription. RoActemra may affect how some medicines work, and the dose of these medicines may need adjustment. Inform your doctor if you are taking medicines containing the following active substances:

• methylprednisolone, dexamethasone, used to reduce inflammation
• simvastatin or atorvastatin, used to reduce cholesterol levels
• calcium channel blockers (e.g. amlodipine), used to treat high blood pressure
• theophylline, used to treat asthma
• warfarin or fenprocoumon, anticoagulants used to thin the blood
• phenytoin, used to treat seizures
• cyclosporine, used to suppress the immune system during organ transplantation
• benzodiazepines (e.g. temazepam), used to treat anxiety

Due to lack of clinical experience, RoActemra is not indicated for use with other biological drugs for the treatment of RA, sJIA or pJIA.

Pregnancy, breastfeeding and fertility

RoActemra must not be used during pregnancy unless strictly necessary.
Inform your doctor if you are pregnant, think you may be pregnant, or if you are planning a pregnancy.
Women of childbearing potential must use effective contraception during treatment and for 3 months after treatment ends.
Stop breastfeeding if you are about to be given RoActemra and inform your doctor.
At least 3 months must pass from the last dose of RoActemra before breastfeeding can be resumed.
It is not known whether RoActemra passes into breast milk.
Available data so far do not indicate an effect of this treatment on fertility.

Driving and using machines

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

RoActemra contains sodium

After dilution with 0.9% sodium chloride saline solution, this medicine contains 230.6 mg of sodium per maximum dose of 800 mg, equivalent to 11.5% of the maximum daily intake recommended by the WHO of 2 g of sodium for an adult.

RoActemra contains polysorbate

This medicine contains 5 mg of polysorbate 80 in each 200 mg/10 mL vial, 10 mg of polysorbate 80 in each 400 mg/20 mL vial, and 2 mg of polysorbate 80 in each 80 mg/4 mL vial, equivalent to 0.5 mg/mL. Polysorbates may cause allergic reactions. Inform your doctor if you or your child have any known allergies.

3. How RoActemra is administered

This medicine is subject to medical prescription restricted to physicians.
RoActemra will be administered by a doctor or nurse as an intravenous infusion (drip) into a vein. They will dilute a solution, prepare the intravenous infusion, and monitor you during and after administration.

Adult patients with RA
The usual dose of RoActemra is 8 mg per kg of body weight. Depending on your response, your doctor may reduce the dose to 4 mg/kg and increase it back to 8 mg/kg when appropriate.
Adult patients will receive RoActemra every 4 weeks via a one-hour intravenous infusion (drip into a vein).

Children with sJIA (aged 2 years and older)
The usual dose of RoActemra depends on body weight.

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

Children with sJIA will receive RoActemra every 2 weeks via a one-hour intravenous infusion (drip into a vein).

Children with pJIA (aged 2 years and older)
The usual dose of RoActemra depends on body weight.

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

Children with pJIA will receive RoActemra every 4 weeks via a one-hour intravenous infusion (drip into a vein).

Patients with CRS
In patients weighing 30 kg or more, the usual dose of RoActemra is 8 mg per kilogram of body weight.
In patients weighing less than 30 kg, the dose is 12 mg per kilogram of body weight.
RoActemra may be given alone or in combination with corticosteroids.

Patients with COVID-19
The recommended dose of RoActemra is 8 mg per kilogram of body weight. A second dose may be necessary.

If you are given more RoActemra than you should
Since RoActemra will be administered by a doctor or nurse, it is unlikely that you will receive too much. However, if you have any concerns, speak to your doctor.

If you miss a dose of RoActemra
Since RoActemra will be administered by a doctor or nurse, it is unlikely that you will miss a dose. However, if you have any concerns, speak to your doctor or nurse.

If you stop treatment with RoActemra
You must not stop treatment with RoActemra without first discussing it with your doctor.
If you have any questions about the use of this medicine, ask your doctor or nurse.

4. Possible side effects

Like all medicines, RoActemra can cause side effects, although not everybody gets them. Side effects may occur up to 3 months after the last dose of RoActemra.
Possible serious common side effects: Inform your doctor immediately if you experience any of the following:
These are common: may affect up to 1 in 10 people
Allergic reactions during or after infusion:

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

Signs of serious infections

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

Signs and symptoms of liver toxicity
These are rare: may affect up to 1 in 1000 people

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

List of other possible side effects
If you notice any of these symptoms, inform your doctor as soon as possible.
Very common side effects
These may 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
• elevated levels of blood lipids (cholesterol)

Common side effects
These may affect up to 1 in 10 people

• lung infection (pneumonia)
• shingles (herpes zoster)
• cold sores (oral herpes simplex), blistering
• skin infections (cellulitis), sometimes associated with fever and chills
• rash and itching, hives
• allergic reactions (hypersensitivity)
• eye infection (conjunctivitis)
• headache, dizziness, high blood pressure
• mouth ulcers, stomach pain
• fluid retention (oedema) in the lower legs, weight gain
• cough, shortness of breath
• low white blood cell count (neutropenia, leucopenia) detected by blood tests
• abnormalities in liver function tests (increased transaminases)
• increased bilirubin levels as shown in blood tests
• low levels of fibrinogen in the blood (a protein involved in blood clotting)

Uncommon side effects
These may affect up to 1 in 100 people

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

Rare side effects
These may affect up to 1 in 1000 people

• Stevens-Johnson syndrome (skin rash, which may lead to severe blistering and skin peeling)
• fatal allergic reactions (anaphylaxis)
• inflammation of the liver (hepatitis), jaundice

Very rare side effects
These may affect up to 1 in 10,000 people

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

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system referred to in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

Children with sJIA
In general, patients with sJIA have experienced side effects similar to those in adult patients with RA. Some side effects were observed more frequently: inflammation of nose and throat, diarrhoea, low white blood cell count and increased liver transaminases.

Children with pJIA
In general, side effects in pJIA patients were similar to those observed in adult patients with RA. Some side effects were observed more frequently: inflammation of nose and throat, headache, feeling unwell (nausea) and low white blood cell count.

5. How to store RoActemra

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 after “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 vial in the outer packaging to protect the medicine from light.

6. Package contents and other information

What RoActemra 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 sucrose, polysorbate 80, disodium phosphate dodecahydrate, sodium dihydrogen phosphate dihydrate and water for injections (see section 2 “RoActemra contains sodium” and “RoActemra contains polysorbate”).

Description of the appearance of RoActemra and contents of the pack
RoActemra is a concentrate for solution for infusion. The concentrate is a liquid, from clear to opalescent, from colourless to pale yellow.
RoActemra is supplied in vials containing 4 mL, 10 mL and 20 mL of concentrate for solution for infusion. Packs of 1 and 4 vials are available. Not all pack sizes may be marketed.

Marketing Authorisation Holder
Roche Registration GmbH
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany

Manufacturer
Roche Pharma AG
Emil-Barell-Str. 1
79639 Grenzach-Wyhlen
Germany

For further information about this medicinal product, please contact the local representative of the marketing authorisation holder:

België/Belgique/Belgien Luxembourg/Luxemburg
N.V. Roche S.A. (See/siehe Belgique/Belgien)
Tél/Tel: +32 (0) 2 525 82 11

България Magyarország
Рош България ЕООД Roche (Magyarország) Kft.
Тел: +359 2 474 5444 Tel: +36 - 1 279 4500

Česká republika Malta
Roche s. r. o. (See Ireland)
Tel: +420 - 2 20382111

Danmark Nederland
Roche Pharmaceuticals A/S Roche Nederland B.V.
Tlf.: +45 - 36 39 99 99 Tel: +31 (0) 348 438050

Deutschland Norge
Roche Pharma AG Roche Norge AS
Tel: +49 (0) 7624 140 Tlf: +47 - 22 78 90 00
or
Chugai Pharma Europe Ltd.
Zweigniederlassung Deutschland
Tel: +49 (0) 69 663000 0

Eesti Österreich
Roche Eesti OÜ Roche Austria GmbH
Tel: + 372 - 6 177 380 Tel: +43 (0) 1 27739

Ελλάδα Polska
Roche (Hellas) A.E. Roche Polska Sp.z o.o.
Τηλ: +30 210 61 66 100 Tel: +48 - 22 345 18 88

España Portugal
Roche Farma S.A. Roche Farmacêutica Química, Lda
Tel: +34 - 91 324 81 00 Tel: +351 - 21 425 70 00

France România
Roche Roche România S.R.L.
Tél: +33 (0) 1 47 61 40 00 Tel: +40 21 206 47 01
or
Chugai Pharma France
Tél: +33 (0) 1 56 37 05 20

Hrvatska
Roche d.o.o
Tel: +385 1 47 22 333

Ireland Slovenija
Roche Products (Ireland) Ltd. Roche farmacevtska družba d.o.o.
Tel: +353 (0) 1 469 0700 Tel: +386 - 1 360 26 00

Ísland Slovenská republika
Roche Pharmaceuticals A/S Roche Slovensko, s.r.o.
c/o Icepharma hf Tel: +421 - 2 52638201
Sími: +354 540 8000

Italia Suomi/Finland
Roche S.p.A. Roche Oy
Tel: +39 - 039 2471 Puh/Tel: +358 (0) 10 554 500

Kύπρος Sverige
Roche (Hellas) A.E. Roche AB
Τηλ: +30 210 61 66 100 Tel: +46 (0) 8 726 1200

Latvija
Roche Latvija SIA
Tel: +371 - 6 7039831

Lietuva
UAB “Roche Lietuva”
Tel: +370 5 2546799

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

The following information is intended exclusively for healthcare professionals:

Instructions for dilution prior to administration
Parenterally administered medicinal products must be visually inspected before administration to ensure there is no particulate matter or discoloration. Only solutions that appear from clear to opalescent, colorless to pale yellow, and free of visible particles should be diluted. Use a sterile needle and syringe to prepare RoActemra.

Adult patients with RA, COVID-19 and CRS (≥ 30 kg)
Under aseptic conditions, withdraw a volume of sterile, non-pyrogenic sodium chloride 9 mg/mL (0.9%) injection solution from a 100 mL infusion bag equal to the volume of concentrated RoActemra required for the patient's dose. The required amount of concentrated RoActemra ( 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 foaming.

Use in the pediatric population
Patients with sJIA, pJIA and CRS weighing ≥ 30 kg
Under aseptic conditions, withdraw a volume of sterile, non-pyrogenic sodium chloride 9 mg/mL (0.9%) injection solution from a 100 mL infusion bag equal to the volume of concentrated RoActemra required for the patient's dose. The required amount of concentrated RoActemra ( 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 foaming.

Patients with sJIA and CRS weighing < 30 kg
Under aseptic conditions, withdraw a volume of sterile, non-pyrogenic sodium chloride 9 mg/mL (0.9%) injection solution from a 50 mL infusion bag equal to the volume of concentrated RoActemra required for the patient's dose. The required amount of concentrated RoActemra ( 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 foaming.

Patients with pJIA weighing < 30 kg
Under aseptic conditions, withdraw a volume of sterile, non-pyrogenic sodium chloride 9 mg/mL (0.9%) injection solution from a 50 mL infusion bag equal to the volume of concentrated RoActemra required for the patient's dose. The required amount of concentrated RoActemra (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 foaming.

RoActemra is for single use only.
Any unused medicinal product and waste materials derived from its use must be disposed of in accordance with local regulations.

Package leaflet: Information for the user

RoActemra 162 mg solution for injection in pre-filled syringe

tocilizumab
Please read this leaflet carefully before taking this medicine, because 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 give it to others, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor, pharmacist or nurse. See section 4. In addition to this patient information leaflet, you will be given a Patient Alert Card, which contains important safety information that you must know before starting RoActemra and during treatment with RoActemra.

Contents of this leaflet:

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

1. What RoActemra is and what it is used for

RoActemra 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 inflammatory processes in the body, and blocking it may reduce inflammation in your body. RoActemra is used to treat:

• Adults with moderately to severely active rheumatoid arthritis (RA), an autoimmune disease, when previous treatments have not worked well enough.
• Adults with severe, active and progressive rheumatoid arthritis (RA) who have not been previously treated with methotrexate.

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

• Adults with a blood vessel disease called giant cell arteritis (GCA), caused by inflammation of the large arteries in the body, especially those supplying blood to the head and neck. Symptoms include headache, fatigue and jaw/mouth pain. Complications may include stroke and blindness.

RoActemra 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 may cause side effects if used at high doses for prolonged periods. In addition, reducing steroid dosage may lead to a flare-up of GCA. Adding RoActemra to treatment allows for shorter use of steroids while still keeping GCA under control.

• Children and adolescents aged 1 year 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.

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

• Children and adolescents aged 2 years and older with active polyarticular juvenile idiopathic arthritis (pJIA), an inflammatory disease causing pain and swelling in one or more joints.

RoActemra is used to improve the symptoms of pJIA. It may be given in combination with methotrexate or alone.

2. What you should know before using RoActemra

Do not use RoActemra

• if you or a pediatric patient under your care is allergic to tocilizumab or to any of the excipients of this medicine (listed in section 6).
• if you or a pediatric patient under your care has an active severe infection.

If any of these conditions apply to you, inform your doctor. Do not use RoActemra.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using RoActemra.

• If you experience allergic reactions, such as chest tightness, wheezing, severe dizziness or a feeling of fainting, swelling of the lips or tongue, skin or facial itching, hives, or skin rash during or immediately after the injection, inform your doctor immediately.
• If you develop any symptoms of an allergic reaction after receiving RoActemra, do not take the next dose until you have informed your doctor and he or she has advised you to continue.
• If you have an infection, either short-term or long-term, or if you frequently get infections. Inform your doctor immediately if you feel unwell. RoActemra may reduce your body’s ability to respond to infections and could worsen an existing infection or increase the risk of developing 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 RoActemra. If symptoms of tuberculosis (persistent cough, weight loss, fatigue, low-grade fever) or any other infection appear during or after treatment, inform your doctor immediately.
• If you have had intestinal ulcers or diverticulitis, inform your doctor. Symptoms may include abdominal pain and unexplained changes in bowel habits associated with fever.
• If you have liver disease, inform your doctor. Before using RoActemra, your doctor may want to perform a blood test to assess your liver function.
• If a patient has recently been vaccinated or is scheduled to receive a vaccination, inform your doctor. All patients should be up to date with all vaccinations before starting treatment with RoActemra. Some types of vaccines should not be administered during treatment with RoActemra.
• If you have a tumor, inform your doctor. Your doctor will need to decide whether you can still receive RoActemra.
• If you have cardiovascular risk factors, such as high blood pressure or elevated cholesterol levels, inform your doctor. These factors should be monitored while you are taking RoActemra.
• If you have moderate to severe kidney function problems, your doctor will monitor you.
• If you have persistent headaches.

Your doctor will perform a blood test before administering RoActemra to determine whether you have a low white blood cell count or platelet count, or elevated liver enzymes.
Children and adolescents
The use of RoActemra in the subcutaneous injectable solution is not recommended in children under 1 year of age. RoActemra must not be administered to children with sJIA weighing less than 10 kg.
If a child has a history of macrophage activation syndrome (uncontrolled activation and proliferation of specific blood cells), inform your doctor. Your doctor will need to decide whether the patient can still be treated with RoActemra.
Other medicines and RoActemra
Inform your doctor if you are currently taking any other medicines or if you have recently taken any.
RoActemra may affect how certain medicines work, and the dose of these medicines may need to be adjusted. Inform your doctor if you are taking medicines containing the following active substances:

• methylprednisolone, dexamethasone, used to reduce inflammation
• simvastatin or atorvastatin, used to reduce cholesterol levels
• calcium channel blockers (e.g., 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 (e.g., temazepam), used to treat anxiety

Due to lack of clinical experience, RoActemra is not indicated for use with other biological agents for the treatment of RA, sJIA, pJIA, or GCA.
Pregnancy, breastfeeding, and fertility
RoActemra must not be used during pregnancy unless strictly necessary. Inform your doctor if you are pregnant, think you might be pregnant, or are planning a pregnancy.
Women of childbearing potential must use an effective contraceptive method during treatment and for up to 3 months after treatment ends.
Stop breastfeeding if you are about to be given RoActemra and inform your doctor. At least 3 months must pass from the last dose of RoActemra before breastfeeding can be resumed. It is not known whether RoActemra passes into breast milk.
Driving and using machines
This medicine may cause dizziness. If you experience dizziness, do not drive or operate machinery.
RoActemra contains polysorbate
This medicine contains 0.18 mg of polysorbate 80 in each 162 mg/0.9 mL of PFS, 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 RoActemra

Always use this medicine exactly as instructed by your doctor, pharmacist, or nurse. If you are unsure, you must consult your doctor, pharmacist, or nurse.
Treatment will be prescribed and initiated by healthcare professionals experienced in the diagnosis and treatment of RA, sJIA, pJIA, or GCA.

Recommended dose
The dose for adults with RA and GCA is 162 mg (the content of 1 pre-filled syringe) administered once a week.

Children and adolescents with sJIA (aged 1 year and older)
The usual dose of RoActemra depends on the patient's body 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 pJIA (aged 2 years and older)
The usual dose of RoActemra depends on the patient's body 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.

RoActemra is administered by subcutaneous injection (subcutaneous). Initially, RoActemra may be administered to you by your doctor or nurse. However, your doctor may decide that you are able to self-inject RoActemra. In this case, you will be trained on how to self-inject RoActemra. Parents and caregivers of patients will be trained on how to inject RoActemra in patients who cannot self-inject, such as children.
Speak to your doctor if you have any questions about self-administering the injection or about the child you are caring for. Detailed “Instructions for Administration” can be found at the end of this leaflet.

If you use more RoActemra than you should
Since RoActemra is administered via a pre-filled syringe, it is unlikely that you will receive too much. However, if you have any concerns, speak to your doctor, pharmacist, or nurse.

If an adult with RA or GCA, or a child or adolescent with sJIA, misses or forgets a dose
It is very important to use RoActemra exactly as prescribed by your doctor. Keep track of your next dose.

• If you missed your weekly dose and less than 7 days have passed since the missed dose, take the dose on the next scheduled day.
• If you missed your every-other-week dose and less than 7 days have passed since the missed dose, inject the dose as soon as you remember and take the next dose at the regularly scheduled time.
• If you missed a dose and more than 7 days have passed since the missed dose, or if you are unsure when to inject RoActemra, consult your doctor or pharmacist.

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

• If a dose was missed and less than 7 days have passed since the missed dose, inject the dose as soon as you remember, and administer the next dose at the regularly scheduled time.
• If a dose was missed and more than 7 days have passed since the missed dose, or if you are unsure when to inject RoActemra, consult your doctor or pharmacist.

If you stop treatment with RoActemra
You must not stop treatment with RoActemra without first discussing it with your doctor.
If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

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

Possible serious side effects:
Contact your doctor immediately if you experience any of the following:

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

Allergic reactions during or after injection:

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

Signs of serious infections:

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

Signs and symptoms of liver toxicity
These are rare: they may affect up to 1 in 1,000 people

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

List of other possible side effects
If you notice any of the following symptoms, inform 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
• elevated blood lipid levels (cholesterol)
• injection site reactions

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
• rash and itching, hives
• allergic reactions (hypersensitivity)
• eye infection (conjunctivitis)
• headache, dizziness, high blood pressure
• mouth ulcers, stomach pain
• fluid retention (oedema) in the lower legs, weight gain
• cough, shortness of breath
• low white blood cell count as shown in blood tests (neutropenia, leucopenia)
• abnormalities in liver function tests (increased transaminases)
• increased bilirubin levels as shown in 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, diarrhoea, 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:
May affect up to 1 in 1,000 people

• Stevens-Johnson syndrome (skin rash, which may lead to severe blistering and peeling of the skin)
• fatal allergic reactions (anaphylaxis)
• inflammation of the liver (hepatitis), jaundice

Very rare side 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

Side effects in children and adolescents with sJIA or pJIA
Side effects observed in children and adolescents with sJIA or pJIA are generally similar to those seen in adults. Some side effects occur more frequently 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 experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via 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 RoActemra

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on the label of the pre-filled syringe (Scad./EXP). The expiry date refers to the last day of the month.
Store in a refrigerator (2 °C – 8 °C). Do not freeze. After removal from the refrigerator, the pre-filled syringe may be stored for up to 2 weeks at a temperature not exceeding 30°C.
Keep the pre-filled syringes in the outer packaging to protect them from light and moisture.
The medicine should not be used if the solution is cloudy or contains particles, is not transparent, has 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 should be started within 5 minutes to prevent the medicine from drying and blocking the needle. If the pre-filled syringe is not used within 5 minutes after removing the cap, it must be disposed of in a puncture-resistant container and a new pre-filled syringe must be used.
If, after inserting the needle, the plunger cannot be pushed, the pre-filled syringe must be discarded into a puncture-resistant container and a new pre-filled syringe must be used.

6. Package Contents and Other Information

What RoActemra Contains

• The active substance is tocilizumab. Each 0.9 mL pre-filled syringe contains 162 mg of tocilizumab.
• The other excipients are L-histidine, L-histidine monohydrochloride monohydrate, L-arginine/L-arginine hydrochloride, L-methionine, polysorbate 80, and water for injections (see section 2 “RoActemra contains polysorbate”).

Description of the Appearance of RoActemra and Contents of the Package
RoActemra is an injectable solution. The solution ranges from clear to slightly yellowish.
RoActemra is supplied in a 0.9 mL pre-filled syringe containing 162 mg of tocilizumab as an injectable solution.
Each pack contains 4 pre-filled syringes. Multiple packs contain 12 syringes (3 packs of 4). Not all pack sizes may be marketed.

Marketing Authorization Holder
Roche Registration GmbH
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany

Manufacturer
Roche Pharma AG
Emil-Barell-Str. 1
79639 Grenzach-Wyhlen
Germany

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

België/Belgique/Belgien Luxembourg/Luxemburg
N.V. Roche S.A. (See/siehe Belgique/Belgien)
Tél/Tel: +32 (0) 2 525 82 11

България Magyarország
Рош България ЕООД Roche (Magyarország) Kft.
Тел: +359 2 474 5444 Tel: +36 - 1 279 4500

Česká republika Malta (See Ireland)
Roche s. r. o.
Tel: +420 - 2 20382111

Danmark Nederland
Roche Pharmaceuticals A/S Roche Nederland B.V.
Tlf.: +45 - 36 39 99 99 Tel: +31 (0) 348 438050

Deutschland Norge
Roche Pharma AG Roche Norge AS
Tel: +49 (0) 7624 140 Tlf: +47 - 22 78 90 00
or
Chugai Pharma Europe Ltd.
Zweigniederlassung Deutschland
Tel: +49 (0) 69 663000 0

Eesti Österreich
Roche Eesti OÜ Roche Austria GmbH
Tel: + 372 - 6 177 380 Tel: +43 (0) 1 27739

Ελλάδα Polska
Roche (Hellas) A.E. Roche Polska Sp. z o.o.
Τηλ: +30 210 61 66 100 Tel: +48 - 22 345 18 88

España Portugal
Roche Farma S.A. Roche Farmacêutica Química, Lda
Tel: +34 - 91 324 81 00 Tel: +351 - 21 425 70 00

France România
Roche Roche România S.R.L.
Tél: +33 (0) 1 47 61 40 00 Tel: +40 21 206 47 01
or
Chugai Pharma France
Tél: +33 (0) 1 56 37 05 20

Hrvatska
Roche d.o.o.
Tel: +385 1 47 22 333

Ireland Slovenija
Roche Products (Ireland) Ltd. Roche farmacevtska družba d.o.o.
Tel: +353 (0) 1 469 0700 Tel: +386 - 1 360 26 00

Ísland Slovenská republika
Roche Pharmaceuticals A/S Roche Slovensko, s.r.o.
c/o Icepharma hf
Sími: +354 540 8000 Tel: +421 - 2 52638201

Italia Suomi/Finland
Roche S.p.A. Roche Oy
Tel: +39 - 039 2471 Puh/Tel: +358 (0) 10 554 500

Kύπρος Sverige
Roche (Hellas) A.E. Roche AB
Τηλ: +30 210 61 66 100 Tel: +46 (0) 8 726 1200

Latvija
Roche Latvija SIA
Tel: +371 - 6 7039831

Lietuva
UAB “Roche Lietuva”
Tel: +370 5 2546799

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

Instructions for Safe Use of RoActemra in Pre-filled Syringe
To ensure that you or the person assisting you correctly uses RoActemra in pre-filled syringe, it is important to read, understand, and follow these instructions. These instructions do not replace training provided by a healthcare professional. Before using RoActemra in pre-filled syringe for the first time, a healthcare professional will show you how to properly prepare and inject the medicine. Ask your healthcare professional any questions you may have. Do not attempt to self-administer an injection until you are certain you understand how to use RoActemra in pre-filled syringe.

Please also read the Patient Information Leaflet supplied with RoActemra in pre-filled syringe for the most important information you need to know about this medicine. It is important to remain under the supervision of a healthcare professional while using RoActemra.

Important Information:

• Do not use the syringe if it appears damaged.
• Do not use if the solution is cloudy, not clear, discolored, or contains particles.
• Never attempt to disassemble the syringe.
• Do not remove the needle protective cap until you are ready to inject the medicine.
• Do not administer the injection through clothing covering the skin.
• Never reuse the same syringe.
• Do not touch the activation wings of the syringe to avoid damaging the medical device.

Storage
Keep RoACTEMRA in syringe and all medicines out of the sight and reach of children.
Store the syringe in the refrigerator at a temperature of 2°C – 8°C. After removal from the refrigerator, the pre-filled syringe may be stored for a total of 2 weeks at a temperature not exceeding 30°C, but not beyond the original expiry date (Exp.). Mark the relevant date on the packaging.
Protect the syringe from freezing and light. Keep syringes dry.

Parts of the Pre-filled Syringe

Supplies Needed for Injection Administration:
Included in the package:

• Pre-filled syringe
  Not included in the package:
• Alcohol swab
• Sterile cotton ball or gauze
• Puncture-resistant container or sharps container for safe disposal of the needle protective cap and used syringe.
  Where to prepare supplies:
• Use a clean, flat, well-lit surface, such as a table.

Step 1. Visually inspect the pre-filled syringe.

• Remove the syringe packaging from the refrigerator. Open the packaging. Do not touch the activation wings on the syringe to avoid damaging it.
• Remove the syringe from the packaging. Perform a visual inspection of the syringe and the medicine inside. This step is important to ensure the safety of using the syringe and medicine.
• Check the expiry date printed on the packaging and syringe (see Fig. A) to ensure it has not passed. Do not use the syringe if the expiry date has passed. This step is important to ensure the safety of using the syringe and medicine.

Discard the pre-filled syringe and do not use it if:

• the medicine inside appears cloudy;
• the medicine contains particles;
• the medicine is not clear or has a color different from slightly yellowish;
• any part of the pre-filled syringe appears damaged.

Step 2. Allow the pre-filled syringe to reach room temperature.

• Do not remove the needle protective cap from the syringe until Step 5. Premature removal of the needle cap may cause the medicine to dry and block the needle.
• Place the syringe on a clean, flat surface and allow it to warm to room temperature (18°C – 28°C) for approximately 25–30 minutes. If the syringe is not allowed to reach room temperature, the injection may be uncomfortable and depressing the plunger may be difficult.
• Do not heat the pre-filled syringe in any other way.

Step 3. Wash your hands.

• Wash your hands thoroughly with soap and water.

Step 4. Choose and prepare the injection site.

• Recommended injection sites are the front and middle part of the thighs and the abdominal area (stomach) below the navel, except for the area within five centimeters around the navel. (See Fig. B)
• If the injection is administered by an assistant, the outer area of the upper arms may also be used. (See Fig. B)

• Each time you self-administer an injection, use a different site at least three centimeters away from the previous injection site.
• Do not administer the injection into areas that might be irritated by a belt or bandage. Do not inject into moles, scars, bruises, or areas where the skin is painful, red, hardened, or not intact.
• Disinfect the chosen injection site using an alcohol swab (see Fig. C) to reduce the risk of infection.

• Allow the skin to dry for about 10 seconds.
• Make sure not to touch this area before injecting. Do not blow on or fan the disinfected area.

Step 5. Remove the needle protective cap.

• Do not hold the syringe by the plunger while removing the needle protective cap.
• Hold the safety sleeve of the pre-filled syringe firmly with one hand and pull the needle protective cap straight off with the other hand. (See Fig. D) If you cannot remove the needle protective cap, ask for help from your assistant or contact a healthcare professional.

• Do not touch the needle and avoid contact with any surface.
• There may be a small air bubble in the RoActemra pre-filled syringe. It is not necessary to remove it.
• You may notice a drop of liquid at the tip of the needle. This is normal.
• Dispose of the needle protective cap in a puncture-resistant container or sharps container.

Note: Once the needle protective cap is removed, the syringe must be used immediately.

• If not used within 5 minutes after cap removal, the syringe must be discarded into a puncture-resistant container or sharps container, and a new syringe must be used. If the needle cap is removed for more than 5 minutes, injection may become difficult because the medicine may dry and block the needle.
• Do not reinsert the needle protective cap after removal.

Step 6. Administer the injection.

• Hold the body of the syringe comfortably in one hand.
• To ensure correct needle insertion under the skin, use the other hand to pinch a fold of relaxed skin at the previously disinfected injection site. This step is important to ensure the injection is delivered under the skin (into subcutaneous fat tissue) and not deeper (into muscle). Injection into muscle may be painful.
• Do not hold or push the plunger during needle insertion into the skin.
• Insert the needle fully into the skin fold at an angle between 45° and 90° with a quick, firm motion. (See Fig. E)

Choosing the correct angle of insertion is important because it ensures the medicine is delivered under the skin (into subcutaneous fat tissue); otherwise, the injection may be painful and the medicine may not be effective.

• Keep the syringe in place and release the skin fold.
• Inject the full dose slowly by gently pushing the plunger all the way down. (See Fig. F) The plunger must be fully depressed to ensure the entire dose is administered and the activation wings are fully pushed to the side. If the plunger is not fully depressed, the safety sleeve will not extend to cover the needle upon needle withdrawal. If the needle is not covered, handle with caution and place the syringe in a puncture-resistant container to avoid needlestick injury.

• When the plunger stops, continue applying pressure before withdrawing the needle from the skin to ensure the full dose is injected.
• Continue pressing the plunger while withdrawing the needle from the skin, maintaining the same angle used during insertion. (See Fig. G)
• If, after needle insertion, the plunger cannot be depressed, discard the pre-filled syringe into a puncture-resistant container and use a new pre-filled syringe (starting again from Step 2). If difficulties persist, consult your healthcare professional.

• After completely withdrawing the needle from the skin, release the plunger, allowing the safety sleeve to extend and cover the needle. (See Fig. H)

• If you notice a small drop of blood at the injection site, press a cotton ball or sterile gauze on the site for about 10 seconds.
• Do not rub the injection site.

Step 7. Dispose of the syringe.

• Do not attempt to re-cap the needle.
• Dispose of used syringes in a puncture-resistant container or sharps container. Ask your healthcare professional or pharmacist where to obtain a sharps container or what other types of puncture-resistant containers may be used for safe disposal of used syringes if you do not have one. (See Fig. I)

Check with your healthcare professional for proper disposal instructions for used syringes.
Local or national regulations may apply.
Do not dispose of used syringes or puncture-resistant containers in household waste and do not recycle them.

• Dispose of the full container according to instructions provided by your healthcare professional or pharmacist.
• Always keep the puncture-resistant container out of sight and reach of children.

Patient Instructions on Hypersensitivity Reactions (also known as anaphylaxis, if severe)
If, during or after an injection of RoActemra, you develop at any time—especially when not in a clinical setting—symptoms such as, but not limited to: rash, itching, chills, swelling of the face, lips, tongue, or throat, chest pain, wheezing, difficulty breathing or swallowing, dizziness, or fainting, seek immediate emergency medical attention.

Patient Instructions on Recognizing and Early Treatment to Reduce the Risk of Serious Infection
Carefully evaluate early signs of infection, such as:

• generalized body aches, fever, chills
• cough, chest discomfort or tightness, shortness of breath
• redness, warmth, unusual swelling of the skin or joints
• abdominal pain/tenderness and/or changes in bowel function

If you suspect you are developing an infection, contact your doctor and seek immediate evaluation.
If you have any doubts or questions about the syringe, contact your healthcare professional or pharmacist for assistance.

Patient Information Leaflet: Information for the User

RoActemra 162 mg solution for injection in pre-filled pen

tocilizumab
Please read all of this leaflet carefully before taking this medicine, because 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 give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

In addition to this patient information leaflet, you will be provided with a Patient Safety Card containing important safety information that you must know before starting and during treatment with RoActemra.
Contents of this leaflet:

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

1. What RoActemra is and what it is used for

RoActemra 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 inflammatory processes in the body, and blocking it
can reduce inflammation in your body. RoActemra is used to treat:

• adults with moderate to severe active rheumatoid arthritis (RA), an autoimmune disease, when previous treatments have not been sufficiently effective.
• adults with severe, active and progressive rheumatoid arthritis (RA) who have not been previously treated with methotrexate.

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

• 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 include headache, fatigue, and jaw/mouth pain. Consequences may include stroke and blindness.

RoActemra 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 side effects if used at high doses over long periods. In addition, reducing the steroid dose may lead to a flare-up of GCA. Adding
RoActemra to treatment allows steroids to be used for a shorter period while still
keeping GCA under control.

• children and adolescents aged 12 years 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 rash.

RoActemra is used to improve the symptoms of sJIA. It may be administered in combination with methotrexate or alone.

• children and adolescents aged 12 years and older with active polyarticular juvenile idiopathic arthritis (pJIA), an inflammatory disease causing pain and swelling in one or more joints.

RoActemra is used to improve the symptoms of pJIA. It may be administered in combination with methotrexate or alone.

2. What you need to know before using RoActemra

Do not use RoActemra

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

If any of these conditions apply to you, inform your doctor. Do not use RoActemra.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using RoActemra.

• If you experience allergic reactions, such as chest tightness, wheezing, severe dizziness or feeling faint, swelling of the lips or tongue, skin or facial itching, hives, or rash during or immediately after the injection, inform your doctor immediately.
• If you develop any symptoms of an allergic reaction after receiving RoActemra, do not take the next dose until you have informed your doctor AND they have told you it is safe to continue.
• If you have any type of infection, short- or long-term, or if you frequently get infections, inform your doctor immediately if you feel unwell. RoActemra may reduce your body’s ability to respond to infections and could worsen an existing infection or increase your risk of developing 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 RoActemra. If symptoms of tuberculosis (persistent cough, weight loss, fatigue, low-grade fever) or any other infection occur during or after treatment, inform your doctor immediately.
• If you have had intestinal ulcers or diverticulitis, inform your doctor. Symptoms may include abdominal pain and unexplained changes in bowel habits associated with fever.
• If you have liver disease, inform your doctor. Before using RoActemra, your doctor may perform a blood test to assess your liver function.
• If a patient has recently been vaccinated or plans to receive a vaccination, inform the doctor. All patients should be up to date with all vaccinations before starting treatment with RoActemra. Some types of vaccines should not be administered during treatment with RoActemra.
• If you have a tumor, inform your doctor. Your doctor will need to decide whether you can still receive RoActemra.
• If you have cardiovascular risk factors, such as high blood pressure or elevated cholesterol levels, inform your doctor. These factors should be monitored while you are taking RoActemra.
• If you have moderate to severe kidney function problems, your doctor will monitor you closely.
• If you have persistent headaches.

Your doctor will perform blood tests before administering RoActemra to determine whether you have low levels of white blood cells or platelets, or elevated liver enzymes.
Children and adolescents
The use of RoActemra in a pre-filled pen is not recommended in children under 12 years of age.
RoActemra must not be administered to children with sJIA weighing less than 10 kg.
If a child has a history of macrophage activation syndrome (uncontrolled activation and proliferation of specific blood cells), inform the doctor. The doctor will need to decide whether the patient can still be treated with RoActemra.
Other medicines and RoActemra
Inform your doctor if you are taking, or have recently taken, any other medicines. RoActemra may affect how some medicines work, and their doses may need to be adjusted. Inform your doctor if you are taking medicines containing the following active substances:

• methylprednisolone, dexamethasone, used to reduce inflammation
• simvastatin or atorvastatin, used to lower cholesterol levels
• calcium channel blockers (e.g. 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 (e.g. temazepam), used to treat anxiety.

Due to lack of clinical experience, RoActemra is not indicated for use with other biological medicines for the treatment of RA, sJIA, pJIA, or GCA.
Pregnancy, breastfeeding, and fertility
RoActemra must not be used during pregnancy unless absolutely necessary. Inform your doctor if you are pregnant, think you might be pregnant, or are planning a pregnancy.
Women of childbearing potential must use an effective contraceptive method during treatment and for at least 3 months after the last dose.
Stop breastfeeding if you are about to be given RoActemra and inform your doctor. At least 3 months must pass after the last dose of RoActemra before breastfeeding can be resumed. It is not known whether RoActemra passes into breast milk.
Driving and using machines
This medicine may cause dizziness. If you experience dizziness, do not drive or operate machinery.
RoActemra contains polysorbate
This medicine contains 0.18 mg of polysorbate 80 in each 162 mg/0.9 mL of PFP, equivalent to 0.2 mg/mL. Polysorbates may cause allergic reactions. Inform your doctor if you or your child have any known allergies.

3. How to use RoActemra

Use this medicine exactly as prescribed by your doctor, pharmacist, or nurse. If you have any doubts, consult your doctor, pharmacist, or nurse.
Treatment will be prescribed and initiated by healthcare professionals experienced in the diagnosis and treatment of RA, sJIA, pJIA, or GCA.
Recommended dose
The dose for all adults with RA or GCA is 162 mg (the content of 1 pre-filled pen) administered once weekly.
Adolescents with sJIA (aged 12 years and older)
The usual dose of RoActemra depends on the patient's body 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.

The pre-filled pen must not be used to treat children under 12 years of age.
Adolescents with pJIA (aged 12 years and older)
The usual dose of RoActemra depends on the patient's body 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.

The pre-filled pen must not be used to treat children under 12 years of age.
RoActemra is administered by subcutaneous injection (under the skin). Initially, RoActemra may be administered by your doctor or nurse. However, your doctor may decide that you are able to self-inject RoActemra. In this case, you will be trained on how to self-administer RoActemra. Parents and caregivers of patients will be trained on how to inject RoActemra in patients who cannot self-inject the medicine.
Talk to your doctor if you have any questions about self-administering an injection or administering an injection to an adolescent patient you are caring for. At the end of this

Package leaflet, you will find detailed "Instructions for administration".

If you use more RoActemra than you should
Since RoActemra 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 about this, consult your doctor, pharmacist, or nurse.

If an adult with RA or GCA or an adolescent with PJIA misses or forgets a dose
It is very important that you use RoActemra 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 alternate-week injection within 7 days, take the missed dose as soon as you remember and continue with the following doses as scheduled.
• If you miss your weekly injection or your alternate-week injection for more than 7 days, or if you are unsure when to inject RoActemra, call your doctor or pharmacist.

If an adolescent with sJIA misses or forgets a dose
It is very important to use RoActemra exactly as prescribed by your doctor. Keep track of your 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, then administer the next dose at the regularly scheduled day and time.
• If a dose has been missed and more than 7 days have passed since the missed dose, or if you are unsure when to inject RoActemra, consult your doctor or pharmacist.

If you stop treatment with RoActemra
You must not stop treatment with RoActemra without first talking to your doctor.
If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

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

Possible serious side effects:
Contact your doctor immediately if you experience any of the following:

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.

Signs of serious infections:

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

Signs and symptoms of liver toxicity
These are rare: may affect up to 1 in 1,000 people

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

List of other possible side effects
If you notice any of these symptoms, inform your doctor as soon as possible.

Very common side effects:
May affect more than 1 in 10 people

• upper respiratory tract infections with typical symptoms such as cough, stuffy nose, runny nose, sore throat and headache
• elevated levels of blood lipids (cholesterol)
• injection site reactions

Common side effects:
May affect up to 1 in 10 people

• lung infection (pneumonia)
• shingles (herpes zoster)
• cold sores (oral herpes simplex), blistering
• 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 (oedema) in the lower legs, weight gain
• cough, shortness of breath
• low white blood cell count as shown in blood tests (neutropenia, leucopenia)
• 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:
May affect up to 1 in 100 people

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

Rare side effects:
May affect up to 1 in 1,000 people

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

Very rare side 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

Side effects in children and adolescents with sJIA or pJIA
Side effects observed in children and adolescents with sJIA or pJIA are generally similar to those seen in adults. Some side effects occur more frequently in children and adolescents: inflammation of the nose and throat, headache, feeling unwell (nausea), and lower white blood cell counts.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please contact 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 RoActemra

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on the label of the pre-filled pen (Exp/EXP). The expiry date refers to the last day of that month.
Store in a refrigerator (2°C–8°C). Do not freeze. Once removed from the refrigerator, the pre-filled pen may be stored for up to 2 weeks at a temperature not exceeding 30°C.
Keep pre-filled pens in their outer packaging to protect them from light and moisture.
The medicine must not be used if the solution is cloudy or contains particles, if it is not clear, or if it has a colour different from pale yellow, or if any part of the pre-filled syringe appears damaged.
Do not shake the pen. After removing the cap, the injection must be started within 3 minutes to avoid the medicine drying and blocking the needle. If the pre-filled pen is not used within 3 minutes of removing the cap, it must be disposed of in a puncture-resistant container and a new pre-filled pen must be used.
If the purple indicator does not move after pressing the activation button, the pre-filled pen must be discarded into a puncture-resistant container. Do not attempt to reuse the pre-filled pen. Do not repeat the injection with another pre-filled pen. Contact your healthcare provider for assistance.

6. Package Contents and Other Information

What RoActemra Contains

• The active substance is tocilizumab. Each pre-filled pen contains 162 mg of tocilizumab in 0.9 mL.
• The other components are L-histidine, L-histidine monohydrochloride monohydrate, L-arginine/L-arginine hydrochloride, L-methionine, polysorbate 80, and water for injections (see section 2 “RoActemra contains polysorbates”).

Description of the Appearance of RoActemra and Contents of the Pack
RoActemra is an injectable solution. The solution is from clear to slightly yellowish.
RoActemra is supplied in a 0.9 mL pre-filled pen containing 162 mg of tocilizumab as an injectable solution.
Each pack contains 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
Roche Registration GmbH
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany
Manufacturer
Roche Pharma AG
Emil-Barell-Str. 1
79639 Grenzach-Wyhlen
Germany
For further information about this medicinal product, please contact the local representative of the marketing authorisation holder:
België/Belgique/Belgien Luxembourg/Luxemburg
N.V. Roche S.A. (Voir/siehe Belgique/Belgien)
Tél/Tel: +32 (0) 2 525 82 11
България Magyarország
Рош България ЕООД Roche (Magyarország) Kft.
Тел: +359 2 474 5444 Tel: +36 - 1 279 4500
Česká republika Malta
Roche s. r. o. (See Ireland)
Tel: +420 - 2 20382111
Danmark Nederland
Roche Pharmaceuticals A/S Roche Nederland B.V.
Tlf.: +45 - 36 39 99 99 Tel: +31 (0) 348 438050
Deutschland Norge
Roche Pharma AG Roche Norge AS
Tel: +49 (0) 7624 140 Tlf: +47 - 22 78 90 00
Eesti Österreich
Roche Eesti OÜ Roche Austria GmbH
Tel: + 372 - 6 177 380 Tel: +43 (0) 1 27739
Ελλάδα Polska
Roche (Hellas) A.E. Roche Polska Sp.z o.o.
Τηλ: +30 210 61 66 100 Tel: +48 - 22 345 18 88
España Portugal
Roche Farma S.A. Roche Farmacêutica Química, Lda
Tel: +34 - 91 324 81 00 Tel: +351 - 21 425 70 00
France România
Roche Roche România S.R.L.
Tél: +33 (0) 1 47 61 40 00 Tel: +40 21 206 47 01
Hrvatska Slovenija
Roche d.o.o. Roche farmacevtska družba d.o.o.
Tel: +385 1 47 22 333 Tel: +386 - 1 360 26 00
Ireland
Roche Products (Ireland) Ltd.
Tel: +353 (0) 1 469 0700
Ísland Slovenská republika
Roche Pharmaceuticals A/S Roche Slovensko, s.r.o.
c/o Icepharma hf Tel: +421 - 2 52638201
Sími: +354 540 8000
Italia Suomi/Finland
Roche S.p.A. Roche Oy
Tel: +39 - 039 2471 Puh/Tel: +358 (0) 10 554 500
Kύπρος Sverige
Roche (Hellas) A.E. Roche AB
Τηλ: +30 210 61 66 100 Tel: +46 (0) 8 726 1200
Latvija
Roche Latvija SIA
Tel: +371 - 6 7039831
Lietuva
UAB “Roche Lietuva”
Tel: +370 5 2546799
Other Sources of Information
More detailed information about this medicine is available on the website of the European Medicines Agency: https://www.ema.europa.eu.
Instructions for Safe Use of RoActemra Pre-filled Pen (ACTPen)
Read and follow the instructions for use provided with your pre-filled pen of RoActemra before starting to use it and each time you receive a prescription renewal. Before using the RoActemra pre-filled pen for the first time, a healthcare professional will show you how to use it correctly.
Important: Keep unused pre-filled pens in their original carton and refrigerated at a temperature between 2°C and 8°C. Do not freeze.
Once removed from the refrigerator, the pre-filled pen may be stored for a total of 2 weeks at a temperature not exceeding 30°C, but not beyond the original expiry date (Exp.).
Mark the relevant date on the packaging.
Always keep the pre-filled pens in their outer packaging to protect them from light and moisture.

• Do not remove the cap from the pre-filled pen until you are ready to administer the RoActemra injection.
• Never attempt to disassemble the pre-filled pen.
• Never reuse the same pre-filled pen.
• Do not administer the injection through clothing.
• Do not leave the pre-filled pen unattended.
• Keep out of reach and sight of children. Parts of the RoActemra pre-filled pen (see Figure A).

Before use After use
Green
activation
button
Expiry
date
Indicator
Purple
window
“injection
completed”
Safety
sleeve
Safety
sleeve
(extended
and locked)
Green
cap
Figure A
Items needed to administer the injection with the RoActemra pre-filled pen (see Figure B):

• 1 pre-filled pen of RoActemra
• 1 alcohol swab
• 1 sterile cotton ball or gauze pad
• 1 puncture-resistant container or sharps container for safe disposal of the pen cap and used pre-filled pen (see Step 4 “Disposal of the pre-filled pen” )

Alcohol
swab

Puncture-
resistant
container
for sharps
Pre-filled
pen of
ROACTEMRA
Sharps
disposal
container
Sterile
cotton ball
Figure B
Step 1. Preparing the RoActemra Injection
Find a comfortable place with a clean, flat work surface.

• Remove the pre-filled pen packaging from the refrigerator.
• If opening the packaging for the first time, check that it is properly sealed. Do not use the pre-filled pen if the packaging appears to have been opened previously.
• Check that the pre-filled pen packaging is undamaged. Do not use the RoActemra pre-filled pen if the packaging appears damaged.
• Check the expiry date printed on the pre-filled pen packaging. Do not use the pre-filled pen if the expiry date has passed, as it may not be safe.
• Open the packaging and remove one single-dose pre-filled pen of RoActemra.
• Return any remaining pre-filled pens in the pack to the refrigerator.
• Check the expiry date printed on the RoActemra pre-filled pen packaging (see Figure A). Do not use the pre-filled pen if the expiry date has passed, as it may not be safe. If the expiry date has passed, dispose of the pre-filled pen in a sharps container and use a new one.
• Inspect the pre-filled pen for damage. Do not use the pre-filled pen if it appears damaged or if it has been accidentally dropped.
• Place the pre-filled pen on a clean, flat surface and allow it to warm to room temperature for 45 minutes. If the pre-filled pen is not allowed to warm to room temperature, the injection may be uncomfortable and take longer than expected.
• Do not warm the pre-filled pen in any other way, for example by placing it in a microwave or in hot water.
• Do not allow the pre-filled pen to warm in direct sunlight. Do not remove the green cap while the RoActemra pre-filled pen is warming to room temperature.
• Hold the RoActemra pre-filled pen with the green cap pointing downward (see Figure C).

Figure C

• Look through the transparent window. Check the liquid inside the RoActemra pre-filled pen (see Figure C). It should be clear and colourless to slightly yellow. Do not administer the RoActemra injection if the liquid is cloudy, discoloured, or contains flakes or particles, as it may not be safe to use. Dispose of the pre-filled pen in a sharps container and use a new one.
• Wash your hands thoroughly with soap and water.
  Step 2. Choosing and Preparing the Injection Site
  Choose an injection site
• Recommended injection sites are the front of the thighs or abdomen, except for the area within five centimetres around the navel (see Figure D).
• If the injection is administered by a caregiver, the outer area of the upper arms may also be used. Do not attempt to use the outer area of the upper arms by yourself (see Figure D).
  Rotate injection sites
• Each time you self-administer an injection, use a different injection site, at least 2.5 centimetres away from the site used for the previous injection.
• Do not administer the injection into moles, scars, bruises, or areas where the skin is painful, red, hardened, or broken.

Front Back
Injection sites
Figure D
Preparing the injection site

• Disinfect the chosen injection site using the alcohol swab with circular motions, and allow it to dry to reduce the risk of infection. Make sure not to touch this area before administering the injection.
• Do not blow on or fan the disinfected area.
  Step 3. Administering the RoActemra Injection
• Hold the RoActemra pre-filled pen firmly in one hand. With the other hand, twist and remove the green cap (see Figure E). The green cap contains a wide metal tube.
• If you are unable to remove the green cap, ask your caregiver for help or contact your healthcare professional.

Figure E
Important: Do not touch the needle safety sleeve located at the tip of the pre-filled pen below the window (see Figure A) to avoid accidental needle sticks.

• Dispose of the green cap in a sharps container.
• Once the green cap is removed, the pre-filled pen is ready for use. If it is not used within 3 minutes after removing the cap, the pre-filled pen must be disposed of in a sharps container and a new pre-filled pen must be used.
• Do not reinsert the green cap after removal.
• Hold the pre-filled pen comfortably in one hand by the upper part, so that you can see the viewing window of the pre-filled pen (see Figure F).

Figure F

• Use your other hand to pinch the disinfected skin area to create a stable injection site (see Figure G). A stable injection site is necessary for the pre-filled pen to activate properly.
• Pinching the skin is important to ensure the needle is correctly inserted under the skin (into the fatty tissue) and not deeper (into the muscle). Injecting into the muscle may be painful.

Figure G

• Do not press the green activation button yet.
• Insert the needle safety sleeve of the pre-filled pen into the skin fold at a 90° angle (see Figure H).
• Choosing the correct angle is important to ensure the medicine is delivered under the skin (into the fatty tissue); otherwise, the injection may be painful and the medicine may not be effective.

Figure H

• To use the pre-filled pen, you must first unlock the green activation button.
• To unlock it, press the pre-filled pen firmly against the skin fold until the needle sleeve retracts completely (see Figure I).

Figure I

• Continue to hold the needle sleeve pressed firmly.
• If you do not keep the needle sleeve fully pressed against the skin, the green activation button will not work.
• Continue to pinch the skin while the pre-filled pen remains in position.
• Press the green activation button to start the injection. A “click” will indicate that the injection has started. Continue to press the button and keep the pre-filled pen firmly pressed against the skin (see Figure J). If you are unable to start the injection, ask your caregiver for help or contact your healthcare professional.

Figure J

• The purple indicator will move across the viewing window during the injection (see Figure K).
• Follow the purple indicator until it stops to ensure you inject the full dose of medicine.

Figure K

• The injection may take up to 10 seconds.
• You may hear a second “click” during the injection; continue to keep the pre-filled pen firmly pressed against the skin until the purple indicator stops.
• When the purple indicator stops, release the green button. Lift the pre-filled pen away from the injection site at a 90° angle to withdraw the needle from the skin. The safety sleeve will extend and cover the needle (see Figure L).

Figure L

• Check the viewing window to ensure the purple indicator completely covers it (see Figure L).
• If the viewing window is not completely covered by the purple indicator:
• The safety sleeve may not have locked. Do not touch the safety sleeve of the pre-filled pen, as you may be pricked by the needle. If the needle is not covered, carefully place the pre-filled pen into the sharps container to avoid injury.
• You may not have received the full dose of RoActemra. Do not attempt to reuse the pre-filled pen. Do not repeat the injection with another pre-filled pen. Contact your healthcare professional for advice.
  After the injection
• If you notice a drop of blood at the injection site, you may press a sterile cotton ball or gauze pad onto the site.
• Do not rub the injection site.
• If needed, you may cover the injection site with a plaster.
  Step 4. Disposal of the Pre-filled Pen
• The RoActemra pre-filled pen must not be reused.
• Place the pre-filled pen into a sharps container (see “Instructions for Disposal of Pre-filled Pens”).
• Do not attempt to recap the pre-filled pen.
• If the injection is administered by someone else, that person must be careful when removing and disposing of the pre-filled pen to avoid accidental needle stick injury and transmission of infection.
  Instructions for Disposal of Pre-filled Pens
• Immediately after use, place the RoActemra pre-filled pen and green cap into a sharps container (see Figure M).
• Do not dispose of (throw away) the pre-filled pen and green cap in household waste and do not recycle them.

Figure M

• Dispose of the full container according to instructions provided by your healthcare professional or pharmacist.
• Always keep the puncture-resistant container out of sight and reach of children.

Keep the RoActemra pre-filled pen and puncture-resistant container out of sight and reach of children.
Recording the Injection

• After administering the injection, record the date, time, and specific body site where the injection was given. It may also be helpful to note any questions or concerns about the injection to discuss with your healthcare professional. If you have any questions or doubts about the RoActemra pre-filled pen, speak with your RoActemra-experienced healthcare professional.