Prospecto: Information for the User

RoActemra 162 mg, Pre-filled Syringe Solution

tocilizumab

Read this prospect carefully before starting to take this medicine, as it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist or nurse.
• This medicine has been prescribed only for you, and you must not give it to other people, even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist or nurse, even if they do not appear in this prospect. See section 4.

In addition to this prospect, you will be given aPatient Information Leaflet, which contains important safety information that you should know before receiving RoActemra and during treatment with RoActemra.

1. What is RoActemra and what is it used for

2. What you need to know before starting to use RoActemra

3. How to use RoActemra

4. Possible adverse effects

5. Storage of RoActemra

6. Contents of the pack and additional information

RoActemra contains an active substance called tocilizumab, which is a protein obtained from specific immune cells (monoclonal antibody), that blocks the action of a specific type of protein (cytokine) called interleukin 6. This protein is involved in inflammatory processes in the body, and blocking it can reduce inflammation. RoActemra is indicated for the treatment of:

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

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

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

RoActemra is usually used in combination with another RA medication called methotrexate. However, RoActemra can be administered alone if your doctor determines that methotrexate is not suitable.

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

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

GCA is often treated with medications called steroids. They are usually effective, but can have side effects if used at high doses for a long time. Reducing the dose of steroids can also lead to a flare-up of GCA. Adding RoActemra to treatment makes the time of use of steroids shorter, while still controlling GCA.

• children and adolescents, 12 years of age and older, withsystemic juvenile idiopathic arthritis (sJIA)active,an inflammatory disease that causes 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 can be administered in combination with methotrexate or alone.

• children and adolescents,12 years of age and older, withpolyarticular juvenile idiopathic arthritis (pJIA)active. This is an inflammatory disease that causes pain and swelling in one or more joints.

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

You will not be administered RoActemra

?If you or the pediatric patient you care for is allergic totocilizumab or any of the other components of this medication (listed in section 6).

?If you or the pediatric patient you care for has an active severe infection.

?If any of this happens, consult with your doctor. Do not use RoActemra.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to receive RoActemra.

?If you experienceallergic reactionssuch as chest tightness, wheezing, dizziness, intense drowsiness, swelling of the lips, tongue, face, or skin rash, hives, or itching during or after the injection,inform your doctor immediately.

?If you have experienced any symptoms of an allergic reaction after receiving RoActemra, do not take the next dose until you have informed your doctor and your doctor has instructed you to take the next dose.

?If you have any type ofinfection,whether short-term or long-term, or if you frequently contract infectionsInform your doctor immediatelyif you feel unwell.RoActemra may reduce your body's ability to respond to infections and may make an existing infection worse or increase the likelihood of acquiring a new infection.

?If you have hadtuberculosis, inform your doctor.Your doctor will check for signs and symptoms of tuberculosis before starting treatment with RoActemra. Inform your doctor immediately if tuberculosis symptoms (persistent cough, weight loss, general malaise, low-grade fever), or any other infection appear during or after treatment.

?If you have hadulcerative colitis or diverticulitis,inform your doctor.Symptoms would include abdominal pain and unexplained changes in bowel habits with fever.

?If you haveliver disease, inform your doctor.Before using RoActemra, your doctor will perform a blood test to measure your liver function.

?If any patient has recently been vaccinated,or is planning to be vaccinated,inform your doctor.All patients must be up to date with their vaccination schedule before starting treatment with RoActemra.Determined types of vaccines should not be administered while receiving RoActemra.

?If you havecancer, inform your doctor. Your doctor will decide if you can continue receiving treatment with RoActemra.

?If you havecardiovascular risk factors, such as high blood pressure, and high cholesterol levels, inform your doctor. These factors need to be controlled while receiving treatment with RoActemra.

?If you havemoderate to severe kidney problems, your doctor will monitor you.

?If you havepersistent headaches.

Your doctor will perform blood tests before you receive RoActemra to determine if you have a low white blood cell count, low platelet count, or elevated liver enzymes.

Children and adolescents

RoActemra should not be injected with a pre-filled pen in children under 12 years old. RoActemra should not be administered to children with AIJs weighing less than 10 kg.

If the child has a history ofmacrophage activation syndrome(uncontrolled activation and proliferation of a specific type of blood cell), inform your doctor. Your doctor will decide if RoActemra can continue to be administered.

Other medications and RoActemra

Inform your doctor if you are taking any other medication, or have taken one recently.This is because RoActemra may affect how some medications work, and a dose adjustment may be needed.Inform your doctorif you have recently used medications containing any of the following active substances:

?prednisolone, dexamethasone, used to reduce inflammation

?simvastatin or atorvastatin, used to reduce cholesterol levels

?calcium channel blockers, such as amlodipine used in the treatment of

high blood pressure

?theophylline used in the treatment of asthma

?warfarin or phenprocoumon, used as anticoagulants

?phenytoin used in the treatment of seizures

?ciclosporin used in organ transplants as an immunosuppressant

?benzodiazepines, such as temazepam used to calm anxiety.

Since there is no clinical experienceRoActemra should not be used with other biologic medications used to treat RA, AIJs, AIJp, or ACG.

Pregnancy, breastfeeding, and fertility

RoActemra should not be used during pregnancy,unless clearly necessary. Talk to your doctor if you are pregnant, think you may be, or plan to become pregnant.

Women of childbearing age shoulduse effective contraceptive methods during and for 3 months after completing treatment.

Stop breastfeeding if you start treatment with RoActemra, and consult your doctor. Before resuming breastfeeding, at least 3 months should have passed since your last treatment with RoActemra.The effects of RoActemra on breast milk are unknown.

Driving and operating machinery

This medication may cause dizziness, if you feel dizzy, do not drive or operate machinery.

RoActemra contains polysorbate

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

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

The treatment should be initiated by a healthcare professional with experience in the diagnosis and treatment of AR, AIJs, AIJp, or ACG.

Dose recommended

The dose for all adults with AR or ACG is 162 mg (the content of one pre-filled pen) administered once a week.

Adolescents with AIJs (12 years of age and older)

The dose of RoActemra depends on the patient's weight.

•If the patient weighsless than 30 kg: the dose is 162 mg (the content of 1 pre-filled pen),

once every 2 weeks

•If the patient weighs30 kg or more: the dose is 162 mg (the content of 1 pre-filled pen),

once a week.

The pre-filled pen should not be used to treat children under 12 years of age.

Adolescents with AIJp (12 years of age and older)

The dose of RoActemra depends on the patient's weight.

•If the patient weighsless than 30 kg: the dose is 162 mg (the content of 1 pre-filled pen),

once every 3 weeks

•If the patient weighs30 kg or more: the dose is 162 mg (the content of 1 pre-filled pen),

once every 2 weeks.

The pre-filled pen should not be used to treat children under 12 years of age.

RoActemra is administered by subcutaneous injection. At the beginning, your doctor or nurse may inject RoActemra (ACTPen®). However, your doctor may decide that you yourself inject RoActemra. In this case, you will receive information on how to self-inject RoActemra. Parents and caregivers will be trained on how to inject RoActemra in patients who cannot inject themselves.

Consult your doctor if you have any questions about how you or an adolescent you care for can self-administer an injection. At the end of this prospectus, you will find “administration instructions” in detail.

If more RoActemra is administered than it should

Since RoActemra is administered in a pre-filled pen, it is unlikely that too much will be administered. However, if you are concerned, consult your doctor, pharmacist, or nurse.

If an adult with AR or GCA or an adolescent with AIJs missed or forgot a dose of RoActemra

It is very important to use RoActemra exactly as prescribed by your doctor. Keep a record of your next dose.

?If you forget your weekly dose within 7 days, take your dose on the next scheduled day.

?If you forget your dose every 2 weeks within 7 days, inject a dose as soon as you remember and take your next dose according to your original calendar.

?If you forget your weekly dose or every 2 weeks for more than 7 days or are unsure when to inject RoActemra, call your doctor or pharmacist.

If an adolescent with AIJp missed or forgot a dose

It is very important to use RoActemra exactly as prescribed by your doctor. Keep a record of the next dose.

?If you forget a dose within 7 days, inject a dose as soon as you remember and administer the next dose according to your original calendar.

?If you forget a dose for 7 days or more, or are unsure when to inject RoActemra, call your doctor or pharmacist.

If treatment with RoActemra is interrupted

Do not stop treatment with RoActemra without consulting your doctor beforehand.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

The side effects may occur up to at least 3 months after your last dose of RoActemra.

Possible serious side effects

Consult your doctor immediately if you experience any of the following side effects:

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

Allergic reactionsduring or after the injection:

?difficulty breathing, chest tightness, or dizziness

?skin rash, itching, hives, swelling of the lips, tongue, or face

Signs of severe infections:

?fever and chills

?blistering in the mouth or skin

?abdominal pain

Signs and symptoms of liver toxicity

They may affect up to 1 in 1,000 patients

?fatigue

?abdominal pain

?jaundice (yellowing of the skin or eyes)

Other possible side effects

If you notice any of these symptoms, inform your doctor immediately.

Very common side effects:

They may affect more than 1 in 10 patients

?upper respiratory tract infections, with typical symptoms such as cough, nasal congestion, runny nose, sore throat, and headache

?high levels of fat in the blood (cholesterol)

?reactions at the injection site

Common side effects:

They may affect up to 1 in 10 patients

?lung infection (pneumonia)

?herpes (herpes zoster)

?fever blisters (herpes simplex oral), blisters

?skin infections (cellulitis), sometimes with fever and chills

?skin rash and itching, urticaria

?allergic reactions (hypersensitivity)

?eye infection (conjunctivitis)

?headache, dizziness, hypertension

?mouth ulcers, abdominal pain

?fluid retention (edema) in the lower legs, weight gain

?cough, shortness of breath

?low white blood cell count in blood tests (neutropenia, leucopenia)

?abnormal liver function tests (elevated transaminases)

?increased bilirubin measured in blood tests

?low fibrinogen levels in blood (protein involved in blood clotting)

Uncommon side effects:

They may affect up to 1 in 100 patients

?diverticulitis (fever, nausea, diarrhea, constipation, abdominal pain)

?swollen and red areas in the mouth

?high levels of fat in the blood (triglycerides)

?stomach ulcers

?kidney stones

?hypothyroidism

Rare side effects:

They may affect up to 1 in 1,000 patients

?Stevens-Johnson syndrome (skin rash that can lead to blisters and severe skin peeling)

?fatal allergic reactions (anaphylaxis)

?inflammation of the liver (hepatitis), jaundice

Very rare side effects:

They may affect up to 1 in 10,000 patients

?low white blood cell, red blood cell, and platelet counts in blood tests

?liver failure

Side effects in children and adolescents with JIA or JIAp

The side effects in children and adolescents with JIA or JIAp are generally similar to those in adults. Some side effects that are more commonly seen in children and adolescents include: nasal and throat inflammation, headache, nausea, and decreased white blood cell count.

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet.

You can also report them directly through the national reporting system included in the Appendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the pre-filled pen label and on the box after EXP. The expiration date is the last day of the month indicated.

Store in refrigerator (between 2°C – 8°C). Do not freeze. Once out of the refrigerator, the pre-filled pen can be stored for up to 2 weeks at a temperature equal to or below 30°C.

Keep the pre-filled pens in the outer packaging to protect from light and moisture.

Do not use this medication if you observe that it is cloudy or contains particles, is of any color other than colorless and slightly yellowish, or any part of the pre-filled pen appears damaged.

Do not shake the pen. After removing the cap from the needle, the injection should be started within 3 minutes to prevent the medication from drying and blocking the needle. If the pre-filled pen is not used within 3 minutes after removing the cap, it should be discarded in a sharps container and a new pre-filled pen should be used.

If after pressing the dose activation button the purple indicator does not move, the pre-filled pen should be discarded in a sharps container.Do notattempt to reuse the pre-filled pen. Do not repeat the injection with another pre-filled pen. If you have any questions or problems, consult with your healthcare professional.

Composition of RoActemra

?The active ingredient is tocilizumab.

Each pre-filled syringe contains 162mg of tocilizumab in 0.9 ml.

?The other components are L-Histidine, Monohydrochloride of L-histidine monohydrate, L-Arginine/Hydrochloride of L-arginine, L-Methionine,Polysorbate 80,Water for injection (see section 2‘Roactemra contains polysorbates’).

Appearance of the product and contents of the pack

RoActemra is a solution for injection. The solution is colourless to slightly yellowish.

RoActemra is supplied in pre-filled syringes of 0.9 ml containing 162mg of tocilizumab solution for injection.

Each pack contains 4 pre-filled syringes. The multiple pack contains 12 (3 packs of 4) pre-filled syringes. Some pack sizes may only be marketed..

Marketing Authorisation Holder and Responsible Person for Manufacturing

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

Responsible Person for Manufacturing

Roche Pharma AG

Emil-Barell-Str. 1

79639 Grenzach-Wyhlen

Germany

You can obtain more information about this medicinal product by contacting the local representative of the marketing authorisation holder:

Last update of the summary of product characteristics

Other sources of information

The detailed information on this medicinal product is available on the website of the European Medicines Agencyhttps://www.ema.europa.eu..

What you need to know to use your pre-filled syringe (ACTPluma) of RoActemra safely

It is important to read and follow the instructions for use that come with the pre-filled syringe of RoActemra before you use the pre-filled syringe and each time your doctor prescribes this medication again. Your healthcare professional will show you how to use the pre-filled syringe of RoActemra properly before you use it for the first time.

Important information: Keep unused pre-filled syringes in the original packaging and in the refrigerator at a temperature between 2°C and 8°C.Do not freeze.

Once out of the refrigerator, the pre-filled syringe can be stored for a total of 2 weeks at a temperature equal to or below 30°C, but not exceeding the original expiry date (EXP). Mark the corresponding date on the box. Always keep the pre-filled syringes in the outer packaging to protect them from light and moisture.

Parts of the pre-filled syringe of RoActemra(see Figure A).

Figure A

Equipment needed to prepare the injection with your pre-filled syringe of RoActemra (see Figure B):

• 1 pre-filled syringe of RoActemra
• 1 alcohol-soaked swab
• 1 sterile cotton ball or gauze
• 1 sharps container or puncture-resistant container for safe disposal of the green cap and used pre-filled syringe (seeStep 4 “Disposal of the pre-filled syringe”)

Figure B

Step 1. Preparation for a RoActemra injection

Find a comfortable place to work with a clean and flat surface.

Do notuse the pre-filled syringe if the expiry date has passed, as its use may not be safe. If the expiry date has passed, dispose of the pre-filled syringe safely in a sharps container and use a new one.

orDo notaccelerate the warming process in any way, such as using the microwave or submerging the pre-filled syringe in warm water.

orDo notleave the pre-filled syringe under direct sunlight to warm up.

Do not remove the green cap while the pre-filled syringe of RoActemra is warming up.

Figure C

Step 2. Choose and prepare the injection site

Choose an injection site

Rotate the injection site

Figure D

Prepare the injection site

Step 3. Inject RoActemra

Figure E

Important information: Do not touch the needle guard located at the end of the pre-filled syringe below the visibility window (see Figure A), to avoid accidental needlestick.

Figure F

Figure G

• Do notpress the green activation button yet.
• Position the needle guard of the pre-filled syringe at an angle of 90° with respect to the fold in your skin (see Figure H).
• It is essential to choose the correct angle to ensure that the medication is released under the skin (in the subcutaneous tissue), otherwise the injection may be painful and the medication may not work.

Figure H

Figure I

Figure J

Figure K

Figure L

After the injection

Step 4. Dispose of the pre-filled syringe

How to dispose of used pre-filled syringes?

Figure M

Keep the pre-filled syringe of RoActemra and the sharps container out of sight and out of reach of children.

Mark your injection

If you have any questions or concerns about your pre-filled syringe of RoActemra, consult with your healthcare professional familiar with RoActemra.