Prospecto: Information for the User

RoActemra 162 mg, pre-filled syringe injectable solution

tocilizumab

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

• Keep this prospectus, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist or nurse.
• This medicine has been prescribed to you alone,and you must not give it to othersalthough they may 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 prospectus. See section 4.

In addition to this prospectus, 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:

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

• adultswith severe active and progressive 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 may 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 it possible to use steroids for a shorter period while still controlling GCA.

• children and adolescents, 1 year of age and older with systemic juvenile idiopathic arthritis (sJIA) active,a 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,2 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 a child (if he is the patient you care for) are allergic totocilizumab or any of the other components of this medication (listed in section 6).

?If you or a child (if he is the patient you care for)have an active severe infection.

If this happens, consult 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 or 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, 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 a 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 have to 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, a low platelet count, or elevated liver enzymes.

Children and adolescents

RoActemra should not be injected subcutaneously in children under 1 year of age.

RoActemra should not be administered to children with AIJs weighing less than 10 kg.

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

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 the way 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 to treat high blood pressure

?theophylline used to treat asthma

?warfarin or phenprocoumon, used as anticoagulants

?phenytoin used to treat seizures

?ciclosporin used in organ transplants as an immunosuppressant

?benzodiazepines, such as temazepam used to calm anxiety.

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 are planning 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 syringe with 162 mg/0.9 ml, which is 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 of this medication as indicated by your doctor, pharmacist, or nurse. In case of 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.

Recommended dose

The dose for adults with AR and ACG is 162 mg (the content of a pre-filled syringe) administered once a week.

Children and adolescents with AIJs (1 year of age and older)

The usual 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 syringe), once every 2 weeks

•If the patient weighs30 kg or more: the dose is 162 mg (the content of 1 pre-filled syringe), once a week.

Children and adolescents with AIJp (2 years of age and older)

The usual 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 syringe),once every 3 weeks

•If the patient weighs30 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. At the beginning, your doctor or nurse may inject RoActemra for you. However, your doctor may decide that you can administer RoActemra yourself. In this case, you will receive information on how to self-administer RoActemra. Parents and caregivers will receive instructions on how to inject RoActemra in patients who cannot administer it themselves, such as children.

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

If you are administered more RoActemra than you should

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

If an adult with AR and ACG or a child or adolescent with AIJs missed or forgot a doseIt 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 administer your next dose according to your original schedule.

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

If a child or adolescent with AIJp missed or forgot a dose

It is very important to use RoActemra exactly as prescribed by the 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 schedule.

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

If you interrupt treatment with RoActemra

You should 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.

Severe side effects: consult your doctor immediately.

Consult your doctorimmediatelyif 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)

List of other possible side effects:

If you notice any of these symptoms, inform your doctoras soon as possible.

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

?pneumonia

?herpes (herpes zoster)

?fever blisters (herpes simplex oral), blisters

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

?skin rash and itching, urticaria

?allergic reactions (hypersensitivity)

?eye infection (conjunctivitis)

?headache, dizziness, hypertension

?mouth ulcers, abdominal pain

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

?cough, shortness of breath

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

?abnormal liver function tests (elevated transaminases)

?high bilirubin levels measured in blood tests

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

Rare 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, which can lead to severe blistering and peeling of the skin)

?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:

In children and adolescents with JIA or JIAp, side effects are generally similar to those in adults. Some side effects are observed more frequently in children and adolescents: nasal and throat inflammation, headache, nausea, and decreased white blood cell count.

Reporting of side effects:

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

You can also report them directly through thenational reporting system included in theAppendix 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 syringe 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 syringe can be stored for up to 2 weeks at a temperature equal to or below 30°C.

Keep the pre-filled syringes 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 yellow, or any part of the pre-filled syringe appears damaged.

Do not shake the syringe. After removing the cap from the needle, the injection should be initiated within 5 minutes to prevent the medication from drying and blocking the needle. If the pre-filled syringe is not used within 5 minutes after removing the cap, it should be discarded in a sharps container and a new pre-filled syringe should be used.

If after inserting the needle, the plunger of the syringe cannot be pressed, the pre-filled syringe should be discarded in a special container for sharps and another new one should be used.

Composition of RoActemra

?The active ingredient is tocilizumab.

Each pre-filled syringe contains 162 mg 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 polysorbate”).

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 162 mg of tocilizumab solution for injection.

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

Marketing authorisation holder and responsible person for manufacture

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

Responsible person for manufacture

Roche Pharma AG Emil-Barell-Str. 1

79639 Grenzach-Wyhlen

Germany

For further information about this medicinal product, please consult the representative of the marketing authorisation holder in your country:

Last update of this leaflet

Other sources of information

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

What you need to know to use your RoActemra pre-filled syringe safely

It is important to read, understand and follow the instructions to ensure that you or your caregiver use the RoActemra pre-filled syringe correctly. These instructions do not replace the information that your healthcare professional should give you. Your healthcare professional will show you how to prepare and inject correctly before you use the RoActemra pre-filled syringe for the first time. Ask your healthcare professional any questions you may have. Do not attempt to administer an injection until you are sure you understand how to use the RoActemra pre-filled syringe.

Please also read the patient leaflet that comes with the RoActemra pre-filled syringe for the most important information you need to know about this medicinal product. It is essential that you are under the care of your healthcare professional during the time you are being treated with RoActemra.

Important information:

?Do not use it if the syringe appears damaged.

?Do not use it if the medicine is cloudy, turbid, discoloured or contains particles.

?Do not attempt to disassemble the syringe at any time.

?Do not remove the needle cap until you are ready for the injection.

?Do not inject through clothing that covers your skin.

?Never reuse the same syringe.

?Do not touch the activation clips of the syringe protector as this may damage the syringe.

Storage

Keep the RoActemra pre-filled syringe and all medicines out of the sight and reach of children. Store the syringe in the refrigerator at a temperature of 2-8 ºC. 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 ºC, but not exceeding the original expiry date (EXP). Mark the corresponding date on the box. The pre-filled syringe must always be stored in the original packaging. Protect the syringe from freezing and light. Keep the syringes dry.

Parts of the pre-filled syringe

To administer your injection you will need:

Included in the pack:

?Pre-filled syringe.

Not included in the pack:

?Alcohol-soaked swab.

?Sterile cotton or gauze.

?Sharps container for safe disposal of the needle cap and used syringe.

A place to prepare your equipment:

?Find a well-lit, clean and flat surface such as a table.

Step 1. Visual inspection of the syringe

?Take the box containing the syringe from the refrigerator and open the box.Do not touch the activation clips of the syringe protector as this may damage the syringe.

?Remove the syringe from the box and visually inspect the syringe, as well as the medicine in the syringe. This is important to ensure that the syringe and medicine can be used safely.

?Check the expiry date that appears on the box and on the syringe (see Figure A) to ensure that it has not passed (expired). Do not use the syringe if the expiry date has passed. This is important to ensure that the syringe and medicine can be used safely.

Discard the syringe and do not use it if:

?The medicine is cloudy.

?The medicine contains particles.

?The medicine has a different colour apart from colourless to pale yellow.

?Any part of the syringe appears damaged.

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

?Do not remove the needle cap from your syringe before Step 5. Doing so may cause the medication to dry out and block the needle.

?Place the syringe on a clean, flat surface and allow the syringe to reach room temperature (18 ºC – 28 ºC) for 25-30 minutes to warm up. If you do not allow the syringe to reach room temperature, the injection may be uncomfortable and it may be difficult to push the plunger.

?Do not heat the syringe in any other way.

Step 3. Wash your hands

• Wash your hands with water and soap.

Step 4. Choose and prepare the injection site

• The recommended injection sites are the front and middle of the thighs and the lower abdomen below the navel, except for the area within five centimetres of the navel (see Figure B).

• If a caregiver is administering the injection, the outer surface of the upper arms may also be used (see Figure B).

?You will need to use a different site each time you self-administer an injection at least three centimetres away from the site used in your previous injection.

?Do not inject in areas where clothing may rub against the skin. Do not inject in moles, scars, bruises, or areas where the skin is sensitive, red, hard or not intact.

?Clean the area using an alcohol-soaked swab (see Figure C) to reduce the risk of infection.

?Allow the skin to dry for approximately 10 seconds.

?Ensure you do not touch the cleaned area before the injection. Do not fan or blow on the cleaned area.

Step 5.Remove the needle cap

?Do not hold the syringe by the plunger while removing the needle cap.

?Hold the syringe protector firmly with one hand, and remove the needle cap with the other hand (see Figure D). If you cannot remove the needle cap, you should ask your caregiver for help or contact your healthcare professional.

?Do not touch the needle or let it touch any surface.

• You may see a small air bubble in the RoActemra pre-filled syringe. It is not necessary to remove it.

?You may see a drop of liquid at the end of the needle. This is normal.

?Dispose of the needle cap in thesharps container.

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

?If the needle cap is removed and the syringe is not used within 5 minutes, the syringe must be disposed of in thesharps containerand a new syringe must be used. If the needle cap is removed and the syringe is not used within 5 minutes, it may be more difficult to administer the injection as the medicine may dry out and block the needle.

?Never put the needle cap back on the needle after it has been removed.

Step 6. Administer the injection

?Hold the syringe comfortably in your hands.

?To ensure that the needle can be inserted correctly into your skin, pinch a fold of skin loosely in the cleaned injection site with your free hand. Pinching the skin is important to ensure that you inject under your skin (in the fatty tissue) but not too deeply (in the muscle). Injecting into the muscle may result in an uncomfortable injection.

?Do not hold or push the plunger while inserting the needle into the skin.

?Insert the needle completely into the skin fold at an angle of between 45 º to 90 º with a quick and firm movement (see Figure E).

It is essential to choose the correct angle to ensure that the medicine is released under the skin (in the fatty tissue), otherwise the injection may be painful and the medicine may not work.

?Afterwards, hold the syringe in position and release the skin fold.

?Inject the medicine slowly by pushing the plunger slowly until the end (see Figure F). You must push the plunger until the end to ensure that the entire dose of medicine is administered and to ensure that theactivation clips of the syringe protectorare fully pushed to the side. If the plunger is not pushed fully, the syringe protector will not extend to cover the needle when it is removed. If the needle is not covered, proceed with caution, and place the syringe in thesharps containerto avoid injury from the needle.

?Once the plunger is pushed fully, hold it in place to ensure that all the medicine is injected before removing the needle from the skin.

?Hold the plunger in place while removing the needle from the skin at the same angle that it was inserted (see Figure G).

?If you are unable to push the plunger after inserting the needle, you must dispose of the pre-filled syringe in asharps containerand use a new pre-filled syringe (starting again from Step 2). If you still have difficulty, you should consult your healthcare professional.

?Once the needle is completely removed from the skin, you can release the plunger, allowing the syringe protector to cover the needle (see Figure H).

?If you see blood droplets at the injection site, you can press the injection site with a sterile cotton or gauze for approximately 10 seconds.

?Do not rub the injection site.

Step 7. Disposal of the syringe

?Do not attempt to put the syringe back together.

?Dispose of the used syringe in asharps container.Ask your doctor or pharmacist for information on where you can obtain asharps containeror what other type of puncture-resistant container you can use for safe disposal of your used syringes, if you do not have one (see Figure I).

Speak with your healthcare professional for guidance on the best way to dispose of your used syringes. There may be national regulations on how to dispose of used syringes.

Do not throw used syringes or the sharps container in your household waste and do not recycle them.

?Dispose of the full container as instructed by your doctor or pharmacist.

?Always keep the sharps container out of sight and reach of children.

Patient advice related to hypersensitivity reactions (also known as anaphylaxis, if severe)

If you develop symptoms such as, but not limited to, skin rash, itching, chills, facial, lip, tongue or throat swelling, chest pain, wheezing, difficulty breathing or swallowing, or a feeling of dizziness or fainting at any time outside of the clinic, during or after the injection of RoActemra, you must seek immediate medical attention.

Patient advice related to early recognition and treatment to limit the risk of severe infections

Be aware of the first signs of infection such as:

?Dull aches, fever, chills.

?Cough, chest discomfort, shortness of breath.

?Redness, heat, unusual inflammation of the skin or joints.

?Abdominal pain/sensitivity and/or changes in bowel function.

Call your doctor and seek medical attention without delay if you think you may be developing an infection.

If you have any concerns or questions about your syringe, contact your doctor or pharmacist for help.