RoActemra 20 mg/ml concentrate for solution for infusion

RoActemra contains the active substance tocilizumab, a monoclonal antibody that blocks the action of a specific protein (cytokine) called interleukin-6. This protein is involved in inflammatory processes of the body, and blocking it can reduce the inflammation in your body.

RoActemra is used to treat adults with moderate to severe active rheumatoid arthritis (RA), an autoimmune disease, if previous therapies did not work well enough. RoActemra helps to reduce symptoms such as pain and swelling in your joints and can also improve your performance of daily tasks. RoActemra has been shown to slow the damage to the cartilage and bone of the joints caused by the disease and to improve your ability to do normal daily activities.

RoActemra is usually given in combination with methotrexate. However, RoActemra can be given alone if your doctor determines that methotrexate is inappropriate.

Do not use RoActemra

• if you are allergic (hypersensitive) to tocilizumab or any of the other ingredients of RoActemra (listed in section 6, ?What RoActemra contains?).
• if you have an active, severe infection.

Take special care with RoActemra

• If you experience allergic reactions such as chest tightness, wheezing, severe dizziness or light-headedness, swelling of the lips or skin rash during or after the infusion, then tell your doctor immediately.
• If you have any kind ofinfection,short- or long-term,or if you often get infections. Tell your doctor immediately if you feel unwell. RoActemra can reduce your body?s ability to respond to

infections and may make an existing infection worse or increase the chance of getting a new infection.

• If you have hadtuberculosis, tell your doctor. Your doctor will check for signs and symptoms of tuberculosis before starting RoActemra.
• If you have hadintestinal ulcers or diverticulitis, tell your doctor. Symptoms would include abdominal pain and unexplained changes in bowel habits with a fever.
• If you have liver disease,tell your doctor. Before you use RoActemra, your doctor may examine your liver function.
• If you have recently got or are planning to get vaccinated , tell your doctor. Certain types of vaccines should not be given while receiving RoActemra.
• If you have cancer, tell your doctor. Your doctor will have to decide if you can still be given RoActemra.
• If you have cardiovascular risk factors such as raised blood pressure and raised cholesterol levels, tell your doctor. These factors need to be monitored while receiving RoActemra.
• If you have moderate to severe kidney function problems, your doctor will monitor you.

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

RoActemra is not recommended for use in children or adolescents under 18 years of age.

Using other medicines

Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. RoActemra can affect the way some medicines work, and the dose of these may require adjustment. You should tell your doctor if you are using medicines containing any of the following active substances:

• atorvastatin, used to reduce cholesterol levels
• calcium channel blockers (e.g. amlodipine), used to treat raised blood pressure
• theophylline, used to treat asthma
• warfarin, used as a blood thinning agent
• phenytoin, used to treat convulsions
• ciclosporin, used to suppress your immune system during organ transplants
• benzodiazepines (e.g. temazepam), used to relieve anxiety

Due to lack of clinical experience, RoActemra is not recommended for use with other biological medicines for the treatment of RA.

Pregnancy and breast-feeding

Talk to your doctor if you are pregnant, may be pregnant, intend to become pregnant or if you are breast-feeding. Women of childbearing potential must use effective contraception during and up to 3 months after treatment. RoActemra should not be used during pregnancy unless clearly necessary.

It is not known whether RoActemra is excreted in breast milk. If you are a nursing mother, you should stop breast-feeding if you are to be given RoActemra. Before starting breast-feeding, your last treatment with RoActemra should be at least 3 months ago.

Driving and using machines

There are no studies on the effects of RoActemra on the ability to drive and use machines. However, if you experience dizziness, a common side effect, then you should not drive or use machines.

Important information about some of the ingredients of RoActemra

This medicinal product contains 26.55 mg sodium per maximum dose of 1200 mg (8.85 mg sodium per 400 mg vial). To be taken into consideration by patients on a controlled sodium diet. Doses below 1025 mg of this medicinal product contain less than 1 mmol sodium (23 mg), i.e. essentially ?sodium free?.

The usual dose of RoActemra is 8 mg per kg of body weight. Depending on your response, your doctor may decrease your dose to 4 mg/kg then increase back to 8 mg/kg when appropriate.

You will receive RoActemra once every 4 weeks through a drip in your vein (intravenous infusion) over one hour.

After dilution, RoActemra will be given to you by a doctor or nurse, who will also monitor you during and after administration.

If you use more RoActemra than you should

Since RoActemra is given by a doctor or nurse, it is unlikely that you will be given too much. However, if you are worried, talk to your doctor.

If you forget to use RoActemra

Since RoActemra is given by a doctor or nurse, it is unlikely that you will miss a dose. However, if you are worried, talk to your doctor.

If you stop using RoActemra

You should not stop using RoActemra without discussing with your doctor first.

If you have any further questions on the use of RoActemra, then please ask your doctor or pharmacist.

Like all medicines, RoActemra can cause side effects, although not everybody gets them. Side effects could occur at least up to 3 months after your last dose of RoActemra.

The most common side effects of RoActemra are upper respiratory tract infections, with typical symptoms such as cough, blocked nose, runny nose, sore throat and headache.

Possible serious side effects include serious infections and allergic (hypersensitivity) reactions, that may, in a small number of cases, be life-threatening.
If you notice any of the following signs of:

allergic reactions during or after infusion, tell your doctor immediately:

• difficulty with breathing or light-headedness
• rash, itching, hives, swelling of the lips.

infections, tell your doctor as soon as possible:

• fever and chills
• mouth or skin blisters
• stomach ache
• persistent headaches.

The symptoms described above can be signs of the side effects listed below, all of which have been observed with RoActemra in clinical studies.

Side effects may occur with certain frequencies, which are defined as follows:

• very common: affects more than 1 user in 10
• common: affects 1 to 10 users in 100
• uncommon: affects 1 to 10 users in 1,000
• rare: affects 1 to 10 users in 10,000
• very rare: affects less than 1 user in 10,000
• not known: frequency cannot be estimated from the available data.

Very common side effects:upper respiratory tract infections like coughs and colds, and high cholesterol levels.

Common side effects:lung infection (pneumonia),cold sores (oral herpes simplex), blisters, shingles (herpes zoster), skin infection sometimes with fever and chills, low white blood cell counts shown by blood tests (neutropenia, leucopenia), headache, dizziness, high blood pressure,mouth ulceration, stomach pain, abnormal liver function tests (increased transaminases), increased bilirubin shown by blood tests, rash and itching, hives, fluid retention (oedema) in the lower legs, cough, shortness of breath, weight increase, eye infection (conjunctivitis) and allergic (hypersensitivity) reactions

Uncommon side effects:diverticulitis (fever, nausea, diarrhoea, constipation, stomach pain), red swollen (inflamed) areas in the mouth, high blood fat (triglycerides), stomach ulcer, kidney stones and underactive thyroid.

Very rare side effects: low blood measurements for white blood cells, red blood cells and platelet count.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Keep out of the reach and sight of children.

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

Keep the vial in the outer carton in order to protect from light.

What RoActemra contains

• The active substance is tocilizumab. Each 4 ml vial contains 80 mg tocilizumab (20 mg/ml). Each 10 ml vial contains 200 mg tocilizumab (20 mg/ml). Each 20 ml vial contains 400 mg tocilizumab (20 mg/ml).
• The other ingredients are sucrose, polysorbate 80, disodium phosphate dodecahydrate, sodium dihydrogen phosphate dihydrate and water for injections.

What RoActemra looks like and contents of the pack

RoActemra is a concentrate for solution for infusion. The concentrate is a clear to opalescent, colourless to pale yellow liquid.
RoActemra is supplied as vials containing 4 ml, 10 ml and 20 ml concentrate for solution for infusion. Pack size of 1 and 4 vials. Not all pack sizes may be marketed.

Marketing Authorisation Holder

Roche Registration Limited

6 Falcon Way
Shire Park
Welwyn Garden City
AL7 1TW
United Kingdom

Manufacturer

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

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

LuxembourgLuxemburg Voirsiehe BelgiqueBelgien BelgiëBelgiqueBelgien N.V. Roche S.A. TélTel 32 0 2 525 82 11

359 2 818 44 44 Magyarország Roche Magyarország Kft. Tel 36 - 23 446 800

eská republika Roche s. r. o. Tel 420 - 2 20382111 Malta See United Kingdom, Roche Products Ltd. Tel 44 0 1707 366000

Danmark Roche as Tlf 45 - 36 39 99 99 Nederland Roche Nederland B.V. Tel 31 0 348 438050

Norge Roche Norge AS Tlf 47 - 22 78 90 00 Deutschland Roche Pharma AG Tel 49 0 7624 140 oder Chugai Pharma Marketing Ltd. Zweigniederlassung Deutschland Tel 49 0 69 663000 0

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

Roche Hellas A.E. 30 210 61 66 100 Polska Roche Polska Sp.z o.o. Tel 48 - 22 345 18 88

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

România Roche România S.R.L. Tel 40 21 206 47 01 France Roche Tél 33 0 1 46 40 50 00 ou Chugai Pharma France Tél 33 0 1 56 37 05 20

Ireland Roche Products Ireland Ltd. Tel 353 0 1 469 0700 Slovenija Roche farmacevtska druba d.o.o. Tel 386 - 1 360 26 00

Slovenská republika Roche Slovensko, s.r.o. Tel 421 - 2 52638201 Ísland Roche as co Icepharma hf Sími 354 540 8000

Italia Roche S.p.A. Tel 39 - 039 2471 SuomiFinland Roche Oy PuhTel 358 0 10 554 500

K .. . 357 - 22 76 62 76 Sverige Roche AB Tel 46 0 8 726 1200

Latvija Roche Latvija SIA Tel 371 - 6 7039831 United Kingdom Roche Products Ltd. Tel 44 0 1707 366000 or Chugai Pharma UK Ltd. Tel 44 0 208 987 5600

Lietuva

UAB ?Roche Lietuva?
Tel: +370 5 2546799

This leaflet was last approved

The following information is intended for medical or healthcare professionals only

Instructions for dilution prior to administration
Parenteral medicinal products should be inspected visually for particulate matter or discoloration prior to administration. Only solutions which are clear to opalescent, colourless to pale yellow and free of visible particles should be diluted

Withdraw a volume of sterile, non-pyrogenic sodium chloride 9 mg/ml (0.9%) solution for injection from a 100 ml infusion bag, equal to the volume of RoActemra concentrate required for the patients dose, under aseptic conditions. The required amount of RoActemra concentrate (0.4 ml/kg) should be withdrawn from the vial and placed in the 100 ml infusion bag. This should be a final volume of 100 ml. To mix the solution, gently invert the infusion bag to avoid foaming.

RoActemra is for single-use only.

Any unused product or waste material should be disposed of in accordance with local requirements.