ROACTEMRA 20 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

RoActemra 20 mg/ml, concentrate for solution for infusion

tocilizumab

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• If you experience any side effects, talk to your doctor or nurse, even if they are not listed in this leaflet. See section 4.

In addition to this leaflet, you will be given a patient information card, which contains important safety information that you should know before receiving RoActemra and during treatment with RoActemra.

Contents of the package leaflet

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

1. What is RoActemra and what is it used for

RoActemra contains the active substance 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 by blocking it, inflammation can be reduced. RoActemra helps reduce symptoms such as pain and swelling in your joints and can also improve your ability to perform daily tasks. RoActemra has been shown to slow down the progression of damage to the cartilage and bones of the joints caused by the disease and improve your ability to perform daily activities.

• RoActemra is used to treat adultswith moderate to severe active rheumatoid arthritis (RA), which is an autoimmune disease, if previous treatments have not worked well. RoActemra is normally used in combination with methotrexate. However, RoActemra may be given alone if your doctor decides that methotrexate is not suitable.

• RoActemracan also be used to treat adults who have not been previously 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 that causes pain and swelling in one or more joints, as well as fever and rash. RoActemra is used to improve the symptoms of sJIA and can be given in combination with methotrexate or alone.

• RoActemra is used to treat children with pJIA. RoActemra is used in children aged 2 years and older with active polyarticular juvenile idiopathic arthritis (pJIA), an inflammatory disease that causes pain and swelling in one or more joints. RoActemra is used to improve the symptoms of pJIA and can be given in combination with methotrexate or alone.

• RoActemra is used to treat adults and childrenaged 2 years and older with cytokine release syndrome (CRS), a serious or potentially life-threatening side effect in patients treated with chimeric antigen receptor (CAR) T-cell therapy, used to treat certain types of cancer.

• RoActemra is used to treat adultswith coronavirus disease 2019 (COVID-19), who are receiving systemic corticosteroids and require oxygen supplementation or mechanical ventilation.

2. What you need to know before you start using RoActemra

You will not be given RoActemra

• If you are allergic to tocilizumab or any of the other ingredients of this medicine (listed in section 6).
• If you have a severe active infection (except for COVID-19).

If any of these apply to you, talk to your doctor or nurse.

Warnings and precautions

Talk to your doctor or nurse before you start receiving RoActemra.

• If you experience allergic reactionssuch as chest tightness, wheezing, dizziness, or severe dizziness, swelling of the lips, or skin rash during or after the infusion, tell your doctor immediately.

• If you have any type of infection, either short-term or long-term, or if you get infections often. Tell 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 chance of getting a new infection.

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

• If you have had intestinal ulcer or diverticulitis, tell your doctor. Symptoms would include abdominal pain and unexplained changes in bowel habits with fever.

• If you have liver disease, tell your doctor. Before using RoActemra, your doctor will perform a blood test to measure your liver function.

• If a patienthas been vaccinated recently(adult or child) or is scheduled to be vaccinated, tell your doctor. All patients, especially children, must be up to date with their vaccination schedule before starting treatment with RoActemra, unless urgent treatment is required. Certain types of vaccines must not be given while receiving RoActemra.

• If you have cancer, tell your doctor. Your doctor will decide if you can continue treatment with RoActemra.

• If you have cardiovascular risk factors, such as high blood pressure, and high cholesterol levels, tell your doctor. These factors need to be controlled while receiving treatment with RoActemra.

• If you have moderate to severe kidney problems, your doctor will monitor you.

• If you have persistent headaches.

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

Children and adolescents

RoActemra is not recommended for use in children under 2 years of age.

Tell your doctor if the child has a history of macrophage activation syndrome(uncontrolled activation and proliferation of specific blood cells). Your doctor will decide if the child can continue receiving RoActemra.

Other medicines and RoActemra

Tell your doctor if you are taking, have recently taken, or might take any other medicines (or if your child is taking them, if they are the patient). This includes medicines obtained without a prescription. RoActemra may affect how some medicines work, and a dose adjustment may be needed. Tell your doctorif you are using medicines that contain any of the following active substances:

• methylprednisolone, dexamethasone, used to reduce inflammation
• simvastatin or atorvastatin, used to reduce cholesterol levels
• calcium channel blockers, such as amlodipine, used to treat high blood pressure
• theophylline, used to treat asthma
• warfarin or phenprocoumon, used as anticoagulants
• phenytoin, used to treat seizures
• cyclosporin, used in organ transplants as an immunosuppressant
• benzodiazepines, such as temazepam, used to calm anxiety

Because there is no clinical experience, the use of RoActemra with other biologic medicines used to treat RA, sJIA, or pJIA is not recommended.

Pregnancy, breastfeeding, and fertility

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

Women of childbearing agemust use effective contraceptive methods during and up to 3 months after finishing treatment.

Stop breastfeeding if you start treatment with RoActemra, and consult your doctor. Before restarting breastfeeding, at least 3 months must have passed since your last treatment with RoActemra. It is not known if RoActemra passes into breast milk.

Data available so far do not suggest that this treatment has any effect on fertility.

Driving and using machines

This medicine may cause dizziness, if you feel dizzy, do not drive or use machines.

RoActemra contains sodium

After dilution with sodium chloride 0.9% solution, this medicine contains 230.6 mg of sodium per maximum dose of 800 mg, which is equivalent to 11.5% of the WHO recommended maximum daily intake 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, which is equivalent to 0.5 mg/ml. Polysorbates may cause allergic reactions. Tell your doctor if you or your child has any known allergy.

3. How to use RoActemra

This medicine is subject to medical prescription and must be administered by a doctor or nurse.

RoActemra will be administered by intravenous infusion, by a doctor or nurse. They will dilute the solution, prepare the intravenous infusion, and monitor you during and after treatment.

Adult patients with RA

The usual dose of RoActemra is 8 milligrams (mg) per kilogram (kg) of body weight.

Depending on the response, your doctor may decide to reduce the dose to 4 mg/kg and then increase it back to 8 mg/kg when appropriate.

Adults will be given RoActemra once every 4 weeks through a vein (intravenous infusion) over 1 hour.

Children with sJIA (aged 2 years and older)

The usual dose of RoActemra depends on body weight.

• If you weigh less than 30 kg, the dose is 12 mg per kilogram of body weight.
• If you weigh 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 be given RoActemra once every 2 weeks through a vein (intravenous infusion) over 1 hour.

Children with pJIA (aged 2 years and older)

The usual dose of RoActemra is calculated based on body weight.

• If you weigh less than 30 kg: the dose is 10 mg per kilogram of body weight.
• If you weigh 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 once every 4 weeks by intravenous infusion over 1 hour.

CRS patients

The usual dose of RoActemra is 8 mg per kilogram of body weight if you weigh 30 kg or more.

The dose is 12 mg per kilogram of body weight if you weigh less than 30 kg.

RoActemra may be given alone or in combination with corticosteroids.

COVID-19 patients

The usual dose of RoActemra is 8 mg per kilogram of body weight. A second dose may be necessary.

If you are given too much RoActemra

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

If you miss a dose of RoActemra

As RoActemra is administered by a doctor or nurse, it is unlikely that you will miss a dose. However, if you are concerned, talk to your doctor or nurse.

If you stop treatment with RoActemra

You must not stop treatment with RoActemra without talking to your doctor first.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

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

Serious side effects

Talk to your doctor immediatelyif you experience any of the following side effects:

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

Allergic reactionsduring or after the infusion:

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

Signs of serious infections

• fever and chills
• mouth or skin blisters
• stomach pain

Signs and symptoms of liver damage

May affect up to 1 in 1,000 people

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

List of other possible side effects

If you notice any of these symptoms, tell 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, nasal congestion, runny nose, sore throat, and headache
• high levels of fat in the blood (cholesterol)

Common side effects:

May affect up to 1 in 10 people

• lung infection (pneumonia)
• shingles (herpes zoster)
• fever (oral herpes), blisters
• skin infections (cellulitis), sometimes 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 (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 by blood tests
• low levels of fibrinogen in the blood (protein involved in blood clotting)

Uncommon side effects:

May affect up to 1 in 100 people

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

Rare side effects:

May affect up to 1 in 1,000 people

• Stevens-Johnson syndrome (skin rash that can lead to severe blistering and peeling of the skin)

• life-threatening allergic reactions (anaphylaxis)
• liver inflammation (hepatitis), jaundice

Very rare side effects:

May affect up to 1 in 10,000 people

• low levels of white blood cells, red blood cells, and platelets
• liver failure

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

Children with sJIA

Generally, side effects in patients with sJIA were of a similar type to those in adults with RA. Some side effects were seen more frequently: nasal and throat inflammation, diarrhea, low white blood cell count, and elevated liver enzymes.

Children with pJIA

Generally, side effects in patients with pJIA were of a similar type to those in adults with RA. Some side effects were seen more frequently: nasal and throat inflammation, headache, feeling unwell (nausea), and low white blood cell count.

5. Storage of 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 is the last day of the month shown.

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

Keep the vials in the outer packaging to protect them from light.

6. Container contents and additional information

Composition of RoActemra

• 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 other ingredients 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").

Appearance and container contents of the product

RoActemra is a concentrate for solution for infusion. The concentrate is a clear to opalescent, colorless to pale yellow liquid.

RoActemra is supplied in vials containing 4 ml, 10 ml, and 20 ml of concentrate for solution for infusion. Pack size of 1 and 4 vials. Not all pack sizes may be marketed.

Marketing authorisation holder and manufacturer

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

Manufacturer

Roche Pharma AG

Emil-Barell-Str. 1

79639 Grenzach-Wyhlen

Germany

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

Date of last revision of this leaflet

Other sources of information

Detailed information on this medicinal product is available on the European Medicines Agency website https://www.ema.europa.eu.

This information is intended for healthcare professionals only:

Instructions for dilution prior to administration

Parenteral drugs should be inspected visually for particulate matter and color change prior to administration. Only solutions that are 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 sJIA (with weight ≥30 kg)

Remove from a 100 ml infusion bag a volume of sterile and apyrogenic sodium chloride 9 mg/ml (0.9%) solution equal to the volume of RoActemra concentrate needed for the patient's dose, under aseptic conditions. The required amount of RoActemra concentrate (0.4 ml/kg) should be withdrawn from the vial and added to the 100 ml infusion bag. The final volume should be 100 ml. To mix the solution, gently invert the infusion bag to avoid foam formation.

Use in pediatric population

Patients with sJIA, pJIA, and sJIA with weight ≥30 kg

Remove from a 100 ml infusion bag a volume of sterile and apyrogenic sodium chloride 9 mg/ml (0.9%) solution equal to the volume of RoActemra concentrate needed for the patient's dose, under aseptic conditions. The required amount of RoActemra concentrate (0.4 ml/kg) should be withdrawn from the vial and added to the 100 ml infusion bag. The final volume should be 100 ml. To mix the solution, gently invert the infusion bag to avoid foam formation.

Patients with sJIA and weight <30 kg

Remove from a 50 ml infusion bag a volume of sterile and apyrogenic sodium chloride 9 mg/ml (0.9%) solution equal to the volume of RoActemra concentrate needed for the patient's dose, under aseptic conditions. The required amount of RoActemra concentrate (0.6 ml/kg) should be withdrawn from the vial and added to the 50 ml infusion bag. The final volume should be 50 ml. To mix the solution, gently invert the infusion bag to avoid foam formation.

Patients with pJIA and weight <30 kg

Remove from a 50 ml infusion bag a volume of sterile and apyrogenic sodium chloride 9 mg/ml (0.9%) solution equal to the volume of RoActemra concentrate needed for the patient's dose, under aseptic conditions. The required amount of RoActemra concentrate (0.5 ml/kg) should be withdrawn from the vial and added to the 50 ml infusion bag. The final volume should be 50 ml. To mix the solution, gently invert the infusion bag to avoid foam formation.

RoActemra is for single use only.

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