Roactemra 20 mg/ml concentrate for solution for infusion

Package leaflet: Information for the user

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 using this medicine, because it contains important information for you.

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

In addition to this leaflet, you will be given a patient alert card containing important safety information you should know before receiving 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 an active substance called tocilizumab, which is a protein derived 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 joint pain and swelling and may also improve your ability to perform daily tasks. RoActemra has been shown to reduce the progression of cartilage and bone damage in the joints caused by the disease and to improve your ability to carry out daily activities.

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

• RoActemra can also be used to treat adults who have not previously been treated with methotrexate and who have severe, active, and progressive rheumatoid arthritis.

• RoActemra is used to treat children with systemic juvenile idiopathic arthritis (sJIA). RoActemra is used in children from 2 years of age onwards who have 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 and may be administered either in combination with methotrexate or alone.

• RoActemra is used to treat children with polyarticular juvenile idiopathic arthritis (pJIA). RoActemra is used in children from 2 years of age onwards 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 and may be administered in combination with methotrexate or alone.

• RoActemra is used to treat adults and children from 2 years of age onwards with severe or potentially life-threatening cytokine release syndrome (CRS), an adverse reaction in patients treated with chimeric antigen receptor (CAR) T-cell therapy used to treat certain types of cancer.

• 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 need to know before starting to use RoActemra

RoActemra will not be administered to you if:

• You are allergic to tocilizumab or to any of the other components of this medicine (listed in section 6).
• You have an active severe infection (with the exception of covid-19).

If any of these apply to you, consult the doctor or nurse administering the infusion.

Warnings and precautions

Talk to your doctor or nurse before starting to receive RoActemra:

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

• If you have any type of infection, whether 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 the likelihood of acquiring 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. Inform 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, inform your doctor. Symptoms may include abdominal pain and unexplained changes in bowel habits with fever.

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

• If a patient has recently been vaccinated (adult or child) or is planning to be vaccinated, inform your doctor. All patients, especially children, should be up to date with their vaccination schedule before starting treatment with RoActemra, unless urgent treatment is required. Certain types of vaccines should not be administered while receiving RoActemra.

• If you have cancer, inform your doctor. Your doctor will need to decide whether you can continue receiving RoActemra.

• If you have cardiovascular risk factors, such as high blood pressure or elevated cholesterol levels, inform your doctor. These factors need to be managed while you are receiving 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 whether you have a low white blood cell count, a low platelet count, or elevated liver enzymes.

Children and adolescents

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

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

Other medicines and RoActemra

Inform your doctor if you are taking any other medicines (or if your child is taking them, if the child is the patient), including those obtained without a prescription. RoActemra may affect how some medicines work, and dose adjustments may be needed. Inform your doctor if you are using medicines containing any of the following active substances:

• methylprednisolone, dexamethasone, used to reduce inflammation
• simvastatin or atorvastatin, used to reduce cholesterol levels
• calcium channel antagonists, such as amlodipine, used in the treatment of high blood pressure
• theophylline, used in the treatment of asthma
• warfarin or fenprocoumon, used as anticoagulants
• phenytoin, used in the treatment of seizures
• cyclosporine, used in organ transplantation as an immunosuppressant
• benzodiazepines, such as temazepam, used to treat anxiety.

Because of the lack of clinical experience, the use of RoActemra with other biological medicines used to treat RA, AIJs or AIJp is not recommended.

Pregnancy, breastfeeding and fertility

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

Women of childbearing potential should use effective contraceptive methods during treatment and for at least 3 months after stopping treatment.

Interrupt breastfeeding if you start treatment with RoActemra, and consult your doctor. Breastfeeding should not be resumed until at least 3 months after your last dose of RoActemra. It is unknown whether RoActemra passes into breast milk.

Available data to date do not suggest that this treatment has any effect on fertility.

Driving and use of 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 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 80 (E433)

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 has any known allergies.

3. How to use RoActemra

This medicine is subject to restricted medical prescription by your doctor.

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 your 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 receive RoActemra once every 4 weeks via intravenous infusion over one hour.

Children with sJIA (from 2 years of age onwards)
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 receive RoActemra once every 2 weeks via intravenous infusion over one hour.

Children with pJIA (from 2 years of age onwards)
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 via intravenous infusion over one hour.

Patients with GCA

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

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

RoActemra may be administered alone or in combination with corticosteroids.

Patients with COVID-19

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

If you are given more RoActemra than you should

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

If you stop treatment with RoActemra

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

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

4. Possible adverse effects

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

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

Possible serious adverse effects

Contact your doctor immediately if you experience any of the following adverse effects:

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

Allergic reactions during 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 toxicity

May affect up to 1 in 1,000 patients

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

List of other possible adverse effects

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

Very common adverse effects:

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)

Common adverse effects:

May affect up to 1 in 10 patients

• lung infection (pneumonia)
• shingles (herpes zoster)
• cold sores (oral herpes simplex), 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 counts in blood tests (neutropenia, leucopenia)
• abnormal liver function tests (elevated transaminases)
• increased bilirubin levels in blood tests
• low levels of fibrinogen in the blood (a protein involved in blood clotting)

Uncommon adverse effects:

May affect up to 1 in 100 patients

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

Rare adverse effects:

May affect up to 1 in 1,000 patients

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

Very rare adverse effects:

May affect up to 1 in 10,000 patients

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

Reporting of adverse effects

If you experience any type of adverse effect, talk to your doctor, pharmacist, or nurse, even if these are possible adverse effects not listed in this leaflet.

You may also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

Children with JIA

In general, adverse effects in patients with JIA were of a similar type to those in adults with RA. Some adverse effects were observed more frequently: inflammation of the nose and throat, diarrhea, decreased white blood cell count, and increased liver enzymes.

Children with pJIA

In general, adverse effects in patients with pJIA were of a similar type to those in adults with RA. Some adverse effects were observed more frequently: inflammation of the nose and throat, headache, feeling unwell (nausea), and decreased 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 stated on the container after EXP. The expiry date is the last day of the month indicated.

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

Keep vials in the outer packaging to protect from light.

6. Contents of the pack and other 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 components 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 80 (E 433)").

Appearance of the product and contents of the pack

RoActemra is a concentrate for solution for infusion. The concentrate is a transparent to opalescent, colourless to pale yellow liquid.

RoActemra is supplied in vials containing 4 ml, 10 ml, and 20 ml of concentrate for solution for infusion. Pack sizes 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

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

Date of the most recent review 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 medicinal products should be inspected visually for particles and discoloration 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 GCA (with body weight ≥30 kg)

Under aseptic conditions, remove from a 100 ml infusion bag a volume of sterile, pyrogen-free sodium chloride 9 mg/ml (0.9%) solution for injection equal to the volume of RoActemra concentrate required for the patient's dose. 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 must be 100 ml. To mix the solution, gently invert the infusion bag to avoid foaming.

Use in the paediatric population

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

Under aseptic conditions, remove from a 100 ml infusion bag a volume of sterile, pyrogen-free sodium chloride 9 mg/ml (0.9%) solution for injection equal to the volume of RoActemra concentrate required for the patient's dose. 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 must be 100 ml. To mix the solution, gently invert the infusion bag to avoid foaming.

Patients with sJIA and GCA with body weight < 30 kg

Under aseptic conditions, remove from a 50 ml infusion bag a volume of sterile, pyrogen-free sodium chloride 9 mg/ml (0.9%) solution for injection equal to the volume of RoActemra concentrate required for the patient's dose. 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 must be 50 ml. To mix the solution, gently invert the infusion bag to avoid foaming.

Patients with pJIA with body weight < 30 kg

Under aseptic conditions, remove from a 50 ml infusion bag a volume of sterile, pyrogen-free sodium chloride 9 mg/ml (0.9%) solution for injection equal to the volume of RoActemra concentrate required for the patient's dose. 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 must be 50 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.