Roactemra 20 mg/ml, concentrado para solucion para perfusion

Package Leaflet: Information for the User

RoActemra 20 mg/ml, Concentrate for Solution for Infusion

tocilizumab

Read this leaflet carefully before you start taking 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 side effects, consult 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 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 it is used for

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

3. How to use RoActemra

4. Possible side 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 helps to reduce symptoms 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 the joints caused by the disease and improve your ability to perform your 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 can be administered alone if your doctor determines that methotrexate is not suitable.

• RoActemra can 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 in the treatment of children with JIA. RoActemra is used in children aged 2 years and older who havesystemic juvenile idiopathic arthritis (JIA), 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 JIA and can be administered alone or in combination with methotrexate or alone.

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

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

• RoActemra is used in the treatment of adultswith coronavirus disease 2019 (COVID-19), who receive systemic corticosteroids and require oxygen supplementation or mechanical ventilation.

You will not be administered RoActemra

?If you are allergic totocilizumab or any of the other components of this medication (including those listed in section 6).

?If you have an active severe infection (except for COVID-19).

If this happens, consult your doctor or nurse administering the infusion.

Warnings and precautions

Consult your doctor or nurse before starting to receive RoActemra.

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

?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 worsen an existing infection 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 may 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 patienthas recently been vaccinated(adult or child) or plans to be vaccinated,inform your doctor.All patients, especially children, should be up-to-date on their vaccination schedule before starting treatment with RoActemra, unless urgent treatment is required.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, and during 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 children under 2 years old.

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

Other medications and RoActemra

Inform your doctor if you are taking, have recently taken, or may need to take any other medication (or if your child is taking it, if they are the patient).This includes over-the-counter medications.RoActemra may affect how some medications work, and dose adjustments may be needed.Inform your doctorif you are using medications containing any of the following active substances:

?methylprednisolone, dexamethasone, used to reduce inflammation

?simvastatin or atorvastatin, used to reducecholesterol levels

?calcium channel blockers, such as amlodipine used in the treatment ofhigh blood pressure

?theophylline used in the treatment ofasthma

?warfarin or phenprocoumon used asanticoagulants

?phenytoin used in the treatment ofseizures

?ciclosporin used in organ transplants as animmunosuppressant

?benzodiazepines, such as temazepam used to calmanxiety.

Since there is no clinical experienceRoActemra is not recommended for use with other biologic medications used to treat RA, AIJs, or AIJp.

Pregnancy, breastfeeding, and fertility

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

Women of childbearing ageshould use effective contraceptive methods during and up to 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 available data do not suggest that this treatment has any effect on fertility.

Driving and operating machinery

This medication 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 medication contains 230.6mg of sodium per maximum dose of 800mg, which is equivalent to 11.5% of the recommended daily maximum intake of 2 g of sodium by the WHO for an adult.

RoActemra contains polysorbate

This medication 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. Inform your doctor if you or your child has any known allergy.

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

RoActemra will be administeredby 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 AR

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 to 8 mg/kg when appropriate.

Adults will receive RoActemra once every 4 weeks through intravenous infusion (intravenous infusion) for 1 hour.

Children with AIJs (2 years of age and older)

The usual dose of RoActemra depends on your weight.

• If you weigh less than 30 kg, the dose is12 mg per kilogram of body weight.
• If you weigh 30 kg or more, the dose is8 mg per kilogram of body weight.

The dose is calculated based on your body weight at each administration.

Children with AIJs will receive RoActemra once every 2 weeks through intravenous infusion (intravenous infusion) for 1 hour.

Children with AIJp (2 years of age and older)

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

• If you weigh less than 30 kg: the dose is10 mg per kilogram of body weight.
• If you weigh 30 kg or more: the dose is8 mg per kilogram of body weight.

The dose is calculated based on your body weight at each administration.

Children with AIJp will receive RoActemra once every 4 weeks through intravenous infusion (intravenous infusion) for 1 hour.

Patients with SLC

The usual dose of RoActemra is8 mg per kg of body weight if you weigh 30 kg or more.

The dose is12 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 necessary.

If you are given more RoActemra than you should

Since a doctor or nurse administers RoActemra, it is unlikely that you will receive too much. However, if you are concerned, talk to your doctor.

If you forget a dose of RoActemra

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

If you interrupt treatment with RoActemra

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

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

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

The side effects can 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 can affect up to 1 in 10 patients

Allergic reactionsduring or after infusion:

?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 can 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 doctor as soon as possible.

Very common side effects:

They can affect more than 1 in 10 patients

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

?high levels of fat in the blood (cholesterol)

Common side effects:

They can affect up to 1 in 10 patients

?pneumonia (lung infection)

?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)

Uncommon side effects:

They can 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 can affect up to 1 in 1,000 patients

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

?Fatal allergic reactions (anaphylaxis)

?liver inflammation (hepatitis), jaundice

Very rare side effects:

They can affect up to 1 in 10,000 patients

?low white blood cell count, low red blood cell count, and low platelet count

?liver failure

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 notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Children with AIJs

In general, the side effects in patients with AIJs were of a similar type to those in adults with AR. Some side effects were observed more frequently: nasal and throat inflammation, diarrhea, decreased white blood cell count, and elevated liver enzymes.

Children with AIJp

In general, the side effects in patients with AIJp were of a similar type to those in adults with AR. Some side effects were observed more frequently: nasal and throat inflammation, headache, feeling unwell (nausea), and decreased white blood cell count.

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

Do not use this medication after the expiration date that appears on the packaging after EXP. The expiration date is the last day of the month indicated.

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

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

Composition of RoActemra

?The active ingredient is tocilizumab.

Each vial of 4ml contains 80mg of tocilizumab(20mg/ml).

Each vial of 10ml contains 200mg of tocilizumab(20mg/ml).

Each vial of 20ml contains 400mg of tocilizumab(20mg/ml).

?The other components are sucrose, polisorbate 80, disodium dodecahydrate phosphate, sodium dihydrogen phosphate dihydrate, and water for injection.(see section 2 "RoActemra contains sodium" and "RoActemra contains polisorbate").

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 4ml, 10ml, and 20ml of concentrate for solution for infusion. Pack size of 1 and 4 vials.It may not be marketed in all pack sizes.

Marketing authorisation holder and responsible person for manufacture

Roche Registration GmbH

Emil-Barell-Strasse 1

79639Grenzach-Wyhlen

Germany

Responsible person for manufacture

Roche Pharma AG

Emil-Barell-Str.1

79639 Grenzach-Wyhlen

Germany

Further information on this medicinal product can be obtained by contacting the local representative of the marketing authorisation holder:

Date of the last revision of this leaflet

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.

This information is intended solely for healthcare professionals:

Instructions for pre-dilution before administration

Parenteral medicines must be visually inspected before administration to ensure that they have no particles or change in colour. Only dilute solutions that are transparent to opalescent, colourless to pale yellow and free of visible particles should be used. Use a sterile needle and syringe to prepare RoActemra.

Adult patients with AR, COVID 19 and SLC (with a body weight ≥30 kg)

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

Use in pediatric population

Patients with AIJs, with AIJp and SLC with a body weight ≥30kg

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

Patients with AIJs and SLC with a body weight <30 kg

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

Patients with AIJp with a body weight <30kg

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

RoActemra is for single use.

All unused or waste product must be disposed of in accordance with local requirements.