Avtozma 20 mg/ml concentrate for solution for infusion
Spain
Table of Contents
Patient Information Leaflet
Introduction
Package leaflet: Information for the user
Avtozma 20 mg/ml concentrate for solution for infusion
tocilizumab
This medicinal product is subject to additional monitoring, which will facilitate the rapid detection of new safety information. You can help by reporting any adverse reactions you may experience. Section 4 at the end of this leaflet includes information on how to report adverse reactions.
Read this entire leaflet carefully before starting to use 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, consult your doctor or nurse.
- This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
- 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 information card containing important safety information that you should know before receiving Avtozma and during treatment with Avtozma.
Contents of this leaflet:
- What Avtozma is and what it is used for
- What you need to know before using Avtozma
- How to use Avtozma
- Possible side effects
- How to store Avtozma
- Contents of the pack and other information
1. What Avtozma is and what it is used for
Avtozma 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. Avtozma helps reduce symptoms such as joint pain and swelling and may also improve your ability to perform daily activities. Avtozma has been shown to reduce the progression of cartilage and bone damage in joints caused by the disease and to improve your ability to carry out daily tasks.
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Avtozma 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. Avtozma is usually used in combination with methotrexate. However, Avtozma may be given alone if your doctor determines that methotrexate is not suitable.
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Avtozma may also be used to treat adults who have not previously been treated with methotrexate if they have severe, active, and progressive rheumatoid arthritis.
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Avtozma is used to treat children with sJIA. Avtozma is used in children from 2 years of age onwards 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. Avtozma is used to improve the symptoms of sJIA and may be administered either in combination with methotrexate or alone.
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Avtozma is used to treat children with pJIA. Avtozma is used in children from 2 years of age onwards with active polyarticular juvenile idiopathic arthritis (pJIA), an inflammatory disease that causes pain and swelling in one or more joints. Avtozma is used to improve the symptoms of pJIA and may be administered in combination with methotrexate or alone.
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Avtozma 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 receiving chimeric antigen receptor (CAR) T-cell therapy used to treat certain types of cancer.
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Avtozma 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 Avtozma
You will not be given Avtozma
- If you are allergic to tocilizumab or to any of the other ingredients of this medicine (listed in section 6). (See special warnings at the end of this section under the subtitle “Avtozma contains polysorbate”).
- If you have a serious active infection.
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 treatment with Avtozma.
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If you experience allergic reactions such as chest tightness, wheezing, dizziness or severe lightheadedness, swelling of the lips, or skin rash during or after the infusion, inform your doctor immediately.
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If you have any type of infection, whether short-term or long-term, or if you get infections frequently**. Inform your doctor immediately if you feel unwell. Avtozma 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.
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If you have had tuberculosis, inform your doctor. Your doctor will check for signs and symptoms of tuberculosis before starting treatment with Avtozma. 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.
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If you have had intestinal ulcers or diverticulitis, inform your doctor. Symptoms may include abdominal pain and unexplained changes in bowel habits with fever.
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If you have liver disease, inform your doctor. Before using Avtozma, your doctor will perform a blood test to assess your liver function.
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If any patient has recently been vaccinated (adult or child) or plans to be vaccinated, inform your doctor. All patients, especially children, should be up to date with their vaccination schedule before starting treatment with Avtozma, unless urgent treatment is required. Certain types of vaccines should not be administered while receiving Avtozma.
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If you have cancer, inform your doctor. Your doctor will need to decide whether you can continue treatment with Avtozma.
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If you have cardiovascular risk factors, such as high blood pressure or high cholesterol levels, inform your doctor. These factors need to be managed while you are receiving Avtozma.
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If you have moderate to severe kidney problems, your doctor will monitor you.
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If you have persistent headaches.
Your doctor will perform blood tests before you receive Avtozma and during your treatment to determine whether you have low white blood cell counts, low platelet counts, or elevated liver enzymes.
Children and adolescents
Avtozma is not recommended for use 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 Avtozma.
Other medicines and Avtozma
Inform your doctor if you are taking, have recently taken, or might need to take any other medicines (or if your child, if he is the patient, is taking them). This includes medicines obtained without a prescription. Avtozma may affect how some medicines work, and dose adjustments may be needed. Inform your doctor if you are taking medicines containing 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 in the treatment of high blood pressure
- theophylline, used in the treatment of asthma
- warfarin or phenprocoumon, used as anticoagulants
- phenytoin, used in the treatment of seizures
- cyclosporine, used in organ transplantation as an immunosuppressant
- benzodiazepines, such as temazepam, used to relieve anxiety.
Due to lack of clinical experience, the use of tocilizumab with other biological medicines used to treat RA, sJIA or pJIA is not recommended.
Pregnancy, breastfeeding, and fertility
Avtozma must 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.
Stop breastfeeding if you start treatment with Avtozma, and consult your doctor. Breastfeeding should not be resumed until at least 3 months after your last dose of Avtozma. It is unknown whether Avtozma 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.
Avtozma contains polysorbate
This medicine contains 0.5 mg of polysorbate 80 per ml. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergies.
3. How to use Avtozma
This medicine is subject to restricted medical prescription by your doctor.
Avtozma 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 Avtozma 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 receive Avtozma once every 4 weeks by intravenous infusion over one hour.
Children with JIA (from 2 years of age onwards)
The usual dose of Avtozma 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 JIA will receive Avtozma once every 2 weeks by intravenous infusion over one hour.
Children with pJIA (from 2 years of age onwards)
The usual dose of Avtozma 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 Avtozma once every 4 weeks by intravenous infusion over one hour.
SLC patients
The usual dose of Avtozma 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.
Avtozma may be administered alone or in combination with corticosteroids.
Patients with COVID-19
The usual dose of Avtozma is 8 mg per kg of body weight. A second dose may be required.
If you are given more Avtozma than you should
As Avtozma 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 Avtozma
As Avtozma 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 Avtozma
You must not stop treatment with Avtozma without first consulting your doctor.
If you have any further 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 everyone gets them.
Side effects may occur up to at least 3 months after your last dose of Avtozma.
Possible serious side effects: consult your doctor immediately.
These are common: may affect up to 1 in 10 patients
Allergic reactions during or after infusion:
- difficulty breathing, chest tightness, or dizziness
- skin rash, itching, hives, swelling of the lips, tongue, or face
If you experience any of these symptoms, consult your doctor immediately.
Signs of serious infections
- fever and chills
- blisters in the mouth or on the skin
- 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)
If you notice any of these symptoms, inform your doctor as soon as possible.
Very common side 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 side 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, urticaria
- allergic reactions (hypersensitivity)
- eye infection (conjunctivitis)
- headache, dizziness, hypertension
- 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 measured by blood test
- low levels of fibrinogen in the blood (a protein involved in blood clotting)
Uncommon side effects:
May affect up to 1 in 100 patients
- diverticulitis (fever, nausea, diarrhea, constipation, stomach pain)
- swollen and red areas in the mouth
- elevated fats in the blood (triglycerides)
- stomach ulcers
- kidney stones
- hypothyroidism
Rare side 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 [fatal])
- liver inflammation (hepatitis), jaundice
Very rare side 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 side effects
If you experience any side effect, talk to your doctor, pharmacist, or nurse, even if it is a possible side effect not listed in this leaflet. You can also report them 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 AIJs
In general, side effects in patients with AIJs were of a similar type to those in adults with RA. Some side effects were observed more frequently: inflammation of the nose and throat, diarrhea, decreased white blood cell count, and increased liver enzymes.
Children with AIJp
In general, side effects in patients with AIJp were of a similar type to those in adults with RA. Some side effects were observed more frequently: inflammation of the nose and throat, headache, feeling unwell (nausea), and decreased white blood cell count.
5. Storage of Avtozma
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the container. The expiry date refers to the last day of the month indicated.
Store in a refrigerator (between 2°C and 8°C). Do not freeze.
The unopened vial may be stored at a maximum temperature of 25°C for up to 5 weeks. If necessary, it may be refrigerated again once within these 5 weeks and kept refrigerated until the expiry date. The vial must be discarded if not used within 5 weeks.
Keep vials in the outer packaging to protect them from light.
If necessary, the diluted infusion solution in 0.9% or 0.45% sodium chloride injection solution may be stored for up to 1 month under refrigerated conditions or up to 48 hours at room temperature up to 30°C.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.
6. Contents of the container and other information
Composition of Avtozma
- 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 L-histidine, L-histidine monohydrochloride monohydrate, L-threonine, L-methionine, polysorbate 80, and water for injections.
Appearance of the product and contents of the container
Avtozma is a concentrate for solution for infusion. The concentrate is a clear to slightly opalescent, colourless to pale yellow liquid.
Avtozma 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 Authorization Holder and Manufacturer Responsible
Celltrion Healthcare Hungary Kft.
1062 Budapest
Váci út 1-3. WestEnd Office Building B tower
Hungary
Manufacturer Responsible
Nuvisan France SARL
2400, Route des Colles,
06410, Biot,
France
Midas Pharma GmbH
Rheinstr. 49,
55218 Ingelheim,
Germany
KYMOS S.L.
Ronda Can Fatjó, 7B.
08290 Cerdanyola del Vallès,
Barcelona,
Spain
Further information on this medicinal product is available upon request by contacting the local representative of the Marketing Authorization Holder:
Belgium/Belgium/Belgium Celltrion Healthcare Belgium BVBA Tel/Tel: +32 2 643 71 81 | Lithuania Celltrion Healthcare Hungary Kft. Tel.: +36 1 231 0493 |
Celltrion Healthcare Hungary Kft. Tel.: +36 1 231 0493 | Luxembourg/Luxembourg Celltrion Healthcare Belgium BVBA Tel/Tel: +32 2 643 71 81 |
Czech Republic Celltrion Healthcare Hungary Kft. Tel: +36 1 231 0493 | Hungary Celltrion Healthcare Hungary Kft. Tel.: +36 1 231 0493 |
Denmark Celltrion Healthcare Hungary Kft. Tlf: +36 1 231 0493 | Malta Mint Health Ltd. Tel: +356 2093 9800 |
Germany Celltrion Healthcare Deutschland GmbH Tel: +49(0)30 346494150 | Netherlands Celltrion Healthcare Netherlands B.V. Tel: + 31 20 888 7300 |
Estonia Celltrion Healthcare Hungary Kft. Tel: +36 1 231 0493 | Norway Celltrion Healthcare Hungary Kft. Tlf: +36 1 231 0493 |
Spain CELLTRION FARMACEUTICA (SPAIN) S.L. Tel: +34 910 498 478 | Austria Astro-Pharma GmbH Tel: +43 1 97 99 860 |
Greece BIANEX S.A. Tel: +30 210 8009111 | Poland Celltrion Healthcare Hungary Kft. Tel.: +36 1 231 0493 |
France Celltrion Healthcare France SAS Tél.: +33 (0)1 71 25 27 00 | Portugal CELLTRION PORTUGAL, UNIPESSOAL LDA. Tel: +351 21 936 8542 |
Croatia Oktal Pharma d.o.o. Tel: +385 1 6595 777 | Romania Celltrion Healthcare Hungary Kft. Tel: +36 1 231 0493 |
Ireland Celltrion Healthcare Ireland Limited Tel: +353 1 223 4026 | Slovenia OPH Oktal Pharma d.o.o. Tel.: +386 1 519 29 22 |
Iceland Celltrion Healthcare Hungary Kft. Sími: +36 1 231 0493 | Slovakia Celltrion Healthcare Hungary Kft. Tel: +36 1 231 0493 |
Italy Celltrion Healthcare Italy S.r.l. Tel: +39 02 47927040 | Finland/Sweden Celltrion Healthcare Finland Oy. Puh/Tel: +358 29 170 7755 |
Cyprus C.A. Papaellinas Ltd Tel: +357 22741741 | Sweden Celltrion Sweden AB |
Latvia Celltrion Healthcare Hungary Kft. Talr.: +36 1 231 0493 |
Date of the most recent review of this leaflet
Other sources of information
Detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu , and on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS): http://www.aemps.gob.es.
This information is intended for healthcare professionals only:
Instructions for dilution prior to administration
Parenteral medicines should be inspected visually for particulate matter and discoloration prior to administration. Only solutions that are clear to slightly opalescent, colorless to pale yellow, and free of visible particles should be diluted. Use a sterile needle and syringe to prepare Avtozma. For polyvinyl chloride (PVC) infusion bags, infusion bags that do not contain di(2-ethylhexyl)phthalate (DEHP-free) must be used.
Adult patients with RA, COVID-19, and SLE (with weight ≥30 kg)
Under aseptic conditions, remove from a 100 ml infusion bag a volume of sterile, non-pyrogenic 9 mg/ml (0.9%) or 4.5 mg/ml (0.45%) sodium chloride injection solution equal to the volume of Avtozma concentrate required for the patient's dose. The required amount of Avtozma 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 foaming.
Use in pediatric population
Patients with JIA, JIA with SLE, and weight ≥ 30 kg
Under aseptic conditions, remove from a 100 ml infusion bag a volume of sterile, non-pyrogenic 9 mg/ml (0.9%) or 4.5 mg/ml (0.45%) sodium chloride injection solution equal to the volume of Avtozma concentrate required for the patient's dose. The required amount of Avtozma 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 foaming.
Patients with JIA and SLE with weight < 30 kg
Under aseptic conditions, remove from a 50 ml infusion bag a volume of sterile, non-pyrogenic 9 mg/ml (0.9%) or 4.5 mg/ml (0.45%) sodium chloride injection solution equal to the volume of Avtozma concentrate required for the patient's dose. The required amount of Avtozma 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 foaming.
Patients with JIAp with weight < 30 kg
Under aseptic conditions, remove from a 50 ml infusion bag a volume of sterile, non-pyrogenic 9 mg/ml (0.9%) or 4.5 mg/ml (0.45%) sodium chloride injection solution equal to the volume of Avtozma concentrate required for the patient's dose. The required amount of Avtozma 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 foaming.
Avtozma is for single use only.
Any unused product or waste material must be disposed of in accordance with local requirements.