TOFIDENCE 20 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Tofidence 20mg/ml concentrate for solution for infusion

tocilizumab

This medicine is subject to additional monitoring, which will allow for quicker identification of new safety information. You can help by reporting any side effects you may get. The last section of section 4 will tell you how to report side effects.

Read all of this leaflet carefully before you are given 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 get any side effects, talk to your doctor or nurse, even if you think they are not related to the medicine. See section 4.

In addition to this leaflet, you will be given a patient information card, which contains important safety information that you should be aware of before and during treatment with Tofidence 20 mg/ml concentrate for solution for infusion.

Contents of the pack

1. What is Tofidence and what is it used for
2. What you need to know before you are given Tofidence
3. How Tofidence is given
4. Possible side effects
5. Storage of Tofidence
6. Contents of the pack and other information

1. What is Tofidence and what is it used for

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

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

• Tofidence can also be used to treat adultswho have not been previously treated with methotrexate if they have severe, active and progressive rheumatoid arthritis.

• Tofidence is used to treat children with sJIA. Tofidence is used in children aged 2 years and older with 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. Tofidence is used to improve the symptoms of sJIA and may be given in combination with methotrexate or alone.

• Tofidence is used to treat children with pJIA. Tofidence 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. Tofidence is used to improve the symptoms of pJIA and may be given in combination with methotrexate or alone.

• Tofidence 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 are given Tofidence

You will not be given Tofidence

• If you are allergicto tocilizumab or any of the other ingredients of this medicine (listed in section 6).
• If you have a severe active infection.

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

Warnings and precautions

Talk to your doctor or nurse before you are given Tofidence.

• If you experience allergic reactionssuch as feeling of 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. Tofidence 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 Tofidence. Tell your doctor immediately if symptoms of tuberculosis (persistent cough, weight loss, general feeling of being unwell, low-grade fever), or any other infection appear during or after treatment.

• If you have had intestinal ulceror 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 Tofidence, your doctor will do a blood test to measure your liver function.

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

• If you have cancer, tell your doctor. Your doctor will have to decide whether you can continue treatment with Tofidence.

• 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 you are receiving treatment with Tofidence.

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

• If you have persistent headaches.

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

Children and adolescents

Tofidence 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 whether you can continue treatment with Tofidence.

Tofidence contains polysorbate

This medicine contains 0.5 mg of polysorbate 80 (E 433) in each 20 mg/ml of tocilizumab. Polysorbates may cause allergic reactions. Tell your doctor if you have any known allergies.

Other medicines and Tofidence

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. Tofidence may affect how some medicines work, and a dose adjustment may be needed. Tell your doctorif you are using medicines that contain any of these active substances:

• methylprednisolone or 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 Tofidence with other biologic medicines used to treat RA, sJIA or pJIA is not recommended.

Pregnancy, breastfeeding and fertility

Tofidence must not be used during pregnancy, unless clearly necessary. If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

Women of childbearing agemust use effective contraception during and for 3 months after finishing treatment.

Stop breastfeeding if you start treatment with Tofidenceand ask your doctor for advice. You should not start breastfeeding again until at least 3 months after your last treatment with Tofidence. It is not known whether tocilizumab 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, ride a bicycle or use machines.

3. How Tofidence is given

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

Tofidence will be given to you 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 Tofidence is 8 milligrams (mg) per kilogram (kg) of body weight. Depending on the response, the 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 Tofidence once every 4 weeks through a vein (intravenous infusion) over 1 hour.

Children with sJIA (aged 2 years and older)

The usual dose of Tofidence 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 Tofidence once every 2 weeks through a vein (intravenous infusion) over 1 hour.

Children with pJIA (aged 2 years and older)

The usual dose of Tofidence 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 Tofidence once every 4 weeks through a vein (intravenous infusion) over 1 hour.

Patients with COVID-19

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

If you are given too much Tofidence

Because Tofidence is given to you 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 Tofidence

Because Tofidence is given to you 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 Tofidence

You should not stop treatment with Tofidence 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 Tofidence.

Serious side effects:tell your doctor immediately.

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

If you notice any of these symptoms, tell your doctor immediately.

Signs of serious infections

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

Signs and symptoms of liver damage

These are rare: may affect up to 1 in 1,000 people

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

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)
• red and swollen 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 skin peeling)
• fatal allergic reactions (anaphylaxis)
• inflammation of the liver (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 you think they are not related to the medicine. You can also report side effects directly to the Spanish Medicines Agency (AEMPS) at www.notificaRAM.es. 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 Tofidence

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 outer packaging and on the label of the vials after EXP. The expiry date refers to the last day of the month shown.

Store the vials in a refrigerator (between 2°C and 8°C). Do not freeze.

Information on the storage and use of tocilizumab, once diluted and ready for use, is described in the section "This information is intended only for healthcare professionals".

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

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Contents and Additional Information

Composition of Tofidence

• The active ingredient 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 (E 473), polysorbate 80 (E 433), L-histidine, L-histidine hydrochloride monohydrate, arginine hydrochloride, and water for injectable preparations.

Appearance of the Product and Container Contents

Tofidence is a concentrate for solution for infusion. The concentrate is a clear to opalescent, colorless to light yellow liquid.

Tofidence is supplied in a vial (Type I glass) with a stopper (butyl rubber) containing 4 ml, 10 ml, or 20 ml of concentrate. Package sizes of 1 and 4 vials. Not all package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Biogen Netherlands B.V.

Prins Mauritslaan 13

1171 LP Badhoevedorp

Netherlands

For further information on this medicinal product, please contact the local representative of the marketing authorization holder:

Date of Last Revision of this Prospectus: 11/2024

Other Sources of Information

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