Tysabri 300 mg concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Tysabri 300mg concentrate for solution for infusion

Natalizumab

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

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

• Keep this leaflet and the patient information card, as you may need to read them again. Keep the leaflet and the patient information card with you during treatment and for six months after the last dose of this medicine, because adverse effects may occur even after treatment has been stopped.
• If you have any questions, consult your doctor.
• If you experience any adverse effects, consult your doctor, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of this leaflet:

1. What Tysabri is and what it is used for
2. What you need to know before receiving Tysabri
3. How Tysabri is administered
4. Possible side effects
5. How to store Tysabri
6. Contents of the pack and other information

1. What Tysabri is and what it is used for

Tysabri is used to treat multiple sclerosis (MS) in adults. It contains the active substance natalizumab. It is what is known as a monoclonal antibody.

MS causes inflammation in the brain that damages nerve cells. This inflammation occurs when white blood cells enter the brain and spinal cord. This medicine prevents white blood cells from reaching the brain. This reduces nerve damage caused by MS.

Symptoms of multiple sclerosis

MS symptoms can vary from one patient to another; you may experience some or none of them.

They may include: difficulty walking, tingling in the face, arms, or legs; vision problems; fatigue; feelings of imbalance or dizziness; bladder and bowel problems; difficulty thinking and concentrating; depression; acute or chronic pain; sexual problems; muscle stiffness and spasms.

When symptoms worsen, it is called a relapse (also known as exacerbation or flare-up). During a relapse, you may notice symptoms suddenly, within a few hours, or they may develop gradually over several days. Symptoms usually improve gradually (this is known as remission).

How Tysabri can help

In clinical trials, this medicine reduced the progression of disability caused by MS by about half and reduced the number of MS relapses by approximately two-thirds. While you are receiving treatment with this medicine, you may not notice any improvement, but it may still be working to prevent worsening of MS.

2. What you need to know before starting Tysabri

Before beginning treatment with this medicine, it is important that you and your doctor have discussed the expected benefits of this treatment and the associated risks.

Do not use Tysabri

• If you are allergic to natalizumab or to any of the other ingredients of this medicine (listed in section 6).

• If you have been diagnosed with progressive multifocal leukoencephalopathy (PML). PML is a rare brain disease.

• If your immune system has a serious problem. This may be due to an illness (such as HIV infection) or to medicines you are taking or have taken in the past (see below).

• If you are taking medicines that affect the immune system, including certain medicines used to treat MS. These medicines must not be used with Tysabri.

• If you have cancer (unless it is a type of skin cancer called basal cell carcinoma).

Warnings and precautions

Talk to your doctor about whether Tysabri is the most appropriate treatment for you. Do this before starting Tysabri and again if you have been receiving it for more than two years.

Possible brain infection (PML)

Some people receiving this medicine (fewer than 1 in 100) have developed a rare brain infection called PML (progressive multifocal leukoencephalopathy). PML can lead to severe disability or death.

• Before starting treatment, your doctor will perform a blood test on all patients to detect infection with the JC virus. The JC virus is a common virus that normally does not make you ill. However, PML is associated with an increase in the JC virus in the brain. The reason for this increase in some patients treated with Tysabri is not clear. Before and during treatment, your doctor will perform a blood test to check whether you have antibodies against the JC virus (anti-JCV antibodies), which are a sign that you have been infected with the JC virus.

• Your doctor will perform a magnetic resonance imaging (MRI) scan, which will be repeated during treatment to rule out PML.

• Symptoms of PML may be similar to those of an MS relapse (see section 4, Possible side effects). You may also develop PML up to 6 months after stopping treatment with Tysabri.

Tell your doctor as soon as possible if you notice your MS worsening or if you experience any new symptoms while being treated with Tysabri or up to 6 months after treatment has ended.

• Inform your partner or caregivers about what they should watch for (see also section 4, Possible side effects). Some symptoms may be difficult to detect on your own, such as changes in mood or behavior, confusion, speech and communication difficulties. If you experience any of these, you may need further testing. Remain vigilant for symptoms for 6 months after stopping Tysabri.

• Keep the patient information card provided by your doctor. It includes this information. Show it to your partner or caregivers.

Three factors may increase the risk of PML with Tysabri. If you have two or more of these risk factors, your risk increases further:

• If you have anti-JCV antibodies in your blood. These are a sign that the virus is present in your body. You will be tested before and during treatment with Tysabri.

• If you are receiving prolonged treatment with Tysabri, especially if for more than two years.

• If you have taken a medicine known as animmunosuppressant , which reduces the activity of your immune system.

The JC virus can also cause another condition called JCV GCN (JC virus granule cell neuropathy), which has occurred in some patients receiving Tysabri treatment. Symptoms of JCV GCN are similar to those of PML.

For patients at lower risk of PML, your doctor may repeat tests periodically to check:

• Whether you still do not have anti-JCV antibodies in your blood.

• If you have been treated for more than 2 years, whether you still have a lower level of anti-JCV antibodies in your blood.

If someone develops PML

PML may be treated and treatment with Tysabri will be stopped. However, some people experience a reaction when Tysabri is cleared from the body. This reaction (known as IRIS or immune reconstitution inflammatory syndrome) may worsen your condition, including deterioration of brain function.

Be alert for other infections

Some infections other than PML may also be serious and may be caused by viruses, bacteria, or other factors.

Tell your doctor or nurse immediately if you think you have an infection (see also section 4, Possible side effects).

Changes in platelet count in blood

Natalizumab may reduce the number of platelets in the blood, which are responsible for blood clotting. This may lead to a disorder called thrombocytopenia (see section 4), in which your blood may not clot quickly enough to stop bleeding. This may result in bruising and other more serious problems such as excessive bleeding. Inform your doctor immediately if you have unexplained bruising, red or purple spots on the skin (called petechiae), bleeding from cuts in the skin that does not stop or oozes, prolonged bleeding from gums or nose, blood in urine or stools, or bleeding in the white part of the eyes.

Children and adolescents

Do not give this medicine to children or adolescents under 18 years of age.

Other medicines and Tysabri

Tell your doctor if you are taking, have recently taken, or might need to take any other medicines.

• You must not be given this medicine if you are currently being treated with medicines that affect your immune system, including certain medicines used to treat MS.

• You may not be able to use this medicine if you have ever taken a medicine that affects the immune system.

Pregnancy and breastfeeding

• Do not use this medicine if you are pregnant, unless you have discussed it with your doctor. If you are pregnant, think you may be pregnant, or plan to become pregnant, you must inform your doctor immediately.

• Do not breastfeed while using Tysabri. Your doctor will help you decide whether to stop breastfeeding or stop using the medicine.

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine. Your doctor will consider the risk to the baby and the benefit to the mother.

Driving and use of machines

Dizziness is a very common side effect. If you experience this symptom, do not drive or operate machinery.

Tysabri contains polysorbate 80 (E433)

This medicine contains 3 mg of polysorbate 80 in each vial. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergies.

Tysabri contains sodium

Each vial of this medicine contains 2.3 mmol (52 mg) of sodium. After dilution prior to use, the medicine contains 17.7 mmol (406 mg) of sodium per dose. You should take this into account if you are on a low-sodium diet.

3. How Tysabri is administered

Tysabri intravenous infusion must be administered to the patient by a physician experienced in the treatment of MS. Your doctor may directly switch your current MS treatment to Tysabri if no problems associated with the previous treatment are observed.

• Your doctor will request blood tests to detect anti-JC virus (anti-JCV) antibodies and other potential problems.

• Your doctor will perform an MRI scan, which will be repeated during treatment.

• To switch from certain MS medications, your doctor may recommend waiting a certain period to ensure that most of the previous medication has been eliminated from your body.

• The recommended dose for adults is 300 mg once every four weeks.

• Tysabri must be diluted before administration. It is given through an intravenous infusion (via a drip into a vein), usually in the arm. Administration takes approximately 1 hour.

• At the end of this leaflet, information on how to prepare and administer the medicine is provided for medical or healthcare professionals.

If you interrupt treatment with Tysabri

Continuous administration of Tysabri is important, especially during the first months of treatment. It is important to continue treatment as long as you and your doctor decide it is helping you. Patients who received one or two doses of Tysabri and then paused treatment for three months or longer had an increased risk of experiencing an allergic reaction upon resuming treatment.

Monitoring for allergic reactions

Some patients have experienced an allergic reaction to this medicine. Your doctor may monitor you for allergic reactions during the infusion and for 1 hour afterwards. See also section 4, Possible side effects.

If you forget to use Tysabri

If you miss your scheduled dose of Tysabri, speak with your doctor to have it administered as soon as possible. After that, you may continue receiving Tysabri every four weeks.

Will Tysabri always work?

In some patients receiving Tysabri, the body's natural defenses may eventually prevent the medicine from working properly, as the body produces antibodies against the drug over time. Your doctor may determine whether the medicine is no longer effective based on your blood tests and may discontinue treatment if necessary.

If you have any further questions about using Tysabri, ask your doctor. Always follow exactly the instructions for administering this medicine provided in this leaflet or those given by your doctor. If in doubt, consult your doctor.

4. Possible adverse effects

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

Tell your doctor or nurse immediately if you notice any of the following symptoms.

Signs of brain infection

• Changes in personality and behaviour such as confusion, delirium or loss of consciousness
• Seizures (epileptic fits)
• Headache
• Nausea/vomiting
• Stiff neck
• Extreme sensitivity to bright light
• Fever
• Skin rash (anywhere on the body)

These symptoms may be due to an infection of the brain (encephalitis or PML) or of the membrane covering the brain (meningitis).

Signs of other serious infections

• Unexplained fever
• Severe diarrhoea
• Shortness of breath
• Prolonged dizziness
• Headache
• Weight loss
• Lack of energy
• Vision changes
• Pain or redness in eye(s)

Signs of allergic reaction

• Hives (itchy rash)
• Swelling of face, lips or tongue
• Difficulty breathing
• Chest pain or discomfort
• Increase or decrease in blood pressure (your doctor or nurse will notice this if they are monitoring your blood pressure)

These are more likely to occur during or shortly after the infusion.

Signs of a possible liver problem

• Yellowing of the skin or whites of the eyes
• Unusually dark urine
• Abnormal liver function test

If you experience any of the adverse effects listed above or think you may have an infection, consult your doctor or nurse immediately. Show your patient alert card and this leaflet to any doctor or nurse treating you, not just your neurologist.

Other adverse effects

Very common (may affect more than 1 in 10 people)

• Urinary tract infection
• Sore throat and nasal congestion or discharge
• Headache
• Dizziness
• Feeling unwell (nausea)
• Joint pain
• Fatigue
• Dizziness, feeling unwell (nausea), itching and chills during or shortly after the infusion

Common (may affect up to 1 in 10 people)

• Anaemia (reduced number of red blood cells which may make your skin look pale and cause breathlessness or lack of energy)
• Allergy (hypersensitivity)
• Chills
• Hives (itchy rash)
• Vomiting
• Fever
• Difficulty breathing (dyspnoea)
• Redness of face or body (flushing)
• Herpes virus infections
• Discomfort around the site where the infusion was given. You may experience bruising, redness, pain, itching or swelling

Uncommon (may affect up to 1 in 100 people)

• Severe allergy (anaphylactic reaction)
• Progressive multifocal leukoencephalopathy (PML)
• Inflammatory disorder after stopping the medicine
• Swelling of the face
• Increase in number of white blood cells (eosinophilia)
• Reduction in number of platelets
• Easy bruising (purpura)

Rare (may affect up to 1 in 1,000 people)

• Herpes virus infection in the eye
• Severe anaemia (reduced number of red blood cells which may make your skin look pale and cause breathlessness or lack of energy)
• Severe swelling under the skin
• High levels of bilirubin in the blood (hyperbilirubinemia) which may cause symptoms such as yellowing of eyes or skin, fever and fatigue

Frequency not known (cannot be estimated from available data)

• Uncommon infections (so-called “opportunistic infections”)
• Liver damage

Tell your doctor as soon as possible if you think you have an infection.

You will also find this information on the patient alert card provided by your doctor.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Tysabri

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

Do not use this medicine after the expiry date stated on the label and carton. The expiry date refers to the last day of the month indicated.

Unopened vial:

Store in a refrigerator.

Do not freeze.

Keep the vial in the outer packaging to protect it from light.

Diluted solution:

The product should be used immediately after dilution. If this is not possible, the diluted solution should be stored between 2°C and 8°C and infused within a maximum of 24 hours after dilution.

Do not use this medicine if you observe particles or changes in colour in the liquid.

6. Contents of the pack and other information

Composition of Tysabri

The active substance is natalizumab. Each 15 ml vial of concentrate contains 300 mg of natalizumab (20 mg/ml). When diluted, the solution for infusion contains approximately 2.6 mg per ml of natalizumab.

The other components are:

Monosodium phosphate monohydrate
Disodium phosphate heptahydrate
Sodium chloride (see section 2 “Tysabri contains sodium”)
Polysorbate 80 (E 433)
Water for injections

Nature and contents of the container

Tysabri is a colourless, clear liquid or slightly opalescent solution.

Each carton pack contains one glass vial.

Marketing Authorisation Holder and Manufacturer

Biogen Netherlands B.V.
Prins Mauritslaan 13
1171 LP Badhoevedorp
The Netherlands

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

Date of the most recent revision of this leaflet:

Other sources of information

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

This information is intended for healthcare professionals only:

1. Inspect the Tysabri vial to check for the absence of particles before dilution and administration. If particles are observed or if the liquid is not colourless and clear or slightly opalescent, the vial must not be used.

2. Use an aseptic technique when preparing the medicine. Remove the flip-off cap from the vial. Insert the syringe needle into the vial through the centre of the stopper and withdraw 15 ml of concentrate for infusion solution.

3. Add the 15 ml of concentrate for infusion solution to 100 ml of sodium chloride 9 mg/ml (0.9%) injection solution. Gently invert the solution to ensure complete mixing. Do not shake.

4. Tysabri must not be mixed with other medicines or diluents.

5. Visually inspect the diluted medicine to check for the absence of particles or changes in colour before administration. The diluted product must not be used if foreign particles or changes in colour are observed.

6. The diluted medicine should be used as soon as possible and within a maximum of 24 hours after dilution. If the diluted medicine is stored between 2 °C and 8 °C (do not freeze), allow the solution to reach room temperature before infusion.

7. The diluted solution is intended for intravenous infusion over 1 hour at an approximate rate of 2 ml per minute.

8. After completion of the infusion, intravenous infusion lines should be flushed with sodium chloride 9 mg/ml (0.9%) injection solution.

9. Vials are for single use only.

10. In order to improve traceability of biological medicines, the name (Tysabri) and batch number of the administered medicine should be clearly recorded.

11. Disposal of unused medicine and of all materials that have been in contact with it must be carried out in accordance with local requirements.