Tysabri 150 mg solution for injection in pre-filled syringe

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Tysabri 150mg solution for injection in pre-filled syringe

Natalizumab

Read the entire 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 and, if self-administering or administration by a caregiver, a Pre-administration Checklist. These contain important safety information that you must 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 patient information card with you during treatment and for six months after the last dose of this medicine, because adverse reactions may occur even after treatment has been stopped.

If you or your caregiver administer the treatment, review the Pre-administration Checklist before each dose.

• If you have any questions, consult your doctor.

• 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 adverse reactions, consult your doctor, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the 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 may 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 unsteadiness 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 attack). 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 called 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 on treatment with this medicine, you may not notice any improvement, but it may still be working to prevent MS from worsening.

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 components of this medicine (listed in section 6).

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

• If you have a serious problem with your immune system. 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 cannot 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 this medicine and after you have been receiving it for more than two years.

Keep a record

To improve traceability of this medicine, your doctor or pharmacist should record the name and batch number of the medicine administered to you in your medical record. You may also wish to note down this information in case you are asked for it in the future.

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 in 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 JC virus in the brain. The reason for this increase in some patients treated with Tysabri is not fully understood. Before and during treatment, your doctor will test your blood for antibodies to the JC virus (anti-JCV antibodies), which indicate 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 Tysabri treatment.

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.

• Inform your partner or caregivers about what they should look out 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 during the 6 months following discontinuation of Tysabri.

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

• If you or your caregiver administer the treatment, review the Pre-infusion Checklist before each dose.

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

• If you have anti-JCV antibodies in your blood. These indicate 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 for more than two years.

• If you have taken a medicine called an immunosuppressant, which reduces the activity of the immune system.

The JC virus can also cause another condition, called JCV granule cell neuropathy (JCV GCN), which has occurred in some patients receiving this medicine. 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.

• Whether, after more than 2 years of treatment, you still have a lower level of anti-JCV antibodies in your blood.

If someone develops PML

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

Be alert to other infections

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

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 cause bruising and other more serious problems such as excessive bleeding. Tell your doctor immediately if you experience 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 use this medicine in 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.

• Do not use this medicine if you are currently being treated with medicines that affect your immune system, such as 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, talk to 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 0.4 mg of polysorbate 80 in each pre-filled syringe, equivalent to 0.8 mg per dose. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergies.

Tysabri contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per 300 mg dose, i.e., essentially “sodium-free”.

3. How Tysabri is administered

Tysabri injections will be prescribed by a doctor experienced in the treatment of MS. Your doctor may switch you directly from another treatment to Tysabri if there are no signs of problems caused by the previous treatment.

• Your doctor will order blood tests to detect anti-JC virus 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 advise you to wait a certain period to ensure most of the previous medication has been cleared from your body.

• If your condition allows, your doctor may consider with you the option of receiving injections outside a hospital setting (e.g., at home). These injections may be administered by a healthcare professional, by yourself, or by a caregiver, provided certain criteria are met. You will still need to attend medical appointments for scheduled visits, including periodic blood tests and MRI scans.

• If your doctor determines you are suitable for self-administration (or administration by your caregiver), a healthcare professional will supervise you during the administration of the first two doses (2 injections each).

• The healthcare professional will provide you or your caregiver with detailed instructions and demonstrate how to prepare and inject the medication before using the syringes for the first time.

• If your doctor decides you are suitable for self-administration (or administration by a caregiver), make sure to read the patient information card to review the list of PML symptoms and go through the Pre-Administration Checklist before each dose. If any symptom appears or worsens, do not administer the dose and contact your doctor immediately.

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

• Each dose is given as two subcutaneous injections into the thigh, abdomen (at least 6 cm from the navel), or the back of the arm (only if administered by a healthcare professional or caregiver). Administration may take up to 30 minutes.

• Instructions on how to prepare and inject the medication are provided at the end of this leaflet.

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. Do not stop taking this medication without consulting your doctor. Patients who received one or two doses of Tysabri and then paused treatment for 3 months or more have had a higher risk of experiencing an allergic reaction when restarting treatment.

Monitoring for allergic reactions

Some patients have experienced an allergic reaction to this medication. Your doctor will monitor you for allergic reactions during and for 1 hour after the injections. In the case of self-administration or administration by a caregiver, if you experience an allergic reaction, stop the injection immediately and contact your doctor right away. See also section 4, Possible side effects.

If you forget to use Tysabri

If you miss your scheduled Tysabri dose, speak with your doctor to have it administered as soon as possible. After that, you may continue receiving Tysabri every 4 weeks.

Two syringes are required to deliver the full dose. It is important that both syringes are administered and that you follow the prescribed dosing schedule. If you or your caregiver administer the injections and have missed a dose or injected only one syringe, contact your doctor as soon as possible for guidance.

Will Tysabri always work?

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

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

Subcutaneous is abbreviated as SC on the syringe label.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience 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
• Neck stiffness
• 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 it (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
• Pain or discomfort in the chest
• Increase or decrease in blood pressure (your doctor or nurse will notice this if monitoring your blood pressure)

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

Signs of a possible liver problem

• Yellowing of the skin or whites of the eyes
• Unusual darkening of the urine
• Abnormal liver function test

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

Common (may affect up to 1 in 10 people)

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

Uncommon (may affect up to 1 in 100 people)

• Severe allergy (anaphylactic reaction)
• Progressive multifocal leukoencephalopathy (PML)
• Immune reconstitution inflammatory syndrome after stopping the medicine
• Swelling of the face
• Increase in white blood cells (eosinophilia)
• Reduction in platelet count
• Easy bruising (purpura)

Rare (may affect up to 1 in 1000 people)

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

Frequency not known (cannot be estimated from available data)

• Uncommon infections of the brain and eyes
• 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 information 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.

Store in a refrigerator (between 2 °C and 8 °C).

Do not freeze.

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

The prefilled syringes may be stored at room temperature (up to 30 °C) for a total cumulative time of up to 24 hours, including the time required for them to reach room temperature prior to administration. The syringes may be returned to the refrigerator and used before the expiry date stated on the label and carton. The date and time when the container is removed from the refrigerator must be recorded on the carton. Discard the syringes if they are left outside the refrigerator for more than 24 hours. Do not use external heat sources, such as warm water, to warm the prefilled syringes.

Do not use this medicine if you notice particles in the liquid or any change in the liquid's colour.

6. Package contents and other information

Composition of Tysabri

The active substance is natalizumab.

Each 1 ml pre-filled syringe contains 150 mg of natalizumab.

The other components are:

Monobasic sodium phosphate monohydrate

Dibasic sodium phosphate heptahydrate

Sodium chloride (see section 2 “Tysabri contains sodium”)

Polysorbate 80 (E 433)

Water for injections

Appearance of the medicinal product and contents of the pack

Tysabri is a liquid, colourless to slightly yellow, slightly opalescent to opalescent.

Each carton contains two pre-filled syringes.

Tysabri is available in packs containing 2 pre-filled syringes or 6 pre-filled syringes.

Only certain pack sizes may be marketed.

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:

Belgium/Belgium/Belgium Biogen Belgium N.V./S.A. Tel/Tel: +32 2 219 12 18	Lithuania Biogen Lithuania UAB Tel: +370 5 259 6176
	Luxembourg/Luxembourg Biogen Belgium N.V./S.A. Tel/Tel: +352 2 219 12 18
Czech Republic Biogen (Czech Republic) s.r.o. Tel: +420 255 706 200	Hungary Biogen Hungary Kft. Tel.: +36 (1) 899 9880
Denmark Biogen (Denmark) A/S Tlf.: +45 77 41 57 57	Malta Pharma MT limited Tel: +356 213 37008/9
Germany Biogen GmbH Tel: +49 (0) 89 99 6170	Netherlands Biogen Netherlands B.V. Tel: +31 20 542 2000
Estonia Biogen Estonia OÜ Tel: +372 618 9551	Norway Biogen Norway AS Tlf: +47 23 40 01 00
Greece Genesis Pharma SA Tel: +30 210 8771500	Austria Biogen Austria GmbH Tel: +43 1 484 46 13
Spain Biogen Spain SL Tel: +34 91 310 7110	Poland Biogen Poland Sp. z o.o. Tel.: +48 22 351 51 00
France Biogen France SAS Tél: +33 (0)1 41 37 95 95	Portugal Biogen Portugal Sociedade Farmacêutica Unipessoal, Lda Tel: +351 21 318 8450
Croatia Biogen Pharma d.o.o. Tel: +358 (0) 1 775 73 22	Romania Johnson & Johnson Romania S.R.L. Tel: +40 21 207 18 00
Ireland Biogen Idec (Ireland) Ltd. Tel: +353 (0)1 463 7799	Slovenia Biogen Pharma d.o.o. Tel: +386 1 511 02 90
Iceland Icepharma hf Tel: +354 540 8000	Slovakia Biogen Slovakia s.r.o. Tel: +421 2 323 340 08
Italy Biogen Italia s.r.l. Tel: +39 02 584 9901	Finland Biogen Finland Oy Tel: +358 207 401 200
Cyprus Genesis Pharma (Cyprus) Ltd Tel: +357 22 76 57 15	Sweden Biogen Sweden AB Tel: +46 8 594 113 60
Latvia Biogen Latvia SIA Tel: +371 68 688 158

Date of the most recent review 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

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INSTRUCTIONS FOR USE

Tysabri 150mg

injectable solution

natalizumab

subcutaneous injection

Full dose = Two pre-filled syringes

These "Instructions for use" contain information on how to inject the medicine using the Tysabri pre-filled syringe.

Read these Instructions for use before you start using the Tysabri pre-filled syringe (referred to as "syringe" in these instructions) and each time you receive a new pack. There may be new information.

This information does not replace consultation with your healthcare professional regarding your medical condition or your treatment.

Parts of the Tysabri device

Do not remove the grip wings. The grip wings allow you to hold the syringe more securely during the injection process.

Important information you should know before injecting Tysabri

Tysabri is supplied in a pre-filled syringe (referred to as "syringe" in these instructions). Each Tysabri pack contains two syringes. You must use both syringes, within a maximum interval of 30 minutes between them, to receive your full dose.

• For self-administration or administration by a caregiver, your healthcare professional must train you or your caregiver on how to prepare and inject the syringes before first use. If you or your caregiver administer the injections and a dose has been missed or only one syringe was injected, contact your pharmacist or treating physician.
• The syringes are intended solely for subcutaneous injection (inject directly into the fatty layer beneath the skin).
• Each syringe is for single use only. Do not reuse.
• Do not share syringes with other people, even if they have the same condition as you. You could transmit an infection to them or acquire an infection from them.

Note for healthcare professionals:

Patients must be monitored during subcutaneous injections and for 1 hour after to detect signs and symptoms of injection reactions, including hypersensitivity. After the first six doses of Tysabri, regardless of the route of administration, patients should be monitored after subcutaneous injection at the physician's discretion.

Storage of Tysabri

• Keep the syringe and all medicines out of the sight and reach of children.
• Store syringes in the refrigerator (between 2 °C and 8 °C).
• If necessary, syringes may be stored at room temperature (up to 30 °C) for up to a total of 24 hours. If syringes have been outside the refrigerator for more than 24 hours, do not use them.
• Store syringes in their original carton to protect from light.
• Do not freeze syringes or expose them to temperatures above 30 °C.
• Syringes may be returned to the refrigerator and used before the expiry date stated on the label and carton.

Preparation of the Tysabri injection:

Gather the materials. Gather the materials and place them on a clean, flat surface in a well-lit area.
Remove 2 syringes from the refrigerator and wait 30 minutes. Remove the box containing TWO syringes from the refrigerator and allow them to reach room temperature (up to 30 °C) for at least 30 minutes.
Do not use external heat sources, such as warm water, to warm the syringes.
Wash and dry your hands. Wash your hands thoroughly with soap and water. Then dry them completely.
Check the syringes. Check the expiration date of both syringes (image a).
Do not use the syringe if it has passed the expiration date.
Inspect the syringes for damage or cracks (image b).
Do not use the syringe if it is damaged or cracked.
Check that the medication in both syringes is colorless to slightly yellow, clear to slightly opalescent (pearly), and free of visible particles (image c).
Do not use the syringe if the liquid contains visible particles. Do not use the syringe if it has been dropped before use. Inform your healthcare professional if you have any of these issues with the syringes.
You may see bubbles in the medication. This is normal. Note: The appearance of the medication may change after removing it from the refrigerator. This is normal.
Choose the first injection site. Use one of the following injection sites: Abdomen (at least 6 centimeters away from the navel). Front of the thigh. Outer upper arm (only for administration by a caregiver). Do not administer the injection into areas where the skin is tender, red, infected, bruised, or scarred. Rotate injection sites between doses.
Clean the first injection site. Clean the skin with an alcohol wipe. Allow the injection site to air dry before administering the dose.
Do not touch, fan, or blow on the cleaned area.

Injection from the first syringe

Remove the needle cap. Hold the syringe body in one hand with the needle pointing upward. With the other hand, firmly grasp the needle cap and pull it straight off the needle. Dispose of the needle cap immediately after removal. Note: You may see a drop of liquid at the tip of the needle. This is normal.
Do not touch or reattach the cap to the needle. You could get a needlestick injury. Do not pull the plunger rod.
Insert the needle into the first injection site. Pinch the skin around the clean injection site. With the other hand, hold the syringe like a pencil and insert the needle quickly, in a dart-like motion, at an angle of 45 to 90 degrees until the needle is completely under the skin.
Administer the first injection. After inserting the needle into the skin, release the pinched skin. Slowly push the plunger all the way down to inject all the medication.
Make sure to push the plunger rod completely down so that all the medication is delivered and the needle shield engages.
Remove the needle from the injection site. When the syringe is empty, begin releasing the plunger and withdraw the syringe straight out from the injection site until the needle is fully covered by the needle shield.
If the needle shield does not activate to cover the needle, do not re-cap the syringe. Place it in a sharps disposal container and contact your healthcare provider for assistance.
Examine and care for the injection site. Apply gauze or a bandage to the injection site, if needed.

Injection from the second syringe

Choose the second injection site. Choose another area for the injection. You may use one of the following injection sites: Abdomen (at least 6 centimeters away from the navel). Front of the thigh. Outer upper arm (only for administration by a caregiver). Do not administer the injection in an area of skin that is tender, red, infected, bruised, or scarred. Change (rotate) injection sites between injections. If using the same body area, make sure the site of the second injection is at least 3 centimeters away from the first.
Clean the second injection site. Clean the skin with an alcohol wipe. Allow the injection site to air dry before administering the dose.
Do not touch, fan, or blow on the cleaned area.
Administer the second injection. Repeat steps 7 to 11 to administer the SECOND syringe and receive your complete dose. Administer the injections one after the other without significant delay. The second injection should be given no later than 30 minutes after the first.

Tysabri elimination

Dispose of both syringes. Immediately place both used syringes into a sharps disposal container after use.
Do not throw the sharps disposal container or used syringes into your household trash.
If you do not have a sharps disposal container, you may request one from your healthcare provider or you may use a household container that: is made of heavy-duty plastic, has a tight-fitting, puncture-resistant lid that prevents sharps from coming out, stands upright and is stable during use, is leak-proof, and is properly labeled to warn of hazardous waste inside the container. When the sharps disposal container is nearly full, follow your community's guidelines for proper disposal. There may be state or local regulations regarding how to dispose of used syringes. Do not throw the used sharps disposal container into your household trash unless your community guidelines allow it. Do not recycle the sharps disposal container.