TYSABRI 300 mg concentrate for solution for infusion

TYSABRI is used to treat multiple sclerosis (MS).

The symptoms of MS vary from patient to patient, and you may experience some or none of them. Symptoms can include; walking problems, numbness in the face, arms or legs, problems seeing things, tiredness, feeling off-balance or light headed, bladder and bowel problems, difficulty in thinking and concentrating, depression, acute or chronic pain, sexual problems, and stiffness and muscle spasms. When the symptoms flare up, it is called a relapse (also known as an exacerbation or an attack). When a relapse occurs, you may notice the symptoms suddenly, within a few hours, or slowly progressing over several days. Your symptoms will then usually improve gradually (this is called a remission).

MS causes inflammation in the brain that damages the nerve cells. In TYSABRI the active ingredient is natalizumab, a protein similar to your own antibodies. It stops the cells that cause inflammation from going into your brain. This reduces nerve damage caused by MS.

In clinical trials, TYSABRI approximately halved the progression of the disabling effects of MS and also decreased the number of MS attacks by about two-thirds. However, TYSABRI cannot repair the damage that has already been caused by MS. When you receive TYSABRI you might not notice any improvement, but TYSABRI may still be working to prevent your MS becoming worse.

It is important to continue with your medicine for as long as you and your doctor decide that it is helping you.

Before you start treatment with TYSABRI, it is important that you and your doctor have discussed the benefits you would expect to receive from this treatment and the risks that are associated with it.

Do not use TYSABRI

• If you are allergic (hypersensitive) to natalizumab or any of the other ingredients of TYSABRI (see section 6 for the ingredients).
• If your doctor has told you that you have PML (progressive multifocal leukoencephalopathy). PML is a rare infection of the brain.
• If your doctor tells you that you have aserious problem with your immune system (due to disease for example, leukaemia or HIV or due to a medicine you are taking or have previously taken).
• If you are taking medicines that cannot be used with TYSABRI (see Using other medicines, below).
• If you have cancer (unless it is a type of skin cancer called basal cell carcinoma).
• If you are under 18 years of age.

Take special care with TYSABRI

There have been cases of a rare brain infection called PML (progressive multifocal leukoencephalopathy) that have occurred in patients who have been given TYSABRI. PML may lead to severe disability or death. The risk of PML increases the longer that you are on treatment especially if you have been on treatment for more than two years. It is not known if the chance of getting PML continues to rise, remains the same, or falls after you have been on TYSABRI for more than three years. The risk of PML is also greater if you have previously taken a medicine that weakens your immune system.In patients with PML a reaction known as IRIS (Immune Reconstitution Inflammatory Syndrome) is likely to occur after treatment for PML, as TYSABRI is removed from your body. IRIS may lead to your condition getting worse, including worsening of brain function.

The symptoms of PML may be similar to an MS relapse (e.g. weakness or visual changes). Therefore, if you believe your MS is getting worse or if you notice any new symptoms, it is very important that you speak to your doctor as soon as possible.

Speak with your partner or caregivers and inform them about your treatment. Symptoms might arise that you might not become aware of by yourself, such as changes in mood or behaviour, memory lapses, speech and communication difficulties, which your doctor may need to investigate further to rule out PML.

You will also find this information in the Patient Alert Card you have been given by your doctor. It is important that you keep this Alert Card and show it to your partner or caregivers.

Serious infections may occur with TYSABRI. If you develop any infection, or if you develop symptoms like an unexplained fever, severe diarrhoea, prolonged dizziness / headache / stiff neck, weight loss, or listlessness, or other symptoms potentially associated with an infection whilst receiving TYSABRI, speak to your doctor as soon as possible and show the Patient Alert Card and this package leaflet to him.

You will also find this information in the Patient Alert Card you have been given by your doctor. It is important that you keep this Alert Card.

Using other medicines
Please tell your doctor if you are taking or have recently taken any other medicines, including medicines you may have obtained without a prescription. You may not be able to use TYSABRI with some medicines that affect your immune system.

Pregnancy and breast-feeding
You should not use TYSABRI if you are pregnantunless you have discussed this with your doctor. Be sure to tell your doctor immediately if you are pregnant, think you may be pregnant, or if you are planning to become pregnant.

Do not breast-feed whilst using TYSABRI. You should discuss with your doctor whether you choose to breast-feed or to use TYSABRI.

Ask your doctor or pharmacist for advice before taking any other medicine with TYSABRI.

Driving and using machines
TYSABRI is not expected to have an effect on your ability to drive or to operate machines. If you are concerned, discuss this with your doctor.

TYSABRI will be prepared and given to you by a doctor.

Information for medical or healthcare professionals on how to prepare and administer TYSABRI is provided at the end of this leaflet.

The adult dose is 300 mg given once every 4 weeks.

TYSABRI must be diluted before it is given to you. It is given as a drip into a vein (by intravenous infusion), usually in your arm. This takes about 1 hour.

A few patients have had an allergic reaction to TYSABRI. Your doctor will check for allergic reactions during the infusion and for 1 hour afterwards.

It is important to continue with your medicine for as long as you and your doctor decide that it is helping you. Continuous dosing with TYSABRI is important, especially during the first few months of treatment. This is because patients who received one or two doses of TYSABRI and then had a gap in treatment of three months or more, were more likely to have an allergic reaction when resuming treatment.

If you miss your dose of TYSABRI
If you miss your usual dose of TYSABRI, arrange with your doctor to receive it as soon as you can. You can then continue to receive your dose of TYSABRI every 4 weeks.

If you have any further questions on TYSABRI, ask your doctor.

Like all medicines, TYSABRI can cause side effects, although not everybody gets them.

If you have any worrying side effects, including any not listed in this leaflet, please tell your doctor, nurse or pharmacist as soon as possible.

Speak to your doctor or nurse immediately if you notice any of the following:

Signs of allergy to TYSABRI, during or shortly after your infusion:

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

Signs of a possible liver problem:

• Yellowing of your skin or the whites of your eyes
• Unusual darkening of the urine.

TYSABRI can also have other side effects.

Side effects are listed below by how commonly they have been reported in clinical trials:

Common side effects that may occur in less than 10 in 100 patients:

• Urinary tract infection
• Sore throat and runny or blocked up nose
• Shivering
• Itchy rash (hives)
• Headache
• Dizziness
• Feeling sick (nausea)
• Being sick (vomiting)
• Joint pain
• Fever
• Tiredness.

Uncommon side effects that may occur in less than 1 in 100 patients:

• Severe allergy (hypersensitivity).

Rare side effects that may occur in less than 1 in 1000 patients :

• Unusualinfections (so-called ?Opportunistic infections?)
• Progressive multifocal leukoencephalopathy (PML), a rare brain infection.

What to do if your MS gets worse or you notice new symptoms

There have been reports of a rare brain infection called PML (progressive multifocal leukoencephalopathy) that have occurred in patients who have been given TYSABRI. PML usually leads to severe disability or death.

The symptoms of PML may be similar to an MS relapse.

• Therefore, if you believe your MS is getting worse or if you notice any new symptoms, it is important that you speak to your doctor as soon as possible.
• Discuss your treatment with your partner or caregivers. They might see new symptoms that you might not notice such as changes in mood or behaviour, memory lapses, speech and communication difficulties, which your doctor may need to investigate further to rule out PML.
• Show the Alert Card and this package leaflet to any doctor involved with your treatment, not only to your neurologist.

Serious infections may occur with TYSABRI. The symptoms of infections include:

• an unexplained fever
• severe diarrhoea
• shortness of breath
• prolonged dizziness
• headache
• stiff neck
• weight loss
• listlessness.
• Speak to your doctor as soon as possible if you think you have an infection .
• Show the Alert Card and this package leaflet to any doctor involved with your treatment, not only to your neurologist.

You will also find this information in the Patient Alert Card you have been given by your doctor.

Will TYSABRI always work?

In a few patients who use TYSABRI, over time the body?s natural defence may stop TYSABRI from working properly (the body develops antibodies to TYSABRI). Your doctor can decide whether TYSABRI is not working properly for you by testing your blood and will stop TYSABRI, if necessary.

Keep out of the reach and sight of children.

Unopened vial:

Store in a refrigerator (2°C to 8°C).
Do not freeze.
Keep the vial in the outer carton in order to protect from light.

Do not use TYSABRI after the expiry date stated on the label and carton.

Diluted solution:

After dilution, immediate use is recommended. If not used immediately, the diluted solution must be stored at 2-C - 8-C and infused within 8 hours of dilution.

Do not use TYSABRI if you notice particles in the liquid and/or the liquid in the vial is discoloured.

What TYSABRI contains

Each 15 ml vial of concentrate contains 300 mg natalizumab (20 mg/ml).

The other ingredients are:
Sodium phosphate, monobasic, monohydrate
Sodium phosphate, dibasic, heptahydrate
Sodium chloride
Polysorbate 80 (E433)
Water for injections.

What TYSABRI looks like and contents of the pack

TYSABRI is a clear, colourless to slightly cloudy liquid. Each carton contains one glass vial.

TYSABRI must be diluted before it is given to you.

Marketing Authorisation Holder
Elan Pharma International Ltd.
Monksland
Athlone
County Westmeath
Ireland

Manufacturer

Biogen Idec Denmark Manufacturing ApS
Biogen Idec Allé 1
DK-3400 Hillerød
Denmark

For any further information about this medicine, please contact the local representative of the Marketing Authorisation Holder. This information is provided at the end of the leaflet.

BelgiëBelgiqueBelgien Biogen Idec Belgium N.V.S.A. TélTel 32 2 219 12 18 LuxembourgLuxemburg Biogen Idec Belgium N.V.S.A. TélTel 32 2 219 12 18

Te. 359 2 962 12 00 Magyarország Gedeon Richter Plc. Tel. 36 1 505 7032

eská republika Biogen Idec Czech Republic s.r.o. Tel 420 255 706 200 Malta Pharma MT Limited Tel 356 213 370089

Danmark Biogen Idec Denmark AS Tlf 45 77 41 57 88 Nederland Biogen Idec International B.V. Tel 31 20 542 2000

Deutschland Biogen Idec GmbH Tel 49 0 89 99 6170 Norge Biogen Idec Norway AS Tlf 47 23 00 52 50

Eesti Richter Gedeon Eesti filiaal Tel 372 742 0200 Österreich Biogen Idec Austria GmbH Tel 43 1 484 46 13

Genesis Pharma SA 30 210 8771500 Polska Gedeon Richter Polska Sp.z.o.o. Tel. 48 22 755 96 48

España Biogen Idec Iberia SL Tel 34 91 310 7110 Portugal Biogen Idec Portugal Sociedade Farmacêutica Unipessoal, Lda Tel 351 21 318 8450

France Biogen Idec France Tél 33 01 41 37 95 95 România MEDISON PHARMA SRL Tel 40 31 7104035

Ireland Biogen Idec Ireland Ltd. Tel 353 01 463 7799 Slovenija Biogen Idec d.o.o. Tel 386 1 511 02 90

Ísland Icepharma hf Sími 354 540 8000 Slovenská republika Biogen Idec Slovak Republic s.r.o. Tel 421 2 324 101 88

Italia Biogen-Dompé s.r.l. Tel 39 02 583 831 SuomiFinland Biogen Idec Finland Oy PuhTel 358 207 401 200

Genesis Pharma Cyprus Ltd 357 22 769946 Sverige Biogen Idec Sweden AB Tel 46 8 594 113 60

Latvija Gedeon Richter Plc. Tel 37 16 784 5338 United Kingdom Biogen Idec Limited Tel 44 0 1628 50 1000

Lietuva
Gedeon Richter Plc.
Tel: +37 05 268 5392

This leaflet was last approved in {MM/YYYY}.

--------------------------------------------------------------------------------------------------------------------------- The following information is intended for medical or healthcare professionals only:

1. Inspect the TYSABRI vial for particles prior to dilution and administration. If particles are observed and/or the liquid in the vial is not colourless, clear to slightly opalescent, the vial must not be used.

2. Use aseptic technique when preparing TYSABRIsolution for intravenous (IV) infusion. Remove flip-top from the vial. Insert the syringe needle into the vial through the centre of the rubber stopper and remove 15 ml concentrate for solution for infusion.

3. Add the 15 ml concentrate for solution for infusion to 100 ml sodium chloride 9 mg/ml (0.9%) solution for injection. Gently invert the TYSABRI solution to mix completely. Do not shake.

4. TYSABRI must not be mixed with other medicinal products or diluents.

5. Visually inspect the diluted product for particles or discolouration prior to administration. Do not use if it is discoloured or if foreign particles are seen.

6. The diluted product is to be used as soon as possible and within 8 hours of dilution. If the diluted product is stored at 2°C - 8°C (do not freeze), allow the solution to warm to room temperature prior to infusion.

7. The diluted solution is to be infused intravenously over 1 hour at a rate of approximately 2 ml/minute.

8. After the infusion is complete, flush the intravenous line with sodium chloride 9 mg/ml (0.9%) solution for injection.

9. Each vial is for single?use only.

10. Any unused product or waste material must be disposed of in accordance with local requirements.