TYSABRI 300 mg Concentrate For Infusion Solution

Зміст інструкції

1. Tysabri 300 mg concentrate for solution for infusion
   1. What is Tysabri and what is it used for
   2. What you need to know before you receive Tysabri
   3. How Tysabri is administered
   4. Possible side effects
   5. How to store Tysabri
   6. Contents of the pack and other information
2. Tysabri 150 mg injectable solution in pre-filled syringe
   1. What is Tysabri and what is it used for
   2. What you need to know before you receive Tysabri
   3. How Tysabri is administered
   4. Possible side effects
   5. How to store Tysabri
   6. Contents of the pack and other information

Tysabri 300 mg concentrate for solution for infusion

natalizumab

Read this leaflet carefully before using this medicine as it contains important
information for you.
It contains important safety information that you must know before and during treatment with Tysabri.

• Keep this leaflet and the patient alert card. You may need to read them again. Carry the patient alert card with you during treatment and for six months after the last dose of this medicine, as adverse effects may occur even after stopping treatment.
• If you have any questions, ask your doctor.
• If any side effects occur, including those not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet

• 1. What Tysabri is and what it is used for
• 2. What you need to know before you receive 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 is Tysabri and what is it used for

Tysabri is used to treat multiple sclerosis (MS). It contains the active substance natalizumab.
This is called 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 the nerve damage caused by
MS.

Symptoms of multiple sclerosis
The symptoms of MS vary from patient to patient, and you may experience some or none of them.

They can include: problems walking, a feeling of numbness in the face, arms or legs, vision problems, fatigue, loss of balance or dizziness, problems with the bladder and bowel, difficulty thinking and concentrating, depression, acute or chronic pain, sexual problems, stiffness and muscle spasms. If symptoms worsen, this is called a relapse (also called an exacerbation or attack). When
a relapse occurs, you may notice that your symptoms progress suddenly, within a few
hours, or slowly, over several days. Usually, the symptoms will then gradually improve
(in this case, it is referred to as remission).

How Tysabri can help
In studies, this medicine has reduced the increase in disability caused by MS by about half,
and has reduced the number of MS attacks by about two-thirds. During treatment with this
medicine, you may not notice any effect on MS, but it can help prevent the disease from
worsening.

2. What you need to know before you receive Tysabri

Before starting treatment with this medicine, it is important that you discuss with your doctor the
possible benefits you may have as a result of the treatment and the risks associated with it.

Tysabri must not be given to you

• If you are allergicto 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 an uncommon brain infection.
• If you have a serious problem with your immune system. This could be caused by an illness (such as HIV), or by some medicines you are taking, or have taken in the past (see below).
• If you are taking medicines that act on the immune system, including some medicines used for the treatment of 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
You should discuss with your doctorwhether Tysabri is the most appropriate treatment for you.
This should be done before you start taking Tysabri, and when you have received Tysabri for more than 2
years.

Possible brain infection (PML)
Some people who were receiving this medicine (less than 1 in 100) developed an uncommon brain
infection called progressive multifocal leukoencephalopathy (PML). PML can
cause severe disability or be fatal.

• Before starting treatment, all patients will undergo blood testsarranged by the doctor for JC virus infection. JC virus is a common virus that normally does not make you sick. However, PML is linked to an increase in 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 test your blood to check if you have antibodies to JC virus, which is a sign that you have a JC virus infection.
• The doctor will plan a magnetic resonance imaging (MRI)scan which will be repeated during treatment to exclude PML.
• The symptoms of PMLcan be similar to those of an MS relapse (see section 4, Possible side effects). You can become ill with PML up to 6 months after stopping treatment with Tysabri.

Talk to your doctor as soon as possibleif you notice a worsening of your MS, if you notice any new symptoms
during the treatment period with Tysabri or up to 6 months after.

• Talk to your partner or those who care for youabout what needs to be monitored (see also section 4, Possible side effects). Some symptoms can be difficult to notice yourself, such as changes in mood or behaviour, confusion,

difficulty with speech and communication. If you develop any of these, you may need further tests. Continue to pay attention to symptoms for 6 months after
stopping treatment with Tysabri.

• Keep the patient alert card that your doctor has given you. It includes this information. Show it to your partner or those who care for you.

Three things can increase the risk of PMLwith Tysabri. If you have two or more of these
risk factors, the risk increases further:

• if you have antibodies to JC virus in your blood. These are a sign that the virus is in your body. You will be tested before and during treatment with Tysabri.
• If you have been treated with Tysabri for a long time,especially for more than two years.
• if you have taken a medicine called an immunosuppressantthat reduces the activity of the immune system.

Another condition, called JC virus granule cell neuronopathy (JC virus granule cell neuronopathy

• JCV GCN) is also caused by the JC virus and has occurred in some patients treated with Tysabri. The symptoms of JCV GCN are similar to the symptoms of PML.

The doctor may repeat the test regularly for those at lower risk of PML, to assess that:

• you continue to have no antibodies to JC virus in your blood
• if you have received treatment for more than 2 years, you have a still low level of antibodies to JC virus in your blood.

If someone develops PML
PML can be treated and treatment with Tysabri will be stopped. However, some people

develop a reactionwhen Tysabri is removed from the body. This reaction (known as IRISor immune reconstitution inflammatory syndrome) can cause your condition to worsen, including worsening of brain function.

Monitoring for other infections
Some infections other than PML can also be serious and can be caused by viruses,
bacteria and other causes.

Talk to a doctor or nurseif you think you have an infection (see also section 4,

Possible side effects).

Changes in platelet counts
Natalizumab can reduce the number of platelets, which are responsible for blood clotting, in the blood.
This may cause a condition called thrombocytopenia (see section 4) which causes
the blood not to clot quickly enough to stop bleeding. This condition can in turn cause bruising and other more serious problems such as excessive bleeding. See a doctor immediately if you notice unexplained bruising, red or purple spots on the skin (called petechiae), bleeding from cuts that does not stop or oozes, bleeding gums or nose prolonged, blood in the urine or stool, bleeding in the
white of the eye.

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

Other medicines and Tysabri
Tell your doctor if you are taking, have recently taken or might take any other
medicines.

• You must notbe given this medicine if you are currently taking medicines that act on the immune system, including some other medicines for the treatment of MS.
• You may not be able to use this medicine if you have taken in the pastmedicines that act on the immune system.

Pregnancy and breastfeeding

• Do not use this medicine if you are pregnantunless you have discussed it with your doctor. Tell your doctor immediately if you become pregnant, suspect you are pregnant or are planning to become pregnant.
• Do not breastfeed during treatment with Tysabri. Your doctor will help you decide whether to stop breastfeeding or stop using the medicine.

If you are pregnant, suspect or are planning a pregnancy or are breastfeeding, ask your doctor for advice before taking this medicine. The risk to the baby and the
benefit to the mother will be considered by the doctor.

Driving and using machines
Dizziness is a very common side effect. If you experience it, do not drive or use
machines.

Tysabri contains sodium
Each vial of this medicine contains 2.3 mmol (or 52 mg) of sodium. After dilution, the
medicine contains 17.7 mmol (406 mg) of sodium per dose. You should be aware of this
information if you are on a low sodium diet.

3. How Tysabri is administered

The intravenous infusion of Tysabri will be administered by a doctor specialized in the treatment
of MS. The doctor may prescribe a direct transition from another medication for MS to Tysabri, if
there are no problems caused by the previous treatment.

• The doctor will order a blood testfor JC virus antibodies and other possible problems.
• The doctor will subject you to an MRIwhich will be repeated during treatment.
• To switch from some medications for MS, the doctor may advise you to wait a certain period to ensure that most of the previous medication has been eliminated from the body.
• For adults, the recommended dose is 300 mg, to be administered once every 4 weeks.
• Before administration, Tysabri must be diluted. It is administered into a vein with an IV (intravenous infusion), generally in an arm. The infusion lasts approximately 1 hour.
• Information for doctors and healthcare professionals on how to prepare and

If you stop taking Tysabri
Regular intake of Tysabri is important, especially in the first few months of treatment. It is important
that you continue treatment until you and your doctor believe it is benefiting you. Patients who
have received one or two doses of Tysabri and subsequently discontinued treatment for three months
or more have been shown to have a higher probability of developing an allergic reaction if treatment
is resumed.

Monitoring for allergic reactions
Some patients have experienced an allergic reaction to this medication. The doctor may
monitor for any allergic reactions that may occur during the infusion and within one hour
afterwards. See also paragraph 4, Possible side effects.

If you forget to take Tysabri
If you miss your usual dose of Tysabri, agree with your doctor to receive it as soon as possible.
Subsequently, you should continue to receive the Tysabri dose every 4 weeks.

Will Tysabri always work?
In some patients treated with Tysabri, over time the body's natural defenses
may prevent the medication from working properly. The doctor will be able to establish whether this
medication is not working as it should through blood tests and, if necessary, will suspend the
treatment.
For further information on the use of Tysabri, consult your doctor. Use this medication following
exactly as stated in this leaflet or the doctor's instructions. If you have any doubts, consult your
doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Immediately inform your doctor or nurseif you notice any of the following:

Signs of a serious brain infection:

• changes in personality and behaviour such as confusion, delirium (confusional state) or loss of consciousness
• seizures (convulsions)
• headache
• nausea/vomiting
• stiff neck
• extreme sensitivity to bright light
• fever
• skin rash (on any part of the body).

These symptoms may be caused by an infection of the brain (encephalitis or PML) or its
lining (meningitis).

Signs of other serious infections:

• unexplained fever
• severe diarrhoea
• shortness of breath
• prolonged dizziness
• headache
• weight loss
• apathy
• impaired vision
• pain or redness of one or both eyes

Signs of an allergic reaction

• skin rash (urticaria)
• swelling of the face, lips or tongue
• difficulty breathing
• chest pain or discomfort
• increase or decrease in blood pressure (which will be noticed by the doctor or nurse if blood pressure is being monitored).

These are more likely during or immediately after the infusion.

Signs of a possible liver problem:

• yellowing of the skin or whites of the eyes
• unusually dark urine
• abnormal liver function tests

Speak to a doctor or nurse immediatelyif you experience any of the side effects
listed above or if you think you have an infection. Show your patient alert cardand
your neurologist.

Other side effects
Very common(may affect more than 1 in 10 people):

• urinary tract infection
• sore throat and increased or congested nasal secretions
• headache
• dizziness
• feeling sick (nausea)
• joint pain
• fatigue
• dizziness, feeling sick (nausea), itching and chills during or immediately after the infusion

Common(may affect up to 1 in 10 people):

• anaemia (decrease in red blood cells which can make the skin pale and make you feel breathless or without energy)
• allergy (hypersensitivity)
• chills
• urticaria
• feeling unwell (vomiting)
• fever
• difficulty breathing (dyspnoea)
• redness of the face and body (flushing)
• herpes zoster infection
• discomfort at the site where you had the infusion. 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
• facial swelling
• increased number of white blood cells (eosinophilia)
• reduction in platelets in the blood
• bruising easily (purpura)

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

• herpes zoster infection in the eye
• severe anaemia (decrease in red blood cells which can make the skin pale and make you feel breathless or without energy).
• severe swelling under the skin
• high levels of bilirubin in the blood (hyperbilirubinemia) which can cause symptoms such as yellowing of the eyes or skin, fever and fatigue

Not known(frequency cannot be estimated from the available data)

• unusual infections (so-called "opportunistic infections")
• liver damage

See your doctor as soon as possibleif you think you have an infection.
You will also find this information on the patient alert card given to you by your doctor.

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed in this leaflet. You can also report side effects directly through the national reporting system detailed in Annex V. By reporting side effects you can help to provide more information on the safety of this medicine.

5. How to store Tysabri

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 label and on the packaging. The expiry
date refers to the last day of that month.

Intact vial:
Store in a refrigerator.
Do not freeze.
Keep the vial in the outer packaging to protect the medicine from light.

Diluted solution:
After dilution, immediate use is recommended. If not used immediately, the diluted
solution must be stored at a temperature between 2 °C and 8 °C and administered within
24 hours of dilution.
Do not use this medicine if you notice particles in the liquid and/or if the liquid in the vial shows
a change in colour.

6. Contents of the pack and other information

What Tysabri contains
The active ingredient is natalizumab. Each 15 mL vial of concentrate contains 300 mg of
natalizumab (20 mg/mL). After dilution, the infusion solution contains approximately 2.6
mg/mL of natalizumab.
The other ingredients are:
sodium phosphate, monobasic, monohydrate,
sodium phosphate, dibasic, heptahydrate,
sodium chloride (see section 2 ‘Tysabri contains sodium’),
polysorbate 80 (E 433)
water for injections

Description of Tysabri and contents of the pack
Tysabri is a liquid ranging from colourless to slightly opalescent.
Each pack contains one glass vial.

Marketing Authorisation Holder and Manufacturer
Biogen Netherlands B.V.
Prins Mauritslaan 13
1171 LP Badhoevedorp
Netherlands
For further information on this medicinal product, contact the local representative of the Marketing
Authorisation Holder:

België/Belgique/Belgien
Biogen Belgium N.V./S.A.
Tél/Tel: +32 2 219 12 18

Lietuva
Biogen Lithuania UAB
Tel: +370 5 259 6176

България
ТП ЕВОФАРМА
Teл.: +359 2 962 12 00

Luxembourg/Luxemburg
Biogen Belgium N.V./S.A.
Tél/Tel: +352 2 219 12 18

Česká republika
Biogen (Czech Republic) s.r.o.
Tel: +420 255 706 200

Magyarország
Biogen Hungary Kft.
Tel.: +36 (1) 899 9883

Malta
Pharma MT limited
Tel: +356 213 37008/9

Danmark
Biogen (Denmark) A/S
Tlf.: +45 77 41 57 57

Deutschland
Biogen GmbH
Tel: +49 (0) 89 99 6170

Nederland
Biogen Netherlands B.V.
Tel: +31 20 542 2000

Norge
Biogen Norway AS
Tlf: +47 23 40 01 00

Eesti
Biogen Estonia OÜ
Tel: +372 618 9551

Ελλάδα
Genesis Pharma SA
Τηλ: +30 210 8771500

Österreich
Biogen Austria GmbH
Tel: +43 1 484 46 13

España
Biogen Spain SL
Tel: +34 91 310 7110

Polska
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

România
Johnson & Johnson Romania S.R.L.
Tel: +40 21 207 18 00

Hrvatska
Biogen Pharma d.o.o.
Tel: +358 (0) 1 775 73 22

Ireland
Biogen Idec (Ireland) Ltd.
Tel: +353 (0)1 463 7799

Slovenija
Biogen Pharma d.o.o.
Tel: +386 1 511 02 90

Ísland
Icepharma hf
Sími: +354 540 8000

Slovenská republika
Biogen Slovakia s.r.o.
Tel: +421 2 323 340 08

Italia
Biogen Italia s.r.l.
Tel: +39 02 584 9901

Suomi/Finland
Biogen Finland Oy
Puh/Tel: +358 207 401 200

Κύπρος
Genesis Pharma (Cyprus) Ltd
Τηλ: +357 22 76 57 15

Sverige
Biogen Sweden AB
Tel: +46 8 594 113 60

Latvija
Biogen Latvia SIA
Tel: +371 68 688 158

Other sources of information
More detailed information on this medicinal product is available on the website of the European
Medicines Agency, https://www.ema.europa.eu .
---------------------------------------------------------------------------------------------------------------------------

The following information is intended exclusively for healthcare professionals:

• 1. Before dilution and administration, inspect the Tysabri vial for the presence of particles. If particles are present and/or if the liquid in the vial does not appear colourless, clear or slightly opalescent, the vial must not be used.
• 2. Use aseptic technique when preparing the medicinal product. Remove the flip-top cap from the vial. Insert the needle of the syringe into the vial through the centre of the rubber stopper and withdraw 15 mL of concentrate for solution for infusion.
• 3. Add the 15 mL of concentrate for solution for infusion to 100 mL of sodium chloride 9 mg/mL (0.9 % ) for injection. Gently invert the solution to mix thoroughly. Do not shake.
• 4. Tysabri must not be mixed with other medicinal products or diluents.
• 5. Before administration, visually inspect the diluted product for the presence of particles and colour change. Do not use the medicinal product if the colour is altered or if suspended particles are present.

• 6. The diluted medicinal product must be used as soon as possible and within 24 hours of dilution. If the diluted medicinal product is stored at a temperature between 2 °C and 8  C (do not freeze), bring the solution to room temperature before infusion.
• 7. The diluted solution must be administered intravenously over 1 hour, at a rate of approximately 2 mL per minute.
• 8. After completion of the infusion, flush the intravenous line with sodium chloride 9 mg/mL (0.9 % ) for injection.
• 9. Each vial is for single use only.
• 10. To improve the traceability of biological medicinal products, the name (Tysabri) and batch number of the administered product must be clearly recorded.
• 11. Unused medicinal product and waste materials derived from such medicinal product must be disposed of in accordance with local regulations.

Tysabri 150 mg injectable solution in pre-filled syringe

natalizumab

Read this leaflet carefully before using this medicine as it contains important
information for you.
It contains important safety information that you must know before and during treatment with Tysabri.

• Keep this leaflet and the patient alert card. You may need to read them again. Keep the patient alert card with you during treatment and for six months after the last dose of this medicine, as side effects may occur even after stopping treatment.
• If you have any questions, ask your doctor.
• If any side effects occur, including those not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet

• 1. What Tysabri is and what it is used for
• 2. What you need to know before you receive 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 is Tysabri and what is it used for

Tysabri is used to treat multiple sclerosis (MS). It contains the active substance natalizumab. This
is called 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 the damage to the nerves caused by
MS.

Symptoms of multiple sclerosis
The symptoms of MS vary from patient to patient and you may experience some or none
at all.

They can include:problems walking, a feeling of numbness in the face, arms or legs, vision problems, fatigue, loss of balance or dizziness, problems with the bladder and bowel, difficulty thinking and concentrating, depression, acute or chronic pain, sexual problems, stiffness and muscle spasms. If symptoms worsen, this is called a relapse (also called an exacerbation or attack). When a relapse occurs, you may notice that your symptoms progress suddenly, within a few
hours, or slowly, over several days. Usually, the symptoms will then gradually improve
(this is called remission).

How Tysabri can help
In studies, this medicine has reduced by about half the increase in disability caused by MS,
and has reduced, by about two-thirds, the number of MS attacks. During treatment with this
medicine, you may not notice any effect on MS, but it can help prevent the disease from
getting worse.

2. What you need to know before you receive Tysabri

Before starting treatment with this medicine, it is important that you discuss with your doctor the
possible benefits you may have as a result of the treatment and the risks associated with it.

Tysabri must not be given to you

• If you are allergicto natalizumab or any of the other ingredients of this medicine (listed in section 6).
• If you have been diagnosed with progressive multifocal leukoencephalopathy(PML). PML is an uncommon brain infection.
• If you have a serious problem with your immune system.This could be caused by an illness (such as HIV), or by some medicines you are taking or have taken in the past (see below).
• If you are taking medicines that act on the immune system, including some medicines used for the treatment of 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
You should discuss with your doctorif Tysabri is the most suitable treatment for you. This should be done
before you start taking this medicine, and when you have received this medicine for more than 2
years.

Possible brain infection (PML)
Some people who were receiving this medicine (less than 1 in 100) developed an uncommon brain
infection called progressive multifocal leukoencephalopathy(PML). PML can
cause severe disability or be fatal.

• Before starting treatment, all patients will have blood testsarranged by your doctor for JC virus infection. JC virus is a common virus that normally does not make you sick. However, PML is linked to an increase in 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 test your blood to check if you have antibodies to JC virus, which is a sign that you have a JC virus infection.
• Your doctor will plan a magnetic resonance imaging (MRI)scan that will be repeated during treatment to rule out PML.
• The symptomsof PML can be similar to those of an MS relapse (see section 4, Possible side effects). You can become ill with PML up to 6 months after stopping treatment with Tysabri.

Talk to your doctor as soon as possibleif you notice a worsening of your MS, if you notice any new symptoms
during the treatment period with Tysabri or up to 6 months after.

• Talk to your partner or those who care for youabout what needs to be monitored (see also section 4, Possible side effects). Some symptoms can be difficult to

recognize yourself, such as changes in mood or behaviour, confusion,
difficulty with speech and communication. If you develop any of these, you may
need further tests. Continue to pay attention to symptoms for 6 months after
stopping treatment with Tysabri.

• Keep the patient alert card that your doctor has given you. It includes this information. Show it to your partner or those who care for you.

Three things can increase the risk of PMLwith Tysabri. If you have two or more of these
risk factors, the risk increases further:

• if you have antibodies to JC virusin your blood. These are a sign that the virus is in your body. You will be tested before and during treatment with Tysabri.
• if you have been treated for a long timewith Tysabri, especially for more than two years.
• if you have taken a medicine called an immunosuppressantthat reduces the activity of the immune system.

Another condition, called JC virus granule cell neuronopathy (JC virus granule cell neuronopathy

• JCV GCN) is also caused by JC virus and has occurred in some patients treated with this medicine. The symptoms of JCV GCN are similar to the symptoms of PML.

The doctor may repeat the test regularly for those at lower risk of PML, to assess that:

• you continue to have no antibodies to JC virus in your blood
• if you have received treatment for over 2 years, you have a still low level of antibodies to JC virus in your blood.

If someone develops PML
PML can be treated and treatment with Tysabri will be stopped. However, some people

develop a reactionwhen Tysabri is removed from the body. This reaction (known as IRISor immune reconstitution inflammatory syndrome) can cause your condition to worsen, including worsening of brain function.

Monitoring for other infections
Some infections other than PML can also be serious and can be caused by viruses,
bacteria and other causes.

Talk to a doctor or nurseif you think you have an infection (see also section 4,

Possible side effects).

Changes in platelet counts
Natalizumab can reduce the number of platelets, which are responsible for blood clotting, in the blood.
This may cause a condition called thrombocytopenia (see section 4) that causes
the blood to not clot quickly enough to stop bleeding. This condition can in turn cause bruising and other more serious problems such as excessive bleeding.
See a doctor immediately if you notice unexplained bruising, red or purple spots on the skin (called petechiae), bleeding from cuts that does not stop or oozes, bleeding gums or nosebleeds that last a long time, blood in your urine or stools, bleeding in the
whites of your eyes.

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

Other medicines and Tysabri
Tell your doctor if you are taking, have recently taken or might take any other
medicines.

• This medicine must not be given to youif you are currently taking medicines that act on the immune system, including some other medicines for the treatment of MS.
• You may not be able to use this medicine if you have taken in the pastmedicines that act on the immune system.

Pregnancy and breastfeeding

• Do not use this medicine if you are pregnantunless you have discussed it with your doctor. Tell your doctor immediately if you become pregnant, suspect you are pregnant or are planning to become pregnant.
• Do not breastfeed during treatment with Tysabri. Your doctor will help you decide whether to stop breastfeeding or stop using the medicine.

If you are pregnant, suspect or are planning a pregnancy, or are breastfeeding, ask your doctor for advice before taking this medicine. The risk to the baby and the benefit to the mother will be considered by the doctor.

Driving and using machines
Dizziness is a very common side effect. If you experience it, do not drive or use
machines.

Tysabri contains sodium
This medicine contains less than 1 mmol of sodium per 300 mg dose, i.e. it is essentially
sodium-free.

3. How Tysabri is administered

Tysabri injections will be prescribed by a doctor specializing in the treatment of MS. The
doctor may prescribe a direct switch from another medication to Tysabri, if there are no signs of
problems caused by the previous treatment. Tysabri injections will be administered by a
healthcare professional.

• The doctor will order a blood testfor JC virus antibodies and other possible problems.
• The doctor will subject you to an MRIwhich will be repeated during treatment.
• To switch from certain medications for MS, the doctor may advise you to wait a certain period to ensure that most of the previous medication has been eliminated from the body.
• If your condition allows, the doctor may discuss with you the possibility of receiving injections outside of a hospital environment (e.g., at home).
• For adults, the recommended dose is 300 mg, to be administered once every 4 weeks.
• Each dose is administered in the form of two injectionsunder the skin, in the thigh, abdomen, or the back of the arm. This takes up to 30 minutes.
• Information for doctors and healthcare professionals on how to prepare and

If you stop taking Tysabri
Regular intake of this medication is important, especially in the first months of treatment. It is
important that you continue treatment as long as you and your doctor believe it is beneficial. Patients who have received one or two doses of Tysabri and have subsequently discontinued
treatment for three months or more have been shown to have a higher probability of developing an allergic
reaction if treatment is resumed.

Monitoring for allergic reactions
Some patients have experienced an allergic reaction to this medication. The doctor may
monitor for any allergic reactions that may occur during the infusion and within one
hour afterwards. See also section 4, Possible side effects.

If you forget to take Tysabri
If you miss your usual dose of Tysabri, agree with your doctor to receive it as soon as
possible. You will then need to continue to receive the Tysabri dose every 4 weeks.

Will Tysabri always work?
In some patients treated with Tysabri, over time the body's natural defenses
may prevent the medication from working properly, as the body develops antibodies to
the drug. The doctor will be able to establish whether this medication is not working as it should through blood tests and, if necessary, will suspend treatment.
For further information on the use of Tysabri, consult your doctor. Always use this medication exactly as
described in this leaflet or as instructed by your doctor. If you have any doubts, consult your
doctor.
The term subcutaneous is abbreviated as SC on the syringe label.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will get them.

Tell your doctor or nurse immediately if you notice any of the following:
Signs of a serious brain infection:

• changes in personality and behaviour such as confusion, delirium (a state of confusion) or loss of consciousness
• seizures (convulsions)
• headache
• nausea/vomiting
• stiff neck
• extreme sensitivity to bright light
• fever
• skin rash (on any part of the body).

These symptoms can be caused by an infection of the brain (encephalitis or PML) or its
covering (meningitis).

Signs of other serious infections:

• unexplained fever
• severe diarrhoea
• shortness of breath
• prolonged dizziness
• headache
• weight loss
• apathy
• impaired vision
• pain or redness of one or both eyes

Signs of an allergic reaction

• skin rash (urticaria)
• swelling of the face, lips or tongue
• difficulty breathing
• chest pain or discomfort
• increase or decrease in blood pressure (which will be noticed by your doctor or nurse if your blood pressure is being monitored).

These are more likely during or immediately after the injection

Signs of a possible liver problem:

• yellowing of the skin or whites of the eyes
• unusually dark urine
• abnormal liver function tests

Tell a doctor or nurse immediatelyif you experience any of the side effects
listed above or if you think you have an infection. Show your patient alert card and this
neurologist.

Other side effects
Very common(may affect more than 1 in 10 people):

• urinary tract infection
• sore throat and increased nasal secretion or congestion
• headache
• dizziness
• feeling sick (nausea)
• joint pain
• fatigue

Common(may affect up to 1 in 10 people):

• anaemia (a decrease in red blood cells which can make your skin pale and make you feel breathless or tired)
• allergy (hypersensitivity)
• feeling cold
• urticaria
• feeling unwell (vomiting)
• fever
• difficulty breathing (dyspnoea)
• redness of the face and body (flushing)
• herpes infection
• discomfort at 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)
• inflammatory disorder after stopping the medicine
• swelling of the face
• an increase in the number of white blood cells (eosinophilia)
• Reduced platelets in the blood
• Bruising easily (purpura)

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

• herpes infection in the eye
• severe anaemia (a decrease in red blood cells which can make your skin pale and make you feel breathless or tired).
• severe swelling under the skin
• high levels of bilirubin in the blood (hyperbilirubinaemia) which can cause symptoms such as yellowing of the eyes or skin, fever and fatigue

Not known(frequency cannot be estimated from the available data)

• unusual infections of the brain and eyes
• liver damage

See your doctor as soon as possibleif you think you have an infection.
You will also find this information on the patient alert card given to you by your doctor.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor. You can also report side effects directly through the national reporting system
mentioned in Annex V. By reporting side effects you can help provide more
information on the safety of this medicine.

5. How to store Tysabri

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 label and the packaging. The expiry
date refers to the last day of that month.
Store in a refrigerator.
Do not freeze.
The syringes can be stored in their original packaging for a maximum of 24 hours at
room temperature (up to 25 °C). The syringes must not be returned to the refrigerator.
Keep the syringes in the outer packaging to protect the medicine from light.
Do not use this medicine if you notice particles in the liquid and/or if the liquid in the syringe shows
a change in color.

6. Contents of the pack and other information

What Tysabri contains
The active ingredient is natalizumab.
Each pre-filled syringe of 1 mL contains 150 mg of natalizumab.
The other ingredients are:
sodium phosphate, monobasic, monohydrate,
sodium phosphate, dibasic, heptahydrate,
sodium chloride (see section 2 ‘Tysabri contains sodium’),
polysorbate 80 (E 433)
water for injections

Description of the appearance of Tysabri and contents of the pack
Tysabri is a colourless to slightly yellow, from slightly opalescent to opalescent liquid.
Each pack contains two syringes.
Tysabri is available in packs containing 2 pre-filled syringes

Marketing Authorisation Holder and Manufacturer
Biogen Netherlands B.V.
Prins Mauritslaan 13
1171 LP Badhoevedorp
The Netherlands
For further information on this medicine, contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
Biogen Belgium N.V./S.A.
Tél/Tel: +32 2 219 12 18

Lietuva
Biogen Lithuania UAB
Tel: +370 5 259 6176

България
ТП ЕВОФАРМА
Teл.: +359 2 962 12 00

Luxembourg/Luxemburg
Biogen Belgium N.V./S.A.
Tél/Tel: +352 2 219 12 18

Česká republika
Biogen (Czech Republic) s.r.o.
Tel: +420 255 706 200

Magyarország
Biogen Hungary Kft.
Tel.: +36 (1) 899 9883

Danmark
Biogen (Denmark) A/S
Tlf.: +45 77 41 57 57

Malta
Pharma MT limited
Tel: +356 213 37008/9

Nederland
Biogen Netherlands B.V.
Tel: +31 20 542 2000

Deutschland
Biogen GmbH
Tel: +49 (0) 89 99 6170

Eesti
Biogen Estonia OÜ
Tel: +372 618 9551

Norge
Biogen Norway AS
Tlf: +47 23 40 01 00

Ελλάδα
Genesis Pharma SA
Τηλ: +30 210 8771500

Österreich
Biogen Austria GmbH
Tel: +43 1 484 46 13

España
Biogen Spain SL
Tel: +34 91 310 7110

Polska
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

România
Johnson & Johnson Romania S.R.L.
Tel: +40 21 207 18 00

Hrvatska
Biogen Pharma d.o.o.
Tel: +358 (0) 1 775 73 22

Ireland
Biogen Idec (Ireland) Ltd.
Tel: +353 (0)1 463 7799

Slovenija
Biogen Pharma d.o.o.
Tel: +386 1 511 02 90

Ísland
Icepharma hf
Sími: +354 540 8000

Slovenská republika
Biogen Slovakia s.r.o.
Tel: +421 2 323 340 08

Italia
Biogen Italia s.r.l.
Tel: +39 02 584 9901

Suomi/Finland
Biogen Finland Oy
Puh/Tel: +358 207 401 200

Κύπρος
Genesis Pharma (Cyprus) Ltd
Τηλ: +357 22 76 57 15

Sverige
Biogen Sweden AB
Tel: +46 8 594 113 60

Latvija
Biogen Latvia SIA
Tel: +371 68 688 158

Other sources of information
More detailed information on this medicine is available on the website of the European Medicines Agency, https://www.ema.europa.eu.
---------------------------------------------------------------------------------------------------------------------------

The following information is intended exclusively for healthcare professionals
Before administering the subcutaneous injection of Tysabri outside of the clinical setting, for example,
at home, the healthcare professional must complete the administration checklist outside of the
hospital environment for each patient, before each administration, to ensure that
the injection can be performed.

The recommended dose of 300 mg should be administered using two pre-filled syringes of
150 mg, see section 3 below.

Instructions for administration
The pre-filled syringe is equipped with an automatic needle protection system that is activated
when the plunger is fully depressed. When you release the plunger, the needle cover
will cover the exposed needle.

Before
administration
C D
A B

• A. Plunger
• B. Finger flange
• C. Pre-filled syringe (glass)
• D. Needle protection
• E. Needle
• F. Needle cover C E F After administration

• 1. Remove the dose pack from the refrigerator and allow it to reach room temperature (up to 25 °C) before administering the injections. The recommended time to reach room temperature is 30 minutes.

The date and time of removal of the dose pack from the refrigerator must be recorded
on the box.
○ Do not use external heat sourcessuch as hot water to heat the pre-filled syringes.
o Do not touchor recap the needle at any stage. This is to avoid injury from
accidental needle stick.

• 2. Remove both syringes fromthe tray. Check that the medicine in each pre-filled syringe is a colourless to slightly yellow and slightly opalescent solution that is essentially free of visible particles. You may see air bubbles through the glass. This is normal and does not affect the dose.
• Check bothpre-filled syringes. Do notuse them if: o they are past the expiry date indicated on the syringe label (EXP). oro they have been stored at room temperature (up to 25 °C) for more than 24 hours. o the colour and clarity of the liquid are not consistent with that described above or if the liquid contains suspended particles. o there are signs of damage (cracks, chips, etc.).
• If you notice any of these, contact immediatelythe pharmacy.
• 3. A full dose is equivalent to two syringes administered consecutively and within 30 minutes of each other.

Use two 150 mg syringes
Full dose = 300 mg.

• 4. Use aseptic (clean and germ-free) technique and a flat work surface during the injection procedure.
• 5. Choose the first subcutaneous injection site in the thigh, abdomen or the back of the arm.

• Do notinject into an area of the body where the skin is irritated, red, bruised, infected or chafed in any way.
• 6. Administer the first injection.
• Choose an injection site and clean the skin with an alcohol wipe. o Allow the injection site to air dry on its own before injecting. o Do not touchor blow on this area again before performing the injection. o Remove the needle protection. o Gently pinch the skin around the cleaned injection site using your thumb and index finger to create a slight bulge. o Hold the pre-filled syringe at an angle of 45°-90° to the injection site. Insert the needle quickly and directly into the skin fold until the needle is fully under the skin.
• 7. Slowly push the plunger with a single smooth motion until the syringe is completely empty. Do not pull back the plunger.

• 8. Before removing the syringe, verify that the syringe is empty. If you see blood, press a cotton ball or gauze onto the injection site. Do not rub the skin after the injection. When removing the syringe from the injection site, release the plunger WHILE withdrawing the needle. When you release the plunger, the needle cover will cover the exposed needle.

• 9. Administer the injections one after the other without significant delays. If the second injection cannot be administered immediately after the first, the second injection must be administered no later than 30 minutes after the first. The second injection must be at least 3 cm away from the point where the first injection was made.

Patients must be observed during subcutaneous injections and for 1 hour
afterwardsto check for signs and symptoms of injection reactions, including hypersensitivity.

After the first 6 doses of Tysabri, regardless of the route of administration, patients must
be observed after the subcutaneous injection according to clinical judgment.
Promptly discontinue the injection at the first observation of any sign or symptom
consistent with an allergic reaction [see SmPC section 4.4].

1st injection

At least
3 cm

2nd injection

• 10. Dispose of the used syringe in accordance with local requirements.