Package Insert: Information for the Patient

Tysabri 300mg Concentrate for Infusion Solution

Natalizumab

Read this package insert carefully before starting to use this medication, because it contains important information for you.

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

• Keep this package insert and the patient information leaflet, as you may need to refer to them again. Keep the package insert and the patient information leaflet with you during treatment and for six months after the last dose of this medication, as 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 not listed in this package insert.See section4.

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

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

Multiple sclerosis symptoms

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

They may include:problems walking, tingling in the face, arms, or legs; vision problems; fatigue; feeling unsteady or dizzy; urinary and intestinal 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 exacerbation or flare-up). When a relapse occurs, you may notice symptoms suddenly, within a few hours, or with a gradual progression over several days. Symptoms generally improve gradually (this is called remission).

How Tysabri can help

In studies, this medication reduced approximately half of the increase in disability caused by MS and reduced the number of MS relapses by approximately two-thirds. While you are taking this medication, you may not notice any improvement but you can continue to act to prevent the worsening of MS.

Before starting treatment with this medicine, it is essential that you and your doctor have discussed the beneficial effects you can expect from this treatment and the associated risks.

Do not administer Tysabri

• If you are allergic to natalizumab or any of the other components of this medication (listed in section6).

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

• If yourimmune systemhas a severe problem. This may be due to an illness (such as HIV infection) or medications you are using or have used in the past (see below).

• If you are takingmedications that affect the immune system, including certain medications used to treat MS. These medications cannot be used with Tysabri.

• If youhave cancer(except for a type of skin cancer calledbasal cell carcinoma).

Warnings and precautions

Consult your doctorif Tysabri is the most suitable treatment for you. Do this before starting to use Tysabri and when you have been receiving it for more than two years.

Possible cerebral infection (PML)

Some people who receive this medication (less than 1 in 100) have had a rare cerebral infection called PML (progressive multifocal leukoencephalopathy). PML can cause severe disability or death.

• Before starting treatment, your doctor will perform ablood test on all patientsto detect JC virus infection. The JC virus is a common virus that usually does not make you sick. However, PML is related 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 perform a blood test to check if you have antibodies against the JC virus (anti-JC antibodies), which are a sign that you have been infected with the JC virus.

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

• PML symptomscan be similar to those of an MS relapse (see section 4,Adverse reactions). You may also develop PML up to 6months after stopping Tysabri treatment.

Inform your doctor as soon as possibleif you notice that your MS is worsening or if you experience any new symptoms while on Tysabri treatment or up to 6months after.

• Inform your partner or caregiverswhat they should be aware of (also see section4,Adverse reactions). Some symptoms may be difficult to detect on your own, such as mood or behavior changes, confusion, speech and communication difficulties. If you experience any of them,you may need to undergo further tests. Be aware of symptoms during the 6months following Tysabri discontinuation.

• Keep the patient information card that your doctor has given you. Include this information. Show it to your partner or caregivers.

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

• If you have anti-JC antibodiesin your blood. They are a sign that the virus is in your body. You will undergo tests before and during Tysabri treatment.

• If you are receiving prolonged treatmentwith Tysabri, especially if it is for more than two years.

• If you have taken a medication known asimmunosuppressant, which reduces the activity of your immune system.

The JC virus also causes another conditioncalled NCG by JC virus, which has occurred in some patients receiving Tysabri treatment. The symptoms of NCG by JC virus are similar to those of PML.

In the case of patients with lower PML risk, your doctor may repeat the tests periodically to check:

• If you still do not have anti-JC antibodies in your blood.

• If you have received treatment for more than 2years, if you still have a lower level ofanti‑JCantibodies in your blood.

If someone develops PML

PML can be treated, and Tysabri treatment will be discontinued. However, some people experience a reaction when Tysabri is eliminated from the body. This reaction (known as SIRI or immune reconstitution inflammatory syndrome) can make your condition worse, including a decline in brain function.

Be aware of other infections

Other infections, different from PML, can also be severe and may be caused by viruses, bacteria, and other causes.

Inform your doctor or nurse immediatelyif you think you have an infection (also see section4,Adverse reactions).

Changes in blood platelet count

Natalizumab can reduce the number of platelets in the blood, which are responsible for clotting. This can lead to a condition called thrombocytopenia (see section 4) by which your blood may not clot quickly enough to stop bleeding. This can cause the appearance of bruises, as well as more serious problems such as excessive bleeding.Inform your doctor immediately if you experienceunexplained bruises, red or purple spots on the skin (called petechiae), bleeding from cuts on the skin that does not stop or oozes, prolonged bleeding from the gums or nose, blood in the urine or stool, or bleeding in the white part of the eyes.

Children and adolescents

Do not administer this medication to children or adolescents under 18years of age.

Other medications and Tysabri

Inform your doctor if you are using, have used recently, or may need to use any other medication.

• Do not administer this medication if you are currently being treated with medications that affect yourimmune system, including certain medications used to treat MS.

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

Pregnancy and breastfeeding

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

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

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

Driving and operating machinery

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

Tysabri contains sodium

Each vial of this medication contains 2.3mmol (52mg) of sodium. After dilution before use, the medication contains 17.7mmol (406mg) of sodium per dose. You should be aware of this if you are following a low-sodium diet.

Tysabri intravenous infusion should be administered to the patient by a doctor experienced in treating MS. Your doctor may switch you directly to Tysabri for treating your MS if no problems associated with the previous treatment are observed.

• Your doctor will requestblood teststo detect anti-VJC antibodies and other possible issues.

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

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

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

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

• At the end of the prospectus, information is provided on how to prepare and administer the medication intended for medical or healthcare professionals.

If you interrupt Tysabri treatment

Continuous administration of Tysabri is essential, especially during the first months of treatment. It is essential that you continue treatment while you and your doctor decide that it is helping you. Patients who received one or two doses of Tysabri and then took a three-month or longer pause in treatment had a higher probability of experiencing an allergic reaction upon resuming treatment.

Allergic reaction check

Some patients have presented an allergic reaction to this medication. Your doctor may check for allergic reactions during infusion and within 1hour afterwards. See also section4,possible side effects.

If you forgot to use Tysabri

If you did not receive your usual dose of Tysabri, talk to your doctor to have it administered as soon as possible. Afterwards, you can continue receiving Tysabri every four weeks.

Will Tysabri always work?

In some patients receiving Tysabri, the body's natural defenses may prevent the medication from working correctly over time as the body produces antibodies against the medication. Your doctor may decide that this medication is not working correctly for you based on your blood test and will stop treatment if necessary.

If you have any other questions about using Tysabri, ask your doctor.Follow exactly the medication administration instructions contained in this prospectus or those indicated by your doctor. In case of doubt, ask your doctor.

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

Inform your doctor or nurse immediatelyif you notice any of the following symptoms.

Signs of brain infection

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

These symptoms may be due to a brain infection (encephalitis or LMP) or the covering that surrounds it (meningitis).

Signs of other serious infections

• Unexplained fever
• Severe diarrhea
• Lack of breath
• Prolonged dizziness
• Headache
• Weight loss
• Lack of energy
• Visual disturbance
• Pain or redness of the eye(s)

Signs of allergic reaction

• Urticaria(hives)
• Swelling of the face, lips, or tongue
• Difficulty breathing
• Pain or discomfort in the chest
• Increased or decreased blood pressure (your doctor or nurse will advise you if they are monitoring your blood pressure)

It is more likely to occur during or shortly after infusion.

Signs of possible liver problem

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

If you experience any of the side effects described above or if you think you have an infectionconsult your doctor or nurse immediately.Show your patient information card and this leaflet to any doctor or nurse who treats you, not just your neurologist.

Other side effects

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

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

Common(may affect 1 in 10 people)

• Anemia (decrease in the number of red blood cells that may make your skin pale and feel short of breath or lacking in energy)
• Allergy(hypersensitivity)
• Chills
• Urticaria(hives)
• Vomiting
• Fever
• Difficulty breathing(dyspnea)
• Redness of the face or body(flushing)
• Herpes virus infections
• Discomfort around the area where the infusion was administered. It may present with bruises, redness, pain, itching, or swelling

Rare(may affect up to 1 in 1000 people)

• Eye herpes virus infection
• Severe anemia (decrease in the number of red blood cells that may make your skin pale and feel short of breath or lacking in energy)
• Intense swelling under the skin
• High levels of bilirubin in the blood(hyperbilirubinemia)that may cause symptoms such as yellowing of the eyes or skin, fever, and fatigue

Frequency not known(cannot be estimated from available data)

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

Inform your doctor as soon as possibleif you think you have an infection.

You will also find this information on the patient information card that your doctor has given you.

Reporting side effects

If you experienceany type of side effect, consult your doctor, even if it is apossibleside effect that does not appear in this leaflet.You can also report them directly through thenational reporting system included in theAppendix V.By reporting side effects, you can contribute to providing more information about the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the label and the box. The expiration date is the last day of the month indicated.

Unopened vial:

Store in the refrigerator.

Do not freeze.

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

Diluted solution:

It is recommended to use the product immediately after dilution. If not, 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 medication if you observe particles or color changes in the liquid.

Composition of Tysabri

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

The other components are:

Sodium monobasic phosphate monohydrate

Dibasic sodium phosphate heptahydrate

Sodium chloride (see section2 “Tysabri contains sodium”)

Polysorbate 80(E433)

Water for injection

Appearance of the product and contents of the pack

Tysabri is a clear, colorless or slightly turbid liquid.

Each carton contains a glass vial.

Marketing authorization holder and manufacturer

Biogen Netherlands B.V.

Prins Mauritslaan 13

1171 LP Badhoevedorp

Netherlands

For more information about this medicine, please contact the local representative of the marketing authorization holder:

Last update of this leaflet:09/2024

Other sources of information

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

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