Tyruko 300 mg concentrate for solution for infusion

Patient Information Leaflet

Introduction

Patient Information Leaflet

Tyruko 300mg concentrate for solution for infusion

natalizumab

This medicinal product is subject to additional monitoring, which will enable rapid identification of new safety information. You can help by reporting any side effects you may experience. Information on how to report side effects is included at the end of section 4.

Read this entire leaflet carefully before starting to use this medicine, because it contains important information for you.

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

• Keep this leaflet and the patient alert card, as you may need to read them again. Keep the leaflet and 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 treatment has been stopped.
• If you have any questions, consult your doctor.
• If you experience any side effects, consult your doctor, even if they are side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

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

1. What Tyruko is and what it is used for

Tyruko 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

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

They may include: difficulty walking, tingling in the face, arms, or legs; vision problems; fatigue; feelings of 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 flare-up). During a relapse, you may notice symptoms suddenly, within a few hours, or they may progress slowly over several days. Symptoms usually improve gradually (this is known as remission).

How Tyruko can help

In clinical trials, this medicine reduced the progression of disability caused by MS by approximately half and reduced the number of MS relapses by about two-thirds. While you are receiving 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 Tyruko

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 Tyruko

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

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

• If 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 must not be used with Tyruko.

• 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 Tyruko is the most appropriate treatment for you. Do this before starting Tyruko and after you have been receiving it for more than two years.

Possible brain infection (PML)

Some people receiving this medicine (fewer than 1 in 100) have developed a rare brain infection called PML (progressive multifocal leukoencephalopathy). PML can cause 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 increased JC virus in the brain. The reason for this increase in some patients treated with Tyruko is not clear. Before and during treatment, your doctor will perform blood tests to check whether you have antibodies against the JC virus (anti-JCV antibodies), which are a sign that you have been infected with the JC virus.

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

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

• Tell your doctor as soon as possible if you notice your MS worsening or if you experience any new symptoms while on Tyruko treatment or up to 6 months after stopping.

• 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, and speech or communication difficulties. If you experience any of these, you may need further testing. Remain vigilant for symptoms for 6 months after stopping Tyruko.

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

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

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

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

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

The JC virus can also cause another condition called JCV GCN (granule cell neuronopathy due to JC virus), which has occurred in some patients receiving Tyruko. The symptoms of JCV GCN are similar to those of PML.

For patients at lower risk of PML, your doctor may repeat blood 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 Tyruko will be stopped. However, some people experience a reaction when Tyruko is cleared from the body. This reaction (known as IRIS or immune reconstitution inflammatory syndrome) may worsen your condition, including worsening brain function.

Be alert for other infections

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

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

Changes in platelet count in blood

Natalizumab may reduce the number of platelets in your 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 develop unexplained bruising, red or purple spots on the skin (called petechiae), bleeding from cuts that does not stop or oozes, prolonged bleeding from gums or nose, blood in your urine or stools, or bleeding in the white part of the eyes.

Children and adolescents

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

Other medicines and Tyruko

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

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

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

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, talk to your doctor before using this medicine.

• 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 Tyruko. Your doctor will help you decide whether to stop breastfeeding or stop using the medicine.

Your doctor will consider the risk to the baby and the benefit to the mother.

Driving and using machines

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

Tyruko contains sodium

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

Tyruko contains polysorbates

This medicine contains 3.0 mg of polysorbate 80 (E 433) in each vial, equivalent to 3.0 mg/15 ml. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergies.

3. How Tyruko is administered

Tyruko intravenous infusion must be administered to the patient by a physician experienced in the treatment of MS. Your physician may directly switch your current MS treatment to Tyruko if no issues related to the previous treatment are observed.

• Your physician will request blood tests to detect anti-JCV antibodies and other potential problems.

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

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

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

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

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

If you interrupt treatment with Tyruko

Continuous administration of Tyruko is important, especially during the first few months of treatment. It is important to continue treatment as long as you and your physician determine it is benefiting you. Patients who received one or two doses of Tyruko and then paused treatment for three months or longer 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 medicine. Your physician may monitor you for allergic reactions during the infusion and for 1 hour afterward. See also section 4, Possible side effects.

If you forget to use Tyruko

If you miss your scheduled dose of Tyruko, speak with your physician so it can be administered as soon as possible. After that, you may continue receiving Tyruko every four weeks.

Will Tyruko always work?

In some patients receiving Tyruko, the body's natural defenses may interfere over time with the medicine's effectiveness, as the body produces antibodies against the drug. Your physician may determine whether the medicine is no longer working properly based on your blood tests and may discontinue treatment if necessary.

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

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
• Stiff neck
• Extreme sensitivity to bright light
• Fever
• Skin rash (anywhere on the body)

These symptoms may be due to an infection of the brain (encephalitis or PML) or of the membrane covering 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
• Chest pain or discomfort
• 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 infusion.

Signs of a possible liver problem

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

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

Other adverse effects

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

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

Common (may affect up to 1 in 10 people)

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

Uncommon (may affect up to 1 in 100 people)

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

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

• Herpes virus infection in the eye
• Severe anaemia (reduced number of red blood cells which may make your skin look pale and cause breathlessness or lack of energy)
• Severe swelling under the skin
• High levels of bilirubin in the blood (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 (so-called “opportunistic infections”)
• Liver damage

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

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

Reporting of adverse effects

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

5. Storage of Tyruko

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

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

Unopened vial:

Store in the refrigerator. Do not freeze.

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

Diluted solution:

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

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

6. Contents of the pack and other information

Composition of Tyruko

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

The other components are:

Sodium chloride (see section 2 "Tyruko contains sodium")

Histidine

Histidine monohydrochloride

Polysorbate 80 (E 433) (see section 2 "Tyruko contains polysorbates")

Water for injections

Nature and contents of the container

Tyruko is a sterile, colourless concentrate solution, ranging from transparent to slightly opalescent.

Each carton pack contains one glass vial.

Marketing Authorization Holder and Manufacturer

Sandoz GmbH

Biochemiestrasse 10

6250 Kundl

Austria

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

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: http://www.ema.europa.eu.

This information is intended for healthcare professionals only:

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

2. Use an aseptic technique when preparing the medicine. Remove the flip-off cap from the vial. Insert the syringe needle into the vial through the centre of the stopper, and withdraw 15 ml of concentrate for 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%) injection solution. Gently invert the solution to ensure complete mixing. Do not shake.

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

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

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

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

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

9. Vials are for single use only.

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

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