Tyrkuko

Package leaflet: Information for the patient

Tyruko 300 mg concentrate for solution for infusion

natalizumab
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before using this medicine because it contains important information for you.
Along with this package leaflet, you will be given a patient alert card containing important safety information that you must know before and during treatment with Tyruko.

• 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 still occur after stopping treatment.
• If you have any questions, consult your doctor.
• If you experience any side effect, including those not listed in this leaflet, consult your doctor. 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). It contains the active substance natalizumab.
This is known as a monoclonal antibody.
MS causes inflammation in the brain that damages nerve cells. This inflammation
occurs when white blood cells enter the brain and spinal cord. This medicine
prevents white blood cells from reaching the brain. This reduces nerve damage caused by
MS.
Symptoms of multiple sclerosis
MS symptoms vary from patient to patient, and you may experience some or none
at all.
They may include: problems walking, a sensation of numbness in the face, arms or legs, vision problems, fatigue, loss of balance or mental fogginess, bladder and bowel problems, difficulties with thinking and concentration, depression, acute or chronic pain, sexual problems, muscle stiffness and spasms. When symptoms flare up, this is known as a relapse (also called an exacerbation or attack). During a relapse, you may notice your symptoms suddenly worsen within a few hours, or gradually over several days. Usually, symptoms then gradually improve (this is known as remission).
How Tyruko can help
In studies, this medicine reduced the progression of MS-related disability by about half,
and reduced the number of MS attacks by approximately two-thirds. During treatment with this
medicine, you may not notice any effect on your MS, but it may help prevent the disease from worsening.

2. What you need to know before receiving Tyruko

Before starting treatment with this medicine, it is important that you discuss with your doctor the potential benefits you may receive from the treatment and the risks associated with it.
Tyruko must not be given to you

• 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 an uncommon brain infection.
• If you have a serious problem affecting your immune system. This could be caused by a disease (such as HIV), or by a medicine you are taking, or have taken in the past (see below).
• If you are taking medicines that affect the immune system, including some medicines used to treat MS. These medicines cannot be used together with Tyruko.
• If you have cancer (unless it is a type of skin cancer called basal cell carcinoma).

Warnings and precautions
You must discuss with your doctor whether Tyruko is the most suitable treatment for you.
This should be done before starting Tyruko and again after you have received Tyruko for more than 2 years.
Possible brain infection (PML)
Some people receiving this medicine (less than 1 in 100) have developed a rare brain infection called progressive multifocal leukoencephalopathy (PML). PML can cause severe disability or be fatal.

• Before starting treatment, all patients will undergo blood tests arranged by the doctor to check for JC virus infection. The JC virus is a common virus that normally does not cause illness. However, PML is linked to an increase in 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 determine whether you have antibodies against the JC virus, which indicate that you have a JC virus infection.
• Your doctor will schedule 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 develop PML up to 6 months after stopping treatment with Tyruko.
• Speak to your doctor as soon as possible if you notice worsening of MS symptoms, or any new symptoms during treatment with Tyruko or up to 6 months after stopping treatment.
• Talk to your partner or caregivers about what to watch for (see also section 4, Possible side effects). Some symptoms may be difficult to detect yourself, such as changes in mood or behavior, confusion, or problems with language and communication. If you develop any of these symptoms, you may need further tests. Continue to monitor for symptoms for 6 months after stopping treatment with Tyruko.
• Keep the patient alert card given to you 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 JC virus antibodies in your blood. These indicate that the virus is present in your body. You will be tested before and during treatment with Tyruko.
• if you have been treated for a long time with Tyruko, especially for more than two years.
• if you have taken a medicine called an immunosuppressant that reduces the activity of your immune system.

Another condition, called JC virus granule cell neuronopathy (JCV GCN), is also caused by the JC virus and has occurred in some patients treated with Tyruko. Symptoms of JCV GCN are similar to those of PML.
Your doctor may repeat testing regularly for those at lower risk of PML to confirm that:

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

If someone develops PML
PML can be treated and treatment with Tyruko will be stopped. However, some people develop a reaction when Tyruko is cleared from the body. This reaction (known as IRIS or immune reconstitution inflammatory syndrome) may worsen their condition, including worsening of brain function.
Monitoring for other infections
Other infections besides PML may also be serious and may be caused by viruses, bacteria, or other agents.
Speak to a doctor or nurse if you think you have an infection (see also section 4, Possible side effects).
Changes in blood platelets
Natalizumab may reduce the number of platelets, which are responsible for blood clotting. This could lead to a condition called thrombocytopenia (see section 4), which causes blood to clot too slowly to stop bleeding. This condition may in turn cause unexplained bruising and other more serious problems such as excessive bleeding. Contact a doctor immediately if you notice unexplained bruising, red or purple skin spots (called petechiae), bleeding from cuts that does not stop or oozes, prolonged gum or nose bleeding, blood in urine or stools, or 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 Tyruko
Tell your doctor if you are taking, have recently taken, or might take any other medicine.

• Do not be given this medicine if you are currently taking medicines that affect 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 past medicines that affect the immune system.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor before taking this medicine.

• Do not use this medicine during pregnancy unless you have discussed it with your doctor. Inform your doctor immediately if you become pregnant, suspect you are pregnant, or intend to become pregnant.
• Do not breastfeed during treatment with Tyruko. Your doctor will help you decide whether to stop breastfeeding or to stop using the medicine.

The risk to the child and the benefit to the mother will be considered by your doctor.
Driving and using machines
Dizziness is a very common side effect. If you experience dizziness, do not drive or operate machinery.
Tyruko 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 take this information into account if you are on a low-sodium diet.
Tyruko contains polysorbates
This medicine contains 3.0 mg of polysorbate 80 (E 433) per vial, equivalent to 3.0 mg/15 mL. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How Tyruko is administered

The intravenous infusion of Tyruko will be administered to you by a doctor specialized in the treatment of MS. Your doctor may prescribe a direct switch from another MS medicine to Tyruko, if there are no problems caused by the previous treatment.

• Your doctor will order a blood test for JC virus antibodies and other possible issues.
• Your doctor will perform an MRI which will be repeated during treatment.
• When switching from certain MS medicines, your doctor may advise you to wait a certain period to ensure that most of the previous medicine has been eliminated from your body.
• For adults, the recommended dose is 300 mg, administered once every 4 weeks.
• Before administration, Tyruko must be diluted. It is given into a vein through an intravenous infusion, usually in the arm. The infusion lasts about 1 hour.
• Information for doctors and healthcare professionals on how to prepare and administer this medicine is provided at the end of this leaflet.

If you stop treatment with Tyruko
Taking Tyruko regularly is important, especially during the first months of treatment. It is important that you continue treatment for as long as you and your doctor consider it beneficial. Patients who have received one or two doses of Tyruko and then stopped treatment for three months or more have shown a higher likelihood of developing an allergic reaction if treatment is restarted.

Monitoring for allergic reactions
Some patients have experienced an allergic reaction to this medicine. Your doctor may monitor you for possible allergic reactions during the infusion and for one hour afterwards. See also section 4, Possible side effects.

If you forget to take Tyruko
If you miss your scheduled dose of Tyruko, contact your doctor to arrange to receive it as soon as possible. After that, you should continue receiving your Tyruko dose every 4 weeks.

Will Tyruko always work?
In some patients treated with Tyruko, over time the body's natural defenses may prevent the medicine from working properly. Your doctor may determine whether this medicine is not working as expected through blood tests and, if necessary, will discontinue treatment.

For further information on the use of Tyruko, please consult your doctor. Always use this medicine exactly as stated in this leaflet or as instructed by your doctor. If you have any doubts, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
Immediately inform your doctor or nurse if 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
• epileptic seizures (fits)
• headache
• nausea/vomiting
• neck stiffness
• extreme sensitivity to bright light
• fever
• rash (anywhere on the body)

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

Signs of other serious infections:

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

Signs of an allergic reaction:

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

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 (jaundice)
• unusually dark urine
• abnormal liver function tests

Contact a doctor or nurse immediately if you experience any of the side effects listed above or if you think you may have an infection. Show your patient alert card and this leaflet to any doctor or nurse treating you, not only to your neurologist.

Other side effects

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

• urinary tract infection
• sore throat and increased mucus production or nasal congestion
• headache
• dizziness
• feeling sick (nausea)
• joint pain
• fatigue
• dizziness, feeling sick (nausea), itching, and chills during or shortly after infusion

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

• anaemia (reduction in red blood cells which may make the skin pale and cause breathlessness or lack of energy)
• allergy (hypersensitivity)
• chills
• urticaria
• feeling unwell (vomiting)
• fever
• breathing difficulty (dyspnoea)
• redness of the face and body (flushing)
• herpes infection
• discomfort at the infusion site. You may experience bruising, redness, pain, itching, or swelling

Uncommon (may affect up to 1 in 100 people):

• severe allergic reaction (anaphylactic reaction)
• progressive multifocal leukoencephalopathy (PML)
• inflammatory disorder after stopping the medicine
• facial swelling
• increased number of white blood cells (eosinophilia)
• reduced number of platelets in the blood
• easy bruising (purpura)

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

• herpes infection in the eye
• severe anaemia (reduction in red blood cells which may make the skin 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

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

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

Contact your doctor as soon as possible if you think you may have an infection.
You can also find this information on the patient alert card provided by your doctor.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, contact your doctor. You may also report side effects directly via the national reporting system listed in Annex V. Reporting side effects helps provide more information on the safety of this medicine.

5. How to store 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 that month.
Unopened vial:
Store in the 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 after dilution.
Do not use this medicine if you notice particles in the liquid and/or if the liquid in the vial has changed in colour.

6. Package contents and other information

What Tyruko contains
The active substance 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 components are:
sodium chloride (see section 2 'Tyruko contains sodium')
histidine
monohydrochloride histidine
polysorbate 80 (E 433) (see section 2 'Tyruko contains polysorbates')
water for injections

Description of the appearance of Tyruko and contents of the pack
Tyruko is a colourless, sterile solution ranging from clear to slightly opalescent (concentrate).
Each carton contains one glass vial.

Marketing Authorisation Holder and Manufacturer
Sandoz GmbH
Biochemiestrasse 10
6250 Kundl
Austria

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

België/Belgique/Belgien Latvija
Sandoz nv/sa Sandoz d.d. Latvia filiāle
Tél/Tel: +32 2 722 97 97 Tel: +371 67 892 006

България Lietuva
Сандоз България КЧТ Sandoz Pharmaceuticals d.d filialas
Тел.: +359 2 970 47 47 Tel: +370 5 2636 037

Česká republika Luxembourg/Luxemburg
Sandoz s.r.o. Sandoz nv/sa (Belgique/Belgien)
Tel: +420 234 142 222 Tél/Tel: +32 2 722 97 97

Danmark/Norge/Ísland/Sverige Magyarország
Sandoz A/S Sandoz Hungária Kft.
Tlf./Tlf/Sími/Tel: +45 63 95 10 00 Tel.: +36 1 430 2890

Deutschland Malta
Hexal AG Sandoz Pharmaceuticals d.d.
Tel: +49 8024 908 0 Tel: +356 99644126

Eesti Nederland
Sandoz d.d. Eesti filiaal Sandoz B.V.
Tel: +372 665 2400 Tel: +31 36 52 41 600

Ελλάδα Österreich
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε. Sandoz GmbH
Τηλ: +30 216 600 5000 Tel: +43 5338 2000

España Polska
Sandoz Farmacéutica, S.A. Sandoz Polska Sp. z o.o.
Tel: +34 900 456 856 Tel.: +48 22 209 70 00

France Portugal
Sandoz SAS Sandoz Farmacêutica Lda.
Tél: +33 1 49 64 48 00 Tel: +351 21 000 86 00

Hrvatska România
Sandoz d.o.o. Sandoz Pharmaceuticals SRL
Tel: +385 1 23 53 111 Tel: +40 21 407 51 60

Ireland Slovenija
Rowex Ltd. Sandoz farmacevtska družba d.d.
Tel: +353 27 50077 Tel: +386 1 580 29 02

Italia Slovenská republika
Sandoz S.p.A. Sandoz d.d. - organizačná zložka
Tel: +39 02 81280696 Tel: +421 2 48 200 600

Κύπρος Suomi/Finland
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε. Sandoz A/S
(Greece) Puh/Tel: +358 10 6133 400
Τηλ: +30 216 600 5000

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

The following information is intended for healthcare professionals only:

1. Prior to dilution and administration, inspect the Tyruko vial to ensure the absence of particles. If particles are present and/or if the liquid in the vial does not appear colourless, from clear to slightly opalescent, the vial must not be used.
2. Use an aseptic technique for the preparation of the medicinal product. Remove the flip-top cap from the vial. Insert the needle of the syringe through the centre of the rubber stopper and withdraw 15 mL of concentrate for infusion solution.
3. Add the 15 mL of concentrate for infusion solution to 100 mL of sodium chloride 9 mg/mL (0.9%) solution for injection. Gently invert the solution to ensure complete mixing. Do not shake.
4. Tyruko must not be mixed with other medicinal products or diluents.
5. Prior to administration, visually inspect the diluted product for the presence of particles and discoloration. Do not use the medicinal product if discoloration is observed or if particulate matter is present.
6. The diluted medicinal product should be used as soon as possible and within 24 hours after dilution. If the diluted medicinal product is stored at a temperature between 2 °C and 8 °C (do not freeze), allow the solution to reach room temperature before infusion.
7. The diluted solution should be administered by intravenous infusion 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%) solution for injection.
9. Each vial is for single use only.
10. To improve traceability of biological medicinal products, the name and batch number of the administered medicinal product should be clearly recorded.
11. Unused medicinal product and waste materials derived from such medicinal product should be disposed of in accordance with local regulations.