Tysabri
natalizumab
natalizumab
In addition to this leaflet you will be given a patient alert card. This contains important safety information that you need to know before and during treatment with Tysabri.
Keep this leaflet and the patient alert card. 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 you have stopped treatment.
If you have any further questions, ask your doctor.
If you get any side effects talk to your doctor. This includes any possible side effects not listed in this leaflet. See section 4.
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 the nerve cells. This inflammation happens when white blood cells get into the brain and spinal cord. This medicine stops the white blood cells getting through to the brain. This reduces nerve damage caused by MS.
The symptoms of MS vary from patient to patient, and you may experience some or none of them.
When the symptoms flare up, it is called a relapse (also known as an exacerbation or an attack). When a relapse occurs, you may notice the symptoms suddenly, within a few hours, or slowly progressing
over several days. Your symptoms will then usually improve gradually (this is called a remission).
In trials, this medicine approximately halved the build-up of disability caused by MS, and decreased the number of MS attacks by about two-thirds. While you are treated with this medicine you might not notice any improvement, but it may still be working to prevent your MS becoming worse.
Before you start treatment with this medicine, it is important that you and your doctor have discussed the benefits you could expect to receive from this treatment and the risks that are associated with it.
If you are allergic to natalizumab or any of the other ingredients of this medicine (listed in section 6).
If you have been diagnosed with PML (progressive multifocal leukoencephalopathy). PML is an uncommon infection of the brain.
If your immune system has a serious problem. This may be due to disease (such as HIV), or to a medicine you are taking, or have taken in the past (see below).
If you are taking medicines that affect your immune system, including certain other medicines used to treat MS. These medicines cannot be used with Tysabri.
If you have cancer (unless it is a type of skin cancer called basal cell carcinoma).
Some people receiving this medicine (fewer than 1 in 100) have had an uncommon brain infection called PML (progressive multifocal leukoencephalopathy). PML can lead to severe disability or death.
Before starting treatment, all patients will have blood tests arranged by the doctor for JC virus infection. JC virus is a common virus that does not normally make you ill. However, PML is linked to an increase of 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 the JC virus, which are a sign that you have been infected by the JC virus.
Your doctor will arrange a Magnetic Resonance Imaging (MRI) scan, which will be repeated during treatment to rule out PML.
The symptoms of PML may be similar to an MS relapse (see section 4, Possible side effects).
You can also get PML up to 6 months after stopping Tysabri treatment.
Tell your partner or caregivers about what to look out for (see also section 4, Possible side effects). Some symptoms might be difficult to spot by yourself, such as changes in mood or behaviour, confusion, speech and communication difficulties. If you get any of these, you may need further tests. Keep looking out for symptoms in the 6 months after stopping Tysabri.
Keep the patient alert card you have been given by your doctor. It includes this information.
Show it to your partner or caregivers.
Another condition, called JCV GCN (JC virus granule cell neuronopathy), is also caused by JC virus and has occurred in some patients receiving Tysabri. The symptoms of JCV GNC are similar to PML.
You still do not have antibodies to the JC virus in your blood.
If you have been treated for more than 2 years, you still have a lower level of JC virus antibodies in your blood.
PML can be treated, and Tysabri treatment will be stopped. However, some people get a reaction as Tysabri is removed from the body. This reaction (known as IRIS or immune reconstitution
inflammatory syndrome) may lead to your condition getting worse, including worsening of brain
function.
Some infections other than PML may also be serious and can be due to viruses, bacteria, and other causes.
Tell a doctor or nurse immediately if you think you have an infection (see also section 4, Possible side effects).
Natalizumab may reduce platelets in the blood which are responsible for clotting. This may result in a condition called thrombocytopenia (see section 4) in which your blood may not clot quickly enough to stop bleeding. This can lead to bruising as well as other more serious problems such as excessive bleeding. You should talk to your doctor immediately if you have unexplained bruising, red or purple spots on the skin (called petechiae), bleeding from skin cuts that does not stop or oozes, prolonged bleeding from the gums or nose, blood in urine or stools, or bleeding in the whites of your eyes.
Do not give this medicine to children or adolescents under the age of 18 years.
Tell your doctor if you are taking, have recently taken or might take any other medicines.
You must not be given this medicine if you are now being treated with medicines that affect your immune system, including certain other medicines to treat your MS.
You might not be able to use this medicine if you have previously had any that affect your immune system.
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. The risk to the baby and benefit to the mother will be taken into consideration by your doctor.
Dizziness is a very common side effect. If you are affected, do not drive or use machines.
Each vial of this medicine contains 2.3 mmol (or 52 mg) of sodium. After dilution for use, this medicinal product contains 17.7 mmol (or 406 mg) sodium per dose. This should be considered if you
are on a controlled sodium diet.
Tysabri IV infusion will be given to you by a doctor experienced in the treatment of MS. Your doctor may switch you directly from another medicine for MS to Tysabri if there are no problems caused by your previous treatment.
Your doctor will order blood tests for antibodies to the JC virus and other possible problems.
Your doctor will arrange an MRI scan, which will be repeated during treatment.
For adults the recommended dose is 300 mg, given once every 4 weeks.
Tysabri must be diluted before it is given to you. It is given as a drip into a vein (by intravenous infusion), usually in your arm. This takes about 1 hour.
Information for medical or healthcare professionals on how to prepare and administer the medicine is provided at the end of this leaflet.
Regular dosing with Tysabri is important, especially in the first few months of treatment. It is important to continue with your medicine for as long as you and your doctor decide that it is helping you. Patients who received one or two doses of Tysabri, and then had a gap in treatment of three months or more, were more likely to have an allergic reaction when restarting treatment.
A few patients have had an allergic reaction to this medicine. Your doctor may check for allergic reactions during the infusion and for 1 hour afterwards. See also section 4, Possible side effects.
If you miss your usual dose of Tysabri, arrange with your doctor to receive it as soon as you can. You can then continue to receive your dose of Tysabri every 4 weeks.
In a few patients receiving Tysabri, the body’s natural defences may stop the medicine from working properly over time, as the body develops antibodies to the medicine. Your doctor can decide whether
this medicine is not working properly for you from blood tests and will stop the treatment, if necessary.
If you have any further questions on Tysabri, ask your doctor. Always use this medicine exactly as described in this leaflet or as your doctor has told you. Check with your doctor if you are not sure.
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Changes in personality and behaviour such as confusion, delirium or loss of consciousness,
Seizures (fits)
Headache
Nausea / vomiting
Stiff neck
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 its covering layer (meningitis).
An unexplained fever
Severe diarrhoea
Shortness of breath
Prolonged dizziness
Headache
Weight loss
Listlessness
Impaired vision
Pain or redness of the eye(s)
Itchy rash (hives)
Swelling of your face, lips or tongue
Difficulty breathing
Chest pain or discomfort
Increase or decrease in your blood pressure (your doctor or nurse will notice this if they are monitoring your blood pressure)
These are most likely during or shortly after the infusion.
Yellowing of your skin or the whites of your eyes
Unusual darkening of the urine
Abnormal liver function test
Urinary tract infection
Sore throat and runny or blocked up nose
Headache
Dizziness
Feeling sick (nausea)
Joint pain
Tiredness
Dizziness, feeling sick (nausea), itching and chills during or shortly after infusion
Anaemia (decrease in your red blood cells which can make your skin pale and can make you feel breathless or lacking energy)
Allergy (hypersensitivity)
Shivering
Itchy rash (hives)
Being sick (vomiting)
Fever
Difficulty breathing (dyspnoea)
Reddening of the face or body (flushing)
Herpes infections
Discomfort around the place you have had your infusion. You could experience bruising, redness, pain, itching or swelling
Severe allergy (anaphylactic reaction)
Progressive multifocal leukoencephalopathy (PML)
Inflammatory disorder after discontinuation of the medicinal product
Facial swelling
An increase in the number of white blood cells (eosinophilia)
Reduction in blood platelets
Easy bruising (purpura)
Herpes infection in the eye
Severe anaemia (decrease in your red blood cells which can make your skin pale and can make you feel breathless or lacking energy).
Severe swelling under the skin
High levels of bilirubin in the blood (hyperbilirubinaemia) which may cause symptoms such as yellowing of your eyes or skin, fever and tiredness
Unusual infections (so-called “opportunistic infections”)
Damage to your liver
You will also find this information in the patient alert card you have been given by your doctor.
By reporting side effects you can help provide more information on the safety of this medicine.
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.
Store in a refrigerator . Do not freeze.
Keep the vial in the outer carton in order to protect from light.
After dilution, immediate use is recommended. If not used immediately, the diluted solution must be
stored at 2˚C to 8˚C and infused within 8 hours of dilution.
Do not use this medicine if you notice particles in the liquid and/or the liquid in the vial is discoloured.
The active substance is natalizumab. Each 15 mL vial of concentrate contains 300 mg natalizumab (20 mg per mL). When diluted, the solution for infusion contains approximately 2.6 mg per 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
Biogen Netherlands B.V. Prins Mauritslaan 13
1171 LP Badhoevedorp
The Netherlands
FUJIFILM Diosynth Biotechnologies Denmark ApS Biotek Allé 1
DK-3400 Hillerød
Denmark
Biogen Netherlands B.V. | ||
Prins Mauritslaan 13 | ||
1171 LP Badhoevedorp | ||
The Netherlands | ||
For any further information about this medicine, please contact the local representative of the Marketing Authorisation Holder.
Biogen Lithuania UAB Tel: +370 5 259 6176
ТП ЕВОФАРМА
Teл.: +359 2 962 12 00
Biogen (Czech Republic) s.r.o. Tel: +420 255 706 200
Biogen Hungary Kft. Tel.: +36 (1) 899 9883
Biogen (Denmark) A/S Tlf: +45 77 41 57 57
Pharma MT limited Tel: +356 213 37008/9
Biogen GmbH
Tel: +49 (0) 89 99 6170
Biogen Netherlands B.V. Tel: +31 20 542 2000
Biogen Estonia OÜ Tel: +372 618 9551
Biogen Norway AS Tlf: +47 23 40 01 00
Genesis Pharma SA
Τηλ: +30 210 8771500
Biogen Austria GmbH Tel: +43 1 484 46 13
Biogen Spain SL Tel: +34 91 310 7110
Biogen Poland Sp. z o.o.
Tel.: +48 22 351 51 00
Biogen France SAS
Tél: +33 (0)1 41 37 95 95
Biogen Portugal Sociedade Farmacêutica Unipessoal, Lda
Tel: +351 21 318 8450
Biogen Pharma d.o.o. Tel: +358 (0) 1 775 73 22
Johnson & Johnson Romania S.R.L. Tel: +40 21 207 18 00
Biogen Idec (Ireland) Ltd. Tel: +353 (0)1 463 7799
Biogen Pharma d.o.o. Tel: +386 1 511 02 90
Icepharma hf
Sími: +354 540 8000
Biogen Italia s.r.l. Tel: +39 02 584 9901
Biogen Finland Oy Puh/Tel: +358 207 401 200
Genesis Pharma (Cyprus) Ltd
Τηλ: +357 22 76 57 15
Biogen Sweden AB Tel: +46 8 594 113 60
Biogen Latvia SIA Tel: +371 68 688 158
Biogen Idec (Ireland) Limited Tel: +44 (0) 1628 50 1000
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Inspect the Tysabri vial for particles prior to dilution and administration. If particles are observed and/or the liquid in the vial is not colourless, clear to slightly opalescent, the vial must not be used.
Use aseptic technique when preparing the medicine. Remove flip-top from the vial. Insert the syringe needle into the vial through the centre of the rubber stopper and remove 15 mL concentrate for solution for infusion.
Add the 15 mL concentrate for solution for infusion to 100 mL sodium chloride 9 mg/mL (0.9%) solution for injection. Gently invert the solution to mix completely. Do not shake.
4. Tysabri must not be mixed with other medicinal products or diluents.
Visually inspect the diluted medicinal product for particles or discolouration prior to administration. Do not use if it is discoloured or if foreign particles are seen.
The diluted medicinal product is to be used as soon as possible and within 8 hours of dilution. If the diluted medicinal product is stored at 2 to 8°C (do not freeze), allow the solution to warm to room temperature prior to infusion.
The diluted solution is to be infused intravenously over 1 hour at a rate of approximately 2 mL per minute.
After the infusion is complete, flush the intravenous line with sodium chloride 9 mg/mL (0.9%) solution for injection.
Each vial is for single–use only.
In order to improve traceability of biological medicinal products, the product name (Tysabri) and batch number of the administered product should be clearly recorded.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.