Tysabri

Natalizumab.

Each 15 ml vial of concentrate contains 300 mg natalizumab (20 mg/‍ml). When diluted, the solution for infusion contains approximately 2.6 mg/ml of natalizumab.
Excipients/Inactive Ingredients: Sodium phosphate, monobasic, monohydrate; Sodium phosphate, dibasic, heptahydrate; Sodium chloride (see Precautions); Polysorbate 80 (E433); Water for injections.

TYSABRI contains the active substance (natalizumab). This active ingredient is called a monoclonal antibody. These antibodies work by binding to proteins in the body so that the harmful effect of that protein is removed.
Multiple sclerosis (MS) causes inflammation in the brain that damages the nerve cells. TYSABRI stops the cells that cause inflammation from going into the brain. This reduces nerve damage caused by MS.
Symptoms of multiple sclerosis: The symptoms of MS vary from patient to patient, and the patient may experience some or none of them.
Symptoms can include: walking problems, numbness in the face, arms or legs, problems seeing things, tiredness, feeling off-balance or light headed, bladder and bowel problems, difficulty in thinking and concentrating, depression, acute or chronic pain, sexual problems, and stiffness and muscle spasms. When the symptoms flare up, it is called a relapse (also known as an exacerbation or an attack). When a relapse occurs, the patient may notice the symptoms suddenly, within a few hours, or slowly progressing over several days. The symptoms will then usually improve gradually (this is called a remission).
In clinical trials, TYSABRI approximately halved the progression of the disabling effects of MS and also decreased the number of MS attacks by about two-thirds. When the patient receives TYSABRI he/she might not notice any improvement, but TYSABRI may still be working to prevent the MS becoming worse.

TYSABRI is used to treat multiple sclerosis (MS).

TYSABRI will be given by a doctor experienced in the treatment of MS.
Always use this medicine exactly as the doctor has prescribed. Check with the doctor if not sure.
The recommended dose for adults is 300 mg given once every 4 weeks.
TYSABRI must be diluted before it is given. It is given as a drip into a vein (by intravenous infusion), usually in the arm. This takes about 1 hour.
Information for medical or healthcare professionals on how to prepare and administer TYSABRI is provided at Cautions for Usage.
It is important to continue with the medicine for as long as the patient and the doctor decide that it is helping. Continuous dosing with TYSABRI is important, especially during the first few months of treatment. This is because 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 resuming treatment.
If the patient misses the dose of TYSABRI: If the patient misses the usual dose of TYSABRI, arrange with the doctor to receive it as soon as possible. The patient can then continue to receive the dose of TYSABRI every 4 weeks.
Always use this medicine exactly as described previously or as the doctor has prescribed. Check with the doctor if not sure.
For any further questions on TYSABRI, ask the doctor.

Do not use TYSABRI: If the patient is allergic to natalizumab or any of the other ingredients of this medicine (listed Description).
If doctor has told the patient that he/she has PML (progressive multifocal leukoencephalopathy). PML is a rare infection of the brain.
If the doctor tells the patient that he/she has a serious problem with the immune system (due to disease for example, HIV or due to a medicine the patient is taking or has previously taken, e.g. mitoxantrone or cyclophosphamide).
If the patient is taking either beta-interferon or glatiramer acetate. These medicines are for MS and cannot be used with TYSABRI (see Interactions).
If the patient has an active cancer (unless it is a type of skin cancer called basal cell carcinoma).
If the patient is under 18 years of age.

Infections: Tell the doctor immediately if the patient has, or thinks he/she has, any sort of infection (see Side Effects). Some infections other than PML may also be serious and can be due to viruses, bacteria, or other causes.
There have been cases of a rare brain infection called PML (progressive multifocal leukoencephalopathy) that have occurred in patients who have been given TYSABRI. PML may lead to severe disability or death.
The symptoms of PML may be similar to an MS relapse (e.g. weakness or visual changes). Therefore, if the patient believes the MS is getting worse or if he/she notices any new symptoms while on TYSABRI treatment or for up to 6 months after stopping TYSABRI treatment, it is very important that the patient speak to the doctor as soon as possible.
Speak with the partner or caregivers and inform them about the treatment. Symptoms might arise that the patient might not become aware of by himself/herself, such as changes in mood or behaviour, memory lapses, speech and communication difficulties, which the doctor may need to investigate further to rule out PML. The patient should remain aware for symptoms that might arise for up to 6 months after stopping TYSABRI treatment.
The patient will also find this information in the Patient Alert Card he/she has been given by the doctor. It is important to keep this Alert Card and show it to the patient's partner or caregivers.
PML is associated with an uncontrolled increase of the JC virus in the brain, although the reason for this increase in some patients treated with TYSABRI is unknown. A condition called JCV GCN (JC virus granule cell neuronopathy) is also caused by JC virus and has occurred in some patients who have been given TYSABRI. The symptoms of JCV GCN are similar to PML. JC virus is a common virus which infects many people but does not normally cause noticeable illness.
The doctor may test the blood to check if the patient has antibodies to the JC virus before he/she starts treatment with TYSABRI. These antibodies are a sign that the patient has been infected by JC virus. The doctor may repeat this blood test while the patient is on TYSABRI treatment to check if anything has changed.
The risk of PML with TYSABRI is higher: If the patient has antibodies to the JC virus in the blood.
The longer that the patient is on treatment especially if he/she has been on treatment for more than two years.
If the patient has previously taken a medicine called an immunosuppressant. These medicines reduce the activity of the body's immune system.
If the patient has all three risks described previously, the chance of getting PML is higher.
If the patient has previously not been treated with immunosuppressants and has received TYSABRI for 2 years or longer, the level of the anti-JCV antibody response may be associated with the risk of getting PML.
For those with a lower risk of PML, the doctor may repeat the test regularly to check if anything has changed if: If the patient does not have antibodies to the JC virus in the blood OR; if the patient has been treated for more than 2 years and he/she has a lower level of JCV antibodies in the blood.
Discuss with the doctor if TYSABRI is the most suitable treatment for the patient before he/she starts taking TYSABRI and when he/she has been taking TYSABRI for more than two years.
In patients with PML a reaction known as IRIS (Immune Reconstitution Inflammatory Syndrome) is likely to occur after treatment for PML, as TYSABRI is removed from the body. IRIS may lead to the condition getting worse, including worsening of brain function.
Allergic reactions: A few patients have had an allergic reaction to TYSABRI. The doctor will check for allergic reactions during the infusion and for 1 hour afterwards.
Will TYSABRI always work?: In a few patients who use TYSABRI, over time the body's natural defence may stop TYSABRI from working properly (the body develops antibodies to TYSABRI). The doctor can decide whether TYSABRI is not working properly for the patient by testing the blood and will stop TYSABRI, if necessary.
TYSABRI contains sodium: Each vial of TYSABRI 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 the patient is on a controlled sodium diet.
Driving and using machines: There are no studies on the effects of TYSABRI on the ability to drive and use machines. However, if the patient experiences dizziness, a common side effect, then the patient should not drive or use machines.

If the patient is pregnant or breast-feeding, thinks she might be pregnant or is planning to have a baby, ask the doctor for advice before taking this medicine.
Do not use TYSABRI if the patient is pregnant unless she discussed this with the doctor. Be sure to tell the doctor immediately if the patient is pregnant, thinks she might be pregnant, or if she is planning to become pregnant.
Do not breast-feed whilst using TYSABRI. Discuss with the doctor whether the patient chooses to breast-feed or to use TYSABRI.

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Speak to the doctor or nurse immediately if the patient notices any of the following: Symptoms of serious infections including: An unexplained fever, Severe diarrhea, Shortness of breath, Prolonged dizziness, Headache, Weight loss, Listlessness.
A group of symptoms caused by a serious infection of the brain including: 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 its covering layer (meningitis).
Signs of allergy to TYSABRI, during or shortly after the infusion: Itchy rash (hives); Swelling of the face, lips or tongue; Difficulty breathing; Chest pain or discomfort; Increase or decrease in the blood pressure (the doctor or nurse will notice this if they are monitoring the blood pressure).
Signs of a possible liver problem: Yellowing of the skin or the whites of the eyes; Unusual darkening of the urine.
TYSABRI can also have other side effects: Side effects are listed as follows by how commonly they have been reported in clinical trials: Common side effects that may affect up to 1 in 10 people: Urinary tract infection, Sore throat and runny or blocked up nose, Shivering, Itchy rash (hives), Headache, Dizziness, Feeling sick (nausea), Being sick (vomiting), Joint pain, Fever, Tiredness.
Uncommon side effects that may affect up to 1 in 100 people: Severe allergy (hypersensitivity), Progressive multifocal leukoencephalopathy (PML).
Rare side effects that may affect up to 1 in 1,000 people: Unusual infections (so-called "Opportunistic infections"), Severe anaemia (decrease in the red blood cells which can make the skin pale and can make the patient feel breathless or lacking energy).
Speak to the doctor as soon as possible if the patient thinks he/she has an infection.
Show the Alert Card and package leaflet to any doctor involved with the treatment, not only to the neurologist.
The patient will also find this information in the Patient Alert Card given by the doctor.

Other medicines and TYSABRI: Tell the doctor if the patient is taking or has recently taken or might take any other medicines.
The patient must not use TYSABRI if he/she is being treated with other medicines to treat the MS, such as beta-interferons or glatiramer acetate.
The patient may not be able to use TYSABRI if he/she is currently receiving or has previously received medicines that affect the immune system, e.g. mitoxantrone or cyclophosphamide.

The following information is intended for healthcare professionals only: 1. 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.
2. Use aseptic technique when preparing TYSABRI solution for intravenous infusion. 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.
3. 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 TYSABRI solution to mix completely. Do not shake.
4. TYSABRI must not be mixed with other medicinal products or diluents.
5. 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.
6. 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°C - 8°C (do not freeze), allow the solution to warm to room temperature prior to infusion.
7. The diluted solution is to be infused intravenously over 1 hour at a rate of approximately 2 ml/minute.
8. After the infusion is complete, flush the intravenous line with sodium chloride 9 mg/ml (0.9%) solution for injection.
9. Each vial is for single-use only.
10. Any unused medicinal product or waste material must be disposed of in accordance with local requirements.

Unopened vial: Store in a refrigerator (2°C to 8°C).
Do not freeze.
Keep the vial in the outer carton in order to protect from light.
Diluted solution: After dilution, immediate use is recommended. If not used immediately, the diluted solution must be stored at 2°C - 8°C and infused within 8 hours of dilution.
Do not use this medicine if particles are noticed in the liquid and/or the liquid in the vial is discoloured.
Keep this medicine out of the sight and reach of children.

Immunosuppressants

L04AG03 - natalizumab ; Belongs to the class of monoclonal antibodies. Used as immunosuppressants.

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