TYSABRI Concentrate for solution for infusion Ref.[8303] Active ingredients: Natalizumab

TYSABRI therapy is to be initiated and continuously supervised by specialised physicians experienced in the diagnosis and treatment of neurological conditions, in centres with timely access to MRI.

Patients treated with TYSABRI must be given the patient alert card and be informed about the risks of the medicinal product (see also package leaflet). After 2 years of treatment, patients should be re-informed about the risks of TYSABRI, especially the increased risk of Progressive Multifocal Leukoencephalopathy (PML), and should be instructed together with their caregivers on early signs and symptoms of PML.

Resources for the management of hypersensitivity reactions and access to MRI should be available.

Some patients may have been exposed to immunosuppressive medicinal products (e.g. mitoxantrone, cyclophosphamide, azathioprine). These medicinal products have the potential to cause prolonged immunosuppression, even after dosing is discontinued. Therefore the physician must confirm that such patients are not immunocompromised before starting treatment with TYSABRI (see also section 4.4).

Posology

TYSABRI 300 mg is administered by intravenous infusion once every 4 weeks.

Continued therapy must be carefully reconsidered in patients who show no evidence of therapeutic benefit beyond 6 months

Data on the safety and efficacy of natalizumab at 2 years were generated from controlled, double– blind studies. After 2 years continued therapy should be considered only following a reassessment of the potential for benefit and risk. Patients should be re-informed about the risk factors for PML, like duration of treatment, immunosuppressant use prior to receiving TYSABRI and the presence of anti-John Cunningham virus (JCV) antibodies (see section 4.4.).

Readministration

The efficacy of re-administration has not been established, for safety see section 4.4.

Special populations

Elderly

TYSABRI is not recommended for use in patients aged over 65 due to a lack of data in this population.

Renal and hepatic impairment

Studies have not been conducted to examine the effects of renal or hepatic impairment.

The mechanism for elimination and results from population pharmacokinetics suggest that dose adjustment would not be necessary in patients with renal or hepatic impairment.

Paediatric population

The safety and efficacy of TYSABRI in children and adolescents up to 18 years have not been established. No recommendation on a posology can be made. Currently available data are described in sections 4.8 and 5.1.

Method of administration

TYSABRI is for intravenous use.

For instructions on dilution of the medicinal product before administration, see section 6.6.

After dilution (see section 6.6), the infusion is to be administered over approximately 1 hour and patients are to be observed during the infusion and for 1 hour after the completion of the infusion for signs and symptoms of hypersensitivity reactions.

TYSABRI must not be administered as a bolus injection.

No case of overdose has been reported.

Shelf life

Unopened vial: 4 years.

Diluted solution: After dilution with sodium chloride 9 mg/ml (0.9%) solution for injection, 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. In-use storage times and conditions prior to use are the responsibility of the user.

Store in a refrigerator (2°C-8°C).

Do not freeze.

Keep the vial in the outer carton in order to protect from light.

For storage conditions after dilution of the medicinal product see section 6.3.

15 ml concentrate in a vial (type I glass) with a stopper (chlorobutyl rubber) and a seal (aluminium) with a flip-off cap.

Pack size of one vial per carton.

Instructions for use:

• 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 TYSABRI solution for intravenous (IV) infusion. Remove flip-off cap 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 TYSABRI solution to mix completely. Do not shake.
• 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°C-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/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.
• Any unused medicinal product or waste material must be disposed of in accordance with local requirements.