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Updated on 28/06/2011 and displayed until Current
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Updated on 09/05/2011 and displayed until 28/06/2011
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Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
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Change to section 10 date of revision of the text
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| Date of revision of text on the SPC: 01-Apr-2011 |
| Legal Category: POM |
| Black Triangle (CHM):
YES |
Free-text change information supplied by the pharmaceutical company
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In section 4.5 (Interaction with other medicinal products and other forms of interaction), vaccination information with TYSABRI has been included
In section 10 (Date of revision of the text), the date has been amended to April 2011
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Updated on 15/03/2011 and displayed until 09/05/2011
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Change to section 4.6 - Pregnancy and Lactation
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Change to section 5.3 - Preclinical Safety Data
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| Date of revision of text on the SPC: 01-Feb-2011 |
| Legal Category: POM |
| Black Triangle (CHM):
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Free-text change information supplied by the pharmaceutical company
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- In section 4.6 (fertility, pregnancy and lactation), lactation information has been updated.
- In section 5.3 (preclinical safety data), the following information has been removed: Indicating the possibility for transfer of natalizumab into breast milk in humans (see section 4.6).
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Updated on 07/12/2010 and displayed until 15/03/2011
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Change to section 4.4 - Special warnings and precautions for Use
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Change to section 10 date of revision of the text
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Change to section 4.2 - Posology and method of administration
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| Date of revision of text on the SPC: 01-Nov-2010 |
| Legal Category: POM |
| Black Triangle (CHM):
YES |
Free-text change information supplied by the pharmaceutical company
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Modifications have been made to section 4.2 Posology and Method of Administration and 4.4 Special Warnings and Precautions for Use. In addition, the Product Information has also been revised in-line with the latest QRD template.
The following wording changes were made to section 4.4 of the SmPC (new text in blue, underline, deleted text struck-through, red):
The risk of PML appears to increases with treatment duration, especially beyond 2 years. There is limited experience in patients who received more than 3 years of Tysabri treatment therefore the risk of PML in these patients cannot currently be estimated. The risk of PML is also increased in patients who have been treated with an immunosuppressant prior to receiving TYSABRI. This increased risk appears to be independent of TYSABRI treatment duration.
Patients with a treatment history of immunosuppressant medications
, including cyclophosphamide and mitoxantrone, may experience prolonged immunosuppression and therefore may be are at increased risk for PML.
The following additional wording was included in section 2, under the heading 'Take special care with Tysabri' of the Package Leaflet
The risk of PML is also greater if you have previously taken a medicine that weakens your immune system.
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Updated on 25/05/2010 and displayed until 07/12/2010
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Change to section 4.1 - Therapeutic indications
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Change to section 4.2 - Posology and method of administration
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Change to section 4.4 - Special warnings and precautions for Use
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Change to section 5.1 - Pharmacodynamic Properties
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Change to section 10 date of revision of the text
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| Date of revision of text on the SPC: 01-May-2010 |
| Legal Category: POM |
| Black Triangle (CHM):
YES |
Free-text change information supplied by the pharmaceutical company
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Section 4.1 Therapeutic indications
The following text in bold has been moved from section 5.1 and inserted here
Patients with high disease activity despite treatment with a beta-interferon
These patients may be defined as those who have failed to respond to a full and adequate course (normally at least one year of treatment) of beta-interferon. Patients should have had at least 1 relapse in the previous year while on therapy, and have at least 9 T2‑hyperintense lesions in cranial MRI or at least 1 Gadolinium‑enhancing lesion. A “non-responder” could also be defined as a patient with an unchanged or increased relapse rate or ongoing severe relapses, as compared to the previous year.
Patients with rapidly evolving severe relapsing remitting multiple sclerosis defined by 2 or more disabling relapses in one year, and with 1 or more Gadolinium enhancing lesions on brain MRI or a significant increase in T2 lesion load as compared to a previous recent MRI.
4.2 Posology and method of administration
The following text in bold has been inserted here
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 Tysabri (see also patient information leaflet). After 2 years of treatment, patients should be re-informed about the risks of Tysabri, especially the increased risk of PML, and should be instructed together with their caregivers on early signs and symptoms of PML.
Data on the safety and efficacy of natalizumab at 2 years were generated from controlled, double–blind studies. Continued therapy beyond this time should be considered only following a reassessment of the potential for benefit and risk.
4.4 Special warnings and precautions for use
The following text has been inserted
Progressive Multifocal Leukoencephalopathy (PML)
Use of TYSABRI has been associated with an increased risk of PML which may be fatal or result in severe disability. The risk of PML appears to increase with treatment duration, especially beyond 2 years. There is limited experience in patients who received more than 3 years of Tysabri treatment therefore the risk of PML in these patients cannot currently be estimated. Due to this increased risk of developing PML, the benefits and risks of Tysabri treatment should be individually reconsidered by the specialist physician and the patient. The patient should be re-informed about the risks of Tysabri after 2 years especially the increased risk of PML, and should be instructed together with their caregivers on early signs and symptoms of PML.
Before initiation of treatment with TYSABRI, a recent (usually within 3 months) Magnetic Resonance Image (MRI) should be available as a reference, and be repeated on a yearly routine basis to update this reference. Patients must be monitored at regular intervals throughout treatment for any new or worsening neurological symptoms or signs that may be suggestive of PML.
PML and IRIS (Immune Reconstitution Inflammatory Syndrome)
IRIS occurs in almost all TYSABRI PML patients after withdrawal or removal of TYSABRI, e.g. by plasma exchange (see section 5.2). IRIS is thought to result from the restoration of immune function in patients with PML, which can lead to serious neurological complications and may be fatal. Monitoring for development of IRIS, which has occurred within days to several weeks after plasma exchange in TYSABRI treated patients with PML, and appropriate treatment of the associated inflammation during recovery from PML should be undertaken (see the Physician Information and Management Guidelines for further
5.1 Pharmacodynamic properties
See section 4.1 for the text that has been deleted from 5.1 and inserted into 4.1
Section 10 Date of revision of text
05/2010
Updated European Medicines Agency abbrevation (EMA) and website address www.ema.europa.eu
See section 4.1 for the text that has been deleted from 5.1 and inserted into 4.1Section 10 Date of revision of text05/2010Updated European Medicines Agency abbrevation (EMA) and website address
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Updated on 03/02/2009 and displayed until 25/05/2010
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Reasons for adding or updating:
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Change to section 10 date of revision of the text
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Change to section 4.8 - Undesirable Effects
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| Date of revision of text on the SPC: 01-Jan-2009 |
| Legal Category: POM |
| Black Triangle (CHM):
YES |
Free-text change information supplied by the pharmaceutical company
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| The following information (highlighted in bold) on hypersensitivity symptoms has been added to;
section 4.8 Undesirable effects ;
Hypersensitivity reaction
In 2-year controlled clinical trials in MS patients, hypersensitivity reactions occurred in up to 4% of patients. Anaphylactic/anaphylactoid reactions occurred in less than 1% of patients receiving TYSABRI. Hypersensitivity reactions usually occurred during the infusion or within the 1-hour period after the completion of the infusion (See section 4.4). In post-marketing experience, there have been reports of hypersensitivity reactions which have occurred with one or more of the following associated symptoms: hypotension, hypertension, chest pain, chest discomfort, dyspnoea, angioedema, in addition to more usual symptoms such as rash and urticaria.
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Updated on 14/11/2008 and displayed until 03/02/2009
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Reasons for adding or updating:
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Change to section 4.4 - Special warnings and precautions for Use
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Change to section 4.8 - Undesirable Effects
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Change to section 5.2 - Pharmacokinetic Properties
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Change to section 10 date of revision of the text
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| Date of revision of text on the SPC: 01-Oct-2008 |
| Legal Category: POM |
| Black Triangle (CHM):
YES |
Free-text change information supplied by the pharmaceutical company
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The following PML wording highlighted in red has been added.
4.4 Special warnings and precautions for use.
Progressive Multifocal Leukoencephalopathy (PML)
If PML is suspected, further dosing must be suspended until PML has been excluded.
The clinician should evaluate the patient to determine if the symptoms are indicative of neurological dysfunction, and if so, whether these symptoms are typical of MS or possibly suggestive of PML. If any doubt exists, further evaluation, including MRI scan preferably with contrast (compared with pre-treatment MRI), CSF testing for JC Viral DNA and repeat neurological assessments, should be considered as described in the Physician Information and Management Guidelines (see educational guidance). Once the clinician has excluded PML (if necessary, by repeating clinical, imaging and/or laboratory investigations if clinical suspicion remains), dosing of natalizumab may resume.
Educational guidance
All physicians who intend to prescribe TYSABRI must ensure they are familiar with the Physician Information and Management Guidelines.
4.8 Undesirable effects
Infections, including PML and opportunistic infections
Although each case of PML occurred in patients either with concomitant use of immune modulating drugs or with evidence of immunosuppression, it remains possible that the risk of PML is associated with natalizumab alone.
PML has been reported in post-marketing experience in patients treated with TYSABRI monotherapy.
5.2 Pharmacokinetic properties
The effect of plasma exchange on natalizumab clearance and pharmacodynamics was evaluated in a study of 12 MS patients. Estimates of the total drug removal after 3 plasma exchanges (over a 5-8 day interval) was approximately 70-80%. This compares to approximately 40% seen in earlier studies in which measurements occurred after drug discontinuation over a similar period of observation. The impact of plasma exchange on the restitution of lymphocyte migration and ultimately its clinical usefulness is unknown.
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Updated on 18/09/2008 and displayed until 14/11/2008
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Reasons for adding or updating:
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Change to section 6. 3 - Shelf Life
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| Date of revision of text on the SPC: 01-Sep-2008 |
| Legal Category: POM |
| Black Triangle (CHM):
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Free-text change information supplied by the pharmaceutical company
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| In section 6.3, the shelf life for concentrate has increased from 2 years to 4 years.
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Updated on 10/07/2008 and displayed until 18/09/2008
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Reasons for adding or updating:
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Change to section 4.4 - Special warnings and precautions for Use
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Change to section 4.8 - Undesirable Effects
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Change to section 10 date of revision of the text
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| Date of revision of text on the SPC: 01-Jun-2008 |
| Legal Category: POM |
| Black Triangle (CHM):
YES |
Free-text change information supplied by the pharmaceutical company
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Section 4.4 (Special warnings and precautions for use) the following has been added;
Hepatic Events
Spontaneous serious adverse reactions of liver injury have been reported during the post marketing phase. These liver injuries may occur at any time during treatment, even after the first dose. In some instances, the reaction reoccurred when TYSABRI was reintroduced. Some patients with a past medical history of an abnormal liver test have experienced an exacerbation of abnormal liver test while on TYSABRI. Patients should be monitored as appropriate for impaired liver function, and be instructed to contact their physician in case signs and symptoms suggestive of liver injury occur, such as jaundice and vomiting. In cases of significant liver injury TYSABRI should be discontinued.
Section 4.8 (Undesirable Effects) the following has been added;
Hepatic Events
Spontaneous cases of serious liver injuries, increased liver enzymes, hyperbilirubinaemia have been reported during the post marketing phase (see section 4.4).
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Updated on 07/05/2008 and displayed until 10/07/2008
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Reasons for adding or updating:
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Change to section 4.4 - Special warnings and precautions for Use
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Change to section 4.8 - Undesirable Effects
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Change to section 10 date of revision of the text
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| Date of revision of text on the SPC: 01-Apr-2008 |
| Legal Category: POM |
| Black Triangle (CHM):
YES |
Free-text change information supplied by the pharmaceutical company
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Section 4.4 (Special warnings and precautions for use)
Educational guidance
"Physicians should counsel patients on the importance of uninterrupted dosing, particularly in the early months of treatment (see hypersensitivity)." has been added.
Hypersensitivity
The risk for hypersensitivity was greatest with early infusions "and in patients re-exposed to TYSABRI following an initial short exposure (one or two infusions) and extended period (three months or more) without treatment has been added" has been added.
Immunogenicity
"Since patients who have received an initial short exposure to TYSABRI and then had an extended period without treatment are more at risk for hypersensitivity upon redosing, the presence of antibodies should be evaluated and if these remain positive in a confirmatory test after 6 weeks treatment should not be resumed." has been added.
Section 4.8 (undesirable effects)
"In clinical trials, herpes infections (Varicella-Zoster virus, Herpes-simplex virus) occurred slightly more frequently in natalizumab-treated patients than in placebo-treated patients. In post marketing experience, there have been reports of serious cases..." has been added.
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Updated on 19/06/2007 and displayed until 07/05/2008
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Reasons for adding or updating:
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Addition of Black Triangle
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| Date of revision of text on the SPC: 11/2006 |
| Legal Category: POM |
| Black Triangle (CHM):
YES |
Free-text change information supplied by the pharmaceutical company
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| Section 1 - addition of black triangle
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Updated on 02/02/2007 and displayed until 19/06/2007
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Reasons for adding or updating:
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Change to section 5.1 - Pharmacodynamic Properties
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Improved Electronic Presentation
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| Date of revision of text on the SPC: 11/2006 |
| Legal Category: POM |
| Black Triangle (CHM):
NO |
Free-text change information supplied by the pharmaceutical company
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- Addition of the word "median" to the AFFIRM study table in section 5.1
- Deletion of "time to progression" from AFFIRM study table in section 5.1
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Updated on 18/07/2006 and displayed until 02/02/2007
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