« Back to Medicines list

Tysabri 300mg concentrate for solution for infusion

  • Name:

    Tysabri 300mg concentrate for solution for infusion

  • Company:
    info
  • Active Ingredients:

    Natalizumab

  • Legal Category:

    Product subject to medical prescription which may not be renewed (A)

Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 07/05/20

files-icon(Click to Download)

XPIL

Summary of Product Characteristics last updated on medicines.ie: 7/5/2020
This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions.

Click on this link to Download PDF directly

Biogen Idec Ltd

Biogen Idec Ltd

Company Products

Medicine NameActive Ingredients
Medicine Name AVONEX 30 micrograms/0.5 ml solution for injection Active Ingredients Interferon beta-1a
Medicine Name AVONEX 30 micrograms/0.5ml solution for injection, in pre-filled pen Active Ingredients Interferon beta-1a
Medicine Name Fampyra 10 mg prolonged-release tablets Active Ingredients Fampridine
Medicine Name Plegridy 63 mcg, 94 mcg and 125mcg solution for injection in pre-filled pen Active Ingredients peginterferon beta-1a
Medicine Name Spinraza 12 mg solution for injection Active Ingredients Nusinersen sodium
Medicine Name Tecfidera 120mg and 240mg gastro-resistant hard capsules Active Ingredients Dimethyl fumarate
Medicine Name Tysabri 300mg concentrate for solution for infusion Active Ingredients Natalizumab
1 - 0 of 7 items.Total: Infinity pages

When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 7 May 2020 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.2 - Pharmacokinetic properties

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Location and update

Tracked changes

SmPC Section 4.4

 

Wording closely aligned to CDSv24 and 25 has been added to reflect further information around use of PLEX

Based on a retrospective analysis of natalizumab-treated patients since its approval, no difference was observed on 2-year survival after PML diagnosis between patients who received PLEX and those who did not. For other considerations on the management of PML, see the Physician Information and Management Guidelines.

PML and IRIS (Immune Reconstitution Inflammatory Syndrome)

IRIS occurs in almost all TYSABRI PML patients after withdrawal or removal of the medicinal

product, 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 information).

SmPC Section 4.8

Correction to ADR  frequency classifications

Tabulated list of adverse reactions

Very common (≥ 1/10), Ccommon (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100).

 

MedDRA System Organ Class

Adverse reaction

Frequency category

 

Infections and infestations

Urinary tract infection

Very Ccommon

Nasopharyngitis

Very Ccommon

Immune system disorders

Urticaria

Common

Hypersensitivity

Uncommon

Nervous system disorders

Headache

Very Ccommon

Dizziness

Very Ccommon

Progressive Multifocal

Leukoencephalopathy (PML)

Uncommon

Gastrointestinal disorders

Vomiting

Common

Nausea

Very Ccommon

Musculoskeletal and connective

tissue disorders

Arthralgia

Very Ccommon

General disorders and

administration site

conditions

Rigors

Common

Pyrexia

Common

Fatigue

Very Ccommon

 

 

 

SmPC Section 5.2

Pharmacokinetic properties

The pharmacokinetics of natalizumab in paediatric MS patients has not been established. The

pharmacokinetics of natalizumab in patients with renal or hepatic insufficiency has not been studied.

 

The effect of plasma exchange on natalizumab clearance and pharmacodynamics was evaluated in a study

of 12 MS patients. Estimates of the total natalizumab 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 natalizumab 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.

Updated on 7 May 2020 PIL

Reasons for updating

  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 4 - possible side effects

Free text change information supplied by the pharmaceutical company

Driving and using machines

There are no studies on the effects of TYSABRI on the ability to drive and use machines. However, if you experience dizziness, a very common side effect, then you should not drive or use machines.

 

Very common side effects that may affect more than 1 in 10 people:

  • Urinary tract infection
  • Sore throat and runny or blocked up nose
  • Headache
  • Dizziness
  • Feeling sick (nausea)
  • Joint pain
  • Tiredness

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

Updated on 28 February 2020 Ed-Ptnt

Reasons for updating

  • Add New Doc

Updated on 28 February 2020 Ed-HCP

Reasons for updating

  • Add New Doc

Updated on 28 February 2020 Ed-HCP

Reasons for updating

  • Add New Doc

Updated on 28 February 2020 Ed-HCP

Reasons for updating

  • Add New Doc

Updated on 28 February 2020 Ed-HCP

Reasons for updating

  • Add New Doc

Updated on 20 November 2019 PIL

Reasons for updating

  • Change to information for healthcare professionals

Free text change information supplied by the pharmaceutical company

Added batch traceability details to Infomration to healthcare Professionals section.

Updated on 13 November 2019 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

 New text on batch traceability and Extended Interval dosing added to section 4.4 Warnings and Precautions:

Traceability

In order to improve the traceability of biological medicinal products, the name and batch number of the administered product should be clearly recorded.

Progressive Multifocal Leukoencephalopathy (PML)

(……..)

In anti-JCV antibody positive patients, extended interval dosing of TYSABRI (average dosing interval of approximately 6 weeks) is suggested to be associated with a lower PML risk compared to approved dosing. If utilising extended interval dosing, caution is required because the efficacy of extended interval dosing has not been established and the associated benefit risk balance is currently unknown (see section 5.1). For further information, refer to the Physician Information and Management Guidelines.

 

Additional text on Extended Interval dosing added to section 5.1 Pharmacodynamic properties:

(……..)

In a pre-specified, retrospective analysis of US anti-JCV antibody positive TYSABRI patients (TOUCH registry), the risk of PML was compared between patients treated with the approved dosing interval and patients treated with extended interval dosing as identified in the last 18 months of exposure (EID, average dosing intervals of approximately 6 weeks). The majority (85%) of patients dosed with EID had received the approved dosing for ≥1 year prior to switching to EID. The interim analysis showed a lower risk of PML in patients treated with EID (hazard ratio = 0.06 95% CI of hazard ratio = 0.01- 0.22). The efficacy of TYSABRI when administered with EID has not been established, and therefore the benefit/risk balance of EID is unknown (see section 4.4).

Efficacy has been modelled for patients who switch to longer dosing after ≥1 year of approved TYSABRI dosing and who did not experience a relapse in the year prior to switching. Current pharmacokinetic/pharmacodynamic statistical modelling and simulation indicate that the risk of MS disease activity for patients switching to longer dosing intervals may be higher for patients with body weight >80kg or those with dosing intervals ≥7 weeks. No prospective clinical studies have been completed to validate these findings.

Updated on 17 August 2018 PIL

Reasons for updating

  • Change to section 6 - marketing authorisation holder
  • Change to section 6 - date of revision

Updated on 17 August 2018 SmPC

Reasons for updating

  • Change to section 7 - Marketing authorisation holder
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Update of MAH to Biogen Netherlands B.V.

Updated on 29 March 2017 SmPC

Reasons for updating

  • New SmPC for new product

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 29 March 2017 SmPC

Reasons for updating

  • Change to section 6.5 - Nature and contents of container
  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

The contraindication for using Tysabri in children and adolescents under 18 years of age has been removed.

Updated on 22 March 2017 PIL

Reasons for updating

  • New PIL for new product

Updated on 22 March 2017 PIL

Reasons for updating

  • Change to section 2 - what you need to know - contraindications

Updated on 26 October 2016 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Details of the effects of PLEX/ IVIg on the interpretation of serum anti-JCV antibody testing added to section 4.4.
Reports of ARN added to sections 4.4 and 4.8.

Updated on 21 October 2016 PIL

Reasons for updating

  • Change to section 4 - possible side effects

Updated on 7 July 2016 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 5.1 - Pharmacodynamic properties

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Location

Update

SmPC Section 4.1

Streamlining and amendment of the indication statement to allow Tysabri to be used in MS patients who have previously failed treatment with any initial disease modifying therapy (DMT)

SmPC Section 4.2

Consequential change to sections 4.1

SmPC Section 4.3

Consequential change to sections 4.1 & 4.2

SmPC Section 4.4     

Consequential change to section 4.4

SmPC Section 5.1

Update to include summary of Interim analysis  results from the ongoing TYSABRI Observational Program (TOP) study

Updated on 5 July 2016 PIL

Reasons for updating

  • Change to how the medicine works
  • Change to drug interactions

Updated on 10 May 2016 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.3 - Shelf life
  • Change to section 6.4 - Special precautions for storage
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 9 - Date of renewal of authorisation
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

SmPC has been updated to incorporate changes agreed during the recent Article 20 procedure and licence renewal.

Updated on 5 May 2016 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to storage instructions
  • Change to date of revision

Updated on 6 January 2016 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

 
SmPC section 4.4 - Update to “opportunistic infections” subsection with information regarding herpes simplex and varicella zoster viruses
                                - Update to “Immunogenicity” subsection: upon redosing patients at higher risk of developing anti-natalizumab antibodies and/or hypersensitivity
SmPC section 4.8 - Update to “Infections, including PML and opportunistic infections” subsection with undesirable effects (encephalitis and meningitis) that may occur as a result of herpes simplex and varicella zoster viruses

Updated on 4 January 2016 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to side-effects
  • Change to date of revision

Updated on 11 November 2015 PIL

Reasons for updating

  • Change to side-effects
  • Change to date of revision

Updated on 11 November 2015 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

In section 4.8 (undesirable effects), the following information has been added:

Rare, serious cases of anaemia and haemolytic anaemia have been reported in patients treated with TYSABRI in post-marketing observational studies.

Updated on 30 June 2015 SmPC

Reasons for updating

  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

In section 4.6 (fertility, pregnancy and lacation): Information on the pregnancy registery has been included and a warning for risk of haematological abnormalities in the newborn.
In section 10 (date of revision of text): date amended to May 2015.

Updated on 6 November 2014 PIL

Reasons for updating

  • Change to further information section
  • Change to date of revision

Updated on 26 November 2013 PIL

Reasons for updating

  • Change to further information section
  • Change to date of revision
  • Addition of black triangle

Updated on 25 November 2013 SmPC

Reasons for updating

  • Addition of black triangle
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Changes due to update to QRD9 template - addition of black triangle and wording around additional monitoring, contact details for MHRA and IMB added to Section 4.8 for AE reporting, Date of Last Revision updated accordingly

Updated on 7 September 2013 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

In section 4.4 (Special Warnings and Precautions for Use): The following statement has been added: "Anti-JCV antibody negative patients may still be at risk of PML for reasons such as a new JCV infection, fluctuating antibody status or a false negative test result. Re-testing of anti-JCV antibody negative patients every 6 months is recommended."
In section 10 (date of revision of text). Date updated to August 2013.

Updated on 6 September 2013 PIL

Reasons for updating

  • Change to date of revision

Updated on 24 July 2013 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

In Section 4.1, Tysabri is now indicated for adult patients aged 18 years and over with high disease activity despite treatment with a beta-interferon or glatiramer acetate
In Section 5.1, a statement has been added indicating that the EMA has deferred the obligation to submit the results of studies with Tysabri in one or more subsets of the paediatric population in multiple sclerosis
In Section 10, the Date of revision of text is now July 2013

Updated on 24 July 2013 PIL

Reasons for updating

  • Change to date of revision
  • Change of distributor details

Updated on 26 June 2013 PIL

Reasons for updating

  • Change to date of revision
  • Change to marketing authorisation holder

Updated on 25 June 2013 SmPC

Reasons for updating

  • Change to section 7 - Marketing authorisation holder
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

In section 7, the MAH has changed from Elan to Biogen Idec Limited
In section 10, the date of the revision of text has changed to 06/2013

Updated on 8 March 2013 PIL

Reasons for updating

  • Change to date of revision

Updated on 6 March 2013 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

The following text has been added to Section 4.4 (Special warnings and precautions for use):
PML has been reported following discontinuation of TYSABRI in patients who did not have findings suggestive of PML at the time of discontinuation. Patients and Physicians should continue to be alert for any new signs or symptoms that may be suggestive of PML for approximately six months following discontinuation of TYSABRI.

Updated on 5 December 2012 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

  • In Section 4.4 (Special warnings and precautions for use), additional recommendations have been added regarding testing for serum anti-JCV antibodies prior to initiating therapy and in patients with an unknown anitbody status, and retesting of anti-JCV antibody negative patients every 6 months
  • In Section 4.8 (Undesirable effects), reports of eosinophilia without clinical symptoms in the post-marketing setting, has been added
  • In Section 10, the date of revision of the SPC text has been updated

Updated on 3 December 2012 PIL

Reasons for updating

  • Change to further information section

Updated on 11 June 2012 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 10 - Date of revision of the text
  • Change to MA holder contact details
  • Change to improve clarity and readability

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

In section 4.4 (Special warnings and precautions for use): PML section has been reworded and reordered. In addition, the following has been added: The anti-JCV antibody assay (ELISA) should not be used to diagnose PML. Anti-JCV antibody testing should not be performed during, or for at least two weeks following, plasma exchange due to the removal of antibodies from the serum.

In section 4.7 (Effects on ability to drive and use machines)- this section has been reworded and the statement amended.

In section 7 (MAH)- Address for Elan has been updated.

In section 10 (Date of revision of the text) - Date has been updated

Updated on 7 June 2012 PIL

Reasons for updating

  • Change to MA holder contact details
  • Change due to user-testing of patient information
  • Change to date of revision

Updated on 28 June 2011 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 9 - Date of renewal of authorisation
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

In section 2 (Qualitative and Quantitative composition), sodium content information now included.

In section 4.2 (Posology and method of administration), risk factors for PML are highlighted including: treatment duration, immunosuppressant use and presence of anti-JCV antibodies.

In section 4.4 (Special warnings and precautions for use), Risk factors for PML are highlighted including anti-JCV antibody status. Sodium content information added.

In section 4.8 (Undesirable effects), PML listed as an uncommon undesirable effect.

In section 9 (Date of first authorisation/renewal of authorisation), renewal date added.

In section 10 (Date of revision of the text), date updated. 

Updated on 28 June 2011 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to side-effects
  • Change to date of revision

Updated on 16 May 2011 SmPC

Reasons for updating

  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

In section 4.5 (Interaction with other medicinal products and other forms of interaction), information on vaccinations with TYSABRI has been added
In section 10 (Date of revision of the text), the date has been amended to April 2011

Updated on 15 March 2011 SmPC

Reasons for updating

  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 5.3 - Preclinical safety data

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

  • In section 4.6 (Fertility, pregnancy and lactation), the lactation information has been updated.
  • In section 5.3 (Preclinical safety data), the following text has been removed: ...indicating the possibility for transfer of natalizumab into breast milk in humans (see section 4.6).

Updated on 3 December 2010 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

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.

 

Updated on 2 December 2010 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to date of revision

Updated on 25 May 2010 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

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 textUpdated European Medicines Agency abbrevation (EMA) and website address

Updated on 18 May 2010 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to date of revision

Updated on 2 February 2009 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company


The following information has been added regarding hypersensitivity symptoms- highlighted in bold
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.

10. DATE OF REVISION OF THE TEXT 01/2009

Updated on 2 February 2009 PIL

Reasons for updating

  • Change to side-effects
  • Change to date of revision

Updated on 21 November 2008 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

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.

 

Updated on 12 November 2008 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to side-effects

Updated on 19 September 2008 SmPC

Reasons for updating

  • Change to section 6.3 - Shelf life
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 6.3 shelf life was extended from 2 to 4 years

Updated on 27 June 2008 PIL

Reasons for updating

  • Change to side-effects

Updated on 27 June 2008 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company


4.4     Special warnings and precautions for use

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
 
 
4.8     Undesirable effects
 
Hepatic Events
 
Spontaneous cases of serious liver injuries, increased liver enzymes, hyperbilirubinaemia have been reported during the post marketing phase (see section 4.4

Updated on 12 May 2008 PIL

Reasons for updating

  • Change to warnings or special precautions for use

Updated on 7 May 2008 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

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. 

Updated on 13 December 2007 PIL

Reasons for updating

  • Correction of spelling/typing errors

Updated on 11 December 2007 SmPC

Reasons for updating

  • Correction of spelling/typing errors

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 4 December 2007 PIL

Reasons for updating

  • Change to name of manufacturer

Updated on 8 March 2007 PIL

Reasons for updating

  • Change to marketing authorisation holder address

Updated on 8 March 2007 SmPC

Reasons for updating

  • Change to section 5.1 - Pharmacodynamic properties

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

SmPC

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

Small format change to the instructions for use (2nd instruction split into 2 separate instructions to improve clarity).

Updated on 15 August 2006 SmPC

Reasons for updating

  • New SPC for new product

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 15 August 2006 PIL

Reasons for updating

  • New PIL for new product