Removal of contraindication related to pregnancy, Inclusion of statement regarding batch traceability, Updated guidance on pregnancy and breastfeeding

Section 4.3: Removal of contraindication related to pregnancy

Section 4.4: Inclusion of statement regarding batch traceability

Section 4.6: Updated guidance on pregnancy and breastfeeding following closure of INF pregnancy registry.

Update MAH to Biogen Netherlands B.V.

• In Section 4.4, information has been added on the occurrence of thrombotic microangiopathy in multiple sclerosis patients treated with interferon beta products, including diagnosis of the condition and subsequent patient management
• In Section 4.8, thrombotic microangiopathy including thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome has been added as a rare adverse reaction (class label for interferon beta products)
• In Section 4.8, the contact details for the Irish Regulatory Agency have been updated, following their change of name from IMB to HPRA
• In Section 10, the date of revision of the text has been changed to August 2014

In Section 4.4 (Special warnings and precautions for use), the following text has been added:

Nephrotic Syndrome: Cases of nephrotic syndrome with different underlying nephropathies including collapsing focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranoproliferative glomerulonephritis (MPGN) and membranous glomerulopathy (MGN) have been reported during treatment with interferon-beta products. Events were reported at various time points during treatment and may occur after several years of treatment with interferon-beta. Periodic monitoring of early signs or symptoms, e.g. oedema, proteinuria and impaired renal function is recommended, especially in patients at higher risk of renal disease. Prompt treatment of nephrotic syndrome is required and discontinuation of treatment with Avonex should be considered.

In Section 4.6 (Fertility, pregnancy and lactation), the following text has been added:

Fertility

Fertility and developmental studies in rhesus monkeys have been carried out with a related form of interferon beta 1a. At very high doses, anovulatory and abortifacient effects in test animals were observed (see section 5.3).

No information is available on the effects of interferon beta 1a on male fertility.

In Section 4.8 (Undesirable effects), nephrotic syndrome and glomerulosclerosis have been added as renal and urinary disorders reported rarely, and the following text has been added:

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via:

United Kingdom

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard

Ireland

IMB Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2

Tel: +353 1 6764971

Fax: +353 1 6762517

Website: www.imb.ie

e-mail: imbpharmacovigilance@imb.ie

In Section 6.3, the shelf life has been increased from 2 years to 3 years.

Previous Text
4.2 Posology and method of administration
Children and adolescents: No formal clinical trials or pharmacokinetic studies have been conducted in children or adolescents. However, limited published data suggest that the safety profile in adolescents from 12 to 16 years of age receiving AVONEX 30 micrograms IM once per week is similar to that seen in adults.

There is no information on the use of AVONEX in children under 12 years of age and therefore AVONEX should not be used in this population.

New Approved Text

4.2 Posology and method of administration
Paediatric population: The safety and efficacy of AVONEX in adolescents aged 12 to 16 years have not yet been established. Currently available data are described in section 4.8 and 5.1 but no recommendation on a posology can be made.

The safety and efficacy of AVONEX in children below 12 years of age have not yet been established.

No data are available.

4.8 Undesirable effects
Paediatric population: Limited published data suggest that the safety profile in adolescents from 12 to 16 years of age receiving AVONEX 30 micrograms IM once per week is similar to that seen in adults.

5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Paediatric population: Limited data of the efficacy/safety of AVONEX 15 micrograms IM once per week (n=8) as compared to no treatment (n=8) with follow up for 4 years showed results in line to those seen in adults, although the EDSS scores increased in the treated group over the 4 year follow-up thus indicating disease progression. No direct comparison with the dose currently recommended in adults is available.

10. DATE OF REVISION OF THE TEXT
03/2010 
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMA) http://www.ema.europa.eu

Section 4.3 Contraindication

Patients with a history of hypersensitivity to natural or recombinant interferon-b or to any excipients

" pregnant patients" removed from being in the contraindications section

Section 4.4  Special warnings and Special Precautions for Use  " or other mood disorders, conditions that are common with MS . Depression has been reported in association with Avonex use and it may occur at any time during treatment" removed from the section

“Patients with current severe depression and / or suicidal ideation” added to the above section

“ Epileptic patients with a history of seizures not adequately controlled by treatment” removed from the above section

“Patients with a history of hypersensitivity to natural or recombinant interferon - b or to any excipient “ added

"Caution should be exercised when administering AVONEX to patients  with pre existing seizure disorder. For patients without a pre existing seizure disorder who develop seizures during therapy with AVONEX, an etiologic basis should be established and appropriate anti-convulsant therapy instituted prior to resuming AVONEX treatment" removed from the above section

Section 4.6  - Pregnancy and Lactation “Because of the potential hazards to the foetus, AVONEX  is contraindicated in pregnancy. There are no studies of interferon beta 1a in pregnant women. At high doses, in rhesus monkeys, abortifacient effects were observed. It cannot be excluded that such side effects will be observed in humans" - removed

"Fertile women receiving AVONEX should take appropriate contraceptive measures. Patients planning for pregnancy and those becoming pregnant should be informed of the potential hazards and AVONEX should be discontinued" - removed

" Breast feeding " Changed to Lactation .

“Breast fed”  - removed

“to discontinue” = removed