Benepali 50 mg solution for injection in pre-filled pen

Product Information *

  • Company:

    Biogen Biosimilar
  • Status:

    No Recent Update
  • Active Ingredients :

    *Additional information is available upon request

  • Legal Category:

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

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 21 May 2021

File name

Benepali IE_MT_NIR 50mg PFP PL May 21_1621606382.pdf

Reasons for updating

  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 2 - excipient warnings
  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Free text change information supplied by the pharmaceutical company

Section 2 has been updated as follows:

Children and adolescents

Benepali is not indicated for use in children and adolescents who weigh less than 62.5 kg.

• Vaccinations: If possible, children should be up to date with all vaccinations before using Benepali. Some vaccines, such as oral polio vaccine, should not be given while using Benepali. Please consult your doctor before you or the child receive any vaccines.

Inflammatory bowel disease (IBD): There have been cases of IBD in patients with juvenile idiopathic arthritis (JIA) treated with etanercept. Tell the doctor if the child develops any abdominal cramps and pain, diarrhoea, weight loss or blood in the stool.

Benepali contains sodium

This medicinal product contains less than 1 mmol sodium (23 mg) per 25 mg, that is to say essentially ‘sodium-free’.

Benepali contains sodium

This medicinal product contains less than 1 mmol sodium (23 mg) per 50 mg, that is to say essentially ‘sodium-free’

Section 4 has been updated as follows:

Other side effects

The known side effects of Benepali include the following in groups of decreasing frequency:

Very common (may affect more than 1 in 10 people)

Infections (including colds, sinusitis, bronchitis, urinary tract infections and skin infections); injection site reactions (including bleeding, bruising, redness, itching, pain, and swelling).

Reactions at the injection site (these do not occur as often after the first month of treatment); some patients have developed a reaction at an injection site that was used before; and headache.

Updated on 21 May 2021

File name

Benepali IE_MT_NIR 50mg SPC May 21_1621603035.pdf

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • 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 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • 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 2

Etanercept is a human tumour necrosis factor receptor p75 Fc fusion protein produced by recombinant DNA technology in a Chinese hamster ovary (CHO) mammalian expression system. Etanercept is a dimer of a chimeric protein genetically engineered by fusing the extracellular ligand binding domain of human tumour necrosis factor receptor-2 (TNFR2/p75) to the Fc domain of human IgG1. This Fc component contains the hinge, CH2 and CH3 regions, but not the CH1 region of IgG1. Etanercept contains 934 amino acids and has an apparent molecular weight of approximately 150 kilodaltons. The specific activity of etanercept is 1.7 × 106 units/mg.

 

Section 4.1 and 4.2:

Text regarding studies in children aged less than 2 years moved between sections:

4.2: Paediatric population

The dosage of etanercept is based on body weight for paediatric patients. Patients weighing less than 62.5 kg should be accurately dosed on a mg/kg basis using the powder and solvent for solution for injection presentations or the powder for solution for injection presentations (see below for dosing for specific indications). Patients weighing 62.5 kg or more may be dosed using a fixed-dose pre-filled syringe or pre-filled pen.

The safety and efficacy of etanercept in children aged less than 2 years has not been established.

No data are available

Section 4:4

Paediatric population

Vaccinations

It is recommended that paediatric patients, if possible, be brought up to date with all immunisations in agreement with current immunisation guidelines prior to initiating etanercept therapy (see Vaccinations, above).

 Inflammatory bowel disease (IBD) and uveitis in patients with juvenile idiopathic arthritis (JIA)

There have been reports of IBD and uveitis in JIA patients being treated with etanercept (see section 4.8).

Benepali contains sodium            

 This medicinal product contains less than 1 mmol sodium (23 mg) per 25 mg, that is to say essentially ‘sodium-free’.

  This medicinal product contains less than 1 mmol sodium (23 mg) per 50 mg, that is to say essentially ‘sodium-free’

 

Section 4.7:

No studies on the effects on the ability to drive and use machines have been performed.

 

Etanercept has no or neglegible influence on the ability to drive and use machines.

Section 4.8:

Headache added as a very common side effect.

Paediatric population

                …

There were 4 reports of macrophage activation syndrome in juvenile idiopathic arthritis clinical trials.

There have been reports of inflammatory bowel disease and uveitis in JIA patients being treated with etanercept from post-marketing sources, including a very small number of cases indicating a positive rechallenge (see section 4.4).

Section 5.1

Additional study in “Adult patients with non-radiographic axial spondyloarthritis” (Study 1 and study 2).

Updated on 13 April 2021

File name

Benepali IE_MT_NIR 50mg SPC Mar 21_1618300781.pdf

Reasons for updating

  • 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

Section 4,8

Reporting of suspected adverse reactions sub section has been updated to include the following:

United Kingdom (Northern Ireland)
Yellow Card Scheme. Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store

Updated on 02 April 2021

File name

Benepali IE_MT_NIR 50mg PFP PL Mar 21_1617375824.pdf

Reasons for updating

  • Change to section 6 - manufacturer
  • Change to section 6 - date of revision
  • Addition of information on reporting a side effect.

Free text change information supplied by the pharmaceutical company

In section 6, local representative contact details for United Kingdom (Northern Ireland) have been added;  Biogen Netherlands BV has been added as a manufaturer, and name and address of Biogen Hillerod  has been changed to FUJIFILM .

Updated on 27 November 2020

File name

Benepali 50mg PFP IE PL Nov 20_1606498642.pdf

Reasons for updating

  • Change to Section 1 - what the product is
  • Change to section 4 - possible side effects
  • Removal of Black Inverted Triangle
  • Change to date of revision

Free text change information supplied by the pharmaceutical company

Patient Alert Card' has been renamed to 'Patient Card'.

- Black triangle and explanation have been removed.

- In section 1, 'psoriasis' has been updated to 'plaque psoriasis'.

In section 4, the following changes have been made:

'Rare (may affect up to 1 in 1,000 people):
..
...opportunistic infections (infections that occur because of a weakened immune system); lichenoid reactions (itchy reddish-purple skin rash and/or threadlike white-grey lines on mucous membranes), opportunistic infections (which include tuberculosis and other infections that occur when resistance to disease is lowered), erythema multiforme (inflammatory skin rash), cutaneous vasculitis (inflammation of blood vessels in the skin); damage to nerves, including Guillain-Barré syndrome (a serious condition which can affect breathing and damage body organs).'

Very rare (may affect up to 1 in 10,000 people):
Failure of the bone marrow to produce crucial blood cells; damage to nerves, including Guillain-Barré syndrome (a serious condition which can affect breathing and damage body organs); toxic epidermal necrolysis (a life-threatening skin condition). 

Not known (frequency cannot be estimated from available data)
Merkel cell carcinoma (a type of skin cancer); Kaposi’s sarcoma (a rare cancer related to infection with human herpes virus 8. Kaposi’s sarcoma most commonly appears as purple lesions on the skin); excessive activation of white blood cells associated with inflammation (macrophage activation syndrome); recurrence of hepatitis B (a liver infection); worsening of a condition called dermatomyositis (muscle inflammation and weakness with an accompanying skin rash); Llisteria (a bacterial infection).

 

 - Minor editorial changes have been made throughout the PL as requested and/or to align with reference product.

Updated on 27 November 2020

File name

Benepali 50mg SPC IE MT Nov 20_1606498523.pdf

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 4.8 - Undesirable effects
  • Change to section 9 - Date of first authorisation/renewal of the authorisation
  • Change to section 10 - Date of revision of the text
  • Correction of spelling/typing errors
  • Removal of Black Inverted Triangle

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

Free text change information supplied by the pharmaceutical company

Section 4.2: 'Patient Alert Card' has been renamed to 'Patient Card'.

Section 4.4: 'Patient Alert Card' has been renamed to 'Patient Card'.

Formatting changes have also been made to this section, including the following:

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded (or stated) in the patient file.


Benepali contains sSodium contents

No clinically significant pharmacokinetic drug-drug interactions were observed in studies with methotrexate, digoxin or warfarin.

Section 4.8: Kaposi’s sarcoma was added to the tabulated list of adverse reactions, with unknown frequency to align with reference product.

 

Minor editorial changes have been made to other sections of the SPC as requested and/or to align with reference product.

EDM Updated on 19 June 2020

File name

v2.0-Benepali Quick Reference Guide for Pre-filled Pen_06.2020_1592556544.pdf

Reasons for updating

  • Replace File

Free text change information supplied by the pharmaceutical company

Annotation that was visible on doc has been deleted

EDM Updated on 18 June 2020

File name

Benepali-HCP training_aRMM_V12_May 2020_1592496081.pdf

Reasons for updating

  • Replace File

Free text change information supplied by the pharmaceutical company

Update to ADR reporting details for Ireland and UK.

EDM Updated on 18 June 2020

File name

v2.0-Benepali Quick Reference Guide for Pre-filled Pen_06.2020_1592496044.pdf

Reasons for updating

  • Replace File

Free text change information supplied by the pharmaceutical company

Update to ADR reporting details for Ireland and UK.

EDM Updated on 09 June 2020

File name

PATIENT ALERT CARD_BENEPALI_1591719523.pdf

Reasons for updating

  • Replace File

Free text change information supplied by the pharmaceutical company

Item number now reflects irish pack.

Updated on 27 January 2020

File name

Benepali 50mg PFP PL 27.01.2020_1580140302.pdf

Reasons for updating

  • Change to section 6 - manufacturer
  • Change to section 6 - date of revision

Free text change information supplied by the pharmaceutical company

Samsung Bioepis NL B.V has been added as a manufacturer responsible for batch release.

Updated on 09 December 2019

File name

Benepali 50mg PFP PL_09.12.2019_1575908402.pdf

Reasons for updating

  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Free text change information supplied by the pharmaceutical company

 Uncommon side effects section has been updated to include 'abdominal cramps and pain, diarrhoea, weight loss or blood in the stool (signs of bowel problems).'

Updated on 09 December 2019

File name

Benepali 50mg SPC_09.12.2019_1575908349.pdf

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 section has been updated as follows:

​​Traceability

In order to improve the traceability of biological medicinal products, the trademark name and the batch number of the administered product should be clearly recorded (or stated) in the patient file.

​​4.8     Undesirable effects section has been updated to include Inflammatory bowel disease in the tabulated list of adverse reactions.

EDM Updated on 06 December 2019

File name

Benepali Patient Alert Card__1575651072.pdf

Reasons for updating

  • Replace File

EDM Updated on 01 November 2019

File name

Benepali-HCP training slide deck_Mar 2019_1572619773.pdf

Reasons for updating

  • Replace File

Free text change information supplied by the pharmaceutical company

Previous version was uploaded in error.

EDM Updated on 01 August 2019

File name

Slide deck_1533214377.pdf

Reasons for updating

  • Add New Doc

EDM Updated on 01 August 2019

File name

Benepali Patient Alert Card_1533214286.pdf

Reasons for updating

  • Add New Doc

EDM Updated on 01 August 2019

File name

Benepali Quick Reference Guide for Pre-filled Pen (PFPen EN v1.1) _1533214260.pdf

Reasons for updating

  • Add New Doc

Updated on 01 August 2019

File name

Benepali 50mg SPC_23.05.19_1564675388.pdf

Reasons for updating

  • Correction of spelling/typing errors

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

Updated on 23 May 2019

File name

Benepali 50mg PFP PL_23.05.2019_1558610222.pdf

Reasons for updating

  • Change to section 2 - pregnancy, breast feeding and fertility
  • Change to section 6 - date of revision

Updated on 23 May 2019

File name

Benepali 50mg SPC_23.05.2019_1558610193.pdf

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

Section 4.6:

Update to align with the reference product to add additional information to this section - the following text has been added:

The effects of etanercept on pregnancy outcomes have been investigated in two observational cohort studies.....In another observational multi‑country registry study comparing the risk of adverse pregnancy outcomes in women exposed to etanercept during the first 90 days of pregnancy (n=425) to those exposed to non-biologic drugs (n=3497), there was no observed increased risk of major birth defects (crude odds ratio [OR]= 1.22, 95% CI: 0.79-1.90; adjusted OR = 0.96, 95% CI: 0.58-1.60 after adjusting for country, maternal disease, parity, maternal age and smoking in early pregnancy). This study also showed no increased risks of minor birth defects, preterm birth, stillbirth, or infections in the first year of life for infants born to women exposed to etanercept during pregnancy.

The following text has been updated to read: Benepali should only be used during pregnancy if clearly needed

Updated on 22 March 2019

File name

Benepali 50mg PFP PL Mar 2019_1553197867.pdf

Reasons for updating

  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Updated on 21 March 2019

File name

Benepali 50mg SPC Mar 2019_1553197920.pdf

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

Section 4.8 has been updated to include lichenoid skin reactions as a rare adverse event.

Updated on 16 November 2018

File name

Benepali 50mg PFP PL_16.11.18_1542381122.pdf

Reasons for updating

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

Updated on 16 November 2018

File name

Benepali 50mg PFS PFP SPC_16.11.18_1542381040.pdf

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)

Updated on 29 May 2018

File name

Benepali_50mg_solution_for_injection_in pre-filled_pen_and_ pre-filled_ syringe_SPC.docx

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)

Updated on 29 May 2018

File name

Benepali 50 mg solution for injection in pre-filled pen (PIL).pdf

Reasons for updating

  • Improved presentation of PIL

Updated on 13 February 2018

Reasons for updating

  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Updated on 13 February 2018

File name

PIL_16720_987.pdf

Reasons for updating

  • New PIL for new product

Updated on 29 January 2018

Reasons for updating

  • Change to section 6 - date of revision

Updated on 23 August 2017

Reasons for updating

  • Change to section 7 - Marketing authorisation holder

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

Free text change information supplied by the pharmaceutical company

$0$0$07.       MARKETING AUTHORISATION HOLDER$0

Updated on 23 August 2017

Reasons for updating

  • New SPC for new product

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

Updated on 22 August 2017

Reasons for updating

  • Change to section 6 - marketing authorisation holder

Updated on 07 August 2017

Reasons for updating

  • 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

·         Summary of Product Characteristics (SmPC),

 

Location

Update

SmPC, section 4.8 Undesirable effects

Hepatobiliary disorders:

Uncommon:        Elevated liver enzymes*

Rare:      Elevated liver enzymes, aAutoimmune hepatitis

SmPC, section 4.8 Undesirable effects

Elevated liver enzymes

In the double-blind periods of controlled clinical trials of etanercept across all indications, the frequency (incidence proportion) of adverse events of elevated liver enzymes in patients receiving etanercept without concomitant methotrexate was 0.54% (frequency uncommon). In the double-blind periods of controlled clinical trials that allowed concomitant treatment with etanercept and methotrexate, the frequency (incidence proportion) of adverse events of elevated liver enzymes was 4.18% (frequency common).

PiL, section 4 Possible side effects

·         Uncommon (may affect up to 1 in 100 people):

elevated liver blood tests (in patients also receiving methotrexate treatment, the frequency of elevated liver blood tests is common).

·         Rare (may affect up to 1 in 1,000 people):

elevated liver blood tests;

Updated on 25 July 2017

Reasons for updating

  • Change to section 4 - possible side effects

Updated on 22 June 2017

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 6.1 - List of excipients
  • Change to section 6.4 - Special precautions for storage
  • Change to section 6.5 - Nature and contents of container
  • Change to section 6.6 - Special precautions for disposal and other handling
  • 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 to the SPC due to approval of new strength of this product.

Updated on 13 June 2017

Reasons for updating

  • Change to section 1 - what the product is used for
  • Change to section 2 - use in children and adolescents
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 2 - pregnancy, breast feeding and fertility
  • Change to section 2 - driving and using machines
  • Change to section 3 - use in children/adolescents
  • Change to section 3 - how to take/use
  • Change to section 4 - possible side effects
  • Change to section 4 - how to report a side effect
  • Change to section 6 - what the product contains
  • Change to section 6 - date of revision

Updated on 10 February 2017

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 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • 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

In section 4.1, Juvenile Idiopathic Arthritis, Paediatric plaque psoriasis, enthesitis-related arthritis and Psoriatic Arthritis added. Consequential updates implemented in other impacted sections.

Updated on 09 February 2017

Reasons for updating

  • Change to section 1 - what the product is used for
  • Change to section 2 - what you need to know - contraindications
  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 2 - use in children and adolescents
  • Change to section 3 - use in children/adolescents
  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Updated on 11 July 2016

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 4.8 – Undesirable effects - how to report a side effect
  • Change to section 5.1 - Pharmacodynamic properties
  • 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



In section 4.2 and in Section 4.8, under the subtitle "special populations", "elderly (above 65 years)" was changed to state "elderly".

In Section 4.4 Special warnings and precautions for use, the text highlighted in red was added.

Congestive heart failure
Physicians should use caution when using Benepali in patients who have congestive heart failure (CHF). There have been postmarketing reports of worsening of CHF, with and without identifiable precipitating factors, in patients taking Etanercept.
There have also been rare (< 0.1%) reports of new onset CHF, including CHF in patients without known pre-existing cardiovascular disease. Some of these patients have been under 50 years of age. Two large clinical trials evaluating the use of Etanercept in the treatment of CHF were terminated early due to lack of efficacy. Although not conclusive, data from one of these trials suggest a possible tendency toward worsening CHF in those patients assigned to Etanercept treatment.

In section 4.8 Undesirable effects: "Worsening of congestive heart failure" was changed to "Congestive heart failure".

Section 5.1, under the subheader "Adult patients with non-radiographic axial spondyloarthritis" was updated due to new originator etanercept data as indicated below. The strike through text was deleted and purple text added.

 

MRIs  of  the  sacroiliac joint and spine were obtained to assess inflammation at  baseline  and  at  week  12.  The double-blind period was followed by an open- label period during which all patients receive etanercept 50 mg weekly for up to an additional 92 weeks.  

MRIs of the sacroiliac joint and spine were obtained to assess inflammation at baseline and at weeks 12 and 104.

 

 

 

 

 

 

 

 

 

 

 

 

In Section 5.2, formatting changes only occurred to introduce a line space was added between text and subheaders

 

 

 

Updated on 07 July 2016

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to side-effects
  • Addition of information on reporting a side effect.

Updated on 10 May 2016

Reasons for updating

  • New SPC for new product

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

Free text change information supplied by the pharmaceutical company

None provided

Updated on 04 May 2016

Reasons for updating

  • New PIL for new product