Zeffix 100mg Film-Coated Tablets *
Pharmacy Only: Prescription

  • Company:

    GlaxoSmithKline (Ireland) Ltd
  • Status:

    No Recent Update
  • Legal Category:

    Product subject to medical prescription which may not be renewed (A)
  • Active Ingredient(s):

    *Additional information is available within the SPC or upon request to the company

Updated on 08 July 2022

File name

62c7e960390bb.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

Type IAIN - Variation for the name change of the Poznan site (responsible for manufacturing, packaging, QC testing and batch release of the finished product) from GlaxoSmithKline Pharmaceutical S.A. to Delpharm Poznań Spółka Akcyjna

Section 6 of the PIL - Manufacturer has been impacted.

Updated on 05 October 2021

File name

ieukni-spc-zeffixtablets-issue7draft1_1633446184.pdf

Reasons for updating

  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 4.9 - Overdose

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

Free text change information supplied by the pharmaceutical company

Type II Variation – Update to the Overdose symptoms and signs text

Type II Variation – Update to Lamivudine-HBV elimination half-life

Updated on 05 October 2021

File name

ieukni-pl-combined-zeffix-issue9draft1_1633445957.pdf

Reasons for updating

  • Change to section 3 - overdose, missed or forgotten doses

Free text change information supplied by the pharmaceutical company

Type II Variation – Update to the Overdose symptoms and signs text

Updated on 24 September 2021

File name

ieukni-pl-combined-zeffix-issue8draft1eMC_1632489801.pdf

Reasons for updating

  • Change to section 6 - date of revision
  • Change to information for healthcare professionals

Updated on 02 February 2021

File name

ie-pl-zeffix-issue7draft1_1612254455.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

Section 6 - deletion of the inactive Site of Batch Release.

Updated on 13 November 2020

File name

ie-spc-zeffixtablets-issue6draft1-medicines.ie_1605269587.pdf

Reasons for updating

  • 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 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

Section 4.4: Addition the statement ‘Each Zeffix tablet contains less than 1 mmol sodium (23 mg), that is to say essentially ‘sodium free’’.
Section 4.8 Update to reporting of side effects statement in section 4.8 the SmPC.

Section 6.6 Addition of "waste material" to special precaucios for disposal
minor editorial and formatting updates across the SmPC.

Updated on 13 November 2020

File name

ie-pl-zeffixtabs-issue6draft-medicines.ie_1605269359.pdf

Reasons for updating

  • Change to section 2 - excipient warnings
  • Change to section 4 - how to report a side effect
  • Change to section 6 - date of revision

Updated on 07 December 2018

File name

ie-pl-zeffixtabs-issue5draft1 - Meds ie_1544192911.pdf

Reasons for updating

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

Updated on 07 December 2018

File name

ie-spc-zeffixtablets-issue5draft1 - Meds ie_1544192953.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 01 June 2018

File name

ukie-spc-zeffixtablets.docx

Reasons for updating

  • New SPC for new product

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

Updated on 02 February 2018

File name

PIL_9925_948.pdf

Reasons for updating

  • New PIL for new product

Updated on 02 February 2018

Reasons for updating

  • New SPC for new product

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

Updated on 02 February 2018

Reasons for updating

  • 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 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 4.4: a minor amendment has been implemented throughout the SmPC in order to update the clinical terminology of Pneumocystis carinii pneumonia to Pneumocystis jiroveci pneumonia.

Section 4.5: add information regarding the interaction between lamivudine and sorbitol

Section 4.8: UK reporting details updated in line with EMA Appendix V

Updated on 02 February 2018

Reasons for updating

  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 4 - how to report a side effect
  • Change to section 6 - date of revision
  • Change to other sources of information section

Updated on 09 February 2017

Reasons for updating

  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 10 - Date of revision of the text
  • Change to section 4.4 - Special warnings and precautions for use

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 
Updated in relation to the clinical outcome data from the Antiretroviral Pregnancy Registry (APR). In addition, an introductory paragraph for Pregnancy has. been added to section 4.6 in order to align with the Epivir (lamivudine for Human Immunodeficiency Virus indication) text that has previously been approved by the EMA.

Section 4.4
As a result of the literature search in connection with the above, an update was required to the pregnancy-related statement in section 4.4.

Updated on 07 July 2016

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

Update to the information in SmPC sections 4.4 Warnings and Precautions, 4.8 Undesirable Effects in relation to lactic acidosis.

Updated on 06 July 2016

Reasons for updating

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

Updated on 24 June 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 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 4.2 was updated for a switch to or addition of an alternative agent without cross-resistance to lamivudine based on therapeutic guidelines. Subsequence changes were deemed necessary in sections 4.4 and 5.1 of the SmPC to support this information.

Updated on 23 June 2016

Reasons for updating

  • Change to date of revision
  • Change to improve clarity and readability

Updated on 02 December 2015

Reasons for updating

  • Change to date of revision
  • Change to MA holder contact details

Updated on 15 July 2014

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 4.6 - Pregnancy and lactation
  • 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 5.2 - Pharmacokinetic properties
  • Change to section 6.1 - List of excipients
  • 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

Section 2 – Removal of trade name reference; administrative updates

Section 3 – QRD update, inclusion of tablet dimensions

Section 4.2 – Layout & format update, removal of trade name reference, inclusion of dosing in HIV infected patients & dosing in elderly population, route of administration included

Section 4.4 – Layout & format update to warnings and precautions to include info on lactic acidosis, exacerbations of hepatitis (during treatment, after treatment discontinuation, in patients with decompensated cirrhosis, mitochondrial dysfunction.  Headings have also been included for Paediatric patients, delta hepatitis, immunosuppressive treatments, monitoring

Section 4.5 – update to drug interactions to include emtricitabine

Section 4.6 – update to data for use in breast-feeding, inclusion of statement on fertility

Section 4.7 – update to wording to include new warning about driving/using machinery

Section 4.8 – reference to ADRs in paediatric & other special populations, reporting of side effects

Sections 5.1, 5.2, 6.1 and 7 – Admin updates

Updated on 11 July 2014

Reasons for updating

  • Change to, or new use for medicine
  • Change to warnings or special precautions for use
  • Change of contraindications
  • Change to side-effects
  • Change to information about pregnancy or lactation
  • Change to information about driving or using machinery
  • Change to improve clarity and readability
  • Addition of information on reporting a side effect.

Updated on 21 October 2013

Reasons for updating

  • Change to MA holder contact details

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

Free text change information supplied by the pharmaceutical company

Change of Product Authorisation holder

Updated on 18 October 2013

Reasons for updating

  • Change to marketing authorisation holder

Updated on 24 April 2013

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

 

7.       MARKETING AUTHORISATION HOLDER

 

Glaxo Group Ltd

980 Great West Road

Brentford

Middlesex

TW8 9GS

United Kingdom

Updated on 24 April 2013

Reasons for updating

  • Change of licence holder

Updated on 24 February 2011

Reasons for updating

  • Change to information about pregnancy or lactation

Updated on 04 February 2011

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 4.6 - Pregnancy and lactation
  • 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

4.2       Posology and method of administration

Updated wording regarding use in children and adolescents from:

Children and adolescents: Zeffix is not recommended for use in children and adolescents below 18 years of age due to lack of data on safety and efficacy (see section 5.2).

to:

The safety and efficacy of Zeffix in children and adolescents aged below 18 years have not been established.  Currently available data are described in sections 4.4 and 5.1 but no recommendation on a posology can be made.

 

4.4           Special warnings and precautions for use

Updated warnings regarding exacerbation of hepatitis, adding the following:

Exacerbations on treatment:  Spontaneous exacerbations in chronic hepatitis B are relatively common and are characterised by transient increases in serum ALT.  After initiating antiviral therapy, serum ALT may increase in some patients as serum HBV DNA levels decline. In patients with compensated liver disease, these increases in serum ALT were generally not accompanied by an increase in serum bilirubin concentrations or signs of hepatic decompensation.

 

Replacing:

If Zeffix is discontinued or there is a loss of efficacy due to the development of YMDD mutant HBV (see section 4.2), some patients may experience clinical or laboratory evidence of recurrent hepatitis.

with:

Exacerbations after treatment discontinuation:  Acute exacerbation of hepatitis has been observed in patients who have discontinued hepatitis B therapy and is usually detected by serum ALT elevations and re-emergence of HBV DNA.  In the controlled Phase III trials with no-active-treatment follow-up, the incidence of post-treatment ALT elevations (more than 3 times baseline) was higher in lamivudine-treated patients (21%) compared with those receiving placebo (8%).  However, the proportion of patients who had post-treatment elevations associated with bilirubin elevations was low and similar in both treatment arms.  See Table 3 in section 5.1 for more information regarding frequency of post treatment ALT elevations.  For lamivudine-treated patients, the majority of post-treatment ALT elevations occurred between 8 and 12 weeks post-treatment.  Most events have been self-limiting, however some fatalities have been observed.  If Zeffix is discontinued, patients should be periodically monitored both clinically and by assessment of serum liver function tests (ALT and bilirubin levels), for at least four months, and then as clinically indicated.

 

Deleting the following:

Exacerbation of hepatitis has primarily been detected by serum ALT elevations, in addition to the re-emergence of HBV DNA. See Table 3 in section 5.1 for more information regarding frequency of post treatment ALT elevations. Most events have been self-limited, however some fatalities have been observed.

 

For patients who develop evidence of recurrent hepatitis post-treatment, there are insufficient data on the benefits of re-initiation of lamivudine treatment.

 

Added the subheading Exacerbations in patients with decompensated cirrhosis and replaced the term advanced liver disease with decompensated cirrhosis.

 

Added the following warning:

For patients who develop evidence of recurrent hepatitis post-treatment, there are insufficient data on the benefits of re-initiation of lamivudine treatment.

 

4.6       Fertility, pregnancy and lactation

Added subheadings Pregnancy, Breast-feeding and Fertility, and included that ‘No data available’ for Fertility.

 

4.8       Undesirable effects

Updated the statement regarding frequency categories from:

The frequency categories assigned to the adverse reactions below are estimates: for most reactions, suitable data for calculating incidence are not available. Very common and common adverse drug reaction frequency categories were determined from clinical trial data and the background incidence in placebo groups was not taken into account.

 

to

The frequency categories assigned to the adverse reactions are mainly based on experience from clinical trials including a total of 1171 patients with chronic hepatitis B receiving lamivudine at 100mg.

 

Recategorised Angio dema to ‘rare’ from ‘not known’ frequency

 

Recategorised Muscle disorders, including myalgia and cramps to ‘common’ from ‘not known’ frequency

 

5.1       Pharmacodynamic properties

Added ‘Antivirals for systemic use’ to the definition of Pharmacotherapeutic group

 

5.2       Pharmacokinetic properties

Changed the subheading from ‘Metabolism’ to ‘Biotransformation

Updated on 13 August 2010

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 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • 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

Section 4.1 Therapeutic indications

 

Added the following conditional statements that when useed in the treatment of chronic hepatitis B in adults with compensated liver disease:

Initiation of lamivudine treatment should only be considered when the use of an alternative antiviral agent with a higher genetic barrier is not available or appropriate (see in section 5.1).

 

and in decompensated liver disease,. Zeffix should be used:

in combination with a second agent without cross-resistance to lamivudine (see section 4.2).

 

 

Section 4.2 Posology and method of administration

 

Added the following statement regarding requirementfor use in combination with a second agent:

In patients with decompensated liver disease, lamivudine should always be used in combination with a second agent, without cross-resistance to lamivudine, to reduce the risk of resistance and to achieve rapid viral suppression. 

 

Removed reference to the unknown nature of optimal treatment duration in with either HBeAg positive or HBeAg negative CHB and replaced it with the following statement regarding Clinical resistance:

Clinical resistance: In patients with either HBeAg positive or HBeAg negative CHB, the development of YMDD (tyrosine-methionine-aspartate-aspartate) mutant HBV may result in a diminished therapeutic response to lamivudine, indicated by a rise in HBV DNA and ALT from previous on-treatment levels.  In order to reduce the risk of resistance in patients receiving lamivudine monotherapy, a modification of treatment should be considered if serum HBV DNA remains detectable at or beyond 24 weeks of treatment. In patients with YMDD mutant HBV, addition of an alternative agent without cross-resistance to lamivudine should be considered (see section 5.1).

 

 

Section 4.4 Special warnings and precautions for use

 

Warning added that regular monitoring required for HBV DNA in HbeAg positive patients

 

Updated the statements regarding HBV viral subpopulations with reduced susceptibility to lamivudine that the addtion of a second agent without cross resistance to lamivudine, should be considered.

 

4.5       Interaction with other medicinal products and other forms of interaction

 

Removed recommendation not to use with zalcitabine

 

4.6       Pregnancy and lactation

 

Updated statement regarding use while breastfeeding.

 

 

5.1       Pharmacodynamic properties

Added statement regarding mantenence of viral suppression:

Viral suppression was maintained (follow-on study NUC20917) with combined therapy during the second year of treatment to week 104 with patients having continued improvement in virologic and biochemical responses.

 

Added statement regarding the factors associated with HBV DNA breakthrough:

In a retrospective study to determine the factors associated with HBV DNA breakthrough, 159 Asian HBeAg-positive patients were treated with lamivudine and followed up for a median period of almost 30 months.  Those with HBV DNA levels greater than 200 copies/mL at 6 months (24 weeks) of lamivudine therapy had a 60 % chance of developing the YMDD mutant compared with 8 % of those with HBV DNA levels less than 200 copies/mL at 24 weeks of lamivudine therapy.  The risk for developing YMDD mutant was 63% versus 13% with a cut off of 1000 copies/ml (NUCB3009 and NUCB3018).

 

Updated statement on viral suppression:

Forty patients (HBeAg negative or HBeAg positive) with either decompensated liver disease or recurrent HBV following liver transplantation and YMDD mutant were enrolled into an open label arm of study NUC20904. Addition of 10 mg adefovir dipivoxil once daily to ongoing lamivudine 100mg for 52 weeks resulted in a median decrease in HBV DNA of 4.6 log10 copies/ml. Improvement in liver function was also seen after one year of therapy. This degree of viral suppression was maintained (follow-on study NUC20917) with combined therapy during the second year of treatment to week 104 and most patients had improved markers of liver function and continued to derive clinical benefit.

 

Section 9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

 

Updated date of latest renewal to

27 August 2009

Updated on 29 October 2008

Reasons for updating

  • Correction of spelling/typing errors

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

Updated on 02 October 2008

Reasons for updating

  • Change to name of manufacturer

Updated on 29 August 2007

Reasons for updating

  • Improved electronic presentation

Updated on 04 April 2007

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • 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

4.2 'Posology and method of administration' and 5.1 'Pharmacodynamic properties' of the SPC to increase the continuation of therapy from HBeAg seroconversion from 3 months to at least 3-6 months and to include a warning relating to the rate of late virological relapses.

Updated on 31 July 2006

Reasons for updating

  • Improved electronic presentation

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

Updated on 02 June 2006

Reasons for updating

  • Change of manufacturer

Updated on 01 June 2005

Reasons for updating

  • New PIL for medicines.ie

Updated on 20 August 2003

Reasons for updating

  • Improved electronic presentation

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

Updated on 19 August 2003

Reasons for updating

  • Improved electronic presentation

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

Updated on 25 June 2003

Reasons for updating

  • New SPC for medicines.ie

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