Kivexa film-coated tablets

  • Name:

    Kivexa film-coated tablets

  • Company:
    info
  • Active Ingredients:

    Abacavir Sulfate, Lamivudine

  • Legal Category:

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

Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 31/10/18

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Summary of Product Characteristics last updated on medicines.ie: 31/10/2018

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ViiV Healthcare UK Ltd

ViiV Healthcare UK Ltd

Company Products

Medicine NameActive Ingredients
Medicine Name Celsentri film-coated tablets Active Ingredients Maraviroc
Medicine Name Combivir Film-Coated Tablets Active Ingredients Lamivudine, Zidovudine
Medicine Name Dovato 50 mg/300 mg film-coated tablets Active Ingredients Dolutegravir sodium
Medicine Name Epivir Film-Coated Tablets 150mg Active Ingredients Lamivudine
Medicine Name Epivir Film-Coated Tablets 300mg Active Ingredients Lamivudine
Medicine Name Epivir Oral Solution 10mg/ml Active Ingredients Lamivudine
Medicine Name Juluca 50 mg/25 mg film-coated tablets Active Ingredients Dolutegravir sodium, Rilpivirine Hydrochloride
Medicine Name Kivexa film-coated tablets Active Ingredients Abacavir Sulfate, Lamivudine
Medicine Name Retrovir Capsules 100mg Active Ingredients Zidovudine
Medicine Name Retrovir IV Active Ingredients Zidovudine
Medicine Name Retrovir Oral Solution Active Ingredients Zidovudine
Medicine Name Telzir 50mg/ml Oral Suspension Active Ingredients Fosamprenavir calcium
Medicine Name Telzir 700mg Film-Coated Tablets Active Ingredients Fosamprenavir calcium
Medicine Name Tivicay film-coated tablets Active Ingredients Dolutegravir sodium
Medicine Name Triumeq 50 mg/600 mg/300 mg film-coated tablets Active Ingredients Abacavir Sulfate, Dolutegravir sodium, Lamivudine
Medicine Name Trizivir Film-Coated Tablets Active Ingredients Abacavir Sulfate, Lamivudine, Zidovudine
Medicine Name Ziagen Film-Coated Tablets 300mg Active Ingredients Abacavir Sulfate
Medicine Name Ziagen Oral Solution 20mg/ml Active Ingredients Abacavir Sulfate
1 - 0 of 18 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 31 October 2018 PIL

Reasons for updating

  • Change to section 4 - how to report a side effect
  • Change to section 6 - marketing authorisation holder
  • Change to section 6 - date of revision

Updated on 31 October 2018 SmPC

Reasons for updating

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

Section 7 updated: MAH transfer
Section 4.8 update: removal of the IE reporting information in the UK only SPC and removal of the UK reporting information in the IE only SPC.
 

Updated on 16 October 2018 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

Type IA (IN) PRAC recommended variation to add Autoimmune Hepatitis (AIH) to the SmPC sections 4.4 and 4.8.

SmPC Section 4.4 Warnings:
Autoimmune disorders (such as Graves' disease and autoimmune hepatitis) have also been reported to occur in the setting of immune reactivation; however, the reported time to onset is more variable and these events can occur many months after initiation of treatment.

SmPC Section 4.8 Undesirable events:
Autoimmune disorders (such as Graves' disease and autoimmune hepatitis) have also been reported; however, the reported time to onset is more variable and these events can occur many months after initiation of treatment. (see section 4.4).

Updated on 1 June 2018 SmPC

Reasons for updating

  • New SmPC for new product

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

Updated on 16 May 2018 SmPC

Reasons for updating

  • Other

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

Updated on 11 May 2018 SmPC

Reasons for updating

  • New SmPC for new product

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

Updated on 11 May 2018 SmPC

Reasons for updating

  • New SmPC for new product

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

Updated on 11 May 2018 SmPC

Reasons for updating

  • New SmPC for new product

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

Updated on 1 February 2018 SmPC

Reasons for updating

  • New SmPC for new product

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

Updated on 1 February 2018 SmPC

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 31 January 2018 PIL

Reasons for updating

  • New PIL for new product

Updated on 31 January 2018 PIL

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 other sources of information section

Updated on 28 July 2016 SmPC

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 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 sections 4.4 and 4.5 of the SmPC to remove the current information regarding a potential interaction between abacavir and ribavirin.

Updated on 28 July 2016 PIL

Reasons for updating

  • Change to drug interactions
  • Change to date of revision

Updated on 12 April 2016 SmPC

Reasons for updating

  • 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 5.2 - Pharmacokinetic 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

Update of SmPC sections 4.2, 4.3, 4.4 and 5.2 in order to align the Hepatic Impairment wording for the 3 older abacavir-containing products (ZIAGEN™, KIVEXA™ and TRIZIVIR™) with the TRIUMEQ™ SmPC.  In addition, the MAH has taken the opportunity to correct some minor administrative errors in the labelling for the 3 products.

SmPC section 4.4 - Mitochondrial dysfunction following exposure in utero.

Updated on 11 April 2016 PIL

Reasons for updating

  • Change to information about pregnancy or lactation
  • Change to date of revision

Updated on 9 February 2016 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

EU Labelling revisions on Lipodystrophy & Lactic Acidosis–PRAC recommendations

Updated on 8 February 2016 PIL

Reasons for updating

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

Updated on 23 October 2015 SmPC

Reasons for updating

  • 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

Correction made to SPC as we found section 4.9 (Overdose) to be missing from the previously published SPC.

Updated on 25 September 2015 SmPC

Reasons for updating

  • 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 5.1 – antiviral activity update

Updated on 18 September 2015 SmPC

Reasons for updating

  • Change to section 6.5 - Nature and contents of container
  • Change to section 8 - MA number
  • 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

Description of change to SPC:

Update to Section 6.5 –  description of CR enclosure added

Section 8 – deletion of 001 licence number

Updated on 16 September 2015 PIL

Reasons for updating

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

Updated on 21 July 2015 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 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 of sections 4.1, 4.2, 4.3, 4.4 and 4.8 of the SmPC to revise the information on hypersensitivity reactions

Updated on 17 July 2015 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change of contraindications
  • Change to side-effects
  • Change to date of revision
  • Correction of spelling/typing errors

Updated on 15 July 2015 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic 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



Reverted back to previous version of SPC on medicines.ie

Update of sections 4.1, 4.2, 4.8, 5.1 and 5.2 of the SmPC to include an update to the once-daily dosing recommendation for Kivexa to lower the threshold for use in paediatric patients from >40kg to >25 kg, which will harmonize the EU dosing recommendations with those in the WHO treatment guidelines, based on data from study COL105677 (ARROW).

Updated on 14 July 2015 PIL

Reasons for updating

  • Change to, or new use for medicine
  • Change to date of revision
  • Change to dosage and administration

Updated on 13 July 2015 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 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 of sections 4.1, 4.2, 4.3, 4.4 and 4.8 of the SmPC to revise the information on hypersensitivity reactions

Updated on 10 July 2015 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to side-effects
  • Change to date of revision
  • Correction of spelling/typing errors

Updated on 8 July 2015 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic 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

To include an update to the posology once-daily dosing recommendation for Kivexa for use in paediatric patients >25 kg, in order to harmonize the EU dosing recommendations with those in the WHO treatment guidelines, based on data from study COL105677 (ARROW). The SmPC sections 4.1, 4.2, 4.8, 5.1, and 5.2 have been updated.

Updated on 6 July 2015 PIL

Reasons for updating

  • Change to, or new use for medicine
  • Change to date of revision
  • Change to dosage and administration

Updated on 7 May 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

Update Section 4.6 of SmPC  to include WHO Breast-feeding guidance

Updated on 6 May 2015 PIL

Reasons for updating

  • Change to information about pregnancy or lactation
  • Change to date of revision
  • Addition of information on reporting a side effect.

Updated on 8 December 2014 SmPC

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 4.3 - Contraindications
  • 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 4.8 – Undesirable effects - how to report a side effect
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.3 - Preclinical safety data
  • Change to section 6.1 - List of excipients
  • Change to section 6.5 - Nature and contents of container
  • Change to section 9 - Date of renewal of authorisation
  • Change to section 10 - Date of revision of the text
  • Correction of spelling/typing errors

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

Free text change information supplied by the pharmaceutical company

Update to SPC – please refer to attached tracked document for detailed changes.  The following sections have been updated:

·         Section 2 – description of excipient

·         Section 4.1 - Indications section reworded, removal of screening before re-initiation of ABC in patients with  unknown HLA B*5707 status

·         Section 4.2 – layout of information changed, rewording of use in paediatric population and use in renal impairment

·         Section 4.3 – HIV transmission labelling update, formatting changes, rewording of use in patients with hep B/C

·         Section 4.5 – statement added to re-iterate that Kivexa should not be used with any other products containing lamividine (now mentioned in Section 4.4 & 4.5), DI with emtricitatbine/lamivudine added to table, re-wording of recommendation for use of Kivexa with anti-infective products

·         Section 4.6 – Pregnancy/lactation wording updated

·         Section 4.8 - Angioedema added as rare ADR, QRD update to include reporting details

·         Section 5.1, 5.3, 6.1, 6.5 & 9 all updated

Updated on 3 December 2014 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change of contraindications
  • Change to storage instructions
  • Change to side-effects
  • Change to drug interactions
  • Change to information about driving or using machinery
  • Change to further information section
  • Change to date of revision
  • Correction of spelling/typing errors

Updated on 2 January 2014 SmPC

Reasons for updating

  • Improved electronic presentation

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

Free text change information supplied by the pharmaceutical company

.

Updated on 23 December 2013 PIL

Reasons for updating

  • Change to side-effects
  • Change to drug interactions
  • Change to dosage and administration
  • Change to MA holder contact details

Updated on 17 May 2013 SmPC

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

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

Free text change information supplied by the pharmaceutical company

·         There are a number of editorial changes in sections 4.5, 10

·         The following text was added to section 4.4 of the SPC with regards to cladribine

The combination of lamivudine with cladribine is not-recommended (see section 4.5).

·         The following text was added to section 4.5 of the SPC with regards to autoimmune disorders

CYTOTOXICS

Cladribine/Lamivudine

Interaction not studied.

 

In vitro lamivudine inhibits the intracellular phosphorylation of cladribine leading to a potential risk of cladribine loss of efficacy in case of combination in the clinical setting. Some clinical findings also support a possible interaction between lamivudine and cladribine

Therefore, the concomitant use of lamivudine with cladribine is not recommended (see section 4.4).

Updated on 16 May 2013 PIL

Reasons for updating

  • Change to drug interactions

Updated on 10 February 2012 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to drug interactions

Updated on 10 February 2012 SmPC

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

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

Free text change information supplied by the pharmaceutical company

Changes to section 4.4 & 4.5

Updated on 16 September 2011 PIL

Reasons for updating

  • Change of contraindications

Updated on 4 July 2011 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • 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

4.2       Posology and method of administration

Added subheading ‘Posology’.

 

4.3       Contraindications

Added the following contraindication:

Kivexa should not be taken with any other medicinal products containing lamivudine or medicinal products containing emtricitabine.

 

4.5       Interaction with other medicinal products and other forms of interaction

Added warning that the co-administration of inducers or inhibitors of UGT enzymes or with compounds eliminated through alcohol dehydrogenase could alter abacavir exposure and the co-administration of lamivudine with OCT inhibitors may increase lamivudine exposure.

 

Interaction data was updated in line with the tabular format described in the HIV guideline

 

4.6       Fertility, pregnancy and lactation

Updated statements regarding use in pregnancy, lactation and added statement regarding fertility.

Added ‘fertility’ to the heading

 

5.1       Pharmacodynamic properties

Updated in line with the Annex B template of the guideline on the clinical development of medicinal products for the treatment of HIV infection, as requested by the CHMP: Restructured with data obtained from literature review and reports previously submitted by the MAH, in line with the HIV guideline EMEA/CPMP/EWP/633/02. The revision concerned the data on in vitro antiviral activity against HIV-1, including non-B subtypes, and HIV-2 for the individual drug components abacavir and lamivudine and/or in combination; data on the impact of selection for additional resistance mutations upon the susceptibility to abacavir or lamivudine in-vitro and in vivo and for therapy-naive versus experienced patients. Furthermore the clinical experience data was organised under separate headings for treatment naïve patients and treatment-experienced patients. In addition the results of treatment-naïve studies CNA30021, EPZ104057 (HEAT), CNA109586 (ASSERT) are now presented in the proposed tabulated format. The tables for CNA30021, EPZ104057 (HEAT) and CNA109586 (ASSERT) have been updated with additional sub-group analyses for baseline ribonucleic acid (RNA) for each of the studies and also for baseline CD4 categories for the CNA30021 study. Data from studies CAL30001 and ESS30008 has been revised to expand on the statistical test results of the analyses. Two tables were introduced from CAL30001 and CNA30021 studies on the Proportion of Patients with <50 cps/mL at Week 48 by Genotypic

Updated on 3 December 2010 PIL

Reasons for updating

  • Change to marketing authorisation holder
  • Change due to user-testing of patient information

Updated on 21 October 2010 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • 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

4.1       Therapeutic indications

Added reference to sections 4.4 and 5.1 of the SPC

 

 

4.4       Special warnings and precautions for use

Added a new sub-heading ‘Risk of virological failure’, under which the following statement was added to the existing statement regarding Triple nucleoside therapy:

- The risk of virological failure with Kivexa might be higher than with other therapeutic options (see section 5.1).

 

 

5.1       Pharmacodynamic properties

Updated the Clinical Experience with data from the HEAT and ASSERT studies regarding virological response in the treatment of therapy-naïve patients.

 

Updated on 13 August 2010 SmPC

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

Change to Section 7

Updated on 8 May 2010 PIL

Reasons for updating

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

Updated on 11 March 2010 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • 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

Important safety update regarding recommendations for HLA-B*5701 screening and reinitiation of abacavir - 'Screening is also recommended prior to re-initiation of abacavir in patients of unknown HLA-B*5701 status who have previously tolerated abacavir




Section 4.1 -Therapeutic indications,
Section 4.4 - Special warnings and precautions for use,
 Section 4.8 - Undesirable effects

Updated on 16 July 2009 SmPC

Reasons for updating

  • 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

Amended text Highlighted in Red 

4.4   Special warnings and precautions for use

………………

Myocardial Infarction: Observational studies have shown an association between myocardial infarction and the use of abacavir. Those studied were mainly antiretroviral experienced patients. Data from clinical trials showed limited numbers of myocardial infarction and could not exclude a small increase in risk.  Overall the available data from observational cohorts and from randomised trials show some inconsistency so can neither confirm nor refute a causal relationship between abacavir treatment and the risk of myocardial infarction.  To date, there is no established biological mechanism to explain a potential increase in risk.  When prescribing Ziagen, action should be taken to try to minimize all modifiable risk factors (e.g. smoking, hypertension, and hyperlipidaemia).

 

5.1   Pharmacodynamic properties

 

Pharmacotherapeutic group: 'nucleoside reverse transcriptase inhibitors (NTRIs).Antivirals for treatment of HIV infections, combinations. ATC code: J05AR02.

 

 

Updated on 8 July 2009 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to how the medicine works

Updated on 27 August 2008 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Introduction of new pack/pack size
  • Correction of spelling/typing errors

Updated on 26 August 2008 SmPC

Reasons for updating

  • Improved electronic presentation

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

Updated on 5 March 2008 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • 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

Changes to Sections 4.1 and 4.4

* Before initiating treatment with abacavir, screening for carriage of HLA-B*5701 should be performed in any HIV-infected patient, irrespective of racial origin.

* Abacavir should not be used in patients known to carry HLA-B*5701, unless no other therapeutic option is available in these patients, based on the treatment history and resistance testing.

Updated on 12 November 2007 SmPC

Reasons for updating

  • Improved electronic presentation

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

Updated on 9 November 2007 SmPC

Reasons for updating

  • 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

Section 5.1 Pharmacodynamic Properties

...

In vivo resistance (Therapy experienced patients): The M184V or M184I variants arise in HIV-1 infected patients treated with lamivudine-containing antiretroviral therapy and confer high-level resistance to lamivudine. In vitro data tend to suggest that the continuation of lamivudine in antiretroviral regimen despite the development of M184V might provide residual anti-retroviral activity (likely through impaired viral fitness). The clinical relevance of these findings is not established. Indeed, the available clinical data are very limited and preclude any reliable conclusion in the field. In any case, initiation of susceptible NRTIs should always be preferred to maintenance of lamivudine therapy. Therefore, maintaining lamivudine therapy despite emergence of M184V mutation should only be considered in cases where no other active NRTIs are available.

 

Section 5.2 Pharmacokenetic properties

...

Intracellular pharmacokinetics

In a study of 20 HIV-infected patients receiving abacavir 300 mg twice daily, with only one 300 mg dose taken prior to the 24 hour sampling period, the geometric mean terminal carbovir-TP intracellular half-life at steady-state was 20.6 hours, compared to the geometric mean abacavir plasma half-life in this study of 2.6 hours. In a crossover study in 27 HIV-infected patients, intracellular carbovir-TP exposures were higher for the abacavir 600 mg once daily regimen (AUC24,ss + 32 %, Cmax24,ss + 99 % and Ctrough + 18 %) compared to the 300 mg twice daily regimen. For patients receiving lamivudine 300 mg once daily, the terminal intracellular half-life of lamivudine-TP was prolonged to 16-19 hours, compared to the plasma lamivudine half-life of 5-7 hours. In a crossover study in 60 healthy volunteers, intracellular lamivudine-TP pharmacokinetic parameters were similar (AUC24,ss and Cmax24,ss) or lower (Ctrough – 24 %) for the lamivudine 300 mg once daily regimen compared to the lamivudine 150 mg twice daily regimen. Overall, tThese data support the use of lamivudine 300 mg and abacavir 600 mg once daily for the treatment of HIV-infected patients. Additionally, the efficacy and safety of this combination given once daily has been demonstrated in a pivotal clinical study (CNA30021- See Clinical experience).

Updated on 28 August 2007 SmPC

Reasons for updating

  • Improved electronic presentation

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

Updated on 8 March 2007 PIL

Reasons for updating

  • Change to, or new use for medicine

Updated on 5 January 2007 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

Section 4.4

· Risk Factors

Analyses of clinical risk factors for hypersensitivity to abacavir have consistently identified the risk for those of black race to be approximately half the risk of other racial groups combined. As this still represents a significant risk (based on the fact that approximately 5% of subjects receiving abacavir develop a hypersensitivity reaction in clinical studies), the same close monitoring should apply to patients of all racial groups.

In addition, two retrospective, case-controlled pharmacogenetic studies have shown that carriage of HLA-B*5701 is associated with a significantly increased risk of clinically suspected hypersensitivity in Caucasians. It is estimated that approximately 50% of patients with the HLA-B*5701 allele develop a suspected hypersensitivity reaction (HSR) during the course of abacavir treatment versus less than 3% of patients who do not have HLA-B*5701 allele in the Caucasian population. This genetic association has not been assessed in prospective controlled clinical studies but such studies are ongoing to better appreciate the association between occurrence of HSR and carriage of HLA-B*5701 allele. However, it is noteworthy that among patients with a suspected hypersensitivity reaction, 50% did not carry HLA-B*5701 in the Caucasian population. Therefore, the clinical diagnosis of suspected hypersensitivity to abacavir must remain the basis for clinical decision-making. It is important to permanently discontinue abacavir and not rechallenge with abacavir if hypersensitivity cannot be ruled out on clinical grounds. Absence of the HLA-B*5701 allele does not justify rechallenge with abacavir due to the potential for a fatal rechallenge reaction. The same recommendation should apply for other races and ethnic groups, although data are more limited in these groups.

Osteonecrosis: Although the etiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported particularly in patients with advanced HIV-disease and/or long-term exposure to combination antiretroviral therapy (CART). Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement.

 

Section 4.8:

Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term exposure to combination antiretroviral therapy (CART). The frequency of this is unknown (see section 4.4).

Updated on 20 December 2006 PIL

Reasons for updating

  • Improved electronic presentation

Updated on 29 August 2006 PIL

Reasons for updating

  • New PIL for medicines.ie

Updated on 27 July 2006 SmPC

Reasons for updating

  • Improved electronic presentation

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

Updated on 5 April 2005 SmPC

Reasons for updating

  • New SPC for new product

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