Atripla 600 mg/200 mg/245 mg film- coated tablets

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Summary of Product Characteristics last updated on medicines.ie: 30/11/2018

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Gilead Sciences Ltd

Gilead Sciences Ltd

Company Products

Medicine NameActive Ingredients
Medicine Name AmBisome (Liposomal Amphotericin) Active Ingredients Amphotericin B
Medicine Name Atripla 600 mg/200 mg/245 mg film- coated tablets Active Ingredients Efavirenz, Emtricitabine, Tenofovir disoproxil fumarate
Medicine Name Biktarvy 50 mg/200 mg/25 mg film-coated tablets Active Ingredients Emtricitabine, Tenofovir alafenamide fumarate, Bictegravir sodium
Medicine Name Cayston 75 mg powder and solvent for nebuliser solution Active Ingredients Aztreonam lysine
Medicine Name Descovy 200 mg/10 mg film-coated tablets Active Ingredients Emtricitabine, Tenofovir alafenamide fumarate
Medicine Name Descovy 200 mg/25 mg film-coated tablets Active Ingredients Emtricitabine, Tenofovir alafenamide fumarate
Medicine Name Emtriva 10 mg/ml oral solution Active Ingredients Emtricitabine
Medicine Name Emtriva 200 mg hard capsules Active Ingredients Emtricitabine
Medicine Name Epclusa 400 mg/100 mg film coated tablets. Active Ingredients Sofosbuvir, Velpatasvir
Medicine Name Eviplera 200 mg/25 mg/245 mg film-coated tablets Active Ingredients Emtricitabine, Rilpivirine Hydrochloride, Tenofovir disoproxil fumarate
Medicine Name Genvoya 150mg/150mg/200mg/10mg film coated tablets Active Ingredients Cobicistat, Elvitegravir, Emtricitabine, Tenofovir alafenamide fumarate
Medicine Name Harvoni 90 mg/400 mg film-coated tablets Active Ingredients Ledipasvir, Sofosbuvir
Medicine Name Hepsera 10 mg tablets Active Ingredients Adefovir dipivoxil
Medicine Name Odefsey 200 mg/25 mg/25 mg film-coated tablets Active Ingredients Emtricitabine, Rilpivirine Hydrochloride, Tenofovir alafenamide fumarate
Medicine Name Sovaldi 400 mg film coated tablets Active Ingredients Sofosbuvir
Medicine Name Stribild 150 mg/150 mg/200 mg/245 mg film coated tablets Active Ingredients Cobicistat, Elvitegravir, Emtricitabine, Tenofovir disoproxil fumarate
Medicine Name Truvada film-coated tablets Active Ingredients Emtricitabine, Tenofovir disoproxil fumarate
Medicine Name Tybost 150mg film coated tablets Active Ingredients Cobicistat
Medicine Name Vemlidy 25 mg film coated tablets Active Ingredients Tenofovir alafenamide fumarate
Medicine Name Viread 245 mg film-coated tablets Active Ingredients Tenofovir disoproxil fumarate
Medicine Name Vosevi 400 mg/100 mg/100 mg film coated tablets Active Ingredients Sofosbuvir, Velpatasvir, Voxilaprevir
Medicine Name YESCARTA (axicabtagene ciloleucel) Active Ingredients Axicabtagene Ciloleucel
Medicine Name Zydelig (idelalisib) 100mg Active Ingredients Idelalisib
Medicine Name Zydelig (idelalisib) 150mg Active Ingredients Idelalisib
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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 13 February 2019 PIL

Reasons for updating

  • Change to MA holder contact details

Updated on 30 November 2018 PIL

Reasons for updating

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

Updated on 30 November 2018 SmPC

Reasons for updating

  • 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)

Updated on 8 October 2018 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)

Updated on 3 August 2018 PIL

Reasons for updating

  • Change to MA holder contact details

Updated on 14 June 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

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

Updated on 14 June 2018 PIL

Reasons for updating

  • Change to section 2 - what you need to know - warnings and precautions

Updated on 7 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 2 May 2018 SmPC

Reasons for updating

  • Change to section 4.3 - Contraindications
  • 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 5.1 - Pharmacodynamic properties

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

Updated on 17 April 2018 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change of contraindications
  • Change to side-effects
  • Change to drug interactions

Updated on 2 June 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 2 June 2017 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
  • 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

Updates to section 4.4 and 4.5 to include data on co-administration with sofosbuvir/velpatasvir

Updated on 25 May 2017 PIL

Reasons for updating

  • New PIL for new product

Updated on 25 May 2017 PIL

Reasons for updating

  • Change to section 2 - what you need to know - contraindications
  • Change to section 6 - date of revision

Updated on 27 September 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

$0·Section 4.4 Special warnings and precautions foruse - reference co-administration with TAF$0$0·Section 4.5 Interaction with other medicinalproducts and other forms of interaction - reference co-administration with TAF $0

Updated on 23 September 2016 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to drug interactions
  • Change to date of revision
  • Change to MA holder contact details

Updated on 17 May 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

·         Section 4.4

 

o    Revise the HIV class label wording on mitochondrial dysfunction following the review of existing data on mitochondrial toxicity including the Mitochondrial Toxicity in Children (MITOC) Study

o    The PILs were also updated accordingly

 

·         Sections 4.4 and 4.5  

o     Addition of a warning update to the safety information with the potential drug interaction of ledipasvir/sofosbuvir (LDV/SOF), as well as that of LDV and SOF as single agents with tenofovir disoproxil fumarate

o    The PILs were also updated accordingly

 

Updated on 13 May 2016 PIL

Reasons for updating

  • Change to side-effects
  • Change to information about pregnancy or lactation
  • Change to date of revision

Updated on 15 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

Sections 4.4 & 4.8:

- Update to delete previous lipodystrophy class labelling text and, to add new class labelling regarding weight and metabolic parameters (blood lipids and glucose).

Section 10:

- Change to the date of revision to January 2016.

Updated on 12 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 28 January 2016 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

Section 4.4:

- Inclusion to state that the most pronounced decreases in bone mineral density were seen in patients treated with tenofovir DF as part of a regimen containing a boosted protease inhibitor, and also to advise that alternative treatment regimens should be considered for patients with osteoporosis that are at a high risk for fractures, in line with HIV European guidelines.

Section 10:

- Change to the date of revision to December 2015.

Updated on 3 August 2015 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

Sections 4.5:

- Information that co-administration of simeprevir with efavirenz is not recommended. The interactions table has also been updated to reflect the observed lack of clinically relevant interaction between simeprevir and tenofovir, and the expected lack of interaction between simeprevir and emtricitabine

Section 10:

- Change to the date of revision to June 2015

Updated on 29 July 2015 PIL

Reasons for updating

  • Change to drug interactions
  • Change to date of revision

Updated on 23 June 2015 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

Sections 4.4 & 4.8:

- Removal of the warnings related to lactic acidosis

Section 10:

- Change to the date of revision to May 2015

Updated on 22 June 2015 PIL

Reasons for updating

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

Updated on 13 March 2015 PIL

Reasons for updating

  • Change to date of revision
  • Change to name of manufacturer

Updated on 3 February 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:

- Inclusion of a reference to the tenofovir resistance-associated substitution K70E.

Section 10:

- Change to the date of revision to December 2014.

Updated on 3 September 2014 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 of the SmPC:

- Addition of safety information on the risk of renal injury in patients with risk factors for renal dysfunction after co-administration of non-steroidal anti-inflammatory drugs (NSAIDs) with tenofovir.
- Change of wording around the monitoring of renal function “In patients at risk for renal impairment consideration should be given to a more frequent monitoring of renal function is required.”/ “Interrupting treatment with Atripla should also be considered in case of progressive decline of renal function when no other cause has been identified.”

Section 4.8 of the SmPC:

- Addition of information about proximal renal tubulopathy.

Updated on 28 August 2014 PIL

Reasons for updating

  • Change to warnings or special precautions for use

Updated on 31 July 2014 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 to section 4.6 to incorporate the efavirenz pregnancy registry data

• Change to the date of revision in section 10 to July 2014

Updated on 25 July 2014 PIL

Reasons for updating

  • Change to date of revision

Updated on 8 July 2014 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

• Update to section 4.5 around cannabinoid tests interaction

• Change to the date of revision to May 2014 in section 10

Updated on 4 July 2014 PIL

Reasons for updating

  • Change to date of revision

Updated on 7 April 2014 SmPC

Reasons for updating

  • 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 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 section 4.5 on interactions with artemether/lumefantrine

• Update of section 4.6 with information on the excretion of efavirenz (EFV) into human breast milk and other minor changes for consistency

• Update of section 10 with the new date of revision

Updated on 28 March 2014 PIL

Reasons for updating

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

Updated on 3 March 2014 SmPC

Reasons for updating

  • 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

Section 4.5:

·         Information on the drug-drug interaction with the HCV protease inhibitors boceprevir and telaprevir

 

·         Additional information on the interaction with rifabutin

Updated on 25 February 2014 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

·         Sections 4. 4 and 4.5 - concomitant use of Ginkgo biloba extracts is not recommended

 

·         Change to the date of revision in section 10

Updated on 25 February 2014 PIL

Reasons for updating

  • Change to drug interactions

Updated on 24 January 2014 PIL

Reasons for updating

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

Updated on 25 June 2013 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


- Sections 4.4 and 4.8 of the SPC have been updated to include the below wording:

 

·         “Autoimmune disorders (such as Graves’ disease) 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”

 

- Additional changes to sections 4.4 and 4.8 are as follows:

 

  • Expression of combination antiretroviral therapy (CART) was amended throughout sections 4.4 and 4.8 of the SPC

 

Section 10

 

- Change to date of revision to May 2013

Updated on 21 June 2013 PIL

Reasons for updating

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

Updated on 22 February 2013 SmPC

Reasons for updating

  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 10 - Date of revision of the text
  • 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 4.8 - Undesirable effects

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

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Section 4.2 (Posology & method of administration)

  • Tenofovir exposure (AUC) will be approximately 30% (changed from 35%) lower following administration of Atripla on an empty stomach as compared to the individual component TDF when taken with food

Section 4.4 (Special warnings & precautions for use) 

  • Addition to state that Atripla should not be co-administered with products containing efavirenz unless needed for dose adjustment e.g. with rifampicin

Section 4.5 (Interactions with other medicinal products) 

  • Addition to state that Atripla should not be co-administered with products containing efavirenz unless needed for dose adjustment e.g. with rifampicin
  • Amendment to the biotransformation data on P450 enzymes and also that efavirenz has shown to induce UGT1A1
  • Antimalarials, acenocoumarol, norephinephrine and dopamine re-uptake inhibitor interaction data included

Section 4.8 (Undesirable effects) 

  • In the metabolism and nutrition disorders section, hypertriglyceridaemia is listed as common and hypercholesterolaemia is listed as uncommon adverse reactions to the efavirenz individual component
  • In the hepatobiliary disorders section, elevated aspartate aminotransferase, elevated alanine aminotransferase, elevated gamma-glutamyltransferase listed as common adverse reactions to the efavirenz individual component

Section 5.1 (Pharmacodynamic properties) 

  • Inclusion of a paragraph to discuss resistance & 96 week data from the open-label extended phase of study GS‑01‑934

Section 5.2 (Pharmacokinetic properties)  

  • Tenofovir exposure (AUC) will be approximately 30% (changed from 35%) lower following administration of Atripla on an empty stomach as compared to the individual component TDF when taken with food
  • Amendment to the biotransformation data on P450 enzymes and also that efavirenz has shown to induce UGT1A1
  • Change in the effect of food section to state that dosing of TDF and FTC in combination with either a high fat meal or a light meal increased the mean AUC of tenofovir by 43.6% and 40.5%, and Cmax by 16% and 13.5%

Section 10 (Date of revision of the text) 

  • Date changed for the revision of the text to January 2013

Updated on 21 February 2013 PIL

Reasons for updating

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

Updated on 22 November 2012 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 extension from 36 to 48 months

·         Section 10- Date changed for the revision of the text to November 2012

Updated on 4 October 2012 SmPC

Reasons for updating

  • Change to section 4.3 - Contraindications
  • Change to section 6.1 - List of excipients
  • Change to section 6.5 - Nature and contents of container
  • Change to section 10 - Date of revision of the text
  • Improved electronic presentation
  • Change to improve clarity and readability
  • Introduction of new pack/pack size

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

Free text change information supplied by the pharmaceutical company

·         Section 4.3  - use of word ‘Co-administration instead of administration’

·         Section 4.3  - use of word ‘adverse reactions instead of undesirable effects’

·         Section 6.1 – ‘List of excipients’ – from hydroxypropylcellulose to hyprolose. This is just change in name and not the excipient (also reflected in the PIL)

·         Section 6.5 - addition of new pack size ’90 (3 bottles of 30) film-coated tablets’.

·         Updated to improve clarity and readability

Updated on 2 October 2012 PIL

Reasons for updating

  • Change to improve clarity and readability
  • Introduction of new pack/pack size
  • Improved electronic presentation

Updated on 3 January 2012 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • 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 to:

 

4.4       Special warnings and precautions for use

 

Minor correction to Renal Impairment statement (page 6 of SPC)

 

Renal impairment: Atripla is not recommended for patients with moderate or severe renal impairment (creatinine clearance < 50 ml/min).

 

In previous SPC update this read (creatinine clearance < 30 ml/min) which was incorrect.

 

4.6         Fertility, pregnancy and lactation – in particular the efavirenz section

 

1)

 

Women of childbearing potential: see below and section 5.3.  Pregnancy should be avoided in women receiving Atripla.  Women of childbearing potential should undergo pregnancy testing before initiation of Atripla.

 

2)

 

Pregnancy

Efavirenz: As of July 2010, the Antiretroviral Pregnancy Registry (APR) has received prospective reports of 718 pregnancies with first-trimester exposure to efavirenz-containing regimens, resulting in 604 live births. One child was reported to have a neural tube defect, and the frequency and pattern of other birth defects were similar to those seen in children exposed to non‑efavirenz‑containing regimens, as well as those in HIV negative controls. The incidence of neural tube defects in the general population ranges from 0.5‑1 case per 1,000 live births. In retrospective reports, there have been six cases of findings consistent with neural tube defects including meningomyelocele, all in mothers exposed to efavirenz‑containing regimens in the first trimester. A causal relationship of these events to the use of efavirenz has not been established and the total number of pregnant women exposed to efavirenz-containing regimens is unknown. As neural tube defects occur within the first 4 weeks of foetal development (at which time neural tubes are sealed), this potential risk would concern women exposed to efavirenz during the first trimester of pregnancy.

 

Malformations have been observed in foetuses from efavirenz-treated monkeys (see section 5.3).

 

3)

 

Atripla should not be used during pregnancy unless the clinical condition of the woman requires treatment with efavirenz/emtricitabine/tenofovir disoproxil fumarate.

 


10.     DATE OF REVISION OF THE TEXT

 

11/2011

 

Updated on 16 December 2011 PIL

Reasons for updating

  • Change to improve clarity and readability

Updated on 7 September 2011 SmPC

Reasons for updating

  • Change to section 3 - Pharmaceutical form
  • 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 4.6 - Pregnancy and lactation
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 5.3 - Preclinical safety data
  • 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 is a summary of main amendments/inclusions to the:

 

SPC:

 

  • Section 3 - Pink, capsule‑shaped, film‑coated tablet, of dimensions 20 mm x 10.4 mm, debossed with “123” on one side, plain on the other side.

 

  • Section 4.1 – Update to indication statement to:Atripla is a fixed‑dose combination of efavirenz, emtricitabine and tenofovir disoproxil fumarate.  It is indicated for the treatment of human immunodeficiency virus‑1 (HIV‑1) infection in adults aged 18 years and over with virologic suppression to HIV‑1 RNA levels…….’

     

    • Section 4.2 – additional statements for the Posology section - inclusion of paragraphs describing what to do when a dose of Atripla is missed or when a patient vomits within an hour of taking the tablet and amendment to statements on discontinuation of therapy.

     

    • Section 4.4 – Inclusion of statement: Bone: In a 144‑week controlled clinical study that compared tenofovir disoproxil fumarate with stavudine in combination with lamivudine and efavirenz in antiretroviral‑naïve patients, small decreases in bone mineral density of the hip and spine were observed in both treatment groups.  Decreases in bone mineral density of spine and changes in bone biomarkers from baseline were significantly greater in the tenofovir disoproxil fumarate treatment group at 144 weeks.  Decreases in bone mineral density of the hip were significantly greater in this group until 96 weeks.  However, there was no increased risk of fractures or evidence for clinically relevant bone abnormalities over 144 weeks.’

    Bone abnormalities (infrequently contributing to fractures) may be associated with proximal renal tubulopathy (see section 4.8).  If bone abnormalities are suspected then appropriate consultation should be obtained.

     

    • Section 4.6 – Now titled ‘Fertility, pregnancy and lactation’ – within this section amendments to the Pregnancy, Breast-feeding & Fertility statements: including:

     

    Emtricitabine and tenofovir disoproxil fumarate: A moderate amount of data on pregnant women (between 300‑1,000 pregnancy outcomes) indicate no malformations or foetal/neonatal toxicity associated with emtricitabine and tenofovir disoproxil fumarate.  Animal studies on emtricitabine and tenofovir disoproxil fumarate do not indicate reproductive toxicity (see section 5.3).

     

    Atripla should not be used during pregnancy unless clearly necessary (there are no other appropriate treatment options).

     

    Breast‑feeding

    Emtricitabine and tenofovir have been shown to be excreted in human milk.  There is insufficient information on the effects of emtricitabine and tenofovir in newborns/infants.  Studies in rats have demonstrated that efavirenz is excreted in milk; concentrations of efavirenz were much higher than those in maternal plasma.  Therefore Atripla should not be used during breast-feeding.

     

    As a general rule, it is recommended that HIV infected women do not breast-feed their infants in order to avoid transmission of HIV to the infant.

     

    Fertility

    No human data on the effect of Atripla are available.  Animal studies do not indicate harmful effects of efavirenz, emtricitabine or tenofovir disoproxil fumarate on fertility.

     

     

    • Section 5.1 - Inclusion of statement Paediatric population: The safety and efficacy of Atripla in children under the age of 18 years have not been established.’

     

    • Section 5.2 – Inclusion of statements on Gender, Ethnicity and paediatric populations

     

    • Section 5.3 – Inclusion of information on pre-clinical safety data

     

    • Section 10 – Change to date of revision

Updated on 5 September 2011 PIL

Reasons for updating

  • Change to, or new use for medicine
  • Change to warnings or special precautions for use
  • Change to information about pregnancy or lactation
  • Change to further information section
  • Change to date of revision

Updated on 8 February 2011 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

Change to:

Section 4.8: update for the efavirenz component is consistent with the SPC proposed in the Sustiva Type II variation procedure EMEA/H/C/249/II/104 (submission date, 18 December 2009). Correspondingly, the update for the tenofovir disoproxil (as fumarate) and emtricitabine components is consistent with the SPC proposed for Truvada Type II variation procedure EMEA/H/C/594/II/54 (submission date, 13 March 2009).


Section 10:  Change of Date or Revision to December 2010

Updated on 24 January 2011 PIL

Reasons for updating

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

Updated on 7 July 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 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
  • 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: revised wording for the dosing recommendation for coadministration with rifampicin
  • section 4.4: statement on closer monitoring of patients who have previously experienced renal events while receiving adefovir dipivoxil
  • section 4.5: complete review of interactions section
  • section 4.6: update to pregnancy data
  • section 4.8: details of exacerbation of hepatitis after the discontinuation of treatment to the postmarketing experience section and inclusion of the new postmarketing event of angioedema, tinnitus, tremor and flushing.
  • section 10: Change to date of revision
  • Updated on 25 May 2010 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

    Update to Section 5.1 to include data from the Kaiser Observational Study: Please see below:

    A similar trend was observed in a sub-group analysis of treatment-experienced patients with baseline HIV‑1 RNA < 75 copies/ml from a retrospective cohort study (data collected over 20 months, see Table 7).

     

    Table 7: Maintenance of pure virologic response (Kaplan Meier % (Standard Error) [95%CI]) at week 48 for treatment-experienced patients with baseline HIV‑1 RNA < 75 copies/ml who had therapy switched to Atripla according to the type of prior antiretroviral regimen (Kaiser Permanente patient database)

     

    Prior Atripla components

    (N=299)

    Prior NNRTI‑based regimen

    (N=104)

    Prior PI‑based regimen

    (N=34)

    98.9% (0.6%)

    [96.8%, 99.7%]

    98.0% (1.4%)

    [92.3%, 99.5%]

    93.4% (4.5%)

    [76.2%, 98.3%]


    Update to Section 10: Change of date of revision to April 2010

    Updated on 10 December 2009 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

    Section 7:

    been updated to reflect the
    change of address of the EU Marketing Authorisation Holder for Atripla from Dublin to Cork.

    Section 10:

    Date of revision changed to August 09.

    Updated on 7 December 2009 PIL

    Reasons for updating

    • Change of manufacturer
    • Change to date of revision

    Updated on 29 April 2009 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)

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    • In section 6.3, the shelf-life has been changed from 2 to 3 years.

     

    • In section 10, the date of revision of the text has been updated to March 2009

    Updated on 24 April 2009 PIL

    Reasons for updating

    • Change to date of revision

    Updated on 30 January 2009 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 4.5 - Interaction with other medicinal products and other forms of interaction
    • 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 4.1

    Statement regarding demonstration of benefit being based on 48-week data rather than 24-week data.

    Section 4.4

    Addition of the following statements:

    • Currently available data indicate a trend that in patients on a PI‑based antiretroviral regimen the switch to Atripla may lead to a reduction of the response to the therapy (see section 5.1).  These patients should be carefully monitored for rises in viral load and, since the safety profile of efavirenz differs from that of protease inhibitors, for adverse reactions.
    • Atripla should not be administered concomitantly with adefovir dipivoxil.
    • Bone abnormalities (infrequently contributing to fractures) may be associated with proximal renal tubulopathy (see section 4.8). 

    Update to the section on co-infection with HBV or HCV.

    Section 4.5

    Updated to include adefovir dipivoxil.

    Section 4.8

    Extensive changes made to the information at the beginning of the section relating to adverse reactions reported in the 48 week study AI266073 including the addition of a new table (Table 2) for this study and subsequent renumbering of later tables.

    The following statement added under Adverse reactions associated with individual components of Atripla

    • The most notable adverse reactions that have been reported in clinical studies with efavirenz are rash and nervous system symptoms.  The administration of efavirenz with food may increase efavirenz exposure and may lead to an increase in the frequency of adverse reactions (see section 4.4).  There have been post-marketing reports in association with tenofovir disoproxil fumarate of renal and urinary disorders including renal failure, proximal tubulopathy (including Fanconi syndrome), acute tubular necrosis and nephrogenic diabetes insipidus.

    The following adverse reactions added:

    • Cerebellar coordination and balance disturbances, rhabdomyolysis, osteomalacia (manifested as bone pain and infrequently contributing to fractures), muscular weakness, hypokalaemia, hepatic steatosis,  (all frequency not known)

    The following statement has also been added:

             The following adverse reactions, listed under the body system headings above, may occur as a consequence of proximal renal tubulopathy: rhabdomyolysis, osteomalacia (manifested as bone pain and infrequently contributing to fractures), hypokalaemia, muscular weakness, myopathy and hypophosphataemia.  These events are not considered to be causally associated with tenofovir disoproxil fumarate therapy in the absence of proximal renal tubulopathy.

    Section 5.1

    In vivo resistance updated from none to extremely limited

    The Clinical experience information relating to Study AI266073 has been extensively updated to reflect the 48-week data rather than 24-week data.

    Section 10

    Date of revision updated to 12/2008

    Updated on 30 January 2009 PIL

    Reasons for updating

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

    Updated on 11 September 2008 SmPC

    Reasons for updating

    • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
    • Change to section 4.8 - Undesirable effects
    • Change to section 5.1 - Pharmacodynamic properties
    • Introduction of new pack/pack size

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

    Free text change information supplied by the pharmaceutical company

    Section 4.5 Interaction with other medicinal products and other forms of interaction - addition of tacrolimus interaction information.
    Section 4.8 
    Undesirable effects - revision of information relating to HIV/HBV or HCV co-infected patients relating to data from study GS-01-934 144 week data.
    Section 5.1 
    Pharmacodynamic properties In vivo resistance  -
    update to information relating to study GS-01-934 144 week data.
    Section 8.          MARKETING AUTHORISATION NUMBER(S) - new 90-day pack.

    Updated on 11 September 2008 PIL

    Reasons for updating

    • Change to drug interactions
    • Introduction of new pack/pack size

    Updated on 26 March 2008 PIL

    Reasons for updating

    • Change of manufacturer
    • Change to marketing authorisation holder
    • Change to further information section

    Updated on 26 March 2008 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

    Variation 1A/01 to change the MAH name.

    Updated on 8 January 2008 SmPC

    Reasons for updating

    • New SPC for new product

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

    Updated on 8 January 2008 PIL

    Reasons for updating

    • New PIL for new product