Cervarix Suspension for Injection

  • Name:

    Cervarix Suspension for Injection

  • Company:
    info
  • Active Ingredients:

    human papillomavirus vaccine

  • Legal Category:

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

Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 15/04/19

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Summary of Product Characteristics last updated on medicines.ie: 27/5/2020

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GlaxoSmithKline (Ireland) Ltd

GlaxoSmithKline (Ireland) Ltd

Company Products

Medicine NameActive Ingredients
Medicine Name Amoxil Vial for Injection 500mg Active Ingredients Amoxicillin sodium
Medicine Name ANORO ELLIPTA 55 micrograms/22 micrograms inhalation powder, pre-dispensed Active Ingredients Umeclidinium bromide, Vilanterol trifenatate
Medicine Name Augmentin 250 mg/125 mg film-coated tablets Active Ingredients Amoxicillin trihydrate, Potassium clavulanate
Medicine Name Augmentin 500mg/125mg Film-coated Tablets Active Ingredients Amoxicillin trihydrate, Potassium clavulanate
Medicine Name Augmentin 875/125mg Film Coated tablets Active Ingredients Amoxicillin trihydrate, Clavulanic Acid
Medicine Name Augmentin Duo Mixed Fruit 400 mg/57 mg /5 ml Powder for Oral Suspension Active Ingredients Amoxicillin trihydrate, Clavulanic Acid
Medicine Name Augmentin DUO Suspension 400/57mg Active Ingredients Amoxicillin trihydrate, Potassium clavulanate
Medicine Name Augmentin Intravenous 1.2g Active Ingredients Amoxicillin sodium, Potassium clavulanate
Medicine Name Augmentin Paediatric 125mg/31.25mg per 5ml Powder for Oral Suspension Active Ingredients Amoxicillin trihydrate, Potassium clavulanate
Medicine Name AVAMYS 27.5 micrograms/spray nasal spray suspension Active Ingredients Fluticasone furoate
Medicine Name Avodart Soft Capsules 0.5mg Active Ingredients Dutasteride
Medicine Name Babyhaler Active Ingredients No Active Ingredients
Medicine Name Bactroban Nasal Ointment Active Ingredients Mupirocin calcium
Medicine Name Bactroban Ointment Active Ingredients Mupirocin
Medicine Name Becotide Evohaler 100 Active Ingredients Beclometasone Dipropionate
Medicine Name Becotide Evohaler 250 Active Ingredients Beclometasone Dipropionate
Medicine Name Becotide Evohaler 50 Active Ingredients Beclometasone Dipropionate
Medicine Name Benlysta 120 mg and 400 mg powder for concentrate for solution for infusion Active Ingredients Belimumab
Medicine Name Betnovate C 0.1% / 3% w/w Cream Active Ingredients Betamethasone Valerate, Clioquinol
Medicine Name Betnovate Cream 0.1% w/w Active Ingredients Betamethasone Valerate
Medicine Name Betnovate Ointment 0.1% w/w Active Ingredients Betamethasone Valerate
Medicine Name Betnovate RD Cream Active Ingredients Betamethasone Valerate
Medicine Name Betnovate RD Ointment Active Ingredients Betamethasone Valerate
Medicine Name Betnovate Scalp Application 0.1% w/v Cutaneous Solution Active Ingredients Betamethasone Valerate
Medicine Name Bexsero, suspension for injection in pre-filled syringe Active Ingredients Meningococcal group-B vaccine (rDNA, component, adsorbed)
1 - 0 of 134 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 27 May 2020 SmPC

Reasons for updating

  • 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)

Updated on 19 May 2020 SmPC

Reasons for updating

  • 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)

Updated on 15 April 2019 PIL

Reasons for updating

  • Change to section 1 - what the product is used for
  • Change to section 2 - use in children and adolescents
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 6 - date of revision

Updated on 15 April 2019 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

section 4.5 - coadministration with meningococcal serogroups A, C, W-135, Y tetanus toxoid conjugate vaccine (MenACWY-TT);

Updated on 9 October 2018 PIL

Reasons for updating

  • Change to section 4 - how to report a side effect

Updated on 9 October 2018 SmPC

Reasons for updating

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

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

Free text change information supplied by the pharmaceutical company

Section 4.8 Reporting details amended due to pack split (removal of UK details).

No submission to agency so date of revision is not amended.

 

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 29 May 2018 SmPC

Reasons for updating

  • Change to section 1 - Name of medicinal product
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.3 - Shelf life
  • Change to section 6.4 - Special precautions for storage
  • Change to section 6.5 - Nature and contents of container
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 8 - Marketing authorisation number(s)
  • 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 1: Vial and multidose container presentations added
Section 4.4: 'against HPV-16/18' added to 'see section 5.1' cross reference
Section 4.8: UK adverse event reporting details updated
Section 5.1: Formatting changes to table, commas added
Section 6.3: Shelf life changed from 4 to 5 years. Paragraph on multidose vial added
Section 6.4: Line on multidose vial added
Section 6.5: Text on prefilled syringe and multidose vial added. Heading of 'vial' added for the text that was previously there.
Section 6.6: Subheading 'pre-filled syringe' added. instructions for administration by pre-filled syringe added. Paragraphs on instructions for use of vial and multidose vial added.
Section 8: MA numbers for prefilled syringe, vial and multidose vial added

 

Updated on 29 May 2018 PIL

Reasons for updating

  • Change to section 4 - how to report a side effect
  • Change to MA holder contact details
  • Change to further information section
  • Change to date of revision

Updated on 3 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 30 April 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 9 March 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 9 March 2017 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

5.1: Addition of information relating to study HPV-060 (a long term follow-up immunogenicity and safety study in female 15 to 55 years of age) and study HPV-015 (A phase III, double-blind, randomized, controlled study to evaluate the safety, immunogenicity and efficacy of Cervarix in healthy adult female subjects aged 26 years and above)

Updated on 15 August 2016 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 4.5 - Interaction with other medicinal products and other forms of interaction
  • 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 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

• Update to section 4.1 (indications) to include prevention of premalignant anal lesions and anal cancers causally related to HPV.
• Update to section 4.2 (posology/administration) to replace reference to “girls” with “children” and include instructions not to administer intravascularly or intradermally, or to co-administer with another injectable vaccine at the same site.
• Update to section 4.3 (contraindications) to remove instruction to postpone administration in subjects suffering from acute febrile illness. NB – this text is moved to section 4.4
• Update to section 4.4 (warnings & precautions) to insert instruction to postpone administration in subjects suffering from acute febrile illness.
• Update to section 4.5 (interactions) to remove detail related to use with immunosuppressive medicines. Instruction inserted to refer to section 4.4
• Update to section 4.7 (driving/using machines) to include statement that undesirable effects (section 4.8) may temporarily affect ability to drive/use machines.
• Update to section 4.8 (undesirable effects) to include reference to additional clinical studies in males. Section reformatted into tabular format (per QRD).
• Update to section 5.1 (pharmacodynamics) to include information related to anal cancers and neoplasia.
• Update to section 6.3 (shelf life) to include instruction to discard vaccine after certain period.

Updated on 12 August 2016 PIL

Reasons for updating

  • New PIL for new product

Updated on 12 August 2016 PIL

Reasons for updating

  • Change to, or new use for medicine
  • Change to warnings or special precautions for use
  • Change to storage instructions
  • Change to date of revision
  • Change to dosage and administration

Updated on 30 November 2015 PIL

Reasons for updating

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

Updated on 10 March 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

Description of change to SPC:

Section 4.6  - updated to reflect recently available data

Updated on 9 March 2015 PIL

Reasons for updating

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

Updated on 8 December 2014 SmPC

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

Update sections 4.2 and 5.1 of the SPC to extend the current 2-dose 0, 6 months schedule to 0, 5-13 months schedule.

Updated on 5 December 2014 PIL

Reasons for updating

  • Change to date of revision
  • Change to dosage and administration
  • Addition of information on reporting a side effect.

Updated on 2 September 2014 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

Update section 4.4 to delete the sentence “The decision to vaccinate an individual woman should take into account her risk for previous HPV exposure and her potential benefit from vaccination”  in line with changes requested by the CHMP

Section 4.8 has been updated with the addition of HPRA details for adverse reporting.

Updated on 13 January 2014 SmPC

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

Updated to introduce a 2 dose schedule for vaccinees aged 9 to 14 years, with specific instructions regarding the factors requiring a third dose, i.e. administration in vaccinees from 15 years and older and in all vaccinees where the second vaccine dose is administered before the 5th month after the first dose.

 

5.1       Pharmacodynamic properties

Updated to describe the updated seroconversion and immune response data report in clinical trials, which justified the changes to the Posology described above.

 

 

 

Package leaflet

 

3.         How Cervarix is given

 

Under the sub-heading ‘How much is given’, the description is changed in-line with the Posology updates in the SPC.

Updated on 10 January 2014 PIL

Reasons for updating

  • Change to, or new use for medicine
  • Change to how the medicine works

Updated on 8 October 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 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

Changes to:

Section 4.4 - Special warnings and precautions for use,
Section 4.8 - Undesirable effects,
Section 5.1 - Pharmacodynamic properties

Updated on 8 October 2013 PIL

Reasons for updating

  • Change to side-effects

Updated on 26 April 2013 PIL

Reasons for updating

  • Change to, or new use for medicine

Updated on 26 April 2013 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • 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

Updated the indication to include vulvar and vaginal lesions, grouped with cervical legions under the term genital lesions, to read:

Cervarix is a vaccine for use from the age of 9 years for the prevention of premalignant genital (cervical, vulvar and vaginal) lesions and cervical cancer causally related to certain oncogenic Human Papillomavirus (HPV) types. See sections 4.4 and 5.1 for important information on the data that support this indication.

 

 

5.1          Pharmacodynamic properties

 

Mechanism of action

Updated the statement regarding the effects HPV-16 and HPV-18 is responsible for to include ‘HPV-related high grade vulvar and vaginal intraepithelial neoplasia’, to read:

HPV-16 and HPV-18 are estimated to be responsible for approximately 70% of cervical cancers and 70% of HPV-related high grade vulvar and vaginal intraepithelial neoplasia. Other oncogenic HPV types can also cause cervical cancer (approximately 30%). HPV 45, -31 and -33 are the 3 most common non-vaccine HPV types identified in squamous cervical carcinoma (12.1%) and adenocarcinoma (8.5%).

 

Updated the term of ‘premalignant cervical lesions’ to ‘premalignant genital lesions’ and changed it’s definition to include ‘high-grade vulvar intraepithelial neoplasia (VIN2/3) and high-grade vaginal intraepithelial neoplasia (VaIN2/3)’, to read:

The term “premalignant genital lesions” in section 4.1 corresponds to high-grade Cervical Intraepithelial Neoplasia (CIN2/3), high-grade vulvar intraepithelial neoplasia (VIN2/3) and high-grade vaginal intraepithelial neoplasia (VaIN2/3).

 

Clinical studies

Prophylactic efficacy against HPV-16/18 in women naïve to HPV-16 and/or HPV-18

Added the following paragraph:

At end of study analysis, there were 2 cases of VIN2+ or VaIN2+ associated with HPV-16 or HPV-18 in the vaccine group and 7 cases in the control group in the ATP cohort.  The study was not powered to demonstrate a difference between the vaccine and the control group for these endpoints.

 

 

 

Updated on 16 November 2012 SmPC

Reasons for updating

  • Change to section 6.3 - Shelf life
  • Change to section 6.5 - Nature and contents of container
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 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 4.5 - 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

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

Free text change information supplied by the pharmaceutical company

SPC UPDATE

 

Editorial changes to sections 2, 4.3, 4.4, 4.5, 4.7, 4.8, 5.2, 6.3, 6.5 and 6.6

 

3.         Pharmaceutical Form

Removed the statement regarding the appearance of the product upon storage, i.e.;

Upon storage, a fine white deposit with a clear colourless supernatant may be observed.

 

4.2          Posology and method of administration

The Posology statement has been updated to specify 3 separate doses, i.e.;

The recommended vaccination consists of 3 separate 0.5 ml doses administered according to the schedule:  0, 1, 6 months.

 

4.6          Fertility, pregnancy and lactation

Added the subheadings ‘Pregnancy’, ‘Breast-feeding’ and ‘Fertility’.

 

Under the subheading ‘Pregnancy’ regarding the specific studies of the vaccine in pregnant women, changed the total number of pregnancies reported from 3,993 to 10,476, and the number of pregnancies reported in women who received Cervarix from 2,009 to 5,387.

 

Added the following statement regarding ‘Fertility’:

No fertility data are available.

 

5.1          Pharmacodynamic properties

Under ‘Clinical studies’ added two subheadings ‘Clinical efficacy in women aged 15 to 25 years’ and ‘Clinical efficacy in women aged 26 years and older’.

 

Added the following updated under the new subheading ‘Clinical efficacy in women aged 26 years and older’ further to the interim analysis of the clinical trial HPV-015

The efficacy of Cervarix was assessed in a double-blind, randomised Phase III clinical trial (HPV-015) that included a total of 5777 women aged 26 years and older. The study was conducted in North America, Latin America, Asia Pacific and Europe, and allowed women with previous history of HPV disease/infection to be enrolled. An interim analysis was performed when all subjects had completed the month 48 study visit.

The primary analyses of efficacy were performed on the ATP cohort for efficacy and the TVC.

 

Vaccine efficacy against 6 month persistent infection with HPV-16/18 (relevant surrogate marker for cervical cancer) is summarised in the following table.

 

Table 7: Vaccine efficacy against 6M PI with HPV 16/18 in ATP and TVC

HPV-16/18 endpoint

ATP(1)

TVC(2)

Cervarix

Control

% Efficacy (97.7% CI)

Cervarix

Control

% Efficacy (97.7% CI)

n/N

n/N

n/N

n/N

6M PI

6/1859

34/1822

82.9% (53.8; 95.1)

71/2767

132/2776

47% (25.4; 62.7)

N= number of subject in each group

n= number of subjects reporting at least one event in each group

6M PI = 6-month persistent infection

CI = Confidence Interval

(1) 3 doses of vaccine, DNA negative and seronegative at month 0 and DNA negative at month 6 for the relevant HPV type (HPV-16 and/or HPV-18)

(2) at least one dose of vaccine, irrespective of HPV DNA and serostatus at month 0. Includes 15% of subjects with previous history of HPV disease/infection

 

Vaccine efficacy against 6-month persistent infection was 79.1% (97.7% CI [27.6; 95.9]) for HPV-31 and 76.9% (97.7% CI [18.5; 95.6]) for HPV-45 in the ATP cohort (3 doses of vaccine, DNA negative at months 0 and 6 for the relevant HPV type).

 

Vaccine efficacy against 6-month persistent infection was 23.2% (97.7% CI [-23.3; 52.5]) for HPV-31 and 67.7% (97.7% CI [35.9; 84.9]) for HPV-45 in the TVC.

 

Added the new subheading ‘Immunogenicity in women aged 26 years and older’, with the following information:

In the Phase III study (HPV-015) in women 26 years and older, at the 48-month time point, i.e. 42 months after completion of the full vaccination course, 100% and 99.4% of initially seronegative women remained seropositive for anti-HPV-16 and anti-HPV-18 antibodies, respectively. All initially seropositive women remained seropositive for both anti-HPV-16 and anti-HPV-18 antibodies. Antibody titers peaked at month 7 then gradually declined up to month 18 and stabilized to reach a plateau up to month 48.

 

Updated on 13 November 2012 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to storage instructions
  • Change to drug interactions
  • Change to information about pregnancy or lactation
  • Change to information about driving or using machinery

Updated on 21 September 2011 SmPC

Reasons for updating

  • 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

5.1          Pharmacodynamic properties

Up-dated regarding Final Analysis of Efficacy study HPV-008, to include end-of study data.

 

Updated on 19 May 2011 PIL

Reasons for updating

  • Change to drug interactions

Updated on 28 March 2011 SmPC

Reasons for updating

  • Change to section 5.1 - Pharmacodynamic properties
  • 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

4.5          Interaction with other medicinal products and other forms of interaction

Updated to include the statement that Cervarix can be administered concomittantly with a combined hepatitis A (inactivated) and hepatitis B (rDNA) vaccine (Twinrix) or with hepatitis B (rDNA) vaccine (Engerix B), with specific inclusion of the ‘Twinrix’ and ‘Engerix B’ product names

 

5.1          Pharmacodynamic properties

Under the subheading ‘Persistence of Immune Response to Cervarix’ updated the data regarding study 023, including the update that:

Vaccine-induced IgG GMTs for both HPV-16 and HPV-18 peaked at month 7 and then declined to reach a plateau from month 18 up to the [M95-M101] interval with ELISA GMTs for both HPV-16 and HPV-18 at least still 10-fold higher [previously 11-fold higher] than the ELISA GMTs observed in women who cleared a natural HPV infection.

 

Previous to the approval of V0018, this was ‘11-fold higher

Updated on 1 December 2010 PIL

Reasons for updating

  • Change to, or new use for medicine

Updated on 3 September 2010 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - 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

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

·         Removed specific reference to HPV types 16 and 18, using the term ‘certain oncogenic’ HPV types

·         Added reference to section 4.4 of the SPC for more information

·         Added statement that:

The use of Cervarix should be in accordance with official recommendations.

 

4.2        Posology and method of administration

·         Added the following instruction regarding the use of a flexible schedule when necessary:

If flexibility in the vaccination schedule is necessary, the second dose can be administered between 1 month and 2.5 months after the first dose and the third dose between 5 and 12 months after the first dose.

·         Added subheadings ‘Posology’, ‘Paediatric population’ and ‘Method of administration’

 

4.4        Special warnings and precautions for use

·         The following was added:

The decision to vaccinate an individual woman should take into account her risk for previous HPV exposure and her potential benefit from vaccination.

·         Extended the precaution that Cervarix only protects against diseases caused by HPV types 16 and 18 and certain other oncogenic related HPV types and added that;

… appropriate precautions against sexually transmitted diseases should continue to be used.

·         Added warnings that Cervarix is for prophylactic use only and has no effect on active HPV infections or established clinical disease and that routine cervical screening remains critically important and should follow local recommendations.

 

4.6        Fertility, pregnancy and lactation

·         Added ‘Fertility’ to the heading of this section

·         Updated the numbers of pregnancies reported during the clinical development program from a total of 1,737 to 3,993 pregnancies, and of those in women who had received Cervarix from 870 to 2,009

 

4.8        Undesirable effects

·         Moved the following side effect to the top of the list of undesirable effects reported in clinical trials, with no change to the frequency or actual undesirable effect:

Infections and infestations:

Uncommon: upper respiratory tract infection

 

5.1        Pharmacodynamic properties

·         Under the subheading Mechanism of action, added that Cervarix is an adjuvanted vaccine and qualified the statement that HPV-16 and HPV-18 are estimated to be responsible for approximately 70% of cervical cancers. Added the statement that:

Other oncogenic HPV types can also cause cervical cancer (approximately 30%). HPV 45, -31 and -33 are the 3 most common non-vaccine HPV types identified in squamous cervical carcinoma (12.1%) and adenocarcinoma (8.5%).

·         Under the subheading Mechanism of action , added the definition:

The term “premalignant cervical lesions” in section 4.1 corresponds to high-grade Cervical Intraepithelial Neoplasia (CIN2/3).

·         Under the subheading Clinical studies:

Referring to the phase III trial (study 008), extended the primary efficacy end points from CIN2 to include CIN2/3 or AIS, adding the statement that:

Cervical Intraepithelial Neoplasia (CIN) grade 2 and 3 (CIN2/3) and cervical adenocarcinoma in situ (AIS) were used in the clinical trials as surrogate markers for cervical cancer.

Added the satatement that the secondary endpoints included 6-month persistent infection in addition to the previously approved 12-month persistent infection, explaining that:

Persistent infection that lasts for at least 6 months has also been shown to be a relevant surrogate marker for cervical cancer.

Deleted the following statements:

o    Cervical Intraepithelial Neoplasia (CIN) grade 2 and 3 was used in the clinical trials as a surrogate marker for cervical cancer.

o    The term “premalignant cervical lesions” in section 4.1 corresponds to high-grade Cervical Intraepithelial Neoplasia (CIN 2/3).

·         Updated the subheading ‘Prophylactic efficacy in women naïve to HPV-16 and/or HPV-18’ to specify efficacy against HPV-16/18, i.e.:

Prophylactic efficacy against HPV-16/18 in women naïve to HPV-16 and/or HPV-18

·         Under the updated heading Prophylactic efficacy against HPV-16/18 in women naïve to HPV-16 and/or HPV-18, updated all the efficacy data in line with the updated results from study HPV008

·         Replaced the previous subheading ‘Prophylactic efficacy in women with current or prior infection’ with two new subheadings ‘Efficacy against HPV-16/18 in women with evidence of HPV-16 or HPV-18 infection at study entry’ and ‘Efficacy against HPV types 16 and 18 in women with and without prior infection or disease’, and updated the data in line with the updated results from study HPV008

·         Added the subheading ‘Overall impact of the vaccine on cervical HPV disease burden, and updated the data in line with the updated results from study HPV008

·         Added the subheading ‘Cross-protective efficacy’ and updated data regarding cross-protection and vaccine efficacy against 6-months persistent infection.

·         Under the subheading ‘Immunogenicity’ added the following three new subheadings:

‘Immune response to Cervarix after the primary vaccination course’

‘Persistence of Immune Response to Cervarix’

·         …under which the statement regarding immunogenicity observed in study 008 was updated to refer to immunogenicity data ‘up to 36 months’ as opposed to ‘up to 7 months’

‘Evidence of Anamnestic (Immune Memory) Response’

·         …under which a statement was added regarding the results of study 024 in which a challenge dose administered to 65 subject at a mean interval of 6.5 years after administration of the first vaccine dose resulted in an anamnestic immune response to HPV-16 and HPV-18

 

 

Updated on 7 July 2010 SmPC

Reasons for updating

  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.6 - Special precautions for disposal and other handling

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

Free text change information supplied by the pharmaceutical company

5.1          Pharmacodynamic properties

Under Clinical studies and the sub-heading Prophylactic efficacy in women with current or prior infection:

Added the acronym (PBNA) for pseudovirion-based neutralisation assay.

 

Updated the information regarding study 001/007 further to data from the month-12 of Study HPV-023, from:

Study 001/007, which included women from 15 to 25 years of age at the time of vaccination, evaluated the immune response against HPV-16 and HPV-18 up to 76 months post dose 1.

Vaccine-induced IgG Geometric Mean Titres (GMT) for both HPV-16 and HPV-18 peaked at month 7 and then declined to reach a plateau from month 18 up to the end of the follow-up (month 76). At the end of the follow-up period, GMTs for both HPV-16 and HPV-18 were still at least 11-fold higher than titres observed in women previously infected but who cleared HPV infection and >98% of the women were still seropositive for both antigens.

 

to:

Study 001/007, which included women from 15 to 25 years of age at the time of vaccination, evaluated the immune response against HPV-16 and HPV-18 up to 76 months after administration of the first vaccine dose. In study 023 (a subset of study 001/007), the immune response continued to be evaluated up to 88 months. 111 subjects in the vaccine group had immunogenicity data at the [M83-M88] interval after the first vaccine dose with a median follow-up of 7 years. Of these subjects, 100% (95% CI: 96.7;100) remained seropositive for HPV-16 and HPV-18 in the ELISA assay.

Vaccine-induced IgG GMTs for both HPV-16 and HPV-18 peaked at month 7 and then declined to reach a plateau from month 18 up to the [M83-M88] interval with ELISA GMTs for both HPV-16 and HPV-18 at least still 11-fold higher than the ELISA GMTs observed in women who cleared a natural HPV infection.

 

6.6          Special precautions for disposal and other handling

Removed diagram of needle and instruction in point 2 to ‘see picture’

 

Updated on 1 April 2010 PIL

Reasons for updating

  • Change to side-effects
  • Change to drug interactions
  • Change to dosage and administration

Updated on 11 January 2010 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 6.6 - Special precautions for disposal and other handling
  • 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

Cervarix suspension for injection in pre-filled syringe

Human Papillomavirus vaccine [Types 16, 18] (Recombinant, adjuvanted, adsorbed)

 

Updates to SPC and Package Leaflet following the Commission Decision (approval) of 23/11/2009 of variations V0012 and V0013

 

 

SPC UPDATES

 

Section 4.4 Special warnings and precautions for use

Updated to include the following additional warning regarding occurrence of syncope:

Syncope (fainting) can occur following, or even before, any vaccination especially in adolescents as a psychogenic response to the needle injection. This can be accompanied by several neurological signs such as transient visual disturbance, paraesthesia and tonic-clonic limb movements during recovery. It is important that procedures are in place to avoid injury from faints.

 

 

Section 4.5 Interaction with other medicinal products and other forms of interaction

Updated to add the following statement regarding the co-administration of Cervarix and HAB vaccine (Twinrix):

Cervarix may be administered concomitantly with a combined hepatitis A (inactivated) and hepatitis B (rDNA) vaccine (HAB vaccine).

Administration of Cervarix at the same time as Twinrix (HAB vaccine) has shown no clinically relevant interference in the antibody response to the HPV and hepatitis A antigens. Anti-HBs geometric mean antibody titers were lower on co-administration, but the clinical significance of this observation is not known since the seroprotection rates remain unaffected. The proportion of subjects reaching anti-HBs ≥ 10mIU/ml was 98.3% for concomitant vaccination and 100% for Twinrix alone.

 

 

Section 4.8 Undesirable effects

Updated to include the categorization ‘clinical trials’ for the existing undesirable effects and to add the following listing of undesirable effects, as reported through post-marketing surveillance.

Post marketing surveillance

Because these events were reported spontaneously, it is not possible to reliably estimate their frequency.

 

Blood and lymphatic system disorders

Lymphadenopathy

 

Immune system disorders

Allergic reactions (including anaphylactic and anaphylactoid reactions), angioedema

 

Nervous system disorders

Syncope or vasovagal responses to injection, sometimes accompanied by tonic-clonic movements (see section 4.4)

 

 

Section 6.6 Special precautions for disposal and other handling

Updated to include the following instructions for administration of the vaccine:

Instructions for administration of the vaccine presented in pre-filled syringe

 

shown are diagrams of needle and syringe and diagram of step taken
                                                           

 

  

                                                       

 


1.       Holding the syringe barrel in one hand (avoid holding the syringe plunger), unscrew the syringe cap by twisting it anticlockwise.

2.       To attach the needle to the syringe, twist the needle clockwise into the syringe until you feel it lock. (see picture)

3.       Remove the needle protector, which on occasion can be a little stiff.

4.       Administer the vaccine.

Updated on 3 November 2009 PIL

Reasons for updating

  • Change to drug interactions

Updated on 2 November 2009 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

Cervarix suspension for injection in pre-filled syringe (EU/1/07/419/004)

 

Updates due to V0006 (co-administration with other vaccines (dTpa and dTpa-IPV)
Canges in red
 

SPC

 

Section 4.5, Interaction with other medicinal products and other forms of interaction

 

Under the subheading Use with other vaccines’ the instruction was updated from:

Data have not been generated on the concomitant administration of Cervarix and other vaccines.

 

to:

Cervarix may be administered concomitantly with a combined booster vaccine containing diphtheria (d), tetanus (T) and pertussis [acellular] (pa) with or without inactivated poliomyelitis (IPV), (dTpa, dTpa-IPV vaccines), with no clinically relevant interference with antibody response to any of the components of either vaccine. The sequential administration of combined dTpa-IPV followed by Cervarix one month later tended to elicit lower anti-HPV-16 and anti-HPV-18 GMTs as compared to Cervarix alone. The clinical significance of this observation is not known.

 

If Cervarix is to be given at the same time as another injectable vaccine, the vaccines should always be administered at different injection sites

Updated on 8 June 2009 SmPC

Reasons for updating

  • Change to section 6.3 - Shelf life
  • Change to section 8 - MA number

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 (6.3) :

Shelf life extended from 3 years to 4 years.

Recommendation regarding non-refrigerated storage added:

stable for 3 days at 8°-25°C, stable for 1 day at 25°-37°C

Section 8 updated to include the following MA numbers:

EU/1/07/419/005

EU/1/07/419/006

EU/1/07/419/007

EU/1/07/419/008

EU/1/07/419/009

Updated on 20 May 2009 PIL

Reasons for updating

  • Change to storage instructions

Updated on 5 September 2008 PIL

Reasons for updating

  • Changes to therapeutic indications
  • Change to date of revision

Updated on 1 September 2008 PIL

Reasons for updating

  • Changes to therapeutic indications
  • Change to date of revision

Updated on 26 August 2008 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 9 - Date of renewal of authorisation
  • 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 Therapeutic Indications:

Wording updated to 'prevention of premalignant cervical lesions' (previously 'prevention of high-grade cervical intraepithelial neoplasia (CIN grades 2 and 3)').
 

Section 5.1 Pharmacodynamic properties (I'm not sure what the IPHA term is for this, it doesn't appear on the list Fiona gave us):

1. Clinical Study HPV-007 data approved for long-term protection of 6.4 years (previously 5.5 years). Regarding the control group in HPV-007, there were 16 (previously 10) cases of persistent HPV-16 infection and 5 (previously 4) cases of persistent HPV-18 infection.

2. Inclusion of the wording 'Papillomavirus vaccine' as the pharmatherapeutic group.
 

Section 9 Date of First Authorisation/Renewal

Reworded to read Date of first authorisation: 20 September 2007 (previously '21 September 2007')

Section 10 Date of Revision of Text

13/08/2008 (previously blank)

Updated on 28 September 2007 SmPC

Reasons for updating

  • New SPC for new product

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

Updated on 28 September 2007 PIL

Reasons for updating

  • New PIL for new product