Last Updated on eMC 04-07-2018 View medicine  | Merck Sharp & Dohme Limited Contact details

When a pharmaceutical company changes an SPC or PIL, a new version is published on the eMC.  For each version, we show the dates it was published on the eMC and the reasons for change.

Reasons for adding or updating:

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

Date of revision of text on the SPC:17-05-2018

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Variation II-WS1349: update of section 5.1 with final results from 2 Long-term follow-up (LTFU) studies: Protocol V501-020-21 and Extension of Protocol V501-16.

 

 

•             Section 4.8 – Undesirable effects:

Reporting of suspected adverse reactions: addition of reference to Google Play and Apple App Store for search for MHRA Yellow Card

 

•             Section 5.1 - Pharmacodynamic properties:

 

- Protocol V501-020-21: 

Extension of study V501-020 (the pivotal efficacy study of qHPV vaccine in young men 16 to 26 years of age) to assess effectiveness and immunogenicity of the qHPV vaccine for up to 10 years of follow-up.

Men vaccinated with Gardasil at 16-26 years of age in Protocol 020 base study will bewere followed up to 10 years in an extension study. SixTen years after vaccination, 8479%, 8780%, 9795% and 4840% were anti-HPV 6, anti-HPV 11, anti-HPV 16 and anti-HPV 18 seropositive in the cLIA, respectively, and 8992%, 8692%, 100100% and 8292% were anti-HPV 6, anti-HPV 11, anti-HPV 16 and anti-HPV 18 seropositive in the IgG LIA, respectively.

 

- Extension of Protocol V501-16

The base study was an MSD-sponsored randomized clinical trial that assessed the immunogenicity of a 2 dose Schedule of the qHPV in adolescents 9 to 13 years of age compared to a 3-dose schedule in young women 16 to 26 years of age. The study provides additional immunogenicity follow-up through 5 years post-vaccination. The following text is added:

Immune Responses to Gardasil using a 2-dose schedule in individuals 9-13 years of age

[…]

In the same study, in girls aged 9-13 years, the immune response after a 2-dose schedule was numerically lower than after a 3-dose schedule (n = 248 at Month 7; n = 82 at Month 36). The clinical relevance of these findings is unknown. A subset of the study participants from the 2-dose group (n=50) were followed 5-years post-vaccination (Month 60 Postdose 1). Among the girls receiving 2 doses of the vaccine, 96%, 100%, 100%, and 84% remained seropositive to anti-HPV 6, anti-HPV 11, anti-HPV 16, and anti-HPV 18, respectively, in the cLIA.

Reasons for adding or updating:

  • Change to section 5.1 - Pharmacodynamic properties

Date of revision of text on the SPC:23-03-2017

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



The changes made to the SmPC are as follows:

·        Section 5.1 – Pharmacodynamic properties: updated with the newest results from the long-term follow-up studies P015-21 and P019-21 : the subparagraphs related to the Efficacy in women 16 through 26 years, Efficacy in women 24 through 45 years and Persistence of Immune Response of Gardasil have been updated.

Reasons for adding or updating:

  • Change to section 7 - Marketing authorisation holder
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:27-01-2017

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 7 – Marketing Authorisation Holder (MAH): the MAH name has been changed from “Sanofi Pasteur MSD SAS” to “MSD VACCINS”.

Reasons for adding or updating:

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.4 - Special precautions for storage
  • Change to section 6.5 - Nature and contents of container
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:04-04-2016

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Combined SPC to include vial and prefilled syringe.

In section 4.4, update of interchangeability 'immunogenicity or efficacy data to support change during vaccination with Gardasil to other HPV vaccines which do not cover the same HPV types. Therefore, it is important that the same vaccine should be prescribed for the whole dose regimen'.

In section 5.1, addition of Efficacy in women 16 through 26 years: The primary analyses of efficacy, with respect to vaccine HPV types (HPV 6, 11, 16, and 18), were conducted in the per-protocol efficacy (PPE) population (i.e. all 3 vaccinations within 1 year of enrollment, no major protocol deviations and naïve to the relevant HPV type(s) prior to dose 1 and through 1 month Postdose 3 (Month 7)).

The inclusion of 10 year long term follow up data for Gardasil.

In section 6.4, updated to revise 'Data from stability studies demonstrate that the vaccine components are stable for 72 hours when stored at temperatures from 8°C to 42°C' (updated from 25°C to 42°C).

In section 6.5, combined details for both presentations.

In section 6.6, concise bullet points providing clear instructions for Special precautions for disposal and other handling.

In section 10, revision date updated to 04/2016.

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable effects - how to report a side effect
  • Change to section 6.4 - Special precautions for storage
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:26-05-2015

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



In section 4.8 include adverse reaction reporting information


In section 6.4 added out of fridge storage condition statement to read: Gardasil should be administered as soon as possible after being removed from the refrigerator. Stability data indicate that the vaccine components are stable for 72 hours when stored at temperatures from 8°C to 25°C. At the end of this period Gardasil should be used or discarded. These data are intended to guide healthcare professionals in case of temporary temperature excursion only.


In section 10, date of revision 05/2015

Reasons for adding or updating:

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

Date of revision of text on the SPC:24-11-2014

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 4.8 addition of Acute disseminated encephalomyelitis, adverse reaction reporting

Section 5.1 Inclusion of effectiveness results and Immunogenicity results from LTFU studies (P015, P018, P019 and P020).

Section 10 date of revision 6 June 2014 updated to 10/2014

Reasons for adding or 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
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:06-06-2014

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Addition of premalignant anal lesions, anal cancers causally related to certain oncogenic Human Papillomavirus (HPV) types to section therapeutic indications

addition of Long-term follow-up studies are currently ongoing to determine the duration of protection. (see section 5.1). in section warning and precaution

Addition of data related to premalignant anal lesions and anal cancers in Pharmacodynamic properties

Reasons for adding or updating:

  • Change to section 2 - Qualitative and quantitative composition
  • 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 10 - Date of revision of the text

Date of revision of text on the SPC:27-03-2014

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

section 2: QUALITATIVE AND QUANTITATIVE COMPOSITION
for the adjuvant, change the unit from mircogram to milligram

section 4.2 posology and methode of administration:
description of an alternative schedule in 2 doses.

section 4.8 undersirable effects
addition of the Reporting of suspected adverse reactions statement

section 5.1Pharmacodynamic properties

addition of paragraph about Immune Responses to Gardasil using a 2-dose schedule in individuals 9-13 years of age

Reasons for adding or updating:

  • Change to section 1 - Name of the medicinal product

Date of revision of text on the SPC:03-05-2013

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Deletion of the black triangle from the name of the product

Reasons for adding or updating:

  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 9 - Date of first Authorisation/renewal of the Authorisation
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:18-10-2012

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



4.4         Special warnings and precautions for use

(...)

Syncope (fainting), sometimes associated with falling, 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. Therefore, vaccinees should be observed for approximately 15 minutes after vaccine administration. It is important that procedures are in place to avoid injury from faints.


(...)

Reasons for adding or updating:

  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 5.1 - Pharmacodynamic Properties

Date of revision of text on the SPC:30-04-2012

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:

Addition of HIV text in section 5.1 and update 4.4

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable Effects

Date of revision of text on the SPC:21-12-2011

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:

Addition of Cellulitis

Reasons for adding or 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 4.6 - Pregnancy and Lactation
  • Change to section 4.9 - Overdose
  • Change to section 5.1 - Pharmacodynamic Properties
  • Change to section 5.3 - Preclinical Safety Data
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:05-08-2011

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:

Addition of Vaccination for Men and genital warts. and the relevant sections of the SmPC to include this additional information.
Update of the SmpC to be in line with the SmPC guideline
Update of the Study for genital warts in section 5.1.

Reasons for adding or updating:

  • Change to section 4.1 - Therapeutic indications
  • 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

Date of revision of text on the SPC:01-08-2010

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:

Therapeutic indication for Women updated as well as speacial warning. the age limit has been extended.

Added efficacy in women

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable Effects
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:01-05-2010

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:

4.8  adverse events of Idiopathic Thrombocytopenic Purpura is added
 

Reasons for adding or 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 5.1 - Pharmacodynamic Properties
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:01-09-2009

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



Reference to 'subjects' has been amended to read 'individuals' throughout the SmPC.

Change to section 4.2 - Posology and method of administration

Paediatric population: Gardasil is not recommended for use in children below 9 years of age due to insufficient data on immunogenicity, safety and efficacy (see section 5.1).

Has been amended to read:

Paediatric population: There is no experience with the use of Gardasil in children below 9 years of age (see section 5.1).

 

Change to section 4.4 - Special warnings & precautions for use

Addition of the following information:

 

Gardasil is for prophylactic use only and has no effect on active HPV infections or established clinical disease.

 

Gardasil does not prevent lesions due to a vaccine HPV type in women already infected with that HPV type at the time of vaccination (see section 5.1).

 

The use of Gardasil in adult women should take into consideration the variability of HPV type prevalence in different geographical areas.  In the clinical study of adult women (24 to 45 years of age), no statistically significant vaccine efficacy was observed after 2.2 years of follow-up in the full analysis set that includes women regardless of baseline HPV status (see section 5.1). The decision to vaccinate an individual woman 27 to 45 years old should take into account her risk for previous HPV exposure and her potential benefit from vaccination.

 

Change to section 4.5 - Interactions with other medicaments

Update to the numbers of mid-adult women using hormonal contraceptives.

 

Change to section 4.6 - Pregnancy and lactation

Update to the numbers of women in the clinical development program that reported pregnancy.

 

Change to section 4.8 - Undesirable effects

Update to the numbers in the safety population.

The inclusion of the adverse reaction pain in the extremity as common

 

Change to section 5.1 - Pharmacodynamic properties

Update of efficacy in women 16 through 26 years and addition of data regarding efficacy in women 24 through 45 years.

 

Update to immunogenicity.

 

Change to section 10 - Date of revision to 09/2009

 

Reasons for adding or updating:

  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable Effects

Date of revision of text on the SPC:28-07-2009

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



4.5 - Addition on concomitant use with Repevax/other vaccines

4.8 - Information on clinical trials involving concomitant use of Repevax with Gardasil

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable Effects
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:01-05-2009

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:

4.8 - addition of 'Chills'

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable Effects

Date of revision of text on the SPC:01-03-2009

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:

4.8 - Updates to undesirable effects

Reasons for adding or 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

Date of revision of text on the SPC:01-11-2008

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



Change to section 4.4

Addition of warning, fainting (syncope) may follow any vaccination.  Vaccinees should be observed for approximately 15 minutes after administration.

 

Change to section 4.8

Addition of side effects from post marketing experience, nausea, vomiting, arthralgia, myalgia, asthenia, fatigue and malaise.

Reasons for adding or updating:

  • Change to section 5.1 - Pharmacodynamic Properties
  • Change to section 4.4 - Special warnings and precautions for Use

Date of revision of text on the SPC:01-08-2008

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



Section 4.4 – Special warnings and precautions for use – Update to protection offered by Gardasil

Gardasil will only protect against diseases that are caused by HPV types 6, 11, 16 and 18 and to some limited extent against diseases caused by certain related HPV types.

 

Gardasil will not provide protection against every HPV type.

 

Section 5.1 Update to data

Inclusion of data relating to cross protection efficacy.

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 4.6 - Pregnancy and Lactation
  • Change to section 4.8 - Undesirable Effects
  • Change to section 5.1 - Pharmacodynamic Properties
  • Change to section 6. 4 - Special Precautions for Storage

Date of revision of text on the SPC:01-07-2008

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



Section 4.1 – Indication – expansion of the indication,

Gardasil is a vaccine for the prevention of premalignant genital lesions (cervical, vulvar and vaginal), cervical cancer and external genital warts (condyloma acuminata) causally related to Human Papillomavirus (HPV) types 6, 11, 16 and 18 (see section 5.1).

Section 4.2 – Rewording of the route of administration paragraph.

Subcutaneous and intradermal routes of administration have not been studied and are therefore not recommended.

Section 4.4 – Addition of statement regarding interchangeability of vaccine

The interchangeability of the vaccine with other HPV vaccines, has not been studied and is therefore not recommended.

Section 4.6 – Update to data

Update to the numbers involved in the clinical development program and the outcomes.

Section 4.8 – Update to data

Rewording of the side effect ; ‘bleeding’ changed to ‘bruising’

Addition of side effects; Lymphadenopathy, Gullain Barre syndrome and headache.

Section 5.1 – Update to data

Following analysis of 3 year clinical data, the data has been updated and added to reflect the results.

Section 6.4 – Grammatical correction

 

Reasons for adding or updating:

  • Change to section 6. 5 - Nature and Contents of Container
  • Change to section 8 - MARKETING AUTHORISATION NUMBER(S)

Date of revision of text on the SPC:01-08-2007

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Change to section 6.5 to include 20 dose pack of prefilled syringes and change to section 8 to include 20 dose pack licence numbers.

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable Effects
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:01-07-2007

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Change to section 4.8: Addition of post marketing safety data.

Change to section 10: Date changed to July 07

Reasons for adding or updating:

  • Change to section 6. 6 - Instructions for use, handling and disposal

Date of revision of text on the SPC:01-05-2007

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 6.6 has been modified to improve clarity of the instructions for use of the needle guard (safety device).

Reasons for adding or updating:

  • Improved Electronic Presentation

Reasons for adding or updating:

  • New SPC for new product