Infanrix Hexa, Powder and suspension for suspension for injection

Changed date of revision from '08/2020' to '09/2020'

3 How Infanrix hexa is given

• Added clarification regarding the interval between dosing, i.e. 2 months between doses in a 2-dose schedule, and 1 month between doses in a 3 dose schedule

4 Possible side effects

• Clarified the instruction regarding consulting ones doctor if the child experiences fits ‘with or without fever’, replacing the statement that such fits may be when they have a fever.
• Changed the frequency of the side effect ‘sleepiness’ from uncommon to very common, and the frequency of ‘feeling tired’ from very common to uncommon and renamed it as ‘tiredness’.
• Revised the HPRA contact details for reporting adverse reactions 

6 Contents of the pack and other information

• Editorial changes to the contact details of the MA holder representatives in the following countries: Belgium, Greece, Spain, Netherlands, Norway and Finland .

Healthcare professional section of Package Leaflet

• Replaced the instruction ‘discard the vaccine’ to ‘do not administer the vaccine’ if any foreign particulate matter and/or abnormal physical appearance when the vaccine is visually inspected before and after reconstitution

4.4 Special warnings and precautions for use

• Added the subheading ‘Traceability’ and advisory text regarding the clear recording of the name and batch number of the administered product.

 4.8 Undesirable effects

• Added the subheading ‘Safety in infants and toddlers born to mothers vaccinated with dTpa during pregnancy’ with statements regarding the administration of Infanrix to subjects born to mothers that had been vaccinated with dTpa during the third trimester of pregnancy, and the safety profile of Infanrix hexa being similar regardless of the exposure/non-exposure to dTpa during pregnancy.
• Changed the frequencies of the following adverse reactions:
  • Somnolence, from uncommon to very common
  • Fatigue, from very common to uncommon
• Revised the HPRA contact details for reporting adverse reactions.

5.1 Pharmacodynamic properties

• Added the subheading ‘Immunogenicity in infants and toddlers born to mothers vaccinated with dTpa during pregnancy’, with corresponding data and statements.

6.6 Special precautions for disposal and other handling

Replaced the instruction ‘discard the vaccine’ to ‘do not administer the vaccine’ if any foreign particulate matter and/or abnormal physical appearance when the vaccine is visually inspected before and after reconstitution. 

10 Date of Revision of text

• Changed date from 01/08/2019 to 03/09/2020

Section 6:

Deleted reference to the 20 and 50 single dose packs.

Changed the date of evision from 07/2017 to 08/2019

6.5     Nature and contents of container

Deleted all reference to the vial presentation and deleted reference to the 20 and 50 single dose packs.

6.6     Special precautions for disposal and other handling

Deleted all reference to the vial presentation.

8.       MARKETING AUTHORISATION NUMBER(S)

Deleted the MA numbers of the presentations that have been discontinued, i.e. EU/1/00/152/003, 004, 007, 008, 019 and 020. 

10.     Date of Revision of the Text

Changed the date of revision from 07/02/2019 to 01/08/2019

Change to section 4.1 – Therapeutic indications
Added the statement 'The use of Infanrix hexa should be in accordance with official recommendations.'

Change to section 5.1 – Pharmacodynamic properties
Added information on persistence of immunity against hepatitis B up to 14-15 years of age.

SPC: Change to section 4.1 – Therapeutic indications
Clarified age range to include the term 'toddler' in addition to the existing term 'infant'.

SPC: Change to section 4.3 – Contraindications
Clarified age range to include the term 'toddler' in addition to the existing term 'infant'.

SPC: Change to section 4.4 – Special warnings and precautions for use
Added statement regarding the prophylactic use of Antipyretic medicine before or immediately after vaccine administration, in order to reduce the incidence and intensity of post-vaccination febrile reactions.

Section 4.8: Changed the table heading ‘Adverse events’ to Adverse reactions’, and for the ‘apnoea’ adverse reaction listed, changed the wording from ‘premature babies’ to ‘preterm babies’.
Section 6.6: Removed the description ‘reconstituted’ from ‘reconstituted mixture’.

SPC has been updated to combine all registered presentations, i.e. prefilled syringe/vial and vial/vial presentations are now combined, resulting in the following changes to the SPC:
Section 1: Removed ‘prefilled syringe’ from the product name.
Section 3: Removed ‘prefilled syringe’ from the description of pharmaceutical form.
Section 6.5: Added subheadings for both prefilled syringe/vial and vial/vial presentations, and added description of the vial/vial presentation.
Section 6.6: Added subheadings for both prefilled syringe/vial and vial/vial presentations, and added instructions for storage, use and handling and disposal for the vial/vial presentation.
Section 8: Added the MA numbers of the vial/vial presentations.

Section 4.2: Addition of posology instructions for use in pre-term infants.

Section 4.4: Revision of warnings for use in pre-term infants, and subsequent re-organisation of text.

Section 4.8: Added statement regarding side effect data in preterm infants.

Section 5.1: Added sub-section and data ‘Immunogenicity in preterm infants’

EMEA/H/C/0296/II/177
SPC sections 4.4, 4.5 and 4.8 updated safety information of Infanrix hexa on the co-administration with several other paediatric vaccines (pneumococcal conjugate vaccine (PCV7, PCV10 and PCV13), meningococcal serogroup C conjugate vaccine (CRM197 and TT conjugates), meningococcal serogroups A, C, W-135 and Y conjugate vaccine (TT conjugate), oral rotavirus vaccine and measles-mumps-rubella-varicella (MMRV) vaccine).

EMEA/H/C/0296/II/179 

SPC section 5.1 updated to add data generated in study DTPa-HBV-IPV/Hib-MenC-TT-003 for the new 2+1 schedule (2, 4 and 12 months of age).

SPC section 2: Added abbreviations for the vaccine components, e.g. added (PT) to Pertussis toxoid.

EMEA/H/C/0296/II/180
SPC section 5.1 to describe the results of the Hepatitis B immunity persistence data gathered

SPC Section 4.8:

·         Added undesirable effects ‘upper respiratory tract infection and bronchitis.

·         Re-categorised thrombocytopenia from being an undesirable effect reported specifically for hepatitis B vaccine to the more general ‘adverse reactions from spontaneous reporting’

·         Under ‘Experience with hepatitis B vaccine’ added allergic reactions mimicking serum sickness, neuritis, hypotension, vasculitis, lichen planus, erythema multiforme, arthritis and muscular weakness

Section 4.4

Added the following warning: ‘Increased reporting rates of convulsions (with or without fever) and hypotonic hyporesponsive episode (HHE) were observed with concomitant administration of Infanrix hexa and Prevenar 13 (see section 4.8).’

Section 4.8

Added the following statement under the revised sub-heading ‘Experience in co-administration’

‘Analysis of postmarketing reporting rates suggests a potential increased risk of convulsions (with or without fever) and HHE when comparing groups which reported use of Infanrix hexa with Prevenar 13 to those which reported use of Infanrix hexa alone.’

SPC editorial updates

Sections 4.4 and 4.8

Changed the term ‘hyporesponsiveness’ to ‘hyporesponsive’ in the description ‘hypotonic hyporesponsive episode’

Section 4.5

Added reference to section 4.4 for guidance on Prevenar and Prevenar 13.

2.         Qualitative And Quantitative Composition

·         Added statement that vaccine may contain traces of formaldehyde, neomycin and polymyxin.

·         Administrative changes.

4.2        Posology and method of administration

·         Added: The immunisation schedules for Infanrix hexa should be based on official recommendations.

·         Administrative changes.

4.3        Contraindications

·         Added hypersensitivity to formaldehyde.

4.8        Undesirable effects

·         Administrative changes.
 

5.1        Pharmacodynamic properties

·         Added data on the effectiveness of Infanrix Hexa in controlling Hib disease, when the vaccine is administered according to the 3 and 5 months primary vaccination schedule, with a booster dose administered at approximately 11 months

·         Reformatted the presentation of data regarding Efficacy in protecting against pertussis into results of clinical studies and reports from post marketing surveillance. No change to the actual data.

·         Administrative changes.

6.4        Special precautions for storage

·         Administrative changes.

6.5        Nature and contents of container

·         Added new multipack presentation; this presentation is not planned to be launched in IE or UK.

6.6        Special precautions for disposal and other handling

·         Administrative changes.

8.         MARKETING AUTHORISATION NUMBER(S)

·         Added ‘EU/1/00/152/021’ for the new multipack presentation.

9.         Date of First Authorisation/Renewal of the Authorisation

·         Changed the ‘date of last renewal’ to 31/08/2010

Section 6.4 - Special precautions for storage - Update stability data supporting temperature excursion to 25°C for 72 hours.

Section 6.6 - Special precautions for disposal and other handling - Update the handling and preparation instructions.

Section 10 - Update date of revision of text.

Editorial changes to SPC sections 1, 2, 4.2, 4.8 and 6.6 further to the adoption of the QRD Human Product Information Template for Centralised Procedures (Version 7.3.1, 03/2010)

5.1     Pharmacodynamic properties

The statement regarding the effectiveness of the Hib component was updated to reflect the outcome of an extensive post marketing surveillance study conducted over a 7-year follow-up period showed the effectiveness of the Hib components of two hexavalent vaccines, of which one was Infanrix Hexa, was 89.6% for a full primary series (previously 90.4% at 5 year time-point of the study). The effectiveness remained 100% for a full primary plus booster dose, irrespective of the Hib vaccine used for the priming.

2.       Qualitative And Quantitative Composition

Minor update to use the correct formula for the Aluminium cation, adding ‘3+’ to read:

Al³⁺

 

4.4     Special warnings and precautions for use

Minor change to intrduce bullet formatting to the following list:

§   Temperature of ³ 40.0°C within 48 hours, not due to another identifiable cause;

§   Collapse or shock-like state (hypotonic-hyporesponsiveness episode) within 48 hours of vaccination;

§   Persistent, inconsolable crying lasting ³ 3 hours, occurring within 48 hours of vaccination;

§   Convulsions with or without fever, occurring within 3 days of vaccination.

 

4.8     Undesirable effects

Under the heading ‘Clinical trials’, sub-heading ‘General disorders and administration site conditions’, removed the side effect ‘injection site reaction’

 

1.         Name of the Medicinal Product

Added the detail ‘in a pre-filled syringe’ to the pharmaceutical form, to read:

Infanrix hexa, Powder and suspension for suspension for injection in a pre-filled syringe

3.         Pharmaceutical Form

Added the detail ‘in a pre-filled syringe’ to the pharmaceutical form, to read:

Powder and suspension for suspension for injection in a pre-filled syringe

4.1       Therapeutic indications

Deleted the following statement regarding use in children over 36 months (corresponding statement added to section 4.2):

Infanrix hexa is not intended for use in children over 36 months of age

4.2       Posology and method of administration

Added the following statement regarding use in children over 36 months (corresponding statement deleted from section 4.1):

Paediatric population

There is no relevant use of Infanrix hexa in children over 36 months

4.6       Fertility, pregnancy and lactation

Added ‘Fertility’ to the heading

6.4       Special precautions for storage

Added the following reference to section 6.3:

For storage conditions of the reconstituted medicinal product, see section 6.3.

6.6       Special precautions for disposal and other handling