PIL #2: Changed the satatement regarding ability to drive from 'may affect' to unlikely to affect'.

PIL #4: Revised the HPRA reporting details to align with the current guideline.

PIL #6: Change date of revision to April 2020

Information directed to Healthcare Professionals: Revised instructions regarding visual inspection of the vaccine prior to use, and in particular replaced the 'Discard...' instruction with the instruction 'Do not administer the vaccine' in the event of foreign particulate matter and/or abnormal physical appearance.

SPC # 4.7: Revised statement to 'no or negligible effect'.

SPC #4.8: Revised the HPRA reporting details to align with the current guideline.

SPC #6.4: Removed the instruction to 'discard if frozen', and added statement regarding thermostability intended for healthcare professionals in the event of temperature excursions only.

SPC #6.6: Revised instructions regarding visual inspection of the vaccine prior to use, and in particular replaced the 'Discard...' instruction with the instruction 'Do not administer the vaccine' in the event of foreign particulate matter and/or abnormal physical appearance.

SPCC #10: Change the date of revision to 23/09/2020

Updates to: update in line with QRD format

Section 4.2 -  update in line with QRD format

Section 4.4 -  Special warnings- replaced intravenously with intravascularly

Section 4.6 – minor format update

Section 4.7 Deletion of text

Section 4.8 Update to summary of safety profile

Section 5.1 Update to Pharmacodynamic effects

Section 6.4 Deletion of text

Section 6.5 - Deletion of pack sizes

Section 5.1 – addition of seroprotection rates from neonatal clinical data – (addition of data from Persistence studies)

Section 6.6 – precautions for handling vaccine

SPC changes

Minor editorial changes to sections 3, 4.1, 4.2, 4.4, 4.8, 6.5 and 6.6

4.3       Contraindications

Reworded the hypersensitivity warning from:

ENGERIX B should not be administered to subjects with known hypersensitivity to any component of the vaccine, or to subjects having shown signs of hypersensitivity after previous ENGERIX B administration.

to

ENGERIX B should not be administered to subjects with known hypersensitivity to the active substances or to any of the excipients listed in section 6.1, or to subjects having shown signs of hypersensitivity after previous ENGERIX B administration.

4.5       Interaction with other medicinal products and other forms of interaction

Added the following statement regarding coadministration with Cervarix:

ENGERIX B can be given concomitantly with Human Papillomavirus (HPV) vaccine.

Administration of ENGERIX B at the same time as Cervarix (HPV vaccine) has shown no clinically relevant interference in the antibody response to the HPV antigens. Anti-HBs geometric mean antibody concentrations 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 97.9% for concomitant vaccination and 100% for ENGERIX B alone.

4.6       Fertility, pregnancy and lactation

Changed the subheading ‘Lactation’ to ‘Breastfeeding’

Added the subheading ‘Fertility’ with the following statement

Fertility

ENGERIX B has not been evaluated in fertility studies.

5.1       Pharmacodynamic properties

Tabulated the results of seroprotection rates in healthy subjects up to and including 15 years of age and included the explanation that these results were generated with thiomersal containing vaccines. and that two additional clinical studies conducted with the current formulation of ENGERIX B, which does not contain thiomersal, among healthy infants and adults, elicit similar seroprotection rates as compared to former thiomersal containing formulations of ENGERIX B.

Updated the results of seroprotection rates in healthy subjects from 11 years up to and including 15 years of age to include data for up to 66 months after the first dose, obtained in a comparative study with the two different dosages (Junior 10µg/0.5ml and Adult 20µg/1ml) and schedules licensed in subjects from 11 years up to and including 15 years of age, and added the following statement:

All subjects in both vaccine groups (N=74) received a challenge dose 72 to 78 months after primary vaccination. One month later, all subjects mounted an anamnestic response with a GMC increase of 108 and 95 fold from the pre-to the post challenge time points in the 2-dose and 3-dose priming schedule respectively and were shown to be seroprotected. These data suggest that immune memory was induced in all subjects who responded to primary vaccination, even among those who had lost seroprotection at Month 66.

6.2       Incompatibilities

Updated to read:

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

CARTON

Updated the storage instruction/warning to read:

Keep out of the sight and reach of children.

Section 4.4 - Special warnings and precautions for use

1.          name of the Medicinal Product

Updated the active substance name to read:

Hepatitis B (rDNA) vaccine (adsorbed) (HBV)

3.          Pharmaceutical Form

Added the description:

Turbid white suspension.

4.4        Special warnings and special precautions for use

Added the following warning regarding the potential risk of apnoea following administration the primary immunization series to very premature infants (born ≤ 28 weeks of gestation) and particularly for those with a previous history of respiratory immaturity:

The potential risk of apnoea and the need for respiratory monitoring for 48-72h should be considered when administering the primary immunization series to very premature infants (born ≤ 28 weeks of gestation) and particularly for those with a previous history of respiratory immaturity.

As the benefit of vaccination is high in this group of infants, vaccination should not be withheld or delayed.

4.6        Fertility, pregnancy and lactation

Updated heading to include ‘fertility’.

4.8        Undesirable effects

Reorganised under the subheadings ‘Clinical trials’ and ‘Post-marketing surveillance’ with revision of side effects to reflect data from Clinical trials and Post-marketing surveillance (PMS):

Frequency categories were changed for the following

·                 Rare to very common: Headache, fatigue

·                 Common to very common: Pain and redness at injection site

·                 Rare to common: Nausea, vomiting, diarrhoea, abdominal pain, fever, malaise

·                 Rare to uncommon: Dizziness, myalgia, influenza-like symptoms

·                 Very rare to rare: Lymphadenopathy

·                 Very rare to frequency unknown, observed in PMS: Thrombocytopenia, encephalitis, encephalopathy, convulsions, paralysis, neuritis (including Guillain-Barré syndrome, optic neuritis and multiple sclerosis), neuropathy, vasculitis, hypotension, erythema multiforme, anaphylaxis, angioneurotic oedema, arthritis, meningitis

·                 New, very common: Irritability

·                 New, common: Drowsiness, appetite lost

·                 New, frequency unknown, observed in PMS: Apnoea in very premature infants (≤ 28 weeks of gestation), hypoaesthesia, muscular weakness, allergic reactions including anaphylactoid reactions and mimicking serum sickness, lichen planus

·                 Deleted: Syncope, bronchospasm, hepatic function abnormal, serum sickness

Please note that there was no change to the following:

·          Rare: Paraesthesia, arthralgia, urticaria, pruritus, rash

·          Common: Injection site induration

4.9        Overdose

Updated wording (previously ‘not applicable’) to read:

Cases of overdose have been reported during post-marketing surveillance. Adverse events reported following overdosage were similar to those reported with normal vaccine administration.

5.1        Pharmacodynamic properties

Deleted references to the composition and production of the vaccine.

Added a statement that the pharmacodynamic data generated for the vaccine were generated with thiomersal containing vaccines, and that two additional clinical studies conducted with the current formulation of Engerix B, which contains no thiomersal, among healthy infants and adults, elicit similar seroprotection rates as compared to former thiomersal containing formulations of Engerix B.

6.6        Special precautions for disposal and other handling

Updated heading to ‘Special precautions for disposal and other handling’

Added the statement regarding disposal:

Any unused product or waste material should be disposed of in accordance with local requirements.

Section 4.4:

Delete the sentence:

Thiomersal (an organomercuric compound) has been used in the manufacturing process of this medicinal product and residues of it are present in the final product. Therefore, sensitisation reactions may occur.

Section 10

Update to read:

April 2007