Boostrix - Suspension for injection

Updated the warning statement regarding administration in subjects with thrombocytopenia (see section 4.3) or a bleeding disorder to include subcutaneous injection, with the consequential update to the statement regarding applying firm pressure, to read as follows:

If in accordance with official recommendations, the vaccine may be administered subcutaneously to these subjects. With both routes of administration, firm pressure should be applied to the injection site (without rubbing) for at least two minutes.

Change to section 4.6 – Fertility, pregnancy and lactation
Added the statement 'For data relating to the prevention of pertussis disease in infants born to women vaccinated during pregnancy, see section 5.1', and moved the statement 'The use of Boostrix may be considered during the third trimester of pregnancy' to the start of the 'Pregnancy' subsection.
 

Change to section 4.1 Therapeutic indications

·         Deleted the statement ‘Boostrix is not intended for primary immunisation’

·                Added the statement ‘The administration of Boostrix should be based on official recommendations’

Change to section 4.2 – Posology and method of administration

Posology

·                Added the statement: ‘The use of Boostrix may be considered during the third trimester of pregnancy. For the use of the vaccine before the third trimester of pregnancy, see section 4.6’

·                Revised the description of the antigen content of diphtheria, tetanus and pertussis from ‘low adult dose’ to ‘reduced content’

·                Replaced the statements regarding vaccination of adults with the following: ‘Boostrix may be administered to adolescents and adults with unknown vaccination status or incomplete vaccination against diphtheria, tetanus and pertussis as part of an immunisation series against diphtheria, tetanus and pertussis. Based on data in adults, two additional doses of a diphtheria and tetanus containing vaccine are recommended one and six months after the first dose to maximize the vaccine response against diphtheria and tetanus (see section 5.1)’

Change to section 4.3 – Contraindications

·                Revised the spelling of ‘contraindicated’ and ‘contraindication’ (removed hyphenation)

Change to section 4.4 – Special warnings and precautions for use

·                Revised the spelling of ‘contraindication’ (removed hyphenation)

Change to section 4.6 – Pregnancy and lactation

·                Reorganised the order of the text along the sequence of ‘Pregnancy’, Breastfeeding’ and ‘Fertility’

·                Under the subheading ‘Pregnancy’, replaced the existing statements (lack of data for use in pregnancy, risk based use of vaccine in pregnancy and no expected harm to the foetus), with the following:

o    Safety data from a prospective observational study where Boostrix was administered to pregnant women during the third trimester (793 pregnancy outcomes) as well as data from passive surveillance where pregnant women were exposed to Boostrix or to IPV-Boostrix (dTpa-IPV vaccine) in the 3^rd and 2^nd trimester have shown no vaccine related adverse effect on pregnancy or on the health of the foetus/newborn child.

o    The use of Boostrix may be considered during the third trimester of pregnancy.

o    Human data from prospective clinical studies on the use of Boostrix during the first and second trimester of pregnancy are not available. However, as with other inactivated vaccines, it is not expected that vaccination with Boostrix harms the foetus at any trimester of pregnancy. The benefits versus the risks of administering Boostrix during pregnancy should be carefully evaluated.

Change to section 4.8 – Undesirable effects

·                Formatting and typographical updates to align with the current formatting requirements of the QRD Template, including the tabulation of adverse reactions.

Change to section 5.1 – Pharmacodynamic properties

·                Added the following subheading and statement regarding the immune response in subjects without prior or with unknown vaccination history:

Immune response in subjects without prior or with unknown vaccination history

After administration of one dose of Boostrix to 123 adolescents aged from 11 to 18 years, without previous pertussis vaccination and no vaccination against diphtheria and tetanus in the previous 5 years, all subjects were seroprotected against tetanus and diphtheria. The seropositivity rate after one dose varied between 90% and 98% for the different pertussis antigens.

·         Formatting update, to include the following subheadings:

Immune response

Persistence of the immune response

Efficacy in protecting against pertussis

Immune response after a repeat dose of Boostrix

Immune response in subjects without prior or with unknown vaccination history

Section 7 - Change to address of the Irish MA Holder from Stonemasons Way, Rathfarnham, Dublin 16 to 12 Riverwalk, Citywest Business Campus, Dublin 24

Section 4.8 – IMB name change to HPRA

Section 10 – Date update

4.6          Fertility, pregnancy and lactation:

‘Fertility’ and ‘Pregnancy’ sections updated with data from animal studies regarding reproductive toxicity, while confirming that data in humans are not available and therefore the warning remains unchanged, i.e. that the vaccine should be used during pregnancy only when clearly needed, and the possible advantages outweigh the possible risks for the foetus.

4.8        Undesirable effects

Under ‘Post-marketing surveillance’, moved ‘angiodema’ from ‘blood and lymphatic disorders’ to ‘skin and subcutaneous tissue disorders’

Added the instructions regarding the reporting of adverse events to the Pharmacovigilance section of the  IMB.

5.3        Preclinical safety data

4.2       Posology and method of administration

Under the subheading ‘posology’, added pertussis to the following sentence:

Repeat vaccination against diphtheria, tetanus and pertussis should be performed at intervals as per official recommendations (generally 10 years).

4.8       Undesirable effects

Under the subheading ‘For adults and adolescents from the age of 10 years onwards (N = 1,515)’/’Clinical trials’/’Skin and subcutaneous tissue disorders’:

Corrected the spelling for pruritus

Under the subheading ‘Post-marketing surveillance’

Added the statement:

Data suggest that in subjects primed with DTP in childhood a booster dose might give an increase of local reactogenicity.

5.1       Pharmacodynamic properties

Added data on seroprotection / seropositivity rates for 10 years following first vaccination with Boostrix

Added the following statement:

The immunogenicity of Boostrix, administered 10 years after a previous booster dose with reduced-antigen content diphtheria, tetanus and acellular pertussis vaccine(s) has been evaluated. One month post vaccination, > 99 % of  subjects were seroprotected against diphtheria and tetanus and seropositive against pertussis.

4.2       Posology and method of administration

As a result of V025, the following statement was deleted:

Individuals with an incomplete, or no, history of a primary series of diphtheria and tetanus toxoids should not be vaccinated with Boostrix.  Boostrix is not precluded in subjects with an incomplete, or no, history of previous pertussis vaccination.  However a booster response will only be elicited in individuals who have been previously primed by vaccination or by natural infection.

and replaced with:

In subjects ³ 40 years of age that had not received any diphtheria or tetanus containing vaccine in the past 20 years, one dose of Boostrix induces an antibody response against pertussis and protects against tetanus and diphtheria in the majority of cases. Two additional doses of a diphtheria and tetanus containing vaccine will maximize the vaccine response against diphtheria and tetanus when administered one and six months after the first dose (See section 5.1)

As a result of V025, the following statement was deleted:

There are no data on the duration of protection against pertussis following vaccination with Boostrix.

4.4       Special warnings and precautions for use

As a result of the Renewal, deleted reference to vaccination in infants in the following statement:

As for any vaccination, the risk-benefit of immunising with Boostrix or deferring this vaccination should be weighed carefully in an infant or in a child suffering from a new onset or progression of a severe neurological disorder.

4.5       Interaction with other medicinal products and other forms of interaction

As a result of the Renewal, updated the statement regarding concomitant administration to the following:

Concomitant administration of Boostrix with other vaccines or with immunoglobulin has not been studied.  It is unlikely that co-administration will result in interference with the immune responses. According to generally accepted vaccine practices and recommendations, if concomitant administration of Boostrix with other vaccines or immunoglobulin is considered necessary, the products should be given at separate sites.

4.8       Undesirable effects

As a result of V025, added statement regarding local reactogenicity (previously not evaluated):

Data on 146 subjects suggest that there might be a small increase in local reactogenicity (pain, redness, swelling) with repeated vaccination according to a 0, 1, 6 months schedule in adults (> 40 years of age).

5.1       Pharmacodynamic properties

As a result of the Renewal, regarding the one month post vaccination immune responses, added clarification that the vaccine response to pertussis toxoid was

defined as ³ 5 EL.U/ml antibody in subjects who were seronegative prior to boosting or at least two-fold increase in antibody concentrations in subjects who were seropositive prior to boosting.

As a result of the V024, updated the data on seroprotection/seropositivity rates to include results from 5 and 6 years following vaccination (in addition to the data in previous version of the SPC for 3.5 years):

* Percentage of subjects with antibody concentrations associated with protection against disease (³ 0.1 IU/ml by ELISA assay or ³ 0.016 IU/ml by an in-vitro Vero-cell neutralisation assay).

As a result of the V025, added statement regarding immunogenicity (previously not evaluated):

After administration of one dose of Boostrix to 139 adults ³ 40 years of age that had not received any diphtheria and tetanus containing vaccine in the past 20 years, more than 98.5% of adults were seropositive for all three pertussis antigens and 81.5% and 93.4% were seroprotected against diphtheria and tetanus respectively. After administration of two additional doses one and six months after the first dose, the seropositivity rate was 100% for all three pertussis antigens and the seroprotection rates for diphtheria and tetanus reached 99.3% and 100% respectively.

6.1       List of excipients

Deleted Phenoxyethanol

6.6       Special precautions for disposal and other handling

As a result of the Renewal, added statements that vaccine should be at room temperature prior to use and that any unused product or waste material should be disposed of in accordance with local requirements.

Inclusion of the following statement in section 4.4 regarding neurological disorders: 'As for any vaccination, the risk-benefit of immunising with Boostrix or deferring this vaccination should be weighed carefully in an infant or in a child suffering from a new onset or progression of a severe neurological disorder.'