IPV-Boostrix suspension for injection in pre-filled syringe

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 IPV-Boostrix may be considered during the third trimester of pregnancy' to the start of the 'Pregnancy' subsection.
 

Change to section 4.1 Therapeutic indications

·                Changed the minimum age from 4 years to 3 years

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

 Change to section 4.2 – Posology and method of administration

Posology

·                Changed the minimum age from 4 years to 3 years

·                Added the statement: ‘The use of IPV-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: ‘IPV-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, pertussis and poliomyelitis. 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)’

·                Updated the term for the antigen ‘poliomyelitis’ from ‘polio’

·                Under the subheading ‘Paediatric population’ updated the statement to take the reduced age indication of 3 years to read: ‘The safety and efficacy of IPV-Boostrix in children below 3 years of age have not been established’

Change to section 4.3 – Contraindications

·                Updated the term for the antigen ‘poliomyelitis’ from ‘polio’

·         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 4.5 – Interaction with other medicinal products and other forms of interaction

·                Added measles, mumps, rubella and varicella as monovalent or combination vaccines that may be administered concomitantly with IPV-Boostrix

·                Added the acronyms (MMR/V) and (HPV)

 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 (dTpa component of IPV-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 IPV-Boostrix or to Boostrix 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 IPV-Boostrix may be considered during the third trimester of pregnancy.

o    Human data from prospective clinical studies on the use of IPV-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 IPV-Boostrix harms the foetus at any trimester of pregnancy. The benefits versus the risks of administering IPV-Boostrix during pregnancy should be carefully evaluated.

 Change to section 4.8 – Undesirable effects

·                Added the following subheading and statements regarding the coadministration with MMR/V in children aged 3-6 years

Coadministration with MMR/V vaccines in children aged 3-6 years

IPV-Boostrix was coadministered with MMR/V vaccines in 2 clinical studies with 406 children aged 3-6 years. In these studies, upper respiratory tract infection and rash were commonly reported. Fever, irritability, fatigue, loss of appetite and gastrointestinal disorders (including diarrhoea and vomiting) were reported with a higher frequency (very common) when compared to Table 1 while all other adverse reactions occurred at the same or lower frequency

·                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

·                Updated the table representing the immune responses after one month post vaccination with IPV-Boostrix as observed across clinical studies, to include children aged 3-8 years and adults and adolescents aged 10 years and older (previously ‘subjects’ aged 4-8 years and ‘subjects’ aged 10-93 years)

·                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 (dTpa component of IPV-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

Immune response after a repeat dose of IPV-Boostrix or Boostrix

Immune response in subjects without prior or with unknown vaccination history

Efficacy in protecting against pertussis

Update to section 4.8 : IMB name change to HPRA. 

Update to section  10 : change of revision date

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 10 - change to date of revision of text.

4.6      Fertility, pregnancy and lactation

Updated the statement regarding fertility to specify that no human data from prospective clinical studies are available, and added the advice:

Animal studies do not indicate direct or indirect harmful effects with respect to female fertility (see section 5.3).

Updated the information regarding use in Pregnancy, specifying that no human data are available and referred to data from animal studies and that IPV-Boostrix should be used during pregnancy only when clearly needed, and the possible advantages outweigh the possible risks for the foetus, i.e.

Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or post-natal development (see section 5.3).

As with other inactivated vaccines, it is not expected that vaccination with IPV-Boostrix harms the foetus.

However, human data from prospective clinical studies on the use of IPV-Boostrix during pregnancy are not available. Therefore, IPV-Boostrix should be used during pregnancy only when clearly needed, and the possible advantages outweigh the possible risks for the foetus. No teratogenic effect of vaccines containing diphtheria or tetanus toxoids, or inactivated poliovirus has been observed following use in pregnant women.

4.8      Undesirable effects

Clarified that all of the the side effects reported during post-marketing surveillance are relevant to IPV-Boostrix.

Changed the system organ class for the side effect ‘angiodema’ from ‘Blood and lymphatic system’ to ‘Skin and subcutaneous tissue disorders’

Added the the IMB Pharmacovigilance details for the reporting of adverse events, i.e.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions preferably through the online reporting option accessible from the IMB homepage.  A downloadable report form is also accessible from the IMB website, which may be completed manually and submitted to the IMB via ‘freepost’. Alternatively, the traditional post-paid ‘yellow card’ option may also continue to be used.

FREEPOST

Pharmacovigilance Section

Irish Medicines Board

Kevin O’Malley House

Earlsfort Centre

Earlsfort Terrace

Dublin 2

Tel: +353 1 6764971

Fax: +353 1 6762517

Website: www.imb.ie

e-mail: imbpharmacovigilance@imb.ie

5.3      Preclinical safety data

Added new sub-heading ‘Reproductive toxicology’ with new statements regarding fertility and pregnancy, and added new sub-heading Animal toxicology and/or pharmacology to the previously approved statement ‘Preclinical data reveal no special hazard for humans based on conventional studies of safety and of toxicity’, to read:

Reproductive toxicology

Fertility

Non-clinical data obtained with IPV-Boostrix reveal no specific hazard for humans based on conventional studies of female fertility in rats and rabbits.

Pregnancy

Non-clinical data obtained with IPV-Boostrix reveal no specific hazard for humans based on conventional studies of embryo-foetal development in rats and rabbits, and also of parturition and postnatal toxicity in rats (up to the end of the lactation period).

Animal toxicology and/or pharmacology

Preclinical data reveal no special hazard for humans based on conventional studies of safety and of toxicity.

4.4     Special warnings and precautions for use

Added the following warning regarding 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.

4.2       Posology and method of administration

Under the subheading ‘posology’, replaced the following paragraph:

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

with the following:

In subjects ³ 40 years of age that had not received any diphtheria or tetanus containing vaccine in the past 20 years (including those who have never been vaccinated or whose vaccination status was unknown), one dose of IPV-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).

Deleted the following:

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

Added pertussis to the following sentence:

Repeat vaccination against diphtheria, tetanus, pertussis and poliomyelitis should be performed at intervals as per official recommendations.

4.4       Special warnings and precautions for use

Removed reference to ‘infant’ in the following sentence:

As for any vaccination, the risk-benefit of immunising with IPV-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.

4.6       Fertility, pregnancy and lactation

Updated the heading to include ‘fertility.

4.8       Undesirable effects

Corrected the spelling for ‘pruritus’

Under the subheading Post-marketing surveillance, replaced the statement

The reactogenicity of revaccination with IPV-Boostrix has not been evaluated.

with

Data suggest that in subjects 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 five years following a first vaccination of children 4 to 8 years of age with IPV-Boostrix

Added data on seroprotection / seropositivity rates for three to 3.5 years, 5 and 10 years following a first vaccination with Boostrix (dTpa component of IPV-Boostrix)

Added the following statements regarding immunogenicity:

The immunogenicity of IPV-Boostrix, administered 5 years after a first booster dose of IPV-Boostrix at 4 to 8 years of age, has been evaluated. One month post vaccination, > 99 % of subjects were seropositive against pertussis and seroprotected against diphtheria, tetanus and all three polio types.

The immunogenicity of Boostrix (dTpa component of IPV-Boostrix), administered 10 years after a first 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.

After administration of one dose of IPV-Boostrix to 140 adults ³ 40 years of age that had not received any diphtheria and tetanus containing vaccine in the past 20 years, more than 96.4% of adults were seropositive for all three pertussis antigens and 77.7% and 95.7% were seroprotected against diphtheria and tetanus respectively.

Deleted the following statement:

The immunogenicity of revaccination with IPV-Boostrix has not been evaluated.