GlaxoSmithKline (Ireland) Ltd

IPV-Boostrix suspension for injection in pre-filled syringe

Diphtheria, tetanus, pertussis (acellular, component) and poliomyelitis (inactivated) vaccine (adsorbed, reduced antigen(s) content)

1 dose (0.5 ml) contains:

For a full list of excipients, see section 6.1

Suspension for injection in pre-filled syringe.

IPV-Boostrix is a turbid white suspension.

IPV-Boostrix is indicated for booster vaccination against diphtheria, tetanus, pertussis and poliomyelitis of individuals from the age of four years onwards (see section 4.2).

IPV-Boostrix is not intended for primary immunisation. The administration of IPV-Boostrix should be based on official recommendations.

Posology

A single 0.5 ml dose of the vaccine is recommended.

IPV-Boostrix may be administered from the age of four years onwards.

IPV-Boostrix contains low (adult) dose diphtheria, tetanus and pertussis antigens in combination with poliomyelitis antigens. Therefore, IPV-Boostrix should be administered in accordance with official recommendations and/or local practice.

In subjects 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).

IPV-Boostrix can be used in the management of tetanus prone injuries in persons who have previously received a primary vaccination series of tetanus toxoid vaccine and for whom a booster against diphtheria, pertussis and polio is indicated. Tetanus immunoglobulin should be administered concomitantly in accordance with official recommendations.

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

Paediatric population

The safety and efficacy of IPV-Boostrix in children below 4 years of age have not been established.

Method of administration

IPV-Boostrix is for deep intramuscular injection preferably in the deltoid region (see section 4.4).

Hypersensitivity to the active substances or to any of the excipients or to neomycin or polymyxin.

Hypersensitivity after previous administration of diphtheria, tetanus, pertussis or polio vaccines.

IPV-Boostrix is contra-indicated if the subject has experienced an encephalopathy of unknown aetiology, occurring within 7 days following previous vaccination with pertussis-containing vaccine. In these circumstances, pertussis vaccination should be discontinued and the vaccination course should be continued with diphtheria, tetanus and poliomyelitis vaccines.

IPV-Boostrix should not be administered to subjects who have experienced transient thrombocytopenia or neurological complications (for convulsions or hypotonic-hyporesponsive episodes, see section 4.4) following an earlier immunisation against diphtheria and/or tetanus.

As with other vaccines, administration of IPV-Boostrix should be postponed in subjects suffering from acute severe febrile illness. The presence of a minor infection is not a contra-indication.

Vaccination should be preceded by a review of the medical history (especially with regard to previous vaccination and possible occurrence of undesirable events).

If any of the following events are known to have occurred in temporal relation to receipt of pertussis-containing vaccine, the decision to give doses of pertussis-containing vaccines should be carefully considered:

- Temperature of 40.0°C within 48 hours of vaccination, not due to another identifiable cause.

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

- Persistent, inconsolable crying lasting 3 hours, occurring within 48 hours of vaccination.

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

There may be circumstances, such as a high incidence of pertussis, when the potential benefits outweigh possible risks.

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

As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic reaction following the administration of the vaccine.

IPV-Boostrix should be administered with caution to subjects with thrombocytopenia (see section 4.3) or a bleeding disorder since bleeding may occur following an intramuscular administration to these subjects. Firm pressure should be applied to the injection site (without rubbing) for at least two minutes.

IPV-Boostrix should in no circumstances be administered intravascularly.

A history or a family history of convulsions and a family history of an adverse event following DTP vaccination do not constitute contra-indications.

Human Immunodeficiency Virus (HIV) infection is not considered as a contra-indication. The expected immunological response may not be obtained after vaccination of immunosuppressed patients.

As with any vaccine, a protective immune response may not be elicited in all vaccinees.

Use with other vaccines or immunoglobulins

IPV-Boostrix may be administered concomitantly with human papilloma virus vaccine with no clinically relevant interference with antibody response to any of the components of either vaccine.

Concomitant administration of IPV-Boostrix and other vaccines or with immunoglobulins 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 IPV-Boostrix with other vaccines or immunoglobulins is considered necessary, the products should be given at separate sites.

Use with immunosuppressive treatment

As with other vaccines, patients receiving immunosuppressive therapy may not achieve an adequate response.

Fertility

No fertility data are available.

Pregnancy

The effect of IPV-Boostrix on embryo-foetal development has not been assessed. No teratogenic effect of vaccines containing diphtheria or tetanus toxoids, or inactivated poliovirus has been observed following use in pregnant women.

The use of this combined vaccine is not recommended during pregnancy.

Breastfeeding

The effect of administration of IPV-Boostrix during lactation has not been assessed. Nevertheless, as IPV-Boostrix contains toxoids or inactivated antigens, no risk to the breastfed infant should be expected. The benefits versus the risk of administering IPV-Boostrix to breastfeeding women should carefully be evaluated by the health-care providers.

The vaccine is unlikely to produce an effect on the ability to drive and use machines.

IPV-BoostrixThe safety profile presented below is based on data from clinical trials where IPV-Boostrix was administered to 908 children (from 4 to 8 years of age) and 955 adults, adolescents and children (from 10 to 93 years of age).

The most common events occurring after IPV-Boostrix administration in both groups were local injection site reactions (pain, redness and swelling) reported by 31.3 – 82.3% of subjects overall. These usually had their onset within the first 48 hours after vaccination. All resolved without sequelae.

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Clinical trials

- Subjects aged 4 - 8 years (N=908)

Blood and lymphatic system disorders

Uncommon: lymphadenopathy

Metabolism and nutrition disorders

Common: anorexia

Psychiatric disorders

Common: irritability

Uncommon: sleep disorder, apathy

Nervous system disorders

Very common: somnolence

Common: headache

Respiratory, thoracic and mediastinal disorders

Uncommon: dry throat

Gastrointestinal disorders

Uncommon: diarrhoea, vomiting, abdominal pain, nausea

General disorders and administration site conditions

Very common: injection site reactions (such as redness and/or swelling), injection site pain

Common: pyrexia (fever 37.5°C, including fever > 39°C), extensive swelling of vaccinated limb (sometimes involving the adjacent joint), injection site reactions (such as haemorrhage, pruritus and induration)

Uncommon: fatigue

- Subjects aged 10 - 93 years (N = 955)

Infections and infestations

Uncommon: oral herpes

Blood and lymphatic system disorders

Uncommon: lymphadenopathy

Metabolism and nutrition disorders

Uncommon: decreased appetite

Nervous system disorders

Very common: headache

Uncommon: paraesthesia, somnolence, dizziness

Respiratory, thoracic and mediastinal disorders

Uncommon: asthma

Gastrointestinal disorders

Common: gastrointestinal disorders (such as vomiting, abdominal pain, nausea)

Skin and subcutaneous tissue disorders

Uncommon: pruritus

Musculoskeletal and connective tissue disorders

Uncommon: arthralgia, myalgia

General disorders and administration site conditions

Very common: injection site reactions (such as redness and/or swelling), fatigue, injection site pain

Common: pyrexia (fever 37.5°C), injection site reactions (such as haematoma, pruritus, induration and warmth numbness)

Uncommon: extensive swelling of vaccinated limb (sometimes involving the adjacent joint), pyrexia (fever > 39.0°C), chills, pain

The following undesirable effects were additionally reported during clinical trials with GlaxoSmithKline Biologicals' other reduced-antigen content diphtheria-tetanus-acellular pertussis vaccine (Boostrix) where Boostrix was administered to 839 children (from 4 to 8 years of age) and 1931 adults, adolescents and children (from 10 to 76 years of age):

- Subjects aged 4 - 8 years (N = 839)

Infections and infestations

Uncommon: upper respiratory tract infection

Nervous system disorders

Uncommon: disturbances in attention

Eye disorders

Uncommon: conjunctivitis

Gastrointestinal disorders

Common: gastrointestinal disorders

Skin and subcutaneous tissue disorders

Uncommon: rash

General disorders and administration site conditions

Uncommon: pain

- Subjects aged 10 - 76 years (N = 1931)

Infections and infestations

Uncommon: upper respiratory tract infection, pharyngitis

Nervous system disorders

Uncommon: syncope

Respiratory, thoracic and mediastinal disorders

Uncommon: cough

Gastrointestinal disorders

Uncommon: diarrhoea

Skin and subcutaneous tissue disorders

Uncommon: hyperhidrosis, rash

Musculoskeletal and connective tissue disorders

Uncommon: joint stiffness, musculoskeletal stiffness

General disorders and administration site conditions

Very common: malaise

Common: injection site reactions (such as injection site mass and injection site abscess sterile)

Uncommon: influenza like illness

Post-marketing surveillance

Because these events were reported spontaneously, it is not possible to reliably estimate their frequency.

The following undesirable effects were reported during post marketing surveillance after vaccination with IPV-Boostrix:

Immune system disorders

Allergic reactions, including anaphylactic and anaphylactoid reactions

Nervous system disorders

Hypotonic-hyporesponsiveness episodes, convulsions (with or without fever)

The following undesirable effects were additionally reported during post marketing surveillance after vaccination with GlaxoSmithKline Biologicals' other reduced-antigen content diphtheria-tetanus-acellular pertussis vaccine (Boostrix):

Blood and lymphatic system disorders

Angioedema

Skin and subcutaneous tissue disorders

Urticaria

General disorders and administration site conditions

Asthenia

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

Following administration of tetanus toxoid containing vaccines, there have been very rare reports of adverse reactions on the central or peripheral nervous systems, including ascending paralysis or even respiratory paralysis (e.g. Guillain-Barré syndrome).

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

Pharmaco-therapeutic group: Bacterial and viral vaccines combined, ATC code J07CA02

The immune responses to IPV-Boostrix were evaluated in clinical trials carried out in subjects of different ages having different vaccination histories (see section 4.8).

One month post vaccination with IPV-Boostrix, immune responses were the following:

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

**defined as 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

In clinical studies, seroprotection and vaccine response rates to all antigens after a booster dose of IPV-Boostrix were similar to the licensed controlled vaccines studied.

As with other adult-type Td vaccines, IPV-Boostrix induces higher seroprotection rates and higher titres of both anti-D and anti-T antibodies in children and adolescents as compared to adults.

Five years following a first vaccination of children 4 to 8 years of age with IPV-Boostrix, the following seroprotection / seropositivity rates were observed in subjects vaccinated according to protocol (ATP¹):

⁽¹⁾ATP: According to protocol – includes all eligible subjects, who had received a single booster dose of IPV-Boostrix, for whom immunogenicity data was available for at least one antigen at the specified time-point.

⁽²⁾Response: Where, after five years, a concentration of antibodies against diphtheria and tetanus 0.1 IU/ml was considered as seroprotection, a concentration of antibodies against pertussis 5 EL.U/ml was considered as seropositivity and dilution titres against poliovirus types 1, 2 and 3 of 1:8 were considered as positive.

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

N = the minimum number of subjects with available data for each antigen

Three to 3.5 years, 5 and 10 years following a first vaccination with Boostrix (dTpa component of IPV-Boostrix), the following seroprotection / seropositivity rates were observed in subjects vaccinated according to protocol (ATP¹):

⁽¹⁾ATP: According to protocol – includes all eligible subjects, who had received a single booster dose of Boostrix, for whom immunogenicity data was available for at least one antigen at the specified time-point.

⁽²⁾Response: Where, at the specified time point, a concentration of antibodies against diphtheria and tetanus 0.1 IU/ml was considered as seroprotection and a concentration of antibodies against pertussis 5 EL.U/ml was considered as seropositivity.

⁽³⁾The terms 'adult' and 'adolescent' reflect the ages at which subjects received their first vaccination with Boostrix.

⁽⁴⁾Percentage of subjects with antibody concentrations associated with protection against disease ( 0.1 IU/ml by ELISA assay or 0.016 IU/ml by an in-vitro Vero-cell neutralisation assay).

N = the minimum number of subjects with available data for each antigen

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 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.

The pertussis antigens contained in IPV-Boostrix are an integral part of the paediatric acellular pertussis combination vaccine (Infanrix), for which efficacy after primary vaccination has been demonstrated in a household contact efficacy study. The antibody titres to all three pertussis components following vaccination with IPV-Boostrix are at least as high or higher than those observed during the household contact efficacy trial. Based on these comparisons, IPV-Boostrix would provide protection against pertussis, however the degree and duration of protection afforded by the vaccine are undetermined.

Evaluation of pharmacokinetic properties is not required for vaccines.

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

Medium 199 (as stabilizer containing amino acids, mineral salts, vitamins and other substances)

Sodium chloride

Water for injections

For adjuvants, see section 2.

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

3 years

Store in a refrigerator (2°C – 8°C).

Upon removal from refrigerator, the vaccine is stable for 8 hours at 21°C.

Do not freeze.

Store in the original package in order to protect from light.

0.5 ml of suspension in pre-filled syringe (Type I glass) with stopper (butyl rubber) with or without needles in pack sizes of 1 or 10.

Not all pack sizes may be marketed.

Prior to use, the vaccine should be at room temperature, and well shaken in order to obtain a homogeneous turbid white suspension. Prior to administration, the vaccine should be visually inspected for any foreign particulate matter and/or variation of physical aspect. In the event of either being observed, discard the vaccine.

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

GlaxoSmithKline (Ireland) Ltd.

Stonemasons Way

Rathfarnham

Dublin 16

PA 1077/101/001

Date of first authorisation: 10 December 2004

Date of last renewal: 16 December 2008

September 2011