Boostrix

Combined diphtheria, tetanus, acellular pertussis vaccine.

1 dose (0.5 mL) contains: Diphtheria toxoid¹ not less than 2 International units (IU) (2.5 Lf); Tetanus toxoid¹ not less than 20 International units (IU) (5 Lf); Bordetella pertussis antigens: Pertussis toxoid¹ 8 micrograms, Filamentous haemagglutinin¹ 8 micrograms, Pertactin¹ 2.5 micrograms.
¹adsorbed on aluminium hydroxide (Al(OH)₃) 0.3 milligrams Al³⁺ and aluminium phosphate (AlPO₄) 0.2 milligrams Al³⁺.
Upon storage, a white deposit and clear supernatant can be observed. This is a normal finding.
Excipients/Inactive Ingredients: Sodium chloride, water for injections.
Formaldehyde, polysorbate 80, glycine are present as residuals from the manufacturing process.

Pharmacotherapeutic group: Bacterial vaccines combined. ATC Code: J07AJ52.
Pharmacology: Pharmacodynamics: Immune response: Approximately one month following booster vaccination with Boostrix: seropositivity/seroprotection rate against the different vaccine components was at least 99% in children from 4 to 9 years of age.
Seropositivity/seroprotection rate against the different vaccine components was at least 97% in adults and adolescents from 10 years of age.
Results of the comparative studies with commercial dT vaccines indicates that the degree and duration of protection would not be different from those obtained with these vaccines.
Efficacy in protecting against pertussis: There is currently no correlate of protection defined for pertussis; however, the protective efficacy of GlaxoSmithKline Biologicals' DTPa (Infanrix) vaccine against WHO-defined typical pertussis (≥21 days of paroxysmal cough with laboratory confirmation) was demonstrated in the following 3-dose primary studies: a prospective blinded household contact study performed in Germany (3, 4, 5 months schedule). Based on data collected from secondary contacts in households where there was an index case with typical pertussis, the protective efficacy of the vaccine was 88.7%. Protection against laboratory confirmed mild disease, defined as 14 days or more of cough of any type was 73% and 67% when defined as 7 days or more of cough of any type.
An NIH sponsored efficacy study performed in Italy (2, 4, 6 months schedule). The vaccine efficacy was found to be 84%. When the definition of pertussis was expanded to include clinically milder cases with respect to type and duration of cough, the efficacy of Infanrix was calculated to be 71% against >7 days of any cough and 73% against >14 days of any cough.
Vaccinees receiving Boostrix achieved antipertussis antibody titres greater than those in the German household contact study where the protective efficacy was 88.7%.
Passive protection against pertussis in infants (below 3 months of age) born to mothers vaccinated during pregnancy: In a randomised, cross-over, placebo-controlled study, higher pertussis antibody concentrations were demonstrated at delivery in the cord blood of babies born to mothers vaccinated with Boostrix (N=291) versus placebo (N=292) between 27 and 36 weeks of pregnancy. The concentrations of antibodies against the pertussis antigens PT, FHA and PRN were respectively 8, 16 and 21 times higher in the cord blood of babies born to vaccinated mothers versus controls. These antibody titres may provide passive protection against pertussis, as shown by observational effectiveness studies.
Immunogenicity in infants and toddlers born to mothers vaccinated during pregnancy: In follow-up trials in the infants following primary vaccination (n=268) and subsequently following booster vaccination in the same toddlers (n=229) born to the vaccinated mothers, the clinical data did not show clinically relevant interference between maternal vaccination with Boostrix and the infant and toddler response to diphtheria, tetanus, hepatitis B, inactivated polio virus, Haemophilus influenzae type b or pneumococcal antigens. Although lower concentrations of antibodies against some pertussis antigens were observed post-primary and post-booster vaccination in infants born to vaccinated mothers (as compared to infants born to unvaccinated mothers), 92.1-98.1% of the subjects born to vaccinated mothers showed a booster response against all pertussis antigens. Current epidemiological data on pertussis disease do not suggest any clinical relevance of this immune interference.
Effectiveness in the protection against pertussis disease in infants born to women vaccinated during pregnancy: Boostrix or Boostrix Polio vaccine effectiveness (VE) was evaluated in three observational studies, in UK, Spain and Australia. The vaccine was used during the third trimester of pregnancy to protect infants below 3 months of age against pertussis disease, as part of a maternal vaccination programme.
Details of each study design and results are provided in the table as follows.
VE against pertussis disease for infants below 3 months of age born to mothers vaccinated during the third trimester of pregnancy with Boostrix/Boostrix Polio (see table):


Click on icon to see table/diagram/image


If maternal vaccination occurs within two weeks before delivery, vaccine effectiveness in the infant may be lower than the figures in the table.
Persistence of immune system: Five to 6 years following vaccination with Boostrix, at least 94% of children from the age of 4 years onwards were seroprotected or seropositive against all vaccine components, except for the pertussis toxoid component (52% of subjects were seropositive against pertussis toxoid).
Ten years following vaccination with Boostrix, at least 86% of adults were seroprotected or seropositive against all vaccine components.
In adolescents, the percentage of subjects who were seroprotected or seropositive was at least 82% against all vaccine components, except for the pertussis toxoid component (61% of subjects were seropositive against pertussis toxoid).
Immune response after a repeat dose of Boostrix: 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.
Immune response in subjects without prior or with unknown vaccination history: In adolescents aged from 11 to 18 years, without previous pertussis vaccination and no vaccination against diphtheria and tetanus in the previous 5 years, one dose of Boostrix induced an antibody response against pertussis and all subjects were protected against tetanus and diphtheria.
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 Boostrix induced an antibody response against pertussis and protected against tetanus and diphtheria in the majority of cases.
Toxicology: Pre-clinical Safety Data: Animal toxicology and/or pharmacology: Pre-clinical data reveal no special hazard for humans based on conventional studies of safety and of toxicity.

Boostrix is indicated for booster vaccination against diphtheria, tetanus and pertussis of individuals from the age of four years onwards (see Dosage & Administration).
Boostrix is also indicated for passive protection against pertussis in early infancy following maternal immunization during pregnancy (see Posology under Dosage & Administration, Pregnancy under Use in Pregnancy & Lactation and Pharmacology: Pharmacodynamics under Actions).
The use of Boostrix should be in accordance with official recommendations.

Posology: A single 0.5 mL dose of the vaccine is recommended.
Boostrix can be given in accordance with the current local medical practices for booster vaccination with reduced-content combined diphtheria-tetanus vaccine, when a booster against pertussis is desired.
Boostrix can be administered to pregnant women between 27 and 36 weeks of pregnancy in accordance with official recommendations (see Indications/Uses, Pregnancy under Use in Pregnancy & Lactation and Pharmacology: Pharmacodynamics under Actions).
Boostrix may also be administered to adolescents and adults with unknown vaccination status or incomplete vaccination against diphtheria, tetanus and pertussis as part of an immunization series against diphtheria, tetanus and pertussis (see Pharmacology: Pharmacodynamics under Actions). 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.
Repeat vaccination against diphtheria, tetanus and pertussis should be performed at intervals as per official recommendations (generally 10 years).
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. Tetanus immunoglobulin should be administered concomitantly in accordance with official recommendations.
Method of administration: Boostrix is for deep intramuscular injection, preferably in the deltoid region (see Precautions).

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.

Boostrix should not be administered to subjects with known hypersensitivity to any component of the vaccine (see Excipients/Inactive Ingredients under Description), or to subjects having shown signs of hypersensitivity after previous administration of diphtheria, tetanus or pertussis vaccines.
Boostrix is contraindicated 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 and tetanus vaccines.
Boostrix should not be administered to subjects who have experienced transient thrombocytopenia or neurological complications following an earlier immunization against diphtheria and/or tetanus (for convulsions or hypotonic-hyporesponsive episodes, see Precautions).

As with other vaccines, administration of Boostrix should be postponed in subjects suffering from acute severe febrile illness. The presence of a minor infection is not a contraindication.
Vaccination should be preceded by a review of the medical history (especially with regard to previous vaccination and possible occurrence of undesirable events) and a clinical examination.
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.
In children with progressive neurological disorders, including infantile spasms, uncontrolled epilepsy or progressive encephalopathy, it is better to defer pertussis (Pa or Pw) immunization until the condition is corrected or stable. However, the decision to give pertussis vaccine must be made on an individual basis after careful consideration of the risks and benefits.
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.
Boostrix should be administered with caution to subjects with thrombocytopenia or a bleeding disorder since bleeding may occur following an intramuscular administration to these subjects. If in accordance with official recommendations, the vaccine may need to 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.
A history or a family history of convulsions and a family history of an adverse event following DTP vaccination do not constitute contraindications.
Human Immunodeficiency Virus (HIV) infection is not considered as a contraindication for diphtheria, tetanus and pertussis vaccination. The expected immunological response may not be obtained after vaccination of immunosuppressed patients.
Extremely rare cases of collapse or shock-like state (hypotonic-hyporesponsiveness episode) and convulsions within 2 to 3 days of vaccination have been reported in DTPa and DTPa combination vaccines.
Boostrix should under no circumstances be administered intravenously.
Syncope (fainting) can occur following, or even before, any vaccination as a psychogenic response to the needle injection. It is important that procedures are in place to avoid injury from faints.
As with any vaccine, a protective immune response may not be elicited in all vaccinees.
Effects on Ability to Drive and Use Machines: The vaccine is unlikely to produce an effect on the ability to drive and use machines.

Fertility: No human data available. Animal studies do not indicate direct or indirect harmful effects with respect to female fertility.
Pregnancy: Boostrix can be used between 27 and 36 weeks of pregnancy in accordance with official recommendations.
For data relating to the prevention of pertussis disease in infants born to women vaccinated during pregnancy, see Pharmacology: Pharmacodynamics under Actions.
Safety data from a randomised controlled clinical trial (341 pregnancy outcomes) where Boostrix was administered to pregnant women between 27 and 36 weeks of pregnancy have have shown no vaccine related adverse effect on pregnancy or on the health of the foetus/newborn child (see Adverse Reactions).
Safety data from prospective clinical studies on the use of Boostrix during the first and second trimester of pregnancy are not available.
Additional safety data obtained from a prospective observational study with Boostrix (793 pregnancy outcomes) and from post-marketing surveillance with Boostrix and Boostrix Polio, where pregnant women were vaccinated during the third trimester in a period that partially overlaps with the weeks of pregnancy from the randomized controlled clinical trial (i.e. between 27 and 36 weeks), have shown no vaccine related adverse effect on pregnancy or on the health of the foetus/newborn child.
As with other inactivated vaccines, it is not expected that vaccination with Boostrix harms the foetus at any trimester of pregnancy.
Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or post-natal development.
Lactation: The safety of Boostrix when administered to breast-feeding women has not been evaluated.
It is unknown whether Boostrix is excreted in human breast milk.
Boostrix should only be used during breast-feeding when the possible advantages outweigh the potential risks.

Clinical Trial Data: The safety profile as follows is based on data from clinical trials where Boostrix was administered to 839 children (from 4 to 9 years of age) and 1931 adults, adolescents and children (above 10 years of age).
Adverse reactions reported are listed according to the following frequency: Very common ≥1/10; Common ≥1/100 and <1/10; Uncommon ≥1/1,000 and <1/100; Rare ≥1/10,000 and <1/1,000; Very rare <1/10,000.
Children from 4 to 9 years of age: Infections and infestations: Uncommon: upper respiratory tract infection.
Metabolism and nutrition disorders: Common: anorexia.
Psychiatric disorders: Very common: irritability.
Nervous system disorders: Very common: somnolence.
Common: headache.
Uncommon: disturbances in attention.
Eye disorders: Uncommon: conjunctivitis.
Gastrointestinal disorders: Common: diarrhoea, vomiting, gastrointestinal disorders.
Skin and subcutaneous tissue disorders: Uncommon: rash.
General disorders and administration site conditions: Very common: injection site reactions (including pain, redness and swelling), fatigue.
Common: fever ≥37.5°C (including fever >39°C).
Uncommon: other injection site reactions (such as induration), pain.
Adults, adolescents and children from the age of 10 years onwards: Infections and infestations: Uncommon: upper respiratory tract infection, pharyngitis.
Blood and lymphatic system disorders: Uncommon: lymphadenopathy.
Nervous system disorders: Very common: headache.
Common: dizziness.
Uncommon: syncope.
Respiratory, thoracic and mediastinal disorders: Uncommon: cough.
Gastrointestinal disorders: Common: nausea, gastrointestinal disorders.
Uncommon: diarrhoea, vomiting.
Skin and subcutaneous tissue disorders: Uncommon: hyperhidrosis, pruritus, rash.
Musculoskeletal and connective tissue disorders: Uncommon: arthralgia, myalgia, joint stiffness, musculoskeletal stiffness.
General disorders and administration site conditions: Very common: injection site reactions (including pain, redness and swelling), fatigue, malaise.
Common: fever ≥37.5°C, injection site reactions (such as injection site mass and injection site abscess sterile).
Uncommon: fever >39°C, influenza like illness, pain.
Reactogenicity after repeat dose of Boostrix: Data on 146 subjects suggest 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).
Subjects fully primed with 4 doses of DTPw followed by a Boostrix dose around 10 years of age show an increase of local reactogenicity after an additional Boostrix dose administered 10 years later.
Safety in women vaccinated with dTpa during pregnancy: In a randomized controlled clinical trial where women were vaccinated between 27 and 36 weeks of pregnancy, the safety profile observed was similar in the dTpa-vaccinated group as compared to the control group. The types and rates of solicited/unsolicited adverse events are in line with the observations available for the general population.
The following adverse events of interest were reported during the randomized controlled clinical trial: No pregnancy/neonate-related adverse events of interest were considered related to Boostrix vaccination during the study.
Pregnancy/neonate-related adverse events of interest were reported at similar rates (below 5%) in both study groups, the most common being premature labor (3.8% of women who received Boostrix vs 3.2% who received placebo during pregnancy) and premature rupture of membranes (3.8% of women who received Boostrix vs 4.3% who received placebo during pregnancy).
There were no maternal or neonatal deaths.
Congenital anomaly of infants born to vaccinated mothers was reported for 2.6% and 2.3% of women who received Boostrix vs those who received placebo during pregnancy, respectively. No safety concern was identified.
Post-Marketing Data: Blood and lymphatic system disorders: Rare: angioedema.
Immune system disorders: Very rare: allergic reactions, including anaphylactic and anaphylactoid reactions.
Nervous system disorders: Rare: convulsions (with or without fever).
Skin and subcutaneous tissue disorders: Rare: urticaria.
General disorders and administration site conditions: Rare: extensive swelling of the vaccinated limb, asthenia.

Concomitant use with other inactivated vaccines and with immunoglobulin is unlikely to result in an interference with the immune responses.
When considered necessary, Boostrix can be administered simultaneously with other vaccines or immunoglobulins.
If Boostrix is to be given at the same time as another injectable vaccine or immunoglobulin, the products should always be administered at different sites.
As with other vaccines, patients receiving immunosuppressive therapy or patients with immunodeficiency may not achieve an adequate response. In these patients, when tetanus vaccine is needed for tetanus prone wound, plain tetanus vaccine will be used.

Instructions for Use/Handling: Prior to vaccination, the vaccine should be well shaken in order to obtain a homogeneous turbid white suspension and visually inspected for any foreign particulate matter and/or variation of physical aspect prior to administration. In the event of either being observed, do not administer the vaccine.
Any unused product or waste material should be disposed of in accordance with local requirements.
Incompatibilities: Boostrix should not be mixed with other vaccines in the same syringe.

Store in a refrigerator (2°C - 8°C).
Do not freeze. Discard if the vaccine has been frozen.
Protect from light.

Vaccines, Antisera & Immunologicals

J07AJ52 - pertussis, purified antigen, combinations with toxoids ; Belongs to the class of pertussis bacterial vaccines.

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