Boostrix suspension for injection 1 dose syringe 0.5 ml with 2 needles No. 1

Instructions for use: Bustrix suspension for injection, 1 dose, 0.5 ml syringe with 2 needles No. 1

Composition

1 dose of vaccine (0.5 ml) contains:

active ingredients:

diphtheria toxoid1 - not less than 2 IU (2.5 Lf);

tetanus toxoid1 - not less than 20 IU (5 Lf);

Bordetella pertussis pertussis antigens: - 8 mcg

pertussis toxoid1 - 8 mcg;

filamentous hemagglutinin1 - 2.5 μg;

pertactin1 - 0.3 mg Al3+;

1 - adsorbed on aluminum hydroxide (Al (OH)3) - 0.2 mg Al3+;

and aluminum phosphate (AlPO4);

excipients: aluminum hydroxide, aluminum phosphate, sodium chloride, water for injection; formaldehyde, polysorbate 80, glycine are present in residual amounts as a result of the manufacturing process.

Dosage form

Suspension for injection.

Main physicochemical properties: cloudy liquid after shaking with slowly settling white precipitate. Colorless supernatant after settling.

Pharmacotherapeutic group

Combined bacterial vaccines. Pertussis vaccines. Pertussis, purified antigen, combinations with toxoids.

ATX code J07A J52.

Pharmacological properties

Pharmacodynamics

Immune response

Administration of the vaccine according to the approved recommendations induces specific immunity against diphtheria, tetanus, and pertussis. The immune response to the diphtheria, tetanus, and pertussis (acellular) components of the vaccine is shown in the table below. Approximately 1 month after booster vaccination with BOOSTERIX™, the following levels of seroprotection/seropositivity were observed (see Table 1).

Table 1

* levels sufficient to protect against disease

The results of comparative trials with commercial dT vaccines indicate that the efficacy and duration of protection are no different from those observed with the administration of these vaccines.

Effectiveness of protection against whooping cough

There are currently no data on the efficacy of BOOSTERIX™ against defined pertussis, however, the protective efficacy of DTPa vaccine (INFANRIX™) manufactured by GlaxoSmithKline Biologicals against typical pertussis disease as defined by WHO (≥ 21 days of laboratory-confirmed paroxysmal cough) has been demonstrated in the following 3-dose primary vaccination studies:

A prospective, blinded study of household contacts conducted in Germany (3, 4, 5 months schedule). Based on data from secondary contacts in households with an index case of pertussis, the protective efficacy of the vaccine was 88.7%. Protection against laboratory-confirmed mild disease, defined as any cough lasting 14 days or more, was 73% and 67% when the disease was defined as any cough lasting 7 days or more. A National Institutes of Health-sponsored efficacy study conducted in Italy (2, 4, 6 months schedule) found that the vaccine was 84%. When the disease definition was expanded to include clinically milder cases in terms of cough type and duration, the estimated efficacy of INFANRIX™ was 71% for cough > 7 days of any type and 73% for cough > 14 days of any type.

Individuals vaccinated with BOOSTERIX™ achieved higher antibody titers against pertussis than in a study among household contacts in Germany, where the protective efficacy of the vaccine was 88.7%.

Effectiveness of protection against pertussis in infants born to women who were vaccinated during pregnancy.

The efficacy of BOOSTERIX™ or BOOSTERIX™ Polio vaccine was evaluated in three observational studies conducted in the United Kingdom, Spain and Australia. The vaccine was administered to women during the third trimester of pregnancy to protect infants up to 3 months of age against pertussis, as part of the prenatal vaccination program.

Detailed information regarding the type of each study and vaccine efficacy results is presented in Table 2.

Table 2

Efficacy of protection against pertussis in infants under 3 months of age born to women who were immunized with BOOSTERIX™ or BOOSTERIX™ Polio vaccine during the third trimester of pregnancy:

If vaccinated 2 weeks before delivery, the effectiveness of protection in infants may be lower than the values indicated in the table.

Duration of immune response

The following seroprotection/seropositivity levels were obtained 3.5 years, 5-6 years and 10 years after immunization with BOOSTERIX™ vaccine (see Table 3).

Table 3

* Percentage of subjects with antibody concentrations associated with protection from disease (≥ 0.01 IU/mL by ELISA or ≥ 0.016 IU/mL by in vitro Vero cell neutralization assay).

Immune response after a repeat dose of BOOSTERIX™ vaccine.

The immunogenicity of BOOSTERIX™ administered 10 years after a previous booster with vaccine(s) containing lower levels of diphtheria, tetanus and acellular pertussis antigens was evaluated. At 1 month post-vaccination, more than 99% of subjects were seroprotected against diphtheria and tetanus and were seropositive for pertussis.

Immune response in patients without previous vaccination or with unknown vaccination history.

In children aged 11 to 18 years without previous vaccination against pertussis and without vaccination against diphtheria and tetanus within the previous 5 years, a single dose of BOOSTERIX™ vaccine induced an immune response against pertussis and all subjects were protected against tetanus and diphtheria.

In patients ≥ 40 years of age who had not received any diphtheria or tetanus vaccine in the past 20 years (including those who had never been immunized or whose vaccination status was unknown), a single dose of BOOSTERIX™ vaccine induced antibodies against pertussis in most cases and provided protection against tetanus and diphtheria.

Preclinical safety data

Reproductive toxicity

Fertility

Non-clinical data obtained for BOOSTERIX™ revealed no special hazard for humans based on conventional studies of female fertility in rats and rabbits.

Pregnancy

Preclinical data obtained for BOOSTERIX™ revealed no special hazard for humans based on conventional studies of embryo-foetal development in rats and rabbits, and no effects on parturition or postnatal toxicity in rats (until the end of lactation).

Animal toxicology and/or pharmacology

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

Pharmacokinetics

Assessment of pharmacokinetic properties is not mandatory for vaccines.

Indication

Booster immunization (revaccination) against diphtheria, tetanus, and pertussis for individuals starting at 4 years of age.

Vaccination of children in Ukraine is carried out in accordance with the requirements of current orders of the Ministry of Health of Ukraine.

Contraindication

BOOSTERIX™ vaccine should not be administered to individuals with known hypersensitivity to any component of the vaccine (see section “Composition”) or to individuals who have shown signs of hypersensitivity after previous administration of a vaccine for the prevention of diphtheria, tetanus and pertussis.

BOOSTERIX™ vaccine is contraindicated if an individual has experienced encephalopathy of unknown etiology within 7 days of previous vaccination with a vaccine containing pertussis. In this case, vaccination with the pertussis component should be abandoned and the immunization course with vaccines intended for the prevention of diphtheria and tetanus should be continued.

BOOSTERIX™ should not be used in individuals who have experienced transient thrombocytopenia or neurological complications following previous immunization against diphtheria and/or tetanus (see information on seizures and hypotonic-hyporesponsive episodes in the section “Special instructions for use”).

As with other vaccines, the administration of BOOSTERIX™ should be postponed in patients with acute febrile illnesses. The presence of a mild infection is not a contraindication.

Interaction with other medicinal products and other types of interactions

BOOSTERIX™ can be administered concomitantly with human papillomavirus vaccine without clinically significant effects on the immune response to either vaccine component.

BOOSTERIX™ can be administered concomitantly with meningococcal serogroups A, C, W-135 and Y conjugate vaccines (MenACWY). Clinical studies in patients 9 to 25 years of age demonstrated that the immune response to tetanus, diphtheria and meningococcal antigens was not altered. Lower geometric mean concentrations (GMCs) were observed for pertussis antigens, but these data do not indicate clinical significance. The concomitant administration of BOOSTERIX™ with other vaccines or immunoglobulins has not been studied.

Concomitant use with other inactivated vaccines and immunoglobulin is unlikely to impair the immune response.

In accordance with generally accepted vaccination practices and recommendations, if BOOSTERIX™ is used concomitantly with other injectable vaccines or immunoglobulin, these products should always be administered at different sites in the body.

Use of BOOSTERIX™ vaccine during treatment with immunosuppressive drugs.

An adequate immune response may not be achieved in patients receiving immunosuppressive therapy.

Application features

Good clinical practice suggests that vaccination should be preceded by a review of the medical history (especially regarding previous vaccination and possible adverse events) and a clinical examination.

If any of the following symptoms are known to have been temporally associated with receipt of a pertussis-containing vaccine, the decision to administer a subsequent dose of pertussis-containing vaccines should be carefully considered:

temperature ≥ 40.0 °C within 48 hours of vaccination, not associated with other identifiable causes; collapse or shock-like state (hypotonic-hyporesponsive episode) within 48 hours of vaccination; persistent continuous crying lasting ≥ 3 hours, observed within 48 hours of vaccination; seizures with or without fever, occurring within 3 days of vaccination.

There may be circumstances, such as a high incidence of whooping cough, when the potential benefit outweighs the possible risk.

In children with progressive neurological disorders, including infantile spasms, uncontrolled epilepsy, or progressive encephalopathy, it is preferable to postpone pertussis immunization (Pa-acellular pertussis component, Pw-whole cell pertussis component) until the condition improves or stabilizes. However, the decision to use pertussis vaccine should be made on an individual basis after careful consideration of the potential risks and benefits.

As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of rare anaphylactic reactions following the administration of the vaccine. Therefore, patients should be observed for at least 30 minutes after vaccination. Vaccination sites should be equipped with facilities for shock treatment.

BOOSTERIX™ should be used with caution in individuals with thrombocytopenia or bleeding disorders, as bleeding may occur when the vaccine is administered intramuscularly to such individuals. To prevent bleeding, the injection site should be pressed firmly (without rubbing) for at least two minutes.

A history of seizures or a family history of seizures and adverse events is not a contraindication for vaccination.

HIV infection is not a contraindication for vaccination against diphtheria, tetanus, and pertussis. The expected immunological response may not be obtained in immunocompromised patients.

Under no circumstances should BOOSTERIX™ be administered intravenously.

Syncope (fainting) may occur during or before any injectable vaccination, especially in adolescents, as a psychogenic reaction to the needle injection. It may be accompanied by several neurological symptoms such as transient visual disturbances, paresthesias and tonic-clonic movements of the limbs during recovery from this state. Vaccination should only be carried out in the sitting or lying position of the vaccinee and the vaccinee should be kept in the same position (sitting or lying) for 15 minutes after vaccination to prevent the risk of injury.

As with any vaccine, a protective immune response may not be achieved in vaccinated individuals.

This medicinal product contains less than 1 mmol (23 mg) sodium/dose, i.e. essentially 'sodium-free'.

Ability to influence reaction speed when driving vehicles or other mechanisms

The ability of the vaccine to affect the reaction speed when driving or operating other mechanisms is unlikely.

Use during pregnancy or breastfeeding

Pregnancy

The use of BOOSTERIX™ vaccine may be considered during the third trimester of pregnancy.

Safety data from a prospective observational study in which BUSTRIX™ was administered to pregnant women during the third trimester (793 pregnant women), as well as data from post-marketing surveillance in which pregnant women received BUSTRIX™ or BUSTRIX™ Polio (dTpa-IPV vaccines) during the second and third trimesters, indicate no adverse reactions related to the effects of the vaccine on pregnancy or the health of the fetus/newborn.

There are no prospective clinical trial data on the use of BUSTRIX™ during the first and second trimesters of pregnancy. However, as with other inactivated vaccines, BUSTRIX™ vaccination is not expected to have a harmful effect on the fetus during any trimester of pregnancy. The benefits and risks of using BUSTRIX™ during pregnancy should be carefully weighed.

Limited data suggest that the presence of antibodies in pregnant women may reduce the level of immune response to some vaccines in infants born to women who received BOOSTERIX™ vaccine during pregnancy. The clinical significance of this observation is unknown.

Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/fetal development, parturition or postnatal development (see section 5.2 for further information).

Breast-feeding

The safety of BUSTRIX™ in women who are breastfeeding has not been studied. However, since BUSTRIX™ contains toxoids or inactivated antigens, no risk to the breastfed infant is expected.

BOOSTERIX™ can be used during breastfeeding only if the benefit of use outweighs the potential risk.

Fertility

There are no clinical data on human fertility. Animal studies do not indicate direct or indirect harmful effects with respect to female fertility.

Method of administration and doses

A single injection of the vaccine at a dose of 0.5 ml is recommended.

BOOSTERIX™ can be administered from the age of 4 years, in accordance with official recommendations and/or in accordance with current medical practice for booster immunization with combined vaccines containing reduced antigens against diphtheria and tetanus for adults when revaccination against pertussis is required. Revaccinations against diphtheria, tetanus and pertussis should be carried out at intervals specified by official recommendations (usually every 10 years).

BOOSTERIX™ can be administered to children and adults whose vaccination status is unknown or to those who have not completed the diphtheria, tetanus and pertussis vaccination course as part of a diphtheria, tetanus and pertussis immunization series (see section 5.1). Based on data in adults, two additional doses of diphtheria and tetanus vaccine are recommended to be administered 1 and 6 months after the first dose to maximize the vaccine response against diphtheria and tetanus.

BOOSTERIX™ can be administered concomitantly with human tetanus immunoglobulin for the prevention of tetanus in case of trauma in individuals who have previously received a primary course of vaccination with tetanus toxoid vaccine and who are indicated for revaccination against pertussis and diphtheria in accordance with official recommendations.

The BUSTRIX™ vaccine is intended for deep intramuscular injection into the deltoid muscle (see also the section “Special instructions for use”).

Under no circumstances should BOOSTERIX™ be administered intravenously.

Instructions for use/application

Before vaccination, the vaccine should be shaken thoroughly until a homogeneous opaque white suspension is obtained and inspected visually for any foreign particles and/or changes in physical appearance prior to administration. In case of any changes, the vaccine should be discarded.

It is advisable for the vaccine to be at room temperature before use.

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

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

Children

The safety and efficacy of BOOSTERIX™ vaccine in children under 4 years of age have not been established (see sections “Indications”, “Method of administration and dosage”).

Overdose

Several cases of vaccine overdose have been reported during post-marketing surveillance. Adverse reactions observed following overdose were similar to those observed with normal use of the vaccine.

Adverse reactions

The safety profile presented in Table 4 is based on data from clinical studies in which BOOSTERIX™ was administered to 839 children (aged 4 to 8 years) and 1931 patients aged 10 to 76 years.

The most common adverse events in both groups of vaccinees were reactions at the injection site (pain, redness, and swelling), which were generally reported in 23.7-80.6% of subjects. Such reactions occurred within the first 48 hours after vaccination and resolved without sequelae.

Adverse reactions are listed in Table 4 below.

Adverse reactions are divided into the following categories according to their frequency of occurrence:

Very common: ≥ 1/10;

Common: ≥ 1/100 to < 1/10;

Uncommon: ≥ 1/1000 to < 1/100;

Rare: ≥ 1/10,000 to < 1/1,000;

Very rare: < 1/10,000.

Table 4

Adverse reactions identified during clinical trials of the vaccine

Adverse reactions

Reactogenicity after a repeat dose of BOOSTERIX™ vaccine.

Data obtained from the results of administering the vaccine to 146 patients indicate a slight increase in local reactogenicity (pain, redness, swelling) during repeated vaccinations of adults (aged 40 years and older) according to the vaccination schedule of 0, 1, 6 months.

The data suggest that subjects who were vaccinated with DTPw vaccine in childhood may experience increased local reactogenicity after revaccination.

Post-marketing surveillance data

The following adverse reactions have been reported spontaneously, so it is not possible to accurately determine their frequency.

Table 5.

Adverse reactions identified during post-marketing surveillance of the BUSTRIK™ vaccine

Adverse reactions

Adverse reactions involving the central or peripheral nervous system, including ascending paralysis or even paralysis of the respiratory muscles (i.e. Guillain-Barré syndrome), have been reported in very rare cases following the administration of vaccines containing tetanus toxoid.

Expiration date

36 months.

The expiration date is indicated on the packaging.

Storage conditions

Store at 2 to 8°C. Do not freeze. Store in a place protected from light and out of reach of children. After removal from the refrigerator, the vaccine is stable for 8 hours at 21°C.

Incompatibility

Do not mix with other vaccines or medications in the same syringe.

Packaging

Suspension for injection, 1 dose (0.5 ml/dose) in a pre-filled syringe No. 1, complete with two needles.

1 pre-filled syringe complete with two needles in a plastic container; 1 container in a cardboard box.

Pre-filled syringes are made of neutral type I glass, which meets the requirements of the European Pharmacopoeia.

Vacation category

According to the recipe.

Producer

GlaxoSmithKline Biologicals S.A., Belgium.

Location of the manufacturer and its business address

Rue de l'Institut, 89 1330 Rixensart, Belgium.