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

Instructions for use: Boostrix Polio 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:

excipients: sodium chloride, medium 199, aluminum salts, water for injection.

Formaldehyde, neomycin sulfate, polymyxin B sulfate are present in residual amounts as a result of the manufacturing process.

Dosage form

Suspension for injection.

Main physicochemical properties: cloudy liquid, white precipitate. Colorless supernatant.

Pharmacotherapeutic group

Combined bacterial and viral vaccines. Diphtheria-pertussis-polio-tetanus vaccine.

ATX code J07C A02.

Pharmacological properties

Immunobiological and biological properties.

Pharmacodynamics

Immune response

In studies, the following immune responses were observed one month after immunization with Boostrix Polio vaccine in children, adolescents and adults (Table 1).

Table 1

N is the number of vaccinated individuals.

* The immune response to revaccination is defined as:

For initially seronegative patients whose antibody concentration level was at least 4 times higher than the cut-off value (post-booster concentration ≥ 20 El.U/ml);

For initially seropositive patients with pre-booster antibody concentrations ≥ 5 El.U/ml and < 20 El.U/ml: an increase in antibody levels of at least 4-fold compared to the pre-booster antibody level;

For initially seropositive patients with pre-booster antibody concentrations ≥ 20 El.U/ml: an increase in antibody levels of at least 2-fold compared to the pre-booster antibody level.

As with other diphtheria-tetanus vaccines, Boostrix Polio induces a higher level of seroprotection and higher titers of anti-diphtheria and anti-tetanus antibodies in children and adolescents compared to adults.

Effectiveness of protection against whooping cough.

The pertussis antigens contained in Bustrix Polio are part of the paediatric acellular pertussis combined vaccine (Infanrix), the efficacy of which has been demonstrated after primary vaccination in a clinical efficacy study of this vaccine. Antibody titres for all three pertussis components following booster vaccination with Bustrix Polio were at or above those observed in the above clinical study. Based on these comparisons, Bustrix Polio will confer protection against pertussis, but the level and duration of this protection have not been determined.

Passive protection against pertussis in infants (up to 3 months of age) by vaccinating their mothers during pregnancy.

In a randomized, crossover, placebo-controlled study, higher concentrations of pertussis antibodies were demonstrated in the umbilical cord blood of infants whose mothers were vaccinated with BOOSTERIX (dTpa group; N = 291) compared with those in the placebo group (control group; N = 292) at 27-36 weeks of gestation. The geometric mean concentrations of antibodies in the umbilical cord blood against the pertussis antigens PT, FHA and PRN were 46.9, 366.1 and 301.8 IU/ml in the dTpa group and 5.5, 22.7 and 14.6 IU/ml in the control group. This corresponds to antibody titers that are 8, 16 and 21 times higher in the umbilical cord blood of infants whose mothers were vaccinated compared with those in the control group. These antibody titers may provide passive protection against pertussis, as observed in efficacy studies.

The immunogenicity of INFANRIX HEXA (diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, diseases caused by Haemophilus influenzae type b) in infants born to healthy mothers who were vaccinated with BOOSTERIX at 27-36 weeks of gestation was evaluated in two clinical studies. For primary vaccination, INFANRIX HEXA was administered concomitantly with 13-valent pneumococcal conjugate vaccine (n = 268) and the same infants were given a booster dose at 11 to 18 months of age (n = 229).

Immunological data after primary and booster vaccination did not show a clinically significant effect of maternal vaccination with BUSTRIX vaccine on the formation of the immune response of infants after vaccination against diphtheria, tetanus, hepatitis B, poliomyelitis, diseases caused by Haemophilus influenzae type b, or on the formation of the immune response to pneumococcal antigens.

Lower antibody concentrations against pertussis antigens after primary (PT, FHA and PRN) and after booster (PT, FHA) vaccination were observed in infants whose mothers had been vaccinated with BOOSTERIX during pregnancy. The increase in pertussis antibody concentrations before and 1 month after booster vaccination was in the same range in infants whose mothers had been vaccinated with BOOSTERIX or placebo, demonstrating an effective immune response. In the absence of correlates of protection against pertussis, the clinical relevance of these observations remains unclear. However, current epidemiological data on pertussis disease after the introduction of maternal dTpa immunization do not suggest any clinical relevance of this immune intervention.

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

The efficacy of the 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 against pertussis in infants up to 3 months of age, as part of a pregnancy 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:

CI – confidence interval

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

Duration of immune response.

The following seroprotection/seropositivity rates were observed five years after vaccination with Bustrix Polio in children and 10 years after vaccination with Bustrix Polio in adolescents and adults (Table 3).

Table 3

Duration of immune response in children and adults

* 98.2% of subjects had disease-associated antibody concentrations ≥ 0.016 IU/mL based on in vitro Vero cell neutralization assay.

** 92.1% of subjects had disease-associated antibody concentrations ≥ 0.01 IU/mL based on in vitro Vero cell neutralization assay.

Immune response after a repeat dose of Boostrix Polio vaccine.

The immunogenicity of the Bustrix Polio vaccine administered 5 years after a previous booster immunization with the Bustrix Polio vaccine at the age of 4 to 8 years was evaluated. At 1 month after vaccination, more than 99% of patients were seropositive for pertussis and had serological protection against diphtheria, tetanus, and all three types of poliovirus.

In adults, 1 dose of Boostrix Polio vaccine administered 10 years after the previous dose resulted in a protective immune response in > 96.8% of subjects (for diphtheria antigen) and in 100% of cases (for tetanus and polio antigens). The booster response against pertussis antigens was between 74.2 and 98.4%.

In adolescents aged 11 to 18 years without previous vaccination against pertussis and without vaccination against diphtheria and tetanus in the previous 5 years, a single dose of BUSTRIX vaccine (dTpa component of BUSTRIX Polio vaccine) induces a humoral response against pertussis and all vaccinees were protected against tetanus and diphtheria.

After a single dose of Boostrix Polio vaccine in 140 adults ≥ 40 years of age (including those who had never been vaccinated or whose vaccination status was unknown) who had not received any diphtheria and tetanus vaccine within the past 20 years, more than 96.4% were seropositive against all three pertussis antigens and 77.7% and 95.7% were seroprotected against diphtheria and tetanus, respectively.

Preclinical safety data

Reproductive toxicity

Fertility

Non-clinical data obtained with Boostrix Polio vaccine revealed no special hazard for humans based on conventional studies of female fertility in rats and rabbits.

Pregnancy

Preclinical data obtained for the vaccine Bustrix Polio revealed no specific hazard for humans based on conventional studies of embryo-foetal development in rats and rabbits, and no effects on the course of labor and postnatal toxicity in rats (until the end of the lactation period).

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

For booster immunization (revaccination) against diphtheria, tetanus, pertussis and poliomyelitis in persons aged 3 years and older. The Bustrix Polio vaccine is not indicated for primary immunization.

For passive protection against pertussis in infants (up to 3 months of age) by vaccination of their mothers during pregnancy (see sections “Immunological and biological properties”, “Use during pregnancy or lactation” and “Method of administration and dosage”).

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

Contraindication

Boostrix Polio vaccine should not be administered to individuals with known hypersensitivity to any component of the vaccine (including neomycin, polymyxin or formaldehyde (see section "Composition")), or to individuals who have shown signs of hypersensitivity after previous administration of vaccines for the prevention of diphtheria, tetanus, pertussis or inactivated vaccines for the prevention of poliomyelitis.

Boostrix Polio is contraindicated if the individual has suffered from encephalopathy of unknown etiology within 7 days of previous vaccination with a pertussis-containing vaccine. In these circumstances, pertussis vaccine should be discontinued and vaccination with diphtheria, tetanus, and polio vaccines should be continued.

Boostrix Polio should not be used in individuals who have had transient thrombocytopenia or neurological complications following previous administration of diphtheria and/or tetanus vaccines (for information on seizures or hypotonic-hyporesponsive episodes, see section “Special warnings and precautions for use”).

As with other vaccines, the administration of Boostrix Polio 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

Use with other vaccines or immunoglobulins.

Boostrix Polio can be administered concomitantly with any of the following monovalent or combination vaccines: measles, mumps, rubella, varicella and human papillomavirus, without clinically significant effects on the immune response to any component of either vaccine (see section "Adverse reactions").

The concomitant use of Bustrix Polio with other vaccines or immunoglobulins has not been studied. It is unlikely that concomitant use with other inactivated vaccines will result in impaired immune responses. In accordance with generally accepted vaccination practices and recommendations, if Bustrix Polio is administered concomitantly with other injectable vaccines or immunoglobulins, these products should always be administered at different sites.

Use of the Bustrix Polio vaccine during treatment with immunosuppressive drugs.

As with other vaccines, an adequate immunological response may not be obtained in patients treated with immunosuppressive drugs.

Application features

In good clinical practice, vaccination should be preceded by a review of the medical history (especially regarding previous vaccination and possible adverse events) and a physical examination.

If any of the following events occur in temporal association with receipt of a pertussis-containing vaccine in a young child, the decision to receive a subsequent dose of pertussis-containing vaccine should be carefully considered:

temperature ≥ 40.0 °C within 48 hours after vaccination, not associated with other identifiable causes;

collapse or shock-like state (hypotonic-hyporesponsive episode) within 48 hours after vaccination;

persistent continuous crying lasting ≥ 3 hours is observed within 48 hours after vaccination;

Convulsions 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.

Under no circumstances should Bustrix Polio vaccine be administered intravascularly.

Bustrix Polio should be used with caution in individuals with thrombocytopenia (see section "Contraindications") or blood clotting disorders, since bleeding may occur with intramuscular administration of the vaccine in such individuals. According to the current Orders of the Ministry of Health of Ukraine, the vaccine can be administered subcutaneously to such individuals. With both routes of administration, the injection site should be pressed firmly (without rubbing) for at least two minutes to prevent bleeding.

Following immunization of children with vaccines containing one or more antigenic components of the Bustrix Polio vaccine, there have been very rare reports of cases of collapse or shock-like states (hypotonic-hyporesponsive episodes) and seizures.

A history of febrile seizures, a family history of seizures, sudden infant death syndrome, and a family history of adverse reactions after DTP vaccines are not contraindications.

HIV infection is not a contraindication for vaccination with the Bustrix Polio vaccine.

The expected immunological response may not be achieved after vaccination of immunocompromised patients.

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

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.

Excipients with known effect

Boostrix Polio contains para-aminobenzoic acid. This may cause allergic reactions (possibly delayed), and exceptionally bronchospasm.

This medicine contains 0.0298 micrograms of phenylalanine in each dose. Phenylalanine may be harmful if you have phenylketonuria (PKU), a rare genetic disorder in which phenylalanine builds up because the body cannot properly excrete it.

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

This medicinal product contains less than 1 mmol (39 mg)/dose of potassium, i.e. essentially potassium-free.

Use during pregnancy or breastfeeding

Pregnancy

Boostrix Polio can be administered to pregnant women during the second or third trimester of pregnancy in accordance with official recommendations.

Data on the efficacy of protection against pertussis in infants born to women vaccinated during pregnancy are provided in the section “Immunological and biological properties”.

Safety data from a randomized controlled clinical trial (341 pregnant women) and a prospective observational study (793 pregnant women) when BOOSTERIX was administered during the third trimester of pregnancy indicate no adverse reactions related to the effects of the vaccine on pregnancy or the health of the fetus/newborn.

There are no safety data from prospective clinical studies regarding the use of BUSTRIX or BUSTRIX Polio vaccine during the first and second trimesters of pregnancy.

Passive observational data when BOOSTERIX or BOOSTERIX Polio (dTpa-IPV vaccine) was administered to pregnant women during the 2nd and 3rd trimesters of pregnancy indicate the absence of adverse reactions related to the effects of the vaccine on pregnancy or the health of the fetus/newborn.

As with other inactivated vaccines, vaccination with Boostrix Polio is not expected to have a harmful effect on the fetus during any trimester of pregnancy.

Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see section "Immunological and biological properties")

The safety of Bustrix Polio vaccine in women who are breastfeeding has not been studied. However, since Bustrix Polio contains toxoids or inactivated antigens, no risk to the breast-fed infant is expected.

Boostrix Polio 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 (see section "Immunological and biological properties").

The ability to influence the reaction speed when driving or working with other mechanisms

The effect on the ability to drive vehicles and operate other mechanisms is unlikely.

Method of administration and doses

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

Bustrix Polio vaccine can be administered from the age of 3 years in accordance with official recommendations and/or current medical practice for vaccines containing reduced antigens against diphtheria, tetanus, pertussis in combination with poliomyelitis antigens. Bustrix Polio can be administered simultaneously with human tetanus immunoglobulin to prevent tetanus in case of trauma in persons who are indicated for revaccination against pertussis, diphtheria and poliomyelitis and who have previously received a primary course of vaccination with tetanus toxoid vaccine in accordance with official recommendations.

Revaccination against diphtheria, tetanus, pertussis and polio should be carried out at the intervals determined according to official recommendations (usually every 10 years).

The Bustrix Polio vaccine is intended for deep intramuscular injection into the deltoid muscle (see section "Special instructions for use").

If 2 needles of different lengths are provided, the appropriate needle size should be selected to ensure deep intramuscular injection depending on the patient's size and weight.

Boostrix Polio can be administered to pregnant women during the second or third trimester in accordance with official recommendations (see sections “Indications”, “Use during pregnancy or lactation” and “Immunological and biological properties”).

Boostrix Polio can also be administered to children and adults whose vaccination status is unknown or to those who have received an incomplete course of diphtheria, tetanus and pertussis vaccination as part of a diphtheria, tetanus, pertussis and polio immunization series (see section 5.2). 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.

Instructions for use/application

Boostrix Polio should be inspected visually for any foreign particulate matter and/or abnormal physical appearance prior to administration. If any of the above are observed, the vaccine should not be used.

Since a white precipitate may form during storage, the Bustrix Polio suspension should be shaken well before use until a homogeneous, cloudy white suspension is obtained. It is advisable to bring the vaccine to room temperature before use.

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

Technique for using a pre-filled syringe:

Hold the syringe by the barrel, not the piston.

Unscrew the syringe cap by turning it counterclockwise.

To attach the needle, connect the hub to the Luer-Lock adapter and turn a quarter turn clockwise until the needle is fully seated.

Do not pull the plunger out of the syringe barrel. If this happens, do not administer the vaccine.

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

Children

The safety and efficacy of the Bustrix Polio vaccine in children under 3 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.

Side effects

The safety profile presented in Table 4 is based on data from clinical studies in which Boostrix Polio was administered to 908 children (aged 4 to 8 years) and 955 patients aged 10 to 93 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 31.3-82.3% of subjects. Such reactions occurred within the first 48 hours after vaccination and resolved without sequelae.

Adverse reactions are listed in Table 4 below.

They are divided into 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 Bustrix Polio vaccine

Concomitant administration with measles, mumps, rubella and varicella vaccines in children aged 3 to 6 years.

Boostrix Polio was administered concomitantly with measles, mumps, rubella and varicella vaccines in two clinical trials involving 406 children aged 3 to 6 years. Upper respiratory tract infections and rashes were commonly reported in these trials. Fever, irritability, fatigue, loss of appetite and gastrointestinal disorders (including diarrhoea and vomiting) were reported at a higher frequency (very common) compared to Table 4, while all other adverse reactions were observed at the same or lower frequency.

Table 4 presents adverse reactions that were additionally reported during clinical trials with BOOSTERIX (dTpa component of BOOSTERIX Polio vaccine) administered to 839 children (aged 4 to 8 years) and 1931 patients aged 10 to 76 years.

Table 5.

Adverse reactions identified during clinical trials of the BOOSTERIX vaccine

Reactogenicity after a repeat dose of BUSTRIX or BUSTRIX Polio vaccine.

The data suggest an increase in local reactogenicity in subjects who were previously administered the DTPw vaccine in childhood.

Patients 15 years of age and older without prior vaccination against diphtheria, tetanus, pertussis, and poliomyelitis who received a dose of Bustrix Polio or another vaccine with a reduced antigenic composition followed by a booster dose of Bustrix Polio 10 years later did not show increased reactogenicity.

Post-marketing surveillance data

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

Adverse reactions identified during post-marketing surveillance of the use of the Bustrix Polio vaccine

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.

Reporting of suspected adverse reactions

Reporting adverse reactions after the registration of a medicinal product is important. This allows monitoring of the benefit/risk ratio of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the link: https://aisf.dec.gov.ua.

Also, all cases of suspected adverse reactions and lack of effectiveness of the drug can be reported to GlaxoSmithKline Pharmaceuticals Ukraine LLC by calling 24/7 at (044) 585-51-85 or by email at oax70065@gsk.com.

Expiration date

36 months. The expiration date of the vaccine is indicated on the label and packaging.

Storage conditions

Store at 2 to 8°C. Do not freeze. Store in a place protected from light, out of the reach of children. After removal from the refrigerator, the vaccine is stable for 8 hours at 21°C. If the vaccine has not been used during this time, it must be discarded. This information is intended only for healthcare professionals in case of temporary deviations in storage temperature conditions.

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.

The cap and rubber plunger stopper of the pre-filled syringe are made of synthetic rubber.

Vacation category

According to the recipe.

Producer

GlaxoSmithKline Biologicals SA, Belgium.

Location of the manufacturer and its business address.

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

Applicant