Synflorix® (Synflorix®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
Read on
Active substanceVaccine for the prevention of pneumococcal infectionsVaccine for the prevention of pneumococcal infections
Dosage form: & nbspsuspension for intramuscular injection
Composition:

1 dose (0.5 ml) contains:

Name of components

amount

Active substances:

Polysaccharides Streptococcus pneumoniae, conjugated to carrier proteins:

Polysaccharide serotype 1

1 μg / PD

Polysaccharide serotype 4

3 μg / PD

Polysaccharide serotype 5

1 μg / PD

Polysaccharide serotype 6AT

1 μg / PD

Polysaccharide serotype 7F

1 μg / PD

Polysaccharide serotype 9V

1 mcg / PD

Polysaccharide serotype 14

1 μg / PD

Polysaccharide serotype 18C

3 μg / TT

Polysaccharide serotype 19F

3 μg / DT

Polysaccharide serotype 23 F

1 μg / PD

Protein carriers (total):

PD: D-protein Haemophilus influenzae.

9-16 mcg *

TT: tetanus toxoid

5-10 μg *

DT: diphtheria toxoid

3-6 μg *

Excipients:

Aluminum phosphate (in terms of aluminum)

0.5 mg

Sodium chloride

~ 4.4 mg

Water for injections

up to 0.5 ml

* The composition of the drug is based on the content of polysaccharides, and the individual content of carrier protein depends on the ratio of "polysaccharide / protein".

Description:

A white suspension, separated upon settling into two layers: a colorless supernatant and a white precipitate, completely broken up by shaking, without flakes and conglomerates.

Pharmacotherapeutic group:MIBP vaccine
ATX: & nbsp

J.07   Vaccines

J.07.A.L   Vaccine for the prevention of pneumococcal infection

Pharmacodynamics:

Epidemiological data

The vaccine contains antigens of 10 serotypes Streptococcus pneumoniae (1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F), causing the greatest number of cases of invasive pneumococcal infection (50-96%) in children under 5 years in the world.

Pneumonia of various etiologies is the main cause of childhood morbidity and mortality throughout the world. According to estimates made in prospective studies, 30-50% of cases of bacterial pneumonia are caused by Streptococcus pneumoniae.

In world practice, no less than 60-70% of clinical cases of acute otitis media of the middle ear (CCA) have a bacterial cause and are most often caused Streptococcus pneumoniae and untypical Haemophilus influenzae.

Immunological efficacy

In clinical studies, Synflorix® elicited an immune response to all 10 serotypes included in the vaccine, but the response varied depending on the serotype. The functional immune response against serotypes 1 and 5 was slightly lower than the remaining serotypes. The effect of this phenomenon on the clinical effectiveness of the vaccine for the prevention of diseases caused precisely by these serotypes is unknown.

It has also been demonstrated that Synflorix® induces an immune response against serotypes Streptococcus pneumoniae 6A and 19A, ne included in the vaccine. One month after the revaccination, an increase in the mean geometric concentrations (SGS) of the antibodies to these serotypes was observed in 5.5 and 6.1 times and in the mean geometric titers (CGT), determined by the opsonophagocytosis activity (OPA), 6.7 and 6.1 times respectively.

Clinical studies have confirmed the high immunogenicity of the Synflorix® vaccine in the use of a two-dose and three-dose primary immunization regimens in children under 2 years of age and 2-5 years of age.

Effectiveness in the prevention of invasive pneumococcal infections

Clinical Trials Data

The effectiveness of the Synflorix® vaccine for the prophylaxis of bacteriologically confirmed cases of invasive pneumococcal infections (IPI) caused by pneumococcal serotypes included in the vaccine was confirmed in clinical studies. The efficacy of the vaccine in children <7 months for the prevention of bacteriologically confirmed cases of IPI was 100% for vaccination but for the 3 + 1 scheme and 91.8% for the 2 + 1 vaccination.

Post-registration data

In Canada, the Sinflorix® vaccine was given to infants in the National Immunization Program (primary vaccination in children younger than 6 months - 2 doses, revaccination at 12 months-1 dose) after 4.5 years of 7-valent conjugate vaccine for the prevention of pneumococcal infections . According to the epidemiological surveillance data accumulated within 1.5 years from the moment of inclusion of the Synflorix® vaccine in the immunization program, when 90% of the children were vaccinated, there was a decrease in the number of cases of IPI caused by vaccine serotypes (mainly due to the serotype 7F), without a concomitant increase in the number of cases of IPI caused by serotypes not included in the vaccine.In general, the incidence of IPI was 35 per 100,000 person-years for the vaccination of Synflorix® and 64 per 100,000 person-years for vaccination with a 7-valent conjugated vaccine for the prevention of pneumococcal infections (p = 0.03).

Efficacy in the prevention of pneumonia

Clinical trial data

The effectiveness of the Synflorix® vaccine in prophylaxis presumably bacteriumcommunity-acquired pneumonia (PFS) was shown in a cohort that received primary immunization with at least 3 doses (p≤0.002). Presumably, bacterial PFS was defined as an x-ray-confirmed case of extra-hospital pneumonia with alveolar densification and / or pleural effusion or with nonalveolar infiltration at a C-reactive protein level ≥ 40 mg / l. The efficacy of the vaccine for presumably bacterial PFS two weeks after the third dose of vaccine was 22%.

The efficacy of the vaccine for PFS with alveolar inspissation or pleural effusion was 22.4% during the observation period of 48 months from the start of the study.

The effectiveness of the Synflorix® vaccine in the prevention of bacteremic pneumococcal pneumonia or empyema caused by vaccine serotypes of pneumococcus was 100%.

The effectiveness of the vaccine in reducing the incidence of pneumonia (established in accordance with the ICD-10 codes for pneumonia) diagnosed in the hospital was 26.7% for the 3 + 1 vaccination; 29,3% for vaccination according to the scheme 2 + 1; 33.2% for vaccination of children aged 7-11 months; 22,4% for vaccination of children aged 12-18 months.

Efficacy in the prevention of acute otitis media of the middle ear (CCA)

Introduction of the vaccine Synflorix® induces an immune response not only to serotypes Streptococcus pneumoniae, part of the vaccine and related to them, but also to D-protein, surface antigen non-typed Haemophilus injluenzae, one of the causative agents of the CCA, which is included in the vaccine Synflorix® as a carrier protein.

Clinical Trials Data

The effectiveness of the Synflorix® vaccine in the prevention of OSO has been confirmed by two clinical studies.

In the first clinical study using a candidate vaccine containing 10 serotypes Streptococcus pneumoniaeincluded in the composition of the vaccine Synflorix®, and one additional serotype, the effectiveness of the vaccine for the prevention of OSO was: 33.6% for a clinically confirmed CCA of any etiology; 51.5% for the CCA caused by any serotype of pneumococcus; 67.9% for the CCA caused by serotypes Streptococcus pneumoniae, antigens of which are included in the vaccine Synflorix®; 65.5% for the CCA caused by serotypes Streptococcus pneumoniae, related serotypes included in the vaccine Synflorix® (6A, 9N, 19A): 35.3% for the CCA caused by the untyped Haemophilus influenzae; 35.6% for the CCA caused by Haemophilus influenzae (including untyped Haentophilus influenzae).

In the second study using the Synflorix® vaccine, the effectiveness of the vaccine in the prevention of OSO was: 16.1% for a clinically validated CCA of any etiology; 56.1% for CCA caused by any pneumococcal serotype; 67.1% - for CCA caused by serotypes Streptococcus pneumoniae, antigens of which are included in the vaccine Synflorix®; 15% for the CCA caused by Haemophilus influenzae (including untyped Haemophilus influenzae); 15% - with regard to CCA caused by only untyped Haemophilus influenzae.

There was a lack of growth in the number of cases acute otitis media of the middle ear caused by non-vaccine and / or non-cross-reactive serotypes or other bacterial pathogens.

After the vaccination is completed, a candidate vaccine containing 10 serotypes Streptococcus pneumoniae, included in the vaccine Synflorix®, and one additional serotype,the frequency of recurrent OCA (≥3 exacerbation after 6 months or ≥4 after 12 months) decreased by 56%, and the number of episodes of the catheterization of the auditory tube by 60.3%.

Effect on the appointment of antimicrobial therapy

In the general cohort of vaccinated children, the decrease in amoxicillin prescription (the most commonly prescribed antibiotic in CCA) in vaccination with Sinflorix® was 7.9% for 3 + 1 and 7.5% for 2 + 1 vaccination. In the Sinflorix® vaccine groups, there was a trend to reduction of all ambulatory appointments of antimicrobial therapy and prescriptions of antimicrobial therapy drugs most often used in otitis media and respiratory infections.

Influence on carriage in the nasopharynx

The effect of the Synflorix® vaccine on the carriage of pathogenic microorganisms in the nasopharynx has been studied in two clinical studies.

In these studies, with the use of the Synflorix® vaccine, the carrier of microorganisms included in the vaccine has decreased, with a clear increase in the carriage of types of microorganisms not included in the vaccine (except for those with cross reactivity) observed after revaccination.When considering the results of the study, in the aggregate, a tendency was found to decrease the overall carrier of pneumococci. In both studies, there was a significant trend towards a decrease in the carriage of the individual serotypes 6B and 19F. In one study, there was also a significant decrease in the carriage of individual serotypes 14, 23F and, when using a 3-dose regimen of primary vaccination, a serotype 19A, which has a cross reactivity.

Immunogenicity of the Synflorix® vaccine in preterm infants

Synflorix® demonstrated high immunogenicity in vaccination of premature infants (27-36 weeks of gestation) with 3 doses in the 2-4-6 months schedule with booster at the age of 15-18 months. In general, 97.6% of children achieved a threshold concentration of antibodies (SGK ≥0.2 μg / ml), measured by ELISA, and 91.9% of children had opsonized antibody (CGT) titres of ≥8 for all serotypes Streptococcus pneumoniae, included in the vaccine.

Indications:

Active immunization of children aged 6 weeks to 5 years with the goal of preventing diseases caused by serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Streptococcus pneumoniae, including sepsis, bacteremia, pneumonia (invasive and non-invasive), meningitis and acute otitis media of the middle ear.

Contraindications:

Hypersensitivity to any component of the vaccine.

Acute infectious and non-infectious diseases, exacerbation of chronic diseases are temporary contraindications for vaccination. Vaccinations are carried out 2-4 weeks after recovery or during the period of convalescence or remission. With mild ARVI, acute intestinal diseases and other vaccinations are carried out immediately after the normalization of temperature. In the presence of mild symptoms of colds, vaccination should not be postponed.

Pregnancy and lactation:

Since the Synflorix® vaccine is not intended for use in adults, studies of the use of the vaccine during pregnancy or during lactation have not been conducted.

Dosing and Administration:

Method of administration

The vaccine should only be administered intramuscularly!

It is forbidden to administer the vaccine intravascularly or intradermally.

Data on subcutaneous injection of the Synflorix® vaccine are not available.

Recommended places of administration are the upper-outer surface of the middle part of the thigh in children of the first year of life or the deltoid muscle of the shoulder in children older than 1 year.

When stored, the vaccine is divided into a white precipitate and transparent supernatant, which is not indicative of a deterioration in the quality of the drug.

Before and after shaking the syringe or vial, its contents should be checked for the content of visible foreign particles and / or for the presence of deviations in the appearance of the contents before administration. In the presence of visible foreign particles and / or in the presence of deviations in the appearance of the contents, the vaccine is not used.

Before use, the vaccine should be shaken well.

Unused preparation and waste from its use must be destroyed in accordance with the requirements adopted in the Russian Federation.

Vaccination schedules

A single dose of the vaccine is 0.5 ml.

Immunization with the vaccine Synflorix® is carried out taking into account the National calendar of preventive vaccinations of the Russian Federation.

If the timing of immunization, as stipulated by the National Calendar of Prophylactic Vaccinations of the Russian Federation, is not met, immunization shall be carried out according to the individual scheme in accordance with the established requirements and instructions for the use of the medicinal product. Persons who received the first dose of the vaccine Synflorix®,it is recommended to complete the full course of immunization with the Sinflorix® vaccine.

Children aged 6 weeks to 6 months (inclusive)

Primary immunization with 2 doses of vaccine

In the framework of mass immunization according to the National Schedule of Prophylactic Inoculations of the Russian Federation, the initial immunization course is carried out in 2 doses: at the age of 2 months and 4.5 months, followed by a booster at 15 months.

Within the framework of individual vaccination, on the recommendation of a doctor, a second dose can be administered 2 months after the first; The revaccinating dose can be administered no earlier than 6 months from the date of the last vaccination of the primary immunization schedule.

Primary immunization with 3 doses of vaccine

Within the framework of individual vaccination, but the doctor's recommendations for the optimal level of protection, the following immunization schedule can be used. The primary course of immunization consists of 3 doses: the first dose is administered at the age of 2 months, subsequent doses - with an interval of at least 1 month between doses. Perhaps an earlier start of vaccination, but not earlier than 6 weeks of life.

Revaccination is recommended not earlier than 6 months from the date of the last vaccination of the primary course of immunization, preferably at the age of 12-15 months.

Premature babies (at least 27 weeks of gestation)

The recommended scheme of immunization consists of 3 doses with subsequent revaccination. The first dose can be administered from 2 months of life, the second and third doses - with an interval of at least 1 month between doses. The revaccination dose should be administered no earlier than 6 months after the date of the last vaccination of the primary immunization schedule.

Children who have not been vaccinated during the first 6 months of life

Children aged 7-11 months

The primary course of immunization consists of 2 doses with an interval of at least 1 month between doses.

The revaccination dose is recommended to be administered in the second year of life not earlier than 2 months from the date of the last vaccination of the primary immunization schedule.

Children aged 12 months to 5 years

The primary course of immunization consists of 2 doses with an interval of at least 2 months between doses.

Instructions for administering the vaccine in a syringe

1. While holding the syringe barrel with one hand (do not hold the syringe behind the piston), unscrew the cap of the syringe by turning it counter-clockwise.

2. To connect the needle and the syringe by clockwise rotation, connect the needle with the syringe until you feel them snap into place (see the picture).

3. Remove the protective cap from the needle (there is a possibility that it is fixed to the needle somewhat tightly).

4. Treat the injection site.

5. Enter the vaccine.

Side effects:

In the framework of security research The Synflorix® vaccine was administered concomitantly with other vaccines recommended for this age.

There was no increase in the incidence or severity of adverse events with each subsequent vaccination in the course of vaccination.

There was a higher reactogenicity in children with simultaneous application of whole-cell pertussis vaccines.

The most frequent adverse reactions in the primary course of vaccination were redness at the injection site (approximately 41%) and irritability (approximately 55%).

During revaccination, the most frequent adverse reactions were pain at the injection site (approximately 51%) and irritability (approximately 53%). In general, these reactions had an easy or moderate degree of severity and were of a transient nature.

The undesirable reactions presented below are listed in accordance with the damage to organs and organ systems and frequency of occurrence. Frequency of occurrence is defined as follows: Often (≥ 1/10), often (≥ 1/100 and <1/10), infrequently (≥ 1/1 000 and <1/100), rarely (≥ 1/10 000 and <1/1 000), rarely (<1/10 000, including individual cases). Frequency categories were formed on the basis of clinical studies of the drug and post-registration surveillance.

Clinical Trials Data

Frequency of occurrence of undesirable reactions

Immune system disorders

Rarely: allergic reactions (allergic dermatitis, atopic dermatitis, eczema).

Very rarely: angioedema edema.

Disorders from the metabolism and nutrition

Very often: loss of appetite.

Disorders of the psyche

Very often: irritability.

Infrequent: pathological crying.

Disturbances from the nervous system

Very often: drowsiness.

Rarely: febrile and afebrile convulsions.

Vascular disorders

Very rarely: Kawasaki syndrome.

Disturbances from the respiratory system, chest and mediastinal organs

Infrequently: apnea in premature infants (≤ 28 weeks of gestation) (see section "Special instructions").

Disorders from the gastrointestinal tract

Infrequent: diarrhea, vomiting.

Disturbances from the skin and subcutaneous tissues

Infrequent: rash.

Rarely: urticaria.

General disorders and disorders at the site of administration

Very often: pain, redness, swelling at the injection site, fever (≥ 38 ° C rectally at the age of <2 years).

Often: local reactions, such as compaction at the injection site, fever (> 39 ° C rectally at the age of <2 years).

Infrequently: local reactions, such as hematoma at the injection site, hemorrhage and Sealing at the injection site.

After the introduction of a booster dose within the framework of primary immunization and / or at the time of administration of the first dose to children older than 6 months, the following adverse reactions were additionally reported:

Disturbances from the nervous system

Infrequent: headache (age 2-5 years).

Disorders from the gastrointestinal tract

Infrequently: nausea (age 2-5 years).

General disorders and disorders at the site of administration

Often: fever (≥ 38 ° C rectally, age 2-5 years).

Infrequently: local reactions such as itching, fever (> 40 ° C rectally at <2 years,> 39 ° C rectally, age 2-5 years), diffuse edema of the extremity into which the injection was made, sometimes with damage to the adjacent the joint.

Probability of development of reactions in place administration is higher in children older than 12 months after revaccination with the Sinflorix® vaccine compared to children who received the Synflorix® vaccine as part of primary immunization at an earlier age.When vaccinating children between the ages of 12 and 23 months, urticaria was more frequent (corresponding to the frequency category "infrequently") compared to children who received the first dose of vaccine before the age of 6 months (primary vaccination course, revaccination).

Post-registration data observation

Immune system disorders

Very rarely: anaphylaxis.

Disturbances from the nervous system

Rarely: hypotonic-hypo-responsive syndrome.

Overdose:

Cases of overdose are not described.

Interaction:

Do not mix the vaccine with other drugs in the same syringe!

Use with other vaccines

Vaccine Sinflorix® can be done concomitantly with any of the following monovalent or combination vaccines (including combination vaccines (AKADS-HepB-IPV / Hib and TZD-HepB / Hib): diphtheria-tetanus acellular pertussis vaccine (ACAP), diphtheria-tetanus cel- lular pertussis vaccine (DTa), a vaccine for the prevention of infection caused by Haemophilus influenzae a type b (Hib), hepatitis B vaccine, inoculated polio vaccine for inactivated (IPV), measles, mumps and rubella vaccine, chickenpox vaccine, meningococcal serogroup C vaccine, conjugated CRM197 and TT), oral polio vaccine (OPV), a vaccine against rotavirus infection.

Injections of various vaccines should always be done in different parts of the body!

The immune response and the safety profile of co-administered vaccines remain unchanged, with the exception of the immune response to the inactivated poliovirus vaccine (inactivated poliovirus type 2), for which a non-uniformity of results was observed (values ​​of seroprotection ranged from 78% to 100%). The clinical significance of this phenomenon is unknown.

There was an increase in the immune response to capsular polysaccharide Haemophilus influenzae a type b, conjugated to tetanus toxoid, and diphtheria and tetanus antigens.

The use of systemic action with immunosuppressive drugs

In patients receiving immunosuppressive therapy, Synflorix® (like other vaccines in the same case) may not cause adequate immune flight.

Use with antipyretic agents

Preventive use of paracetamol as an antipyretic agent may reduce the immune response to the administration of pneumococcal vaccines.The clinical significance of this observation remains unknown.

Special instructions:

Before vaccination, it is necessary to find out an anamnesis, paying special attention to previous vaccinations and the occurrence of possible undesirable phenomena.

Given the extremely rare development of anaphylactic reactions, the patient must be under medical supervision for at least 30 minutes, and the place of vaccination should be provided with anti-shock therapy.

During or before vaccination, syncope may occur as a patient's psychogenic response to an injection. To avoid injury when choosing the site of injection, the possibility of developing fainting should be considered.

As with other vaccines administered intramuscularly, Synflorix® should be administered with caution to patients with thrombocytopenia or other blood clotting disorders because of the risk of bleeding with intramuscular injection.

Synflorix® does not prevent the prevention of diseases caused by pneumococci from other serogroups whose antigens are not included in this vaccine. Although after the introduction of the Synflorix® vaccine, an immune response to diphtheria toxoid, tetanus toxoid and D-protein Haemophilus influenzae, immunization with the Sinflorix® vaccine does not replace scheduled immunization against diphtheria, tetanus or Haemophilus influenzae a type b. It is necessary to follow the official immunization requirements against these infections.

As with any other vaccination, not all vaccines vaccinated with the Synflorix® vaccine may have a protective immune response.

In children with a decreased immune status, possibly due to immunosuppressive therapy, a genetic defect, HIV infection or other causes, a reduced level of antibody production after immunization may be observed.

Currently, vaccine safety and immunogenicity data Sinfloriks® in children with increased risk for pneumococcal infections (sickle cell disease, congenital and acquired disorders of the spleen, HIV infection, malignancy, nephrotic syndrome) are not available. The decision to vaccinate must be taken on a case-by-case basis, and it should be borne in mind that in children aged 12-23 months, a two-dose vaccination scheme may not be sufficient to provide protection, and revaccination may be recommended.Nevertheless, for children with an increased risk of pneumococcal infection (eg, sickle cell anemia, asplenia (absence of spleen), HIV infection, chronic diseases or immune disorders), before age 2, it is recommended that immunization with the Synflorix® vaccine be carried out in accordance with the age recommendations; at the age of 2 years and older, a 23-valent pneumococcal polysaccharide vaccine can be used (the minimum interval after the administration of the Synflorix® vaccine is 8 weeks).

The potential risk of apnea and the need for monitoring should be considered. respiratory function for 48-72 hours with primary vaccination of children born prematurely (<28 weeks gestation) and, especially, children with respiratory distress-syndrome. In view of the need to vaccinate children of this group with primary Vaccination should not be postponed or refused.

Preventive use of antipyretics before or immediately after administration vaccine may reduce the frequency and intensity of post-vaccination febrile reactions and can be recommended to children receiving Synflorix® concomitantly with whole-cell pertussis vaccine, as well as children with febrile reactions in anamnesis. Additional information on combined use with paracetamol is presented in the section "Interaction with other medicinal products".

Effectiveness and safety of the use of the Synflorix® vaccine in children older than 5 years not investigated.

Form release / dosage:

Suspension for intramuscular injection, 0.5 ml / dose.

Packaging:

For 0.5 ml (1 dose) in a syringe from a neutral glass of hydrolytic type I (Hebrew F), equipped with a protective cap or in a bottle of neutral glass of hydrolytic type I (Hef.), Sealed with a plug of butyl rubber and aluminum cap.

Packing for prescription

1 syringe with 1 needle (in a plastic container) in a PVC blister, covered with polyethylene terephthalate film together with instructions for use, or 1 bottle per cardboard pack together with instructions for use.

Packaging for medical institutions

For 5 syringes in a blister made of polyvinyl chloride, covered with a film of polyethylene terephthalate, 2 blisters with syringes and 2 soft contour mesh packs of 5 needles in a cardboard pack together with instructions for use.

For 10 syringes complete with 10 needles (in soft contour acrylic packaging) in a cardboard bundle equipped with a "built-in" cardboard separator with protective perforation from unauthorized opening together with instructions for use.

For 10 or 100 bottles in a cardboard pack together with instructions for use.

Storage conditions:

Store at a temperature of 2 to 8 ° C, in a place protected from light. Do not freeze.

Keep out of the reach of children.

Transportation conditions

At a temperature of 2 to 8 ° C in a dark place. Do not freeze.


Shelf life:

3 years.

Do not use after the expiration date stated on the package.

Expiration date is the last day of the month indicated on the package.

Terms of leave from pharmacies:On prescription
Registration number:LP-001412
Date of registration:11.01.2012
Date of cancellation:2017-01-11
The owner of the registration certificate:GlaxoSmithKline Trading, ZAO GlaxoSmithKline Trading, ZAO Russia
Manufacturer: & nbsp
Representation: & nbspGlaxoSmithKline Trading, ZAOGlaxoSmithKline Trading, ZAO
Information update date: & nbsp17.12.2015
Illustrated instructions
    Instructions
    Up