The pneumococcal conjugated 13-valent vaccine

General characteristics. Structure:

Structure on one dose (0,5 ml):
Active agents:
Pneumococcal conjugates (polysaccharide - CRM197):

• Polysaccharide of a serotype of 1 2,2 mkg
• Polysaccharide of a serotype of 3 2,2 mkg
• Polysaccharide of a serotype of 4 2,2 mkg
• Polysaccharide of a serotype of 5 2,2 mkg
• Polysaccharide of a serotype of 6A 2,2 mkg
• Polysaccharide of a serotype of 6B 4,4 mkg
• Polysaccharide of a serotype of 7F 2,2 mkg
• Polysaccharide of a serotype of 9V 2,2 mkg
• Polysaccharide of a serotype of 14 2,2 mkg
• Oligosaccharide of a serotype of 18C 2,2 mkg
• Polysaccharide of a serotype of 19A 2,2 mkg
• Polysaccharide of a serotype of 19F 2,2 mkg
• Polysaccharide of a serotype of 23F 2,2 mkg
• CRM197 carrier protein ~ 32 mkg

Excipients:
aluminum phosphate – 0,5 mg (in terms of aluminum of 0,125 mg), sodium chloride – 4,25 mg, succinic acid – 0,295 mg, Polisorbat of 80 - 0,1 mg, water for injections – to 0,5 ml.

ПРЕВЕНАР® 13 it is made according to WHO recommendations on production and quality control of the pneumococcal conjugated vaccines.

Pharmacological properties:

Introduction of the vaccine Превенар® 13 causes development of antibodies to kapsulyarny Streptococcus pneumoniae polysaccharides, providing thereby specific protection against the infections caused by the pneumococcus serotypes included in a vaccine 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F.

According to WHO recommendations for the new conjugated antipneumococcal vaccines, assessment of equivalence of an immune response when using the vaccines Превенар® 13 and Prevenar® on set of three independent criteria is carried out: percent of the patients who reached concentration of specific antibodies of IgG0,35 of mkg/ml; average geometrical concentration of immunoglobulins (IgG GMC) and opsonofagotsitarny activity of bactericidal antibodies (OFA caption 1:8). Introduction Превенар® 13 causes development of an immune response on all 13 vaccinal serotypes, equivalent by the above-stated criteria to the vaccine Prevenar®. For adult persons the protective level of antipneumococcal antibodies is not determined and the serotype - specific OFA is used.

The vaccine Превенар® 13 includes up to 90% of all serotypes which are the reason of the invasive pneumococcal infections (IPI) including steady against treatment by antibiotics. The observations made in the USA from the moment of implementation of the 7-valent conjugated vaccine Prevenar® allow to assume that the most hard cases of invasive pneumonia are connected with action of the serotypes included in Превенар® 13 (1, 3, 7F and 19A), in particular, the serotype 3 is directly connected with a disease of necrotizing pneumonia.

Immune response when using three or two doses in a series of primary immunization

After introduction of three doses Превенар® 13 at primary immunization of children aged up to 6 months considerable rise in level of antibodies to all serotypes of a vaccine is noted.

After introduction of two doses at primary immunization Превенар® 13 within mass immunization of children of the same age group considerable raising of antiserum capacities to all components of a vaccine is also noted, but the mkg/ml IgG0,35 level for serotypes 6B and 23F was defined at smaller percent of children. At the same time, concentration of antibodies after introduction of a revaktsiniruyushchy dose Превенар® 13 in comparison with concentration of antibodies before introduction of a revaktsiniruyushchy dose increased for all 13 serotypes. Formation of immune memory is shown for both schemes of vaccination stated above. The secondary immune response on a revaktsiniruyushchy dose at children of the second year of life when using three or two doses in a series of primary immunization is comparable for all 13 serotypes. Превенар® 13 contains the general with the vaccine Prevenar® seven serotypes and CRM197 carrier protein. Comparative identity of both vaccines on an immunogenicity and a profile of safety allows to pass with Prevenara® on Превенар® 13 at any stage of vaccination of the child, and additional 6 serotypes in Превенар® 13 provide broader protection against IPI.

Indications to use:

Prevention of the diseases caused by Streptococcus pneumoniae of serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (including bacteremia, sepsis, meningitis, pneumonia and acute average otitis) at children at the age of 2 months - 5 years.
prevention of the pneumococcal diseases (including pneumonia and invasive diseases) caused by Streptococcus pneumoniae of serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F at adults at the age of 50 years is also more senior.

Route of administration and doses:

The vaccine is entered intramusculary – into the perednebokovy surface of a hip (to children up to 2 years) or into a deltoid muscle of a shoulder (to persons is more senior than 2 years), in a single dose of 0,5 ml.
Before use the syringe with the vaccine Превенар® 13 needs to be stirred up well before receiving homogeneous suspension. Not to use if at survey of contents of the syringe foreign debris come to light, or contents look differently, than in the section "Description" of the present instruction.
Not to enter Превенар® 13 intravenously, vnutrikozhno and intramusculary into a rump!:

Scheme of vaccination:
Age from 2 to 6 months::
Series of triple primary immunization: enter 3 doses Превенар® 13 bucketed between introductions not less than 1 month. Children can enter the first dose from age of 2 months. The revaccination is carried out once in 11-15 months. The scheme is used at implementation of individual immunization of children against a pneumococcal infection.

Series of double primary immunization: enter 2 doses Превенар® 13 with an interval between introductions not less than 2 months. Children can enter the first dose from age of 2 months. The revaccination is carried out once in 11-15 months. The scheme is used at implementation of mass immunization of children against a pneumococcal infection.

For children to whom vaccination was not begun in the first 6 months of life introduction Превенар® 13 is carried out according to the following schemes:
Age from 7 to 11 months: two doses with an interval between introductions not less than 1 month. The revaccination is carried out once on the second year of life.
Age from 12 to 23 months: two doses with an interval between introductions not less than 2 months.
Age from 2 to 5 years (inclusive): once If vaccination is begun Превенар® 13, it is recommended to complete it also the vaccine Превенар® 13.

At forced increase in an interval between injections of any of the stated above vaccination courses, introduction of additional doses Превенар® 13 is not required.
The children who are earlier vaccinated by Prevenar®
The vaccination against a pneumococcal infection begun with the 7-valent vaccine Prevenar® can be continued Превенар® 13 at any stage of the scheme of immunization.

Persons are more senior than 50 years
The adult, including the patients who are earlier vaccinated by a polisakharidny pneumococcal vaccine Превенар® 13 enter once.
Need of a revaccination is not established.

Features of use:

Taking into account exceptional cases of anaphylactic reactions the vaccinated patient after vaccination has to be under medical observation within at least 30 min. Venues of immunization have to be provided with means of antishock therapy.

At making decision on vaccination of the child with heavy degree of prematurity (pregnancy of 28 weeks) who especially have immaturity of respiratory system in the anamnesis it is necessary to consider that the advantage of immunization against a pneumococcal infection at this group of patients is especially high and it is not necessary neither to refuse vaccination, nor to postpone its date. However at the same time, in connection with the potential risk of an apnoea which is available at use of any vaccines performing the first vaccination Превенар® 13 is recommended in the conditions of a hospital under medical observation (not less than 48 h).

As well as other intramuscular injections, to patients with thrombocytopenia and/or other disturbances of coagulant system of blood and/or in case of treatment by anticoagulants, vaccination Превенар® 13 has to be carried out with care, on condition of stabilization of a condition of the patient and achievement of control of a hemostasis. Perhaps hypodermic introduction to Превенара® 13 this group of patients.

Превенар® 13 provides protection only against those serotypes of Streptococcus pneumoniae which are its part, and does not protect from other microorganisms causing invasive diseases, pneumonia or average otitis. At patients with disturbance of an immunoreactivity vaccination can be followed by the lowered antibodyformation level.

There are limited data that the predecessor Превенар® 13, the heptavalent vaccine Prevenar®, causes a proper immune response in children aged up to 6 months with a sickemia, and the profile of safety Prevenar® at them is similar to a safety profile at vaccinated, not belonging to groups of high risk.

Now there are no data on safety and an immunogenicity of a vaccine at patients of groups of high risk on invasive pneumococcal infections (for example, patients with the inborn or acquired dysfunctions have spleens, HIV infection, malignant tumors, after transplantation of a strain of haematopoietic stem cells, a nephrotic syndrome). The decision on performing vaccination of patients from groups of high risk should be made individually.

To children from groups of high risk 2 years are aged younger it is necessary to carry out primary immunization Превенар® 13 according to age. When to children at the age of 2 years is also more senior, entering into group of high risk (for example, with a sickemia, an aspleniya, HIV infection, a chronic disease or immunological dysfunction) and, the 23-valent pneumococcal polisakharidny vaccine is appointed earlier received courses of vaccination Превенар® 13, the interval between introduction of vaccines has to be not less than 8 weeks.

It is desirable to begin immunization against a pneumococcal infection of adults with Превенара® 13.

Because the most various activators (viruses, bacteria, mushrooms, mikst-infections), and not just the pneumococci entering Превенар® 13 serotypes can be the cause of development of average otitis estimated preventive efficiency Превенар® 13 concerning otitis can be less expressed in comparison with efficiency for invasive diseases.

Due to higher risk of development of febrile reactions, including with febrile spasms in the anamnesis, and also receiving Превенар® 13 along with tselnokletochny pertussoid vaccines, preventive purpose of antipyretics is recommended to children with convulsive frustration.

Information on influence of drug on ability to drive the car and to use the equipment, no.

Side effects:

Safety of the vaccine Превенар® 13 is studied on healthy children (4429 children / 14267 vaccine doses) aged from 6 weeks up to 11-16 months. In all researches Превенар® 13 it was applied along with other vaccines recommended for this age.
Besides, safety of the vaccine Превенар® 13 is estimated at 354 children aged from 7 months up to 5 years which are earlier not vaccinated by any of the pneumococcal conjugated vaccines.
Reactions in the place of an injection, temperature increase, irritability, a loss of appetite and disturbance of a sleep pattern were the most frequent undesirable reactions.
At children of advanced age at primary immunization Превенар® 13 higher frequency of local reactions was observed, than children of the first year have lives.

At persons at the age of 65 years is also more senior the smaller amount of side effects regardless of the previous vaccination was noted. However the frequency of development of reactions was same, as well as in younger population.

The undesirable reactions which are listed below are classified by bodies and systems, and also according to the frequency of their manifestation in all age groups.

Frequency of undesirable reactions was defined as follows:
Very frequent (≥ 1/10), frequent (≥ 1/100, but <1/10), infrequent (≥ 1/1000, but <1/100), rare (≥ 1/10000, but <1/1000) and very rare (≤ 1/10000).

The undesirable reactions revealed in clinical trials Превенар® 13 at children
General and local reactions:

Very frequent:	hyperthermia to 39 °C; irritability; a dermahemia, painful feelings, consolidation or hypostasis of 2,5-7,0 cm in size in the place of an injection; drowsiness, deterioration in a dream.
Frequent:	the hyperthermia is above 39 °C; the morbidity in the place of an injection leading to short-term restriction of volume of movements of an extremity.
Infrequent:	dermahemia, consolidation or swelled the sizes more than 7,0 cm in the place of an injection; tearfulness.
Rare:	cases of a hypotonic collapse, reaction of hypersensitivity in the place of an injection (urticaria, dermatitis, an itch) *; rushes of blood to лицу*.

Blood and lymphatic system:

Very rare:

regional лимфоаденопатия*.

Immune system:

Rare:

hypersensitivity reaction, including an asthma, a bronchospasm, a Quincke's edema of different localization; anaphylactic/anaphylactoid reaction, including шок*.

Nervous system:

Rare:

spasms (including febrile).

Digestive tract:

Very frequent:	loss of appetite.
Infrequent:	vomiting, diarrhea.

Skin and hypodermic cellulose:

Rare:	rash, urticaria.
Very rare:	poliformny эритема*.

* - were noted at post-marketing observations of the vaccine Prevenar®; it is possible to consider as possible and for Превенар® 13.
The undesirable reactions revealed in clinical trials Превенар® 13 at adults

Digestive tract:

Very frequent:	loss of appetite, diarrhea.
Frequent:	vomiting.
Infrequent:	nausea.

Nervous system:

Very frequent:

headaches.

Immune system:

Rare:

hypersensitivity reactions, including an asthma, a bronchospasm, a face edema.

Skin and hypodermic cellulose:

Very frequent:

rash.

Skeletal and muscular and connecting fabric:

Very frequent:

generalized new or an aggravation of the available joint pains and muscular pains.

General and local reactions:

Very frequent:	fever, fatigue; the erythema, hypostasis, pain or consolidation in the place of an injection leading to short-term restriction of volume of movements of an extremity.
Frequent:	fervescence.
Infrequent:	lymphadenopathy in the field of the place of an injection.

In general significant differences in the frequency of development of side effects in the adults who are earlier vaccinated by a 23-valent pneumococcal polisakharidny vaccine and not vaccinated by this vaccine were not noted.

Frequency of development of local side reactions was identical to persons at the age of 50-59 years and 65 years at vaccination Превенар® 13 are more senior than persons, also the number of local side reactions did not increase at vaccination along with the inactivated influenza vaccine.

Frequency of usual vaccinal system reactions was higher at simultaneous introduction Превенар® 13 and the inactivated influenza vaccine in comparison with use only than the inactivated influenza vaccine (a headache, a fever, rash, a loss of appetite, a joint pain and muscles) or only Превенар® 13 (a headache, fatigue, a fever, a loss of appetite and a joint pain).

Interaction with other medicines:

Data on interchangeability of Prevenar® and Превенар® 13 on not - CRM197 - the conjugated vaccines based pneumococcal are absent.

At simultaneous vaccination Превенар® 13 and other vaccines of an injection become in different body parts.

Children aged from 2 months up to 5 years
Превенар® 13 it is combined with any other vaccines entering a calendar of immunization of children of the first years of life. Превенар® 13 children can enter at the same time (in one day) with any following antigens which are a part both the monovalent, and combined vaccines: diphtheritic, tetanic, acellular or tselnokletochny pertussoid, Haemophilus influenzae type b inactivated poliomyelitic, hepatitis B clumsy, epidemic parotitis, a rubella and chicken pox – without change of reactogenicity and immunological indicators.

Persons at the age of 50 years are also more senior
Превенар® 13 it is possible to enter along with the trivalent inactivated influenza vaccine.
Simultaneous use with other vaccines was not investigated.

Contraindications:

- Hypersensitivity on the previous introduction Превенар® 13 or Prevenar® (including, an acute anaphylaxis, heavy generalized allergic reactions);
- hypersensitivity to a diphtherial anatoxin and/or excipients;
- acute infectious or noninfectious diseases, exacerbations of chronic diseases. Vaccination is carried out after recovery or during remission.

PREGNANCY AND PERIOD OF FEEDING BY THE BREAST
Data on use Превенар® 13 during pregnancy are absent. It is unknown whether it is allocated Превенар® 13 in breast milk.

Overdose:

The overdose Превенар® 13 is improbable as the vaccine is released in the syringe containing only one dose.

Storage conditions:

At a temperature from 2 to 8 °C. Not to freeze.
To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Suspension for intramuscular introduction of 0,5 ml / a dose. On 0,5 ml in the syringe with a capacity of 1 ml from transparent colourless glass (type I).
1 syringe and 1 sterile needle in the plastic packaging sealed by a polyethylene film. 1 plastic packaging together with the application instruction in a cardboard pack.

5 syringes in the plastic packaging sealed by a polyethylene film. 2 plastic packagings and 10 sterile needles together with the application instruction in a cardboard pack.

When packaging LLC NPO Petrovax Pharm, Russian Federation:
1 syringe and 1 sterile needle in the plastic packaging sealed by a polyethylene film. 1 plastic packaging together with the application instruction in a cardboard pack.