Bexsero is indicated for active immunization of subjects from the age of 2 months against invasive meningococcal disease caused by Neisseria meningitidis group B. The impact of invasive infection at different d As well as the epidemiological variability of the antigens of Group B strains in different geographical areas must be taken into account when vaccinating. See section Pharmacodynamic properties for more information on protection, against strains specific to group B.

This vaccine should be used in accordance with official recommendations.
Dosage

Table 1. Summary of the dosage

Slice of age

Primovaccination

Intervals between Primary Vaccination Doses

Reminder

Infants

From 2 to 5 months

Three doses

Of 0.5 ml each with a first dose administered

At the age of 2 months a

1, minimum month

Yes, a dose

Between 12 and 15, month b, c

Infants, unvaccinated

From 6 to 11 months

Two doses

Of 0.5 ml each

2, minimum month

Yes, a dose, during

The second year with an interval of at least 2 months between the primary vaccination and

The booster dose c

Children not vaccinated

From 12 to 23 months

Two doses

Of 0.5 ml each

2, minimum month

Yes, a dose with a

Interval of 12 to 23 months

Between the primary vaccination

And the booster dose c

Children

From 2 to 10 years

Two doses

Of 0.5 ml each

2, minimum month

Requirement no, established d

Teenagers

(From

Of 11 years)

And adults *

Two doses

Of 0.5 ml each

1, minimum month

Requirement no, established d

The first dose should be administered at the age of 2 months. The safety and effectiveness of Bexsero in infants under 8 weeks have not yet been established. No data is available

B In case of delay, the booster dose should not be administered beyond 24 months.

C See Pharmacodynamic properties. The need and the time of administration of a booster dose have not yet been determined.

D See Pharmacodynamic Properties.

* There is no data in adults over 50

Administration mode

The vaccine is administered by deep intramuscular injection, preferably in the anterolateral face, thigh in the infant or muscle region, upper deltoid in older subjects

Separate injection sites should be used if several vaccines are administered simultaneously
The vaccine should not be injected intravenously, subcutaneously or intradermally and should not be mixed with other vaccines in the same syringe.
For instructions on handling the vaccine before administration, see section Instructions for Use, Handling and Disposal.


Class: Pharmacotherapeutic drugs: meningococcal vaccines ATC code: J07AH09

Mechanism of action

Immunization with Bexsero aims to stimulate the production of antibodies, which recognize the antigens, NHBA, NadA, fHbp and PorA P1.4 vaccines (the antigen, immunodominant in the OMV component) and are considered protective Against invasive meningococcal disease (IIM). As these antigens are expressed differently according to the strains, the meningococci which express them at sufficient levels are liable to be killed by the antibodies produced by the vaccine. The MATS (Meningococcal Antigen Typing System) was developed to correlate the antigenic profiles of different strains of meningococcal B bacteria to the destruction of these strains in the study of serum bactericidal activity in the presence of Human complement (hSBA). Analysis of approximately 1,000 isolates of invasive strains of meningococcus B from 2007 to 2008 in 5 European countries showed that, depending on the country of origin, between 73 and 87% of meningococcus B isolates A MATS antigenic profile covered by the vaccine

Overall, 78% (95% confidence interval between 63 and 90%) of the 1,000 strains were potentially susceptible to antibodies induced by vaccination. Br>
Efficacy, clinical

The efficacy of Bexsero has not been evaluated in clinical trials. The efficacy of the vaccine was deduced by demonstrating the induction of bactericidal antibody responses in the serum against each of the vaccine antigens (see section Immunogenicity).

Immunogenicity

The serum bactericidal antibody responses to each of the vaccine antigens NadA, fHbp, NHBA and PorA P1.4 were evaluated using four meningococcal reference strains B
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The bactericidal antibodies against these strains were measured by studying serum bactericidal activity using human serum as a complement source (hSBA). We do not have data for all vaccine regimens using the NHBA reference strain

Most immunogenicity studies were randomized, controlled and multicentric clinical trials, immunogenicity was assessed in infants, children, adolescents and adults.
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Immunogenicity in infants and children

In the infant studies, participants received three doses of Bexsero at the age of 2, 4 and 6 months or 2, 3 and 4 months and a booster dose in their second year of life, From the age of 12 months. Serum was taken prior to vaccination one month after the third dose of vaccine (see Table 2) and one month after the booster dose (see Table 3). In an extension study, the persistence of the immune response was evaluated one year after the booster dose (see Table 3). Children not previously vaccinated were also given two doses in their second year of life, the persistence of the antibodies being measured one year after the second dose (see Table 4). Immunogenicity after two doses has also been documented in another study on infants aged 6-8 months at baseline (see Table 4).

Immunogenicity in infants between 2 and 6 months

The immunogenicity results one month after three doses of Bexsero administered at the age of 2, 3 and 4 months and 2, 4 and 6 months are summarized in Table 2. The bactericidal antibody responses one month After the third dose of vaccine against the reference meningococcal strains were raised against the antigens fHbp, NadA and PorA P1.4 in both vaccine regimens of Bexsero. The bactericidal responses to the NHBA antigen were also elevated in infants vaccinated according to the scheme at 2, 4, 6 months, but this antigen appeared to be less immunogenic in the 2, 3, 4 months. The clinical consequences of reduced immunogenicity of NHBA antigen in this scheme are unknown.


Antigen

Study: V72P13

2, 4, 6; month
Study: V72P12

2, 3, 4; month
Study: V72P16

2, 3, 4; month
FHbp

% Seropositive *

(95% CI)

N '= 1,149

100%; (99-100)

N '= 273

99,% (97-100)

N '= 170

100%; (98-100)

MGT; hSBA **

(95% CI)

91

(87-95)

82

(75-91)

101

(90-113)

NadA

% Seropositive

(95% CI)

N '= 1 152; 100% (99-100)
N '= 275

100%; (99-100)

N '= 165

99,% (97-100)

MGT; hSBA

(95% CI)

635

(606-665)

325

(292-362)

396

(348-450)

PorA; P1.4

% Seropositive

(95% CI)

N '= 1 152

84;% (82-86)

N '= 274

81;% (76-86)

N '= 171

78;% (71-84)

MGT; hSBA

(95% CI)

14

(13-15)

11

(9,14-12)

10

(8,59-12)

NHBA

% Seropositive

(95% CI)

N '= 100

84;% (75-91)

N '= 112

37,% (28-46)

N '= 35

43;% (26-61)

MGT; hSBA

(95% CI)

16

(13-21)

3,24

(2,49-4,21)

3.29

(1,85-5,83)

'% Seropositive' = percentage of subjects with hSBA ≥ 1: 5.

** MGT '= mean, geometric titles.

Data on the persistence of bactericidal antibodies 8 months after vaccination with Bexsero at 2, 3 and 4 months and 6 months after vaccination with Bexsero at 2, 4 and 6 months of age Before booster), as well as recall data after administration of a fourth dose of Bexsero at the age of 12 months are summarized in the table; The persistence of the immune response one year after the booster dose is also presented in Table 3. The need for additional booster doses in order to maintain immune protection at longer term has not been established.

Table 3. Responses to serum bactericidal antibody titers after a 12-month booster following a 2, 3 and 4 months or 2, 4, and 6 months primary vaccination schedule and persistence of bactericidal titres One year after the recall
Antigen

2, 3, 4, 12; month

2, 4, 6, 12;

FHbp

Before the callback

% Seropositive ** (95% CI)

MGT hSBA *** (95% CI)

N '= 81

58;% (47-69)

5.79, (4.54-7.39)

N '= 426

82;% (78-85)

10; (9.55-12)

1 month after the recall

% Seropositive (95% CI)

MGT hSBA (95% CI)

N '= 83

100% (96-100)

135; (108-170)

N '= 422

100%; (99-100)

128; (118-139)

12 months after the recall

% Seropositive (95% CI)

MGT hSBA (95% CI)

-

N '= 299

62;% (56-67)

6,5; (5,63-7,5)

NadA

Before the reminder%

Seropositive (95% CI)

MGT hSBA (95% CI)

N '= 79

97;% (91-100)

63; (49-83)

N '= 423

99,% (97-100)

81; (74-89)

1 month after the recall

% Seropositive (95% CI)

MGT hSBA (95% CI)

N '= 84

100% (96-100)

1, 558 (1 262-1 923)

N '= 421

100% (99-100)

1, 465 (1 350-1 590)

12 months after the recall

% Seropositive (95% CI)

MGT hSBA (95% CI)

Bexsero is indicated for active immunization of subjects from the age of 2 months against invasive meningococcal disease caused by Neisseria meningitidis group B. The impact of invasive infection at different d As well as the epidemiological variability of the antigens of Group B strains in different geographical areas must be taken into account when vaccinating. See section 'Pharmacodynamic properties' for further information on protection against strains specific to group B. This vaccine should be used according to official recommendations.
-

N '= 298

97;% (95-99)

81; (71-94)

PorA; P1.4

Before the callback

% Seropositive (95% CI)

MGT hSBA (95% CI)

N '= 83

19;% (11-29)

1.61, (1.32-1.96)

N '= 426

22;% (18-26)

2.14, (1.94-2.36)

1 month after the recall

% Seropositive (95% CI)

MGT hSBA (95% CI)

N '= 86

97;% (90-99)

47; (36-62)

N '= 424

95;% (93-97)

35; (31-39)

12 months after the recall

% Seropositive (95% CI)

MGT hSBA (95% CI)

-

N '= 300

17;% (13-22)

1.91, (1.7-2.15)

NHBA

Before the callback

% Seropositive (95% CI)

MGT hSBA (95% CI)

N '= 69

25,% (15-36)

2.36, (1.75-3.18)

N '= 100

61;% (51-71)

8,4; (6,4-11)

% Seropositive 1 month after recall (95% CI)

MGT hSBA (95% CI)

N '= 67

76;% (64-86)

12; (8,52-17)

N '= 100

98;% (93-100)

42; (36-50)

12 months after the recall

% Seropositive (95% CI)

MGT hSBA (95% CI)

Bexsero has no or negligible effect on the ability to drive and use machines. However, some of the effects mentioned in the section "Undesirable effects" may temporarily affect the ability to drive or use machines.

Hypersensitivity to the active substances or to any of the excipients mentioned in section Composition.
As with other vaccines, administration of Bexsero should be reported in patients with severe acute febrile illness. However, the presence of a minor infection, such as a common cold, should not lead to postponement of the vaccination.

Do not inject intravascularly.

As with any vaccine, injectable, appropriate medical treatment and surveillance should always be available in the event of an anaphylactic reaction following the administration of the vaccine. >
This vaccine should not be administered to patients with thrombocytopenia or any other coagulation disorder which would be a contraindication to an intramuscular injection unless the potential benefit is clearly greater than the risks; Inherent in the administration.

It is not expected that Bexsero will provide protection against all circulating strains of meningococcus B (see section 5.2).



There is no data on the use of Bexsero in subjects older than 50 years or suffering from chronic diseases

The potential risk of apnea and the need for respiratory monitoring for 48 to 72 hours should be carefully considered when administering primary vaccine doses in very preterm infants (born at 28 weeks of pregnancy Or less), especially in those with a history of respiratory immaturity. Because of the high benefit of vaccination in these infants, the administration should not be suspended or postponed.

Kanamycin is used at the beginning of the manufacturing process and is removed during subsequent stages of manufacture. The levels of kanamycin possibly detectable in the final vaccine are less than 0.01 microgram per dose.

Use with other vaccines

Bexsero may be administered concomitantly with all of the following vaccine antigens, whether they are vaccines, monovalent or combined: diphtheria, tetanus, acellular pertussis, Haemophilus, influenzae type b, inactivated poliomyelitis, hepatitis B, pneumococcal Heptavalent conjugate, measles, mumps, rubella and chicken pox

Clinical studies have demonstrated that the immune responses of co-administered routine vaccines were not affected by the concomitant administration of Bexsero with their antibody response rates being not less than those of routine vaccines; Administered alone. Contradictory results were obtained from one study to another, concerning responses to inactivated poliovirus type 2 and serotype 6B of the pneumococcal conjugate vaccine and lower titres of antibody to one of the pertussis antigens , Pertactin, have also been found, but these data do not suggest clinically significant interference.


Concomitant administration of Bexsero with vaccines other than those mentioned above has not been studied

When administered concomitantly with other vaccines, Bexsero should be injected into a separate site (see section 4.2).



In the absence of studies and compatibility, this medicinal product should not be mixed with other medicines.
The vaccine should be visually inspected to demonstrate the presence of particles and a change in color before administration. In the presence of foreign particles and / or a change in physical appearance, discard the vaccine.

The experience of overdosage is limited. In case of overdose, vital control and symptomatic treatment are recommended.

Pregnancy

Clinical data available on pregnancies exposed to the vaccine are insufficient

The potential risk for pregnant women is unknown. However, vaccination should not be discarded if there is a clear risk of exposure to a meningococcal infection

A study in which rabbits received a dose of Bexsero about 10 times higher than the human dose, equivalent to body weight, showed no evidence of maternal or fetal toxicity and no effect on Pregnancy, maternal behavior, fertility of the female or on postnatal development

Breastfeeding

No information is available on the safety of the vaccine in women and their children during breastfeeding. The benefit / risk report should be reviewed before making the decision to vaccinate during breastfeeding.


Fertility

There are no data on fertility in humans.

No effect on the fertility of females has been found in animal studies.


The safety of Bexsero was evaluated in 14 studies, including 10 trials, randomized controlled trials involving 8776 subjects (aged 2 months minimum) receiving at least one dose of Bexsero. Among the subjects vaccinated by Bexsero, 5849 were infants and children (under 2 years of age), 250 were children (2 to 10 years), and 2677 were adolescents and adults. Among the infants who received Primovaccination doses of Bexsero, 3285 received a booster dose during their second year of life.

In clinical studies in infants vaccinated at 2, 4, and 6 months, fever (≥ 38 ° C) was reported in 69% to 79% of subjects when Bexsero was co-administered with vaccines Routine (containing the following antigens, conjugated heptavalent pneumococcal, diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliomyelitis and Haemophilus type b), compared with 44% to 59% of subjects receiving routine vaccines alone. A more frequent use of antipyretics was also reported in infants, vaccinated with Bexsero and routine vaccines. When Bexsero was administered alone, the frequency of fever was similar to that associated with routine vaccines administered to infants during clinical trials. Cases of fever generally followed a pattern, predictable, usually resolved, the day after vaccination.
In adolescents and adults, the most frequent local and systemic adverse reactions were: injection site pain, malaise, and headache.
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No increase in incidence or severity, adverse reactions have been observed with successive doses of the vaccination scheme

Tabulated List of Adverse Reactions

The undesirable effects (consecutive to the primary vaccination or booster dose) considered to be at least probably related to vaccination were classified by frequency. >
The frequencies are defined as follows

Very common (≥1 / 10)

Frequency (≥1 / 100; to