Bexsero

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 
 

  



 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Bexsero suspension for injection in pre-filled syringe 
Meningococcal group B Vaccine (rDNA, component, adsorbed) 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
One dose (0.5 ml) contains: 
 
Recombinant Neisseria meningitidis group B NHBA fusion protein 1, 2, 3 50 micrograms 
Recombinant Neisseria meningitidis group B NadA protein 1, 2, 3 50 micrograms 
Recombinant Neisseria meningitidis group B fHbp fusion protein 1, 2, 3 50 micrograms 
Outer membrane vesicles (OMV) from Neisseria meningitidis group B 
strain NZ98/254 measured as amount of total protein containing the PorA P1.4 2 

25 micrograms 

 
1 produced in E. coli cells by recombinant DNA technology 
2 adsorbed on aluminium hydroxide (0.5 mg Al³+) 
³ NHBA (Neisserial Heparin Binding Antigen), NadA (Neisseria adhesin A), fHbp 

(factor H binding protein) 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension for injection. 
White opalescent liquid suspension. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Bexsero is indicated for active immunisation of individuals from 2 months of age and older against 
invasive meningococcal disease caused by Neisseria meningitidis group B. The impact of invasive 
disease in different age groups as well as the variability of antigen epidemiology for group B strains in 
different geographical areas should be considered when vaccinating. See section 5.1 for information 
on protection against specific group B strains. The use of this vaccine should be in accordance with 
official recommendations. 
 
4.2 Posology and method of administration 
 
Posology 
 



 

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Table 1. Summary of posology 
 

Age at first dose Primary Immunisation 
Intervals 
between 

Primary Doses 
Booster 

Infants, 2 months 
to 5 months a 

Three doses each 
of 0.5 ml 

Not less 
than 1 month 

Yes, one dose 
between 12 and 15 months of 

age with an interval of at 
least 6 months between the 
primary series and booster 

dose b, c 
Two doses  

each of 0.5 ml 
Not less 

than 2 months 

Infants, 6 months 
to 11 months 

Two doses each 
of 0.5 ml 

Not less 
than 2 months 

Yes, one dose in the second 
year of life with an interval 
of at least 2 months between 

the primary series and 
booster dose c 

Children, 12 months 
to 23 months 

Two doses each 
of 0.5 ml 

Not less 
than 2 months 

Yes, one dose with an 
interval of 12 months 

to 23 months between the 
primary series and booster 

dose c 

Children, 2 years 
to 10 years 

Two doses each 
of 0.5 ml 

Not less 
than 1 month 

A booster dose should be 
considered in individuals at 

continued risk of exposure to 
meningococcal disease, 

based on official 
recommendations d 

Adolescents 
(from 11 years) and 

adults* 
 
a The first dose should be given no earlier than 2 months of age. The safety and efficacy of 

Bexsero in infants less than 8 weeks of age has not yet been established. No data are available. 
b In case of delay, the booster should not be given later than 24 months of age. 
c See section 5.1. The need for and timing of further booster doses has not yet been determined. 
d See section 5.1. 
* There are no data in adults above 50 years of age. 
 
Method of administration 
 
The vaccine is given by deep intramuscular injection, preferably in the anterolateral aspect of the thigh 
in infants or in the deltoid muscle region of the upper arm in older subjects. 
 
Separate injection sites must be used if more than one vaccine is administered at the same time. 
 
The vaccine must not be injected intravenously, subcutaneously or intradermally and must not be 
mixed with other vaccines in the same syringe. 
 
For instructions on the handling of the vaccine before administration, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 



 

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As with other vaccines, administration of Bexsero should be postponed in subjects suffering from an 
acute severe febrile illness. However, the presence of a minor infection, such as cold, should not result 
in the deferral of vaccination. 
 
Do not inject intravascularly. 
 
As with all injectable vaccines, appropriate medical treatment and supervision should always be 
readily available in case of an anaphylactic event following the administration of the vaccine. 
 
Anxiety-related reactions, including vasovagal reactions (syncope), hyperventilation or stress-related 
reactions may occur in association with vaccination as a psychogenic response to the needle injection 
(see section 4.8). It is important that procedures are in place to avoid injury from fainting. 
 
This vaccine should not be given to individuals with thrombocytopenia or any coagulation disorder 
that would contraindicate intramuscular injection, unless the potential benefit clearly outweighs the 
risk of administration. 
 
As with any vaccine, vaccination with Bexsero may not protect all vaccine recipients.  
Bexsero is not expected to provide protection against all circulating meningococcal group B strains 
(see section 5.1). 
 
As with many vaccines, healthcare professionals should be aware that a temperature elevation may 
occur following vaccination of infants and children (less than 2 years of age). Prophylactic 
administration of antipyretics at the time and closely after vaccination can reduce the incidence and 
intensity of post-vaccination febrile reactions. Antipyretic medication should be initiated according to 
local guidelines in infants and children (less than 2 years of age). 
 
Individuals with impaired immune responsiveness, whether due to the use of immune-suppressive 
therapy, a genetic disorder, or other causes, may have reduced antibody response to active 
immunisation. 
Immunogenicity data are available in individuals with complement deficiencies, asplenia, or splenic 
dysfunctions (see section 5.1). 
 
Individuals with familial complement deficiencies (for example, C3 or C5 deficiencies) and 
individuals receiving treatments that inhibit terminal complement activation (for example, eculizumab) 
are at increased risk for invasive disease caused by Neisseria meningitidis group B, even if they 
develop antibodies following vaccination with Bexsero. 
 
There are no data on the use of Bexsero in subjects above 50 years of age and limited data in patients 
with chronic medical conditions. 
 
The potential risk of apnoea and the need for respiratory monitoring for 48-72 hours should be 
considered when administering the primary immunisation series to very premature infants 
(born ≤ 28 weeks of gestation) and particularly for those with a previous history of respiratory 
immaturity. As the benefit of vaccination is high in this group of infants, vaccination should not 
be withheld or delayed. 
 
The tip cap of the syringe may contain natural rubber latex. Although the risk for developing allergic 
reactions is very small, healthcare professionals should consider the benefit-risk prior to administering 
this vaccine to subjects with known history of hypersensitivity to latex. 
 
Kanamycin is used in early manufacturing process and is removed during the later stages of 
manufacture. If present, kanamycin levels in the final vaccine are less than 0.01 micrograms per dose. 
The safe use of Bexsero in kanamycin-sensitive individuals has not been established. 
 
Traceability 



 

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In order to improve the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Use with other vaccines 
 
Bexsero can be given concomitantly with any of the following vaccine antigens, either as monovalent 
or as combination vaccines: diphtheria, tetanus, acellular pertussis, Haemophilus influenzae type b, 
inactivated poliomyelitis, hepatitis B, heptavalent pneumococcal conjugate, measles, mumps, rubella, 
varicella, and meningococcal groups A, C, W, Y conjugate. 
 
Clinical studies demonstrated that the immune responses of the co-administered routine vaccines were 
unaffected by concomitant administration of Bexsero, based on non-inferior antibody response rates to 
the routine vaccines given alone. Inconsistent results were seen across studies for responses to 
inactivated poliovirus type 2 and pneumococcal conjugate serotype 6B and lower antibody titers to the 
pertussis pertactin antigen were also noted, but these data do not suggest clinically significant 
interference. 
 
Due to an increased risk of fever, tenderness at the injection site, change in eating habits and 
irritability when Bexsero was co-administered with the above vaccines, separate vaccinations can be 
considered when possible. Prophylactic use of paracetamol reduces the incidence and severity of fever 
without affecting the immunogenicity of either Bexsero or routine vaccines. The effect of antipyretics 
other than paracetamol on the immune response has not been studied. 
 
Concomitant administration of Bexsero with vaccines other than those mentioned above has not been 
studied. 
 
When given concomitantly with other vaccines Bexsero must be administered at separate injection 
sites (see section 4.2). 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
Insufficient clinical data on exposed pregnancies are available. 
 
The potential risk for pregnant women is unknown. Nevertheless, vaccination should not be withheld 
when there is a clear risk of exposure to meningococcal infection. 
 
There was no evidence of maternal or foetal toxicity, and no effects on pregnancy, maternal behaviour, 
female fertility, or postnatal development in a study in which female rabbits received Bexsero at 
approximately 10 times the human dose equivalent based on body weights. 
 
Breast-feeding 
 
Information on the safety of the vaccine to women and their children during breast-feeding is not 
available. The benefit-risk ratio must be examined before making the decision to immunise during 
breast-feeding. 
 
No adverse reactions were seen in vaccinated maternal rabbits or in their offspring through day 29 of 
lactation. Bexsero was immunogenic in maternal animals vaccinated prior to lactation, and antibodies 
were detected in the offspring, but antibody levels in milk were not determined. 
 
Fertility 
 
There are no data on fertility in humans. 



 

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There were no effects on female fertility in animal studies. 
 
4.7 Effects on ability to drive and use machines 
 
Bexsero has no or negligible influence on the ability to drive and use machines. However, some of the 
effects mentioned under section 4.8 “Undesirable effects” may temporarily affect the ability to drive or 
use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The safety of Bexsero was evaluated in 17 studies including 10 randomised controlled clinical trials 
with 10565 subjects (from 2 months of age) who received at least one dose of Bexsero. Among 
Bexsero recipients, 6837 were infants and children (less than 2 years of age), 1051 were children 
(2 to 10 years of age) and 2677 were adolescents and adults. Of the subjects who received primary 
infant series of Bexsero, 3285 received a booster dose in the second year of life.   
 
In infants and children (less than 2 years of age) the most common local and systemic adverse 
reactions observed in clinical trials were tenderness and erythema at the injection site, fever and 
irritability. 
 
In clinical studies in infants vaccinated at 2, 4 and 6 months of age, fever (≥ 38°C) was reported 
by 69% to 79% of subjects when Bexsero was co-administered with routine vaccines (containing the 
following antigens: pneumococcal 7-valent conjugate, diphtheria, tetanus, acellular pertussis, hepatitis 
B, inactivated poliomyelitis and Haemophilus influenzae type b) compared with 44% to 59% of 
subjects receiving the routine vaccines alone. Higher rates of antipyretic use were also reported for 
infants vaccinated with Bexsero and routine vaccines. When Bexsero was given alone, the frequency 
of fever was similar to that associated with routine infant vaccines administered during clinical trials. 
When fever occurred, it generally followed a predictable pattern, with the majority resolving by the 
day after vaccination. 
 
In adolescents and adults the most common local and systemic adverse reactions observed were pain at 
the injection site, malaise and headache. 
 
No increase in the incidence or severity of the adverse reactions was seen with subsequent doses of the 
vaccination series. 
 
Tabulated list of adverse reactions 
 
Adverse reactions (following primary immunisation or booster dose) considered as being at least 
possibly related to vaccination have been categorised by frequency. 
 
Frequencies are defined as follows: 
Very common: (≥1/10) 
Common: (≥1/100 to <1/10) 
Uncommon: (≥1/1,000 to <1/100) 
Rare: (≥1/10,000 to <1/1,000) 
Very rare: (<1/10,000) 
Not known:  (cannot be estimated from the available data) 
 
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 
In addition to reports in clinical trials, worldwide voluntary reports of adverse reactions received for 
Bexsero since market introduction are included in the list. Because these reactions are reported 



 

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voluntarily from a population of uncertain size, it is not always possible to reliably estimate their 
frequency and they are consequently listed with the frequency unknown. 
 
Infants and children (up to 10 years of age) 
 
Immune system disorders 
Not known: allergic reactions (including anaphylactic reactions) 
 
Metabolism and nutrition disorders 
Very common: eating disorders 
 
Nervous system disorders 
Very common: sleepiness, unusual crying, headache 
Uncommon: seizures (including febrile seizures) 
Not known: hypotonic-hyporesponsive episode, meningeal irritation (signs of meningeal irritation, 
such as neck stiffness or photophobia, have been sporadically reported shortly after vaccination. These 
symptoms have been of mild and transient nature) 
 
Vascular disorders 
Uncommon: pallor (rare after booster) 
Rare: Kawasaki syndrome 
 
Gastrointestinal disorders 
Very common: diarrhoea, vomiting (uncommon after booster) 
 
Skin and subcutaneous tissue disorders 
Very common: rash (children aged 12 to 23 months) (uncommon after booster) 
Common: rash (infants and children 2 to 10 years of age) 
Uncommon: eczema 
Rare: urticaria 
 
Musculoskeletal and connective tissue disorders 
Very common: arthralgia  
 
General disorders and administration site conditions 
Very common: fever (≥38°C), injection site tenderness (including severe injection site tenderness 
defined as crying when injected limb is moved), injection site erythema, injection site swelling, 
injection site induration, irritability 
Uncommon: fever (≥40°C) 
Not known: injection site reactions (including extensive swelling of the vaccinated limb, blisters at or 
around the injection site and injection site nodule which may persist for more than one month) 
 
Adolescents (from 11 years of age) and adults 
 
Immune system disorders 
Not known: allergic reactions (including anaphylactic reactions) 
 
Nervous system disorders 
Very common: headache 
Not known: syncope or vasovagal responses to injection, meningeal irritation (signs of meningeal 
irritation, such as neck stiffness or photophobia, have been sporadically reported shortly after 
vaccination. These symptoms have been of mild and transient nature) 
 
Gastrointestinal disorders 
Very common: nausea 
 
Skin and subcutaneous tissue disorders 



 

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Not known: rash 
 
Musculoskeletal and connective tissue disorders 
Very common: myalgia, arthralgia 
 
General disorders and administration site conditions 
Very common: injection site pain (including severe injection site pain defined as unable to perform 
normal daily activity), injection site swelling, injection site induration, injection site erythema, malaise 
Not known: fever, injection site reactions (including extensive swelling of the vaccinated limb, blisters 
at or around the injection site and injection site nodule which may persist for more than one month) 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
Experience of overdose is limited. In the event of overdose, monitoring of vital functions and possible 
symptomatic treatment is recommended. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: meningococcal vaccines, ATC code: J07AH09 
 
Mechanism of action 
 
Immunisation with Bexsero is intended to stimulate the production of bactericidal antibodies that 
recognize the vaccine antigens NHBA, NadA, fHbp, and PorA P1.4 (the immunodominant antigen 
present in the OMV component) and are expected to be protective against Invasive Meningococcal 
Disease (IMD). As these antigens are variably expressed by different strains, meningococci that 
express them at sufficient levels are susceptible to killing by vaccine-elicited antibodies. The 
Meningococcal Antigen Typing System (MATS) was developed to relate antigen profiles of different 
strains of meningococcal group B bacteria to killing of the strains in the serum bactericidal assay with 
human complement (hSBA). A survey of approximately 1,000 different invasive meningococcal group 
B isolates collected during 2007-2008 in 5 European countries showed that, depending on the country 
of origin, between 73% and 87% of meningococcal group B isolates had an appropriate MATS antigen 
profile to be covered by the vaccine. Overall, 78% (95% confidence limits from 63-90%) of the 
approximately 1,000 strains were potentially susceptible to vaccine-induced antibodies. 
 
Clinical efficacy 
 
The efficacy of Bexsero has not been evaluated through clinical trials. Vaccine efficacy has been 
inferred by demonstrating the induction of serum bactericidal antibody responses to each of the 
vaccine antigens (see section Immunogenicity). 
 
Immunogenicity 
 
Serum bactericidal antibody responses to each of the vaccine antigens NadA, fHbp, NHBA and 
PorA P1.4 were evaluated using a set of four meningococcal group B reference strains. Bactericidal 
antibodies against these strains were measured by the Serum Bactericidal Assay using human serum 
as the source of complement (hSBA). Data are not available from all vaccine schedules using the 
reference strain for NHBA. 

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Most of the primary immunogenicity studies were conducted as randomized, controlled, multicenter, 
clinical trials. Immunogenicity was evaluated in infants, children, adolescents and adults. 
 
Immunogenicity in infants and children 
 
In infant studies, participants received three doses of Bexsero either at 2, 4 and 6 or 2, 3 and 4 months 
of age and a booster dose in their second year of life, as early as 12 months of age. Sera were obtained 
both before vaccination, one month after the third vaccination (see Table 2) and one month after 
booster vaccination (see Table 3). In an extension study the persistence of the immune response was 
assessed one year after the booster dose (see Table 3). The immunogenicity after two or three doses 
followed by a booster has been evaluated in infants 2 months to 5 months of age in another clinical 
study. The immunogenicity after two doses has been also documented in another study in 
infants 6 months to 8 months of age at enrolment (see Table 4).  
Previously unvaccinated children also received two doses in the second year of life, with antibody 
persistence being measured at one year after the second dose (see Table 4). 
 
Immunogenicity in infants 2 months to 5 months of age 
 
Three-dose primary series followed by a booster 
 
Immunogenicity results at one month after three doses of Bexsero administered 
at 2, 3, 4 and 2, 4, 6 months of age are summarised in Table 2. Bactericidal antibody responses one 
month after the third vaccination against meningococcal reference strains were high against the fHbp, 
NadA and PorA P1.4 antigens at both Bexsero vaccination schedules. The bactericidal responses 
against the NHBA antigen were also high in infants vaccinated at the 2, 4, 6-month schedule, but this 
antigen appeared to be less immunogenic at the 2, 3, 4-month schedule. The clinical consequences of 
the reduced immunogenicity of the NHBA antigen at this schedule are not known. 
 
Table 2. Serum bactericidal antibody responses at 1 month following the third dose of 

Bexsero given at 2, 3, 4 or 2, 4, 6 months of age 
 

Antigen  Study V72P13 2, 4, 6 months 
Study V72P12 
2, 3, 4 months 

Study V72P16 
2, 3, 4 months 

fHbp 

% seropositive* 
(95% CI) 

N=1149 
100% (99-100) 

N=273 
99% (97-100) 

N=170 
100% (98-100) 

hSBA GMT** 
(95% CI) 

91 
(87-95) 

82 
(75-91) 

101 
(90-113) 

NadA 

% seropositive 
(95% CI) 

N=1152 
100% (99-100) 

N=275 
100% (99-100) 

N=165 
99% (97-100) 

hSBA GMT 
(95% CI) 

635 
(606-665) 

325 
(292-362) 

396 
(348-450) 

PorA P1.4 

% seropositive 
(95% CI) 

N=1152 
84% (82-86) 

N=274 
81% (76-86) 

N=171 
78% (71-84) 

hSBA GMT 
(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) 

hSBA GMT 
(95% CI) 

16 
(13-21) 

3.24 
(2.49-4.21) 

3.29 
(1.85-5.83) 

* % seropositive = the percentage of subjects who achieved an hSBA ≥ 1:5. 
** GMT = geometric mean titer. 
 
Data on bactericidal antibody persistence at 8 months after Bexsero vaccination at 2, 3 and 4 months 
of age, and at 6 months after Bexsero vaccination at 2, 4 and 6 months of age (pre-booster time point) 
and booster data after a fourth dose of Bexsero administered at 12 months of age are summarised in 



 

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Table 3. Persistence of the immune response one year after the booster dose is also presented in 
Table 3. 
 
Table 3. Serum bactericidal antibody responses following a booster at 12 months of age after 

a primary series administered at 2, 3 and 4 or 2, 4 and 6 months of age, and 
persistence of bactericidal antibody one year after the booster 

 
Antigen  2, 3, 4, 12 months 2, 4, 6, 12 months 

fHbp 

pre-booster* 
% seropositive** (95% 

CI) 
hSBA GMT*** (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 booster 
% seropositive (95% CI) 
hSBA GMT (95% CI) 

N=83 
100% (96-100) 
135 (108-170) 

N=422 
100% (99-100) 
128 (118-139) 

12 months after booster 
% seropositive (95% CI) 
hSBA GMT (95% CI) 

- 
N=299 

62% (56-67) 
6.5 (5.63-7.5) 

NadA 

pre-booster 
% seropositive (95% CI) 
hSBA GMT (95% CI) 

N=79 
97% (91-100) 

63 (49-83) 

N=423 
99% (97-100) 

81 (74-89) 
1 month after booster 

% seropositive (95% CI) 
hSBA GMT (95% CI) 

N=84 
100% (96-100) 

1558 (1262-1923) 

N=421 
100% (99-100) 

1465 (1350-1590) 
12 months after booster 
% seropositive (95% CI) 
hSBA GMT (95% CI) 

- 
N=298 

97% (95-99) 
81 (71-94) 

PorA P1.4 

pre-booster 
% seropositive (95% CI) 
hSBA GMT (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 booster 

% seropositive (95% CI) 
hSBA GMT (95% CI) 

N=86 
97% (90-99) 
47 (36-62) 

N=424 
95% (93-97) 
35 (31-39) 

12 months after booster 
% seropositive (95% CI) 
hSBA GMT (95% CI) 

- 
N=300 

17% (13-22) 
1.91 (1.7-2.15) 

NHBA 

pre-booster 
% seropositive (95% CI) 
hSBA GMT (95% CI) 

N=69 
25% (15-36) 

2.36 (1.75-3.18) 

N=100 
61% (51-71) 
8.4 (6.4-11) 

1 month after booster % 
seropositive (95% CI) 
hSBA GMT (95% CI) 

N=67 
76% (64-86) 
12 (8.52-17) 

N=100 
98% (93-100) 

42 (36-50) 
12 months after booster 
% seropositive (95% CI) 
hSBA GMT (95% CI) 

- 
N=291 

36% (31-42) 
3.35 (2.88-3.9) 

* pre-booster time point represents persistence of bactericidal antibody at 8 months after Bexsero 
vaccination at 2, 3 and 4 months of age and 6 months after Bexsero vaccination 
at 2, 4 and 6 months of age. 

** % seropositive = the percentage of subjects who achieved an hSBA ≥ 1:5. 
*** GMT = geometric mean titer. 
 
A decline in antibody titers to PorA P1.4 and fHbp antigens (reaching 9%-10% and 12%-20% of 
subjects with an hSBA ≥ 1:5, respectively) has been observed in an additional study in 
children 4 years of age who received a full priming and booster schedule as infants. In the same study 
the response to a further dose was indicative of immunological memory as 81%-95% of subjects 
reached an hSBA ≥ 1:5 to PorA P1.4 and 97%-100% to fHbp antigens following further vaccination. 



 

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The clinical significance of this observation and the need for additional booster doses to maintain 
longer term protective immunity has not been established. 
 
Two-dose primary series followed by a booster 
 
The immunogenicity after two primary doses (at 3 and a half and 5 months of age) or three primary 
doses (at 2 and a half, 3 and a half and 5 months of age) of Bexsero followed by a booster dose in 
infants starting vaccination between 2 and 5 months of age has been evaluated in an additional phase 3 
clinical study. The percentages of seropositive subjects (i.e. achieving an hSBA of at least 1:4) ranged 
from 44% to 100% one month after the second dose and from 55% to 100% one month after the third 
dose. At one month following a booster administered 6 months after the last dose, the percentages of 
seropositive subjects ranged from 87% to 100% for the two-dose schedule, and from 83% to 100% for 
the three-dose schedule. 
 
Antibody persistence was evaluated in an extension study in children 3 to 4 years of age. Comparable 
percentages of subjects were seropositive at 2 to 3 years after being previously vaccinated with either 
two doses followed by a booster of Bexsero (ranging from 35% to 91%) or three doses followed by a 
booster (ranging from 36% to 84%). In the same study the response to an additional dose administered 
2 to 3 years after the booster was indicative of immunological memory as shown by a robust antibody 
response against all Bexsero antigens, ranging from 81% to 100% and from 70% to 99%, respectively. 
These observations are consistent with adequate priming in infancy with both a two-dose and a three-
dose primary series followed by a booster of Bexsero. 
 
Immunogenicity in infants 6 to 11 months and children 12 to 23 months of age 
 
The immunogenicity after two doses administered two months apart in children 6 months to 23 months 
of age has been documented in two studies whose results are summarised in Table 4. Against each of 
the vaccine antigens, seroresponse rates and hSBA GMTs were high and similar after the two-dose 
series in infants 6-8 months of age and children 13-15 months of age. Data on antibody persistence 
one year after the two doses at 13 and 15 months of age are also summarised in Table 4. 
 



 

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Table 4. Serum bactericidal antibody responses following Bexsero vaccination at 6 and 8 months 
of age or 13 and 15 months of age and persistence of bactericidal antibody one year 
after the two doses at 13 and 15 months of age 

 

Antigen  

Age range 
6 to 11 

months of age 
12 to 23 

months of age  
Age of vaccination 

6, 8 months 13, 15 months 

fHbp 

1 month after 2nd dose N=23 N=163 
% seropositive* (95% CI) 100% (85-100) 100% (98-100) 
hSBA GMT** (95% CI) 250 (173-361) 271 (237-310) 
12 months after 2nd dose  N=68 
% seropositive (95% CI) - 74% (61-83) 

hSBA GMT (95% CI)  14 (9.4-20) 

NadA 

1 month after 2nd dose N=23 N=164 
% seropositive (95% CI) 100% (85-100) 100% (98-100) 

hSBA GMT (95% CI) 534 (395-721) 599 (520-690) 
12 months after 2nd dose  N=68 
% seropositive (95% CI) - 97% (90-100) 

hSBA GMT (95% CI)  70 (47-104) 

PorA 
P1.4 

1 month after 2nd dose N=22 N=164 
% seropositive (95% CI) 95% (77-100) 100% (98-100) 

hSBA GMT (95% CI) 27 (21-36) 43 (38-49) 
12 months after 2nd dose  N=68 
% seropositive (95% CI) - 18% (9-29) 

hSBA GMT (95% CI)  1.65 (1.2-2.28) 

NHBA 

1 month after 2nd dose  N=46 
% seropositive (95% CI) - 63% (48-77) 

hSBA GMT (95% CI)  11 (7.07-16) 
12 months after 2nd dose  N=65 
% seropositive (95% CI) - 38% (27-51) 

hSBA GMT (95% CI)  3.7 (2.15-6.35) 
* % seropositive = the percentage of subjects who achieved an hSBA ≥ 1:4 (in the 6 to 11 months 

range of age) and an hSBA ≥ 1:5 (in the 12 to 23 months range of age). 
** GMT = geometric mean titer. 
 
Immunogenicity in children 2 to 10 years of age 
 
The immunogenicity after two doses of Bexsero administered either one or two months apart in 
children 2 to 10 years of age has been evaluated in an initial phase 3 clinical study and its extension. In 
the initial study, whose results are summarised in Table 5, participants received two doses of Bexsero 
two months apart. The seroresponse rates and hSBA GMTs were high after the two-dose schedule in 
children against each of the vaccine antigens (Table 5). 
 



 

 13 

Table 5.  Serum bactericidal antibody responses at 1 month following the second dose of 
Bexsero given to children 2-10 years of age following a 0, 2-month schedule 

 

* % seropositive = the percentage of subjects who achieved an hSBA ≥ 1:4 (against reference 
strains for fHbp, NadA, PorA P1.4 antigens) and an hSBA ≥ 1:5 (against reference strain for 
NHBA antigen). 

** GMT = geometric mean titer. 
 
In the extension study, in which two doses of Bexsero were administered one month apart in 
unvaccinated children, high percentages of subjects were seropositive one month after the second 
dose. An early immune response after the first dose was also evaluated. The percentages of 
seropositive subjects (i.e. achieving an hSBA of at least 1:4) across strains ranged from 46% to 95% at 
one month after the first dose and from 69% to 100% at one month after the second dose (Table 6). 
 

Antigen  2 to 5 years of age 6 to 10 years of age 

fHbp 

% seropositive* 
(95% CI) 

N=99 
100% (96-100) 

N=287 
99% (96-100) 

hSBA GMT** 
(95% CI) 

140 
(112-175) 

112 
(96-130) 

NadA 

% seropositive 
(95% CI) 

N=99 
99% (95-100) 

N=291 
100% (98-100) 

hSBA GMT 
(95% CI) 

584 
(466-733) 

457 
(392-531) 

PorA P1.4 

% seropositive 
(95% CI) 

N=100 
98% (93-100) 

N=289 
99% (98-100) 

hSBA GMT 
(95% CI) 

42 
(33-55) 

40 
(34-48) 

NHBA 

% seropositive 
(95% CI) 

N=95 
91% (83-96) 

N=275 
95% (92-97) 

hSBA GMT 
(95% CI) 

23 
(18-30) 

35 
(29-41) 



 

 14 

Table 6.  Serum bactericidal antibody responses at 1 month following the second dose of 
Bexsero given to children 2-10 years of age following a 0, 1-month schedule 

 

* % seropositive = the percentage of subjects who achieved an hSBA ≥ 1:4 (against reference 
strains for fHbp, NadA, PorA P1.4 antigens) and an hSBA ≥ 1:5 (against reference strain for 
NHBA antigen). 

** GMT = geometric mean titer. 
 
The same extension study also evaluated antibody persistence and the response to a booster dose in 
children who received the two-dose primary series at 2-5 or 6-10 years of age. After 24-36 months, the 
percentages of seropositive subjects (i.e. achieving an hSBA of at least 1:4) declined, ranging across 
strains from 21% to 74% in children 4-7 years of age and from 47% to 86% in children 8-12 years of 
age. The response to a booster dose administered 24-36 months after the primary series was indicative 
of immunological memory as the percentages of seropositive subjects ranged across strains from 93% 
to 100% in children 4-7 years of age and from 96% to 100% in children 8-12 years of age. 
 
Immunogenicity in adolescents (from 11 years of age) and adults 
 
Adolescents received two doses of Bexsero with one, two or six-month intervals between doses; these 
data are summarised in Tables 7 and 8.  
 
In studies with adults, data were obtained after two doses of Bexsero with a one-month or two-month 
interval between doses (see Table 9). 
 
The vaccination schedules of two doses administered with an interval of one or two months showed 
similar immune responses in both adults and adolescents. Similar responses were also observed for 
adolescents administered two doses of Bexsero with an interval of six months. 
 

Antigen  35 to 47 months of age 4 to 7 years of age 8 to10 years of age 

fHbp 

% seropositive* 
(95% CI) 

N=98 
100% (96.3-100) 

N=54 
98% (90.1-99.95) 

N=34 
100% (89.7-100) 

hSBA GMT** 
(95% CI) 

107 
(84-135) 

76.62 
(54-108) 

52.32 
(34-81) 

NadA 

% seropositive 
(95% CI) 

N=98 
100% (96.3-100) 

N=54 
100% (93.4-100) 

N=34 
100% (89.7-100) 

hSBA GMT 
(95% CI) 

631 
(503-792) 

370.41 
(264-519) 

350.49 
(228-540) 

PorA P1.4 

% seropositive 
(95% CI) 

N=98 
100% (96.3-100) 

N=54 
100% (93.4-100) 

N=33 
100% (89.4-100) 

hSBA GMT 
(95% CI) 

34 
(27-42) 

30.99 
(28-49) 

30.75 
(20-47) 

NHBA 

% seropositive 
(95% CI) 

N=91 
75% (64.5-83.3) 

N=52 
69% (54.9-81.3) 

N=34 
76% (58.8-89.3) 

hSBA GMT 
(95% CI) 

12 
(7.57-18) 

9.33 
(5.71-15) 

12.35 
(6.61-23) 



 

 15 

Table 7. Serum bactericidal antibody responses in adolescents one month after two doses of 
Bexsero administered according to different two-dose schedules and persistence of 
bactericidal antibody 18 to 23 months after the second dose 

 

Antigen  0, 1 months 0, 2 months 0, 6 months 

fHbp 

1 month after 2nd dose N=638 N=319 N=86 
% seropositive* 

(95% CI) 
100%  

(99-100) 
100%  

(99-100) 
100%  

(99-100) 
hSBA GMT** 

(95% CI) 
210 

(193-229) 
234 

(209-263) 
218 

(157-302) 
18-23 months after 2nd dose N=102 N=106 N=49 

% seropositive 
(95% CI) 

82% 
(74-89) 

81% 
(72-88) 

84% 
(70-93) 

hSBA GMT 
(95% CI) 

29 
(20-42) 

34 
(24-49) 

27 
(16-45) 

NadA 

1 month after 2nd dose N=639 N=320 N=86 
% seropositive 

(95% CI) 
100%  

(99-100) 
99%  

(98-100) 
99%  

(94-100) 
hSBA GMT 

(95% CI) 
490 

(455-528) 
734 

(653-825) 
880 

(675-1147) 
18-23 months after 2nd dose N=102 N=106 N=49 

% seropositive 
(95% CI) 

93% 
(86-97) 

95% 
(89-98) 

94% 
(83-99) 

hSBA GMT 
(95% CI) 

40 
(30-54) 

43 
(33-58) 

65 
(43-98) 

PorA 
P1.4 

1 month after 2nd dose N=639 N=319 N=86 
% seropositive 

(95% CI) 
100%  

(99-100) 
100%  

(99-100) 
100%  

(96-100) 
hSBA GMT 

(95% CI) 
92 

(84-102) 
123 

(107-142) 
140 

(101-195) 
18-23 months after 2nd dose N=102 N=106 N=49 

% seropositive 
(95% CI) 

75% 
(65-83) 

75% 
(66-83) 

86% 
(73-94) 

hSBA GMT 
(95% CI) 

17 
(12-24) 

19 
(14-27) 

27 
(17-43) 

NHBA 

1 month after 2nd dose N=46 N=46 - 
% seropositive 

(95% CI) 
100%  

(92-100) 
100%  

(92-100) - 

hSBA GMT 
(95% CI) 

99 
(76-129) 

107 
(82-140) - 

* % seropositive = the percentage of subjects who achieved an hSBA ≥ 1:4. 
** GMT = geometric mean titer. 
 
In the study in adolescents, bactericidal responses following two doses of Bexsero were stratified by 
baseline hSBA less than 1:4 or equal to or greater than 1:4. Seroresponse rates and percentages of 
subjects with at least a 4-fold increase in hSBA titer from baseline to one month after the second dose 
of Bexsero are summarised in Table 8. Following Bexsero vaccination, a high percentage of subjects 
were seropositive and achieved 4-fold increases in hSBA titers independent of pre-vaccination status. 
 



 

 16 

Table 8. Percentage of adolescents with seroresponse and at least 4-fold rise in bactericidal 
titers one month after two doses of Bexsero administered according to different 
two-dose schedules - stratified by pre-vaccination titers 

 

Antigen   0, 1 months 0, 2 months 0, 6 months 

fHbp 

% seropositive* 
after 2nd dose 

(95% CI) 

pre-vaccination 
titer <1:4 

N=369 
100% (98-100) 

N=179 
100% (98-100) 

N=55 
100% (94-100) 

pre-vaccination 
titer ≥1:4 

N=269 
100% (99-100) 

N=140 
100% (97-100) 

N=31 
100% (89-100) 

% 4-fold increase  
after 2nd dose 

(95% CI) 

pre-vaccination 
titer <1:4 

N=369 
100% (98-100) 

N=179 
100% (98-100) 

N=55 
100% (94-100) 

pre-vaccination 
titer ≥1:4 

N=268 
90% (86-93) 

N=140 
86% (80-92) 

N=31 
90% (74-98) 

NadA 
 

% seropositive 
after 2nd dose 

(95% CI) 

pre-vaccination 
titer <1:4 

N=427 
100% (99-100) 

N=211 
99% (97-100) 

N=64 
98% (92-100) 

pre-vaccination 
titer ≥1:4 

N=212 
100% (98-100) 

N=109 
100% (97-100) 

N=22 
100% (85-100) 

% 4-fold increase  
after 2nd dose 

(95% CI) 

pre-vaccination 
titer <1:4 

N=426 
99% (98-100) 

N=211 
99% (97-100) 

N=64 
98% (92-100) 

pre-vaccination 
titer ≥1:4 

N=212 
96% (93-98) 

N=109 
95% (90-98) 

N=22 
95% (77-100) 

PorA P1.4 

% seropositive 
after 2nd dose 

(95% CI) 

pre-vaccination 
titer <1:4 

N=427 
100% (98-100) 

N=208 
100% (98-100) 

N=64 
100% (94-100) 

pre-vaccination 
titer ≥1:4 

N=212 
100% (98-100) 

N=111 
100% (97-100) 

N=22 
100% (85-100) 

% 4-fold increase 
after 2nd dose 

(95% CI) 

pre-vaccination 
titer <1:4 

N=426 
99% (98-100) 

N=208 
100% (98-100) 

N=64 
100% (94-100) 

pre-vaccination 
titer ≥1:4 

N=211 
81% (75-86) 

N=111 
77% (68-84) 

N=22 
82% (60-95) 

NHBA 

% seropositive 
after 2nd dose 

(95% CI) 

pre-vaccination 
titer <1:4 

N=2 
100% (16-100) 

N=9 
100% (66-100) - 

pre-vaccination 
titer ≥1:4 

N=44 
100% (92-100) 

N=37 
100% (91-100) - 

% 4-fold increase 
after 2nd dose 

(95% CI) 

pre-vaccination 
titer <1:4 

N=2 
100% (16-100) 

N=9 
89% (52-100) - 

pre-vaccination 
titer ≥1:4 

N=44 
30% (17-45) 

N=37 
19% (8-35) - 

* % seropositive = the percentage of subjects who achieved an hSBA ≥ 1:4. 
 
Antibody persistence data for the study in adolescents were obtained in an extension phase 3 study. At 
approximately 7.5 years after the two-dose primary series, the percentages of subjects with hSBA ≥ 
1:4 declined, ranging across strains from 29% to 84%. The response to a booster dose administered 7.5 
years after the primary series was indicative of immunological memory as the percentages of subjects 
reaching an hSBA ≥ 1:4 across strains ranged from 93% to 100%. 
The same study also evaluated antibody persistence data from an additional phase 3 initial study in 
adolescents. At approximately 4 years after the two-dose primary series, the percentages of subjects 
with hSBA ≥ 1:5 generally declined from a range across strains of 68% to 100% after the second dose 
to a range across strains of 9% to 84%. The response to a booster dose administered 4 years after the 
primary series was indicative of immunological memory as the percentages of subjects with hSBA ≥ 
1:5 ranged across strains from 92% to 100%. 
 



 

 17 

Table 9. Serum bactericidal antibody responses in adults after two doses of Bexsero 
administered according to different two-dose schedules  

 

Antigen  0, 1 months 0, 2 months 

fHbp 

1 month after 2nd dose N=28 N=46 
% seropositive* 

(95% CI) 
100%  

(88-100) 
100%  

(92-100) 
hSBA GMT** 

(95% CI) 
100 

(75-133) 
93 

(71-121) 

NadA 

1 month after 2nd dose N=28 N=46 
% seropositive 

(95% CI) 
100%  

(88-100) 
100%  

(92-100) 
hSBA GMT 

(95% CI) 
566 

(338-948) 
144 

(108-193) 

PorA P1.4 

1 month after 2nd dose N=28 N=46 
% seropositive 

(95% CI) 
96%  

(82-100) 
91%  

(79-98) 
hSBA GMT 

(95% CI) 
47 

(30-75) 
32 

(21-48) 
*  % seropositive = the percentage of subjects who achieved an hSBA ≥ 1:4.  
**  GMT = geometric mean titer.  
Serum bactericidal response to NHBA antigen has not been evaluated. 
 
Immunogenicity in special populations 
 
Children and adolescents with complement deficiencies, asplenia, or splenic dysfunction 
 
In a phase 3 clinical study, children and adolescents 2 through 17 years of age with complement 
deficiencies (40), with asplenia or splenic dysfunction (107), and age-matched healthy subjects (85) 
received two doses of Bexsero two months apart. At 1 month following the 2-dose vaccination course, 
the percentages of subjects with hSBA ≥1:5 in individuals with complement deficiencies and asplenia 
or splenic dysfunction were 87% and 97% for antigen fHbp, 95% and 100% for antigen NadA, 68% 
and 86% for antigen PorA P1.4, 73% and 94% for antigen NHBA, respectively, indicating an immune 
response in these immunocompromised subjects. The percentages of healthy subjects with hSBA ≥1:5 
were 98% for antigen fHbp, 99% for antigen NadA, 83% for antigen PorA P1.4, and 99% for antigen 
NHBA. 
 
Impact of vaccination on disease incidence 
 
In the UK, Bexsero was introduced into the national immunisation programme (NIP) in September 2015 
using a two-dose schedule in infants (at 2 and 4 months of age) followed by a booster dose (at 12 months 
of age). In this context, Public Health England conducted a 3-year observational study at the national 
level covering the entire birth cohort. 
After three years of the programme, a statistically significant reduction of 75% [Incidence Rate Ratio 
0.25 (95% CI: 0.19;0.36)] in cases of IMD caused by Neisseria meningitidis group B was observed in 
vaccine-eligible infants, irrespective of the infants’ vaccination status or predicted meningococcal 
group B strain coverage.  
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Bexsero in one or more subsets of the paediatric population in the prevention of meningococcal 
disease caused by Neisseria meningitidis group B (see section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Not applicable. 



 

 18 

 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on repeated dose toxicity and 
reproductive and developmental toxicity studies. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sodium chloride 
Histidine 
Sucrose 
Water for injections 
 
For adsorbent see section 2. 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life 
 
3 years 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C – 8°C). 
Do not freeze. 
Store in the original package in order to protect from light. 
 
6.5 Nature and contents of container 
 
0.5 ml suspension in a pre-filled syringe (Type I glass) with a plunger stopper (Type I bromobutyl 
rubber) and with a protective tip cap (Type I or Type II rubber) with or without needles. 
 
Pack sizes of 1 or 10 syringes. Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Upon storage a fine off-white deposit may be observed in the pre-filled syringe containing the suspension. 
 
Before use, the pre-filled syringe should be well shaken in order to form a homogeneous suspension. 
 
The vaccine should be visually inspected for particulate matter and discoloration prior to 
administration. In the event of any foreign particulate matter and/or variation of physical aspect being 
observed, do not administer the vaccine. If two needles of different lengths are provided in the pack, 
choose the appropriate needle to ensure an intramuscular administration. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
GSK Vaccines S.r.l., 



 

 19 

Via Fiorentina 1, 
53100 Siena, 
Italy 
 
 
8. MARKETING AUTHORISTION NUMBER(S) 
 
EU/1/12/812/001 
EU/1/12/812/002 
EU/1/12/812/003 
EU/1/12/812/004 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 14 January 2013 
Date of latest renewal: 18 September 2017 
 
 
10. DATE OF REVISION OF THE TEXT 
 
DD/MM/YYYY 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
  



 

 20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) 
AND MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 
 



 

 21 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND 
MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturers of the biological active substances (NHBA, NadA, fHbp): 
 
Sandoz GmbH 
Biochemiestrasse 10 
A-6250 Kundl 
Austria 
 
Name and address of the manufacturers of the biological active substance (OMV): 
 
GSK Vaccines S.r.l. 
Bellaria-Rosia 
IT-53018 Sovicille-Siena 
Italy 
 
GSK Vaccines S.r.l. 
Via Fiorentina, 1 
IT-53100 Siena 
Italy 
 
Name and address of the manufacturer responsible for batch release: 
 
GSK Vaccines S.r.l. 
Bellaria-Rosia 
IT-53018 Sovicille-Siena 
Italy 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to medical prescription. 
 
• Official batch release 
 
In accordance with Article 114 of Directive 2001/83/EC, the official batch release will be undertaken 
by a state laboratory or a laboratory designated for that purpose. 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic safety update reports (PSURs) 
 
The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 
subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk management plan (RMP) 
 



 

 22 

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities 
and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation 
and any agreed subsequent updates of the RMP. 
 
An updated RMP should be submitted: 
• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
 

  



 

 23 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



 

 24 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



 

 25 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Bexsero suspension for injection in pre-filled syringe 
Meningococcal Group B Vaccine (rDNA, component, adsorbed) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
0.5 ml dose contains: 
 
Recombinant Neisseria meningitidis group B NHBA fusion/NadA/fHbp 
fusion proteins 

50/50/50 micrograms 

Outer membrane vesicles (OMV) from Neisseria meningitidis group B 
strain NZ98/254 measured as amount of total protein containing the PorA 
P1.4 

25 micrograms 

 
Adsorbed on aluminium hydroxide (0.5 mg Al³+). 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium chloride, histidine, sucrose, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection (0.5 ml) 
1 pre-filled syringe containing 0.5 ml suspension with needles 
1 pre-filled syringe containing 0.5 ml suspension without needles 
 
10 pre-filled syringes each containing 0.5 ml suspension with needles 
10 pre-filled syringes each containing 0.5 ml suspension without needles 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intramuscular use only. 
 
Shake well before use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 



 

 26 

 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Store in the original package in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, 
IF APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
GSK Vaccines S.r.l., 
Via Fiorentina 1, 
53100 Siena, 
Italy 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/12/812/001 
EU/1/12/812/002 
EU/1/12/812/003 
EU/1/12/812/004 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 



 

 27 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



 

 28 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PRE-FILLED SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Bexsero suspension for injection 
Meningococcal B vaccine 
IM use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP: 
 
 
4. BATCH NUMBER 
 
Lot: 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 dose (0.5 ml) 
 
 
6. OTHER 
 

  



 

 29 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



 

 30 

Package leaflet: information for the user 
 

Bexsero suspension for injection in pre-filled syringe 
Meningococcal group B Vaccine (rDNA, component, adsorbed) 

 
Read all of this leaflet carefully before you or your child receive this medicine because it 
contains important information for you or your child. 
 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or nurse. 
- This vaccine has been prescribed for you or your child only. 
- If you get any side effects talk to your doctor or nurse. This includes any possible side effects 

not listed in this leaflet. See section 4. 
 
What is in this leaflet: 
 
1. What Bexsero is and what it is used for 
2. What you need to know before you or your child receive Bexsero 
3. How to use Bexsero 
4. Possible side effects 
5. How to store Bexsero 
6. Contents of the pack and other information 
 
 
1. What BEXSERO is and what it is used for 
 
Bexsero is a Meningococcal group B Vaccine. 
 
Bexsero contains four different components from the surface of the bacteria Neisseria meningitidis 
group B. 
 
Bexsero is given to individuals from 2 months of age and older to help protect against disease caused 
by the Neisseria meningitidis group B bacteria. These bacteria can cause serious, and sometimes 
life-threatening, infections such as meningitis (inflammation of the covering of the brain and spinal 
cord) and sepsis (blood poisoning). 
 
The vaccine works by specifically stimulating the body’s natural defense system of the vaccinated 
person. This results in protection against the disease. 
 
 
2. What you need to know before you or your child receive BEXSERO 
 
Do NOT use Bexsero 
 
- if you or your child are allergic to the active substances or any of the other ingredients of this 

vaccine (listed in section 6). 
 
Warnings and precautions 
 
Talk to your doctor or nurse before you or your child receive Bexsero: 
- if you or your child have a severe infection with a high temperature. If this is the case, then 

vaccination will be postponed. The presence of a minor infection, such as a cold, should not 
require postponement of the vaccination, but talk to your doctor or nurse first. 

- if you or your child have haemophilia or any other problem that may stop your blood from 
clotting properly, such as treatment with blood thinners (anticoagulants). Talk to your doctor or 
nurse first. 



 

 31 

- if you or your child receive treatment that blocks the part of the immune system known as 
complement activation, such as eculizumab. Even if you or your child have been vaccinated 
with Bexsero you or your child remain at increased risk of disease caused by the Neisseria 
meningitidis group B bacteria. 

- if your child was born prematurely (before or at 28 weeks of pregnancy), particularly if they had 
breathing difficulties. Stopping breathing or irregular breathing for a short time may be more 
common in the first three days following vaccination in these babies and they may need special 
monitoring. 

- if you or your child have an allergy to the antibiotic kanamycin. If present, the kanamycin level 
in the vaccine is low. If you or your child may have an allergy to kanamycin, talk to your doctor 
or nurse first. 

 
Fainting, feeling faint or other stress-related reactions can occur as a response to any needle injection. 
Tell your doctor or nurse if you have experienced this kind of reaction previously. 
 
Tell your doctor or nurse if you know that you or your child is allergic to latex. The tip cap of the syringe 
may contain natural rubber latex. The risk for developing an allergic reaction is very small, but your doctor 
or nurse needs to be aware of your allergy when deciding if you or your child should receive Bexsero. 
 
There are no data on the use of Bexsero in adults above 50 years of age. There are limited data on the use 
of Bexsero in patients with chronic medical conditions or with weakened immunity. If you or your child 
have weakened immunity (for example, due to the use of immunosuppressive medications, or HIV 
infection, or hereditary defects of the body’s natural defence system), it is possible that the effectiveness 
of Bexsero is reduced. 
 
As with any vaccine, Bexsero may not fully protect all of those who are vaccinated. 
 
Other medicines and Bexsero 
 
Tell your doctor or nurse if you or your child are taking, have recently taken, or might take any other 
medicines, or have recently received any other vaccine. 
 
Bexsero can be given at the same time as any of the following vaccine components: diphtheria, 
tetanus, whooping cough (pertussis), Haemophilus influenzae type b, polio, hepatitis B, 
pneumococcus, measles, mumps, rubella, chickenpox, and meningococcus A, C, W, Y. Talk to your 
doctor or nurse for further information. 
 
When given at the same time with other vaccines Bexsero must be given at separate injection sites. 
 
Your doctor or nurse may ask you to give your child medicines that lower fever at the time and after 
Bexsero has been given. This will help to reduce some of the side effects of Bexsero. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, 
ask your doctor for advice before Bexsero is given. Your doctor may still recommend that you receive 
Bexsero if you are at risk of exposure to meningococcal infection. 
 
Driving and using machines 
 
Bexsero has no or negligible influence on the ability to drive and use machines. However, some of the 
effects mentioned under section 4 “Possible side effects” may temporarily affect the ability to drive or 
use machines. 
 
Bexsero contains sodium chloride 
 
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-free’. 



 

 32 

 
 
3. How to use BEXSERO 
 
Bexsero (0.5 ml) will be given to you or your child by a doctor or nurse. It will be injected into 
a muscle, usually the thigh for infants or the upper arm for children, adolescents and adults. 
 
It is important to follow the instructions from the doctor or nurse so that you or your child completes 
the course of injections. 
 
Infants 2 months to 5 months of age at the time of first dose 
 
Your child should receive an initial course of two or three injections of the vaccine followed by 
an additional injection (booster). 
- The first injection should be given no earlier than 2 months of age. 
- If three initial doses are given, the interval between injections should be at least 1 month. 
- If two initial doses are given, the interval between injections should be at least 2 months. 
- A booster will be given between 12 months and 15 months of age after an interval of at least 6 

months from the last injection of the initial course. In case of delay, the booster should not be 
given later than 24 months of age. 

 
Infants 6 months to 11 months of age at the time of first dose 
 
Infants 6 months to 11 months of age should receive two injections of the vaccine followed by 
an additional injection (booster). 
- The interval between each injection should be at least 2 months. 
- A booster will be given in the second year of life after an interval of at least 2 months from the 

second injection. 
 
Children 12 months to 23 months of age at the time of first dose 
 
Children 12 months to 23 months of age should receive two injections of the vaccine followed by 
an additional injection (booster). 
- The interval between each injection should be at least 2 months. 
- A booster will be given after an interval of 12 to 23 months from the second injection. 
 
Children 2 years to 10 years of age at the time of first dose 
 
Children 2 years to 10 years of age should receive two injections of the vaccine. 
- The interval between each injection should be at least 1 month. 
Your child may receive an additional injection (booster). 
 
Adolescents and adults from 11 years of age at the time of first dose 
 
Adolescents (from 11 years of age) and adults should receive two injections of the vaccine. 
- The interval between each injection should be at least 1 month. 
You may receive an additional injection (booster). 
 
Adults above 50 years of age 
 
There are no data in adults above 50 years of age. Ask your doctor for advice whether it is beneficial 
for you to receive Bexsero. 
 
If you have any further questions on Bexsero, ask your doctor or nurse. 
 
 
4. Possible side effects 



 

 33 

 
Like all vaccines, this vaccine can cause side effects, although not everybody gets them. 
 
When Bexsero is given to you or your child, the very common side effects (may affect more 
than 1 in 10 people) that you or your child may get (reported in all age groups) are: 
- pain/tenderness at the injection site, redness of the skin at the injection site, swelling of the skin 

at the injection site, hardness of the skin at the injection site. 
 
The following side effects may also occur after receiving this vaccine. 
 
Infants and children (up to 10 years of age) 
 
Very common (these may affect more than 1 in 10 people) 
- fever (≥38ºC) 
- loss of appetite 
- tenderness at the injection site (including severe injection site tenderness resulting in crying 

when injected limb is moved) 
- painful joints 
- skin rash (children aged 12 to 23 months) (uncommon after booster) 
- sleepiness 
- feeling irritable 
- unusual crying 
- vomiting (uncommon after booster) 
- diarrhoea 
- headache 
 
Common (these may affect up to 1 in 10 people) 
- skin rash (infants and children 2 to 10 years of age) 
 
Uncommon (these may affect up to 1 in 100 people) 
- high fever (≥40°C) 
- seizures (including febrile seizures) 
- dry skin 
- paleness (rare after booster) 
 
Rare (these may affect up to 1 in 1,000 people) 
- Kawasaki disease which may include symptoms such as fever that lasts for more than five days, 

associated with a skin rash on the trunk of the body, and sometimes followed by a peeling of the 
skin on the hands and fingers, swollen glands in the neck, red eyes, lips, throat and tongue 

- Itchy rash, skin rash 
 
Adolescents (from 11 years of age) and adults 
 
Very common (these may affect more than 1 in 10 people) 
- pain at the injection site resulting in inability to perform normal daily activity 
- painful muscles and joints 
- nausea 
- generally feeling unwell 
- headache 
 
Side effects that have been reported during marketed use include:  
 
Allergic reactions that may include severe swelling of the lips, mouth, throat (which may cause 
difficulty in swallowing), difficulty breathing with wheezing or coughing, rash, loss of consciousness 
and very low blood pressure. 
Collapse (sudden onset of muscle floppiness), less responsive than usual or lack of awareness, and 
paleness or bluish skin discoloration in young children. 



 

 34 

Feeling faint or fainting.  
Skin rash (adolescents from 11 years of age and adults). 
Fever (adolescents from 11 years of age and adults). 
Injection site reactions like extensive swelling of the vaccinated limb, blisters at or around the 
injection site and hard lump at the injection site (which may persist for more than one month). 
Neck stiffness or uncomfortable sensitivity to light (photophobia), indicating meningeal irritation, has 
been sporadically reported shortly after vaccination; these symptoms have been of mild and transient 
nature. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store BEXSERO 
 
Keep this vaccine out of the sight and reach of children. 
 
Do not use this vaccine after the expiry date which is stated on the carton after EXP. The expiry date 
refers to the last day of that month. 
 
Store in a refrigerator (2°C – 8°C). Do not freeze. 
Store in the original package in order to protect from light. 
 
Do not throw away any medicines via wastewater or household waste. Ask your doctor or nurse how 
to throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Bexsero contains 
 
One dose (0.5 ml) contains: 
 
Active substances: 
 
Recombinant Neisseria meningitidis group B NHBA fusion protein 1, 2, 3 50 micrograms 
Recombinant Neisseria meningitidis group B NadA protein 1, 2, 3 50 micrograms 
Recombinant Neisseria meningitidis group B fHbp fusion protein 1, 2, 3 50 micrograms 
Outer membrane vesicles (OMV) from Neisseria meningitidis group B strain 
NZ98/254 measured as amount of total protein containing the PorA P1.4 2 

25 micrograms 

 
1 produced in E. coli cells by recombinant DNA technology 
2 adsorbed on aluminium hydroxide (0.5 mg Al³+) 
³ NHBA (Neisserial Heparin Binding Antigen), NadA (Neisseria adhesin A), fHbp (factor H 

binding protein) 
 
Other ingredients: 
Sodium chloride, histidine, sucrose and water for injections (see section 2 for further information on 
sodium and latex). 
 
What Bexsero looks like and contents of the pack 
 
Bexsero is a suspension for injection in pre-filled syringe (Type I glass) with a plunger stopper (Type I 
bromobutyl rubber) and with a protective tip cap (Type I or Type II rubber) with or without needles. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 

 35 

 
Pack sizes of 1 or 10 syringes. 
The suspension is white opalescent liquid. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder: 
 
GSK Vaccines S.r.l. 
Via Fiorentina 1 
53100 Siena 
Italy. 
 
Manufacturer: 
 
GSK Vaccines S.r.l. 
Bellaria-Rosia 
53018 Sovicille (Siena) 
Italy. 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
GlaxoSmithKline Pharmaceuticals s.a./n.v. 
Tél/Tel: + 32 10 85 52 00 

Lietuva 
GlaxoSmithKline Lietuva UAB 
Tel: +370 5 264 90 00 
info.lt@gsk.com 
 

България 
ГлаксоСмитКлайн ЕООД 
Тел. + 359 2 953 10 34 
 

Luxembourg/Luxemburg 
GlaxoSmithKline Pharmaceuticals s.a./n.v. 
Tél/Tel: + 32 10 85 52 00 

Česká republika 
GlaxoSmithKline s.r.o. 
Tel: + 420 2 22 00 11 11 
cz.info@gsk.com  
 

Magyarország 
GlaxoSmithKline Kft. 
Tel.: + 36-1-2255300 
 

Danmark 
GlaxoSmithKline Pharma A/S 
Tlf: + 45 36 35 91 00 
dk-info@gsk.com 
 

Malta 
GlaxoSmithKline (Malta) Ltd 
Tel: + 356 21 238131  

Deutschland 
GlaxoSmithKline GmbH & Co. KG 
Tel: +49 (0)89 36044 8701 
de.impfservice@gsk.com  

Nederland 
GlaxoSmithKline BV 
Tel: + 31 (0)33 2081100 
 
 

Eesti 
GlaxoSmithKline Eesti OÜ  
Tel: +372 667 6900 
estonia@gsk.com  
 

Norge 
GlaxoSmithKline AS 
Tlf: + 47 22 70 20 00 
 

Ελλάδα 
GlaxoSmithKline Μονοπρόσωπη A.E.B.E 
Tηλ: + 30 210 68 82 100  

Österreich 
GlaxoSmithKline Pharma GmbH 
Tel: + 43 (0)1 97075 0 
at.info@gsk.com 
 



 

 36 

España 
GlaxoSmithKline, S.A. 
Tel: + 34 900 202 700 
es-ci@gsk.com  
 

Polska 
GSK Services Sp. z o.o. 
Tel.: + 48 (22) 576 9000 

France 
Laboratoire GlaxoSmithKline 
Tél: + 33 (0) 1 39 17 84 44 
diam@gsk.com  

Portugal 
GlaxoSmithKline - Produtos Farmacêuticos, 
Lda. 
Tel: + 351 21 412 95 00 
FI.PT@gsk.com 
 

Hrvatska 
GlaxoSmithKline d.o.o. 
Tel.: + 385 (0)1 6051999  

România 
GlaxoSmithKline (GSK) SRL 
Tel: +40 (0)21 3028 208  
 

Ireland 
GlaxoSmithKline (Ireland) Ltd 
Tel: + 353 (0)1 495 5000  
 
 

Slovenija 
GlaxoSmithKline d.o.o. 
Tel: + 386 (0) 1 280 25 00 
medical.x.si@gsk.com  
 

Ísland 
Vistor hf.  
Sími: +354 535 7000  

Slovenská republika 
GlaxoSmithKline Slovakia s.r.o. 
Tel.: + 421 (0)2 48 26 11 11 
recepcia.sk@gsk.com 
 

Italia 
GlaxoSmithKline S.p.A. 
Tel: +39 (0)45 9218 111 

Suomi/Finland 
GlaxoSmithKline Oy 
Puh/Tel: + 358 10 30 30 30 
 

Κύπρος 
GlaxoSmithKline (Cyprus) Ltd 
Τηλ: + 357 22 39 70 00 
gskcyprus@gsk.com 

Sverige 
GlaxoSmithKline AB 
Tel: + 46 (0)8 638 93 00 
info.produkt@gsk.com  
 

Latvija 
GlaxoSmithKline Latvia SIA 
Tel: + 371 67312687 
lv-epasts@gsk.com  

United Kingdom 
GlaxoSmithKline UK 
Tel: +44 (0)800 221 441 
customercontactuk@gsk.com  

 
This leaflet was last revised in {MM/YYYY} 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
------------------------------------------------------------------------------------------------------------- 
 
The following information is intended for healthcare professionals only: 
 
Upon storage a fine off-white deposit may be observed in the pre-filled syringe containing the 
suspension. 
 
Before use, the pre-filled syringe should be well shaken in order to form a homogeneous suspension. 
 
The vaccine should be visually inspected for particulate matter and discoloration prior to 
administration. In the event of any foreign particulate matter and/or variation of physical aspect being 
observed, do not administer the vaccine. If two needles of different lengths are provided in the pack, 
choose the appropriate needle to ensure an intramuscular administration. 



 

 37 

 
Do not freeze. 
Bexsero must not be mixed with other vaccines in the same syringe. 
Should concomitant administration of other vaccines be necessary, vaccines must be administered at 
separate injection sites. 
 
Care must be taken to ensure that the vaccine is injected intramuscularly only. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET