ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
Synflorix suspension for injection in pre-filled syringe
Pneumococcal polysaccharide
conjugate vaccine (adsorbed)
1 dose (0.5 ml) contains:
Pneumococcal polysaccharide serotype 1
1,2
1 microgram
Pneumococcal polysaccharide serotype 4
1,2
3 micrograms
Pneumococcal polysaccharide serotype 5
1,2
1 microgram
Pneumococcal polysaccharide serotype 6B
1,2
1 microgram
Pneumococcal polysaccharide serotype 7F
1,2
1 microgram
Pneumococcal polysaccharide serotype 9V
1,2
1 microgram
Pneumococcal polysaccharide serotype 14
1,2
1 microgram
Pneumococcal polysaccharide serotype 18C
1,3
3 micrograms
Pneumococcal polysaccharide serotype 19F
1,4
3 micrograms
Pneumococcal polysaccharide serotype 23F
1,2
1 microgram
1
adsorbed on aluminium phosphate 0.5 milligram Al
3+
2
conjugated to protein D (derived from non-typeable
Haemophilus influenzae
) carrier protein
9-16 micrograms
3
conjugated to tetanus toxoid carrier protein
5-10 micrograms
4
conjugated to diphtheria toxoid carrier protein
3-6 micrograms
For a full list of excipients, see section 6.1.
Suspension for injection (injection).
The vaccine is a turbid white suspension.
Active immunisation against invasive disease and acute otitis media caused by
Streptococcus
pneumoniae
in infants and children from 6 weeks up to 2 years of age. See sections 4.4 and 5.1 for
information on protection against specific pneumococcal serotypes.
The use of Synflorix should be determined on the basis of official recommendations taking into
consideration the impact of invasive disease in different age groups as well as the variability of
serotype epidemiology in different geographical areas.
Posology
The immunisation schedules for Synflorix should be based on official recommendations.
Infants from 6 weeks to 6 months of age
2
Three-dose primary series
The recommended immunisation series to ensure optimal protection consists of four doses, each of 0.5
ml. The primary infant series consists of three doses with the first dose usually given at 2 months of
age and with an interval of at least 1 month between doses. The first dose may be given as early as six
weeks of age. A booster dose is recommended at least 6 months after the last priming dose and
preferably between 12 and 15 months of age. (see sections 4.4 and 5.1)
Two-dose primary series
Alternatively, when Synflorix is given as part of a routine infant immunisation programme, a series
consisting of three doses, each of 0.5 ml may be given. The first dose may be administered from the
age of 2 months, with a second dose 2 months later. A booster dose is recommended at least 6 months
after the last primary dose (see section
5.1
).
Infants born between 27-36 weeks gestation
In preterm infants born after at least 27 weeks of gestational age, the recommended immunisation
series consists of four doses, each of 0.5ml. The primary infant series consists of three doses with the
first dose given at 2 months of age and with an interval of at least 1 month between doses. A booster
dose is recommended at least 6 months after the last primary dose (see sections 4.4 and 5.1).
Previously unvaccinated older infants and children
- infants aged 7-11 months: The vaccination schedule consists of two doses of 0.5 ml with an interval
of at least 1 month between doses. A third dose is recommended in the second year of life with an
interval of at least 2 months between doses.
- children aged 12-23 months: The vaccination schedule consists of two doses of 0.5 ml with an
interval of at least 2 months between doses. The need for a booster dose after this immunisation
schedule has not been established. (see section 4.4)
It is recommended that subjects who receive a first dose of Synflorix complete the full vaccination
course with Synflorix.
Paediatric population
The safety and efficacy of Synflorix in children over 24 months of age have not been established.
Method of administration
The vaccine should be given by intramuscular injection. The preferred sites are anterolateral aspect of
the thigh in infants or the deltoid muscle of the upper arm in young children.
Hypersensitivity to the active substances or to any of the excipients, or to any of the carrier proteins.
As with other vaccines, the administration of Synflorix should be postponed in subjects suffering from
acute severe febrile illness. However, the presence of a minor infection, such as a cold, should not
result in the deferral of vaccination.
As with all injectable vaccines, appropriate medical treatment and supervision should always be
readily available in case of a rare anaphylactic reaction following the administration of the vaccine.
The potential risk of apnoea and the need for respiratory monitoring for 48-72h should be considered
when administering the primary immunisation series to very premature infants (born ≤ 28 weeks of
3
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.
Synflorix should under no circumstances be administered intravascularly or intradermally. No data are
available on subcutaneous administration of Synflorix.
As for other vaccines administered intramuscularly, Synflorix should be given with caution to
individuals with thrombocytopenia or any coagulation disorder since bleeding may occur following an
intramuscular administration to these subjects.
Official recommendations for the immunisation against diphtheria, tetanus and
Haemophilus
influenzae
type b should also be followed.
There is insufficient evidence that Synflorix provides protection against pneumococcal serotypes not
contained in the vaccine or against non-typeable
Haemophilus influenzae
. Synflorix does not provide
protection against other micro-organisms.
As with any vaccine, Synflorix may not protect all vaccinated individuals against invasive
pneumococcal disease or otitis media caused by the serotypes in the vaccine. Protection against otitis
media caused by pneumococcal serotypes in the vaccine is expected to be substantially lower than
protection against invasive disease. In addition, as otitis media is caused by many micro-organisms
other than the
Streptococcus pneumoniae
serotypes represented in the vaccine, the overall protection
against otitis media is expected to be limited (see section 5.1)
In clinical trials Synflorix elicited an immune response to all ten serotypes included in the vaccine, but
the magnitude of the responses varied between serotypes. The functional immune response to
serotypes 1 and 5 was lower in magnitude than the response against all other vaccine serotypes. It is
not known whether this lower functional immune response against serotypes 1 and 5 will result in
lower protective efficacy against invasive disease or otitis media caused by these serotypes (see
section 5.1).
Synflorix is indicated for use in children aged from 6 weeks up to 2 years. Children should receive
the dose regimen of Synflorix that is appropriate to their age at the time of commencing the
vaccination series (see section 4.2). Safety and immunogenicity data are not yet available in children
above 2 years of age.
Children with impaired immune responsiveness, whether due to the use of immunosuppressive
therapy, a genetic defect, HIV infection, or other causes, may have reduced antibody response to
vaccination.
Safety and immunogenicity data in children with increased risk for pneumococcal infections (e.g.
sickle cell disease, congenital and acquired splenic dysfunction, HIV-infected, malignancy, nephrotic
syndrome) are not yet available for Synflorix. Vaccination in high-risk groups should be considered on
an individual basis (see section 4.2).
The immune response elicited after two doses of Synflorix in children 12-23 months of age is
comparable to the response elicited after three doses in infants (see section 5.1). The immune response
to a booster dose after two doses in children aged 12-23 months has not been evaluated, but a booster
dose may be needed to ensure optimal individual protection.
However, a 2-dose schedule in children aged 12-23 months with high risk of pneumococcal disease
(such as children with sickle-cell disease, asplenia, HIV infection, chronic illness or who are
immunocompromised) may not be sufficient to provide optimal protection. In these children, a 23-
valent pneumococcal polysaccharide vaccine should be given
4
≥ 2 years of age, whenever
recommended. The interval between the pneumococcal conjugate vaccine (Synflorix) and the 23-
valent pneumococcal polysaccharide vaccine should not be less than 8 weeks. There are no data
available to indicate whether the administration of pneumococcal polysaccharide vaccine to Synflorix
primed children may result in hyporesponsiveness to further doses of pneumococcal polysaccharide or
to pneumococcal conjugate vaccine.
Prophylactic administration of antipyretics before or immediately after vaccine administration can
reduce the incidence and intensity of post-vaccination febrile reactions. However, data suggest that the
prophylactic us e of paracetamol might reduce the immune response to Synflorix. The clinical
relevance of this observation, as well as the impact of antipyretics other than paracetamol on the
immune response to Synflorix remains unknown.
The us e of prophylactic antipyretic medicinal products is recommended:
-
for all children receiving Synflorix simultaneously with vaccines containing whole cell pertussis
because of higher rate of febrile reactions (see section 4.8).
-
for children with seizure disorders or with a prior history of febrile seizur es.
Antipyretic treatment should be initiated according to local treatment guidelines.
Use with other vaccines
Synflorix can be given concomitantly with any of the following monovalent or combination vaccines
[including DTPa-HBV-IPV/Hib and DTPw-HBV/Hib]: diphtheria-tetanus-acellular pertussis vaccine
(DTPa), hepatitis B vaccine (HBV), inactivated polio vaccine (IPV),
Haemophilus influenzae
type b
vaccine (Hib), diphtheria-tetanus-whole cell pertussis vaccine (DTPw), measles-mumps-rub ella
vaccine (MMR), varicella vaccine (V), meningococcal serogroup C conjugate vaccine (CRM
197
and
TT conjugates), oral polio vaccine (OPV) and oral rotavirus vaccine. Different injectable vaccines
should always be given at different injection sites.
Clinical studies demonstrated that the immune responses and the safety profiles of the co-administered
vaccines were unaffected, with the exception of the inactivated poliovirus type 2 response, for which
inconsistent results were observed across studies (seroprotection ranging from 78% to 100%). The
clinical relevance of this observation is not known. No negative interference was obs erved with
meningococcal conjugate vaccines irrespective of the carrier protein (CRM
197
and TT conjugates).
Enhancement of antibody response to Hib-TT conjugate, diphtheria and tetanus antigens was
observed.
Use with systemic immunosuppressive medicinal products
As with other vaccines, it may be expected that in patients receiving immunosuppressive treatment an
adequate response may not be elicited.
Use with prophylactic administration of antipyretics
See section 4.4.
Synflorix is not intended for use in adults. Human data on the use during pregnancy or lactation and
animal reproduction studies are not available.
Not relevant.
Clinical trials involved the administration of 12,879 doses of Synflorix to 4,595 healthy children and
137 preterm infants as primary vaccination. Furthermore, 3,870 children and 116 preterm infants
5
received a booster dose of Synflorix in the second year of life. In all trials, Synflorix was
administered concurrently with the recommended childhood vaccines.
The most common adverse reactions observed after primary vaccination were redness at the
injection site and irritability which occurred after 38.3% and 52.3% of all doses respectively.
Following booster vaccination, these adverse reactions occurred at 52.6% and 55.4% respectively.
The majority of these reactions were of mild to moderate severity and were not long lasting.
No increase in the incidence or severity of the adverse reactions was seen with subsequent doses of
the primary vaccination series.
An increase in reactogenicity was reported after booster vaccination compared to the doses of the
primary course with Synflorix.
Reactogenicity was higher in children receiving whole cell pertussis vaccines concomitantly. In a
clinical study children received either Synflorix (N=603) or 7-valent Prevenar (N=203) concomitantly
with a DTPw containing vaccine. After the primary vaccination course, fever ≥38°C and >39°C was
reported respectively in 86.1% and 14.7% of children receiving Synflorix and in 82.9% and 11.6% of
children vaccinated with 7-valent Prevenar.
In comparative clinical studies, the incidence of local and general adverse events reported within 4
days after each vaccination dose was within the same range as after vaccination with 7-valent
Prevenar.
Adverse reactions (following primary immunisation or booster dose) considered as being at least
possibly related to vaccination have been categorised by frequency.
Frequencies are reported as:
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 common: drowsiness
Rare: febrile and non-febrile convulsions
Respiratory, thoracic and mediastinal disorders
Uncommon: apnoea in very premature infants (≤28 weeks of gestation) (see section 4.4)
Gastro-intestinal disorders
Uncommon: diarrhoea, vomiting
Skin and subcutaneous tissue disorders
Metabolism and nutrition disorders
Very common: appetite lost
General disorders and administration site conditions
Very common: pain, redness, swelling at the injection site, fever (≥38°C rectally)
Common: injection site induration, fever (>39°C rectally)
Uncommon: injection site haematoma, haemorrhage and nodule, fever (>40°C rectally)*
Immune system disorders
Rare: allergic reactions (such as allergic dermatitis, atopic dermatitis, eczema)
6
Nervous system disorders
Rare: rash, urticaria
Psychiatric disorders
Very common: irritability
Uncommon: crying abnormal
*reported following booster vaccination
No case of overdose has been reported.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: pneumococcal vaccines, ATC code: J07AL52
Epidemiological data
The 10 pneumococcal serotypes included in this vaccine repr esent the major disease-causing serotypes
in Europe covering approximately 56% to 90% of invasive pneumococcal disease (IPD) in children <5
years of age. In this age group, serotypes 1, 5 and 7F account for 3.3% to 24.1% of IPD depending on
the country and time period studied.
Acute otitis media (AOM) is a common childhood disease with different aetiologies.
Bacteria can be
responsible for 60-70% of clinical episodes of AOM.
Streptococcus pneumoniae
and Non-Typeable
Haemophilus influenzae
(NTHi) are the most common causes of bacterial AOM worldwide.
1. Invasive pneumococcal disease
(which includes sepsis, meningitis, bacteraemic pneumonia and
The protective efficacy of Synflorix against IPD has not been studied. As recommended by WHO, the
assessment of potential efficacy against IPD has been based on a comparison of immune responses to
the seven serotypes shared between Synflorix and another pneumococcal conjugate vaccine for which
protective efficacy was evaluated previously (i.e. 7-valent Prevenar). Immune responses to the extra
three serotypes in Synflorix have also been measured.
In a head-to-head comparative trial with 7-valent Prevenar, non inferiority of the immune response to
Synflorix measured by ELISA was demonstrated for all serotypes, except for 6B and 23F (upper limit
of the 96.5% CI around the difference between groups >10%) (Table 1). For serotypes 6B and 23F,
respectively, 65.9% and 81.4% of infants vaccinated at 2, 3 and 4 months reached the antibody
threshold (i.e. 0.20 µg/ml) one month after the third dose of Synflorix versus 79.0% and 94.1%
respectively, after three doses of 7-valent Prevenar. The clinical relevance of these differences is not
known.
The percentage of vaccinees reaching the threshol d for the three additional serotypes in Synflorix (1, 5
and 7F) was respectively 97.3%, 99.0% and 99.5% and was at least as good as the aggregate 7-valent
Prevenar response against the 7 common serotypes (95.8%).
Table 1: Comparative analysis between 7-valent Prevenar and Synflorix in percentage of
subjects with antibody concentrations
>
0.20 µg/ml one month post-dose 3
Antibody
SYNFLORIX
7-valent Prevenar
Difference in %
≥
0.20
µ
g/ml (
7-valent
Prevenar
minus SYNFLORIX)
N
%
N
%
%
96.5%CI
Anti-4
1106
97.1
373
100
2.89
1.71
4.16
Anti-6B
1100
65.9
372
79.0
13.12
7.53
18.28
7
bacteraemia)
Anti-9V
1103
98.1
374
99.5
1.37
-0.28
2.56
Anti-14
1100
99.5
374
99.5
-0.08
-1.66
0.71
Anti-18C
1102
96.0
374
98.9
2.92
0.88
4.57
Anti-19F
1104
95.4
375
99.2
3.83
1.87
5.50
Anti-23F
1102
81.4
374
94.1
12.72
8.89
16.13
Post-primary antibody geometric mean concentrations (GMCs) elicited by Synflorix against the seven
serotypes in common were lower than those elicited by 7-valent Prevenar. Pre-booster GMCs (8 to 12
months after the last primary dose) were generally similar for the two vaccines. After the booster dose
the GMCs elicited by Synflorix were lower for most serotypes in common with 7-valent Prevenar.
In the same study, Synflorix was shown to elicit functional antibodies to all vaccine serotypes. For
each of the seven serotypes in common, 87.7% to 100% of Synflorix vaccinees and 92.1% to 100% of
7-valent Prevenar vaccinees reached an OPA titre ≥ 8 one month after the third dose. The difference
between both vaccines in terms of percentage of subjects with OPA titres ≥ 8 was <5% for all
serotypes in common, including 6B and 23F. Post-primary and post-booster OPA antibody geometric
mean titres (GMTs) elicited by Synflorix were lower than those elicited by 7-valent Prevenar for the
seven shared serotypes, except for serotype 19F.
For serotypes 1, 5 and 7F, the percentages of Synflorix vaccinees reaching an OPA titre ≥ 8 were
respectively 65.7%, 90.9% and 99.6% after the primary vaccination course and 91.0%, 96.3% and
100% after the booster dose. The OPA response for serotypes 1 and 5 was lower in magnitude than the
response for each of the other serotypes. The implications of these findings for protective efficacy are
not known. The response to serotype 7F was in the same range as for the seven serotypes in common
between the two vaccines.
The administration of a fourth dose (booster dose) in the second year of life elicited an anamnestic
antibody response as measured by ELISA and OPA for the 10 serotypes included in the vaccine
demonstrating the induction of immune memory after the three-dose primary course.
2. Acute Otitis Media (AOM)
In a large randomised double-blind Pneumococcal Otitis Media Efficacy Trial (POET) conducted in
the Czech Repub lic and in Slovakia, 4,968 infants received an 11-valent investigational vaccine
(11Pn-PD) containing the 10 serotypes of Synflorix (along with serotype 3 for which efficacy was not
demonstrated) or a control vaccine (hepatitis A vaccine) according to a 3, 4, 5 and 12-15 months
vaccination schedule.
Efficacy of the 11 Pn-PD vaccine against the first occurrence of vaccine-serotype AOM episode was
52.6% (95% CI: 35.0;65.5). Serotype specific efficacy against the first AOM episode was
demonstrated for serotypes 6B (86.5%, 95%CI: 54.9;96.0), 14 (94.8%, 95% CI: 61.0;99.3), 19F
(43.3%, 95% CI:6.3;65.4) and 23F (70.8%, 95% CI: 20.8;89.2). For other vaccine serotypes, the
number of AOM cases was too limited to allow any efficacy conclusion to be drawn. Efficacy against
any AOM episode due to any pneumococcal serotype was 51.5% (95% CI: 36.8;62.9). No increase in
the incidence of AOM due to other bacterial pathogens or non-vaccine serotypes was observed in this
study. The estimated vaccine efficacy against any clinical episodes of otitis media regardless of
aetiology was 33.6% (95% CI: 20.8; 44.3).
Based on immunological bridging of the functional vaccine response (OPA) of Synflorix with the 11-
valent formulation used within POET, it is expected that Synflorix provides similar protective efficacy
against pneumococcal AOM.
3. Additional immunogenicity data
Infants from 6 weeks to 6 months of age
3-dose primary schedule
8
In total eight studies, conducted in various countries across Europe, in Chile and in the Philippines,
have evaluated the immunogenicity of Synflorix after a three-dose primary series (N=3,089) according
to different vaccination schedules (6-10-14 weeks, 2-3-4, 3-4-5 or 2-4-6 months of age). A fourth
(booster) dose was given in six clinical studies to 1,976 subjects. In general, comparable vaccine
responses were obs erved for the different schedules, although somewhat higher immune responses
were noted for the 2-4-6 month schedule.
2-dose primary schedule
The immunogenicity of Synflorix following a 2-dose primary vaccination schedule in subjects less
than 6 months of age was evaluated in two clinical studies.
In the first study, in a post-hoc analysis, the immunogenicity two months after the second dose of
Synflorix was compared with 7-valent Prevenar and the percentages of subjects with ELISA antibody
concentration ≥ 0.2 µg/ml were within the same range for each of the serotypes common to both
vaccines with the exception of serotypes 6B (64.1% for Synflorix and 30.7% for 7-valent Prevenar)
and 18C (87.1% for Synflorix and 97.6% for 7-valent Prevenar). Antibody GMCs were similar in both
groups, with the exception of some serotypes for which responses were higher (6B) or lower (4, 9V
and 18C) in the Synflorix group. Similarly, the percentage of subjects reaching OPA titres ≥ 8 and the
OPA GMTs two months post dose 2 was within the same range for each of the serotypes common to
both vaccines, with the exception of 6B and 19F for which responses were higher in the Synflorix
group.
In the second study, the immunogenicity after two or three doses of Synflorix was compared.
Although there was no significant difference between the two groups in the percentages of subjects
with antibody concentration ≥ 0.20 µg/mL (ELISA), the percentages of subjects for serotypes 6B and
23F were lower than for the other serotypes (Table 2 and Table 3). The percentage of subjects with
OPA titres ≥ 8 in 2-dose primed subjects compared to 3-dose primed subjects were lower for serotypes
6B, 18C and 23F (74.4%, 82.8%, 86.3% respectively for the 2-dose schedule and 88.9%, 96.2%,
97.7% respectively for the 3-dose schedule). Overall, the persistence of the immune response until the
booster at 11 months of age was lower in the 2-dose primed subjects. In both schedules, a booster
response indicative of immunological priming was observed for each serotype (Table 2 and Table 3).
After the booster dose a lower percentage of subjects with OPA titres ≥ 8 wasobserved in the 2-dose
schedule for serotypes 5 (87.2% versus 97.5% for the 3-dose primed subjects) and 6B (81.1% versus
90.3%), all other responses were comparable.
Table 2: Percentage of 2-dose primed subjects with antibody concentrations≥ 0.20 µg/ml one
month post-primary and one month post-booster
≥0.2µg/mL (ELISA)
Antibody
Post-primary
Post-booster
%
95% CI
%
95%CI
Anti-1
97.4
93.4
99.3
99.4
96.5
100
Anti-4
98.0
94.4
99.6
100
97.6
100
Anti-5
96.1
91.6
98.5
100
97.6
100
Anti-6B
55.7
47.3
63.8
88.5
82.4
93.0
Anti-7F
96.7
92.5
98.9
100
97.7
100
Anti-9V
93.4
88.2
96.8
99.4
96.5
100
Anti-14
96.1
91.6
98.5
99.4
96.5
100
Anti-18C
96.1
91.6
98.5
100
97.7
100
Anti-19F
92.8
87.4
96.3
96.2
91.8
98.6
Anti-23F
69.3
61.3
76.5
96.1
91.7
98.6
Table 3: Percentage of 3-dose primed subjects with antibody concentrations ≥ 0.20 µg/ml one
month post-primary and one month post-booster
9
≥0.2µg/mL (ELISA)
Antibody
Post-primary
Post-booster
%
95% CI
%
95%CI
Anti-1
98.7
95.3
99.8
100
97.5
100
Anti-4
99.3
96.4
100
100
97.5
100
Anti-5
100
97.6
100
100
97.5
100
Anti-6B
63.1
54.8
70.8
96.6
92.2
98.9
Anti-7F
99.3
96.4
100
100
97.5
100
Anti-9V
99.3
96.4
100
100
97.5
100
Anti-14
100
97.6
100
98.6
95.2
99.8
Anti-18C
99.3
96.4
100
99.3
96.3
100
Anti-19F
96.1
91.6
98.5
98.0
94.2
99.6
Anti-23F
77.6
70.2
84.0
95.9
91.3
98.5
In the follow-up of the second study, the persistence of antibodies at 36-46 months of age was
demonstrated in subjects that had received a 2-dose primary series followed by a booster dose with at
least 83.7% of subjects remaining seropositive for vaccine serotypes. In subjects that had received a 3-
dose primary series followed by a booster dose, at least 96.5% of the subjects remained seropositive
for vaccine serotypes. A single dose of Synflorix, administered during the 4th year of life, as a
challenge dose, elicited similar ELISA antibody GMCs when measured 7-10 days after challenge in 2-
dose primed subjects and 3-dose primed subjects. These levels were higher than those seen after
challenge of unprimed subjects. The fold increase in ELISA antibody GMCs and OPA GMTs, pre to
post vaccination, was also similar in 2-dose primed subjects to that in 3-dose primed subjects. These
results are indicative of immunological memory in primed subjects for all vaccine serotypes.
The clinical consequences of the lower post-primary and post-booster immune responses observed
after the two-dose primary schedule are not known.
Previously unvaccinated older infants and children
One clinical study evaluated vaccination in children 7-11 months of age and 12-23 months of age. In
the 7-11 months group, children received 2 primary doses followed by a booster dose in the second
year of life. The immune responses after the booster dos e of Synflorix in this age group were generally
similar to those observed after the booster dose in infants who had been primed with 3 doses below 6
months of age.
The immune response elicited after two doses of Synflorix in children 12-23 months of age was
comparable to the response elicited after three doses in infants, except for 18C and 19F for which
responses were higher in the 12-23 months children. The need for a booster dose after two doses in
children aged 12-23 months has not been established.
Long-term persistence of antibodies has not been investigated after administration of a primary series
in infants plus booster or after a two-dose priming in older children.
In a clinical study, it has been demonstrated that Synflorix can be safely administered as a booster
dose in the second year of life to children who had received 3 primary doses of 7-valent Prevenar.
This study has shown that the immune responses against the 7 common serotypes were comparable to
those elicited by a booster dose of 7-valent Prevenar. However, children who received 7-valent
Prevenar for the primary series would not be primed against the additional serotypes contained in
Synflorix (1, 5, 7F). Therefore the degree and duration of protection against invasive pneumococcal
disease and otitis media due to these three serotypes in children of this age group following a single
dose of Synflorix cannot be predicted.
4. Immunogenicity data in preterm infants
10
Immunogenicity of Synflorix in very preterm (gestation period of 27-30 weeks) (N=42), preterm
(gestation period of 31-36 weeks) (N=82) and full term (gestation period > 36 weeks) (N=132) infants
was evaluated following a 3 dose primary vaccination course at 2, 4, 6 months of age. Immunogenicity
following a fourth dose (booster dose) at 15 to 18 months of age was evaluated in 44 very preterm, 69
preterm and 127 full term infants.
One month after primary vaccination (i.e. after the third dose), at least 92.7% of subjects achieved
ELISA antibody concentrations ≥ 0.2 µg/ml and at least 81.7% achieved OPA titres ≥ 8 for all vaccine
serotypes, except serotype 1 (at least 58. 8% with OPA titres ≥ 8). Similar antibody GMCs and OPA
GMTs were observed for all infants except lower antibody GMCs for serotypes 4, 5 and 9V in very
preterms and serotype 9V in preterms and lower OPA GMT for serotype 5 in very preterms. The
clinical relevance of these differences is not known.
One month after the booster dose increases of ELISA antibody GMCs and OPA GMTs were seen for
all serotypes, indicative of immunological memory. Similar antibody GMCs and OPA GMTs were
observed for all infants except a lower OPA GMT for serotype 5 in very preterm infants. Overall, at
least 97.6% of subjects achieved ELISA antibody concentrations≥ 0.2µg/ml and at least 91.9%
achieved OPA titres ≥ 8 for all vaccine serotypes.
5.2 Pharmacokinetic properties
Evaluation of pharmacokinetic properties is not available for vaccines.
5.3 Preclinical safety data
Studies with an 11-valent vaccine formulation representative for Synflorix revealed no special hazard
for humans based on conventional studies of safety pharmacology, single and repeated dose toxicity.
6.1 List of excipients
Sodium chloride
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 stopper (butyl rubber) with or without
needles. Pack size of 1, 10 or 50.
11
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
A fine white deposit with a clear colourless supernatant may be observed upon storage of the pre-filled
syringe. This does not constitute a sign of deterioration.
The content of the pre-filled syringe should be inspected visually both before and after shaking for any
foreign particulate matter and/or abnormal physical appearance prior to administration. In the event of
either being observed, discard the vaccine.
The vaccine should be allowed to reach room temperature before us e.
The vaccine should be well shaken before use.
Instructions for administration of the vaccine presented in pre-filled syringe
1.
Holding the syringe
barrel
(avoid holding the syringe plunger),
in one hand
unscrew the syringe cap by twisting it anticlockwise.
Syringe plunger
Syringe barrel
Syringe cap
2.
To attach the needle to the syringe,
twist the needle clockwise into the syringe
until you feel it lock.
3.
Remove the needle protector, which on
occasion can be a little stiff.
Needle protector
Any unused product or waste material should be disposed of in accordance with local requirements.
GlaxoSmithKline Biologicals S.A.
Rue de l’Institut 89
B-1330 Rixensart, Belgium
EU/1/09/508/001
EU/1/09/508/002
EU/1/09/508/003
12
EU/1/09/508/004
EU/1/09/508/005
EU/1/09/508/010
Date of first authorisation: 30/03/2009
Detailed information on this medicinal product is available on the website of the European Medicines
Agency http://www.ema.europa.eu/.
13
Synflorix suspension for injection
Pneumococcal polysaccharide
conjugate vaccine (adsorbed)
1 dose (0.5 ml) contains:
Pneumococcal polysaccharide serotype 1
1,2
1 microgram
Pneumococcal polysaccharide serotype 4
1,2
3 micrograms
Pneumococcal polysaccharide serotype 5
1,2
1 microgram
Pneumococcal polysaccharide serotype 6B
1,2
1 microgram
Pneumococcal polysaccharide serotype 7F
1,2
1 microgram
Pneumococcal polysaccharide serotype 9V
1,2
1 microgram
Pneumococcal polysaccharide serotype 14
1,2
1 microgram
Pneumococcal polysaccharide serotype 18C
1,3
3 micrograms
Pneumococcal polysaccharide serotype 19F
1,4
3 micrograms
Pneumococcal polysaccharide serotype 23F
1,2
1 microgram
1
adsorbed on aluminium phosphate 0.5 milligram Al
3+
2
conjugated to protein D (derived from non-typeable
Haemophilus influenzae
) carrier protein
9-16 micrograms
3
conjugated to tetanus toxoid carrier protein
5-10 micrograms
4
conjugated to diphtheria toxoid carrier protein
3-6 micrograms
For a full list of excipients, see section 6.1.
Suspension for injection (injection).
The vaccine is a turbid white suspension.
Active immunisation against invasive disease and acute otitis media caused by
Streptococcus
pneumoniae
in infants and children from 6 weeks up to 2 years of age. See sections 4.4 and 5.1 for
information on protection against specific pneumococcal serotypes.
The use of Synflorix should be determined on the basis of official recommendations taking into
consideration the impact of invasive disease in different age groups as well as the variability of
serotype epidemiology in different geographical areas.
4.2 Posology and method of administr ation
Posology
The immunisation schedules for Synflorix should be based on official recommendations.
Infants from 6 weeks to 6 months of age
14
Three-dose primary series
The recommended immunisation series to ensure optimal protection consists of four doses, each of 0.5
ml. The primary infant series consists of three doses with the first dose usually given at 2 months of
age and with an interval of at least 1 month between doses. The first dose may be given as early as six
weeks of age. A booster dose is recommended at least 6 months after the last priming dose and
preferably between 12 and 15 months of age. (see sections 4.4 and 5.1)
Two-dose primary series
Alternatively, when Synflorix is given as part of a routine infant immunisation programme, a series
consisting of three doses, each of 0.5 ml may be given. The first dose may be administered from the
age of 2 months, with a second dose 2 months later. A booster dose is recommended at least 6 months
after the last primary dose (see section
5.1
).
In preterm infants born after at least 27 weeks of gestational age, the recommended immunisation
series consists of four doses, each of 0.5ml. The primary infant series consists of three doses with the
first dose given at 2 months of age and with an interval of at least 1 month between doses. A booster
dose is recommended at least 6 months after the last primary dose (see sections 4.4 and 5.1).
Previously unvaccinated older infants and children
- infants aged 7-11 months: The vaccination schedule consists of two doses of 0.5 ml with an interval
of at least 1 month between doses. A third dose is recommended in the second year of life with an
interval of at least 2 months between doses.
- children aged 12-23 months: The vaccination schedule consists of two doses of 0.5 ml with an
interval of at least 2 months between doses. The need for a booster dose after this immunisation
schedule has not been established. (see section 4.4)
It is recommended that subjects who receive a first dose of Synflorix complete the full vaccination
course with Synflorix.
Paediatric population
The safety and efficacy of Synflorix in children over 24 months of age have not been established.
Method of administration
The vaccine should be given by intramuscular injection. The preferred sites are anterolateral aspect of
the thigh in infants or the deltoid muscle of the upper arm in young children.
Hypersensitivity to the active substances or to any of the excipients, or to any of the carrier proteins.
As with other vaccines, the administration of Synflorix should be postponed in subjects suffering from
acute severe febrile illness. However, the presence of a minor infection, such as a cold, should not
result in the deferral of vaccination.
As with all injectable vaccines, appropriate medical treatment and supervision should always be
readily available in case of a rare anaphylactic reaction following the administration of the vaccine.
The potential risk of apnoea and the need for respiratory monitoring for 48-72h should be considered
when administering the primary immunisation series to very premature infants (born ≤ 28 weeks of
15
Infants born between 27-36 weeks gestation
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.
Synflorix should under no circumstances be administered intravascularly or intradermally. No data are
available on subcutaneous administration of Synflorix.
As for other vaccines administered intramuscularly, Synflorix should be given with caution to
individuals with thrombocytopenia or any coagulation disorder since bleeding may occur following an
intramuscular administration to these subjects.
Official recommendations for the immunisation against diphtheria, tetanus and
Haemophilus
influenzae
type b should also be followed.
There is insufficient evidence that Synflorix provides protection against pneumococcal serotypes not
contained in the vaccine or against non-typeable
Haemophilus influenzae.
Synflorix does not provide
protection against other micro-organisms.
As with any vaccine, Synflorix may not protect all vaccinated individuals against invasive
pneumococcal disease or otitis media caused by the serotypes in the vaccine. Protection against otitis
media caused by pneumococcal serotypes in the vaccine is expected to be substantially lower than
protection against invasive disease. In addition, as otitis media is caused by many micro-organisms
other than the
Streptococcus pneumoniae
serotypes represented in the vaccine, the overall protection
against otitis media is expected to be limited (see section 5.1)
In clinical trials Synflorix elicited an immune response to all ten serotypes included in the vaccine, but
the magnitude of the responses varied between serotypes. The functional immune response to
serotypes 1 and 5 was lower in magnitude than the response against all other vaccine serotypes. It is
not known whether this lower functional immune response against serotypes 1 and 5 will result in
lower protective efficacy against invasive disease or otitis media caused by these serotypes (see
section 5.1).
Synflorix is indicated for use in children aged from 6 weeks up to 2 years. Children should receive
the dose regimen of Synflorix that is appropriate to their age at the time of commencing the
vaccination series (see section 4.2). Safety and immunogenicity data are not yet available in children
above 2 years of age.
Children with impaired immune responsiveness, whether due to the use of immunosuppressive
therapy, a genetic defect, HIV infection, or other causes, may have reduced antibody response to
vaccination.
Safety and immunogenicity data in children with increased risk for pneumococcal infections (e.g.
sickle cell disease, congenital and acquired splenic dysfunction, HIV-infected, malignancy, nephrotic
syndrome) are not yet available for Synflorix. Vaccination in high-risk groups should be considered on
an individual basis (see section 4.2).
The immune response elicited after two doses of Synflorix in children 12-23 months of age is
comparable to the response elicited after three doses in infants (see section 5.1). The immune response
to a booster dose after two doses in children aged 12-23 months has not been evaluated, but a booster
dose may be needed to ensure optimal individual protection.
However, a 2-dose schedule in children aged 12-23 months with high risk of pneumococcal disease
(such as children with sickle-cell disease, asplenia, HIV infection, chronic illness or who are
immunocompromised) may not be sufficient to provide optimal protection. In these children, a 23-
valent pneumococcal polysaccharide vaccine should be given
16
≥ 2 years of age, whenever
recommended. The interval between the pneumococcal conjugate vaccine (Synflorix) and the 23-
valent pneumococcal polysaccharide vaccine should not be less than 8 weeks. There are no data
available to indicate whether the administration of pneumococcal polysaccharide vaccine to Synflorix
primed children may result in hyporesponsiveness to further doses of pneumococcal polysaccharide or
to pneumococcal conjugate vaccine.
Prophylactic administration of antipyretics before or immediately after vaccine administration can
reduce the incidence and intensity of post-vaccination febrile reactions. However, data suggest that the
prophylactic use of paracetamol might reduce the immune response to Synflorix. The clinical
relevance of this observation, as well as the impact of antipyretics other than paracetamol on the
immune response to Synflorix remains unknown.
The us e of prophylactic antipyretic medicinal products is recommended:
-
for all children receiving Synflorix simultaneously with vaccines containing whole cell pertussis
because of higher rate of febrile reactions (see section 4.8).
-
for children with seizure disorders or with a prior history of febrile seizures.
Antipyretic treatment should be initiated according to local treatment guidelines.
Use with other vaccines
Synflorix can be given concomitantly with any of the following monovalent or combination vaccines
[including DTPa-HBV-IPV/Hib and DTPw-HBV/Hib]: diphtheria-tetanus-acellular pertussis vaccine
(DTPa), hepatitis B vaccine (HBV), inactivated polio vaccine (IPV),
Haemophilus influenzae
type b
vaccine (Hib), diphtheria-tetanus-whole cell pertussis vaccine (DTPw), measles-mumps-rub ella
vaccine (MMR), varicella vaccine (V), meningococcal serogroup C conjugate vaccine (CRM
197
and
TT conjugates), oral polio vaccine (OPV) and oral rotavirus vaccine. Different injectable vaccines
should always be given at different injection sites.
Clinical studies demonstrated that the immune responses and the safety profiles of the co-administered
vaccines were unaffected, with the exception of the inactivated poliovirus type 2 response, for which
inconsistent results were observed across studies (seroprotection ranging from 78% to 100%). The
clinical relevance of this observation is not known. No negative interference was observed with
meningococcal conjugate vaccines irrespective of the carrier protein (CRM
197
and TT conjugates).
Enhancement of antibody response to Hib-TT conjugate, diphtheria and tetanus antigens was
observed.
Use with systemic immunosuppressive medicinal products
As with other vaccines, it may be expected that in patients receiving immunosuppressive treatment an
adequate response may not be elicited.
Use with prophylactic administration of antipyretics
See section 4.4.
Synflorix is not intended for use in adults. Human data on the use during pregnancy or lactation and
animal reproduction studies are not available.
Not relevant.
Clinical trials involved the administration of 12,879 doses of Synflorix to 4,595 healthy children and
137 preterm infants as primary vaccination. Furthermore, 3,870 children and 116 preterm infants
17
received a booster dose of Synflorix in the second year of life. In all trials, Synflorix was
administered concurrently with the recommended childhood vaccines.
The most common adverse reactions observed after primary vaccination were redness at the
injection site and irritability which occurred after 38.3% and 52.3% of all doses respectively.
Following booster vaccination, these adverse reactions occurred at 52.6% and 55.4% respectively.
The majority of these reactions were of mild to moderate severity and were not long lasting.
No increase in the incidence or severity of the adverse reactions was seen with subsequent doses of
the primary vaccination series.
An increase in reactogenicity was reported after booster vaccination compared to the doses of the
primary course with Synflorix.
Reactogenicity was higher in children receiving whole cell pertussis vaccines concomitantly. In a
clinical study children received either Synflorix (N=603) or 7-valent Prevenar (N=203) concomitantly
with a DTPw containing vaccine. After the primary vaccination course, fever ≥38°C and >39°C was
reported respectively in 86.1% and 14.7% of children receiving Synflorix and in 82.9% and 11.6% of
children vaccinated with 7-valent Prevenar.
In comparative clinical studies, the incidence of local and general adverse events reported within 4
days after each vaccination dose was within the same range as after vaccination with 7-valent
Prevenar.
Adverse reactions (following primary immunisation or booster dose) considered as being at least
possibly related to vaccination have been categorised by frequency.
Frequencies are reported as:
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 common: drowsiness
Rare: febrile and non-febrile convulsions
Respiratory, thoracic and mediastinal disorders
Uncommon: apnoea in very premature infants (≤28 weeks of gestation) (see section 4.4)
Gastro-intestinal disorders
Uncommon: diarrhoea, vomiting
Skin and subcutaneous tissue disorders
Metabolism and nutrition disorders
Very common: appetite lost
General disorders and administration site conditions
Very common: pain, redness, swelling at the injection site, fever (≥38°C rectally)
Common: injection site induration, fever (>39°C rectally)
Uncommon: injection site haematoma, haemorrhage and nodule, fever (>40°C rectally)*
Immune system disorders
Rare: allergic reactions (such as allergic dermatitis, atopic dermatitis, eczema)
18
Nervous system disorders
Rare: rash, urticaria
Psychiatric disorders
Very common: irritability
Uncommon: crying abnormal
*reported following booster vaccination
No case of overdose has been reported.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: pneumococcal vaccines, ATC code: J07AL52
Epidemiological data
The 10 pneumococcal serotypes included in this vaccine repr esent the major disease-causing serotypes
in Europe covering approximately 56% to 90% of invasive pneumococcal disease (IPD) in children <5
years of age. In this age group, serotypes 1, 5 and 7F account for 3.3% to 24.1% of IPD depending on
the country and time period studied.
Acute otitis media (AOM) is a common childhood disease with different aetiologies.
Bacteria can be
responsible for 60-70% of clinical episodes of AOM.
Streptococcus pneumoniae
and Non-Typeable
Haemophilus influenzae
(NTHi) are the most common causes of bacterial AOM worldwide.
1. Invasive pneumococcal disease
(which includes sepsis, meningitis, bacteraemic pneumonia and
The protective efficacy of Synflorix against IPD has not been studied. As recommended by WHO, the
assessment of potential efficacy against IPD has been based on a comparison of immune responses to
the seven serotypes shared between Synflorix and another pneumococcal conjugate vaccine for which
protective efficacy was evaluated previously (i.e. 7-valent Prevenar). Immune responses to the extra
three serotypes in Synflorix have also been measured.
In a head-to-head comparative trial with 7-valent Prevenar, non inferiority of the immune response to
Synflorix measured by ELISA was demonstrated for all serotypes, except for 6B and 23F (upper limit
of the 96.5% CI around the difference between groups >10%) (Table 1). For serotypes 6B and 23F,
respectively, 65.9% and 81.4% of infants vaccinated at 2, 3 and 4 months reached the antibody
threshold (i.e. 0.20 µg/ml) one month after the third dose of Synflorix versus 79.0% and 94.1%
respectively, after three doses of 7-valent Prevenar. The clinical relevance of these differences is not
known.
The percentage of vaccinees reaching the threshol d for the three additional serotypes in Synflorix (1, 5
and 7F) was respectively 97.3%, 99.0% and 99.5% and was at least as good as the aggregate 7-valent
Prevenar response against the 7 common serotypes (95.8%).
Table 1: Comparative analysis between 7-valent Prevenar and Synflorix in percentage of
subjects with antibody concentrations
>
0.20 µg/ml one month post-dose 3
Antibody
SYNFLORIX
7-VALENT PREVENAR
Difference in %
≥
0.20
µ
g/ml (7-VALENT
PREVENAR minus SYNFLORIX)
N
%
N
%
%
96.5%CI
Anti-4
1106
97.1
373
100
2.89
1.71
4.16
Anti-6B
1100
65.9
372
79.0
13.12
7.53
18.28
Anti-9V
1103
98.1
374
99.5
1.37
-0.28
2.56
19
bacteraemia)
Anti-14
1100
99.5
374
99.5
-0.08
-1.66
0.71
Anti-18C
1102
96.0
374
98.9
2.92
0.88
4.57
Anti-19F
1104
95.4
375
99.2
3.83
1.87
5.50
Anti-23F
1102
81.4
374
94.1
12.72
8.89
16.13
Post-primary antibody geometric mean concentrations (GMCs) elicited by Synflorix against the seven
serotypes in common were lower than those elicited by 7-valent Prevenar. Pre-booster GMCs (8 to 12
months after the last primary dose) were generally similar for the two vaccines. After the booster dose
the GMCs elicited by Synflorix were lower for most serotypes in common with 7-valent Prevenar.
In the same study, Synflorix was shown to elicit functional antibodies to all vaccine serotypes. For
each of the seven serotypes in common, 87.7% to 100% of Synflorix vaccinees and 92.1% to 100% of
7-valent Prevenar vaccinees reached an OPA titre ≥ 8 one month after the third dose. The difference
between both vaccines in terms of percentage of subjects with OPA titres ≥ 8 was <5% for all
serotypes in common, including 6B and 23F. Post-primary and post-booster OPA antibody geometric
mean titres (GMTs) elicited by Synflorix were lower than those elicited by 7-valent Prevenar for the
seven shared serotypes, except for serotype 19F.
For serotypes 1, 5 and 7F, the percentages of Synflorix vaccinees reaching an OPA titre ≥ 8 were
respectively 65.7%, 90.9% and 99.6% after the primary vaccination course and 91.0%, 96.3% and
100% after the booster dose. The OPA response for serotypes 1 and 5 was lower in magnitude than the
response for each of the other serotypes. The implications of these findings for protective efficacy are
not known. The response to serotype 7F was in the same range as for the seven serotypes in common
between the two vaccines.
The administration of a fourth dose (booster dose) in the second year of life elicited an anamnestic
antibody response as measured by ELISA and OPA for the 10 serotypes included in the vaccine
demonstrating the induction of immune memory after the three-dose primary course.
2. Acute Otitis Media (AOM)
In a large randomised double-blind Pneumococcal Otitis Media Efficacy Trial (POET) conducted in
the Czech Repub lic and in Slovakia, 4,968 infants received an 11-valent investigational vaccine
(11Pn-PD) containing the 10 serotypes of Synflorix (along with serotype 3 for which efficacy was not
demonstrated) or a control vaccine (hepatitis A vaccine) according to a 3, 4, 5 and 12-15 months
vaccination schedule.
Efficacy of the 11 Pn-PD vaccine against the first occurrence of vaccine-serotype AOM episode was
52.6% (95% CI: 35.0;65.5). Serotype specific efficacy against the first AOM episode was
demonstrated for serotypes 6B (86.5%, 95%CI: 54.9;96.0), 14 (94.8%, 95% CI: 61.0;99.3), 19F
(43.3%, 95% CI:6.3;65.4) and 23F (70.8%, 95% CI: 20.8;89.2). For other vaccine serotypes, the
number of AOM cases was too limited to allow any efficacy conclusion to be drawn. Efficacy against
any AOM episode due to any pneumococcal serotype was 51.5% (95% CI: 36.8;62.9). No increase in
the incidence of AOM due to other bacterial pathogens or non-vaccine serotypes was observed in this
study. The estimated vaccine efficacy against any clinical episodes of otitis media regardless of
aetiology was 33.6% (95% CI: 20.8; 44.3).
Based on immunological bridging of the functional vaccine response (OPA) of Synflorix with the 11-
valent formulation used within POET, it is expected that Synflorix provides similar protective efficacy
against pneumococcal AOM.
3. Additional immunogenicity data
Infants from 6 weeks to 6 months of age
3-dose primary schedule
20
In total eight studies, conducted in various countries across Europe, in Chile and in the Philippines,
have evaluated the immunogenicity of Synflorix after a three-dose primary series (N=3,089) according
to different vaccination schedules (6-10-14 weeks, 2-3-4, 3-4-5 or 2-4-6 months of age). A fourth
(booster) dose was given in six clinical studies to 1,976 subjects. In general, comparable vaccine
responses were observed for the different schedules, although somewhat higher immune responses
were noted for the 2-4-6 month schedule.
2-dose primary schedule
The immunogenicity of Synflorix following a 2-dose primary vaccination schedule in subjects less
than 6 months of age was evaluated in two clinical studies.
In the first study, in a post-hoc analysis, the immunogenicity two months after the second dose of
Synflorix was compared with 7-valent Prevenar and the percentages of subjects with ELISA antibody
concentration ≥ 0.2 µg/ml were within the same range for each of the serotypes common to both
vaccines with the exception of serotypes 6B (64.1% for Synflorix and 30.7% for 7-valent Prevenar)
and 18C (87.1% for Synflorix and 97.6% for 7-valent Prevenar). Antibody GMCs were similar in both
groups, with the exception of some serotypes for which responses were higher (6B) or lower (4, 9V
and 18C) in the Synflorix group. Similarly, the percentage of subjects reaching OPA titres ≥ 8 and the
OPA GMTs two months post dose 2 was within the same range for each of the serotypes common to
both vaccines, with the exception of 6B and 19F for which responses were higher in the Synflorix
group.
In the second study, the immunogenicity after two or three doses of Synflorix was compared.
Although there was no significant difference between the two groups in the percentages of subjects
with antibody concentration ≥ 0.20 µg/mL (ELISA), the percentages of subjects for serotypes 6B and
23F were lower than for the other serotypes (Table 2 and Table 3). The percentage of subjects with
OPA titres ≥ 8 in 2-dose primed subjects compared to 3-dose primed subjects were lower for serotypes
6B, 18C and 23F (74.4%, 82.8%, 86.3% respectively for the 2-dose schedule and 88.9%, 96.2%,
97.7% respectively for the 3-dose schedule). Overall, the persistence of the immune response until the
booster at 11 months of age
was lower in the 2-dose primed subjects. In both schedules, a booster
response indicative of immunological priming was observed for each serotype (Table 2 and Table 3).
After the booster dose a lower percentage of subjects with OPA titres ≥ 8 was observed in the 2-dose
schedule for serotypes 5 (87.2% versus 97.5% for the 3-dose primed subjects) and 6B (81.1% versus
90.3%), all other responses were comparable.
Table 2: Percentage of 2-dose primed subjects with antibody concentrations ≥ 0.20 µg/ml one
month post-primary and one month post-booster
≥0.2µg/mL (ELISA)
Antibody
Post-primary
Post-booster
%
95% CI
%
95%CI
Anti-1
97.4
93.4
99.3
99.4
96.5
100
Anti-4
98.0
94.4
99.6
100
97.6
100
Anti-5
96.1
91.6
98.5
100
97.6
100
Anti-6B
55.7
47.3
63.8
88.5
82.4
93.0
Anti-7F
96.7
92.5
98.9
100
97.7
100
Anti-9V
93.4
88.2
96.8
99.4
96.5
100
Anti-14
96.1
91.6
98.5
99.4
96.5
100
Anti-18C
96.1
91.6
98.5
100
97.7
100
Anti-19F
92.8
87.4
96.3
96.2
91.8
98.6
Anti-23F
69.3
61.3
76.5
96.1
91.7
98.6
Table 3: Percentage of 3-dose primed subjects with antibody concentrations ≥ 0.20 µg/ml one
month post-primary and one month post-booster
Antibody
≥0.2µg/mL (ELISA)
21
Post-primary
Post-booster
%
95% CI
%
95%CI
Anti-1
98.7
95.3
99.8
100
97.5
100
Anti-4
99.3
96.4
100
100
97.5
100
Anti-5
100
97.6
100
100
97.5
100
Anti-6B
63.1
54.8
70.8
96.6
92.2
98.9
Anti-7F
99.3
96.4
100
100
97.5
100
Anti-9V
99.3
96.4
100
100
97.5
100
Anti-14
100
97.6
100
98.6
95.2
99.8
Anti-18C
99.3
96.4
100
99.3
96.3
100
Anti-19F
96.1
91.6
98.5
98.0
94.2
99.6
Anti-23F
77.6
70.2
84.0
95.9
91.3
98.5
In the follow-up of the second study, the persistence of antibodies at 36-46 months of age was
demonstrated in subjects that had received a 2-dose primary series followed by a booster dose with at
least 83.7% of subjects remaining seropositive for vaccine serotypes. In subjects that had received a 3-
dose primary series followed by a booster dose, at least 96.5 % of the subjects remained seropositive
for vaccine serotypes. A single dose of Synflorix, administered during the 4th year of life, as a
challenge dose, elicited similar ELISA antibody GMCs when measured 7-10 days after challenge in 2-
dose primed subjects and 3-dose primed sub jects. These levels were higher than those seen after
challenge of unprimed subjects. The fold increase in ELISA antibody GMCs and OPA GMTs, pre to
post vaccination, was also similar in 2-dose primed subjects to that in 3-dose primed subjects. These
results are indicative of immunological memory in primed subjects for all vaccine serotypes.
The clinical consequences of the lower post-primary and post-booster immune responses observed
after the two-dose primary schedule are not known.
Previously unvaccinated older infants and children
One clinical study evaluated vaccination in children 7-11 months of age and 12-23 months of age. In
the 7-11 months group, children received 2 primary doses followed by a booster dose in the second
year of life. The immune responses after the booster dos e of Synflorix in this age group were generally
similar to those observed after the booster dose in infants who had been primed with 3 doses below 6
months of age.
The immune response elicited after two doses of Synflorix in children 12-23 months of age was
comparable to the response elicited after three doses in infants, except for 18C and 19F for which
responses were higher in the 12-23 months children. The need for a booster dose after two doses in
children aged 12-23 months has not been established.
Long-term persistence of antibodies has not been investigated after administration of a primary series
in infants plus booster or after a two-dose priming in older children.
In a clinical study, it has been demonstrated that Synflorix can be safely administered as a booster
dose in the second year of life to children who had received 3 primary doses of 7-valent Prevenar.
This study has shown that the immune responses against the 7 common serotypes were comparable to
those elicited by a booster dose of 7-valent Prevenar. However, children who received 7-valent
Prevenar for the primary series would not be primed against the additional serotypes contained in
Synflorix (1, 5, 7F). Therefore the degree and duration of protection against invasive pneumococcal
disease and otitis media due to these three serotypes in children of this age group following a single
dose of Synflorix cannot be predicted.
4. Immunogenicity data in preterm infants
Immunogenicity of Synflorix in very preterm (gestation period of 27-30 weeks) (N=42), preterm
(gestation period of 31-36 weeks) (N=82) and full term (gestation period > 36 weeks) (N=132) infants
was evaluated following a 3 dose primary vaccination course at 2, 4, 6 months of age. Immunogenicity
22
following a fourth dose (booster dose) at 15 to 18 months of age was evaluated in 44 very preterm, 69
preterm and 127 full term infants.
One month after primary vaccination (i.e. after the third dose), at least 92.7% of subjects achieved
ELISA antibody concentrations ≥ 0.2 µg/ml and at least 81.7% achieved OPA titres ≥ 8 for all vaccine
serotypes, except serotype 1 (at least 58. 8% with OPA titres ≥ 8). Similar antibody GMCs and OPA
GMTs were observed for all infants except lower antibody GMCs for serotypes 4, 5 and 9V in very
preterms and serotype 9V in preterms and lower OPA GMT for serotype 5 in very preterms. The
clinical relevance of these differences is not known.
One month after the booster dose increases of ELISA antibody GMCs and OPA GMTs were seen for
all serotypes, indicative of immunological memory. Similar antibody GMCs and OPA GMTs were
observed for all infants except a lower OPA GMT for serotype 5 in very preterm infants. Overall, at
least 97.6% of subjects achieved ELISA antibody concentrations≥ 0.2µg/ml and at least 91.9%
achieved OPA titres ≥ 8 for all vaccine serotypes.
5.2 Pharmacokinetic properties
Evaluation of pharmacokinetic properties is not available for vaccines.
5.3 Preclinical safety data
Studies with an 11-valent vaccine formulation representative for Synflorix revealed no special hazard
for humans based on conventional studies of safety pharmacology, single and repeated dose toxicity.
6.1 List of excipients
Sodium chloride
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 vial (type I glass) with a stopper (butyl rubber). Pack size of 1, 10 or 100.
Not all pack sizes may be marketed.
23
6.6 Special precautions for disposal and other handling
A fine white deposit with a clear colourless supernatant may be observed upon storage of the vial. This
does not constitute a sign of deterioration.
The content of the vial should be inspected visually both before and after shaking for any foreign
particulate matter and/or abnormal physical appearance prior to administration. In the event of either
being observed, discard the vaccine.
The vaccine should be allowed to reach room temperature before us e.
The vaccine should be well shaken before use.
Any unused product or waste material should be disposed of in accordance with local requirements.
GlaxoSmithKline Biologicals S.A.
Rue de l’Institut 89
B-1330 Rixensart, Belgium
EU/1/09/508/006
EU/1/09/508/007
EU/1/09/508/008
Date of first authorisation: 30/03/2009
Detailed information on this medicinal product is available on the website of the European Medicines
Agency http://www.ema.europa.eu/.
24
Synflorix suspension for injection in multidose container
Pneumococcal polysaccharide
conjugate vaccine (adsorbed)
1 dose (0.5 ml) contains:
Pneumococcal polysaccharide serotype 1
1,2
1 microgram
Pneumococcal polysaccharide serotype 4
1,2
3 micrograms
Pneumococcal polysaccharide serotype 5
1,2
1 microgram
Pneumococcal polysaccharide serotype 6B
1,2
1 microgram
Pneumococcal polysaccharide serotype 7F
1,2
1 microgram
Pneumococcal polysaccharide serotype 9V
1,2
1 microgram
Pneumococcal polysaccharide serotype 14
1,2
1 microgram
Pneumococcal polysaccharide serotype 18C
1,3
3 micrograms
Pneumococcal polysaccharide serotype 19F
1,4
3 micrograms
Pneumococcal polysaccharide serotype 23F
1,2
1 microgram
1
adsorbed on aluminium phosphate 0.5 milligram Al
3+
2
conjugated to protein D (derived from non-typeable
Haemophilus influenzae
) carrier protein
9-16 micrograms
3
conjugated to tetanus toxoid carrier protein
5-10 micrograms
4
conjugated to diphtheria toxoid carrier protein
3-6 micrograms
This is a multidose container. See section 6.5 for the number of doses per vial.
For a full list of excipients, see section 6.1.
Suspension for injection (injection).
The vaccine is a turbid white suspension.
Active immunisation against invasive disease and acute otitis media caused by
Streptococcus
pneumoniae
in infants and children from 6 weeks up to 2 years of age. See sections 4.4 and 5.1 for
information on protection against specific pneumococcal serotypes.
The use of Synflorix should be determined on the basis of official recommendations taking into
consideration the impact of invasive disease in different age groups as well as the variability of
serotype epidemiology in different areas.
4.2 Posology and method of administr ation
Posology
The immunisation schedules for Synflorix should be based on official recommendations.
25
Infants from 6 weeks to 6 months of age
Three-dose primary series
The recommended immunisation series to ensure optimal protection consists of four doses, each of 0.5
ml. The primary infant series consists of three doses with the first dose usually given at 2 months of
age and with an interval of at least 1 month between doses. The first dose may be given as early as six
weeks of age. A booster dose is recommended at least 6 months after the last priming dose and
preferably between 12 and 15 months of age. (see sections 4.4 and 5.1)
Two-dose primary series
Alternatively, when Synflorix is given as part of a routine infant immunisation programme, a series
consisting of three doses, each of 0.5 ml may be given. The first dose may be administered from the
age of 2 months, with a second dose 2 months later. A booster dose is recommended at least 6 months
after the last primary dose (see section
5.1
).
Infants born between 27-36 weeks gestation
In preterm infants born after at least 27 weeks of gestational age, the recommended immunisation
series consists of four doses, each of 0.5ml. The primary infant series consists of three doses with the
first dose given at 2 months of age and with an interval of at least 1 month between doses. A booster
dose is recommended at least 6 months after the last primary dose (see sections 4.4 and 5.1).
Previously unvaccinated older infants and children
- infants aged 7-11 months: The vaccination schedule consists of two doses of 0.5 ml with an interval
of at least 1 month between doses. A third dose is recommended in the second year of life with an
interval of at least 2 months between doses.
- children aged 12-23 months: The vaccination schedule consists of two doses of 0.5 ml with an
interval of at least 2 months between doses. The need for a booster dose after this immunisation
schedule has not been established. (see section 4.4)
It is recommended that subjects who receive a first dose of Synflorix complete the full vaccination
course with Synflorix.
Paediatric population
The safety and efficacy of Synflorix in children over 24 months of age have not been established.
Method of administration
The vaccine should be given by intramuscular injection. The preferred sites are anterolateral aspect of
the thigh in infants or the deltoid muscle of the upp er arm in young children.
4.3
Hypersensitivity to the active substances or to any of the excipients, or to any of the carrier proteins.
As with other vaccines, the administration of Synflorix should be postponed in subjects suffering from
acute severe febrile illness. However, the presence of a minor infection, such as a cold, should not
result in the deferral of vaccination.
As with all injectable vaccines, appropriate medical treatment and supervision should always be
readily available in case of a rare anaphylactic reaction following the administration of the vaccine.
26
The potential risk of apnoea and the need for respiratory monitoring for 48-72h 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.
Synflorix should under no circumstances be administered intravascularly or intradermally. No data are
available on subcutaneous administration of Synflorix.
As for other vaccines administered intramuscularly, Synflorix should be given with caution to
individuals with thrombocytopenia or any coagulation disorder since bleeding may occur following an
intramuscular administration to these subjects.
Official recommendations for the immunization against diphtheria, tetanus and
Haemophilus
influenzae
type b should also be followed.
There is insufficient evidence that Synflorix provides protection against pneumococcal serotypes not
contained in the vaccine or against non-typeable
Haemophilus influenzae
. Synflorix does not provide
protection against other micro-organisms.
As with any vaccine, Synflorix may not protect all vaccinated individuals against invasive
pneumococcal disease or otitis media caused by the serotypes in the vaccine. Protection against otitis
media caused by pneumococcal serotypes in the vaccine is expected to be substantially lower than
protection against invasive disease. In addition, as otitis media is caused by many micro-organisms
other than the
Streptococcus pneumoniae
serotypes represented in the vaccine, the overall protection
against otitis media is expected to be limited (see section 5.1)
In clinical trials Synflorix elicited an immune response to all ten serotypes included in the vaccine, but
the magnitude of the responses varied between serotypes. The functional immune response to
serotypes 1 and 5 was lower in magnitude than the responses against all other vaccine serotypes. It is
not known whether this lower functional immune response against serotypes 1 and 5 will result in
lower protective efficacy against invasive disease or otitis media caused by these serotypes (see
section 5.1).
Synflorix is indicated for use in children aged from 6 weeks up to 2 years. Children should receive
the dose regimen of Synflorix that is appropriate to their age at the time of commencing the
vaccination series (see section 4.2). Safety and immunogenicity data are not yet available in children
above 2 years of age.
Children with impaired immune responsiveness, whether due to the use of immunosuppressive
therapy, a genetic defect, HIV infection, or other causes, may have reduced antibody response to
vaccination.
Safety and immunogenicity data in children with increased risk for pneumococcal infections (e.g.
sickle cell disease, congenital and acquired splenic dysfunction, HIV-infected, malignancy, nephrotic
syndrome) are not yet available for Synflorix. Vaccination in high-risk groups should be considered on
an individual basis (see section 4.2).
The immune response elicited after two doses of Synflorix in children 12-23 months of age is
comparable to the response elicited after three doses in infants (see section 5.1). The immune response
to a booster dose after two doses in children aged 12-23 months has not been evaluated, but a booster
dose may be needed to ensure optimal individual protection.
However, a 2-dose schedule in children aged 12-23 months with high risk of pneumococcal disease
(such as children with sickle-cell disease, asplenia, HIV infection, chronic illness or who are
immunocompromised) may not be sufficient to provide optimal protection. In these children, a 23-
valent pneumococcal polysaccharide vaccine should be given
27
≥ 2 years of age, whenever
recommended. The interval between the pneumococcal conjugate vaccine (Synflorix) and the 23-
valent pneumococcal polysaccharide vaccine should not be less than 8 weeks. There are no data
available to indicate whether the administration of pneumococcal polysaccharide vaccine to Synflorix
primed children may result in hyporesponsiveness to further doses of pneumococcal polysaccharide or
to pneumococcal conjugate vaccine.
Prophylactic administration of antipyretics before or immediately after vaccine administration can
reduce the incidence and intensity of post-vaccination febrile reactions. However, data suggest that the
prophylactic use of paracetamol might reduce the immune response to Synflorix. The clinical
relevance of this observation, as well as the impact of antipyretics other than paracetamol on the
immune response to Synflorix remains unknown.
The us e of prophylactic antipyretic medicinal products is recommended:
-
for all children receiving Synflorix simultaneously with vaccines containing whole cell pertussis
because of higher rate of febrile reactions (see section 4.8).
-
for children with seizure disorders or with a prior history of febrile seizures.
Antipyretic treatment should be initiated according to local treatment guidelines.
Use with other vaccines
Synflorix can be given concomitantly with any of the following monovalent or combination vaccines
[including DTPa-HBV-IPV/Hib and DTPw-HBV/Hib]: diphtheria-tetanus-acellular pertussis vaccine
(DTPa), hepatitis B vaccine (HBV), inactivated polio vaccine (IPV),
Haemophilus influenzae
type b
vaccine (Hib), diphtheria-tetanus-whole cell pertussis vaccine (DTPw), measles-mumps-rub ella
vaccine (MMR), varicella vaccine (V), meningococcal serogroup C conjugate vaccine (CRM
197
and
TT conjugates), oral polio vaccine (OPV) and oral rotavirus vaccine. Different injectable vaccines
should always be given at different injection sites.
Clinical studies demonstrated that the immune responses and the safety profiles of the co-administered
vaccines were unaffected, with the exception of the inactivated poliovirus type 2 response, for which
inconsistent results were observed across studies (seroprotection ranging from 78% to 100%). The
clinical relevance of this observation is not known. No negative interference was observed with
meningococcal conjugate vaccines irrespective of the carrier protein (CRM
197
and TT conjugates).
Enhancement of antibody response to Hib-TT conjugate, diphtheria and tetanus antigens was
observed.
Use with systemic immunosuppressive medicinal products
As with other vaccines, it may be expected that in patients receiving immunosuppr essive treatment an
adequate response may not be elicited.
Use with prophylactic administration of antipyretics
See section 4.4.
Synflorix is not intended for use in adults. Human data on the use during pregnancy or lactation and
animal reproduction studies are not available.
Not relevant.
28
Clinical trials involved the administration of 12,879 doses of Synflorix to 4,595 healthy children and
137 preterm infants as primary vaccination. Furthermore, 3,870 children and 116 preterm infants
received a booster dose of Synflorix in the second year of life. In all trials, Synflorix was
administered concurrently with the recommended childhood vaccines.
The most common adverse reactions obs erved after primary vaccination were redness at the
injection site and irritability which occurred after 38.3% and 52.3% of all doses respectively.
Following booster vaccination, these adverse reactions occurred at 52.6% and 55.4% respectively.
The majority of these reactions were of mild to moderate severity and were not long lasting.
No increase in the incidence or severity of the adverse reactions was seen with subsequent doses of
the primary vaccination series.
An increase in reactogenicity was reported after booster vaccination compared to the doses of the
primary course with Synflorix.
Reactogenicity was higher in children receiving whole cell pertussis vaccines concomitantly. In a
clinical study children received either Synflorix (N=603) or 7-valent Prevenar (N=203) concomitantly
with a DTPw containing vaccine. After the primary vaccination course, fever ≥38°C and >39°C was
reported respectively in 86.1% and 14.7% of children receiving Synflorix and in 82.9% and 11.6% of
children vaccinated with 7-valent Prevenar.
In comparative clinical studies, the incidence of local and general adverse events reported within 4
days after each vaccination dose was within the same range as after vaccination with 7-valent
Prevenar.
Adverse reactions (following primary immunisation or booster dose) considered as being at least
possibly related to vaccination have been categorised by frequency.
Frequencies are reported as:
Very common: (≥ 1/10)
Common:
(≥1/1,000 to <1/100)
Rare:
(≥1/10,000 to <1/1,000)
Nervous system disorders
Rare: febrile and non-febrile convulsions
Uncommon: apnoea in very premature infants (≤28 weeks of gestation) (see section 4.4)
Gastro-intestinal disorders
Uncommon: diarrhoea, vomiting
Skin and subcutaneous tissue disorders
Metabolism and nutrition disorders
General disorders and administration site conditions
Very common: pain, redness, swelling at the injection site, fever (≥38°C rectally)
Common: injection site induration, fever (>39°C rectally)
Uncommon: injection site haematoma, haemorrhage and nodule, fever (>40°C rectally)*
Immune system disorders
29
Uncommon:
(≥1/100 to <1/10)
Very common: drowsiness
Respiratory, thoracic and mediastinal disorders
Rare: rash, urticaria
Very common: appetite lost
Rare: allergic reactions (such as allergic dermatitis, atopic dermatitis, eczema)
Very common: irritability
Uncommon: crying abnormal
*reported following booster vaccination
No case of overdose has been reported.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: pneumococcal vaccines, ATC code: J07AL52
Epidemiological data
The 10 pneumococcal serotypes included in this vaccine repr esent the major disease-causing serotypes
in Europe covering approximately 56% to 90% of invasive pneumococcal disease (IPD) in children <5
years of age. In this age group, serotypes 1, 5 and 7F account for 3.3% to 24.1% of IPD depending on
the country and time period studied.
Acute otitis media (AOM) is a common childhood disease with different aetiologies.
Bacteria can be
responsible for 60-70% of clinical episodes of AOM.
Streptococcus pneumoniae
and Non-Typeable
Haemophilus influenzae
(NTHi) are the most common causes of bacterial AOM worldwide.
1. Invasive pneumococcal disease
(which includes sepsis, meningitis, bacteraemic pneumonia and
bacteraemia)
The protective efficacy of Synflorix against IPD has not been studied. As recommended by WHO, the
assessment of potential efficacy against IPD has been based on a comparison of immune responses to
the seven serotypes shared between Synflorix and another pneumococcal conjugate vaccine for which
protective efficacy was evaluated previously (i.e. 7-valent Prevenar). Immune responses to the extra
three serotypes in Synflorix have also been measured.
In a head-to-head comparative trial with 7-valent Prevenar, non inferiority of the immune response to
Synflorix measured by ELISA was demonstrated for all serotypes, except for 6B and 23F (upper limit
of the 96.5% CI around the difference between groups >10%) (Table 1). For serotypes 6B and 23F,
respectively, 65.9% and 81.4% of infants vaccinated at 2, 3 and 4 months reached the antibody
threshold (i.e. 0.20 µg/ml) one month after the third dose of Synflorix versus 79.0% and 94.1%
respectively, after three doses of 7-valent Prevenar. The clinical relevance of these differences is not
known.
The percentage of vaccinees reaching the threshol d for the three additional serotypes in Synflorix (1, 5
and 7F) was respectively 97.3%, 99.0% and 99.5% and was at least as good as the aggregate 7-valent
Prevenar response against the 7 common serotypes (95.8%).
Table 1: Comparative analysis between 7-valent Prevenar and Synflorix in percentage of
subjects with antibody concentrations
>
0.20 µg/ml one month post-dose 3
Antibody
SYNFLORIX
7-VALENT PREVENAR
Difference in %
≥
0.20
µ
g/ml (7-VALENT
PREVENAR minus SYNFLORIX)
N
%
N
%
%
96.5%CI
30
Psychiatric disorders
Anti-4
1106
97.1
373
100
2.89
1.71
4.16
Anti-6B
1100
65.9
372
79.0
13.12
7.53
18.28
Anti-9V
1103
98.1
374
99.5
1.37
-0.28
2.56
Anti-14
1100
99.5
374
99.5
-0.08
-1.66
0.71
Anti-18C
1102
96.0
374
98.9
2.92
0.88
4.57
Anti-19F
1104
95.4
375
99.2
3.83
1.87
5.50
Anti-23F
1102
81.4
374
94.1
12.72
8.89
16.13
Post-primary antibody geometric mean concentrations (GMCs) elicited by Synflorix against the seven
serotypes in common were lower than those elicited by 7-valent Prevenar. Pre-booster GMCs (8 to 12
months after the last primary dose) were generally similar for the two vaccines. After the booster dose
the GMCs elicited by Synflorix were lower for most serotypes in common with 7-valent Prevenar.
In the same study, Synflorix was shown to elicit functional antibodies to all vaccine serotypes. For
each of the seven serotypes in common, 87.7% to 100% of Synflorix vaccinees and 92.1% to 100% of
7-valent Prevenar vaccinees reached an OPA titre ≥ 8 one month after the third dose. The difference
between both vaccines in terms of percentage of subjects with OPA titres ≥ 8 was <5% for all
serotypes in common, including 6B and 23F. Post-primary and post-booster OPA antibody geometric
mean titres (GMTs) elicited by Synflorix were lower than those elicited by 7-valent Prevenar for the
seven shared serotypes, except for serotype 19F.
For serotypes 1, 5 and 7F, the percentages of Synflorix vaccinees reaching an OPA titre ≥ 8 were
respectively 65.7%, 90.9% and 99.6% after the primary vaccination course and 91.0%, 96.3% and
100% after the booster dose. The OPA response for serotypes 1 and 5 was lower in magnitude than the
response for each of the other serotypes. The implications of these findings for protective efficacy are
not known. The response to serotype 7F was in the same range as for the seven serotypes in common
between the two vaccines.
The administration of a fourth dose (booster dose) in the second year of life elicited an anamnestic
antibody response as measured by ELISA and OPA for the 10 serotypes included in the vaccine
demonstrating the induction of immune memory after the three-dose primary course.
2. Acute Otitis Media (AOM)
In a large randomised double-blind Pneumococcal Otitis Media Efficacy Trial (POET) conducted in
the Czech Repub lic and in Slovakia, 4,968 infants received an 11-valent investigational vaccine
(11Pn-PD) containing the 10 serotypes of Synflorix (along with serotype 3 for which efficacy was not
demonstrated) or a control vaccine (hepatitis A vaccine) according to a 3, 4, 5 and 12-15 months
vaccination schedule.
Efficacy of the 11 Pn-PD vaccine against the first occurrence of vaccine-serotype AOM episode was
52.6% (95% CI: 35.0;65.5). Serotype specific efficacy against the first AOM episode was
demonstrated for serotypes 6B (86.5%, 95%CI: 54.9;96.0), 14 (94.8%, 95% CI: 61.0;99.3), 19F
(43.3%, 95% CI:6.3;65.4) and 23F (70.8%, 95% CI: 20.8;89.2). For other vaccine serotypes, the
number of AOM cases was too limited to allow any efficacy conclusion to be drawn. Efficacy against
any AOM episode due to any pneumococcal serotype was 51.5% (95% CI: 36.8;62.9). No increase in
the incidence of AOM due to other bacterial pathogens or non-vaccine serotypes was observed in this
study. The estimated vaccine efficacy against any clinical episodes of otitis media regardless of
aetiology was 33.6% (95% CI: 20.8; 44.3).
Based on immunological bridging of the functional vaccine response (OPA) of Synflorix with the 11-
valent formulation used within POET, it is expected that Synflorix provides similar protective efficacy
against pneumococcal AOM.
3. Additional immunogenicity data
Infants from 6 weeks to 6 months of age
31
3-dose primary schedule
In total eight studies, conducted in various countries across Europe, in Chile and in the Philippines,
have evaluated the immunogenicity of Synflorix after a three-dose primary series (N=3,089) according
to different vaccination schedules (6-10-14 weeks, 2-3-4, 3-4-5 or 2-4-6 months of age). A fourth
(booster) dose was given in six clinical studies to 1,976 subjects. In general, comparable vaccine
responses were observed for the different schedules, although somewhat higher immune responses
were noted for the 2-4-6 month schedule.
2-dose primary schedule
The immunogenicity of Synflorix following a 2-dose primary vaccination schedule in subjects less
than 6 months of age was evaluated in two clinical studies.
In the first study, in a post-hoc analysis, the immunogenicity two months after the second dose of
Synflorix was compared with 7-valent Prevenar and the percentages of subjects with ELISA antibody
concentration ≥ 0.2 µg/ml were within the same range for each of the serotypes common to both
vaccines with the exception of serotypes 6B (64.1% for Synflorix and 30.7% for 7-valent Prevenar)
and 18C (87.1% for Synflorix and 97.6% for 7-valent Prevenar). Antibody GMCs were similar in both
groups, with the exception of some serotypes for which responses were higher (6B) or lower (4, 9V
and 18C) in the Synflorix group. Similarly, the percentage of subjects reaching OPA titres ≥ 8 and the
OPA GMTs two months post dose 2 was within the same range for each of the serotypes common to
both vaccines, with the exception of 6B and 19F for which responses were higher in the Synflorix
group.
In the second study, the immunogenicity after two or three doses of Synflorix was compared.
Although there was no significant difference between the two groups in the percentages of subjects
with antibody concentration ≥ 0.20 µg/mL (ELISA), the percentages of subjects for serotypes 6B and
23F were lower than for the other serotypes (Table 2 and Table 3). The percentage of subjects with
OPA titres ≥ 8 in 2-dose primed subjects compared to 3-dose primed subjects were lower for serotypes
6B, 18C and 23F (74.4%, 82.8%, 86.3% respectively for the 2-dose schedule and 88.9%, 96.2%,
97.7% respectively for the 3-dose schedule). Overall, the persistence of the immune response until the
booster at 11 months of age was lower in the 2-dose primed subjects. In both schedules, a booster
response indicative of immunological priming was observed for each serotype (Table 2 and Table 3).
After the booster dose, a lower percentage of subjects with OPA titres ≥ 8 was observed in the 2-dose
schedule for serotypes 5 (87.2% versus 97.5% for the 3-dose primed subjects) and 6B (81.1% versus
90.3%), all other responses were comparable.
Table 2: Percentage of 2-dose primed subjects with antibody concentrations ≥ 0.20 µg/ml one
month post-primary and one month post-booster
≥0.2µg/mL (ELISA)
Antibody
Post-primary
Post-booster
%
95% CI
%
95%CI
Anti-1
97.4
93.4
99.3
99.4
96.5
100
Anti-4
98.0
94.4
99.6
100
97.6
100
Anti-5
96.1
91.6
98.5
100
97.6
100
Anti-6B
55.7
47.3
63.8
88.5
82.4
93.0
Anti-7F
96.7
92.5
98.9
100
97.7
100
Anti-9V
93.4
88.2
96.8
99.4
96.5
100
Anti-14
96.1
91.6
98.5
99.4
96.5
100
Anti-18C
96.1
91.6
98.5
100
97.7
100
Anti-19F
92.8
87.4
96.3
96.2
91.8
98.6
Anti-23F
69.3
61.3
76.5
96.1
91.7
98.6
32
Table 3: Percentage of 3-dose primed subjects with antibody concentrations ≥ 0.20 µg/ml one
month post-primary and one month post-booster
≥0.2µg/mL (ELISA)
Antibody
Post-primary
Post-booster
%
95% CI
%
95%CI
Anti-1
98.7
95.3
99.8
100
97.5
100
Anti-4
99.3
96.4
100
100
97.5
100
Anti-5
100
97.6
100
100
97.5
100
Anti-6B
63.1
54.8
70.8
96.6
92.2
98.9
Anti-7F
99.3
96.4
100
100
97.5
100
Anti-9V
99.3
96.4
100
100
97.5
100
Anti-14
100
97.6
100
98.6
95.2
99.8
Anti-18C
99.3
96.4
100
99.3
96.3
100
Anti-19F
96.1
91.6
98.5
98.0
94.2
99.6
Anti-23F
77.6
70.2
84.0
95.9
91.3
98.5
In the follow-up of the second study, the persistence of antibodies at 36-46 months of age was
demonstrated in subjects that had received a 2-dose primary series followed by a booster dose with at
least 83.7% of subjects remaining seropositive for vaccine serotypes. In subjects that had received a 3-
dose primary series followed by a booster dose, at least 96.5 % of the subjects remained seropositive
for vaccine serotypes. A single dose of Synflorix, administered during the 4th year of life, as a
challenge dose, elicited similar ELISA antibody GMCs when measured 7-10 days after challenge in 2-
dose primed subjects and 3-dose primed sub jects. These levels were higher than those seen after
challenge of unprimed subjects. The fold increase in ELISA antibody GMCs and OPA GMTs, pre to
post vaccination, was also similar in 2-dose primed subjects to that in 3-dose primed subjects. These
results are indicative of immunological memory in primed subjects for all vaccine serotypes.
The clinical consequences of the lower post-primary and post-booster immune responses observed
after the two-dose primary schedule are not known.
Previously unvaccinated older infants and children
One clinical study evaluated vaccination in children 7-11 months of age and 12-23 months of age. In
the 7-11 months group, children received 2 primary doses followed by a booster dose in the second
year of life. The immune responses after the booster dos e of Synflorix in this age group were generally
similar to those observed after the booster dose in infants who had been primed with 3 doses below 6
months of age.
The immune response elicited after two doses of Synflorix in children 12-23 months of age was
comparable to the response elicited after three doses in infants, except for 18C and 19F for which
responses were higher in the 12-23 months children. The need for a booster dose after two doses in
children aged 12-23 months has not been established.
Long-term persistence of antibodies has not been investigated after administration of a primary series
in infants plus booster or after a two-dose priming in older children.
In a clinical study, it has been demonstrated that Synflorix can be safely administered as a booster
dose in the second year of life to children who had received 3 primary doses of 7-valent Prevenar.
This study has shown that the immune responses against the 7 common serotypes were comparable to
those elicited by a booster dose of 7-valent Prevenar. However, children who received 7-valent
Prevenar for the primary series would not be primed against the additional serotypes contained in
Synflorix (1, 5, 7F). Therefore the degree and duration of protection against invasive pneumococcal
disease and otitis media due to these serotypes in children of this age group following a single dose of
Synflorix cannot be predicted.
4. Immunogenicity data in preterm infants
33
Immunogenicity of Synflorix in very preterm (gestation period of 27-30 weeks) (N=42), preterm
(gestation period of 31-36 weeks) (N=82) and full term (gestation period > 36 weeks) (N=132) infants
was evaluated following a 3 dose primary vaccination course at 2, 4, 6 months of age. Immunogenicity
following a fourth dose (booster dose) at 15 to 18 months of age was evaluated in 44 very preterm, 69
preterm and 127 full term infants.
One month after primary vaccination (i.e. after the third dose), at least 92.7% of subjects achieved
ELISA antibody concentrations ≥ 0.2 µg/ml and at least 81.7% achieved OPA titres ≥ 8 for all vaccine
serotypes, except serotype 1 (at least 58. 8% with OPA titres ≥ 8). Similar antibody GMCs and OPA
GMTs were observed for all infants except lower antibody GMCs for serotypes 4, 5 and 9V in very
preterms and serotype 9V in preterms and lower OPA GMT for serotype 5 in very preterms. The
clinical relevance of these differences is not known.
One month after the booster dose increases of ELISA antibody GMCs and OPA GMTs were seen for
all serotypes, indicative of immunological memory. Similar antibody GMCs and OPA GMTs were
observed for all infants except a lower OPA GMT for serotype 5 in very preterm infants. Overall, at
least 97.6% of subjects achieved ELISA antibody concentrations≥ 0.2µg/ml and at least 91.9%
achieved OPA titres ≥ 8 for all vaccine serotypes.
5.2 Pharmacokinetic properties
Evaluation of pharmacokinetic properties is not available for vaccines.
5.3 Preclinical safety data
Studies with an 11-valent vaccine formulation representative for Synflorix revealed no special hazard
for humans based on conventional studies of safety pharmacology, single and repeated dose toxicity.
6.1 List of excipients
Sodium chloride
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
After first opening of the multidose vial, immediate use is recommended. If not used immediately, the
vaccine should be stored in a refrigerator (2°C – 8°C). If not used within 6 hours it should be
discarded.
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.
34
6.5 Nature and contents of container
1 ml suspension in a vial (type I glass) with a stopper (butyl rubber) for 2 doses. Pack size x 100.
6.6 Special precautions for disposal and other handling
A fine white deposit with a clear colourless supernatant may be observed upon storage of the vial. This
does not constitute a sign of deterioration.
The content of the vial should be inspected visually both before and after shaking for any foreign
particulate matter and/or abnormal physical appearance prior to administration. In the event of either
being observed, discard the vaccine.
The vaccine should be allowed to reach room temperature before use.
The vaccine should be well shaken before use.
When using a multidose vial, each 0.5 ml dose should be withdrawn using a sterile needle and syringe;
precautions should be taken to avoid contamination of the contents.
Any unused product or waste material should be disposed of in accordance with local requirements.
GlaxoSmithKline Biologicals S.A.
Rue de l’Institut 89
B-1330 Rixensart, Belgium
EU/1/09/508/009
Date of first authorisation: 30/03/2009
Detailed information on this medicinal product is available on the website of the European Medicines
Agency http://www.ema.europa.eu/.
35
ANNEX II
A.
MANUFACTURERS OF THE BIOLOGICAL ACTIVE
SUBSTANCES AND MANUFACTURING
AUTHORISATION HOLDER RESPONSIBLE FOR BATCH
RELEASE
B.
CONDITIONS OF THE MARKETING AUTHORISATION
36
A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCES AND
MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH
RELEASE
Name and address of the manufacturers of the biological active substances
GlaxoSmithKline Biologicals S.A.
Parc de la Noire Epine
Rue Fleming 20
B-1300 Wavre
Belgium
GlaxoSmithKline Biologicals S.A.
89, rue de l'Institut
BE-1330 Rixensart
Belgium
GlaxoSmithKine Biologicals Kft.
HU-2100 Gödöllö
Táncsics Mihály út 82.
Hungary
Name and address of the manufacturer responsible for batch release
GlaxoSmithKline Biologicals S.A.
89, rue de l'Institut
BE-1330 Rixensart
Belgium
B. CONDITIONS OF THE MARKETING AUTHORISATION
•
Medicinal product subject to medical prescription.
•
CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND
EFFECTIVE USE OF THE MEDICINAL PRODUCT
Not applicable
•
OTHER CONDITIONS
Pharmacovigilance system
The MAH must ensure that the system of pharmacovigilance, as described in version 3 presented in
Module 1.8.1. of the Marketing Authorisation Application, is in place and functioning before and
whilst the product is on the market.
Risk Management Plan
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in
the Pharmacovigilance Plan, as agreed in version 3 of the Risk Management Plan (RMP) presented in
Module 1.8.2. of the Marketing Authorisation Application and any subsequent updates of the RMP
agreed by the CHMP.
37
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the
updated RMP should be submitted at the same time as the next Periodic Safety Update Report
(PSUR).
In addition, an updated RMP should be submitted
•
When new information is received that may impact on the current Safety Specification,
Pharmacovigilance Plan or risk minimisation activities
•
Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being
reached
•
At the request of the EMEA
Official batch release: in accordance with Article 114 Directive 2001/83/EC as amended, the official
batch release will be undertaken by a state laboratory or a laboratory designated for that purpose.
38
ANNEX III
LABELLING AND PACKAGE LEAFLET
39
A. LABELLING
40
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
CARTON OF PRE-FILLED SYRINGE WITH OR WITHOUT NEEDLE, PACK OF 1, 10
1.
Synflorix suspension for injection in pre-filled syringe
Pneumococcal polysaccharide
conjugate vaccine (adsorbed)
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each 0.5 ml dose contains 1 microgram of polysaccharide for serotypes 1, 5, 6B, 7F, 9V, 14 and 23F,
and 3 micrograms of serotypes 4, 18C and 19F.
3.
LIST OF EXCIPIENTS
Sodium chloride
Water for injections
4.
Suspension for injection
1 pre-filled syringe
1 dose (0.5 ml)
10 pre-filled syringes
10 doses (0.5 ml)
1 pre-filled syringe + 1 needle
1 dose (0.5 ml)
10 pre-filled syringes + 10 needles
10 x 1 dose (0.5 ml)
1 pre-filled syringe + 2 needles
1 dose (0.5 ml)
50 pre-filled syringes
50 doses (0.5 ml)
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Read the package leaflet before use
Intramuscular use
The vaccine should be allowed to reach room temperature before us e.
Shake well before use
41
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
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
Dispose of in accordance with local regulations.
GlaxoSmithKline Biologicals s.a.
Rue de l’Institut 89
B-1330 Rixensart, Belgium
EU/1/09/508/001 – pack of 1 without needle
EU/1/09/508/002 – pack of 10 without needle
EU/1/09/508/003 – pack of 1 with 1 needle
EU/1/09/508/004 – pack of 10 with 10 needles
EU/1/08/508/005 – pack of 1 with 2 needles
EU/1/09/508/010 – pack of 50 without needle
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
42
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Justification for not including Braille accepted
43
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
PRE-FILLED SYRINGE LABEL
1.
Synflorix suspension for injection in pre-filled syringe
IM
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
44
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
VIAL, PACK OF 1, 10, 100
1.
Synflorix suspension for injection
Pneumococcal polysaccharide
conjugate vaccine (adsorbed)
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each 0.5 ml dose contains 1 microgram of polysaccharide for serotypes 1, 5, 6B, 7F, 9V, 14 and 23F,
and 3 micrograms of serotypes 4, 18C and 19F.
3.
LIST OF EXCIPIENTS
Sodium chloride
Water for injections
4.
Suspension for injection
1 vial
1 dose (0.5 ml)
10 vials
10 x 1 dose (0.5 ml)
100 vials
100 x 1 dose (0.5 ml)
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Read the package leaflet before use
Intramuscular use
The vaccine should be allowed to reach room temperature before use
Shake well before use
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
45
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
Dispose of in accordance with local regulations.
GlaxoSmithKline Biologicals s.a.
Rue de l’Institut 89
B-1330 Rixensart, Belgium
EU/1/09/508/006 – pack of 1
EU/1/09/508/007 – pack of 10
EU/1/09/508/008 – pack of 100
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Justification for not including Braille accepted
46
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
VIAL LABEL
1.
Synflorix suspension for injection
IM
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
47
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
VIAL MULTIDOSE (2 DOSES), PACK OF 100
1.
Synflorix suspension for injection in multidose container
Pneumococcal polysaccharide
conjugate vaccine (adsorbed)
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each 0.5 ml dose contains 1 microgram of polysaccharide for serotypes 1, 5, 6B, 7F, 9V, 14 and 23F,
and 3 micrograms of serotypes 4, 18C and 19F.
3.
LIST OF EXCIPIENTS
Sodium chloride
Water for injections
4.
Suspension for injection
100 MULTIDOSE vials (2 doses per vial – 0.5 ml per dose)
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Read the package leaflet before use
Intramuscular use
The vaccine should be allowed to reach room temperature before use
Shake well before use
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Store in a refrigerator
48
Do not freeze
Store in the original package in order to protect from light
Should be used within 6 hours after first broaching of the vial
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Dispose of in accordance with local regulations.
GlaxoSmithKline Biologicals s.a.
Rue de l’Institut 89
B-1330 Rixensart, Belgium
EU//1/09/508/009
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Justification for not including Braille accepted
49
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
VIAL LABEL MULTIDOSE (2 DOSES)
1.
Synflorix injection
IM
2.
METHOD OF ADMINISTRATION
3.
EXPIRY DATE
EXP
4.
BATCH NUMBER
Lot
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
2 doses (0.5 ml per dose)
6.
OTHER
50
B. PACKAGE LEAFLET
51
PACKAGE LEAFLET: INFORMATION FOR THE USER
Synflorix suspension for injection in pre-filled syringe
Pneumococcal polysaccharide
conjugate vaccine (adsorbed)
Read all of this leaflet carefully before your child receives this vaccine.
•
Keep this leaflet. You may need to read it again.
•
If you have any further questions, ask your doctor or pharmacist.
•
This vaccine has been prescribed for your child. Do not pass it on to others.
•
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor or pharmacist.
In this leaflet
:
1. What Synflorix is and what it is used for
2. Before your child receives Synflorix
3. How Synflorix is given
4. Possible side effects
5.
How to store Synflorix
6.
Further information
1.
WHAT SYNFLORIX IS AND WHAT IT IS USED FOR
Synflorix is a pneumococcal conjugate vaccine. Your doctor or nurse will inject your child with this
vaccine.
It is used to help protect your child from 6 weeks up to 2 years of age against:
a bacteria called ‘Streptococcus pneumoniae’. This bacteria can cause serious illnesses including
meningitis, sepsis or bacteraemia (bacteria in blood stream) or ear infection and pneumonia.
How the vaccine works
Synflorix helps your body to make its own antibodies. The antibodies form a part of the immune
system that will protect your child against these diseases.
2.
BEFORE YOUR CHILD RECEIVES SYNFLORIX
Synflorix should not be given if:
•
your child has ever had an allergic reaction (is hypersensitive) to the active substance, or any of
the other ingredients in this vaccine (listed in Section 6).
Signs of an allergic reaction may include itchy skin rash, being short of breath and swelling of
the face or tongue.
•
your child has a severe infection with a high temperature (over 38°C). If this applies to your
child then the vaccination will be postponed until your child is feeling better. A minor infection
such as a cold should not be a problem. However, talk to your doctor first.
Synflorix should not be given to your child if any of the above applies to them. If you are not sure,
talk to your doctor or pharmacist before they receive Synflorix.
Take special care with Synflorix:
Check with your doctor or pharmacist before giving this vaccine if:
•
your child has a bleeding problem or bruises easily.
52
As with all vaccines, Synflorix may not fully protect all children who are vaccinated.
Synflorix will only protect against infections caused by the bacteria for which the vaccine has been
developed.
Children with a weakened immune system (such as due to HIV infection) may not get the full benefit
from Synflorix.
If you are not sure, talk to your doctor or pharmacist before having Synflorix.
Using other medicines
Please tell your doctor or pharmacist if your child is taking or has recently taken any other medicines.
This includes medicines obtained without a prescription or if they have recently received any other
vaccine. Synflorix may not work as well if your child is taking medicines that affect the immune
system to fight infection.
Synflorix can be given at the same time as other childhood vaccines such as diphtheria, tetanus,
pertussis (whooping cough),
Haemophilus influenzae
type b, oral or inactivated polio, hepatitis B,
measles-mumps -rubella, varicella, oral rotavirus vaccines as well as meningococcal serogroup C
conjugate vaccines. A different place for the injection will be used for each vaccine.
Your doctor may ask you to give your child paracetamol or other medicines that lower fever before
Synflorix is given. This will help to lower some of the side effects of Synflorix. However if your child
has paracetamol, their protection against pneumococcal diseases may not be as good.
Important information about some of the ingredients of Synflorix
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-
free’.
3.
HOW SYNFLORIX IS GIVEN
How the vaccine is given
Synflorix is always injected into a muscle. This is usually in the thigh or upper arm.
How much is given
Usually, your child will receive a course of 4 injections according to official recommendations or an
alternative schedule may be us ed by the health care professional. It is important to follow the
instructions from the doctor or nurse to complete the courses of injections.
•
Each injection will be given at least one month apart except for the last injection, which will be
given at least 6 months after the third injection.
•
The first injection can be given from the age of 6 weeks onwards.
•
You will be told when your child should come back for their next injection.
Preterm infants
Your child will receive three injections with an interval of at least one month between each dose. At
least six months after the last injection, your child will receive an additional injection (booster).
Infants aged 7 to 11 months will receive 2 injections. Each injection will be given at least one month
apart. A third injection will be given in the second year of life with at least two months apart.
Children aged 12 to 23 months will receive 2 injections. Each injection will be given at least two
months apart.
53
If your child misses an injection
If your child misses an injection, it is important that you make another appointment. This is so that you
and your doctor can talk about what steps need to be taken to protect your child.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Synflorix can cause side effects, although not everybody gets them. The following
side effects may happen with this medicine:
Very common
(these may occur with more than 1 in 10 doses of the vaccine)
•
pain, redness and swelling where the injection is given
•
high temperature of 38°C or higher (fever)
•
feeling sleepy
•
feeling irritable
•
loss of appetite.
Common
(these may occur with up to 1 in 10 doses of the vaccine)
•
hardness where the injection is given.
Uncommon
(these may occur with up to 1 in 100 doses of the vaccine)
•
blood clot, bleeding or a small lump where the injection is given
•
diarrhoea or feeling sick (vomiting)
•
unusual crying.
•
temporarily stopping breathing (apnoea) if your child is born prematurely (before or at 28 weeks
of pregnancy).
Rare
(these may occur with up to 1 in 1,000 doses of the vaccine)
•
fits without temperature or due to high temperature (fever)
•
rash, hives, allergic reactions such as skin rash or allergies
Booster doses of Synf lorix may increase the risk of side effects.
In babies born very prematurely (at or before 28 weeks of gestation) longer gaps than normal between
breaths may occur for 2-3 days after vaccination.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.
5.
HOW TO STORE SYNFLORIX
Keep out of the reach and sight of children.
•
Do not use Synflorix after the expiry date which is stated on the carton. The exp iry date refers
to the last day of that month.
•
Store in a refrigerator (2°C - 8°C).
•
Store in the original package in order to protect from light.
•
Do not freeze.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help to protect the environment.
54
6.
FURTHER INFORMATION
What Synflorix contains
•
The active subs tances are:
One 0.5 ml dose contains:
Pneumococcal polysaccharide serotype 1
1,2
1 microgram
Pneumococcal polysaccharide serotype 4
1,2
3 micrograms
Pneumococcal polysaccharide serotype 5
1,2
1 microgram
Pneumococcal polysaccharide serotype 6B
1,2
1 microgram
Pneumococcal polysaccharide serotype 7F
1,2
1 microgram
Pneumococcal polysaccharide serotype 9V
1,2
1 microgram
Pneumococcal polysaccharide serotype 14
1,2
1 microgram
Pneumococcal polysaccharide serotype 18C
1,3
3 micrograms
Pneumococcal polysaccharide serotype 19F
1,4
3 micrograms
Pneumococcal polysaccharide serotype 23F
1,2
1 microgram
1
adsorbed on aluminium phosphate
0.5 milligram Al
3+
2
conjugated to protein D (derived from non-typeable
Haemophilus influenzae
) carrier protein
9-16 micrograms
3
conjugated to tetanus toxoid carrier protein
5-10 micrograms
4
conjugated to diphtheria toxoid carrier protein
3-6 micrograms
•
The other ingredients are: sodium chloride and water for injections
What Synflorix looks like and contents of the pack
•
Suspension for injection in pre-filled syringe
•
Synflorix is a turbid white suspension.
•
Synflorix is available in pre-filled syringes with or without needles in packs of 1, 10 or 50.
•
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
GlaxoSmithKline Biologicals s.a.
Rue de l’Institut 89
B-1330 Rixensart
Belgium
For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder:
België/Belgique/Belgien
GlaxoSmithKline s.a./n.v.
Tél/Tel: + 32 2 656 21 11
Luxembourg/Luxemburg
GlaxoSmithKline s.a./n.v.
Tél/Tel: + 32 2 656 21 11
България
ГлаксоСмитКлайн ЕООД
ул. Димитър Манов бл.10
София 1408
Тел.: + 359 2 953 10 34
Magyarország
GlaxoSmithKline Kft.
Tel.: + 36-1-2255300
Česká republika
Malta
55
GlaxoSmithKline s.r.o.
Tel: + 420 2 22 00 11 11
gsk.czmail@gsk.com
GlaxoSmithKline Malta
Tel: + 356 21 238131
Danmark
GlaxoSmithKline Pharma A/S
Tlf: + 45 36 35 91 00
dk-info@gsk.com
Nederland
GlaxoSmithKline BV
Tel: + 31 (0)30 69 38 100
nlinfo@gsk.com
Deutschland
GlaxoSmithKline GmbH & Co. KG
Tel: + 49 (0)89 360448701
produkt.info@gsk.com
Norge
GlaxoSmithKline AS
Tlf: + 47 22 70 20 00
firmapost@gsk.no
Eesti
GlaxoSmithKline Eesti OÜ
Tel: +372 667 6900
estonia@gsk.com
Österreich
GlaxoSmithKline Pharma GmbH.
Tel: + 43 1 970 75-0
at.info@gsk.com
Ελλάδα
GlaxoSmithKline A.E.B.E
Tηλ: + 30 210 68 82 100
Polska
GSK Commercial Sp. z o.o.
Tel.: + 48 (22) 576 9000
España
GlaxoSmithKline, S.A.
Tel: + 34 902 202 700
es-ci@gsk.com
Portugal
GlaxoSmithKline, Produtos Farmacêuticos, Lda.
Tel: + 351 21 412 95 00
FI.PT@gsk.com
France
Laboratoire GlaxoSmithKline
Tél: + 33 (0) 1 39 17 84 44
diam@gsk.com
România
GlaxoSmithKline (GSK) SRL
Tel: + 40 (0)21 3028 208
Ireland
GlaxoSmithKline (Ireland) Ltd
Tel: + 353 (0)1 4955000
Slovenija
GlaxoSmithKline d.o.o.
Tel: + 386 (0) 1 280 25 00
medical.x.si@gsk.com
Ísland
GlaxoSmithKline ehf.
Sími: +354-530 3700
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 04 59 21 81 11
Suomi/Finland
GlaxoSmithKline Oy
Puh/Tel: + 358 10 30 30 30
Finland.tuoteinfo@gsk.com
Κύπρος
GlaxoSmithKline (Cyprus) Ltd
Τηλ: + 357 22 39 70 00
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)808 100 9997
customercontactuk@gsk.com
56
Lietuva
GlaxoSmithKline Lietuva UAB
Tel. +370 5 264 90 00
info.lt@gsk.com
This leaflet was last approved in
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 medical or healthcare professionals only:
A fine white deposit with a clear colourless supernatant may be observed upon storage of the pre-filled
syringe. This does not constitute a sign of deterioration.
The content of the pre-filled syringe should be inspected visually both before and after shaking for any
foreign particulate matter and/or abnormal physical appearance prior to administration. In the event of
either being observed, discard the vaccine.
The vaccine should be allowed to reach room temperature before us e.
The vaccine should be well shaken before use.
The vaccine is for intramuscular use only. Do not administer intravascularly.
If Synflorix is co-administered with other vaccines, different injection sites should be used.
Synflorix should not be mixed with other vaccines. If a vaccine dose is withdrawn into a syringe for
injection, the needle used for withdrawal must be replaced by a needle suitable for intramuscular
injection.
Instructions for administration of the vaccine presented in pre-filled syringe
1.
Holding the syringe
barrel
(avoid holding the syringe plunger),
unscrew the syringe cap by twisting it anticlockwise.
Syringe plunger
Syringe barrel
Syringe cap
2.
To attach the needle to the syringe,
twist the needle clockwise into the syringe
until you feel it lock.
3.
Remove the needle protector, which on
occasion can be a little stiff.
Needle protector
57
in one hand
Any unused product or waste material should be disposed of in accordance with local requirements.
58
PACKAGE LEAFLET: INFORMATION FOR THE USER
Synflorix suspension for injection
Pneumococcal polysaccharide
conjugate vaccine (adsorbed)
Read all of this leaflet carefully before your child receives this vaccine.
•
Keep this leaflet. You may need to read it again.
•
If you have any further questions, ask your doctor or pharmacist.
•
This vaccine has been prescribed for your child. Do not pass it on to others.
•
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor or pharmacist.
In this leaflet
:
1.
What Synflorix is and what it is used for
2.
Before your child receives Synflorix
3.
How Synflorix is given
4.
Possible side effects
5.
How to store Synflorix
6.
Further information
1.
WHAT SYNFLORIX IS AND WHAT IT IS USED FOR
Synflorix is a pneumococcal conjugate vaccine. Your doctor or nurse will inject your child with this
vaccine.
It is used to help protect your child from 6 weeks up to 2 years of age against:
a bacteria called ‘Streptococcus pneumoniae’. This bacteria can cause serious illnesses including
meningitis, sepsis or bacteraemia (bacteria in blood stream) or ear infection and pneumonia.
How the vaccine works
Synflorix helps your body to make its own antibodies. The antibodies form a part of the immune
system that will protect your child against these diseases.
2.
BEFORE YOUR CHILD RECEIVES SYNFLORIX
Synflorix should not be given if:
•
your child has ever had an allergic reaction (is hypersensitive) to the active substance, or any of
the other ingredients in this vaccine (listed in Section 6).
Signs of an allergic reaction may include itchy skin rash, being short of breath and swelling of
the face or tongue.
•
your child has a severe infection with a high temperature (over 38°C). If this applies to your
child then the vaccination will be postponed until your child is feeling better. A minor infection
such as a cold should not be a problem. However, talk to your doctor first.
Synflorix should not be given to your child if any of the above applies to them. If you are not sure,
talk to your doctor or pharmacist before they receive Synflorix.
Take special care with Synflorix:
Check with your doctor or pharmacist before giving this vaccine if:
•
your child has a bleeding problem or bruises easily.
59
As with all vaccines, Synflorix may not fully protect all children who are vaccinated.
Synflorix will only protect against infections caused by the bacteria for which the vaccine has been
developed.
Children with a weakened immune system (such as due to HIV infection) may not get the full benefit
from Synflorix.
If you are not sure, talk to your doctor or pharmacist before having Synflorix.
Using other medicines
Please tell your doctor or pharmacist if your child is taking or has recently taken any other medicines.
This includes medicines obtained without a prescription or if they have recently received any other
vaccine. Synflorix may not work as well if your child is taking medicines that affect the immune
system to fight infection.
Synflorix can be given at the same time as other childhood vaccines such as diphtheria, tetanus,
pertussis (whooping cough),
Haemophilus influenzae
type b, oral or inactivated polio, hepatitis B,
measles-mumps -rubella, varicella, oral rotavirus vaccines as well as meningococcal serogroup C
conjugate vaccines. A different place for the injection will be used for each vaccine.
Your doctor may ask you to give your child paracetamol or other medicines that lower fever before
Synflorix is given. This will help to lower some of the side effects of Synflorix. However if your child
has paracetamol, their protection against pneumococcal diseases may not be as good.
Important information about some of the ingredients of Synflorix
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-
free’.
3.
HOW SYNFLORIX IS GIVEN
How the vaccine is given
Synflorix is always injected into a muscle. This is usually in the thigh or upper arm.
How much is given
Usually, your child will receive a course of 4 injections according to official recommendations or an
alternative schedule may be used by the health care professional. It is important to follow the
instructions from the doctor or nurse to complete the courses of injections.
•
Each injection will be given at least one month apart except for the last injection, which will be
given at least 6 months after the third dose.
•
The first injection can be given from the age of 6 weeks onwards.
•
You will be told when your child should come back for their next injection.
Preterm infants
Your child will receive three injections with an interval of at least one month between each dose. At
least six months after the last injection, your child will receive an additional injection (booster).
Infants aged 7 to 11 months will receive 2 injections. Each injection will be given at least one month
apart. A third injection will be given in the second year of life with at least two months apart.
Children aged 12 to 23 months will receive 2 injections. Each injection will be given at least two
months apart.
60
If your child misses an injection
If your child misses an injection, it is important that you make another appointment. This is so that you
and your doctor can talk about what steps need to be taken to protect your child.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Synflorix can cause side effects, although not everybody gets them. The following
side effects may happen with this medicine:
Very common
(these may occur with more than 1 in 10 doses of the vaccine)
•
pain, redness and swelling where the injection is given
•
high temperature of 38°C or higher (fever)
•
feeling sleepy
•
feeling irritable
•
loss of appetite.
Common
(these may occur with up to 1 in 10 doses of the vaccine)
•
hardness where the injection is given.
Uncommon
(these may occur with up to 1 in 100 doses of the vaccine)
•
blood clot, bleeding or a small lump where the injection is given
•
diarrhoea or feeling sick (vomiting)
•
unusual crying.
•
temporarily stopping breathing (apnoea) if your child is born prematurely (before or at 28 weeks
of pregnancy).
Rare
(these may occur with up to 1 in 1,000 doses of the vaccine)
•
fits without temperature or due to high temperature (fever)
•
rash, hives, allergic reactions such as skin rash or allergies
Booster doses of Synflorix may increase the risk of side effects.
In babies born very prematurely (at or before 28 weeks of gestation) longer gaps than normal between
breaths may occur for 2-3 days after vaccination.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.
5.
HOW TO STORE SYNFLORIX
Keep out of the reach and sight of children.
•
Do not use Synflorix after the expiry date which is stated on the carton. The expiry date refers
to the last day of that month.
•
Store in a refrigerator (2°C - 8°C).
•
Store in the original package in order to protect from light.
•
Do not freeze.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help to protect the environment.
61
6.
FURTHER INFORMATION
What Synflorix contains
•
The active subs tances are:
One 0.5 ml dose contains:
Pneumococcal polysaccharide serotype 1
1,2
1 microgram
Pneumococcal polysaccharide serotype 4
1,2
3 micrograms
Pneumococcal polysaccharide serotype 5
1,2
1 microgram
Pneumococcal polysaccharide serotype 6B
1,2
1 microgram
Pneumococcal polysaccharide serotype 7F
1,2
1 microgram
Pneumococcal polysaccharide serotype 9V
1,2
1 microgram
Pneumococcal polysaccharide serotype 14
1,2
1 microgram
Pneumococcal polysaccharide serotype 18C
1,3
3 micrograms
Pneumococcal polysaccharide serotype 19F
1,4
3 micrograms
Pneumococcal polysaccharide serotype 23F
1,2
1 microgram
1
adsorbed on aluminium phosphate
0.5 milligram Al
3+
2
conjugated to protein D (derived from non-typeable
Haemophilus influenzae
) carrier protein
9-16 micrograms
3
conjugated to tetanus toxoid carrier protein
5-10 micrograms
4
conjugated to diphtheria toxoid carrier protein
3-6 micrograms
•
The other ingredients are: sodium chloride and water for injections
What Synflorix looks like and contents of the pack
•
Suspension for injection
•
Synflorix is a turbid white suspension.
•
Synflorix is available in vials in packs of 1, 10 or 100
•
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
GlaxoSmithKline Biologicals s.a.
Rue de l’Institut 89
B-1330 Rixensart
Belgium
For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder:
België/Belgique/Belgien
GlaxoSmithKline s.a./n.v.
Tél/Tel: + 32 2 656 21 11
Luxembourg/Luxemburg
GlaxoSmithKline s.a./n.v.
Tél/Tel: + 32 2 656 21 11
България
ГлаксоСмитКлайн ЕООД
ул. Димитър Манов бл.10
София 1408
Тел.: + 359 2 953 10 34
Magyarország
GlaxoSmithKline Kft.
Tel.: + 36-1-2255300
Česká republika
Malta
62
GlaxoSmithKline s.r.o.
Tel: + 420 2 22 00 11 11
gsk.czmail@gsk.com
GlaxoSmithKline Malta
Tel: + 356 21 238131
Danmark
GlaxoSmithKline Pharma A/S
Tlf: + 45 36 35 91 00
dk-info@gsk.com
Nederland
GlaxoSmithKline BV
Tel: + 31 (0)30 69 38 100
nlinfo@gsk.com
Deutschland
GlaxoSmithKline GmbH & Co. KG
Tel: + 49 (0)89 360448701
produkt.info@gsk.com
Norge
GlaxoSmithKline AS
Tlf: + 47 22 70 20 00
firmapost@gsk.no
Eesti
GlaxoSmithKline Eesti OÜ
Tel: +372 667 6900
estonia@gsk.com
Österreich
GlaxoSmithKline Pharma GmbH.
Tel: + 43 1 970 75-0
at.info@gsk.com
Ελλάδα
GlaxoSmithKline A.E.B.E
Tηλ: + 30 210 68 82 100
Polska
GSK Commercial Sp. z o.o.
Tel.: + 48 (22) 576 9000
España
GlaxoSmithKline, S.A.
Tel: + 34 902 202 700
es-ci@gsk.com
Portugal
GlaxoSmithKline, Produtos Farmacêuticos, Lda.
Tel: + 351 21 412 95 00
FI.PT@gsk.com
France
Laboratoire GlaxoSmithKline
Tél: + 33 (0) 1 39 17 84 44
diam@gsk.com
România
GlaxoSmithKline (GSK) SRL
Tel: + 40 (0)21 3028 208
Ireland
GlaxoSmithKline (Ireland) Ltd
Tel: + 353 (0)1 4955000
Slovenija
GlaxoSmithKline d.o.o.
Tel: + 386 (0) 1 280 25 00
medical.x.si@gsk.com
Ísland
GlaxoSmithKline ehf.
Sími: +354-530 3700
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 04 59 21 81 11
Suomi/Finland
GlaxoSmithKline Oy
Puh/Tel: + 358 10 30 30 30
Finland.tuoteinfo@gsk.com
Κύπρος
GlaxoSmithKline (Cyprus) Ltd
Τηλ: + 357 22 39 70 00
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)808 100 9997
customercontactuk@gsk.com
63
Lietuva
GlaxoSmithKline Lietuva UAB
Tel. +370 5 264 90 00
info.lt@gsk.com
This leaflet was last approved in
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 medical or healthcare professionals only:
A fine white deposit with a clear colourless supernatant may be observed upon storage of the vial. This
does not constitute a sign of deterioration.
The content of the vial should be inspected visually both before and after shaking for any foreign
particulate matter and/or abnormal physical appearance prior to administration. In the event of either
being observed, discard the vaccine.
The vaccine should be allowed to reach room temperature before us e.
The vaccine should be well shaken before use.
The vaccine is for intramuscular use only. Do not administer intravascularly.
If Synflorix is co-administered with other vaccines, different injection sites should be used.
Synflorix should not be mixed with other vaccines. If a vaccine dose is withdrawn into a syringe for
injection, the needle used for withdrawal must be replaced by a needle suitable for intramuscular
injection.
Any unused product or waste material should be disposed of in accordance with local requirements.
64
PACKAGE LEAFLET: INFORMATION FOR THE USER
Synflorix suspension for injection in multidose container
Pneumococcal polysaccharide
conjugate vaccine (adsorbed)
Read all of this leaflet carefully before your child receives this vaccine.
•
Keep this leaflet. You may need to read it again.
•
If you have any further questions, ask your doctor or pharmacist.
•
This vaccine has been prescribed for your child. Do not pass it on to others.
•
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor or pharmacist.
In this leaflet
:
1.
What Synflorix is and what it is used for
2.
Before your child receives Synflorix
3.
How Synflorix is given
4.
Possible side effects
5.
How to store Synflorix
6.
Further information
1.
WHAT SYNFLORIX IS AND WHAT IT IS USED FOR
Synflorix is a pneumococcal conjugate vaccine. Your doctor or nurse will inject your child with this
vaccine.
It is used to help protect your child from 6 weeks up to 2 years of age against:
a bacteria called ‘Streptococcus pneumoniae’. This bacteria can cause serious illnesses including
meningitis, sepsis or bacteraemia (bacteria in blood stream) or ear infection and pneumonia.
How the vaccine works
Synflorix helps your body to make its own antibodies. The antibodies form a part of the immune
system that will protect your child against these diseases.
2.
BEFORE YOUR CHILD RECEIVES SYNFLORIX
Synflorix should not be given if:
•
your child has ever had an allergic reaction (is hypersensitive) to the active substance, or any of
the other ingredients in this vaccine (listed in Section 6).
Signs of an allergic reaction may include itchy skin rash, being short of breath and swelling of
the face or tongue.
•
your child has a severe infection with a high temperature (over 38°C). If this applies to your
child then the vaccination will be postponed until your child is feeling better. A minor infection
such as a cold should not be a problem. However, talk to your doctor first.
Synflorix should not be given to your child if any of the above applies to them. If you are not sure,
talk to your doctor or pharmacist before they receive Synflorix.
Take special care with Synflorix:
Check with your doctor or pharmacist before giving this vaccine if:
•
your child has a bleeding problem or bruises easily.
65
As with all vaccines, Synflorix may not fully protect all children who are vaccinated.
Synflorix will only protect against infections caused by the bacteria for which the vaccine has been
developed.
Children with a weakened immune system (such as due to HIV infection) may not get the full benefit
from Synflorix.
If you are not sure, talk to your doctor or pharmacist before having Synflorix.
Using other medicines
Please tell your doctor or pharmacist if your child is taking or has recently taken any other medicines.
This includes medicines obtained without a prescription or if they have recently received any other
vaccine. Synflorix may not work as well if your child is taking medicines that affect the immune
system to fight infection.
Synflorix can be given at the same time as other childhood vaccines such as diphtheria, tetanus,
pertussis (whooping cough),
Haemophilus influenzae
type b, oral or inactivated polio, hepatitis B,
measles-mumps -rubella, varicella, oral rotavirus vaccines as well as meningococcal serogroup C
conjugate vaccines. A different place for the injection will be used for each vaccine.
Your doctor may ask you to give your child paracetamol or other medicines that lower fever before
Synflorix is given. This will help to lower some of the side effects of Synflorix. However if your child
has paracetamol, their protection against pneumococcal diseases may not be as good.
Important information about some of the ingredients of Synflorix
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-
free’.
3.
HOW SYNFLORIX IS GIVEN
How the vaccine is given
Synflorix is always injected into a muscle. This is usually in the thigh or upper arm.
How much is given
Usually, your child will receive a course of 4 injections according to official recommendations or an
alternative schedule may be used by the health care professional. It is important to follow the
instructions from the doctor or nurse to complete the courses of injections.
•
Each injection will be given at least one month apart except for the last injection, which will be
given at least 6 months after the third dose.
•
The first injection can be given from the age of 6 weeks onwards.
•
You will be told when your child should come back for their next injection.
Preterm infants
Your child will receive three injections with an interval of at least one month between each dose. At
least six months after the last injection, your child will receive an additional injection (booster).
Infants aged 7 to 11 months will receive 2 injections. Each injection will be given at least one month
apart. A third injection will be given in the second year of life with at least two months apart.
Children aged 12 to 23 months will receive 2 injections. Each injection will be given at least two
months apart.
66
If your child misses an injection
If your child misses an injection, it is important that you make another appointment. This is so that you
and your doctor can talk about what steps need to be taken to protect your child.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Synflorix can cause side effects, although not everybody gets them. The following
side effects may happen with this medicine:
Very common
(these may occur with more than 1 in 10 doses of the vaccine)
•
pain, redness and swelling where the injection is given
•
high temperature of 38°C or higher (fever)
•
feeling sleepy
•
feeling irritable
•
loss of appetite.
Common
(these may occur with up to 1 in 10 doses of the vaccine)
•
hardness where the injection is given.
Uncommon
(these may occur with up to 1 in 100 doses of the vaccine)
•
blood clot, bleeding or a small lump where the injection is given
•
diarrhoea or feeling sick (vomiting)
•
unusual crying.
•
temporarily stopping breathing (apnoea) if your child is born prematurely (before or at 28 weeks
of pregnancy).
Rare
(these may occur with up to 1 in 1,000 doses of the vaccine)
•
fits without temperature or due to high temperature (fever)
•
rash, hives, allergic reactions such as skin rash or allergies
Booster doses of Synf lorix may increase the risk of side effects.
In babies born very prematurely (at or before 28 weeks of gestation) longer gaps than normal between
breaths may occur for 2-3 days after vaccination.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.
5.
HOW TO STORE SYNFLORIX
Keep out of the reach and sight of children.
•
Do not use Synflorix after the expiry date which is stated on the carton. The expiry date refers
to the last day of that month.
•
Store in a refrigerator (2°C - 8°C).
•
Store in the original package in order to protect from light.
•
Do not freeze.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help to protect the environment.
67
6.
FURTHER INFORMATION
What Synflorix contains
•
The active substances are:
One 0.5 ml dose contains:
Pneumococcal polysaccharide serotype 1
1,2
1 microgram
Pneumococcal polysaccharide serotype 4
1,2
3 micrograms
Pneumococcal polysaccharide serotype 5
1,2
1 microgram
Pneumococcal polysaccharide serotype 6B
1,2
1 microgram
Pneumococcal polysaccharide serotype 7F
1,2
1 microgram
Pneumococcal polysaccharide serotype 9V
1,2
1 microgram
Pneumococcal polysaccharide serotype 14
1,2
1 microgram
Pneumococcal polysaccharide serotype 18C
1,3
3 micrograms
Pneumococcal polysaccharide serotype 19F
1,4
3 micrograms
Pneumococcal polysaccharide serotype 23F
1,2
1 microgram
1
adsorbed on aluminium phosphate
0.5 milligram Al
3+
2
conjugated to protein D (derived from non-typeable
Haemophilus influenzae
) carrier protein
9-16 micrograms
3
conjugated to tetanus toxoid carrier protein
5-10 micrograms
4
conjugated to diphtheria toxoid carrier protein
3-6 micrograms
•
The other ingredients are: sodium chloride and water for injections
What Synflorix looks like and contents of the pack
•
Suspension for injection in multidose container
•
Synflorix is a turbid white suspension.
•
Synflorix is available in vials for 2 doses in a pack of 100.
Marketing Authorisation Holder and Manufacturer
GlaxoSmithKline Biologicals s.a.
Rue de l’Institut 89
B-1330 Rixensart
Belgium
For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder:
België/Belgique/Belgien
GlaxoSmithKline s.a./n.v.
Tél/Tel: + 32 2 656 21 11
Luxembourg/Luxemburg
GlaxoSmithKline s.a./n.v.
Tél/Tel: + 32 2 656 21 11
България
ГлаксоСмитКлайн ЕООД
ул. Димитър Манов бл.10
София 1408
Тел.: + 359 2 953 10 34
Magyarország
GlaxoSmithKline Kft.
Tel.: + 36-1-2255300
Česká republika
GlaxoSmithKline s.r.o.
Tel: + 420 2 22 00 11 11
Malta
GlaxoSmithKline Malta
Tel: + 356 21 238131
68
gsk.czmail@gsk.com
Danmark
GlaxoSmithKline Pharma A/S
Tlf: + 45 36 35 91 00
dk-info@gsk.com
Nederland
GlaxoSmithKline BV
Tel: + 31 (0)30 69 38 100
nlinfo@gsk.com
Deutschland
GlaxoSmithKline GmbH & Co. KG
Tel: + 49 (0)89 360448701
produkt.info@gsk.com
Norge
GlaxoSmithKline AS
Tlf: + 47 22 70 20 00
firmapost@gsk.no
Eesti
GlaxoSmithKline Eesti OÜ
Tel: +372 667 6900
estonia@gsk.com
Österreich
GlaxoSmithKline Pharma GmbH.
Tel: + 43 1 970 75-0
at.info@gsk.com
Ελλάδα
GlaxoSmithKline A.E.B.E
Tηλ: + 30 210 68 82 100
Polska
GSK Commercial Sp. z o.o.
Tel.: + 48 (22) 576 9000
España
GlaxoSmithKline, S.A.
Tel: + 34 902 202 700
es-ci@gsk.com
Portugal
GlaxoSmithKline, Produtos Farmacêuticos, Lda.
Tel: + 351 21 412 95 00
FI.PT@gsk.com
France
Laboratoire GlaxoSmithKline
Tél: + 33 (0) 1 39 17 84 44
diam@gsk.com
România
GlaxoSmithKline (GSK) SRL
Tel: + 40 (0)21 3028 208
Ireland
GlaxoSmithKline (Ireland) Ltd
Tel: + 353 (0)1 4955000
Slovenija
GlaxoSmithKline d.o.o.
Tel: + 386 (0) 1 280 25 00
medical.x.si@gsk.com
Ísland
GlaxoSmithKline ehf.
Sími: +354-530 3700
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 04 59 21 81 11
Suomi/Finland
GlaxoSmithKline Oy
Puh/Tel: + 358 10 30 30 30
Finland.tuoteinfo@gsk.com
Κύπρος
GlaxoSmithKline (Cyprus) Ltd
Τηλ: + 357 22 39 70 00
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)808 100 9997
customercontactuk@gsk.com
Lietuva
69
GlaxoSmithKline Lietuva UAB
Tel. +370 5 264 90 00
info.lt@gsk.com
This leaflet was last approved in
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 medical or healthcare professionals only:
A fine white deposit with a clear colourless supernatant may be observed upon storage of the vial. This
does not constitute a sign of deterioration.
The content of the vial should be inspected visually both before and after shaking for any foreign
particulate matter and/or abnormal physical appearance prior to administration. In the event of either
being observed, discard the vaccine.
The vaccine should be allowed to reach room temperature before us e.
The vaccine should be well shaken before use. After first opening of the multidose vial, immediate use
is recommended. If not used immediately, the vaccine should be stored in a refrigerator (2°C – 8°C). If
not used within 6 hours it should be discarded.
When using a multidose vial, each 0.5 ml dose should be withdrawn using a sterile needle and syringe;
precautions should be taken to avoid contamination of the contents.
The vaccine is for intramuscular use only. Do not administer intravascularly.
If Synflorix is co-administered with other vaccines, different injection sites should be used.
Synflorix should not be mixed with other vaccines. If a vaccine dose is withdrawn into a syringe for
injection, the needle used for withdrawal must be replaced by a needle suitable for intramuscular
injection.
Any unused product or waste material should be disposed of in accordance with local requirements.
70
Source: European Medicines Agency
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