Synflorix

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 
 
 
 
 
 
  



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1.  NAME OF THE MEDICINAL PRODUCT 
 
Synflorix suspension for injection in pre-filled syringe 
Synflorix suspension for injection 
Synflorix suspension for injection in multidose container (2 doses) 
Synflorix suspension for injection in multidose container (4 doses) 
 
Pneumococcal polysaccharide conjugate vaccine (adsorbed) 
 
 
2.  QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
1 dose (0.5 ml) contains: 
 
Pneumococcal polysaccharide serotype 11,2 1 microgram 
Pneumococcal polysaccharide serotype 41,2 3 micrograms 
Pneumococcal polysaccharide serotype 51,2 1 microgram 
Pneumococcal polysaccharide serotype 6B1,2 1 microgram 
Pneumococcal polysaccharide serotype 7F1,2 1 microgram 
Pneumococcal polysaccharide serotype 9V1,2 1 microgram 
Pneumococcal polysaccharide serotype 141,2 1 microgram 
Pneumococcal polysaccharide serotype 18C1,3 3 micrograms 
Pneumococcal polysaccharide serotype 19F1,4 3 micrograms 
Pneumococcal polysaccharide serotype 23F1,2 1 microgram  
 
1 adsorbed on aluminium phosphate  0.5 milligram Al3+ in total 
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 the full list of excipients, see section 6.1. 
 
 
3.  PHARMACEUTICAL FORM 
 
Suspension for injection (injection). 
The vaccine is a turbid white suspension. 
 
 
4.  CLINICAL PARTICULARS 
 
4.1  Therapeutic indications 
 
Active immunisation against invasive disease, pneumonia and acute otitis media caused by 
Streptococcus pneumoniae in infants and children from 6 weeks up to 5 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 on pneumococcal diseases in different age groups as well as the variability of 
the epidemiology in different geographical areas.  
 
4.2  Posology and method of administration 
 
Posology 
 
The immunisation schedules for Synflorix should be based on official recommendations.  



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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 
6 weeks of age. A booster (fourth) dose is recommended at least 6 months after the last primary dose 
and may be given from the age of 9 months onwards (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 given as early as 6 
weeks of age with a second dose administered 2 months later. A booster (third) dose is recommended 
at least 6 months after the last primary dose and may be given from the age of 9 months onwards 
(preferably between 12 and 15 months of age) (see section 5.1). 
 
Preterm newborn 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 0.5 ml. 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 
(fourth) dose is recommended at least 6 months after the last primary dose (see sections 4.4 and 5.1). 
 
Unvaccinated infants and children ≥ 7 months of age 
 
–  infants aged 7–11 months: The vaccination schedule consists of two primary doses of 0.5 ml with 

an interval of at least 1 month between doses. A booster (third) dose is recommended in the second 
year of life with an interval of at least 2 months after the last primary dose. 

 
–  children aged 12 months –5 years: The vaccination schedule consists of two doses of 0.5 ml with an 

interval of at least 2 months between doses.  
 
It is recommended that subjects who receive a first dose of Synflorix complete the full vaccination 
course with Synflorix. 
 
Special populations 
 
In individuals who have underlying conditions predisposing them to invasive pneumococcal disease 
(such as Human Immunodeficiency Virus (HIV) infection, sickle cell disease (SCD) or splenic 
dysfunction), Synflorix may be given according to the above mentioned schedules except that a 3-dose 
schedule should be given as primary vaccination in infants starting vaccination from 6 weeks to 6 
months of age (see sections 4.4 and 5.1). 
 
Paediatric population 
 
The safety and efficacy of Synflorix in children over 5 years 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. 
 
4.3 Contraindications 
 



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Hypersensitivity to the active substances or to any of the excipients listed in section 6.1, 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. 
 
4.4  Special warnings and precautions for use 
 
Traceability 
 
In order to improve the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded. 
 
Prior to immunisation 
  
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 48–72 h 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. 
 
In children as of 2 years of age, syncope (fainting) can occur following, or even before, any 
vaccination as a psychogenic response to the needle injection. It is important that procedures are in 
place to avoid injury from faints. 
 
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.  
 
Information on protection conferred by the vaccine 
 
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 except the cross-reactive serotype 19A (see section 5.1) 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, pneumonia or otitis media caused by the serotypes in the vaccine and the 
cross-reactive serotype 19A. In addition, as otitis media and pneumonia are caused by many micro-
organisms other than the Streptococcus pneumoniae serotypes represented by the vaccine, the overall 
protection against these diseases is expected to be limited and substantially lower than protection 
against invasive disease caused by the serotypes in the vaccine and serotype 19A (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 



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lower protective efficacy against invasive disease, pneumonia or otitis media caused by these 
serotypes (see section 5.1). 
 
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).   
 
Immunosuppressive therapy and immunodeficiency 
 
Children with impaired immune responsiveness, whether due to the use of immunosuppressive 
therapy, a genetic defect, HIV infection, prenatal exposure to anti-retroviral therapy and/or to HIV, or 
other causes, may have reduced antibody response to vaccination. 
 
Safety and immunogenicity data are available for HIV infected infants (asymptomatic or with mild 
symptoms according to WHO classification), HIV negative infants born from HIV positive mothers, 
children with sickle cell disease and children with splenic dysfunction (see sections 4.8 and 5.1). 
Safety and immunogenicity data for Synflorix are not available for individuals in other specific 
immunocompromised groups and vaccination should be considered on an individual basis (see section 
4.2). 
 
The use of pneumococcal conjugate vaccine does not replace the use of 23-valent pneumococcal 
polysaccharide vaccines in children ≥ 2 years of age with conditions (such as sickle cell disease, 
asplenia, HIV infection, chronic illness, or those who have other immunocompromising conditions) 
placing them at higher risk for invasive disease due to Streptococcus pneumoniae. Whenever 
recommended, children at risk who are ≥ 24 months of age and already primed with Synflorix should 
receive 23-valent pneumococcal polysaccharide vaccine. 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 use of antipyretics 
 
Prophylactic administration of antipyretics before or immediately after vaccine administration can 
reduce the incidence and intensity of post-vaccination febrile reactions. Clinical data generated with 
paracetamol and ibuprofen suggest that the prophylactic use of paracetamol might reduce the fever 
rate, while prophylactic use of ibuprofen showed a limited effect in reducing fever rate. The clinical 
data suggest that paracetamol might reduce the immune response to Synflorix. However, the clinical 
relevance of this observation is not known. 
 
The use 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. 
   
4.5  Interaction with other medicinal products and other forms of interaction 
 
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-rubella 
vaccine (MMR), varicella vaccine (V), meningococcal serogroup C conjugate vaccine (CRM197 and 
TT conjugates), meningococcal serogroups A, C, W-135 and Y conjugate vaccine (TT conjugate), 
oral polio vaccine (OPV) and oral rotavirus vaccine. Different injectable vaccines should always be 
given at different injection sites. 



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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%). In 
addition when the meningococcal serogroups A, C, W-135 and Y vaccine (TT conjugate) was co-
administered with a booster dose of Synflorix during the second year of life in children primed with 3 
doses of Synflorix, lower antibody geometric mean concentration (GMC) and opsonophagocytic assay 
geometric mean titre (OPA GMT) were observed for one pneumococcal serotype (18 C). There was no 
impact of co-administration on the other nine pneumococcal serotypes. Enhancement of antibody 
response to Hib-TT conjugate, diphtheria and tetanus antigens was observed. The clinical relevance of 
the above observations is unknown. 
 
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 
 
Clinical data suggest that prophylactic administration of paracetamol, used to reduce the rate of 
possible post-vaccination febrile reactions, might reduce the immune response to Synflorix. However, 
the clinical relevance of this observation is not known. See section 4.4. 
 
4.6  Fertility, pregnancy and lactation 
 
Synflorix is not intended for use in adults. Human data on the use during pregnancy or breast-feeding 
and animal reproduction studies are not available. 
 
4.7  Effects on ability to drive and use machines 
 
Not relevant. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
Safety assessment of Synflorix was based on clinical trials involving the administration of 63,905 
doses of Synflorix to 22,429 healthy children and 137 preterm infants as primary vaccination. 
Furthermore, 19,466 children and 116 preterm infants received a booster dose of Synflorix in the 
second year of life. 
Safety was also assessed in 435 previously unvaccinated children from 2 to 5 years old of which 285 
subjects received 2 doses of Synflorix. 
In all trials, Synflorix was administered concurrently with the recommended childhood vaccines. 
 
In infants, the most common adverse reactions observed after primary vaccination were redness at 
the injection site and irritability which occurred after approximately 41% and 55% of all doses 
respectively. Following booster vaccination, the most common adverse reactions were pain at the 
injection site and irritability, which occurred at approximately 51% and 53% 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. 
 
Local reactogenicity of primary vaccination course was similar in infants < 12 months of age and in 
children > 12 months of age except for injection site pain for which the incidence increased with 
increasing age: pain was reported by more than 39% of the infants < 12 months of age and by more 
than 58% of the children > 12 months of age. 



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Following booster vaccination, children > 12 months of age are more likely to experience injection site 
reactions compared to the rates observed in infants during the primary series with Synflorix. 
 
Following catch-up vaccination in children 12 to 23 months of age, urticaria was reported more 
frequently (uncommon) compared to the rates observed in infants during primary and booster 
vaccination. 
 
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. 
 
Tabulated list of adverse reactions 
 
Adverse reactions (for all age groups)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 rare: (<1/10,000) 
 
Within each frequency grouping the adverse reactions are presented in the order of decreasing 
seriousness. 
 
System Organ Class Frequency Adverse reactions 
Clinical trials 
Immune system disorders Rare Allergic reactions (such as eczema, allergic 

dermatitis, atopic dermatitis) 
Very rare Angioedema 

Metabolism and nutrition 
disorders 

Very common Appetite lost 

Psychiatric disorders 
 

Very common Irritability 
Uncommon Crying abnormal 

Nervous system disorders 
 

Very common Drowsiness 
Rare Convulsions (including febrile convulsions) 

Vascular disorders Very rare Kawasaki disease 
Respiratory, thoracic and 
mediastinal disorders 

Uncommon Apnoea in very premature infants (≤ 28 weeks 
of gestation) (see section 4.4) 

Gastrointestinal disorders Uncommon Diarrhoea, vomiting 
Skin and subcutaneous tissue 
disorders 

Uncommon Rash 
Rare Urticaria 

General disorders and 
administration site conditions 
 

Very common Fever ≥ 38 °C rectally (age < 2 years), pain, 
redness, swelling at the injection site. 

Common Fever > 39 °C rectally (age < 2 years), injection 
site reactions like injection site induration  

Uncommon Injection site reactions like injection site 
haematoma, haemorrhage and nodule 

Adverse reactions additionally reported after booster vaccination of primary series and/or catch-up 



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vaccination: 
Nervous system disorders Uncommon Headache (age 2 to 5 years) 
Gastrointestinal disorders Uncommon Nausea (age 2 to 5 years) 
General disorders and 
administration site conditions 

Common Fever ≥ 38 °C rectally (age 2 to 5 years) 
Uncommon Fever > 40 °C rectally (age < 2 years), fever > 

39 °C rectally (age 2 to 5 years), injection site 
reactions like diffuse swelling of the injected 
limb, sometimes involving the adjacent joint, 
pruritus.  

Post-marketing experience 
Immune system disorders Very rare Anaphylaxis 
Nervous system disorders Rare Hypotonic-hyporesponsive episode 
 
Special populations 
 
Safety of Synflorix was assessed in 83 HIV positive (HIV+/+) infants (asymptomatic or with mild 
symptoms according to WHO classification), 101 HIV negative infants born from HIV positive 
mothers (HIV+/-) and 50 infants with sickle cell disease (SCD), receiving primary vaccination. Of 
these, 76, 96 and 49 infants, respectively, received a booster dose. Safety of Synflorix was also 
assessed in 50 children with SCD starting vaccination at 7–11 months of age, all of them receiving 
the booster vaccination, and in 50 children with SCD starting vaccination at 12–23 months of age. 
Results suggest comparable reactogenicity and safety profile of Synflorix between these high risk 
groups and healthy children. 
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9  Overdose 
 
No case of overdose has been reported. 
 
 
5.  PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: vaccines, pneumococcal vaccines, ATC code: J07AL52 
 
Epidemiological data 
 
The 10 pneumococcal serotypes included in this vaccine represent 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. 
 
Pneumonia of different aetiologies is a leading cause of childhood morbidity and mortality globally. In 
prospective studies, Streptococcus pneumoniae was estimated to be responsible for 30-50% of 
pneumonia cases. 
 
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. 
 

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


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Efficacy and effectiveness in clinical trials 
 
In a large-scale phase III/IV, double-blind, cluster-randomized, controlled, clinical trial in Finland 
(FinIP), children were randomised into 4 groups according to the two infant vaccination schedules 
[2-dose (3, 5 months of age) or 3-dose (3, 4, 5 months of age) primary schedule followed by a booster 
dose as of 11 months of age] to receive either Synflorix (2/3rd of clusters) or hepatitis vaccines as 
control (1/3rd of clusters). In the catch-up cohorts, children between 7–11 months of age at first 
vaccine dose received Synflorix or hepatitis B control vaccine according to a 2-dose primary schedule 
followed by a booster dose and children between 12–18 months of age at first vaccine dose received 
2 doses of either Synflorix or hepatitis A control vaccine. Average follow-up, from first vaccination, 
was 24 to 28 months for invasive disease and hospital-diagnosed pneumonia. In a nested study, infants 
were followed up till approximately 21 months of age to assess impact on nasopharyngeal carriage and 
physician-diagnosed AOM reported by parents. 
 
In a large-scale phase III, randomized, double-blind clinical trial (Clinical Otitis Media and 
Pneumonia Study - COMPAS) conducted in Argentina, Panama and Colombia, healthy infants aged 
6 to 16 weeks received either Synflorix or hepatitis B control vaccine at 2, 4 and 6 months of age 
followed respectively by either Synflorix or hepatitis A control vaccine at 15 to 18 months of age. 
 
Invasive pneumococcal disease (which includes sepsis, meningitis, bacteraemic pneumonia and 
bacteraemia) 
 
Effectiveness/efficacy in infant cohort below 7 months of age at enrolment 
 
Vaccine effectiveness or efficacy (VE) was demonstrated in preventing culture-confirmed IPD due to 
vaccine pneumococcal serotypes when Synflorix was given to infants in either 2+1 or 3+1 schedules 
in FinIP or 3+1 schedule in COMPAS (see Table 1). 
 
Table 1: Number of vaccine serotype IPD cases and vaccine effectiveness (FinIP) or efficacy 
(COMPAS) in infants below 7 months of age at enrolment receiving at least one vaccine dose 
(Infant total vaccinated cohort) 

Type of 
IPD 

FinIP COMPAS 

No. of IPD cases VE (95% CI) No. of IPD cases 
VE 

(95% CI) 
Synflorix 

3+1 
schedule 

Synflorix 
2+1 

schedule 

Control(2) 
 3+1 

schedule 
2+1 

schedule 

Synflorix 
3+1 

schedule  
Control 3+1 

schedule N 
10,273 

N 
10,054 

N 
10,200 

N 
11,798 

N 
11,799 

Vaccine 
serotype 

IPD(1) 
0 1 12 100%

(3) 
(82.8; 100) 

91.8%(4) 
(58.3; 99.6) 0 18 

100%(5) 
(77.3; 100) 

Serotype 
6B IPD 0 0 5 

100% 
(54.9; 100) 

100% 
(54.5; 100) 0 2 - 

Serotype 
14 IPD 0 0 4 

100% 
(39.6; 100) 

100% 
(43.3; 100) 0 9 

100% 
(49.5; 100) 

IPD Invasive Pneumococcal Disease 
VE Vaccine effectiveness (FinIP) or efficacy (COMPAS) 
N number of subjects per group 
CI Confidence Interval 
(1) In FinIP apart from serotypes 6B and 14, culture-confirmed vaccine serotype IPD cases 

included 7F (1 case in the Synflorix 2+1 clusters), 18C, 19F and 23F (1 case of each in the 
control clusters). In COMPAS, serotypes 5 (2 cases), 18C (4 cases) and 23F (1 case) were 
detected in control group in addition to serotypes 6B and 14. 

(2) the 2 groups of control clusters of infants were pooled 
(3) p-value<0.0001 
(4) p-value=0.0009 



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(5) in the ATP cohort VE was 100% (95% CI: 74.3; 100; 0 versus 16 cases) 
 
In FinIP the overall observed VE against culture-confirmed IPD was 100% (95% CI: 85.6; 100; 0 
versus 14 cases) for the 3+1 schedule, 85.8% (95% CI: 49.1; 97.8; 2 versus 14 cases) for the 2+1 
schedule and 93.0% (95% CI: 74.9; 98.9; 2 versus 14 cases) regardless of the primary vaccination 
schedule. In COMPAS it was 66.7% (95% CI: 21.8; 85.9; 7 versus 21 cases). 
 
Effectiveness following catch-up immunisation 
 
Among the 15,447 children in the catch-up vaccinated cohorts, there were no culture-confirmed IPD 
cases in the Synflorix groups while 5 vaccine serotype IPD cases were observed in the control groups 
(serotypes 4, 6B, 7F, 14 and 19F). 
 
Pneumonia 
 
Efficacy against pneumonia was assessed in COMPAS. The mean duration follow-up from 2 weeks 
post-dose 3 in the ATP cohort was 23 months (range from 0 to 34 months) for the interim analysis 
(IA) and 30 months (range from 0 to 44 months) for the end-of-study analysis. At the end of this IA or 
end-of-study ATP follow-up period, the mean age was 29 months (range from 4 to 41 months) and 36 
months (range from 4 to 50 months), respectively. The proportion of subjects who received the booster 
dose in the ATP cohort was 92.3% in both analyses. 
 
Efficacy of Synflorix against first episodes of likely bacterial Community Acquired Pneumonia (CAP) 
occurring from 2 weeks after the administration of the 3rd dose was demonstrated in the ATP cohort 
(P value ≤ 0.002) in the interim analysis (event-driven; primary objective).  
Likely bacterial CAP (B–CAP) is defined as radiologically confirmed CAP cases with either alveolar 
consolidation/pleural effusion on the chest X-ray, or with non-alveolar infiltrates but with C reactive 
protein (CRP) ≥ 40 mg/l. 
 
The vaccine efficacy against B–CAP observed at the interim analysis is presented below (table 2). 
 
Table 2: Numbers and percentages of subjects with first episodes of B–CAP occurring from 
2 weeks after the administration of the 3rd dose of Synflorix or control vaccine and vaccine 
efficacy (ATP cohort) 

Synflorix 
N=10,295 

Control vaccine 
N=10,201 Vaccine efficacy 

n % (n/N) n % (n/N) 

240 2.3% 304 3.0% 22.0% 
(95% CI: 7.7; 34.2) 

N number of subjects per group 
n/% number/percentage of subjects reporting a first episode of B–CAP anytime from 2 weeks after 

the administration of the 3rd dose 
CI Confidence Interval 
 
In the interim analysis (ATP cohort), the vaccine efficacy against first episodes of CAP with alveolar 
consolidation or pleural effusion (C–CAP, WHO definition) was 25.7% (95% CI: 8.4; 39.6) and 
against first episodes of clinically suspected CAP referred for X-ray was 6.7% (95% CI: 0.7; 12.3). 
 
At the end-of-study analysis (ATP cohort), the vaccine efficacy (first episodes) against B–CAP was 
18.2% (95% CI: 4.1; 30.3), against C–CAP 22.4% (95% CI: 5.7; 36.1) and against clinically suspected 
CAP referred for X-ray 7.3% (95% CI: 1.6; 12.6). Efficacy was 100% (95% CI: 41.9; 100) against 
bacteraemic pneumococcal pneumonia or empyema due to vaccine serotypes. The protection against 
B–CAP before booster dose and at the time or after booster dose was 13.6% (95% CI: -11.3; 33.0) and 
21.7% (95% CI: 3.4; 36.5) respectively. For C–CAP it was 15.1% (95% CI: -15.5; 37.6) and 26.3% 
(95% CI: 4.4; 43.2) respectively. 



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The reduction in B–CAP and C–CAP was greatest in children < 36 months of age (vaccine efficacy of 
20.6% (95% CI: 6.5; 32.6) and 24.2% (95% CI: 7.4; 38.0) respectively). Vaccine efficacy results in 
children > 36 months of age suggest a waning of protection. The persistence of protection against  
B–CAP and C–CAP beyond the age of 36 months is currently not established. 
 
The results of the COMPAS study, which was performed in Latin America, should be interpreted with 
caution due to possible differences in epidemiology of pneumonia in different geographical locations. 
 
In the FinIP study, vaccine effectiveness in reducing hospital-diagnosed pneumonia cases (identified 
based on the ICD 10 codes for pneumonia) was 26.7% (95% CI: 4.9; 43.5) in the 3+1 infant schedule 
and 29.3% (95% CI: 7.5; 46.3) in the 2+1 infant schedule. For catch-up vaccination, vaccine 
effectiveness was 33.2% (95% CI: 3.0; 53.4) in the 7–11 month cohort and 22.4% (95% CI: -8.7; 44.8) 
in the 12–18 month cohort. 
 
Acute Otitis Media (AOM) 
 
Two efficacy studies, COMPAS and POET (Pneumococcal Otitis Media Efficacy Trial), were 
conducted with pneumococcal conjugate vaccines containing protein D: Synflorix and an 
investigational 11-valent conjugate vaccine (which in addition contained serotype 3), respectively. 
 
In COMPAS, 7,214 subjects [Total Vaccinated cohort (TVC)] were included in the AOM efficacy 
analysis of which 5,989 subjects were in the ATP cohort (Table 3). 
 
Table 3: Vaccine efficacy against AOM(1) in COMPAS 

Type or cause of AOM 
Vaccine efficacy  

(95% CI) 
ATP(2) 

Clinical AOM 16.1% (-1.1; 30.4)(3) 

Any pneumococcal serotype 56.1% (13.4; 77.8) 

10 pneumococcal vaccine serotypes 67.1% (17.0; 86.9) 

Non-typeable Haemophilus influenzae (NTHi) 15.0%
(4) 

(-83.8; 60.7) 
CI Confidence Interval 
(1) First episode 
(2) Follow up period for a maximum of 40 months from 2 weeks after third primary dose 
(3) Not statistically significant by pre-defined criteria (One sided p=0.032). However, in TVC 

cohort, vaccine efficacy against first clinical AOM episode was 19% (95% CI: 4.4; 31.4). 
(4) Not statistically significant. 
 
In another large randomised double-blind trial (POET) conducted in the Czech Republic and in 
Slovakia, 4,907 infants (ATP cohort) received either the 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). The vaccine 
efficacy against the first episode of NTHi AOM was 31.1% (95% CI: -3.7; 54.2, not significant). 
Efficacy against any NTHi AOM episode was 35.3% (95% CI: 1.8; 57.4). The estimated vaccine 



12 

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.  
 
No increase in the incidence of AOM due to other bacterial pathogens or non-vaccine/non-vaccine 
related serotypes was observed in either COMPAS (based on the few cases reported) or POET trial. 
 
Effectiveness against physician-diagnosed AOM reported by parents was studied in the nested study 
within the FinIP trial. Vaccine effectiveness was 6.1% (95% CI: -2.7; 14.1) for the 3+1 schedule and 
7.4% (95% CI -2.8; 16.6) for 2+1 schedule for this AOM endpoint in the infant vaccinated cohort. 
 
Impact on nasopharyngeal carriage (NPC) 
 
The effect of Synflorix on nasopharyngeal carriage was studied in 2 double-blind randomised studies 
using an inactive control: in the nested study of FinIP in Finland (5,023 subjects) and in COMPAS 
(1,700 subjects). 
 
In both COMPAS and the nested Finnish study, Synflorix reduced vaccine type carriage with an 
apparent increase in non-vaccine (excluding vaccine-related) serotypes observed after booster. The 
results were not statistically significant across all analyses in COMPAS. However, taken together 
there was a trend for decrease in overall pneumococcal carriage. 
 
In both studies there were significant decrease of individual serotypes 6B and 19F. In the nested 
Finnish study, a significant reduction was also observed for individual serotypes 14, 23F and, in the  
3 dose primary schedule, for the cross-reactive serotype 19A.   
 
In a clinical study NPC was assessed in HIV positive infants (N = 83) and HIV negative infants born 
from HIV positive mothers (N = 101) and compared to HIV negative infants born from HIV negative 
mothers (N = 100). The HIV exposure or infection did not appear to alter the effect of Synflorix on 
pneumococcal carriage up to 24–27 months of age, i.e. up to 15 months following booster vaccination. 
 
Effectiveness in post-marketing surveillance 
 
In Brazil, Synflorix was introduced into the national immunisation programme (NIP) using a 3+1 
schedule in infants (2, 4, 6 months of age and a booster dose at 12 months) with a catch-up campaign 
in children up to 2 years of age. Based on almost 3 years of surveillance following Synflorix 
introduction, a matched case-control study reported a significant decrease in culture or PCR confirmed 
IPD due to any vaccine serotype, and IPD due to individual serotypes 6B, 14 and 19A. 
 
Table 4: Summary of effectiveness of Synflorix for IPD in Brazil 

Types of IPD(1) Adjusted Effectiveness(2) 
% (95% CI) 

Any vaccine serotype IPD(3) 
 

- Invasive pneumonia or bacteraemia 
 

- Meningitis 

83.8% (65.9; 92.3) 
 

81.3% (46.9; 93.4) 
 

87.7% (61.4; 96.1) 



13 

IPD due to individual serotypes(4) 
 

- 6B 
 

- 14 
 

- 19A 

 
 

82.8% (23.8; 96.1) 
 

87.7% (60.8; 96.1) 
 

82.2% (10.7; 96.4) 

(1) Culture or PCR confirmed IPD 
(2) The adjusted effectiveness represents the percent reduction in IPD in the Synflorix vaccinated 
group compared to the unvaccinated group, controlling for confounding factors. 
(3) Culture or PCR confirmed cases for serotypes 4, 6B, 7F, 9V, 14, 18C, 19F and 23F contributed to 
the analysis. 
(4) Individual serotypes for which statistical significance was reached in the effectiveness analysis 
controlling for confounding factors (no adjustment for multiplicity performed). 
 
In Finland, Synflorix was introduced into NIP with a 2+1 schedule in infants (3, 5 months of age and a 
booster dose at 12 months) without catch-up campaign. Before and after NIP comparison suggests a 
significant decrease in the incidence of any culture confirmed IPD, any vaccine serotype IPD and IPD 
due to serotype 19A. 
 
Table 5: Rates of IPD and the corresponding rate reductions in Finland 

IPD Incidence per 100,000 person years 
 

Relative rate reduction(1)  
% (95% CI) 

Before NIP After NIP 
Any culture confirmed 62.9 12.9 80% (72; 85) 

Any vaccine serotype(2) 49.1 4.2 92% (86; 95) 

Serotype 19A 5.5 2.1 62% (20; 85) 
(1) The relative rate reduction indicates how much the incidence of IPD in children of ≤5 years of age 
was reduced in the Synflorix cohort (followed for 3 years after NIP introduction) versus age and 
season matched non-vaccinated historical cohorts (each followed for 3 year periods before 
introduction of Synflorix into NIP). 
(2) Culture confirmed cases for serotypes 1, 4, 6B, 7F, 9V, 14, 18C, 19F and 23F contributed to the  
analysis. 
 
In Quebec, Canada, Synflorix was introduced into the infant immunisation programme (2 primary 
doses to infants less than 6 months of age and a booster dose at 12 months) following 4.5 years of use 
of 7-valent Prevenar. Based on 1.5 years of surveillance following Synflorix introduction, with over 
90% coverage in the vaccine-eligible age group, a decrease in vaccine serotype IPD incidence (largely 
due to changes in serotype 7F disease) was observed with no concomitant increase in non-vaccine 
serotype IPD incidence. Overall, the incidence of IPD was 35/100,000 person-years in those cohorts 
exposed to Synflorix, and 64/100,000 person-years in those exposed to 7-valent Prevenar, representing 
a statistically significant difference (p = 0.03). No direct cause-and-effect can be inferred from 
observational studies of this type. 
 
Immunogenicity data 
 
Immunologic non-inferiority to 7-valent Prevenar 
 
The assessment of potential efficacy against IPD pre-licensure was 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), as 
recommended by the WHO. Immune responses to the extra three serotypes in Synflorix were also 
measured. 
 



14 

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 6). 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 
unclear, as Synflorix was observed to be effective against IPD caused by serotype 6B in a double-
blind, cluster-randomized clinical study (see Table 1). 
 
The percentage of vaccinees reaching the threshold 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 6: 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 % ≥ 0.20µg/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 
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. 
 
It has also been demonstrated that Synflorix induces an immune response to the cross-reactive 
serotype 19A with 48.8% (95% CI: 42.9; 54.7) of vaccinees reaching an OPA titre ≥ 8 one month after 
a booster dose. 
 
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 vaccine serotypes and the cross-reactive 
serotype 19A demonstrating the induction of immune memory after the three-dose primary course. 
 
Additional immunogenicity data 



15 

 
Infants from 6 weeks to 6 months of age: 
 
3-dose primary schedule 
 
In clinical studies the immunogenicity of Synflorix was evaluated after a 3-dose primary vaccination 
series (6941 subjects) according to different schedules (including 6-10-14 weeks, 2-3-4, 3-4-5 or 2-4-6 
months of age) and after a fourth (booster) dose (5645 subjects) given at least 6 months after the last 
primary dose and from the age of 9 months onwards. 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 
 
In clinical studies the immunogenicity of Synflorix was evaluated after a 2-dose primary vaccination 
series (470 subjects) according to different schedules (including 6–14 weeks, 2–4 or 3–5 months of 
age) and after a third (booster) dose (470 subjects) given at least 6 months after the last primary dose 
and from the age of 9 months onwards.  
 
A clinical study evaluated the immunogenicity of Synflorix in 2-dose or 3-dose primed subjects in 
four European countries. 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 vaccine serotypes (Table 7 and Table 8). 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 
vaccine serotype (Table 7 and Table 8). 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 7: Percentage of 2-dose primed subjects with antibody concentrations ≥ 0.20 µg/ml one 
month post-primary and one month post-booster 

Antibody 
≥ 0.20 µg/ml (ELISA) 

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 8: Percentage of 3-dose primed subjects with antibody concentrations ≥ 0.20 µg/ml one 
month post-primary and one month post-booster 

Antibody 
≥ 0.20 µg/ml (ELISA) 

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 



16 

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 

 
For the cross-reactive serotype 19A, similar ELISA antibody GMCs were observed post-primary and 
post-booster for the 2-dose schedule [0.14 µg/ml (95% CI: 0.12; 0.17) and 0.73 µg/ml (95% CI: 0.58; 
0.92)] and the 3-dose schedule [0.19 µg/ml (95% CI: 0.16; 0.24) and 0.87 µg/ml (95% CI: 0.69; 
1.11)]. The percentage of subjects with OPA titres ≥ 8 and GMTs observed post-primary and post-
booster were lower in the 2-dose schedule than that in the 3-dose schedule. In both schedules, a 
booster response indicative of immunological priming was observed. 
 
The clinical consequences of the lower post-primary and post-booster immune responses observed 
after the 2-dose primary schedule are not known.  
 
A clinical study conducted in South Africa assessed the immunogenicity of Synflorix after 3-dose (6-
10-14 weeks of age) or 2-dose (6-14 weeks of age) priming followed by a booster dose at 9-10 months 
of age. After primary vaccination, for the vaccine serotypes the percentages of subjects reaching 
antibody threshold and with OPA titres ≥ 8 were similar after 2-dose compared to 3-dose except lower 
OPA percentage for serotype 14. The antibody GMCs and OPA GMTs were lower after 2-dose for 
most vaccine serotypes. 
 
For the cross-reactive serotype 19A, similar percentages of subjects reaching antibody threshold and 
OPA titres ≥ 8 and similar antibody GMC and OPA GMT were observed post-primary in both groups. 
Overall, the pre-booster persistence of immune responses was lower in the 2-dose compared to the  
3-dose priming group for most vaccine serotypes and was similar for serotype 19A. 
 
Booster dose at 9–10 months of age 
 
In the study conducted in South Africa, the booster dose given at 9-10 months of age induced marked 
increases in antibody GMCs and OPA GMTs for each vaccine serotype and serotype 19A in both 2-
dose and 3-dose priming groups indicative of immunological priming. 
 
Booster dose at 9–12 versus 15–18 months of age 
 
A clinical study conducted in India assessing a booster dose given at 9-12 or 15-18 months of age in 
66 and 71 children, respectively, following primary vaccination at 6, 10 and 14 weeks of age, did not 
suggest differences between groups in terms of antibody GMCs. Higher OPA GMTs in the group 
boosted at 15-18 months of age were observed for most of the vaccine serotypes and serotype 19A. 
However, the clinical relevance of this observation is not known. 
 
Immune memory 
 
In the follow-up of the European study evaluating the 2-dose and 3-dose primary vaccination 
schedules, 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 and the cross-reactive serotype 19A. 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 and 86.4% for serotype 19A. After a single dose of Synflorix, administered 
during the 4th year of life, as a challenge dose, the fold increase in ELISA antibody GMCs and OPA 
GMTs, pre to post vaccination, was 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 and the cross-reactive serotype 19A. 
 



17 

Unvaccinated infants and children ≥ 7 months of age: 
 
The immune responses elicited by Synflorix in previously unvaccinated older children were evaluated 
in three clinical studies. 
 
The first clinical study evaluated the immune responses for vaccine serotypes and the cross-reactive 
serotype 19A in children aged 7–11 months, 12–23 months and 2 to 5 years: 
 

• Children aged 7–11 months received 2 primary doses followed by a booster dose in the 
second year of life. The immune responses after the booster dose 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. 

• In children aged 12–23 months, the immune responses elicited after two doses were 
comparable to the responses elicited after three doses in infants below 6 months of age, 
except for vaccine serotypes 18C and 19F as well as serotype 19A for which responses 
were higher in the 12–23 months children. 

• In children aged 2 to 5 years that received 1 dose, the ELISA antibody GMCs were similar 
for 6 vaccine serotypes as well as serotype 19A than those achieved following a 3-dose 
vaccination schedule in infants below 6 months of age while they were lower for 
4 vaccine serotypes (serotypes 1, 5, 14 and 23F). The OPA GMTs were similar or higher 
following a single dose than a 3-dose primary course in infants below 6 months of age, 
except for serotype 5. 

  
In the second clinical study, a single dose administered four months after two catch-up doses at 12–20 
months of age elicited a marked increase of ELISA GMCs and OPA GMTs (when comparing the 
responses pre and post the last dose), indicating that two catch-up doses provide adequate priming. 
 
The third clinical study showed that the administration of 2 doses with a 2 month interval starting at 
36–46 months of age resulted in higher ELISA antibody GMCs and OPA GMTs than those observed 
one month after a 3-dose primary vaccination for each vaccine serotype and the cross-reactive 
serotype 19A. The proportion of subjects with an ELISA antibody concentration ≥ 0.20 µg/ml or an 
OPA titre ≥ 8 for each vaccine serotype was comparable or higher in the catch-up group than in the 3-
dose primed infants. 
 
Long-term persistence of antibodies has not been investigated after administration of a primary series 
in infants plus booster or after a 2-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. 
 
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 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), for each vaccine serotype at least 
92.7% of subjects achieved ELISA antibody concentrations ≥ 0.20 µg/ml and at least 81.7% achieved 
OPA titres ≥ 8 except serotype 1 (at least 58.8% with OPA titres ≥ 8). Similar antibody GMCs and 



18 

OPA GMTs were observed for all infants except lower antibody GMCs for serotypes 4, 5, 9V and the 
cross-reactive serotype 19A 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 
each vaccine serotype and the cross-reactive serotype 19A, 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, for each vaccine serotype at least 97.6% of subjects 
achieved ELISA antibody concentrations ≥ 0.20 µg/ml and at least 91.9% achieved OPA titres ≥ 8. 
 
Immunogenicity in special population 
 
HIV positive (HIV+/+) infants and HIV negative infants born from HIV positive mothers (HIV+/-) 
 
In a clinical study conducted in South Africa the immunogenicity of Synflorix administered as a 
3-dose primary vaccination course (at 6, 10 and 14 weeks of age) followed by a booster dose (at 9 to 
10 months of age) was assessed in 70 HIV positive (HIV+/+) infants, 91 HIV negative infants born 
from HIV positive mothers (HIV+/-) and 93 HIV negative infants born from HIV negative mothers  
(HIV-/-). Only HIV+/+ infants with WHO classification stage 1 (asymptomatic) or 2 (mild symptoms) 
were to be enrolled. 
 
For most vaccine serotypes, group comparisons did not suggest any differences in post-primary 
immune responses between the HIV+/+ and HIV-/- groups, or the HIV+/- and HIV-/- groups, except 
for a trend towards a lower percentage of subjects reaching OPA titres ≥ 8 and lower OPA GMTs in 
the HIV+/+ group. The clinical relevance of this lower post-primary OPA response is not known. For 
the cross-reactive serotype 19A, the results did not suggest any differences in ELISA antibody GMCs 
and OPA GMTs between groups. 
 
The booster dose of Synflorix in HIV+/+ and HIV+/- infants induced robust increases in ELISA 
antibody GMCs and OPA GMTs for each vaccine serotype and serotype 19A indicative of 
immunological priming. For most vaccine serotypes and serotype 19A, group comparisons did not 
suggest any differences post-booster dose in ELISA antibody GMCs and OPA GMTs between the 
HIV+/+ and HIV-/- groups, or the HIV+/- and HIV-/- groups. 
 
The results for protein D suggested comparable post-primary and post-booster immune responses 
between groups. 
 
In each group, persistence of the immune responses was observed at 24–27 months of age, i.e. up to 15 
months following booster vaccination. 
 
Children with sickle cell disease 
 
A clinical study conducted in Burkina Faso assessed the immunogenicity of Synflorix administered to 
146 children with SCD (haemoglobin SS disease, haemoglobin SC disease or with β-thalassemia) 
compared to 143 age-matched children without SCD. Among children with SCD, 48 children  
<6 months of age received primary vaccination at 8, 12 and 16 weeks of age, followed by a booster 
dose at 9–10 months of age, 50 children aged 7–11 months and 48 aged 12–23 months started  
catch-up vaccination according to their age. The immune response to Synflorix for each of the vaccine 
serotypes and serotype 19A, as well as for protein D, did not appear to be influenced by SCD. 
 
Children with splenic dysfunction 
 
Immunogenicity and safety of Synflorix were assessed in a limited number of primed or unprimed 
subjects with congenital or acquired asplenia, splenic dysfunction or complement deficiencies:  
6 subjects 2–5 years of age and 40 subjects 6–17 years of age (Synflorix is indicated up to 5 years of 
age). Synflorix was shown to be immunogenic and no new safety concerns were observed in this 
study. 



19 

 
Immunogenicity of Synflorix containing the preservative 2-phenoxyethanol (2-PE) 
 
Immunogenicity of Synflorix containing the preservative 2-PE (presented in a 4-dose container) was 
assessed in healthy infants vaccinated at 6, 10 and 18 weeks of age and compared to those receiving 
Synflorix without added preservative (160 enrolled subjects per group). 
 
Immune responses were compared using non-inferiority criteria in terms of antibody GMC ratio 
(GMC from group of subjects receiving Synflorix without 2-PE over GMC from group of subjects 
receiving Synflorix with 2-PE) for each of the 10 vaccine serotypes and for the cross-reactive serotype 
19A. 
 
Non-inferiority was demonstrated as the upper limit of the 2-sided 95% CI of the antibody GMC ratios 
was below 2 for each of the 10 vaccine serotypes and for serotype 19A. In addition, OPA GMTs were 
in same ranges for both groups. 
 
5.2  Pharmacokinetic properties 
 
Not applicable. 
 
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.  PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
1-dose and 2-dose containers 
Sodium chloride 
Water for injections 
 
4-dose container 
Sodium chloride 
2-phenoxyethanol 
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  
 
1-dose and 2-dose containers 
4 years 
 
4-dose container 
3 years 
 
After first opening of multidose vial: 
 
2-dose vial 



20 

After first opening of the 2-dose 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. 
 
4-dose vial 
After first opening of the 4-dose vial, the vaccine may be stored for a maximum of 28 days in a 
refrigerator (2 °C – 8 °C). If not used within 28 days 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. 
 
Multidose vial 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5  Nature and contents of container 
 
Pre-filled syringe 
0.5 ml of suspension in a pre-filled syringe (type I glass) for 1 dose with a plunger stopper (butyl 
rubber) with or without needles. Pack size of 1, 10 or 50. 
 
Vial 
0.5 ml of suspension in a vial (type I glass) for 1 dose with a stopper (butyl rubber). Pack size of 1, 10 
or 100. 
 
Multidose vial 
1 ml of suspension in a vial (type I glass) for 2 doses with a stopper (butyl rubber). Pack size of 100. 
2 ml of suspension in a vial (type I glass) for 4 doses with a stopper (butyl rubber). Pack size of 10 or 
100. 
 
Not all pack sizes may be marketed. 
 
6.6  Special precautions for disposal and other handling 
 
Pre-filled syringe 
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 use. 
 
The vaccine should be well shaken before use. 
 



21 

Instructions for administration of the vaccine 
 
1. Holding the syringe barrel in one hand  
(avoid holding the syringe plunger),  
unscrew the syringe cap by twisting it anticlockwise. 
 
 
 
 
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. 
 
 
 
 
 
 
Vial 
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.  
 
Multidose vial 
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 medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7.  MARKETING AUTHORISATION HOLDER 
 
GlaxoSmithKline Biologicals S.A. 
Rue de l’Institut 89 

Syringe plunger 

Syringe barrel Syringe cap 

Needle protector 



22 

B-1330 Rixensart, Belgium 
 
 
8.  MARKETING AUTHORISATION NUMBER(S) 

 
Pre-filled syringe 
EU/1/09/508/001 
EU/1/09/508/002 
EU/1/09/508/003 
EU/1/09/508/004 
EU/1/09/508/005 
EU/1/09/508/010 
 
Vial 
EU/1/09/508/006 
EU/1/09/508/007 
EU/1/09/508/008 
 
Multidose vial 
2-dose vial 
EU/1/09/508/009 
4-dose vial 
EU/1/09/508/012 
EU/1/09/508/013 
 
 
9.  DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 30 March 2009 
Date of latest renewal:  
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu/. 
  



23 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE 
SUBSTANCES AND MANUFACTURER RESPONSIBLE 
FOR BATCH RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SYPPLY 

AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 
D. CONDITIONS FOR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

 
  



24 

A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCES AND 
MANUFACTURER 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. 
Homoki Nagy István utca 1. 
2100 Gödöllö  
Hungary 
 
GlaxoSmithKline Biologicals 
10, Tuas South Avenue 8 
Singapore 637421 
Singapore 
 
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 OR RESTRICTION REGARDING SUPPLY AND USE 
 
Medicinal product subject to medical prescription. 
 
• Official batch release 
 
In accordance with Article 114 of Directive 2001/83/EC, the official batch release will be undertaken 
by a state laboratory or a laboratory designated for that purpose. 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

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

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 



25 

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

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

  



26 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



27 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



28 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
CARTON OF PRE-FILLED SYRINGE WITH OR WITHOUT NEEDLE, PACK OF 1, 10, 50 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
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 for serotypes 4, 18C and 19F 
 
 
3. LIST OF EXCIPIENTS 
 
Sodium chloride 
Water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection in pre-filled syringe 
 
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 
 
The vaccine should be allowed to reach room temperature before use 
Shake well before use 
Read the package leaflet before use 
Intramuscular use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 



29 

 
Keep out of the sight and reach 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 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
GlaxoSmithKline Biologicals s.a. 
Rue de l’Institut 89 
B-1330 Rixensart, Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
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 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 



30 

 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN: 
 
  



31 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
PRE-FILLED SYRINGE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
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 
  



32 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
VIAL, PACK OF 1, 10, 100 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
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 for serotypes 4, 18C and 19F 
 
 
3. LIST OF EXCIPIENTS 
 
Sodium chloride 
Water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
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 SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 



33 

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

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
GlaxoSmithKline Biologicals s.a. 
Rue de l’Institut 89 
B-1330 Rixensart, Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
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 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN: 



34 

 



35 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
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 
  



36 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
VIAL MULTIDOSE (2 DOSES), PACK OF 100 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Synflorix suspension for injection in multidose container (2 doses) 
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 for serotypes 4, 18C and 19F 
 
 
3. LIST OF EXCIPIENTS 
 
Sodium chloride 
Water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection in multidose container (2 doses) 
 
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 SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator 
Do not freeze 



37 

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 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
GlaxoSmithKline Biologicals s.a. 
Rue de l’Institut 89 
B-1330 Rixensart, Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU//1/09/508/009  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN: 
  



38 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
VIAL LABEL MULTIDOSE (2 DOSES) 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
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/dose) 
 
 
6. OTHER 
 
 
  



39 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
VIAL MULTIDOSE (4 DOSES), PACK OF 10, 100 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Synflorix suspension for injection in multidose container (4 doses) 
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 for serotypes 4, 18C and 19F 
 
 
3. LIST OF EXCIPIENTS 
 
Sodium chloride 
2-phenoxyethanol 
Water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection in multidose container (4 doses) 
 
10 MULTIDOSE vials (4 doses per vial – 0.5 ml per dose) 
100 MULTIDOSE vials (4 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 SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 



40 

Store in a refrigerator 
Do not freeze 
Store in the original package in order to protect from light 
After first use, the product may be stored in a refrigerator for a maximum of 28 days 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
GlaxoSmithKline Biologicals s.a. 
Rue de l’Institut 89 
B-1330 Rixensart, Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/508/012 – pack of 10 
EU/1/09/508/013 – pack of 100 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN: 
  



41 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
VIAL LABEL MULTIDOSE (4 DOSES) 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Synflorix injection 
IM 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
4 doses (0.5 ml/dose) 
 
 
6. OTHER 
 
 
  



42 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 
  



43 

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 because it contains 
important information for you. 
• 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 only. Do not pass it on to others.  
• If your child gets any side effects, talk to your doctor or pharmacist. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
1. What Synflorix is and what it is used for 
2. What you need to know before your child receives Synflorix 
3. How Synflorix is given 
4. Possible side effects 
5. How to store Synflorix 
6. Contents of the pack and other 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 5 years of age against: 
a bacteria called ‘Streptococcus pneumoniae’. This bacteria can cause serious illnesses including 
meningitis, sepsis and bacteraemia (bacteria in blood stream) as well as ear infection or pneumonia. 
 
How Synflorix 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. What you need to know before your child receives Synflorix 
 
Synflorix should not be given if: 
 
• your child is allergic to the active substance, or any of the other ingredients of 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 if any of the above applies to your child. If you are not sure, talk to your 
doctor or pharmacist before your child is given Synflorix. 
 
Warnings and precautions 
 
Check with your doctor or pharmacist before this vaccine is given if: 
• your child has a bleeding problem or bruises easily. 



44 

 
In children as of 2 years of age, fainting can occur following, or even before, any needle injection, 
therefore tell the doctor or nurse if your child fainted with a previous injection. 
 
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 human immunodeficiency virus (HIV) 
infection or immunosuppressive therapy) may not get the full benefit from Synflorix. 
 
If you are not sure, talk to your doctor or pharmacist before having Synflorix. 
 
Children above 5 years old 
 
For children above 5 years old safety and efficacy of the vaccine have not been established, therefore 
vaccination of these children is not recommended. 
 
Other medicines and Synflorix 
 
Tell your doctor or pharmacist if your child is taking, has recently taken or might take any other 
medicines, 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 and 
serogroups A, C, W-135, Y conjugate vaccines. A different place for the injection will be used for 
each vaccine. 
 
Your doctor may ask you to give your child a medicine that lowers fever (such as paracetamol) before 
or immediately after Synflorix is given, especially in children being vaccinated with Synflorix and 
vaccines containing whole cell pertussis at the same time. It is also recommended to administer a 
medicine that lowers fever in children with convulsion disorders or with prior history of febrile 
convulsions. 
However if your child has received paracetamol before or immediately after Synflorix is given, the 
obtained levels of antibodies may be slightly reduced. It is not known whether the reduction in 
antibody levels has an impact on the protection against pneumococcal disease. 
 
Synflorix contains sodium 
 
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say 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 (from 6 weeks to 6 months of age) 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. 
 



45 

• Each injection will be given at least one month apart except for the last injection (booster), 
which will be given at least 6 months after the third injection. 

• The first injection may be given from the age of 6 weeks onwards. The last injection (booster) 
may be given from the age of 9 months onwards. 

• You will be told when your child should come back for the next injections. 
 
Preterm infants (born after 27 weeks and less than 37 weeks of pregnancy): 
Your child (from 2 months to 6 months of age) will receive 3 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 (booster) will be given in the second year of life with at least two months apart. 
 
Children aged 12 months to 5 years will receive 2 injections. Each injection will be given at least two 
months apart. 
 
Special populations: 
Children from 6 weeks up to 5 years of age considered to be at a higher risk of pneumococcal 
infection (such as those with HIV infection, sickle cell disease or impaired or abnormal functioning of 
the spleen) may receive Synflorix. Please speak to your doctor for information on the number and 
timing of injections for your child. 
 
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. 
 
If you have any further questions on the use of this vaccine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. The 
following side effects may happen with this medicine: 
 
Severe allergic reactions may very rarely occur (with up to 1 in 10,000 doses of the vaccine). These 
can be recognised by: 
- raised and itchy rash (hives) 
- swelling, sometimes of the face or mouth (angioedema), causing difficulty in breathing 
- collapse 
These reactions will usually occur before leaving the doctor’s surgery. However, if your child gets any 
of these symptoms you should contact a doctor urgently. 
 
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) 
• itching, blood clot, bleeding or a small lump where the injection is given 



46 

• nausea, diarrhoea or feeling sick (vomiting) 
• unusual crying 
• temporarily stopping breathing (apnoea) if your child is born prematurely (before or at 28 weeks 

of pregnancy) 
• headache 
• skin rash 
• diffuse swelling of the injected limb, sometimes involving the adjacent joint 
• hives 
 
Rare (these may occur with up to 1 in 1,000 doses of the vaccine) 
• fits without temperature or due to high temperature (fever) 
• allergic reactions such as skin allergies 
• collapse (sudden onset of muscle floppiness), periods of unconsciousness or lack of awareness, 

and paleness or bluish skin discoloration 
 
Very rare ( these may occur with up to 1 in 10,000 doses of the vaccine) 
• Kawasaki disease (major signs of the illness are for instance: fever, skin rash, swollen lymph 

glands, inflammation and rash of the mucous membranes of the mouth and throat) 
 
Booster doses of Synflorix may increase the risk of side effects. 
For children > 12 months of age, the risk of pain at the injection site may increase with increasing age. 
 
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. 
 
Reporting of side effects 
 
If your child gets any side effects, talk to your doctor or pharmacist. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Synflorix 
 
Keep this medicine out of the sight and reach of children. 
 
• Do not use this medicine 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. 
 
Do not throw away any medicines via wastewater or household waste.  Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Synflorix contains 
 
• The active substances are: 

 
One 0.5 ml dose contains: 
Pneumococcal polysaccharide serotype 11,2 1 microgram 
Pneumococcal polysaccharide serotype 41,2 3 micrograms 

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


47 

Pneumococcal polysaccharide serotype 51,2 1 microgram 
Pneumococcal polysaccharide serotype 6B1,2 1 microgram 
Pneumococcal polysaccharide serotype 7F1,2 1 microgram 
Pneumococcal polysaccharide serotype 9V1,2 1 microgram 
Pneumococcal polysaccharide serotype 141,2 1 microgram 
Pneumococcal polysaccharide serotype 18C1,3 3 micrograms 
Pneumococcal polysaccharide serotype 19F1,4 3 micrograms 
Pneumococcal polysaccharide serotype 23F1,2 1 microgram  
 
1 adsorbed on aluminium phosphate  0.5 milligram Al3+ in total 

 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 (see section 2 for further information) 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 for 1 dose 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: 
 
Belgique/België/Belgien  
GlaxoSmithKline Pharmaceuticals s.a./n.v. 
Tél/Tel: + 32 10 85 52 00 
 

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

България 
ГлаксоСмитКлайн ЕООД 
Тел.: + 359 2 953 10 34 
 

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

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

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

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

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



48 

 
Deutschland 
GlaxoSmithKline GmbH & Co. KG 
Tel: + 49 (0)89 360448701 
produkt.info@gsk.com 
 

Nederland 
GlaxoSmithKline BV 
Tel: + 31 (0)30 69 38 100 
nlinfo@gsk.com 
 

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

Norge 
GlaxoSmithKline AS 
Tlf: + 47 22 70 20 00 
 

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

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

España 
GlaxoSmithKline, S.A. 
Tel: + 34 902 202 700 
es-ci@gsk.com 
 

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

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

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

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

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

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

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

Ísland 
Vistor hf.  
Sími: +354 535 7000 
 

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

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

Suomi/Finland 
GlaxoSmithKline Oy 
Puh/Tel: + 358 10 30 30 30 
Finland.tuoteinfo@gsk.com 
 

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

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

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

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

This leaflet was last revised in  
 



49 

Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu 
 
 
The following information is intended for healthcare professionals only: 
 
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 use. 
 
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. 
 
Instructions for administration of the vaccine presented in pre-filled syringe 
 
1. Holding the syringe barrel in one hand  
(avoid holding the syringe plunger),  
unscrew the syringe cap by twisting it anticlockwise. 
 
 
 
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. 
 
 
 
 
 
 
 
Any unused product or waste material should be disposed of in accordance with local requirements. 
 
  

Syringe plunger 

Syringe barrel Syringe cap 

Needle protector 



50 

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 because it contains 
important information for you. 
• 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 only. Do not pass it on to others.  
• If your child gets any side effects, talk to your doctor or pharmacist. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet:  
1. What Synflorix is and what it is used for 
2. What you need to know before your child receives Synflorix 
3. How Synflorix is given 
4. Possible side effects 
5. How to store Synflorix 
6. Contents of the pack and other 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 5 years of age against: 
a bacteria called ‘Streptococcus pneumoniae’. This bacteria can cause serious illnesses including 
meningitis, sepsis and bacteraemia (bacteria in blood stream) as well as ear infection or pneumonia. 
 
How Synflorix 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. What you need to know before your child receives Synflorix 
 
Synflorix should not be given if: 
 
• your child is allergic to the active substance, or any of the other ingredients of 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 if any of the above applies to your child. If you are not sure, talk to your 
doctor or pharmacist before your child is given Synflorix. 
 
Warnings and precautions 
 
Check with your doctor or pharmacist before this vaccine is given if: 
• your child has a bleeding problem or bruises easily. 



51 

 
In children as of 2 years of age, fainting can occur following, or even before, any needle injection, 
therefore tell the doctor or nurse if your child fainted with a previous injection. 
 
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 human immunodeficiency virus (HIV) 
infection or immunosuppressive therapy) may not get the full benefit from Synflorix. 
 
If you are not sure, talk to your doctor or pharmacist before having Synflorix. 
 
Children above 5 years old 
 
For children above 5 years old safety and efficacy of the vaccine have not been established, therefore 
vaccination of these children is not recommended. 
  
Other medicines and Synflorix 
 
Tell your doctor or pharmacist if your child is taking, has recently taken or might take any other 
medicines, 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 and 
serogroups A, C, W-135, Y conjugate vaccines. A different place for the injection will be used for 
each vaccine. 
 
Your doctor may ask you to give your child a medicine that lowers fever (such as paracetamol) before 
or immediately after Synflorix is given, especially in children being vaccinated with Synflorix and 
vaccines containing whole cell pertussis at the same time. It is also recommended to administer a 
medicine that lowers fever in children with convulsion disorders or with prior history of febrile 
convulsions. 
However if your child has received paracetamol before or immediately after Synflorix is given, the 
obtained levels of antibodies may be slightly reduced. It is not known whether the reduction in 
antibody levels has an impact on the protection against pneumococcal disease. 
 
Synflorix contains sodium 
 
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say 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 (from 6 weeks to 6 months of age) 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. 



52 

 
• Each injection will be given at least one month apart except for the last injection (booster), 

which will be given at least 6 months after the third injection. 
• The first injection may be given from the age of 6 weeks onwards. The last injection (booster) 

may be given from the age of 9 months onwards. 
• You will be told when your child should come back for the next injections. 
 
Preterm infants (born after 27 weeks and less than 37 weeks of pregnancy): 
Your child (from 2 months to 6 months of age) will receive 3 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 (booster) will be given in the second year of life with at least two months apart. 
 
Children aged 12 months to 5 years will receive 2 injections. Each injection will be given at least two 
months apart. 
 
Special populations: 
Children from 6 weeks up to 5 years of age considered to be at a higher risk of pneumococcal 
infection (such as those with HIV infection, sickle cell disease or impaired or abnormal functioning of 
the spleen) may receive Synflorix. Please speak to your doctor for information on the number and 
timing of injections for your child. 
 
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. 
 
If you have any further questions on the use of this vaccine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. The 
following side effects may happen with this medicine: 
 
Severe allergic reactions may very rarely occur (with up to 1 in 10,000 doses of the vaccine). These 
can be recognised by: 
- raised and itchy rash (hives) 
- swelling, sometimes of the face or mouth (angioedema), causing difficulty in breathing 
- collapse 
These reactions will usually occur before leaving the doctor’s surgery. However, if your child gets any 
of these symptoms you should contact a doctor urgently. 
 
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) 



53 

• itching, blood clot, bleeding or a small lump where the injection is given 
• nausea, diarrhoea or feeling sick (vomiting) 
• unusual crying 
• temporarily stopping breathing (apnoea) if your child is born prematurely (before or at 28 weeks 

of pregnancy) 
• headache 
• skin rash 
• diffuse swelling of the injected limb, sometimes involving the adjacent joint 
• hives 
 
Rare (these may occur with up to 1 in 1,000 doses of the vaccine) 
• fits without temperature or due to high temperature (fever) 
• allergic reactions such as skin allergies 
• collapse (sudden onset of muscle floppiness), periods of unconsciousness or lack of awareness, 

and paleness or bluish skin discoloration 
 
Very rare ( these may occur with up to 1 in 10,000 doses of the vaccine) 
• Kawasaki disease (major signs of the illness are for instance: fever, skin rash, swollen lymph 

glands, inflammation and rash of the mucous membranes of the mouth and throat) 
 
Booster doses of Synflorix may increase the risk of side effects. 
For children > 12 months of age, the risk of pain at the injection site may increase with increasing age. 
 
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. 
 
Reporting of side effects 
 
If your child gets any side effects, talk to your doctor or pharmacist. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Synflorix 
 
Keep this medicine out of the sight and reach of children. 
 
• Do not use this medicine 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. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Synflorix contains 
 
• The active substances are: 

 
One 0.5 ml dose contains: 
Pneumococcal polysaccharide serotype 11,2 1 microgram 

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


54 

Pneumococcal polysaccharide serotype 41,2 3 micrograms 
Pneumococcal polysaccharide serotype 51,2 1 microgram 
Pneumococcal polysaccharide serotype 6B1,2 1 microgram 
Pneumococcal polysaccharide serotype 7F1,2 1 microgram 
Pneumococcal polysaccharide serotype 9V1,2 1 microgram 
Pneumococcal polysaccharide serotype 141,2 1 microgram 
Pneumococcal polysaccharide serotype 18C1,3 3 micrograms 
Pneumococcal polysaccharide serotype 19F1,4    3 micrograms 
Pneumococcal polysaccharide serotype 23F1,2      1 microgram   
 
1 adsorbed on aluminium phosphate  0.5 milligram Al3+ in total 

 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 (see section 2 for further information) 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 for 1 dose 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: 
 
Belgique/België/Belgien 
GlaxoSmithKline Pharmaceuticals s.a./n.v. 
Tél/Tel: + 32 10 85 52 00 
 

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

България 
ГлаксоСмитКлайн ЕООД 
Тел.: + 359 2 953 10 34 
 

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

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

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

Danmark 
GlaxoSmithKline Pharma A/S 
Tlf: + 45 36 35 91 00 

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



55 

dk-info@gsk.com 
 

 

Deutschland 
GlaxoSmithKline GmbH & Co. KG 
Tel: + 49 (0)89 360448701 
produkt.info@gsk.com 
 

Nederland 
GlaxoSmithKline BV 
Tel: + 31 (0)30 69 38 100 
nlinfo@gsk.com 
 

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

Norge 
GlaxoSmithKline AS 
Tlf: + 47 22 70 20 00 
 

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

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

España 
GlaxoSmithKline, S.A. 
Tel: + 34 902 202 700 
es-ci@gsk.com 
 

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

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

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

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

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

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

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

Ísland 
Vistor hf.  
Sími: +354 535 7000 
 

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

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

Suomi/Finland 
GlaxoSmithKline Oy 
Puh/Tel: + 358 10 30 30 30 
Finland.tuoteinfo@gsk.com 
 

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

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

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

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

This leaflet was last revised in  



56 

 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu 
 
 
The following information is intended for healthcare professionals only: 
 
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. 
 
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. 
  



57 

Package leaflet: Information for the user 
 

Synflorix suspension for injection in multidose container (2 doses) 
Pneumococcal polysaccharide conjugate vaccine (adsorbed) 

 
 
Read all of this leaflet carefully before your child receives this vaccine because it contains 
important information for you. 
• 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 only. Do not pass it on to others.  
• If your child gets any side effects, talk to your doctor or pharmacist. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet:  
1. What Synflorix is and what it is used for 
2. What you need to know before your child receives Synflorix 
3. How Synflorix is given 
4. Possible side effects 
5. How to store Synflorix 
6. Contents of the pack and other 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 5 years of age against: 
a bacteria called ‘Streptococcus pneumoniae’. This bacteria can cause serious illnesses including 
meningitis, sepsis and bacteraemia (bacteria in blood stream) as well as ear infection or pneumonia. 

 
How Synflorix 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. What you need to know before your child receives Synflorix 
 
Synflorix should not be given if: 
 
• your child is allergic to the active substance, or any of the other ingredients of 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 if any of the above applies to your child. If you are not sure, talk to your 
doctor or pharmacist before your child is given Synflorix. 
 
Warnings and precautions 
 
Check with your doctor or pharmacist before this vaccine is given if: 
• your child has a bleeding problem or bruises easily. 



58 

 
In children as of 2 years of age, fainting can occur following, or even before, any needle injection, 
therefore tell the doctor or nurse if your child fainted with a previous injection. 
 
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 human immunodeficiency virus (HIV) 
infection or immunosuppressive therapy) may not get the full benefit from Synflorix. 
 
If you are not sure, talk to your doctor or pharmacist before having Synflorix. 
 
Children above 5 years old 
 
For children above 5 years old safety and efficacy of the vaccine have not been established, therefore 
vaccination of these children is not recommended. 
 
Other medicines and Synflorix 
 
Tell your doctor or pharmacist if your child is taking, has recently taken or might take any other 
medicines, 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 and 
serogroups A, C, W-135, Y conjugate vaccines. A different place for the injection will be used for 
each vaccine. 
 
Your doctor may ask you to give your child a medicine that lowers fever (such as paracetamol) before 
or immediately after Synflorix is given, especially in children being vaccinated with Synflorix and 
vaccines containing whole cell pertussis at the same time. It is also recommended to administer a 
medicine that lowers fever in children with convulsion disorders or with prior history of febrile 
convulsions. 
However if your child has received paracetamol before or immediately after Synflorix is given, the 
obtained levels of antibodies may be slightly reduced. It is not known whether the reduction in 
antibody levels has an impact on the protection against pneumococcal disease. 
 
Synflorix contains sodium 
 
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say 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 (from 6 weeks to 6 months of age) 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. 



59 

 
• Each injection will be given at least one month apart except for the last injection (booster), 

which will be given at least 6 months after the third injection. 
• The first injection may be given from the age of 6 weeks onwards. The last injection (booster) 

may be given from the age of 9 months onwards. 
• You will be told when your child should come back for the next injections. 
 
Preterm infants (born after 27 weeks and less than 37 weeks of pregnancy): 
Your child (from 2 months to 6 months of age) will receive 3 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 (booster) will be given in the second year of life with at least two months apart. 
 
Children aged 12 months to 5 years will receive 2 injections. Each injection will be given at least two 
months apart. 
 
Special populations: 
Children from 6 weeks up to 5 years of age considered to be at a higher risk of pneumococcal 
infection (such as those with HIV infection, sickle cell disease or impaired or abnormal functioning of 
the spleen) may receive Synflorix. Please speak to your doctor for information on the number and 
timing of injections for your child. 
 
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. 
 
If you have any further questions on the use of this vaccine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. The 
following side effects may happen with this medicine: 
 
Severe allergic reactions may very rarely occur (with up to 1 in 10,000 doses of the vaccine). These 
can be recognised by: 
- raised and itchy rash (hives) 
- swelling, sometimes of the face or mouth (angioedema), causing difficulty in breathing 
- collapse 
These reactions will usually occur before leaving the doctor’s surgery. However, if your child gets any 
of these symptoms you should contact a doctor urgently. 
 
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) 



60 

• itching, blood clot, bleeding or a small lump where the injection is given 
• nausea, diarrhoea or feeling sick (vomiting) 
• unusual crying 
• temporarily stopping breathing (apnoea) if your child is born prematurely (before or at 28 weeks 

of pregnancy) 
• headache 
• skin rash 
• diffuse swelling of the injected limb, sometimes involving the adjacent joint 
• hives 
 
Rare (these may occur with up to 1 in 1,000 doses of the vaccine) 
• fits without temperature or due to high temperature (fever) 
• allergic reactions such as skin allergies 
• collapse (sudden onset of muscle floppiness), periods of unconsciousness or lack of awareness, 

and paleness or bluish skin discoloration 
 
Very rare ( these may occur with up to 1 in 10,000 doses of the vaccine) 
• Kawasaki disease (major signs of the illness are for instance: fever, skin rash, swollen lymph 

glands, inflammation and rash of the mucous membranes of the mouth and throat) 
 
Booster doses of Synflorix may increase the risk of side effects. 
For children > 12 months of age, the risk of pain at the injection site may increase with increasing age. 
 
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. 
 
Reporting of side effects 
 
If your child gets any side effects, talk to your doctor or pharmacist. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Synflorix 
 
Keep this medicine out of the sight and reach of children. 
 
• Do not use this medicine 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. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Synflorix contains 
 
• The active substances are: 

 
One 0.5 ml dose contains: 
Pneumococcal polysaccharide serotype 11,2 1 microgram 

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


61 

Pneumococcal polysaccharide serotype 41,2 3 micrograms 
Pneumococcal polysaccharide serotype 51,2 1 microgram 
Pneumococcal polysaccharide serotype 6B1,2 1 microgram 
Pneumococcal polysaccharide serotype 7F1,2 1 microgram 
Pneumococcal polysaccharide serotype 9V1,2 1 microgram 
Pneumococcal polysaccharide serotype 141,2 1 microgram 
Pneumococcal polysaccharide serotype 18C1,3 3 micrograms 
Pneumococcal polysaccharide serotype 19F1,4 3 micrograms 
Pneumococcal polysaccharide serotype 23F1,2 1 microgram  
 
1 adsorbed on aluminium phosphate  0.5 milligram Al3+ in total 

 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 (see section 2 for further information) and water for 

injections 
 
What Synflorix looks like and contents of the pack 
 
• Suspension for injection in multidose container (2 doses) 
 
• 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: 
 
Belgique/België/Belgien 
GlaxoSmithKline Pharmaceuticals s.a./n.v. 
Tél/Tel: + 32 10 85 52 00 
 

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

България 
ГлаксоСмитКлайн ЕООД 
Тел.: + 359 2 953 10 34 
 

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

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

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

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

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

Deutschland Nederland 



62 

GlaxoSmithKline GmbH & Co. KG 
Tel: + 49 (0)89 360448701 
produkt.info@gsk.com 
 

GlaxoSmithKline BV 
Tel: + 31 (0)30 69 38 100 
nlinfo@gsk.com 
 

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

Norge 
GlaxoSmithKline AS 
Tlf: + 47 22 70 20 00 

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

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

España 
GlaxoSmithKline, S.A. 
Tel: + 34 902 202 700 
es-ci@gsk.com 
 

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

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

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

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

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

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

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

Ísland 
Vistor hf.  
Sími: +354 535 7000 
 

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

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

Suomi/Finland 
GlaxoSmithKline Oy 
Puh/Tel: + 358 10 30 30 30 
Finland.tuoteinfo@gsk.com 
 

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

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

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

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

This leaflet was last revised in  
 
Other sources of information 
 



63 

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu 
 
 
The following information is intended for healthcare professionals only: 
 
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.  
 
After first opening of the 2-dose 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. 
 
  



64 

Package leaflet: Information for the user 
 

Synflorix suspension for injection in multidose container (4 doses) 
Pneumococcal polysaccharide conjugate vaccine (adsorbed) 

 
 
Read all of this leaflet carefully before your child receives this vaccine because it contains 
important information for you. 
• 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 only. Do not pass it on to others.  
• If your child gets any side effects, talk to your doctor or pharmacist. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet:  
1. What Synflorix is and what it is used for 
2. What you need to know before your child receives Synflorix 
3. How Synflorix is given 
4. Possible side effects 
5. How to store Synflorix 
6. Contents of the pack and other 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 5 years of age against: 
a bacteria called ‘Streptococcus pneumoniae’. This bacteria can cause serious illnesses including 
meningitis, sepsis and bacteraemia (bacteria in blood stream) as well as ear infection or pneumonia. 

 
How Synflorix 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. What you need to know before your child receives Synflorix 
 
Synflorix should not be given if: 
 
• your child is allergic to the active substance, or any of the other ingredients of 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 if any of the above applies to your child. If you are not sure, talk to your 
doctor or pharmacist before your child is given Synflorix. 
 
Warnings and precautions 
 
Check with your doctor or pharmacist before this vaccine is given if: 
• your child has a bleeding problem or bruises easily. 



65 

 
In children as of 2 years of age, fainting can occur following, or even before, any needle injection, 
therefore tell the doctor or nurse if your child fainted with a previous injection. 
 
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 human immunodeficiency virus (HIV) 
infection or immunosuppressive therapy) may not get the full benefit from Synflorix. 
 
If you are not sure, talk to your doctor or pharmacist before having Synflorix. 
 
Children above 5 years old 
 
For children above 5 years old safety and efficacy of the vaccine have not been established, therefore 
vaccination of these children is not recommended. 
 
Other medicines and Synflorix 
 
Tell your doctor or pharmacist if your child is taking, has recently taken or might take any other 
medicines, 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 and 
serogroups A, C, W-135, Y conjugate vaccines. A different place for the injection will be used for 
each vaccine. 
 
Your doctor may ask you to give your child a medicine that lowers fever (such as paracetamol) before 
or immediately after Synflorix is given, especially in children being vaccinated with Synflorix and 
vaccines containing whole cell pertussis at the same time. It is also recommended to administer a 
medicine that lowers fever in children with convulsion disorders or with prior history of febrile 
convulsions. 
However if your child has received paracetamol before or immediately after Synflorix is given, the 
obtained levels of antibodies may be slightly reduced. It is not known whether the reduction in 
antibody levels has an impact on the protection against pneumococcal disease. 
 
Synflorix contains sodium 
 
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say 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 (from 6 weeks to 6 months of age) 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. 



66 

 
• Each injection will be given at least one month apart except for the last injection (booster), 

which will be given at least 6 months after the third injection. 
• The first injection may be given from the age of 6 weeks onwards. The last injection (booster) 

may be given from the age of 9 months onwards. 
• You will be told when your child should come back for the next injections. 
 
Preterm infants (born after 27 weeks and less than 37 weeks of pregnancy): 
Your child (from 2 months to 6 months of age) will receive 3 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 (booster) will be given in the second year of life with at least two months apart. 
 
Children aged 12 months to 5 years will receive 2 injections. Each injection will be given at least two 
months apart. 
 
Special populations: 
Children from 6 weeks up to 5 years of age considered to be at a higher risk of pneumococcal 
infection (such as those with HIV infection, sickle cell disease or impaired or abnormal functioning of 
the spleen) may receive Synflorix. Please speak to your doctor for information on the number and 
timing of injections for your child. 
 
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. 
 
If you have any further questions on the use of this vaccine, ask your doctor, pharmacist or nurse. 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them.  The 
following side effects may happen with this medicine: 
 
Severe allergic reactions may very rarely occur (with up to 1 in 10,000 doses of the vaccine). These 
can be recognised by: 
- raised and itchy rash (hives) 
- swelling, sometimes of the face or mouth (angioedema), causing difficulty in breathing 
- collapse 
These reactions will usually occur before leaving the doctor’s surgery. However, if your child gets any 
of these symptoms you should contact a doctor urgently. 
 
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) 
• itching, blood clot, bleeding or a small lump where the injection is given 



67 

• nausea, diarrhoea or feeling sick (vomiting) 
• unusual crying 
• temporarily stopping breathing (apnoea) if your child is born prematurely (before or at 28 weeks 

of pregnancy) 
• headache 
• skin rash 
• diffuse swelling of the injected limb, sometimes involving the adjacent joint 
• hives 
 
Rare (these may occur with up to 1 in 1,000 doses of the vaccine) 
• fits without temperature or due to high temperature (fever) 
• allergic reactions such as skin allergies 
• collapse (sudden onset of muscle floppiness), periods of unconsciousness or lack of awareness, 

and paleness or bluish skin discoloration 
 
Very rare ( these may occur with up to 1 in 10,000 doses of the vaccine) 
• Kawasaki disease (major signs of the illness are for instance: fever, skin rash, swollen lymph 

glands, inflammation and rash of the mucous membranes of the mouth and throat) 
 
Booster doses of Synflorix may increase the risk of side effects. 
For children > 12 months of age, the risk of pain at the injection site may increase with increasing age. 
 
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. 
 
Reporting of side effects 
 
If your child gets any side effects, talk to your doctor or pharmacist. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Synflorix 
 
Keep this medicine out of the sight and reach of children. 
 
• Do not use this medicine 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. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Synflorix contains 
 
• The active substances are: 

 
One 0.5 ml dose contains: 
Pneumococcal polysaccharide serotype 11,2 1 microgram 
Pneumococcal polysaccharide serotype 41,2 3 micrograms 

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


68 

Pneumococcal polysaccharide serotype 51,2 1 microgram 
Pneumococcal polysaccharide serotype 6B1,2 1 microgram 
Pneumococcal polysaccharide serotype 7F1,2 1 microgram 
Pneumococcal polysaccharide serotype 9V1,2 1 microgram 
Pneumococcal polysaccharide serotype 141,2 1 microgram 
Pneumococcal polysaccharide serotype 18C1,3 3 micrograms 
Pneumococcal polysaccharide serotype 19F1,4 3 micrograms 
Pneumococcal polysaccharide serotype 23F1,2 1 microgram  
 
1 adsorbed on aluminium phosphate  0.5 milligram Al3+ in total 

 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 (see section 2 for further information),  

2-phenoxyethanol and water for injections 
 

 
What Synflorix looks like and contents of the pack 
 
• Suspension for injection in multidose container (4 doses) 
 
• Synflorix is a turbid white suspension. 
 
• Synflorix is available in vials for 4 doses in packs of 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: 
 
Belgique/België/Belgien 
GlaxoSmithKline Pharmaceuticals s.a./n.v. 
Tél/Tel: + 32 10 85 52 00 
 

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

България 
ГлаксоСмитКлайн ЕООД 
Тел.: + 359 2 953 10 34 
 

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

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

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

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

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



69 

 
Deutschland 
GlaxoSmithKline GmbH & Co. KG 
Tel: + 49 (0)89 360448701 
produkt.info@gsk.com 
 

Nederland 
GlaxoSmithKline BV 
Tel: + 31 (0)30 69 38 100 
nlinfo@gsk.com 
 

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

Norge 
GlaxoSmithKline AS 
Tlf: + 47 22 70 20 00 
 

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

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

España 
GlaxoSmithKline, S.A. 
Tel: + 34 902 202 700 
es-ci@gsk.com 
 

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

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

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

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

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

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

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

Ísland 
Vistor hf.  
Sími: +354 535 7000 
 

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

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

Suomi/Finland 
GlaxoSmithKline Oy 
Puh/Tel: + 358 10 30 30 30 
Finland.tuoteinfo@gsk.com 
 

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

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

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

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

 
This leaflet was last revised in  



70 

 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu 
 
 
The following information is intended for healthcare professionals only: 
 
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.  
 
After first opening of the 4-dose vial, the vaccine may be stored for a maximum of 28 days in a 
refrigerator (2°C – 8°C). If not used within 28 days 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. 
 


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