Prevenar 13
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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS



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1. NAME OF THE MEDICINAL PRODUCT

Prevenar 13 suspension for injection
pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed)

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

1 dose (0.5 ml) contains:

Pneumococcal polysaccharide serotype 11 2.2 µg
Pneumococcal polysaccharide serotype 31 2.2 µg
Pneumococcal polysaccharide serotype 41 2.2 µg
Pneumococcal polysaccharide serotype 51 2.2 µg
Pneumococcal polysaccharide serotype 6A1 2.2 µg
Pneumococcal polysaccharide serotype 6B1 4.4 µg
Pneumococcal polysaccharide serotype 7F1 2.2 µg
Pneumococcal polysaccharide serotype 9V1 2.2 µg
Pneumococcal polysaccharide serotype 141 2.2 µg
Pneumococcal polysaccharide serotype 18C1 2.2 µg
Pneumococcal polysaccharide serotype 19A1 2.2 µg
Pneumococcal polysaccharide serotype 19F1 2.2 µg
Pneumococcal polysaccharide serotype 23F1 2.2 µg

1Conjugated to CRM197 carrier protein, adsorbed on aluminium phosphate.

1 dose (0.5 ml) contains approximately 32 µg CRM197 carrier protein and 0.125 mg aluminium.

Excipients with known effect
For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Suspension for injection.
The vaccine is a homogeneous white suspension.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Active immunisation for the prevention of invasive disease, pneumonia and acute otitis media caused 
by Streptococcus pneumoniae in infants, children and adolescents from 6 weeks to 17 years of age.

Active immunisation for the prevention of invasive disease and pneumonia caused by Streptococcus 
pneumoniae in adults ≥18 years of age and the elderly.

See sections 4.4 and 5.1 for information on protection against specific pneumococcal serotypes.

The use of Prevenar 13 should be determined on the basis of official recommendations taking into 
consideration the risk of invasive disease and pneumonia in different age groups, underlying 
comorbidities as well as the variability of serotype epidemiology in different geographical areas.



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4.2 Posology and method of administration

The immunisation schedules for Prevenar 13 should be based on official recommendations.

Posology

Infants and children aged 6 weeks to 5 years

It is recommended that infants who receive a first dose of Prevenar 13 complete the vaccination 
course with Prevenar 13.

Infants aged 6 weeks-6 months

Three-dose primary series
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 usually given at 2 months of age and with an interval 
of at least 1 month between doses. The first dose may be given as early as six weeks of age. The 
fourth (booster) dose is recommended between 11 and 15 months of age.

Two-dose primary series
Alternatively, when Prevenar 13 is given as part of a routine infant immunisation programme, a series 
consisting of three doses, each of 0.5 ml, may be given. The first dose may be administered from the 
age of 2 months, with a second dose 2 months later. The third (booster) dose is recommended between 
11 and 15 months of age (see section 5.1).

Preterm infants (<37 weeks gestation)

In preterm infants, 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. The first dose may be given as early as six weeks of age. 
The fourth (booster) dose is recommended between 11 and 15 months of age (see sections 4.4 and 
5.1).

Unvaccinated infants and children ≥ 7 months of age

Infants aged 7-11 months
Two doses, each of 0.5 ml, with an interval of at least 1 month between doses. A third dose is 
recommended in the second year of life.

Children aged 12-23 months
Two doses, each of 0.5 ml, with an interval of at least 2 months between doses (see section 5.1).

Children and adolescents aged 2-17 years 
One single dose of 0.5 ml.

Prevenar 13 vaccine schedule for infants and children previously vaccinated with Prevenar (7-valent)
(Streptococcus pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F)
Prevenar 13 contains the same 7 serotypes included in Prevenar, using the same carrier protein 
CRM197.

Infants and children who have begun immunisation with Prevenar may switch to Prevenar 13 at any 
point in the schedule.



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Young children (12-59 months) completely immunised with Prevenar (7-valent)
Young children who are considered completely immunised with Prevenar (7-valent) should receive 
one dose of 0.5 ml of Prevenar 13 to elicit immune responses to the 6 additional serotypes. This dose 
of Prevenar 13 should be administered at least 8 weeks after the final dose of Prevenar (7-valent) (see 
section 5.1).

Children and adolescents 5–17 years 
Children 5 to 17 years of age may receive a single dose of Prevenar 13 if they have been previously 
vaccinated with one or more doses of Prevenar. This dose of Prevenar 13 should be administered at 
least 8 weeks after the final dose of Prevenar (7-valent) (see section 5.1).

Adults ≥18 years of age, and the elderly

One single dose.
The need for revaccination with a subsequent dose of Prevenar 13 has not been established.

Regardless of prior pneumococcal vaccination status, if the use of 23-valent pneumococcal 
polysaccharide vaccine is considered appropriate, Prevenar 13 should be given first (see sections 4.5 
and 5.1).

Special Populations

Individuals who have underlying conditions predisposing them to invasive pneumococcal disease 
(such as sickle cell disease or HIV infection) including those previously vaccinated with one or more 
doses of 23-valent pneumococcal polysaccharide vaccine may receive at least one dose of Prevenar 13 
(see section 5.1).

In individuals with an haematopoietic stem cell transplant (HSCT), the recommended immunisation 
series consists of four doses of Prevenar 13, each of 0.5 ml. The primary series consists of three doses, 
with the first dose given at 3 to 6 months after HSCT and with an interval of at least 1 month between 
doses. A fourth (booster) dose is recommended 6 months after the third dose (see section 5.1).

Method of administration

The vaccine should be given by intramuscular injection. The preferred sites are the anterolateral 
aspect of the thigh (vastus lateralis muscle) in infants or the deltoid muscle of the upper arm in 
children and adults. 

4.3 Contraindications

Hypersensitivity to the active substances, to any of the excipients listed in section 6.1, or to diphtheria 
toxoid.

As with other vaccines, the administration of Prevenar 13 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

Prevenar 13 must not be administered intravascularly.

As with all injectable vaccines, appropriate medical treatment and supervision should always be 
readily available in case of a rare anaphylactic event following the administration of the vaccine.



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This vaccine should not be given as an intramuscular injection to individuals with thrombocytopaenia 
or any coagulation disorder that would contraindicate intramuscular injection, but may be given 
subcutaneously if the potential benefit clearly outweighs the risks (see section 5.1).

Prevenar 13 will only protect against Streptococcus pneumoniae serotypes included in the vaccine, 
and will not protect against other microorganisms that cause invasive disease, pneumonia, or otitis 
media. As with any vaccine, Prevenar 13 may not protect all individuals receiving the vaccine from 
pneumococcal disease. For the most recent epidemiological information in your country you should 
consult with the relevant national organisation.

Individuals with impaired immune responsiveness, whether due to the use of immuno-suppressive 
therapy, a genetic defect, human immunodeficiency virus (HIV) infection, or other causes, may have 
reduced antibody response to active immunisation.

Safety and immunogenicity data are available for a limited number of individuals with sickle cell 
disease, HIV infection, or with an haematopoietic stem cell transplant (see section 5.1). Safety and 
immunogenicity data for Prevenar 13 are not available for individuals in other specific 
immuno-compromised groups (e.g., malignancy or nephrotic syndrome) and vaccination should be 
considered on an individual basis.

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially 
‘sodium-free’.

Infants and children aged 6 weeks to 5 years

In clinical studies, Prevenar 13 elicited an immune response to all thirteen serotypes included in the 
vaccine. The immune response for serotype 3 following the booster dose was not increased above the 
levels seen after the infant vaccination series; the clinical relevance of this observation regarding the 
induction of serotype 3 immune memory is unknown (see section 5.1).

The proportions of functional antibody responders (OPA titres ≥ 1:8) to serotypes 1, 3 and 5 were 
high. However, the OPA geometric mean titres were lower than those against each of the remaining 
additional vaccine serotypes; the clinical relevance of this observation for protective efficacy is 
unknown (see section 5.1). 

Limited data have demonstrated that Prevenar 7-valent (three-dose primary series) induces an 
acceptable immune response in infants with sickle cell disease with a safety profile similar to that 
observed in non-high-risk groups (see section 5.1). 

Children younger than 2 years old should receive the appropriate-for-age Prevenar 13 vaccination 
series (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 are immuno-compromised) 
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 Prevenar 13 
should receive 23-valent pneumococcal polysaccharide vaccine. The interval between the 13-valent 
pneumococcal conjugate vaccine (Prevenar 13) 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 23-valent pneumococcal polysaccharide vaccine to unprimed children or to children 
primed with Prevenar 13 might result in hyporesponsiveness to further doses of Prevenar 13.

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.



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For vaccine serotypes, protection against otitis media is expected to be lower than protection against 
invasive disease. As otitis media is caused by many organisms other than pneumococcal serotypes 
represented in the vaccine, protection against all otitis media is expected to be low (see section 5.1).

When Prevenar 13 is administered concomitantly with Infanrix hexa (DTPa-HBV-IPV/Hib), the rates 
of febrile reactions are similar to those seen with concomitant administration of Prevenar 
(7-valent) and Infanrix hexa (see section 4.8). Increased reporting rates of convulsions (with or 
without fever) and hypotonic hyporesponsive episode (HHE) were observed with concomitant 
administration of Prevenar 13 and Infanrix hexa (see section 4.8).

Antipyretic treatment should be initiated according to local treatment guidelines for children with 
seizure disorders or with a prior history of febrile seizures and for all children receiving Prevenar 13 
simultaneously with vaccines containing whole cell pertussis.

4.5 Interaction with other medicinal products and other forms of interaction

Infants and children aged 6 weeks to 5 years

Prevenar 13 can be given concomitantly with any of the following vaccine antigens, either as 
monovalent or combination vaccines: diphtheria, tetanus, acellular or whole cell pertussis, 
Haemophilus influenzae type b, inactivated poliomyelitis, hepatitis B (see section 4.4 for guidance on 
Infanrix hexa), meningococcal serogroup C, measles, mumps, rubella, varicella and rotavirus vaccine. 

Prevenar 13 can also be given concomitantly between 12-23 months with the tetanus toxoid 
conjugated meningococcal polysaccharide serogroups A, C, W and Y vaccine to children who have 
been adequately primed with Prevenar 13 (as per local recommendations).

Data from a postmarketing clinical study evaluating the impact of prophylactic use of antipyretics 
(ibuprofen and paracetamol) on the immune response to Prevenar 13 suggest that administration of 
paracetamol concomitantly or within the same day of vaccination may reduce the immune response to 
Prevenar 13 after the infant series. Responses to the booster dose administered at 12 months were 
unaffected. The clinical significance of this observation is unknown.

Children and adolescents 6 to 17 years of age

No data are currently available regarding concomitant use with other vaccines. 

Adults 18 to 49 years of age

No data are available regarding concomitant use with other vaccines. 

Adults aged 50 years and older

Prevenar 13 may be administered concomitantly with the seasonal trivalent inactivated influenza 
vaccine (TIV).

In two studies conducted in adults aged 50-59 and 65 years and older, it was demonstrated that 
Prevenar 13 may be given concomitantly with trivalent inactivated influenza vaccine (TIV). The 
responses to all three TIV antigens were comparable when TIV was given alone or concomitantly 
with Prevenar 13.

When Prevenar 13 was given concomitantly with TIV, the immune responses to Prevenar 13 were 
lower compared to when Prevenar 13 was given alone, however, there was no long-term impact on 
circulating antibody levels.



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In a third study in adults aged 50-93 years, it was demonstrated that Prevenar 13 may be given 
concomitantly with the seasonal quadrivalent inactivated influenza vaccine (QIV). The immune 
responses to all four QIV strains were noninferior when Prevenar 13 was given concomitantly with 
QIV compared to when QIV was given alone.

The immune responses to Prevenar 13 were noninferior when Prevenar 13 was given concomitantly 
with QIV compared to when Prevenar 13 was given alone. As with concomitant administration with 
trivalent vaccines, immune responses to some pneumococcal serotypes were lower when both 
vaccines were given concomitantly.

Concomitant use with other vaccines has not been investigated.

Different injectable vaccines should always be given at different vaccination sites.

Concomitant administration of Prevenar 13 and 23-valent pneumococcal polysaccharide vaccine has 
not been studied. In clinical studies when Prevenar 13 was given 1 year after 23-valent pneumococcal 
polysaccharide vaccine the immune responses were lower for all serotypes compared to when 
Prevenar 13 was given to subjects not previously immunised with 23-valent pneumococcal 
polysaccharide vaccine. The clinical significance of this is unknown. 

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no data from the use of pneumococcal 13-valent conjugate vaccine in pregnant women.
Therefore the use of Prevenar 13 should be avoided during pregnancy.

Breast-feeding

It is unknown whether pneumococcal 13-valent conjugate vaccine is excreted in human milk.

Fertility

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity 
(see section 5.3).

4.7 Effects on ability to drive and use machines

Prevenar 13 has no or negligible influence on the ability to drive and use machines. However, some of 
the effects mentioned under section 4.8 “Undesirable effects” may temporarily affect the ability to 
drive or use machines.

4.8 Undesirable effects

Analysis of postmarketing reporting rates suggests a potential increased risk of convulsions, with or 
without fever, and HHE when comparing groups which reported use of Prevenar 13 with 
Infanrix hexa to those which reported use of Prevenar 13 alone.

Adverse reactions reported in clinical studies or from the postmarketing experience for all age groups 
are listed in this section per system organ class, in decreasing order of frequency and seriousness. The 
frequency is defined as follows: very common ( 1/10), common ( 1/100 to < 1/10), uncommon 
( 1/1,000 to < 1/100), rare ( 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be 
estimated from available data).



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Infants and children aged 6 weeks to 5 years
The safety of the vaccine was assessed in controlled clinical studies where 14,267 doses were given to 
4,429 healthy infants from 6 weeks of age at first vaccination and 11-16 months of age at booster 
dose. In all infant studies, Prevenar 13 was co-administered with routine paediatric vaccines (see 
section 4.5).

Safety in 354 previously unvaccinated children (7 months to 5 years of age) was also assessed.

The most commonly reported adverse reactions in children 6 weeks to 5 years of age were 
vaccination-site reactions, fever, irritability, decreased appetite, and increased and/or decreased sleep.

In a clinical study in infants vaccinated at 2, 3, and 4 months of age, fever ≥ 38°C was reported at 
higher rates among infants who received Prevenar (7-valent) concomitantly with Infanrix hexa (28.3% 
to 42.3%) than in infants receiving Infanrix hexa alone (15.6% to 23.1%). After a booster dose at 12 
to 15 months of age, fever ≥ 38°C was reported in 50.0% of infants who received Prevenar (7-valent) 
and Infanrix hexa at the same time as compared to 33.6% of infants receiving Infanrix hexa alone. 
These reactions were mostly moderate (less than or equal to 39°C) and transient.

An increase in vaccination-site reactions was reported in children older than 12 months compared to 
rates observed in infants during the primary series with Prevenar 13.

Adverse reactions from clinical studies
In clinical studies, the safety profile of Prevenar 13 was similar to Prevenar. The following 
frequencies are based on adverse reactions assessed in Prevenar 13 clinical studies:

Immune system disorders:
Rare: Hypersensitivity reaction including face oedema, dyspnoea, bronchospasm

Nervous system disorders:
Uncommon: Convulsions (including febrile convulsions)
Rare: Hypotonic-hyporesponsive episode

Gastrointestinal disorders:
Very common: Decreased appetite
Common: Vomiting; diarrhoea

Skin and subcutaneous tissue disorders:
Common: Rash
Uncommon: Urticaria or urticaria-like rash

General disorders and administration site conditions:
Very common: Pyrexia; irritability; any vaccination-site erythema, induration/swelling or 

pain/tenderness; somnolence; poor quality sleep
Vaccination-site erythema or induration/swelling 2.5 cm–7.0 cm (after the 
booster dose and in older children [age 2 to 5 years])

Common: Pyrexia > 39°C; vaccination-site movement impairment (due to pain); 
vaccination-site erythema or induration/swelling 2.5 cm–7.0 cm (after infant 
series)

Uncommon: Vaccination-site erythema, induration/swelling > 7.0 cm; crying

Additional information in special populations:
Apnoea in very premature infants ( 28 weeks of gestation) (see section 4.4).



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Children and adolescents aged 6 to 17 years of age 
Safety was evaluated in 592 children (294 children aged 5 to 10 years previously immunised with at 
least one dose of Prevenar and 298 children aged 10 to 17 years who had not received a pneumococcal 
vaccine).

The most common adverse events in children and adolescents 6 to 17 years of age were:

Nervous system disorders:
Common: Headaches

Gastrointestinal disorders:
Very common: Decreased appetite
Common: Vomiting; diarrhoea

Skin and subcutaneous tissue disorders:
Common: Rash; urticaria or urticaria-like rash

General disorders and administration site conditions:
Very common: Irritability; any vaccination-site erythema; induration/swelling or 

pain/tenderness; somnolence; poor quality sleep; 
vaccination-site tenderness (including impaired movement)

Common: Pyrexia

Other adverse events previously observed in infants and children 6 weeks to 5 years of age may also 
be applicable to this age group but were not seen in this study possibly due to the small sample size.

Additional information in special populations
Children and adolescents with sickle cell disease, HIV infection, or an haematopoietic stem cell 
transplant have similar frequencies of adverse reactions, except that headaches, vomiting, diarrhoea, 
pyrexia, fatigue, arthralgia, and myalgia were very common.

Adults ≥ 18 years and the elderly
Safety was assessed in 7 clinical studies including 91,593 adults ranging in age from 18 to 101 years. 
Prevenar 13 was administered to 48,806 adults; 2,616 (5.4%) aged 50 to 64 years, and 45,291 (92.8%) 
aged 65 years and older. One of the 7 studies included a group of adults (n=899) ranging from 18 to 
49 years who received Prevenar 13 and who were not previously vaccinated with 23-valent 
pneumococcal polysaccharide vaccine. Of the Prevenar 13 recipients 1,916 adults were previously 
vaccinated with the 23-valent pneumococcal polysaccharide vaccine at least 3 years prior to study 
vaccination, and 46,890 were 23-valent pneumococcal polysaccharide vaccine unvaccinated.

A trend to lower frequency of adverse reactions was associated with greater age; adults > 65 years of 
age (regardless of prior pneumococcal vaccination status) reported fewer adverse reactions than 
younger adults, with adverse reactions generally most common in the youngest adults, 18 to 29 years 
of age.

Overall, the frequency categories were similar for all age groups, with the exception of vomiting 
which was very common ( 1/10) in adults aged 18 to 49 years and common ( 1/100 to < 1/10) in all 
other age groups, and pyrexia was very common in adults aged 18 to 29 years and common in all other 
age groups. Severe vaccination-site pain/tenderness and severe limitation of arm movement was very 
common in adults 18 to 39 years and common in all other age groups.

Adverse reactions from clinical studies
Local reactions and systemic events were solicited daily after each vaccination for 14 days in 6 studies
and 7 days in the remaining study. The following frequencies are based on adverse reactions assessed 
in Prevenar 13 clinical studies in adults:



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Metabolism and nutrition disorders:
Very common: Decreased appetite

Nervous system disorders:
Very common: Headaches

Gastrointestinal disorders: 
Very common: Diarrhoea; vomiting (in adults aged 18 to 49 years)

Common: Vomiting (in adults aged 50 years and over)

Uncommon: Nausea

Immune system disorders:
Uncommon: Hypersensitivity reaction including face oedema, dyspnoea, bronchospasm

Skin and subcutaneous tissue disorders:
Very common: Rash

General disorders and administration site conditions:
Very common: Chills; fatigue; vaccination-site erythema; vaccination-site 

induration/swelling; vaccination-site pain/tenderness (severe vaccination-site 
pain/tenderness very common in adults aged 18 to 39 years); limitation of arm 
movement (severe limitation of arm movements very common in adults aged 
18 to 39 years)

Common: Pyrexia (very common in adults aged 18 to 29 years)

Uncommon: Lymphadenopathy localized to the region of the vaccination-site

Musculoskeletal and connective tissue disorders:
Very common: Arthralgia; myalgia

Overall, no significant differences in frequencies of adverse reactions were seen when Prevenar 13 
was given to adults previously vaccinated with the pneumococcal polysaccharide vaccine.

Additional information in special populations
Adults with HIV infection have similar frequencies of adverse reactions, except that pyrexia and 
vomiting were very common and nausea common.

Adults with an haematopoietic stem cell transplant have similar frequencies of adverse reactions, 
except that pyrexia and vomiting were very common.

Higher frequency in some solicited systemic reactions was observed when Prevenar 13 was 
administered concomitantly with trivalent inactivated influenza vaccine (TIV) compared to TIV given 
alone (headache, chills, rash, decreased appetite, arthralgia, and myalgia) or Prevenar 13 given alone 
(headache, fatigue, chills, decreased appetite, and arthralgia). 

Adverse reactions from Prevenar 13 postmarketing experience
The following are considered adverse drug reactions for Prevenar 13; because these reactions were 
derived from spontaneous reports, the frequencies could not be determined and are thus considered as 
not known.

Blood and lymphatic system disorders:
Lymphadenopathy (localised to the region of the vaccination-site)



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Immune system disorders:
Anaphylactic/anaphylactoid reaction including shock; angioedema

Skin and subcutaneous tissue disorders:
Erythema multiforme

General disorders and administration site conditions:
Vaccination-site urticaria; vaccination-site dermatitis; vaccination-site 
pruritus; flushing

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

Overdose with Prevenar 13 is unlikely due to its presentation as a pre-filled syringe. However, in 
infants and children there have been reports of overdose with Prevenar 13 defined as subsequent doses 
administered closer than recommended to the previous dose. In general, adverse events reported with 
overdose are consistent with those that have been reported with doses given in the recommended 
paediatric schedules of Prevenar 13.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: vaccines, pneumococcal vaccines; ATC code: J07AL02

Prevenar 13 contains the 7 pneumococcal capsular polysaccharides that are in Prevenar (4, 6B, 9V, 
14, 18C, 19F, 23F) plus 6 additional polysaccharides (1, 3, 5, 6A, 7F, 19A) all conjugated to CRM197

carrier protein. 

Burden of disease

Infants and children aged 6 weeks to 5 years

Based on serotype surveillance in Europe performed before the introduction of Prevenar, Prevenar 13 
is estimated to cover 73-100% (depending on the country) of serotypes causing invasive 
pneumococcal disease (IPD) in children less than 5 years of age. In this age group, serotypes 1, 3, 5, 
6A, 7F, and 19A account for 15.6% to 59.7% of invasive disease, depending on the country, the time 
period studied, and the use of Prevenar.

Acute otitis media (AOM) is a common childhood disease with different aetiologies. Bacteria can be 
responsible for 60-70% of clinical episodes of AOM. S. pneumoniae is one of the most common 
causes of bacterial AOM worldwide.

Prevenar 13 is estimated to cover over 90% of serotypes causing antimicrobial-resistant IPD.

Children and adolescents aged 6 to 17 years

In children and adolescents aged 6 to 17 years, the incidence of pneumococcal disease is low, 
however, there is an increased risk of morbidity and mortality in those with underlying comorbidities.



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Adults ≥18 years and the elderly

Pneumonia is the most common clinical presentation of pneumococcal disease in adults.

The reported incidence of community-acquired pneumonia (CAP) and IPD in Europe varies by 
country, increases with age from 50 years and is highest in individuals aged ≥ 65 years. S. pneumoniae
is the most frequent cause of CAP, and is estimated to be responsible for approximately 30% of all 
CAP cases requiring hospitalisation in adults in developed countries.

Bacteraemic pneumonia (approximately 80% of IPD in adults), bacteraemia without a focus, and 
meningitis are the most common manifestations of IPD in adults. Based on surveillance data following
the introduction of Prevenar but before the introduction of Prevenar 13 in childhood vaccination 
programmes, the pneumococcal serotypes in Prevenar 13 may be responsible for at least 50 – 76% 
(depending on country) of IPD in adults.

The risk for CAP and IPD in adults also increases with chronic underlying medical conditions, 
specifically, anatomical or functional asplenia, diabetes mellitus, asthma, chronic cardiovascular, 
pulmonary, kidney or liver disease, and it is highest in those who are immune-suppressed such as 
those with malignant haematological diseases or HIV infection. 

Prevenar 13 immunogenicity clinical studies in infants, children and adolescents

The protective efficacy of Prevenar 13 against IPD has not been studied. As recommended by the 
World Health Organization (WHO) the assessment of potential efficacy against IPD in infants and 
young children has been based on a comparison of immune responses to the seven common serotypes 
shared between Prevenar 13 and Prevenar, for which protective efficacy has been proven (for 
Prevenar (7-valent) efficacy in infants and children, see below). Immune responses to the additional 
6 serotypes were also measured.

Immune responses following a three-dose primary infant series

Clinical studies have been conducted in a number of European countries and the US using a range of 
vaccination schedules, including two randomised non-inferiority studies (Germany using a 2, 3, 
4 month primary series [006] and US using a 2, 4, 6 month primary series [004]). In these two studies 
pneumococcal immune responses were compared using a set of non-inferiority criteria including the
percentage of subjects with serum anti-polysaccharide serotype-specific IgG ≥ 0.35 μg/ml one month 
after the primary series and the comparison of IgG geometric mean concentrations (ELISA GMCs); in 
addition, functional antibody titres (OPA) between subjects receiving Prevenar 13 and Prevenar were 
compared. For the six additional serotypes, these values were compared with the lowest response 
among all of the seven common serotypes in the Prevenar recipients.

The non-inferiority immune response comparisons for study 006, based on the proportion of infants 
achieving anti-polysaccharide IgG concentrations ≥ 0.35 μg/ml, are shown in Table 1. Results for 
study 004 were similar. Prevenar 13 non-inferiority (lower bound of the 95% CI for the difference in 
percentage of responders at 0.35 µg/ml between groups was >-10%) was demonstrated for all 
7 common serotypes, except for serotype 6B in study 006 and serotypes 6B and 9V in study 004, 
which missed by a small margin. All seven common serotypes met pre-defined non-inferiority criteria 
for IgG ELISA GMCs. Prevenar 13 elicited comparable, although slightly lower, antibody levels than 
Prevenar for the 7 common serotypes. The clinical relevance of these differences is not known.

Non-inferiority was met for the 6 additional serotypes based on the proportion of infants achieving 
antibody concentrations ≥ 0.35 μg/ml and comparison of IgG ELISA GMCs in study 006 and was met 
for 5 out of the 6 serotypes, with the exception of serotype 3 for study 004. For serotype 3, the 
percentages of Prevenar 13 recipients with serum IgG ≥ 0.35 μg/ml were 98.2% (study 006) and 
63.5% (study 004).



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Table 1: Comparison of the proportion of subjects achieving a pneumococcal anti-polysaccharide IgG 
antibody concentration ≥ 0.35 μg/ml after dose 3 of the infant series – study 006

Serotypes

Prevenar 13
%

(N=282-285)

7-valent Prevenar
%

(N=277-279)
Difference
(95 % CI)

7-valent Prevenar serotypes
4 98.2 98.2 0.0 (-2.5, 2.6)

6B 77.5 87.1 -9.6 (-16.0, -3.3)
9V 98.6 96.4 2.2 (-0.4, 5.2)
14 98.9 97.5 1.5 (-0.9, 4.1)

18C 97.2 98.6 -1.4 (-4.2, 1.2)
19F 95.8 96.0 -0.3 (-3.8, 3.3)
23F 88.7 89.5 -0.8 (-6.0, 4.5)

Additional serotypes in Prevenar 13
1 96.1 87.1* 9.1 (4.5, 13.9)
3 98.2 87.1 11.2 (7.0, 15.8)
5 93.0 87.1 5.9 (0.8, 11.1)

6A 91.9 87.1 4.8 (-0.3, 10.1)
7F 98.6 87.1 11.5 (7.4, 16.1)

19A 99.3 87.1 12.2 (8.3, 16.8)
* The serotype in Prevenar with the lowest percent response rate was 6B in study 006 (87.1 %).

Prevenar 13 elicited functional antibodies to all 13 vaccine serotypes in studies 004 and 006. For the 
7 common serotypes there were no differences between groups in the proportion of subjects with OPA 
titres ≥ 1:8. For each of the seven common serotypes, > 96% and >90 % of the Prevenar 13 recipients 
reached an OPA titre ≥ 1:8 one month after the primary series in studies 006 and 004, respectively.

For each of the 6 additional serotypes, Prevenar 13 elicited OPA titres ≥ 1:8 in 91.4% to 100% of 
vaccinees one month after the primary series in studies 004/006. The functional antibody (OPA) 
geometric mean titres for serotypes 1, 3 and 5 were lower than the titres for each of the other 
additional serotypes; the clinical relevance of this observation for protective efficacy is unknown. 

Immune responses following a two-dose primary infant series

The immunogenicity after two doses in infants has been documented in four studies. The proportion 
of infants achieving a pneumococcal anti-capsular polysaccharide IgG concentration ≥ 0.35 g/ml one 
month after the second dose ranged from 79.6% to 98.5% across 11 of the 13 vaccine serotypes. 
Smaller proportions of infants achieved this antibody concentration threshold for serotype 6B (27.9% 
to 57.3%) and 23F (55.8% to 68.1%) for all studies using a 2, 4 month regimen, compared to 58.4% 
for serotype 6B and 68.6% for 23F for a study using a 3, 5 month regimen. After the booster dose, all 
vaccine serotypes including 6B and 23F had immune responses consistent with adequate priming with 
a two-dose primary series. In a UK study, the functional antibody (OPA) responses were comparable 
for all serotypes including 6B and 23F in the Prevenar and Prevenar 13 arms after the primary series 
at two and four months of age and after the booster dose at 12 months of age. For Prevenar 13 
recipients, the proportion of responders with an OPA titre  1:8 was at least 87 % following the infant 
series, and at least 93% following the booster dose. The OPA geometric mean titres for serotypes 1, 3 
and 5 were lower than the titres for each of the other additional serotypes; the clinical relevance of 
this observation is unknown.

Booster responses following two-dose and three-dose primary infant series

Following the booster dose, antibody concentrations increased from the pre-booster level for all 13 
serotypes. Post-booster antibody concentrations were higher for 12 serotypes than those achieved after 
the infant primary series. These observations are consistent with adequate priming (the induction of 
immunologic memory). The immune response for serotype 3 following the booster dose was not 



14

increased above the levels seen after the infant vaccination series; the clinical relevance of this 
observation regarding the induction of serotype 3 immune memory is unknown.

Antibody responses to booster doses following two-dose or three-dose infant primary series were 
comparable for all 13 vaccine serotypes.

For children aged from 7 months to 5 years, age appropriate catch-up immunisation schedules (as 
described in section 4.2) result in levels of anti-capsular polysaccharide IgG antibody responses to 
each of the 13 serotypes that are at least comparable to those of a three-dose primary series in infants.

Antibody persistence and immunological memory were evaluated in a study in healthy children who 
received a single dose of Prevenar 13 at least 2 years after they had been previously immunised with 
either 4 doses of Prevenar, a 3-dose infant series of Prevenar followed by Prevenar 13 at 12 months of 
age, or 4 doses of Prevenar 13. 

The single dose of Prevenar 13, in children approximately 3.4 years of age regardless of previous 
vaccination history with Prevenar or Prevenar 13, induced a robust antibody response for both the 
7 common serotypes and the 6 additional serotypes in Prevenar 13.

Since the introduction of 7-valent Prevenar in 2000, pneumococcal disease surveillance data have not 
shown that the immunity elicited by Prevenar in infancy has waned over time. 

Preterm Infants

Safety and immunogenicity of Prevenar 13 given at 2, 3, 4 and 12 months was assessed in 
approximately 100 prematurely born infants (mean Estimated Gestational Age [EGA], 31 weeks; 
range, 26 to 36 weeks) and compared with approximately 100 infants born at term (mean EGA, 
39 weeks; range, 37 to 42 weeks). 

Immune responses in preterm and term infants were compared using the proportion of subjects 
achieving a pneumococcal polysaccharide IgG binding antibody concentration ≥0.35 μg/mL 1 month 
after the infant series, the approach used for immunogenicity comparisons of Prevenar 13 to Prevenar 
based on WHO guidelines.

More than 85% achieved a pneumococcal polysaccharide IgG binding antibody concentration 
≥0.35 µg/mL 1 month after the infant series, except for serotypes 5 (71.7%), 6A (82.7%), and 6B 
(72.7%) in the preterm group. For these 3 serotypes, the proportion of responders among preterm 
infants was significantly lower than among term infants. Approximately one month after the toddler 
dose, the proportion of subjects in each group achieving this same antibody concentration threshold 
was >97%, except for serotype 3 (71% in preterm infants and 79% in term infants). It is unknown 
whether immunological memory to all serotypes is induced in pre-term infants. In general, 
serotype-specific IgG GMCs were lower for preterm infants than term infants.

After the infant series, OPA GMTs were similar in preterm infants compared to term infants except 
for serotype 5, which was lower in preterm infants. OPA GMTs after the toddler dose relative to those 
after the infant series were similar or lower for 4 serotypes (4, 14, 18C, and 19F) and were statistically 
significantly higher for 6 of 13 serotypes (1, 3, 5, 7F, 9V, and 19A) in preterm infants compared to 10 
of 13 serotypes (1, 3, 4, 5, 6A, 7F, 9V, 18C, 19A, and 23F) in term infants.

Children (12-59 months) completely immunised with Prevenar (7-valent)

Following administration of a single dose of Prevenar 13 to children (12-59 months) who are 
considered completely immunised with Prevenar (7-valent) (either 2 or 3 dose primary series plus 
booster), the proportion achieving serum IgG levels ≥0.35 µg/ml and OPA titres ≥1:8 was at least 
90%. However, 3 (serotypes 1, 5 and 6A) of the 6 additional serotypes showed lower IgG GMC and 



15

OPA GMT when compared with children who had received at least one previous vaccination with 

Prevenar 13. The clinical relevance of the lower GMCs and GMTs is currently unknown.

Unvaccinated Children (12-23 months)

Studies in unvaccinated children (12-23 months) with Prevenar (7-valent) demonstrated that 2 doses 
were required to achieve serum IgG concentrations for 6B and 23F similar to those induced by a 
3-dose infant series.

Children and Adolescents 5 to 17 years of age

In an open-label study in 592 healthy children and adolescents including those with asthma (17.4%) 
who may be predisposed to pneumococcal infection, Prevenar 13 elicited immune responses to all 
13 serotypes. A single dose of Prevenar 13 was given to children 5 to 10 years of age previously 
vaccinated with at least 1 dose of Prevenar, and children and adolescents 10 to 17 years of age who 
had never received a pneumococcal vaccine.

In both the children 5 to 10 years of age and children and adolescents aged 10 to 17 years, the immune
response to Prevenar 13 was non inferior to Prevenar for the 7 common serotypes and to Prevenar 13 
for the 6 additional serotypes compared to the immune response after the fourth dose in infants 
vaccinated at 2, 4, 6 and 12-15 months of age as measured by serum IgG.

In children and adolescents aged 10 to 17 years of age OPA GMTs 1 month after vaccination were 
noninferior to OPA GMTs in the 5 to 10 year old age group for 12 of the 13 serotypes (except 
serotype 3). 

Immune responses after subcutaneous administration

Subcutaneous administration of Prevenar 13 was evaluated in a non-comparative study in 185 healthy 
Japanese infants and children who received 4 doses at 2, 4, 6 and 12-15 months of age. The study 
demonstrated that safety and immunogenicity were generally comparable with observations made in 
studies of intramuscular administration.

Prevenar 13 Effectiveness

Invasive Pneumococcal Disease
Data published by Public Health England showed that, four years after the introduction of Prevenar as 
a two dose primary infant series with booster dose in the second year of life and with a 94% vaccine 
uptake, there was a 98% (95% CI 95; 99) reduction in disease caused by the 7 vaccine serotypes in 
England and Wales. Subsequently, four years following the switch to Prevenar 13, the additional
reduction in incidence of IPD due to the 7 serotypes in Prevenar ranged from 76% in children less 
than 2 years of age to 91% in children 5-14 years of age. The serotype specific reductions for each of 
the 5 additional serotypes in Prevenar 13 (no cases of serotype 5 IPD were observed) by age group are 
shown in Table 2 and ranged from 68% (serotype 3) to 100% (serotype 6A) for children less than 
5 years of age. Significant incidence reductions were also observed in older age groups who had not 
been vaccinated with Prevenar 13 (indirect effect).



16

Otitis media (OM)
In a published study performed in Israel, using a 2-dose primary series plus booster dose in the second 
year of life, the impact of Prevenar 13 on OM was documented in a population-based 
active-surveillance system with tympanocentesis culturing of middle ear fluid in Israeli children less 
than 2 years of age with OM. 

Following the introduction of Prevenar and subsequently Prevenar 13 there was a decline in incidence 
from 2.1 to 0.1 cases per 1000 children (95%) for the Prevenar serotypes plus serotype 6A and a 
decline in incidence from 0.9 to 0.1 cases per 1000 children (89%) for the additional serotypes 1, 3, 5, 
7F, and 19A in Prevenar 13. The annual overall pneumococcal incidence of OM declined from 9.6 to 
2.1 cases per 1000 children (78%) between July 2004 (prior to the introduction of Prevenar) and June 
2013 (post Prevenar 13 introduction).

Table 2: Serotype specific number of cases and incidence reductions of IPD in 2013/14 compared to 
2008/09-2009/10 (2008/10) by age in England and Wales

<5 years of age 5 to 64 years of age ≥65 years of age

2008-
10§

2013/
14§

% Incidence 
reduction 
(95% CI*)

2008-
10§

2013/
14§

% 
Incidence 
reduction 
(95% CI*)

2008-
10§

2013/
14§

% Incidence 
reduction 
(95% CI*)

Additional serotypes covered by Prevenar 13

1 59 (54) 5 (5) 91%

(98%; 
68%)**

458 
(382)

77 
(71)

83%

(88%; 
74%)**

102 
(89)

13 
(13)

87%

(94%; 
72%)**

3 26 (24) 8 (8) 68%

(89%; 6%)

178 
(148)

73 
(68)

59%

(72%; 
38%)**

256 
(224)

143 
(146)

44%

(57%; 
27%)**

6A 10 (9) 0 (0) 100%

(100%; 
62%)**

53 (44) 5 (5) 90%

(97%; 
56%)**

94 (82) 5 (5) 95%

(99%; 
81%)**

7F 90 (82) 8 (8) 91%

(97%; 
74%)**

430 
(361)

160
(148)

63%

(71%; 
50%)**

173 
(152)

75 
(77)

56%

(70%; 
37%)**

19A 85 (77) 7 (7) 91%

(97%; 
75%)**

225 
(191)

104 
(97)

54%

(65%; 
32%)**

279 
(246)

97 
(99)

65%

(75%; 
53%)**

§ Corrected for proportion of samples serotyped, missing age, denominator compared with 2009/10, and 
for the trend in total invasive pneumococcal disease up to 2009/10 (after which no trend correction was 
applied).

* 95% CI inflated from a Poisson interval based on over-dispersion of 2.1 seen from modelling of 
2000-06 pre-Prevenar all IPD data.

** p<0.005 to cover 6A where p=0.002



17

Pneumonia
In a multicenter observational study in France comparing the periods before and after the switch from 
Prevenar to Prevenar 13, there was 16% (2060 to 1725 cases) reduction in all community acquired 
pneumonia (CAP) cases in emergency departments in children 1 month to 15 years of age. Reductions 
were 53% (167 to 79 cases) (p<0.001) for CAP cases with pleural effusion and 63% (64 to 24 cases)
(p<0.001) for microbiologically confirmed pneumococcal CAP cases. In the second year after the 
introduction of Prevenar 13 the total number of CAP cases due to the 6 additional vaccine serotypes in 
Prevenar 13 was reduced from 27 to 7 isolates (74%).

The decrease in all cause pneumonia cases was most pronounced in the younger vaccinated age 
groups with a decrease of 31.8% (757 to 516 cases) and 16.6% (833 to 695 cases) in the age groups 
<2 years and 2 to 5 years, respectively. The incidence in older, predominantly non-vaccinated children 
(>5 years) did not change over the duration of the study.

In an ongoing surveillance system (2004 to 2013) to document the impact of Prevenar and 
subsequently Prevenar 13 on CAP in children less than 5 years in Southern Israel using a 2 dose 
primary series with a booster dose in the second year of life, there was a reduction of 68% 
(95% CI 73; 61) in outpatient visits and 32% (95% CI 39; 22) in hospitalizations for alveolar CAP 
following the introduction of Prevenar 13 when compared to the period before the introduction of 
Prevenar.

Effect on nasopharyngeal carriage 

In a surveillance study in France in children presenting with acute otitis media, changes in 
nasopharyngeal (NP) carriage of pneumococcal serotypes were evaluated following the introduction 
of Prevenar (7-valent) and subsequently Prevenar 13. Prevenar 13 significantly reduced NP carriage of 
the 6 additional serotypes (and serotype 6C) combined and individual serotypes 6C, 7F, 19A when 
compared with Prevenar. A reduction in carriage was also seen for serotype 3 (2.5% vs 1.1%; p=0.1). 
There was no carriage of serotypes 1 and 5 observed.

The effect of pneumococcal conjugate vaccination on nasopharyngeal carriage was studied in a 
randomised double-blind study in which infants received either Prevenar 13 or Prevenar (7-valent) at 
2, 4, 6 and 12 months of age in Israel. Prevenar 13 significantly reduced newly identified NP 
acquisition of the 6 additional serotypes (and serotype 6C) combined and of individual serotypes 1, 
6A, 6C, 7F, 19A when compared with Prevenar. There was no reduction seen in serotype 3 and for 
serotype 5 the colonization was too infrequent to assess impact. For 6 of the remaining 7 common 
serotypes, similar rates of NP acquisition were observed in both vaccine groups; for serotype 19F a 
significant reduction was observed.

In this study, reductions of S. pneumoniae serotypes 19A, 19F, and 6A not susceptible to a number of 
antibiotics were documented. The reductions ranged between 34% and 62% depending on serotype 
and antibiotic.

Prevenar (7-valent vaccine) protective efficacy in infants and children

The efficacy of 7-valent Prevenar was evaluated in two major studies – the Northern California Kaiser 
Permanente (NCKP) study and the Finnish Otitis Media (FinOM) study. Both studies were 
randomised, double-blind, active-control studies in which infants were randomised to receive either 
Prevenar or control vaccine (NCKP, meningococcal serogroup C CRM-conjugate [MnCC] vaccine; 
FinOM, hepatitis B vaccine) in a four-dose series at 2, 4, 6, and 12-15 months of age. The efficacy 
results from these studies (for invasive pneumococcal disease, pneumonia, and acute otitis media) are 
presented below (Table 3).



18

Table 3: Summary of efficacy of 7-valent Prevenar1

Test N VE2 95% CI

NCKP: Vaccine-serotype IPD3 30,258 97% 85, 100

NCKP: Clinical pneumonia with abnormal chest X-ray 23,746 35% 4, 56

NCKP: Acute Otitis Media (AOM)4 23,746

Total episodes 7% 4, 10

Recurrent AOM (3 episodes in 6 months, or 4 episodes in 1 year) 9% 3, 15
Recurrent AOM (5 episodes in 6 months, or 6 episodes in 1 year) 23% 7, 36
Tympanostomy tube placement 20% 2, 35

FinOM: AOM 1,662

Total episodes 6% -4, 16

All pneumococcal AOM 34% 21, 45
Vaccine-serotype AOM 57% 44, 67

1Per protocol
2Vaccine efficacy
3October 1995 to April 20, 1999
4October 1995 to April 30, 1998

Prevenar (7-valent) effectiveness

The effectiveness (both direct and indirect effect) of 7-valent Prevenar against pneumococcal disease 
has been evaluated in both three-dose and two-dose primary infant series immunisation programmes,
each with booster doses (Table 4). Following the widespread use of Prevenar, the incidence of IPD 
has been consistently and substantially reduced.

Using the screening method, serotype-specific effectiveness estimates for 2 doses under the age of 
1 year in the UK were 66 % (-29, 91 %) and 100 % (25, 100 %) for serotype 6B and 23F, respectively.

Table 4: Summary of effectiveness of 7-valent Prevenar for invasive pneumococcal disease
Country

(year of introduction)
Recommended schedule Disease reduction, % 95% CI

UK (England & Wales)1 (2006) 2, 4, + 13 months Vaccine serotypes:
Two doses under age 1: 85%

49, 95%

USA (2000)

Children < 52

Persons ≥ 653

2, 4, 6, + 12-15 months

Vaccine serotypes: 98%
All serotypes: 77%

Vaccine serotypes: 76%
All serotypes: 38%

97, 99%
73, 79%

NA
NA

Canada (Quebec)4

(2004)
2, 4, + 12 months All serotypes: 73%

Vaccine serotypes:
2-dose infant series: 99%
Completed schedule:100%

NA

92, 100%
82, 100%

1Children < 2 years of age. Calculated vaccine effectiveness as of June 2008 (Broome method).
22005 data.
32004 data.
4Children < 5 years of age. January 2005 to December 2007. Complete effectiveness for routine 2+1 schedule not 
yet available.

Acute Otitis Media
Effectiveness of Prevenar in a 3+1 schedule has also been observed against acute otitis media and 
pneumonia since its introduction in a national immunisation programme. In a retrospective evaluation 
of a large US insurance database, AOM visits were reduced by 42.7 % (95 % CI, 42.4-43.1 %), and 
prescriptions for AOM by 41.9 % in children younger than 2 years of age, compared with a 
pre-licensure baseline (2004 vs. 1997-99). In a similar analysis, hospitalisations and ambulatory visits 
for all-cause pneumonia were reduced by 52.4 % and 41.1 %, respectively. For those events 



19

specifically identified as pneumococcal pneumonia, the observed reductions in hospitalisations and 
ambulatory visits were 57.6 % and 46.9 %, respectively, in children younger than 2 years of age, 
compared with a pre-licensure baseline (2004 vs. 1997-99). While direct cause-and-effect cannot be 
inferred from observational analyses of this type, these findings suggest that Prevenar plays an 
important role in reducing the burden of mucosal disease (AOM and pneumonia) in the target 
population.

Efficacy study in adults 65 years and older

Efficacy against vaccine-type (VT) pneumococcal CAP and IPD was assessed in a large-scale 
randomised double-blind, placebo-controlled study (Community-Acquired Pneumonia Immunization 
Trial in Adults–CAPiTA) in the Netherlands. 84,496 subjects, 65 years and older received a single 
vaccination of either Prevenar 13 or placebo in a 1:1 randomisation.

The CAPiTA study enrolled volunteers ≥ 65 years of age whose demographic and health 
characteristics may differ from those seeking vaccination.

A first episode of hospitalised, chest X-ray confirmed pneumonia was identified in about 2% of this 
population (n=1,814 subjects) of which 329 cases were confirmed pneumococcal CAP and 182 cases 
were VT pneumococcal CAP in the per protocol and modified intent to treat (mITT) populations.

Efficacy was demonstrated for the primary and secondary endpoints in the per protocol population
(Table 5).

Table 5: Vaccine efficacy (VE) for the primary and secondary endpoints of the CAPiTA study (per 
protocol population)

Efficacy endpoint

Cases

VE (%)
(95.2% CI)

p-value
Total

Prevenar 13
group

Placebo
group

Primary endpoint

First episode of confirmed VT 
pneumococcal CAP

139 49 90
45.56

(21.82, 62.49)
0.0006

Secondary endpoints

First episode of confirmed NB/NI1

vaccine type pneumococcal CAP
93 33 60

45.00
(14.21, 65.31)

0.0067

First episode of VT-IPD2 35 7 28
75.00

(41.06, 90.87)
0.0005

1NB/NI – non-bacteraemic/non-invasive
2VT-IPD – vaccine-type invasive pneumococcal disease

The duration of protective efficacy against a first episode of VT pneumococcal CAP, 
NB/NI VT pneumococcal CAP, and VT-IPD extended throughout the 4-year study.

The study was not designed to demonstrate efficacy in subgroups, and the number of subjects 
≥ 85 years of age was not sufficient to demonstrate efficacy in this age group.

A post-hoc analysis was used to estimate the following public health outcomes against clinical CAP 
(as defined in the CAPiTA study, and based on clinical findings regardless of radiologic infiltrate or 
etiologic confirmation): vaccine efficacy (VE), incidence rate reduction (IRR), and number needed to 
vaccinate (NNV) (Table 6).

IRR, also referred to as vaccine preventable disease incidence, is the number of cases of vaccine 
preventable disease per 100,000 person-years of observation.



20

In Table 6, NNV is a measure that quantifies the number of people that need to be vaccinated in order 
to prevent one clinical CAP case.

Table 6: Vaccine efficacy (VE) against clinical CAP*

Episodes Vaccine efficacy1 % 
(95% CI)

(1-sided p-value)

Incidence per 
100,000 person-

years of observation 
(PYO)

Incidence 
rate 

reduction2

(95% CI)

Number 
needed to 
vaccinate3

Prevenar
13

Placebo Prevenar 
13

Placebo

All 
episodes 
analysis

1375 1495 8.1

(-0.6, 16.1) 

(0.034)

819.1 891.2 72.2 
(-5.3, 149.6)

277

First 
episode 
analysis

1126 1214 7.3

(-0.4, 14.4)

(0.031)

670.7 723.7 53.0
(-2.7, 108.7)

378

* Patients with at least 2 of the following: Cough; purulent sputum, temperature >38°C or <36.1°C; pneumonia 
(auscultatory findings); leukocytosis; C-reactive protein value >3 times the upper limit of normal; hypoxemia with 
a partial oxygen pressure <60 mm Hg while breathing room air.
1 A Poisson regression model with random effects was used to calculate VE.
2 Per 100,000 person-years of observation. IRR is calculated as the incidence in the placebo group minus the 
incidence in the vaccine group, and was mathematically equivalent to VE × the incidence in the placebo group.
3 Based on a 5-year duration of protection. NNV is not a rate but instead indicates the number of cases prevented 
for a given number of persons vaccinated. NNV also incorporates the length of the trial or duration of protection
and is calculated as 1 divided by the product of the IRR and duration of protection (or length of trial) (=1/(IRR ×
duration).

Immunogenicity studies in adults ≥18 years and the elderly

In adults, an antibody threshold of serotype-specific pneumococcal polysaccharide IgG binding 
antibody concentration associated with protection has not been defined. For all pivotal clinical trials, a 
serotype-specific opsonophagocytosis assay (OPA) was used as a surrogate to assess potential 
efficacy against invasive pneumococcal disease and pneumonia. OPA geometric mean titers (GMTs) 
measured 1-month after each vaccination were calculated. OPA titres are expressed as the reciprocal 
of the highest serum dilution that reduces survival of the pneumococci by at least 50 %.

Pivotal trials for Prevenar 13 were designed to show that functional OPA antibody responses for the 
13 serotypes are non-inferior, and for some serotypes superior, to the 12 serotypes in common with 

the licensed 23-valent pneumococcal polysaccharide vaccine [1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 
19F, 23F] one month after vaccine administration. The response to serotype 6A, which is unique to 
Prevenar 13, was assessed by demonstration of a 4-fold increase in the specific OPA titer above 
pre-immunised levels.

Five clinical studies were conducted in Europe and the USA evaluating the immunogenicity of 
Prevenar 13 in different age groups ranging from 18-95 years of age. Clinical studies with Prevenar 13 
currently provide immunogenicity data in adults aged 18 years and older, including adults aged 65 and 
older previously vaccinated with one or more doses of 23-valent pneumococcal polysaccharide 
vaccine, 5 years prior to enrollment. Each study included healthy adults and immuno-competent adults 
with stable underlying conditions known to predispose individuals to pneumococcal infection (i.e.,
chronic cardiovascular disease, chronic pulmonary disease including asthma, renal disorders and 
diabetes mellitus, chronic liver disease including alcoholic liver disease), and adults with risk factors 
such as smoking and alcohol abuse.

Immunogenicity and safety of Prevenar 13 has been demonstrated in adults aged 18 years and older 
including those previously vaccinated with a pneumococcal polysaccharide vaccine.



21

Adults not previously vaccinated with 23-valent pneumococcal polysaccharide vaccine
In a head-to-head, comparative trial conducted in adults aged 60-64 years, subjects received a single 
dose of either Prevenar 13 or 23-valent pneumococcal polysaccharide vaccine. In the same study 
another group of adults aged 50-59 years and another group of adults aged 18-49 years received a 
single dose of Prevenar 13.

Table 7 compares the OPA GMTs, 1-month post-dose, in 60-64 year olds given either a single dose of 
Prevenar 13 or 23-valent pneumococcal polysaccharide vaccine, and in 50-59 year olds given a single 
dose of Prevenar 13.

Table 7: OPA GMTs in adults aged 60-64 years given Prevenar 13 or 23-valent pneumococcal 
polysaccharide vaccine (PPSV23) and in adults aged 50-59 years given Prevenar 13a,b,c

Prevenar 13 Prevenar 13 PPSV23 Prevenar 13
50-59 Relative to

60-64 Years

Prevenar 13 Relative
to PPSV23,
60-64 Years

50-59 Years 
N=350-384

60-64 Years 
N=359-404

60-64 Years 
N=367-402

Serotype GMT GMT GMT GMR (95% CI) GMR (95% CI)
1 200 146 104 1.4 (1.08, 1.73) 1.4 (1.10, 1.78)
3 91 93 85 1.0 (0.81, 1.19) 1.1 (0.90, 1.32)
4 2833 2062 1295 1.4 (1.07, 1.77) 1.6 (1.19, 2.13)
5 269 199 162 1.4 (1.01, 1.80) 1.2 (0.93, 1.62)

6A† 4328 2593 213 1.7 (1.30, 2.15) 12.1 (8.63, 17.08)
6B 3212 1984 788 1.6 (1.24, 2.12) 2.5 (1.82, 3.48)
7F 1520 1120 405 1.4 (1.03, 1.79) 2.8 (1.98, 3.87)
9V 1726 1164 407 1.5 (1.11, 1.98) 2.9 (2.00, 4.08)
14 957 612 692 1.6 (1.16, 2.12) 0.9 (0.64, 1.21)

18C 1939 1726 925 1.1 (0.86, 1.47) 1.9 (1.39, 2.51)
19A 956 682 352 1.4 (1.16, 1.69) 1.9 (1.56, 2.41)
19F 599 517 539 1.2 (0.87, 1.54) 1.0 (0.72, 1.28)
23F 494 375 72 1.3 (0.94, 1.84) 5.2 (3.67, 7.33)

a Non-inferiority was defined as the lower limit of the 2-sided 95% CI for GMR was greater than 0.5. 
b Statistically significantly greater response was defined as the lower bound of the 2-sided 95% CI for the GMR 
was greater than 1. 
c For serotype 6A†, which is unique to Prevenar 13, a statistically significantly greater response was defined as 
the lower bound of the 2-sided 95% CI for the GMR being greater than 2.

In adults aged 60-64 years, OPA GMTs to Prevenar 13 were non-inferior to the OPA GMTs elicited to 
the 23-valent pneumococcal polysaccharide vaccine for the twelve serotypes common to both 
vaccines. For 9 serotypes, the OPA titers were shown to be statistically significantly greater in 
Prevenar 13 recipients. 

In adults aged 50-59 years, OPA GMTs to all 13 serotypes in Prevenar 13 were non-inferior to the 
Prevenar 13 responses in adults aged 60-64 years. For 9 serotypes, immune responses were related to 
age, with adults in the 50-59 years group showing statistically significantly greater responses than 
adults aged 60-64 years.

In all adults ≥ 50 years who received a single dose of Prevenar 13, the OPA titers to serotype 6A were 
significantly greater than in adults ≥ 60 years who received a single dose of 23-valent pneumococcal 
polysaccharide vaccine.

One year after vaccination with Prevenar 13 OPA titers had declined compared to one month after 
vaccination, however, OPA titers for all serotypes remained higher than levels at baseline:



22

OPA GMT levels at baseline OPA GMT levels one year after 
Prevenar 13

Adults 50-59 years not previously 
vaccinated with 23-valent 
pneumococcal polysaccharide vaccine

5 to 45 20 to 1234

Adults 60-64 years not previously 
vaccinated with 23-valent 
pneumococcal polysaccharide vaccine

5 to 37 19 to 733

Table 8 shows OPA GMTs 1-month after a single dose of Prevenar 13 in 18-49 year olds compared to 
60-64 year olds.

Table 8: OPA GMTs in adults aged 18-49 years and 60-64 years given Prevenar 13a,b

18-49 Years
N=836-866

60-64 Years
N=359-404

18-49 Years 
Relative to 

60-64 Years 
Serotype GMTb GMTb GMR (95% CIc)

1 353 146 2.4 (2.03, 2.87)
3 91 93 1.0 (0.84, 1.13)
4 4747 2062 2.3 (1.92, 2.76)
5 386 199 1.9 (1.55, 2.42)

6A 5746 2593 2.2 (1.84, 2.67)
6B 9813 1984 4.9 (4.13, 5.93)
7F 3249 1120 2.9 (2.41, 3.49)
9V 3339 1164 2.9 (2.34, 3.52)
14 2983 612 4.9 (4.01, 5.93)

18C 3989 1726 2.3 (1.91, 2.79)
19A 1580 682 2.3 (2.02, 2.66)
19F 1533 517 3.0 (2.44, 3.60)
23F 1570 375 4.2 (3.31, 5.31)

a Non-inferiority was defined as the lower limit of the 2-sided 95% CI for GMR was greater than 0.5. 
b Statistically significantly greater response was defined as the lower bound of the 2-sided 95% CI for the GMR 
was greater than 1.

c c Confidence intervals (CIs) for the ratio are back transformations of a confidence interval based on the Student t 
distribution for the mean difference of the logarithms of the measures.

In adults aged 18-49 years, OPA GMTs to all 13 serotypes in Prevenar 13 were non-inferior to the 
Prevenar 13 responses in adults aged 60-64 years. 

One year after vaccination with Prevenar 13 OPA titers had declined compared to one month after 
vaccination, however OPA titers for all serotypes remained higher than levels at baseline.

OPA GMT levels at baseline OPA GMT levels one year after 
Prevenar 13

Adults 18-49 years not previously 
vaccinated with 23-valent 
pneumococcal polysaccharide vaccine

5 to 186 23 to 2948

Adults previously vaccinated with 23-valent pneumococcal polysaccharide vaccine
Immune responses to Prevenar 13 and 23-valent pneumococcal polysaccharide vaccine were 
compared in a head to head trial in adults aged ≥ 70 years, who had received a single dose of 
pneumococcal polysaccharide vaccine at least 5 years before study vaccination.



23

Table 9 compares the OPA GMTs, 1-month post-dose, in pneumococcal polysaccharide vaccinated 
adults aged ≥ 70 years given a single dose of either Prevenar 13 or 23-valent pneumococcal 
polysaccharide vaccine.

Table 9: OPA GMTs in pneumococcal polysaccharide vaccinated adults aged 
≥ 70 years given either Prevenar 13 or 23-valent pneumococcal polysaccharide vaccine (PPSV23)a,b,c

Prevenar 13
N=400-426

PPSV23
N=395-445

Prevenar OPA GMT
Relative to PPSV23

Serotype OPA GMT OPA GMT GMR (95% CI)
1 81 55 1.5 (1.17, 1.88)
3 55 49 1.1 (0.91, 1.35)
4 545 203 2.7 (1.93, 3.74)
5 72 36 2.0 (1.55, 2.63)

6A† 903 94 9.6 (7.00, 13.26)
6B 1261 417 3.0 (2.21, 4.13)
7F 245 160 1.5 (1.07, 2.18)
9V 181 90 2.0 (1.36, 2.97)
14 280 285 1.0 (0.73, 1.33)

18C 907 481 1.9 (1.42, 2.50)
19A 354 200 1.8 (1.43, 2.20)
19F 333 214 1.6 (1.17, 2.06)
23F 158 43 3.7 (2.69, 5.09)

a Non-inferiority was defined as the lower limit of the 2-sided 95% CI for GMR was greater than 0.5. 
b Statistically significantly greater response was defined as the lower bound of the 2-sided 95% CI for the GMR 
was greater than 1. 
c For serotype 6A†, which is unique to Prevenar 13, a statistically significantly greater response was defined as the 
lower bound of the 2-sided 95% CI for the GMR greater than 2.

In adults vaccinated with pneumococcal polysaccharide vaccine at least 5 years prior to the clinical 
study, OPA GMTs to Prevenar 13 were non-inferior to the 23-valent pneumococcal polysaccharide 
vaccine responses for the 12 serotypes in common. Furthermore, in this study statistically significantly 
greater OPA GMTs were demonstrated for 10 of the 12 serotypes in common. Immune responses to 
serotype 6A were statistically significantly greater following vaccination with Prevenar 13 than after 
23-valent pneumococcal polysaccharide vaccine.

One year after vaccination with Prevenar 13 in adults aged 70 years and over who were vaccinated 
with 23-valent pneumococcal polysaccharide vaccine, at least 5 years prior to study entry, OPA titers 
had declined compared to one month after vaccination, however, OPA titers for all serotypes 
remained higher than levels at baseline:

Immune responses in Special Populations

Individuals with the conditions described below have an increased risk of pneumococcal disease. The 
clinical relevance of the antibody levels elicited by Prevenar 13 in these special populations is 
unknown.

Sickle cell disease 
An open label single arm study in France, Italy, UK, US, Lebanon, Egypt and Saudi Arabia with 
2 doses of Prevenar 13 given 6 months apart was conducted in 158 children and adolescents ≥ 6 to 

OPA GMT levels at baseline OPA GMT levels one year after 
Prevenar 13

Adults ≥ 70 years vaccinated with 
23-valent pneumococcal 
polysaccharide vaccine at least 5 
years prior

9 to 122 18 to 381



24

< 18 years of age with sickle cell disease who were previously vaccinated with one or more doses of 
23-valent pneumococcal polysaccharide vaccine at least 6 months prior to enrollment. After the first 
vaccination, Prevenar 13 elicited antibody levels measured by both IgG GMCs and OPA GMTs that 
were statistically significantly higher when compared to levels prior to vaccination. After the second 
dose immune responses were comparable to those after the first dose. One year after the second dose, 
antibody levels measured by both IgG GMCs and OPA GMTs were higher than levels prior to the first 
dose of Prevenar 13, except for the IgG GMCs for serotypes 3 and 5 that were numerically similar.

Additional Prevenar (7-valent) immunogenicity data: children with sickle cell disease
The immunogenicity of Prevenar has been investigated in an open-label, multicentre study in 
49 infants with sickle cell disease. Children were vaccinated with Prevenar (3 doses one month apart 
from the age of 2 months), 46 of these children also received a 23-valent pneumococcal
polysaccharide vaccine at the age of 15-18 months. After primary immunisation, 95.6 % of the 
subjects had antibody levels of at least 0.35 μg/ml for all seven serotypes found in Prevenar. 
A significant increase was seen in the concentrations of antibodies against the seven serotypes after 
the polysaccharide vaccination, suggesting that immunological memory was well established.

HIV infection

Children and adults not previously vaccinated with a pneumococcal vaccine
HIV-infected children and adults with CD4 ≥ 200 cells/µL (mean 717.0 cells/μL), viral load 
< 50,000 copies/ml (mean 2090.0 copies/ml), free of active AIDS-related illness and not previously 
vaccinated with a pneumococcal vaccine received 3 doses of Prevenar 13. As per general 
recommendations, a single dose of 23-valent pneumococcal polysaccharide vaccine was subsequently 
administered. Vaccines were administered at 1 month intervals. Immune responses were assessed in 
259-270 evaluable subjects approximately 1 month after each dose of vaccine. After the first dose, 
Prevenar 13 elicited antibody levels, measured by both IgG GMCs and OPA GMTs that were 
statistically significantly higher when compared to levels prior to vaccination. After the second and 
third dose of Prevenar 13, immune responses were similar or higher than those after the first dose.

Adults previously vaccinated with 23-valent pneumococcal polysaccharide vaccine
HIV-infected adults ≥ 18 years of age with CD4 ≥ 200 cells/µL (mean 609.1 cells/µL) and viral load 
< 50,000 copies/ml (mean 330.6 copies/ml), who were free of active AIDS-related illness and were 
previously vaccinated with 23-valent pneumococcal polysaccharide vaccine administered at least 
6 months prior to enrollment, received 3 doses of Prevenar 13, at enrollment, 6 months, and
12 months after the first dose of Prevenar 13. Immune responses were assessed in 231-255 evaluable 
subjects approximately 1 month after each dose of Prevenar 13. After the first dose, Prevenar 13 
elicited antibody levels measured by both IgG GMCs and OPA GMTs that were statistically 
significantly higher when compared to levels prior to vaccination. After the second and third dose of 
Prevenar 13, immune responses were comparable or higher than those after the first dose. In the study 
162 subjects had received one prior dose of 23-valent pneumococcal polysaccharide vaccine, 
143 subjects 2 prior doses and 26 subjects more than 2 prior doses of 23-valent polysaccharide 
vaccine. Subjects who received two or more previous doses of 23-valent pneumococcal 
polysaccharide vaccine showed a similar immune response compared with subjects who received a 
single previous dose.

Haematopoietic stem cell transplant
Children and adults with an allogeneic haematopoietic stem cell transplant (HSCT) at ≥ 2 years of age 
with complete haematologic remission of underlying disease or with very good partial remission in the 
case of lymphoma and myeloma received three doses of Prevenar 13 with an interval of at least 
1 month between doses. The first dose was administered at 3 to 6 months after HSCT. A fourth 
(booster) dose of Prevenar 13 was administered 6 months after the third dose. As per general 
recommendations, a single dose of 23-valent pneumococcal polysaccharide vaccine was administered 
1 month after the fourth dose of Prevenar 13. Immune responses as measured by IgG GMCs were 
assessed in 168-211 evaluable subjects approximately 1 month after vaccination. Prevenar 13 elicited 
increased antibody levels after each dose of Prevenar 13. Immune responses after the fourth dose of 



25

Prevenar 13 were significantly increased for all serotypes compared with after the third dose.
Functional antibody titers (OPA titers) were not measured in this study.

5.2 Pharmacokinetic properties

Not applicable.

5.3 Preclinical safety data

Non-clinical data revealed no special hazard for humans based on conventional studies of safety 
pharmacology, single and repeated dose toxicity, local tolerance, and reproduction and developmental 
toxicity.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sodium chloride
Succinic acid
Polysorbate 80
Water for injections

For adjuvant, see section 2.

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products.

6.3 Shelf life

3 years

6.4 Special precautions for storage

Store in a refrigerator (2C – 8C). Do not freeze.

Prevenar 13 is stable at temperatures up to 25°C for four days. At the end of this period Prevenar 13 
should be used or discarded. These data are intended to guide health care professionals in case of 
temporary temperature excursions.

6.5 Nature and contents of container

0.5 ml suspension for injection in pre-filled syringe (Type I glass) with a plunger stopper (latex-free 
chlorobutyl rubber) and protective-tip cap (latex-free isoprene bromobutyl rubber).

Pack sizes of 1, 10 and 50, with or without needle.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

During storage, a white deposit and clear supernatant can be observed. This does not constitute a sign 
of deterioration.



26

The vaccine should be shaken well to obtain a homogeneous white suspension prior to expelling air 
from the syringe, and should be inspected visually for any particulate matter and/or variation of 
physical aspect prior to administration. Do not use if the content appears otherwise.

No special requirements for disposal.

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.

7. MARKETING AUTHORISATION HOLDER

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/09/590/001
EU/1/09/590/002
EU/1/09/590/003
EU/1/09/590/004
EU/1/09/590/005
EU/1/09/590/006

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 09 December 2009
Date of latest renewal: 18 September 2014

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.



27

1. NAME OF THE MEDICINAL PRODUCT

Prevenar 13 suspension for injection in single dose vial
pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed)

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

1 dose (0.5 ml) contains:

Pneumococcal polysaccharide serotype 11 2.2 µg
Pneumococcal polysaccharide serotype 31 2.2 µg
Pneumococcal polysaccharide serotype 41 2.2 µg
Pneumococcal polysaccharide serotype 51 2.2 µg
Pneumococcal polysaccharide serotype 6A1 2.2 µg
Pneumococcal polysaccharide serotype 6B1 4.4 µg
Pneumococcal polysaccharide serotype 7F1 2.2 µg
Pneumococcal polysaccharide serotype 9V1 2.2 µg
Pneumococcal polysaccharide serotype 141 2.2 µg
Pneumococcal polysaccharide serotype 18C1 2.2 µg
Pneumococcal polysaccharide serotype 19A1 2.2 µg
Pneumococcal polysaccharide serotype 19F1 2.2 µg
Pneumococcal polysaccharide serotype 23F1 2.2 µg

1Conjugated to CRM197 carrier protein, adsorbed on aluminium phosphate.

1 dose (0.5 ml) contains approximately 32 µg CRM197 carrier protein and 0.125 mg aluminium.

Excipients with known effect
For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Suspension for injection in single dose vial.
The vaccine is a homogeneous white suspension.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Active immunisation for the prevention of invasive disease, pneumonia and acute otitis media caused 
by Streptococcus pneumoniae in infants, children and adolescents from 6 weeks to 17 years of age.

Active immunisation for the prevention of invasive disease and pneumonia caused by Streptococcus 
pneumoniae in adults ≥ 18 years of age and the elderly.

See sections 4.4 and 5.1 for information on protection against specific pneumococcal serotypes.

The use of Prevenar 13 should be determined on the basis of official recommendations taking into 
consideration the risk of invasive disease and pneumonia in different age groups, underlying 
comorbidities as well as the variability of serotype epidemiology in different geographical areas.



28

4.2 Posology and method of administration

The immunisation schedules for Prevenar 13 should be based on official recommendations.

Posology

Infants and children aged 6 weeks to 5 years

It is recommended that infants who receive a first dose of Prevenar 13 complete the vaccination 
course with Prevenar 13.

Infants aged 6 weeks-6 months

Three-dose primary series
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 usually given at 2 months of age and with an interval 
of at least 1 month between doses. The first dose may be given as early as six weeks of age. The 
fourth (booster) dose is recommended between 11 and 15 months of age.

Two-dose primary series
Alternatively, when Prevenar 13 is given as part of a routine infant immunisation programme, a series 
consisting of three doses, each of 0.5 ml, may be given. The first dose may be administered from the 
age of 2 months, with a second dose 2 months later. The third (booster) dose is recommended between 

11 and 15 months of age (see section 5.1).

Preterm infants (<37 weeks gestation)

In preterm infants, 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. The first dose may be given as early as six weeks of age. 
The fourth (booster) dose is recommended between 11 and 15 months of age (see sections 4.4 and 
5.1).

Unvaccinated infants and children ≥ 7 months of age

Infants aged 7-11 months
Two doses, each of 0.5 ml, with an interval of at least 1 month between doses. A third dose is 
recommended in the second year of life.

Children aged 12-23 months
Two doses, each of 0.5 ml, with an interval of at least 2 months between doses (see section 5.1).

Children and adolescents aged 2-17 years 
One single dose of 0.5 ml.

Prevenar 13 vaccine schedule for infants and children previously vaccinated with Prevenar (7-valent) 
(Streptococcus pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F)
Prevenar 13 contains the same 7 serotypes included in Prevenar, using the same carrier protein 
CRM197. 

Infants and children who have begun immunisation with Prevenar may switch to Prevenar 13 at any 
point in the schedule.



29

Young children (12-59 months) completely immunised with Prevenar (7-valent)
Young children who are considered completely immunised with Prevenar (7-valent) should receive 
one dose of 0.5 ml of Prevenar 13 to elicit immune responses to the 6 additional serotypes. This dose 
of Prevenar 13 should be administered at least 8 weeks after the final dose of Prevenar (7-valent) (see 
section 5.1).

Children and adolescents 5–17 years 
Children 5 to 17 years of age may receive a single dose of Prevenar 13 if they have been previously 
vaccinated with one or more doses of Prevenar. This dose of Prevenar 13 should be administered at 
least 8 weeks after the final dose of Prevenar (7-valent) (see section 5.1).

Adults ≥ 18 years of age, and the elderly

One single dose.
The need for revaccination with a subsequent dose of Prevenar 13 has not been established.

Regardless of prior pneumococcal vaccination status, if the use of 23-valent pneumococcal 
polysaccharide vaccine is considered appropriate, Prevenar 13 should be given first (see sections 4.5 
and 5.1).

Special Populations

Individuals who have underlying conditions predisposing them to invasive pneumococcal disease 
(such as sickle cell disease or HIV infection) including those previously vaccinated with one or more 
doses of 23-valent pneumococcal polysaccharide vaccine may receive at least one dose of Prevenar 13 
(see section 5.1).

In individuals with an haematopoietic stem cell transplant (HSCT), the recommended immunisation 
series consists of four doses of Prevenar 13, each of 0.5 ml. The primary series consists of three doses, 
with the first dose given at 3 to 6 months after HSCT and with an interval of at least 1 month between 
doses. A fourth (booster) dose is recommended 6 months after the third dose (see section 5.1).

Method of administration

The vaccine should be given by intramuscular injection. The preferred sites are the anterolateral 
aspect of the thigh (vastus lateralis muscle) in infants or the deltoid muscle of the upper arm in 
children and adults. 

4.3 Contraindications

Hypersensitivity to the active substances, to any of the excipients listed in section 6.1, or to diphtheria 
toxoid.

As with other vaccines, the administration of Prevenar 13 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

Prevenar 13 must not be administered intravascularly.

As with all injectable vaccines, appropriate medical treatment and supervision should always be 
readily available in case of a rare anaphylactic event following the administration of the vaccine.



30

This vaccine should not be given as an intramuscular injection to individuals with thrombocytopaenia 
or any coagulation disorder that would contraindicate intramuscular injection, but may be given 
subcutaneously if the potential benefit clearly outweighs the risks (see section 5.1).

Prevenar 13 will only protect against Streptococcus pneumoniae serotypes included in the vaccine, 
and will not protect against other microorganisms that cause invasive disease, pneumonia, or otitis 
media. As with any vaccine, Prevenar 13 may not protect all individuals receiving the vaccine from 
pneumococcal disease. For the most recent epidemiological information in your country you should 
consult with the relevant national organisation.

Individuals with impaired immune responsiveness, whether due to the use of immuno-suppressive 
therapy, a genetic defect, human immunodeficiency virus (HIV) infection, or other causes, may have 
reduced antibody response to active immunisation.

Safety and immunogenicity data are available for a limited number of individuals with sickle cell 
disease, HIV infection, or with an haematopoietic stem cell transplant (see section 5.1). Safety and 
immunogenicity data for Prevenar 13 are not available for individuals in other specific 
immuno-compromised groups (e.g., malignancy or nephrotic syndrome) and vaccination should be 
considered on an individual basis.

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially 
‘sodium-free’.

Infants and children aged 6 weeks to 5 years

In clinical studies, Prevenar 13 elicited an immune response to all thirteen serotypes included in the 
vaccine. The immune response for serotype 3 following the booster dose was not increased above the 
levels seen after the infant vaccination series; the clinical relevance of this observation regarding the 
induction of serotype 3 immune memory is unknown (see section 5.1).

The proportions of functional antibody responders (OPA titres ≥ 1:8) to serotypes 1, 3 and 5 were 
high. However, the OPA geometric mean titres were lower than those against each of the remaining 
additional vaccine serotypes; the clinical relevance of this observation for protective efficacy is 
unknown (see section 5.1). 

Limited data have demonstrated that Prevenar 7-valent (three-dose primary series) induces an 
acceptable immune response in infants with sickle cell disease with a safety profile similar to that 
observed in non-high-risk groups (see section 5.1). 

Children younger than 2 years old should receive the appropriate-for-age Prevenar 13 vaccination 
series (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 are immuno-compromised) 
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 Prevenar 13 
should receive 23-valent pneumococcal polysaccharide vaccine. The interval between the 13-valent 
pneumococcal conjugate vaccine (Prevenar 13) 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 23-valent pneumococcal polysaccharide vaccine to unprimed children or to children 
primed with Prevenar 13 might result in hyporesponsiveness to further doses of Prevenar 13.

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.



31

For vaccine serotypes, protection against otitis media is expected to be lower than protection against 
invasive disease. As otitis media is caused by many organisms other than pneumococcal serotypes 
represented in the vaccine, protection against all otitis media is expected to be low (see section 5.1).

When Prevenar 13 is administered concomitantly with Infanrix hexa (DTPa-HBV-IPV/Hib), the rates 
of febrile reactions are similar to those seen with concomitant administration of Prevenar (7-valent) 
and Infanrix hexa (see section 4.8). Increased reporting rates of convulsions (with or without fever) 
and hypotonic hyporesponsive episode (HHE) were observed with concomitant administration of 
Prevenar 13 and Infanrix hexa (see section 4.8).

Antipyretic treatment should be initiated according to local treatment guidelines for children with 
seizure disorders or with a prior history of febrile seizures and for all children receiving Prevenar 13 
simultaneously with vaccines containing whole cell pertussis.

4.5 Interaction with other medicinal products and other forms of interaction

Infants and children aged 6 weeks to 5 years

Prevenar 13 can be given concomitantly with any of the following vaccine antigens, either as 
monovalent or combination vaccines: diphtheria, tetanus, acellular or whole cell pertussis, 
Haemophilus influenzae type b, inactivated poliomyelitis, hepatitis B (see section 4.4 for guidance on 
Infanrix hexa), meningococcal serogroup C, measles, mumps, rubella, varicella and rotavirus vaccine. 

Prevenar 13 can also be given concomitantly between 12-23 months with the tetanus toxoid 
conjugated meningococcal polysaccharide serogroups A, C, W and Y vaccine to children who have 
been adequately primed with Prevenar 13 (as per local recommendations).

Data from a postmarketing clinical study evaluating the impact of prophylactic use of antipyretics 
(ibuprofen and paracetamol) on the immune response to Prevenar 13 suggest that administration of 
paracetamol concomitantly or within the same day of vaccination may reduce the immune response to 
Prevenar 13 after the infant series. Responses to the booster dose administered at 12 months were 
unaffected. The clinical significance of this observation is unknown.

Children and adolescents 6 to 17 years of age

No data are currently available regarding concomitant use with other vaccines. 

Adults 18 to 49 years of age

No data are available regarding concomitant use with other vaccines. 

Adults aged 50 years and older

Prevenar 13 may be administered concomitantly with the seasonal trivalent inactivated influenza 
vaccine (TIV).

In two studies conducted in adults aged 50-59 and 65 years and older, it was demonstrated that 
Prevenar 13 may be given concomitantly with trivalent inactivated influenza vaccine (TIV). The 
responses to all three TIV antigens were comparable when TIV was given alone or concomitantly 
with Prevenar 13.

When Prevenar 13 was given concomitantly with TIV, the immune responses to Prevenar 13 were 
lower compared to when Prevenar 13 was given alone, however, there was no long-term impact on 
circulating antibody levels.



32

In a third study in adults aged 50-93 years, it was demonstrated that Prevenar 13 may be given 
concomitantly with the seasonal quadrivalent inactivated influenza vaccine (QIV). The immune 
responses to all four QIV strains were noninferior when Prevenar 13 was given concomitantly with 
QIV compared to when QIV was given alone.

The immune responses to Prevenar 13 were noninferior when Prevenar 13 was given concomitantly 
with QIV compared to when Prevenar 13 was given alone. As with concomitant administration with 
trivalent vaccines, immune responses to some pneumococcal serotypes were lower when both 
vaccines were given concomitantly.

Concomitant use with other vaccines has not been investigated.

Different injectable vaccines should always be given at different vaccination sites.

Concomitant administration of Prevenar 13 and 23-valent pneumococcal polysaccharide vaccine has 
not been studied. In clinical studies when Prevenar 13 was given 1 year after 23-valent pneumococcal 
polysaccharide vaccine the immune responses were lower for all serotypes compared to when 
Prevenar 13 was given to subjects not previously immunised with 23-valent pneumococcal 
polysaccharide vaccine. The clinical significance of this is unknown. 

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no data from the use of pneumococcal 13-valent conjugate vaccine in pregnant women.
Therefore the use of Prevenar 13 should be avoided during pregnancy.

Breast-feeding

It is unknown whether pneumococcal 13-valent conjugate vaccine is excreted in human milk.

Fertility

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity 
(see section 5.3).

4.7 Effects on ability to drive and use machines

Prevenar 13 has no or negligible influence on the ability to drive and use machines. However, some of 
the effects mentioned under section 4.8 “Undesirable effects” may temporarily affect the ability to 
drive or use machines.

4.8 Undesirable effects

Analysis of postmarketing reporting rates suggests a potential increased risk of convulsions, with or 
without fever, and HHE when comparing groups which reported use of Prevenar 13 with 
Infanrix hexa to those which reported use of Prevenar 13 alone.

Adverse reactions reported in clinical studies or from the postmarketing experience for all age groups 
are listed in this section per system organ class, in decreasing order of frequency and seriousness. The 
frequency is defined as follows: very common ( 1/10), common ( 1/100 to < 1/10), uncommon 
( 1/1,000 to < 1/100), rare ( 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be 
estimated from available data).



33

Infants and children aged 6 weeks to 5 years
The safety of the vaccine was assessed in controlled clinical studies where 14,267 doses were given to 
4,429 healthy infants from 6 weeks of age at first vaccination and 11-16 months of age at booster 
dose. In all infant studies, Prevenar 13 was co-administered with routine paediatric vaccines (see 
section 4.5).

Safety in 354 previously unvaccinated children (7 months to 5 years of age) was also assessed.

The most commonly reported adverse reactions in children 6 weeks to 5 years of age were 
vaccination-site reactions, fever, irritability, decreased appetite, and increased and/or decreased sleep.

In a clinical study in infants vaccinated at 2, 3, and 4 months of age, fever ≥ 38°C was reported at 
higher rates among infants who received Prevenar (7-valent) concomitantly with Infanrix hexa (28.3% 
to 42.3%) than in infants receiving Infanrix hexa alone (15.6% to 23.1%). After a booster dose at 12 
to 15 months of age, fever ≥ 38°C was reported in 50.0% of infants who received Prevenar (7-valent) 
and Infanrix hexa at the same time as compared to 33.6% of infants receiving Infanrix hexa alone. 
These reactions were mostly moderate (less than or equal to 39°C) and transient.

An increase in vaccination-site reactions was reported in children older than 12 months compared to 
rates observed in infants during the primary series with Prevenar 13.

Adverse reactions from clinical studies
In clinical studies, the safety profile of Prevenar 13 was similar to Prevenar. The following 
frequencies are based on adverse reactions assessed in Prevenar 13 clinical studies:

Immune system disorders:
Rare: Hypersensitivity reaction including face oedema, dyspnoea, bronchospasm

Nervous system disorders:
Uncommon: Convulsions (including febrile convulsions)
Rare: Hypotonic-hyporesponsive episode

Gastrointestinal disorders:
Very common: Decreased appetite
Common: Vomiting; diarrhoea

Skin and subcutaneous tissue disorders:
Common: Rash
Uncommon: Urticaria or urticaria-like rash

General disorders and administration site conditions:
Very common: Pyrexia; irritability; any vaccination-site erythema, induration/swelling or 

pain/tenderness; somnolence; poor quality sleep
Vaccination-site erythema or induration/swelling 2.5 cm–7.0 cm (after the 
booster dose and in older children [age 2 to 5 years])

Common: Pyrexia > 39°C; vaccination-site movement impairment (due to pain); 
vaccination-site erythema or induration/swelling 2.5 cm–7.0 cm (after infant 
series)

Uncommon: Vaccination-site erythema, induration/swelling > 7.0 cm; crying

Additional information in special populations:
Apnoea in very premature infants ( 28 weeks of gestation) (see section 4.4).



34

Children and adolescents aged 6 to 17 years of age 
Safety was evaluated in 592 children (294 children aged 5 to 10 years previously immunised with at 
least one dose of Prevenar and 298 children aged 10 to 17 years who had not received a pneumococcal 
vaccine).

The most common adverse events in children and adolescents 6 to 17 years of age were:

Nervous system disorders:
Common: Headaches

Gastrointestinal disorders:
Very common: Decreased appetite
Common: Vomiting; diarrhoea

Skin and subcutaneous tissue disorders:
Common: Rash; urticaria or urticaria-like rash

General disorders and administration site conditions:
Very common: Irritability; any vaccination-site erythema; induration/swelling or 

pain/tenderness; somnolence; poor quality sleep; 
vaccination-site tenderness (including impaired movement)

Common: Pyrexia

Other adverse events previously observed in infants and children 6 weeks to 5 years of age may also 
be applicable to this age group but were not seen in this study possibly due to the small sample size.

Additional information in special populations
Children and adolescents with sickle cell disease, HIV infection, or an haematopoietic stem cell 
transplant have similar frequencies of adverse reactions, except that headaches, vomiting, diarrhoea, 
pyrexia, fatigue, arthralgia, and myalgia were very common.

Adults ≥ 18 years and elderly
Safety was assessed in 7 clinical studies including 91,593 adults ranging in age from 18 to 101 years. 
Prevenar 13 was administered to 48,806 adults; 2,616 (5.4%) aged 50 to 64 years, and 45,291 (92.8%) 
aged 65 years and older. One of the 7 studies included a group of adults (n=899) ranging from 18 to 
49 years who received Prevenar 13 and who were not previously vaccinated with 23-valent 
pneumococcal polysaccharide vaccine. Of the Prevenar 13 recipients 1,916 adults were previously 
vaccinated with the 23-valent pneumococcal polysaccharide vaccine at least 3 years prior to study 
vaccination, and 46,890 were 23-valent pneumococcal polysaccharide vaccine unvaccinated.

A trend to lower frequency of adverse reactions was associated with greater age; adults > 65 years of 
age (regardless of prior pneumococcal vaccination status) reported fewer adverse reactions than 
younger adults, with adverse reactions generally most common in the youngest adults, 18 to 29 years 
of age.

Overall, the frequency categories were similar for all age groups, with the exception of vomiting 
which was very common ( 1/10) in adults aged 18 to 49 years and common ( 1/100 to < 1/10) in all 
other age groups, and pyrexia was very common in adults aged 18 to 29 years and common in all other 
age groups. Severe vaccination-site pain/tenderness and severe limitation of arm movement was very 
common in adults 18 to 39 years and common in all other age groups.

Adverse reactions from clinical studies
Local reactions and systemic events were solicited daily after each vaccination for 14 days in 6 studies
and 7 days in the remaining study. The following frequencies are based on adverse reactions assessed 
in Prevenar 13 clinical studies in adults:



35

Metabolism and nutrition disorders:
Very common: Decreased appetite

Nervous system disorders:
Very common: Headaches

Gastrointestinal disorders: 
Very common: Diarrhoea; vomiting (in adults aged 18 to 49 years)

Common: Vomiting (in adults aged 50 years and over)

Uncommon: Nausea

Immune system disorders:
Uncommon: Hypersensitivity reaction including face oedema, dyspnoea, bronchospasm

Skin and subcutaneous tissue disorders:
Very common: Rash

General disorders and administration site conditions:
Very common: Chills; fatigue; vaccination-site erythema; vaccination-site 

induration/swelling; vaccination-site pain/tenderness (severe vaccination-site 
pain/tenderness very common in adults aged 18 to 39 years); limitation of arm 
movement (severe limitation of arm movements very common in adults aged 
18 to 39 years)

Common: Pyrexia (very common in adults aged 18 to 29 years)

Uncommon: Lymphadenopathy localized to the region of the vaccination-site

Musculoskeletal and connective tissue disorders:
Very common: Arthralgia; myalgia

Overall, no significant differences in frequencies of adverse reactions were seen when Prevenar 13 
was given to adults previously vaccinated with the pneumococcal polysaccharide vaccine.

Additional information in special populations
Adults with HIV infection have similar frequencies of adverse reactions, except that pyrexia and 
vomiting were very common and nausea common. 

Adults with an haematopoietic stem cell transplant have similar frequencies of adverse reactions, 
except that pyrexia and vomiting were very common.

Higher frequency in some solicited systemic reactions was observed when Prevenar 13 was 
administered concomitantly with trivalent inactivated influenza vaccine (TIV) compared to TIV given 
alone (headache, chills, rash, decreased appetite, arthralgia, and myalgia) or Prevenar 13 given alone 
(headache, fatigue, chills, decreased appetite, and arthralgia). 

Adverse reactions from Prevenar 13 postmarketing experience
The following are considered adverse drug reactions for Prevenar 13; because these reactions were 
derived from spontaneous reports, the frequencies could not be determined and are thus considered as 
not known.

Blood and lymphatic system disorders:
Lymphadenopathy (localised to the region of the vaccination-site)



36

Immune system disorders:
Anaphylactic/anaphylactoid reaction including shock; angioedema

Skin and subcutaneous tissue disorders:
Erythema multiforme

General disorders and administration site conditions:
Vaccination-site urticaria; vaccination-site dermatitis; vaccination-site 
pruritus; flushing

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

Overdose with Prevenar 13 is unlikely due to its presentation as a single dose vial. However, in infants 
and children there have been reports of overdose with Prevenar 13 defined as subsequent doses 
administered closer than recommended to the previous dose. In general, adverse events reported with 
overdose are consistent with those that have been reported with doses given in the recommended 
paediatric schedules of Prevenar 13.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: vaccines, pneumococcal vaccines; ATC code: J07AL02

Prevenar 13 contains the 7 pneumococcal capsular polysaccharides that are in Prevenar (4, 6B, 9V, 
14, 18C, 19F, 23F) plus 6 additional polysaccharides (1, 3, 5, 6A, 7F, 19A) all conjugated to CRM197

carrier protein. 

Burden of disease

Infants and children aged 6 weeks to 5 years

Based on serotype surveillance in Europe performed before the introduction of Prevenar, Prevenar 13 
is estimated to cover 73-100% (depending on the country) of serotypes causing invasive 
pneumococcal disease (IPD) in children less than 5 years of age. In this age group, serotypes 1, 3, 5, 
6A, 7F, and 19A account for 15.6% to 59.7% of invasive disease, depending on the country, the time 
period studied, and the use of Prevenar.

Acute otitis media (AOM) is a common childhood disease with different aetiologies. Bacteria can be 
responsible for 60-70% of clinical episodes of AOM. S. pneumoniae is one of the most common 
causes of bacterial AOM worldwide.

Prevenar 13 is estimated to cover over 90% of serotypes causing antimicrobial-resistant IPD. 

Children and adolescents aged 6 to 17 years

In children and adolescents aged 6 to 17 years, the incidence of pneumococcal disease is low, 
however, there is an increased risk of morbidity and mortality in those with underlying comorbidities.



37

Adults ≥ 18 years and the elderly

Pneumonia is the most common clinical presentation of pneumococcal disease in adults.

The reported incidence of community-acquired pneumonia (CAP) and IPD in Europe varies by 
country, increases with age from 50 years and is highest in individuals aged ≥ 65 years. S. pneumoniae
is the most frequent cause of CAP, and is estimated to be responsible for approximately 30% of all 
CAP cases requiring hospitalisation in adults in developed countries.

Bacteraemic pneumonia (approximately 80% of IPD in adults), bacteraemia without a focus, and 
meningitis are the most common manifestations of IPD in adults. Based on surveillance data following
the introduction of Prevenar but before the introduction of Prevenar 13 in childhood vaccination 
programmes, the pneumococcal serotypes in Prevenar 13 may be responsible for at least 50 – 76% 
(depending on country) of IPD in adults.

The risk for CAP and IPD in adults also increases with chronic underlying medical conditions, 
specifically, anatomical or functional asplenia, diabetes mellitus, asthma, chronic cardiovascular, 
pulmonary, kidney or liver disease, and it is highest in those who are immune-suppressed such as 
those with malignant haematological diseases or HIV infection. 

Prevenar 13 immunogenicity clinical studies in infants, children and adolescents

The protective efficacy of Prevenar 13 against IPD has not been studied. As recommended by the 
World Health Organization (WHO) the assessment of potential efficacy against IPD in infants and 
young children has been based on a comparison of immune responses to the seven common serotypes 
shared between Prevenar 13 and Prevenar, for which protective efficacy has been proven (for 
Prevenar (7-valent) efficacy in infants and children, see below). Immune responses to the additional 
6 serotypes were also measured.

Immune responses following a three-dose primary infant series

Clinical studies have been conducted in a number of European countries and the US using a range of 
vaccination schedules, including two randomised non-inferiority studies (Germany using a 2, 3, 
4 month primary series [006] and US using a 2, 4, 6 month primary series [004]). In these two studies 
pneumococcal immune responses were compared using a set of non-inferiority criteria including the 
percentage of subjects with serum anti-polysaccharide serotype-specific IgG ≥ 0.35 μg/ml one month 
after the primary series and the comparison of IgG geometric mean concentrations (ELISA GMCs); in 
addition, functional antibody titres (OPA) between subjects receiving Prevenar 13 and Prevenar were 
compared. For the six additional serotypes, these values were compared with the lowest response 
among all of the seven common serotypes in the Prevenar recipients.

The non-inferiority immune response comparisons for study 006, based on the proportion of infants 
achieving anti-polysaccharide IgG concentrations ≥ 0.35 μg/ml, are shown in Table 1. Results for 
study 004 were similar. Prevenar 13 non-inferiority (lower bound of the 95% CI for the difference in 
percentage of responders at 0.35 µg/ml between groups was >-10%) was demonstrated for all 
7 common serotypes, except for serotype 6B in study 006 and serotypes 6B and 9V in study 004, 
which missed by a small margin. All seven common serotypes met pre-defined non-inferiority criteria 
for IgG ELISA GMCs. Prevenar 13 elicited comparable, although slightly lower, antibody levels than 
Prevenar for the 7 common serotypes. The clinical relevance of these differences is not known.

Non-inferiority was met for the 6 additional serotypes based on the proportion of infants achieving 
antibody concentrations ≥ 0.35 μg/ml and comparison of IgG ELISA GMCs in study 006 and was met 
for 5 out of the 6 serotypes, with the exception of serotype 3 for study 004. For serotype 3, the 
percentages of Prevenar 13 recipients with serum IgG ≥ 0.35 μg/ml were 98.2% (study 006) and 
63.5% (study 004).



38

Table 1: Comparison of the proportion of subjects achieving a pneumococcal anti-polysaccharide IgG 
antibody concentration ≥ 0.35 μg/ml after dose 3 of the infant series – study 006

Serotypes

Prevenar 13 
%

(N=282-285)

7-valent Prevenar
%

(N=277-279)
Difference
(95 % CI)

7-valent Prevenar serotypes
4 98.2 98.2 0.0 (-2.5, 2.6)

6B 77.5 87.1 -9.6 (-16.0, -3.3)
9V 98.6 96.4 2.2 (-0.4, 5.2)
14 98.9 97.5 1.5 (-0.9, 4.1)

18C 97.2 98.6 -1.4 (-4.2, 1.2)
19F 95.8 96.0 -0.3 (-3.8, 3.3)
23F 88.7 89.5 -0.8 (-6.0, 4.5)

Additional serotypes in Prevenar 13
1 96.1 87.1* 9.1 (4.5, 13.9)
3 98.2 87.1 11.2 (7.0, 15.8)
5 93.0 87.1 5.9 (0.8, 11.1)

6A 91.9 87.1 4.8 (-0.3, 10.1)
7F 98.6 87.1 11.5 (7.4, 16.1)

19A 99.3 87.1 12.2 (8.3, 16.8)
* The serotype in Prevenar with the lowest percent response rate was 6B in study 006 (87.1 %).

Prevenar 13 elicited functional antibodies to all 13 vaccine serotypes in studies 004 and 006. For the 
7 common serotypes there were no differences between groups in the proportion of subjects with OPA 
titres ≥ 1:8. For each of the seven common serotypes, > 96% and > 90% of the Prevenar 13 recipients 
reached an OPA titre ≥ 1:8 one month after the primary series in studies 006 and 004, respectively.

For each of the 6 additional serotypes, Prevenar 13 elicited OPA titres ≥ 1:8 in 91.4% to 100% of 
vaccinees one month after the primary series in studies 004/006. The functional antibody (OPA) 
geometric mean titres for serotypes 1, 3 and 5 were lower than the titres for each of the other 
additional serotypes; the clinical relevance of this observation for protective efficacy is unknown. 

Immune responses following a two-dose primary infant series

The immunogenicity after two doses in infants has been documented in four studies. The proportion 
of infants achieving a pneumococcal anti-capsular polysaccharide IgG concentration ≥ 0.35 g/ml one 
month after the second dose ranged from 79.6% to 98.5% across 11 of the 13 vaccine serotypes. 
Smaller proportions of infants achieved this antibody concentration threshold for serotype 6B (27.9% 
to 57.3%) and 23F (55.8% to 68.1%) for all studies using a 2, 4 month regimen, compared to 58.4% 
for serotype 6B and 68.6% for 23F for a study using a 3, 5 month regimen. After the booster dose, all 
vaccine serotypes including 6B and 23F had immune responses consistent with adequate priming with 
a two-dose primary series. In a UK study, the functional antibody (OPA) responses were comparable 
for all serotypes including 6B and 23F in the Prevenar and Prevenar 13 arms after the primary series 
at two and four months of age and after the booster dose at 12 months of age. For Prevenar 13 
recipients, the proportion of responders with an OPA titre  1:8 was at least 87% following the infant 
series, and at least 93% following the booster dose. The OPA geometric mean titres for serotypes 1, 3 
and 5 were lower than the titres for each of the other additional serotypes; the clinical relevance of 
this observation is unknown.

Booster responses following two-dose and three-dose primary infant series

Following the booster dose, antibody concentrations increased from the pre-booster level for all 
13 serotypes. Post-booster antibody concentrations were higher for 12 serotypes than those achieved 
after the infant primary series. These observations are consistent with adequate priming (the induction 
of immunologic memory). The immune response for serotype 3 following the booster dose was not 



39

increased above the levels seen after the infant vaccination series; the clinical relevance of this 
observation regarding the induction of serotype 3 immune memory is unknown.

Antibody responses to booster doses following two-dose or three-dose infant primary series were 
comparable for all 13 vaccine serotypes.

For children aged from 7 months to 5 years, age appropriate catch-up immunisation schedules (as 
described in section 4.2) result in levels of anti-capsular polysaccharide IgG antibody responses to 
each of the 13 serotypes that are at least comparable to those of a three-dose primary series in infants.

Antibody persistence and immunological memory were evaluated in a study in healthy children who 
received a single dose of Prevenar 13 at least 2 years after they had been previously immunised with 
either 4 doses of Prevenar, a 3-dose infant series of Prevenar followed by Prevenar 13 at 12 months of 
age, or 4 doses of Prevenar 13. 

The single dose of Prevenar 13, in children approximately 3.4 years of age regardless of previous 
vaccination history with Prevenar or Prevenar 13, induced a robust antibody response for both the 
7 common serotypes and the 6 additional serotypes in Prevenar 13.

Since the introduction of 7-valent Prevenar in 2000, pneumococcal disease surveillance data have not 
shown that the immunity elicited by Prevenar in infancy has waned over time. 

Preterm Infants

Safety and immunogenicity of Prevenar 13 given at 2, 3, 4 and 12 months was assessed in 
approximately 100 prematurely born infants (mean Estimated Gestational Age [EGA], 31 weeks; 
range, 26 to 36 weeks) and compared with approximately 100 infants born at term (mean EGA, 
39 weeks; range, 37 to 42 weeks).

Immune responses in preterm and term infants were compared using the proportion of subjects 
achieving a pneumococcal polysaccharide IgG binding antibody concentration ≥0.35 μg/ml 1 month 
after the infant series, the approach used for immunogenicity comparisons of Prevenar 13 to Prevenar 
based on WHO guidelines.

More than 85% achieved a pneumococcal polysaccharide IgG binding antibody concentration 
≥0.35 µg/ml 1 month after the infant series, except for serotypes 5 (71.7%), 6A (82.7%), and 6B 
(72.7%) in the preterm group. For these 3 serotypes, the proportion of responders among preterm 
infants was significantly lower than among term infants. Approximately one month after the toddler 
dose, the proportion of subjects in each group achieving this same antibody concentration threshold 
was >97%, except for serotype 3 (71% in preterm infants and 79% in term infants). It is unknown 
whether immunological memory to all serotypes is induced in pre-term infants. In general, 
serotype-specific IgG GMCs were lower for preterm infants than term infants.

After the infant series, OPA GMTs were similar in preterm infants compared to term infants except 
for serotype 5, which was lower in preterm infants. OPA GMTs after the toddler dose relative to those 
after the infant series were similar or lower for 4 serotypes (4, 14, 18C, and 19F) and were statistically 
significantly higher for 6 of 13 serotypes (1, 3, 5, 7F, 9V, and 19A) in preterm infants compared to 10 
of 13 serotypes (1, 3, 4, 5, 6A, 7F, 9V, 18C, 19A, and 23F) in term infants.

Children (12-59 months) completely immunised with Prevenar (7-valent)

Following administration of a single dose of Prevenar 13 to children (12-59 months) who are 
considered completely immunised with Prevenar (7-valent) (either 2 or 3 dose primary series plus 
booster), the proportion achieving serum IgG levels ≥0.35 µg/ml and OPA titres ≥1:8 was at least 
90%. However, 3 (serotypes 1, 5 and 6A) of the 6 additional serotypes showed lower IgG GMC and 
OPA GMT when compared with children who had received at least one previous vaccination with 



40

Prevenar 13. The clinical relevance of the lower GMCs and GMTs is currently unknown.

Unvaccinated Children (12-23 months)

Studies in unvaccinated children (12 -23 months) with Prevenar (7-valent) demonstrated that 2 doses 
were required to achieve serum IgG concentrations for 6B and 23F similar to those induced by a 
3-dose infant series.

Children and Adolescents 5 to 17 years of age

In an open-label study in 592 healthy children and adolescents including those with asthma (17.4%) 
who may be predisposed to pneumococcal infection, Prevenar 13 elicited immune responses to all 
13 serotypes. A single dose of Prevenar 13 was given to children 5 to 10 years of age previously 
vaccinated with at least 1 dose of Prevenar, and children and adolescents 10 to 17 years of age who 
had never received a pneumococcal vaccine.

In both the children 5 to 10 years of age and children and adolescents aged 10 to 17 years, the immune
response to Prevenar 13 was non inferior to Prevenar for the 7 common serotypes and to Prevenar 13 
for the 6 additional serotypes compared to the immune response after the fourth dose in infants 
vaccinated at 2, 4, 6 and 12-15 months of age as measured by serum IgG.

In children and adolescents aged 10 to 17 years of age OPA GMTs 1 month after vaccination were 
noninferior to OPA GMTs in the 5 to 10 year old age group for 12 of the 13 serotypes (except 
serotype 3). 

Immune responses after subcutaneous administration

Subcutaneous administration of Prevenar 13 was evaluated in a non-comparative study in 185 healthy 
Japanese infants and children who received 4 doses at 2, 4, 6 and 12-15 months of age. The study 
demonstrated that safety and immunogenicity were generally comparable with observations made in 
studies of intramuscular administration.

Prevenar 13 Effectiveness

Invasive Pneumococcal Disease
Data published by Public Health England showed that, four years after the introduction of Prevenar as 
a two dose primary infant series with booster dose in the second year of life and with a 94% vaccine 
uptake, there was a 98% (95% CI 95; 99) reduction in disease caused by the 7 vaccine serotypes in 
England and Wales. Subsequently, four years following the switch to Prevenar 13, the additional
reduction in incidence of IPD due to the 7 serotypes in Prevenar ranged from 76% in children less 
than 2 years of age to 91% in children 5-14 years of age. The serotype specific reductions for each of 
the 5 additional serotypes in Prevenar 13 (no cases of serotype 5 IPD were observed) by age group are 
shown in Table 2 and ranged from 68% (serotype 3) to 100% (serotype 6A) for children less than 
5 years of age. Significant incidence reductions were also observed in older age groups who had not 
been vaccinated with Prevenar 13 (indirect effect).



41

Otitis media (OM)
In a published study performed in Israel, using a 2-dose primary series plus booster dose in the second 
year of life, the impact of Prevenar 13 on OM was documented in a population-based 
active-surveillance system with tympanocentesis culturing of middle ear fluid in Israeli children less 
than 2 years of age with OM. 

Following the introduction of Prevenar and subsequently Prevenar 13 there was a decline in incidence 
from 2.1 to 0.1 cases per 1000 children (95%) for the Prevenar serotypes plus serotype 6A and a 
decline in incidence from 0.9 to 0.1 cases per 1000 children (89%) for the additional serotypes 1, 3, 5, 
7F, and 19A in Prevenar 13. The annual overall pneumococcal incidence of OM declined from 9.6 to 
2.1 cases per 1000 children (78%) between July 2004 (prior to the introduction of Prevenar) and June 
2013 (post Prevenar 13 introduction).

Table 2: Serotype specific number of cases and incidence reductions of IPD in 2013/14 compared to 
2008/09-2009/10 (2008/10) by age in England and Wales

<5 years of age 5 to 64 years of age ≥65 years of age

2008-
10§

2013/
14§

% Incidence 
reduction 
(95% CI*)

2008-
10§

2013/
14§

% 
Incidence 
reduction 
(95% CI*)

2008-
10§

2013/
14§

% Incidence 
reduction 
(95% CI*)

Additional serotypes covered by Prevenar 13

1 59 (54) 5 (5) 91%

(98%; 
68%)**

458 
(382)

77 
(71)

83%

(88%; 
74%)**

102 
(89)

13 
(13)

87%

(94%; 
72%)**

3 26 (24) 8 (8) 68%

(89%; 6%)

178 
(148)

73 
(68)

59%

(72%; 
38%)**

256 
(224)

143 
(146)

44%

(57%; 
27%)**

6A 10 (9) 0 (0) 100%

(100%; 
62%)**

53 (44) 5 (5) 90%

(97%; 
56%)**

94 (82) 5 (5) 95%

(99%; 
81%)**

7F 90 (82) 8 (8) 91%

(97%; 
74%)**

430 
(361)

160
(148)

63%

(71%; 
50%)**

173 
(152)

75 
(77)

56%

(70%; 
37%)**

19A 85 (77) 7 (7) 91%

(97%; 
75%)**

225 
(191)

104 
(97)

54%

(65%; 
32%)**

279 
(246)

97 
(99)

65%

(75%; 
53%)**

§ Corrected for proportion of samples serotyped, missing age, denominator compared with 2009/10, and 
for the trend in total invasive pneumococcal disease up to 2009/10 (after which no trend correction was 
applied).

* 95% CI inflated from a Poisson interval based on over-dispersion of 2.1 seen from modelling of 
2000-06 pre-Prevenar all IPD data.

** p<0.005 to cover 6A where p=0.002



42

Pneumonia
In a multicenter observational study in France comparing the periods before and after the switch from 
Prevenar to Prevenar 13, there was 16% (2060 to 1725 cases) reduction in all community acquired 
pneumonia (CAP) cases in emergency departments in children 1 month to 15 years of age. Reductions 
were 53% (167 to 79 cases) (p<0.001) for CAP cases with pleural effusion and 63% (64 to 24 cases) 
(p<0.001) for microbiologically confirmed pneumococcal CAP cases. In the second year after the 
introduction of Prevenar 13 the total number of CAP cases due to the 6 additional vaccine serotypes in 
Prevenar 13 was reduced from 27 to 7 isolates (74%).

The decrease in all cause pneumonia cases was most pronounced in the younger vaccinated age 
groups with a decrease of 31.8% (757 to 516 cases) and 16.6% (833 to 695 cases) in the age groups 
<2 years and 2 to 5 years, respectively. The incidence in older, predominantly non-vaccinated children 
(>5 years) did not change over the duration of the study.

In an ongoing surveillance system (2004 to 2013) to document the impact of Prevenar and 
subsequently Prevenar 13 on CAP in children less than 5 years in Southern Israel using a 2 dose 
primary series with a booster dose in the second year of life, there was a reduction of 68% 
(95% CI 73; 61) in outpatient visits and 32% (95% CI 39; 22) in hospitalizations for alveolar CAP 
following the introduction of Prevenar 13 when compared to the period before the introduction of 
Prevenar.

Effect on nasopharyngeal carriage 

In a surveillance study in France in children presenting with acute otitis media, changes in 
nasopharyngeal (NP) carriage of pneumococcal serotypes were evaluated following the introduction 
of Prevenar (7-valent) and subsequently Prevenar 13. Prevenar 13 significantly reduced NP carriage of 
the 6 additional serotypes (and serotype 6C) combined and individual serotypes 6C, 7F, 19A when 
compared with Prevenar. A reduction in carriage was also seen for serotype 3 (2.5% vs 1.1%; p=0.1). 
There was no carriage of serotypes 1 and 5 observed.

The effect of pneumococcal conjugate vaccination on nasopharyngeal carriage was studied in a 
randomised double-blind study in which infants received either Prevenar 13 or Prevenar (7-valent) at 
2, 4, 6 and 12 months of age in Israel. Prevenar 13 significantly reduced newly identified NP 
acquisition of the 6 additional serotypes (and serotype 6C) combined and of individual serotypes 1, 
6A, 6C, 7F, 19A when compared with Prevenar. There was no reduction seen in serotype 3 and for 
serotype 5 the colonization was too infrequent to assess impact. For 6 of the remaining 7 common 
serotypes, similar rates of NP acquisition were observed in both vaccine groups; for serotype 19F a 
significant reduction was observed.

In this study, reductions of S. pneumoniae serotypes 19A, 19F, and 6A not susceptible to a number of 
antibiotics were documented. The reductions ranged between 34% and 62% depending on serotype 
and antibiotic.

Prevenar (7-valent vaccine) protective efficacy in infants and children

The efficacy of 7-valent Prevenar was evaluated in two major studies – the Northern California Kaiser 
Permanente (NCKP) study and the Finnish Otitis Media (FinOM) study. Both studies were 
randomised, double-blind, active-control studies in which infants were randomised to receive either 
Prevenar or control vaccine (NCKP, meningococcal serogroup C CRM-conjugate [MnCC] vaccine; 
FinOM, hepatitis B vaccine) in a four-dose series at 2, 4, 6, and 12-15 months of age. The efficacy 
results from these studies (for invasive pneumococcal disease, pneumonia, and acute otitis media) are 
presented below (Table 3).



43

Table 3: Summary of efficacy of 7-valent Prevenar1

Test N VE2 95% CI

NCKP: Vaccine-serotype IPD3 30,258 97% 85, 100

NCKP: Clinical pneumonia with abnormal chest X-ray 23,746 35% 4, 56

NCKP: Acute Otitis Media (AOM)4 23,746

Total episodes 7% 4, 10

Recurrent AOM (3 episodes in 6 months, or 4 episodes in 1 year) 9% 3, 15
Recurrent AOM (5 episodes in 6 months, or 6 episodes in 1 year) 23% 7, 36
Tympanostomy tube placement 20% 2, 35

FinOM: AOM 1,662

Total episodes 6% -4, 16

All pneumococcal AOM 34% 21, 45
Vaccine-serotype AOM 57% 44, 67

1Per protocol
2Vaccine efficacy
3October 1995 to April 20, 1999
4October 1995 to April 30, 1998

Prevenar (7-valent) effectiveness

The effectiveness (both direct and indirect effect) of 7-valent Prevenar against pneumococcal disease 
has been evaluated in both three-dose and two-dose primary infant series immunisation programmes, 
each with booster doses (Table 4). Following the widespread use of Prevenar, the incidence of IPD 
has been consistently and substantially reduced.

Using the screening method, serotype-specific effectiveness estimates for 2 doses under the age of 
1 year in the UK were 66 % (-29, 91 %) and 100 % (25, 100 %) for serotype 6B and 23F, respectively.

Table 4: Summary of effectiveness of 7-valent Prevenar for invasive pneumococcal disease
Country

(year of introduction)
Recommended schedule Disease reduction, % 95% CI

UK (England & Wales)1 (2006) 2, 4, + 13 months Vaccine serotypes:
Two doses under age 1: 85%

49, 95%

USA (2000)

Children < 52

Persons ≥ 653

2, 4, 6, + 12-15 months

Vaccine serotypes: 98%
All serotypes: 77%

Vaccine serotypes: 76%
All serotypes: 38%

97, 99%
73, 79%

NA
NA

Canada (Quebec)4

(2004)
2, 4, + 12 months All serotypes: 73%

Vaccine serotypes:
2-dose infant series: 99%
Completed schedule:100%

NA

92, 100%
82, 100%

1Children < 2 years of age. Calculated vaccine effectiveness as of June 2008 (Broome method).
22005 data.
32004 data.
4Children < 5 years of age. January 2005 to December 2007. Complete effectiveness for routine 2+1 schedule not 
yet available.

Acute Otitis Media
Effectiveness of Prevenar in a 3+1 schedule has also been observed against acute otitis media and 
pneumonia since its introduction in a national immunisation programme. In a retrospective evaluation 
of a large US insurance database, AOM visits were reduced by 42.7 % (95 % CI, 42.4-43.1 %), and 
prescriptions for AOM by 41.9 % in children younger than 2 years of age, compared with a 
pre-licensure baseline (2004 vs. 1997-99). In a similar analysis, hospitalisations and ambulatory visits 
for all-cause pneumonia were reduced by 52.4 % and 41.1 %, respectively. For those events 



44

specifically identified as pneumococcal pneumonia, the observed reductions in hospitalisations and 
ambulatory visits were 57.6 % and 46.9 %, respectively, in children younger than 2 years of age, 
compared with a pre-licensure baseline (2004 vs. 1997-99). While direct cause-and-effect cannot be 
inferred from observational analyses of this type, these findings suggest that Prevenar plays an 
important role in reducing the burden of mucosal disease (AOM and pneumonia) in the target 
population.

Efficacy study in adults 65 years and older

Efficacy against vaccine-type (VT) pneumococcal CAP and IPD was assessed in a large-scale 
randomised double-blind, placebo-controlled study (Community-Acquired Pneumonia Immunization 
Trial in Adults–CAPiTA) in the Netherlands. 84,496 subjects, 65 years and older received a single 
vaccination of either Prevenar 13 or placebo in a 1:1 randomisation.

The CAPiTA study enrolled volunteers ≥ 65 years of age whose demographic and health 
characteristics may differ from those seeking vaccination.

A first episode of hospitalised, chest X-ray confirmed pneumonia was identified in about 2% of this 
population (n=1,814 subjects) of which 329 cases were confirmed pneumococcal CAP and 182 cases 
were VT pneumococcal CAP in the per protocol and modified intent to treat (mITT) populations.

Efficacy was demonstrated for the primary and secondary endpoints in the per protocol population
(Table 5).

Table 5: Vaccine efficacy (VE) for the primary and secondary endpoints of the CAPiTA study (per 
protocol population)

Efficacy endpoint

Cases

VE (%)
(95.2% CI)

p-value
Total

Prevenar 13
group

Placebo
group

Primary endpoint

First episode of confirmed VT 
pneumococcal CAP

139 49 90
45.56

(21.82, 62.49)
0.0006

Secondary endpoints

First episode of confirmed NB/NI1

vaccine type pneumococcal CAP
93 33 60

45.00
(14.21, 65.31)

0.0067

First episode of VT-IPD2 35 7 28
75.00

(41.06, 90.87)
0.0005

1NB/NI – non-bacteraemic/non-invasive
2VT-IPD – vaccine-type invasive pneumococcal disease

The duration of protective efficacy against a first episode of VT pneumococcal CAP, 
NB/NI VT pneumococcal CAP, and VT-IPD extended throughout the 4-year study.

The study was not designed to demonstrate efficacy in subgroups, and the number of subjects 
≥ 85 years of age was not sufficient to demonstrate efficacy in this age group.

A post-hoc analysis was used to estimate the following public health outcomes against clinical CAP 
(as defined in the CAPiTA study, and based on clinical findings regardless of radiologic infiltrate or 
etiologic confirmation): vaccine efficacy (VE), incidence rate reduction (IRR), and number needed to 
vaccinate (NNV) (Table 6).

IRR, also referred to as vaccine preventable disease incidence, is the number of cases of vaccine 
preventable disease per 100,000 person-years of observation.



45

In Table 6, NNV is a measure that quantifies the number of people that need to be vaccinated in order 
to prevent one clinical CAP case.

Table 6: Vaccine efficacy (VE) against clinical CAP*

Episodes Vaccine efficacy1 % 
(95% CI)

(1-sided p-value)

Incidence per 
100,000 person-

years of observation 
(PYO)

Incidence 
rate 

reduction2

(95% CI)

Number 
needed to 
vaccinate3

Prevenar
13

Placebo Prevenar 
13

Placebo

All 
episodes 
analysis

1375 1495 8.1 

(-0.6, 16.1) 

(0.034)

819.1 891.2 72.2 
(-5.3, 149.6)

277

First 
episode
analysis

1126 1214 7.3

(-0.4, 14.4)

(0.031)

670.7 723.7 53.0
(-2.7, 108.7)

378

* Patients with at least 2 of the following: Cough; purulent sputum, temperature >38°C or <36.1°C; pneumonia 
(auscultatory findings); leukocytosis; C-reactive protein value >3 times the upper limit of normal; hypoxemia with 
a partial oxygen pressure <60 mm Hg while breathing room air.
1 A Poisson regression model with random effects was used to calculate VE.
2 Per 100,000 person-years of observation. IRR is calculated as the incidence in the placebo group minus the 
incidence in the vaccine group, and was mathematically equivalent to VE × the incidence in the placebo group.
3 Based on a 5-year duration of protection. NNV is not a rate but instead indicates the number of cases prevented 
for a given number of persons vaccinated. NNV also incorporates the length of the trial or duration of protection
and is calculated as 1 divided by the product of the IRR and duration of protection (or length of trial) (=1/(IRR ×
duration).

Immunogenicity studies in adults ≥18 years and the elderly

In adults, an antibody threshold of serotype-specific pneumococcal polysaccharide IgG binding 
antibody concentration associated with protection has not been defined. For all pivotal clinical trials, a 
serotype-specific opsonophagocytosis assay (OPA) was used as a surrogate to assess potential
efficacy against invasive pneumococcal disease and pneumonia. OPA geometric mean titers (GMTs) 
measured 1-month after each vaccination were calculated. OPA titres are expressed as the reciprocal 
of the highest serum dilution that reduces survival of the pneumococci by at least 50 %.

Pivotal trials for Prevenar 13 were designed to show that functional OPA antibody responses for the 
13 serotypes are non-inferior, and for some serotypes superior, to the 12 serotypes in common with 

the licensed 23-valent pneumococcal polysaccharide vaccine [1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 
19F, 23F] one month after vaccine administration. The response to serotype 6A, which is unique to 
Prevenar 13, was assessed by demonstration of a 4-fold increase in the specific OPA titer above pre-
immunised levels.

Five clinical studies were conducted in Europe and the USA evaluating the immunogenicity of 
Prevenar 13 in different age groups ranging from 18-95 years of age. Clinical studies with Prevenar 13 
currently provide immunogenicity data in adults aged 18 years and older, including adults aged 65 and 
older previously vaccinated with one or more doses of 23-valent pneumococcal polysaccharide 
vaccine, 5 years prior to enrollment. Each study included healthy adults and immuno-competent adults 
with stable underlying conditions known to predispose individuals to pneumococcal infection (i.e., 
chronic cardiovascular disease, chronic pulmonary disease including asthma, renal disorders and 
diabetes mellitus, chronic liver disease including alcoholic liver disease), and adults with risk factors 
such as smoking and alcohol abuse.

Immunogenicity and safety of Prevenar 13 has been demonstrated in adults aged 18 years and older 
including those previously vaccinated with a pneumococcal polysaccharide vaccine.



46

Adults not previously vaccinated with 23-valent pneumococcal polysaccharide vaccine
In a head-to-head, comparative trial conducted in adults aged 60-64 years, subjects received a single 
dose of either Prevenar 13 or 23-valent pneumococcal polysaccharide vaccine. In the same study 
another group of adults aged 50-59 years and another group of adults aged 18-49 years received a 
single dose of Prevenar 13.

Table 7 compares the OPA GMTs, 1-month post-dose, in 60-64 year olds given either a single dose of 
Prevenar 13 or 23-valent pneumococcal polysaccharide vaccine, and in 50-59 year olds given a single 
dose of Prevenar 13.

Table 7: OPA GMTs in adults aged 60-64 years given Prevenar 13 or 23-valent pneumococcal 
polysaccharide vaccine (PPSV23) and in adults aged 50-59 years given Prevenar 13a,b,c

Prevenar 13 Prevenar 13 PPSV23 Prevenar 13
50-59 Relative to

60-64 Years

Prevenar 13 Relative
to PPSV23,
60-64 Years

50-59 Years 
N=350-384

60-64 Years 
N=359-404

60-64 Years 
N=367-402

Serotype GMT GMT GMT GMR (95% CI) GMR (95% CI)
1 200 146 104 1.4 (1.08, 1.73) 1.4 (1.10, 1.78)
3 91 93 85 1.0 (0.81, 1.19) 1.1 (0.90, 1.32)
4 2833 2062 1295 1.4 (1.07, 1.77) 1.6 (1.19, 2.13)
5 269 199 162 1.4 (1.01, 1.80) 1.2 (0.93, 1.62)

6A† 4328 2593 213 1.7 (1.30, 2.15) 12.1 (8.63, 17.08)
6B 3212 1984 788 1.6 (1.24, 2.12) 2.5 (1.82, 3.48)
7F 1520 1120 405 1.4 (1.03, 1.79) 2.8 (1.98, 3.87)
9V 1726 1164 407 1.5 (1.11, 1.98) 2.9 (2.00, 4.08)
14 957 612 692 1.6 (1.16, 2.12) 0.9 (0.64, 1.21)

18C 1939 1726 925 1.1 (0.86, 1.47) 1.9 (1.39, 2.51)
19A 956 682 352 1.4 (1.16, 1.69) 1.9 (1.56, 2.41)
19F 599 517 539 1.2 (0.87, 1.54) 1.0 (0.72, 1.28)
23F 494 375 72 1.3 (0.94, 1.84) 5.2 (3.67, 7.33)

a Non-inferiority was defined as the lower limit of the 2-sided 95% CI for GMR was greater than 0.5. 
b Statistically significantly greater response was defined as the lower bound of the 2-sided 95% CI for the GMR 
was greater than 1. 
c For serotype 6A†, which is unique to Prevenar 13, a statistically significantly greater response was defined as 
the lower bound of the 2-sided 95% CI for the GMR being greater than 2.

In adults aged 60-64 years, OPA GMTs to Prevenar 13 were non-inferior to the OPA GMTs elicited to 
the 23-valent pneumococcal polysaccharide vaccine for the twelve serotypes common to both 
vaccines. For 9 serotypes, the OPA titers were shown to be statistically significantly greater in 
Prevenar 13 recipients. 

In adults aged 50-59 years, OPA GMTs to all 13 serotypes in Prevenar 13 were non-inferior to the 
Prevenar 13 responses in adults aged 60-64 years. For 9 serotypes, immune responses were related to 
age, with adults in the 50-59 years group showing statistically significantly greater responses than 
adults aged 60-64 years.

In all adults ≥ 50 years who received a single dose of Prevenar 13, the OPA titers to serotype 6A were 
significantly greater than in adults ≥ 60 years who received a single dose of 23-valent pneumococcal 
polysaccharide vaccine.

One year after vaccination with Prevenar 13 OPA titers had declined compared to one month after 
vaccination, however, OPA titers for all serotypes remained higher than levels at baseline:



47

OPA GMT levels at baseline OPA GMT levels one year after 
Prevenar 13

Adults 50-59 years not previously 
vaccinated with 23-valent 
pneumococcal polysaccharide vaccine

5 to 45 20 to 1234

Adults 60-64 years not previously 
vaccinated with 23-valent 
pneumococcal polysaccharide vaccine

5 to 37 19 to 733

Table 8 shows OPA GMTs 1-month after a single dose of Prevenar 13 in 18-49 year olds compared to 
60-64 year olds.

Table 8: OPA GMTs in adults aged 18-49 years and 60-64 years given Prevenar 13a,b

18-49 Years
N=836-866

60-64 Years
N=359-404

18-49 Years 
Relative to 

60-64 Years 
Serotype GMTb GMTb GMR (95% CIc)

1 353 146 2.4 (2.03, 2.87)
3 91 93 1.0 (0.84, 1.13)
4 4747 2062 2.3 (1.92, 2.76)
5 386 199 1.9 (1.55, 2.42)

6A 5746 2593 2.2 (1.84, 2.67)
6B 9813 1984 4.9 (4.13, 5.93)
7F 3249 1120 2.9 (2.41, 3.49)
9V 3339 1164 2.9 (2.34, 3.52)
14 2983 612 4.9 (4.01, 5.93)

18C 3989 1726 2.3 (1.91, 2.79)
19A 1580 682 2.3 (2.02, 2.66)
19F 1533 517 3.0 (2.44, 3.60)
23F 1570 375 4.2 (3.31, 5.31)

a Non-inferiority was defined as the lower limit of the 2-sided 95% CI for GMR was greater than 0.5. 
b Statistically significantly greater response was defined as the lower bound of the 2-sided 95% CI for the GMR 
was greater than 1.

c c Confidence intervals (CIs) for the ratio are back transformations of a confidence interval based on the Student t 
distribution for the mean difference of the logarithms of the measures.

In adults aged 18-49 years, OPA GMTs to all 13 serotypes in Prevenar 13 were non-inferior to the 
Prevenar 13 responses in adults aged 60-64 years. 

One year after vaccination with Prevenar 13 OPA titers had declined compared to one month after 
vaccination, however OPA titers for all serotypes remained higher than levels at baseline.

OPA GMT levels at baseline OPA GMT levels one year after 
Prevenar 13

Adults 18-49 years not previously 
vaccinated with 23-valent
pneumococcal polysaccharide vaccine

5 to 186 23 to 2948

Adults previously vaccinated with 23-valent pneumococcal polysaccharide vaccine
Immune responses to Prevenar 13 and 23-valent pneumococcal polysaccharide vaccine were 
compared in a head to head trial in adults aged ≥ 70 years, who had received a single dose of 
pneumococcal polysaccharide vaccine at least 5 years before study vaccination.

Table 9 compares the OPA GMTs, 1-month post-dose, in pneumococcal polysaccharide vaccinated 
adults aged ≥ 70 years given a single dose of either Prevenar 13 or 23-valent pneumococcal 
polysaccharide vaccine.



48

Table 9: OPA GMTs in pneumococcal polysaccharide vaccinated adults aged 
≥ 70 years given either Prevenar 13 or 23-valent pneumococcal polysaccharide vaccine (PPSV23)a,b,c

Prevenar 13
N=400-426

PPSV23
N=395-445

Prevenar OPA GMT 
Relative to PPSV23

Serotype OPA GMT OPA GMT GMR (95% CI)
1 81 55 1.5 (1.17, 1.88)
3 55 49 1.1 (0.91, 1.35)
4 545 203 2.7 (1.93, 3.74)
5 72 36 2.0 (1.55, 2.63)

6A† 903 94 9.6 (7.00, 13.26)
6B 1261 417 3.0 (2.21, 4.13)
7F 245 160 1.5 (1.07, 2.18)
9V 181 90 2.0 (1.36, 2.97)
14 280 285 1.0 (0.73, 1.33)

18C 907 481 1.9 (1.42, 2.50)
19A 354 200 1.8 (1.43, 2.20)
19F 333 214 1.6 (1.17, 2.06)
23F 158 43 3.7 (2.69, 5.09)

a Non-inferiority was defined as the lower limit of the 2-sided 95% CI for GMR was greater than 0.5. 
b Statistically significantly greater response was defined as the lower bound of the 2-sided 95% CI for the GMR 
was greater than 1. 
c For serotype 6A†, which is unique to Prevenar 13, a statistically significantly greater response was defined as the 
lower bound of the 2-sided 95% CI for the GMR greater than 2.

In adults vaccinated with pneumococcal polysaccharide vaccine at least 5 years prior to the clinical 
study, OPA GMTs to Prevenar 13 were non-inferior to the 23-valent pneumococcal polysaccharide 
vaccine responses for the 12 serotypes in common. Furthermore, in this study statistically significantly 
greater OPA GMTs were demonstrated for 10 of the 12 serotypes in common. Immune responses to 
serotype 6A were statistically significantly greater following vaccination with Prevenar 13 than after 
23-valent pneumococcal polysaccharide vaccine.

One year after vaccination with Prevenar 13 in adults aged 70 years and over who were vaccinated 
with 23-valent pneumococcal polysaccharide vaccine, at least 5 years prior to study entry, OPA titers 
had declined compared to one month after vaccination, however, OPA titers for all serotypes 
remained higher than levels at baseline:

Immune responses in Special Populations

Individuals with the conditions described below have an increased risk of pneumococcal disease. The 
clinical relevance of the antibody levels elicited by Prevenar 13 in these special populations is 
unknown.

Sickle cell disease
An open label single arm study in France, Italy, UK, US, Lebanon, Egypt and Saudi Arabia with 
2 doses of Prevenar 13 given 6 months apart was conducted in 158 children and adolescents ≥ 6 to 
< 18 years of age with sickle cell disease who were previously vaccinated with one or more doses of 
23-valent pneumococcal polysaccharide vaccine at least 6 months prior to enrollment. After the first 
vaccination, Prevenar 13 elicited antibody levels measured by both IgG GMCs and OPA GMTs that 

OPA GMT levels at baseline OPA GMT levels one year after 
Prevenar 13

Adults ≥ 70 years vaccinated with 
23-valent pneumococcal 
polysaccharide vaccine at least 5 
years prior

9 to 122 18 to 381



49

were statistically significantly higher when compared to levels prior to vaccination. After the second 
dose immune responses were comparable to those after the first dose. One year after the second dose, 
antibody levels measured by both IgG GMCs and OPA GMTs were higher than levels prior to the first 
dose of Prevenar 13, except for the IgG GMCs for serotypes 3 and 5 that were numerically similar.

Additional Prevenar (7-valent) immunogenicity data: children with sickle cell disease
The immunogenicity of Prevenar has been investigated in an open-label, multicentre study in 
49 infants with sickle cell disease. Children were vaccinated with Prevenar (3 doses one month apart 
from the age of 2 months), 46 of these children also received a 23-valent pneumococcal 
polysaccharide vaccine at the age of 15-18 months. After primary immunisation, 95.6 % of the 
subjects had antibody levels of at least 0.35 μg/ml for all seven serotypes found in Prevenar. 
A significant increase was seen in the concentrations of antibodies against the seven serotypes after 
the polysaccharide vaccination, suggesting that immunological memory was well established.

HIV infection

Children and adults not previously vaccinated with a pneumococcal vaccine
HIV-infected children and adults with CD4 ≥ 200 cells/µL (mean 717.0 cells/μL), viral load 
< 50,000 copies/ml (mean 2090.0 copies/ml), free of active AIDS-related illness and not previously 
vaccinated with a pneumococcal vaccine received 3 doses of Prevenar 13. As per general 
recommendations, a single dose of 23-valent pneumococcal polysaccharide vaccine was subsequently 
administered. Vaccines were administered at 1 month intervals. Immune responses were assessed in 
259-270 evaluable subjects approximately 1 month after each dose of vaccine. After the first dose, 
Prevenar 13 elicited antibody levels, measured by both IgG GMCs and OPA GMTs that were 
statistically significantly higher when compared to levels prior to vaccination. After the second and 
third dose of Prevenar 13, immune responses were similar or higher than those after the first dose.

Adults previously vaccinated with 23-valent pneumococcal polysaccharide vaccine
HIV-infected adults ≥ 18 years of age with CD4 ≥ 200 cells/µL (mean 609.1 cells/µL) and viral load 
< 50,000 copies/ml (mean 330.6 copies/ml), who were free of active AIDS-related illness and were 
previously vaccinated with 23-valent pneumococcal polysaccharide vaccine administered at least 
6 months prior to enrollment, received 3 doses of Prevenar 13, at enrollment, 6 months, and 
12 months after the first dose of Prevenar 13. Immune responses were assessed in 231-255 evaluable 
subjects approximately 1 month after each dose of Prevenar 13. After the first dose, Prevenar 13 
elicited antibody levels measured by both IgG GMCs and OPA GMTs that were statistically 
significantly higher when compared to levels prior to vaccination. After the second and third dose of 
Prevenar 13, immune responses were comparable or higher than those after the first dose. In the study 
162 subjects had received one prior dose of 23-valent pneumococcal polysaccharide vaccine, 
143 subjects 2 prior doses and 26 subjects more than 2 prior doses of 23-valent polysaccharide 
vaccine. Subjects who received two or more previous doses of 23-valent pneumococcal 
polysaccharide vaccine showed a similar immune response compared with subjects who received a 
single previous dose.

Haematopoietic stem cell transplant
Children and adults with an allogeneic haematopoietic stem cell transplant (HSCT) at ≥ 2 years of age 
with complete haematologic remission of underlying disease or with very good partial remission in the 
case of lymphoma and myeloma received three doses of Prevenar 13 with an interval of at least 
1 month between doses. The first dose was administered at 3 to 6 months after HSCT. A fourth 
(booster) dose of Prevenar 13 was administered 6 months after the third dose. As per general 
recommendations, a single dose of 23-valent pneumococcal polysaccharide vaccine was administered 
1 month after the fourth dose of Prevenar 13. Immune responses as measured by IgG GMCs were 
assessed in 168-211 evaluable subjects approximately 1 month after vaccination. Prevenar 13 elicited 
increased antibody levels after each dose of Prevenar 13. Immune responses after the fourth dose of 
Prevenar 13 were significantly increased for all serotypes compared with after the third dose.
Functional antibody titers (OPA titers) were not measured in this study.



50

5.2 Pharmacokinetic properties

Not applicable.

5.3 Preclinical safety data

Non-clinical data revealed no special hazard for humans based on conventional studies of safety 
pharmacology, single and repeated dose toxicity, local tolerance, and reproduction and developmental 
toxicity.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sodium chloride
Succinic acid
Polysorbate 80
Water for injections

For adjuvant, see section 2.

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products.

6.3 Shelf life

3 years

6.4 Special precautions for storage

Store in a refrigerator (2C–8C). Do not freeze.

6.5 Nature and contents of container

0.5 ml suspension for injection in a vial (Type I glass) with a latex-free grey chlorobutyl rubber 
stopper and sealed with an aluminum flip-off seal and a polypropylene flip-off cap.

Pack sizes of 1, 5, 10, 25 and 50.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

During storage, a white deposit and clear supernatant can be observed. This does not constitute a sign 
of deterioration.

The vaccine should be shaken well to obtain a homogeneous white suspension and should be 
inspected visually for any particulate matter and/or variation of physical aspect prior to 
administration. Do not use if the content appears otherwise. 

No special requirements for disposal.



51

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.

7. MARKETING AUTHORISATION HOLDER

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/09/590/007
EU/1/09/590/008
EU/1/09/590/009
EU/1/09/590/010
EU/1/09/590/011

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 09 December 2009
Date of latest renewal: 18 September 2014

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.



52

1. NAME OF THE MEDICINAL PRODUCT

Prevenar 13 suspension for injection in multidose container
pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed)

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

1 dose (0.5 ml) contains:

Pneumococcal polysaccharide serotype 11 2.2 µg
Pneumococcal polysaccharide serotype 31 2.2 µg
Pneumococcal polysaccharide serotype 41 2.2 µg
Pneumococcal polysaccharide serotype 51 2.2 µg
Pneumococcal polysaccharide serotype 6A1 2.2 µg
Pneumococcal polysaccharide serotype 6B1 4.4 µg
Pneumococcal polysaccharide serotype 7F1 2.2 µg
Pneumococcal polysaccharide serotype 9V1 2.2 µg
Pneumococcal polysaccharide serotype 141 2.2 µg
Pneumococcal polysaccharide serotype 18C1 2.2 µg
Pneumococcal polysaccharide serotype 19A1 2.2 µg
Pneumococcal polysaccharide serotype 19F1 2.2 µg
Pneumococcal polysaccharide serotype 23F1 2.2 µg

1Conjugated to CRM197 carrier protein, adsorbed on aluminium phosphate.

1 dose (0.5 ml) contains approximately 32 µg CRM197 carrier protein and 0.125 mg aluminium.

Excipients with known effect
For the full list of excipients, see section 6.1.

This is a multidose presentation. See section 6.5 for the number of doses per container.

3. PHARMACEUTICAL FORM

Suspension for injection in multidose container (4 doses).
The vaccine is a homogeneous white suspension.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Active immunisation for the prevention of invasive disease, pneumonia and acute otitis media caused 
by Streptococcus pneumoniae in infants, children and adolescents from 6 weeks to 17 years of age.

Active immunisation for the prevention of invasive disease and pneumonia caused by Streptococcus 
pneumoniae in adults ≥ 18 years of age and the elderly.

See sections 4.4 and 5.1 for information on protection against specific pneumococcal serotypes.

The use of Prevenar 13 should be determined on the basis of official recommendations taking into 
consideration the risk of invasive disease and pneumonia in different age groups, underlying 
comorbidities as well as the variability of serotype epidemiology in different geographical areas.



53

4.2 Posology and method of administration

The immunisation schedules for Prevenar 13 should be based on official recommendations.

Posology

Infants and children aged 6 weeks to 5 years

It is recommended that infants who receive a first dose of Prevenar 13 complete the vaccination 
course with Prevenar 13.

Infants aged 6 weeks-6 months

Three-dose primary series
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 usually given at 2 months of age and with an interval 
of at least 1 month between doses. The first dose may be given as early as six weeks of age. The 
fourth (booster) dose is recommended between 11 and 15 months of age.

Two-dose primary series
Alternatively, when Prevenar 13 is given as part of a routine infant immunisation programme, a series 
consisting of three doses, each of 0.5 ml, may be given. The first dose may be administered from the 
age of 2 months, with a second dose 2 months later. The third (booster) dose is recommended between 

11 and 15 months of age (see section 5.1).

Preterm infants (<37 weeks gestation)

In preterm infants, 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. The first dose may be given as early as six weeks of age.
The fourth (booster) dose is recommended between 11 and 15 months of age (see sections 4.4 and 
5.1).

Unvaccinated infants and children ≥ 7 months of age

Infants aged 7-11 months
Two doses, each of 0.5 ml, with an interval of at least 1 month between doses. A third dose is 
recommended in the second year of life.

Children aged 12-23 months
Two doses, each of 0.5 ml, with an interval of at least 2 months between doses (see section 5.1).

Children and adolescents aged 2-17 years 
One single dose of 0.5 ml.

Prevenar 13 vaccine schedule for infants and children previously vaccinated with Prevenar (7-valent) 
(Streptococcus pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F)
Prevenar 13 contains the same 7 serotypes included in Prevenar, using the same carrier protein 
CRM197. 

Infants and children who have begun immunisation with Prevenar may switch to Prevenar 13 at any 
point in the schedule.



54

Young children (12-59 months) completely immunised with Prevenar (7-valent)
Young children who are considered completely immunised with Prevenar (7-valent) should receive 
one dose of 0.5 ml of Prevenar 13 to elicit immune responses to the 6 additional serotypes. This dose 
of Prevenar 13 should be administered at least 8 weeks after the final dose of Prevenar (7-valent) (see 
section 5.1).

Children and adolescents 5–17 years 
Children 5 to 17 years of age may receive a single dose of Prevenar 13 if they have been previously 
vaccinated with one or more doses of Prevenar. This dose of Prevenar 13 should be administered at 
least 8 weeks after the final dose of Prevenar (7-valent) (see section 5.1).

Adults ≥ 18 years of age, and the elderly

One single dose.
The need for revaccination with a subsequent dose of Prevenar 13 has not been established.

Regardless of prior pneumococcal vaccination status, if the use of 23-valent pneumococcal 
polysaccharide vaccine is considered appropriate, Prevenar 13 should be given first (see sections 4.5 
and 5.1).

Special Populations

Individuals who have underlying conditions predisposing them to invasive pneumococcal disease 
(such as sickle cell disease or HIV infection) including those previously vaccinated with one or more 
doses of 23-valent pneumococcal polysaccharide vaccine may receive at least one dose of Prevenar 13 
(see section 5.1).

In individuals with an haematopoietic stem cell transplant (HSCT), the recommended immunisation 
series consists of four doses of Prevenar 13, each of 0.5 ml. The primary series consists of three doses, 
with the first dose given at 3 to 6 months after HSCT and with an interval of at least 1 month between 
doses. A fourth (booster) dose is recommended 6 months after the third dose (see section 5.1).

Method of administration

The vaccine should be given by intramuscular injection. The preferred sites are the anterolateral 
aspect of the thigh (vastus lateralis muscle) in infants or the deltoid muscle of the upper arm in 
children and adults. 

4.3 Contraindications

Hypersensitivity to the active substances, to any of the excipients listed in section 6.1, or to diphtheria 
toxoid.

As with other vaccines, the administration of Prevenar 13 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

Prevenar 13 must not be administered intravascularly.

As with all injectable vaccines, appropriate medical treatment and supervision should always be 
readily available in case of a rare anaphylactic event following the administration of the vaccine.



55

This vaccine should not be given as an intramuscular injection to individuals with thrombocytopaenia 
or any coagulation disorder that would contraindicate intramuscular injection, but may be given 
subcutaneously if the potential benefit clearly outweighs the risks (see section 5.1).

Prevenar 13 will only protect against Streptococcus pneumoniae serotypes included in the vaccine, 
and will not protect against other microorganisms that cause invasive disease, pneumonia, or otitis 
media. As with any vaccine, Prevenar 13 may not protect all individuals receiving the vaccine from 
pneumococcal disease. For the most recent epidemiological information in your country you should 
consult with the relevant national organisation.

Individuals with impaired immune responsiveness, whether due to the use of immuno-suppressive 
therapy, a genetic defect, human immunodeficiency virus (HIV) infection, or other causes, may have 
reduced antibody response to active immunisation.

Safety and immunogenicity data are available for a limited number of individuals with sickle cell 
disease, HIV infection, or with an haematopoietic stem cell transplant (see section 5.1). Safety and 
immunogenicity data for Prevenar 13 are not available for individuals in other specific 
immuno-compromised groups (e.g., malignancy or nephrotic syndrome) and vaccination should be 
considered on an individual basis.

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially 
‘sodium-free’.

Infants and children aged 6 weeks to 5 years

In clinical studies, Prevenar 13 elicited an immune response to all thirteen serotypes included in the 
vaccine. The immune response for serotype 3 following the booster dose was not increased above the 
levels seen after the infant vaccination series; the clinical relevance of this observation regarding the 
induction of serotype 3 immune memory is unknown (see section 5.1).

The proportions of functional antibody responders (OPA titres ≥ 1:8) to serotypes 1, 3 and 5 were 
high. However, the OPA geometric mean titres were lower than those against each of the remaining 
additional vaccine serotypes; the clinical relevance of this observation for protective efficacy is 
unknown (see section 5.1). 

Limited data have demonstrated that Prevenar 7-valent (three-dose primary series) induces an 
acceptable immune response in infants with sickle cell disease with a safety profile similar to that 
observed in non-high-risk groups (see section 5.1). 

Children younger than 2 years old should receive the appropriate-for-age Prevenar 13 vaccination 
series (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 are immuno-compromised) 
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 Prevenar 13 
should receive 23-valent pneumococcal polysaccharide vaccine. The interval between the 13-valent 
pneumococcal conjugate vaccine (Prevenar 13) 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 23-valent pneumococcal polysaccharide vaccine to unprimed children or to children 
primed with Prevenar 13 might result in hyporesponsiveness to further doses of Prevenar 13.

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.



56

For vaccine serotypes, protection against otitis media is expected to be lower than protection against 
invasive disease. As otitis media is caused by many organisms other than pneumococcal serotypes 
represented in the vaccine, protection against all otitis media is expected to be low (see section 5.1).

When Prevenar 13 is administered concomitantly with Infanrix hexa (DTPa-HBV-IPV/Hib), the rates 
of febrile reactions are similar to those seen with concomitant administration of Prevenar (7-valent) 
and Infanrix hexa (see section 4.8). Increased reporting rates of convulsions (with or without fever) 
and hypotonic hyporesponsive episode (HHE) were observed with concomitant administration of 
Prevenar 13 and Infanrix hexa (see section 4.8).

Antipyretic treatment should be initiated according to local treatment guidelines for children with 
seizure disorders or with a prior history of febrile seizures and for all children receiving Prevenar 13 
simultaneously with vaccines containing whole cell pertussis.

4.5 Interaction with other medicinal products and other forms of interaction

Infants and children aged 6 weeks to 5 years

Prevenar 13 can be given concomitantly with any of the following vaccine antigens, either as 
monovalent or combination vaccines: diphtheria, tetanus, acellular or whole cell pertussis, 
Haemophilus influenzae type b, inactivated poliomyelitis, hepatitis B (see section 4.4 for guidance on 
Infanrix hexa), meningococcal serogroup C, measles, mumps, rubella, varicella and rotavirus vaccine. 

Prevenar 13 can also be given concomitantly between 12-23 months with the tetanus toxoid 
conjugated meningococcal polysaccharide serogroups A, C, W and Y vaccine to children who have 
been adequately primed with Prevenar 13 (as per local recommendations).

Data from a postmarketing clinical study evaluating the impact of prophylactic use of antipyretics 
(ibuprofen and paracetamol) on the immune response to Prevenar 13 suggest that administration of 
paracetamol concomitantly or within the same day of vaccination may reduce the immune response to 
Prevenar 13 after the infant series. Responses to the booster dose administered at 12 months were 
unaffected. The clinical significance of this observation is unknown.

Children and adolescents 6 to 17 years of age

No data are currently available regarding concomitant use with other vaccines. 

Adults 18 to 49 years of age

No data are available regarding concomitant use with other vaccines. 

Adults aged 50 years and older

Prevenar 13 may be administered concomitantly with the seasonal trivalent inactivated influenza 
vaccine (TIV).

In two studies conducted in adults aged 50-59 and 65 years and older, it was demonstrated that 
Prevenar 13 may be given concomitantly with trivalent inactivated influenza vaccine (TIV). The 
responses to all three TIV antigens were comparable when TIV was given alone or concomitantly 
with Prevenar 13.

When Prevenar 13 was given concomitantly with TIV, the immune responses to Prevenar 13 were 
lower compared to when Prevenar 13 was given alone, however, there was no long-term impact on 
circulating antibody levels.



57

In a third study in adults aged 50-93 years, it was demonstrated that Prevenar 13 may be given 
concomitantly with the seasonal quadrivalent inactivated influenza vaccine (QIV). The immune 
responses to all four QIV strains were noninferior when Prevenar 13 was given concomitantly with 
QIV compared to when QIV was given alone.

The immune responses to Prevenar 13 were noninferior when Prevenar 13 was given concomitantly 
with QIV compared to when Prevenar 13 was given alone. As with concomitant administration with 
trivalent vaccines, immune responses to some pneumococcal serotypes were lower when both 
vaccines were given concomitantly.

Concomitant use with other vaccines has not been investigated.

Different injectable vaccines should always be given at different vaccination sites.

Concomitant administration of Prevenar 13 and 23-valent pneumococcal polysaccharide vaccine has 
not been studied. In clinical studies when Prevenar 13 was given 1 year after 23-valent pneumococcal 
polysaccharide vaccine the immune responses were lower for all serotypes compared to when 
Prevenar 13 was given to subjects not previously immunised with 23-valent pneumococcal 
polysaccharide vaccine. The clinical significance of this is unknown. 

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no data from the use of pneumococcal 13-valent conjugate vaccine in pregnant women. 
Therefore the use of Prevenar 13 should be avoided during pregnancy.

Breast-feeding

It is unknown whether pneumococcal 13-valent conjugate vaccine is excreted in human milk.

Fertility

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity 
(see section 5.3).

4.7 Effects on ability to drive and use machines

Prevenar 13 has no or negligible influence on the ability to drive and use machines. However, some of 
the effects mentioned under section 4.8 “Undesirable effects” may temporarily affect the ability to 
drive or use machines.

4.8 Undesirable effects

Analysis of postmarketing reporting rates suggests a potential increased risk of convulsions, with or 
without fever, and HHE when comparing groups which reported use of Prevenar 13 with 
Infanrix hexa to those which reported use of Prevenar 13 alone.

Adverse reactions reported in clinical studies or from the postmarketing experience for all age groups 
are listed in this section per system organ class, in decreasing order of frequency and seriousness. The 
frequency is defined as follows: very common ( 1/10), common ( 1/100 to < 1/10), uncommon 
( 1/1,000 to < 1/100), rare ( 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be 
estimated from available data).



58

Infants and children aged 6 weeks to 5 years
The safety of the vaccine was assessed in controlled clinical studies where 14,267 doses were given to 
4,429 healthy infants from 6 weeks of age at first vaccination and 11-16 months of age at booster 
dose. In all infant studies, Prevenar 13 was co-administered with routine paediatric vaccines (see 
section 4.5).

Safety in 354 previously unvaccinated children (7 months to 5 years of age) was also assessed.

The most commonly reported adverse reactions in children 6 weeks to 5 years of age were 
vaccination-site reactions, fever, irritability, decreased appetite, and increased and/or decreased sleep.

In a clinical study in infants vaccinated at 2, 3, and 4 months of age, fever ≥ 38°C was reported at 
higher rates among infants who received Prevenar (7-valent) concomitantly with Infanrix hexa (28.3% 
to 42.3%) than in infants receiving Infanrix hexa alone (15.6% to 23.1%). After a booster dose at 12 
to 15 months of age, fever ≥ 38°C was reported in 50.0% of infants who received Prevenar (7-valent) 
and Infanrix hexa at the same time as compared to 33.6% of infants receiving Infanrix hexa alone. 
These reactions were mostly moderate (less than or equal to 39°C) and transient.

An increase in vaccination-site reactions was reported in children older than 12 months compared to 
rates observed in infants during the primary series with Prevenar 13.

Adverse reactions from clinical studies
In clinical studies, the safety profile of Prevenar 13 was similar to Prevenar. The following 
frequencies are based on adverse reactions assessed in Prevenar 13 clinical studies:

Immune system disorders:
Rare: Hypersensitivity reaction including face oedema, dyspnoea, bronchospasm

Nervous system disorders:
Uncommon: Convulsions (including febrile convulsions)
Rare: Hypotonic-hyporesponsive episode

Gastrointestinal disorders:
Very common: Decreased appetite
Common: Vomiting; diarrhoea

Skin and subcutaneous tissue disorders:
Common: Rash
Uncommon: Urticaria or urticaria-like rash

General disorders and administration site conditions:
Very common: Pyrexia; irritability; any vaccination-site erythema, induration/swelling or 

pain/tenderness; somnolence; poor quality sleep
Vaccination-site erythema or induration/swelling 2.5 cm–7.0 cm (after the 
booster dose and in older children [age 2 to 5 years])

Common: Pyrexia > 39°C; vaccination-site movement impairment (due to pain); 
vaccination-site erythema or induration/swelling 2.5 cm–7.0 cm (after infant 
series)

Uncommon: Vaccination-site erythema, induration/swelling > 7.0 cm; crying

Additional information in special populations:
Apnoea in very premature infants ( 28 weeks of gestation) (see section 4.4).



59

Children and adolescents aged 6 to 17 years of age 
Safety was evaluated in 592 children (294 children aged 5 to 10 years previously immunised with at 
least one dose of Prevenar and 298 children aged 10 to 17 years who had not received a pneumococcal 
vaccine).

The most common adverse events in children and adolescents 6 to 17 years of age were:

Nervous system disorders:
Common: Headaches

Gastrointestinal disorders:
Very common: Decreased appetite
Common: Vomiting; diarrhoea

Skin and subcutaneous tissue disorders:
Common: Rash; urticaria or urticaria-like rash

General disorders and administration site conditions:
Very common: Irritability; any vaccination-site erythema; induration/swelling or 

pain/tenderness; somnolence; poor quality sleep; 
vaccination-site tenderness (including impaired movement)

Common: Pyrexia

Other adverse events previously observed in infants and children 6 weeks to 5 years of age may also 
be applicable to this age group but were not seen in this study possibly due to the small sample size.

Additional information in special populations
Children and adolescents with sickle cell disease, HIV infection, or an haematopoietic stem cell 
transplant have similar frequencies of adverse reactions, except that headaches, vomiting, diarrhoea, 
pyrexia, fatigue, arthralgia, and myalgia were very common.

Adults ≥ 18 years and elderly
Safety was assessed in 7 clinical studies including 91,593 adults ranging in age from 18 to 101 years. 
Prevenar 13 was administered to 48,806 adults; 2,616 (5.4%) aged 50 to 64 years, and 45,291 (92.8%) 
aged 65 years and older. One of the 7 studies included a group of adults (n=899) ranging from 18 to 
49 years who received Prevenar 13 and who were not previously vaccinated with 23-valent 
pneumococcal polysaccharide vaccine. Of the Prevenar 13 recipients 1,916 adults were previously 
vaccinated with the 23-valent pneumococcal polysaccharide vaccine at least 3 years prior to study 
vaccination, and 46,890 were 23-valent pneumococcal polysaccharide vaccine unvaccinated.

A trend to lower frequency of adverse reactions was associated with greater age; adults > 65 years of 
age (regardless of prior pneumococcal vaccination status) reported fewer adverse reactions than 
younger adults, with adverse reactions generally most common in the youngest adults, 18 to 29 years 
of age.

Overall, the frequency categories were similar for all age groups, with the exception of vomiting 
which was very common ( 1/10) in adults aged 18 to 49 years and common ( 1/100 to < 1/10) in all 
other age groups, and pyrexia was very common in adults aged 18 to 29 years and common in all other 
age groups. Severe vaccination-site pain/tenderness and severe limitation of arm movement was very 
common in adults 18 to 39 years and common in all other age groups.

Adverse reactions from clinical studies
Local reactions and systemic events were solicited daily after each vaccination for 14 days in 6 studies
and 7 days in the remaining study. The following frequencies are based on adverse reactions assessed 
in Prevenar 13 clinical studies in adults:



60

Metabolism and nutrition disorders:
Very common: Decreased appetite

Nervous system disorders:
Very common: Headaches

Gastrointestinal disorders: 
Very common: Diarrhoea; vomiting (in adults aged 18 to 49 years)

Common: Vomiting (in adults aged 50 years and over)

Uncommon: Nausea

Immune system disorders:
Uncommon: Hypersensitivity reaction including face oedema, dyspnoea, bronchospasm

Skin and subcutaneous tissue disorders:
Very common: Rash

General disorders and administration site conditions:
Very common: Chills; fatigue; vaccination-site erythema; vaccination-site 

induration/swelling; vaccination-site pain/tenderness (severe vaccination-site 
pain/tenderness very common in adults aged 18 to 39 years); limitation of arm 
movement (severe limitation of arm movements very common in adults aged 
18 to 39 years)

Common: Pyrexia (very common in adults aged 18 to 29 years)

Uncommon: Lymphadenopathy localized to the region of the vaccination-site

Musculoskeletal and connective tissue disorders:
Very common: Arthralgia; myalgia

Overall, no significant differences in frequencies of adverse reactions were seen when Prevenar 13 
was given to adults previously vaccinated with the pneumococcal polysaccharide vaccine.

Additional information in special populations
Adults with HIV infection have similar frequencies of adverse reactions, except that pyrexia and 
vomiting were very common and nausea common. 

Adults with an haematopoietic stem cell transplant have similar frequencies of adverse reactions, 
except that pyrexia and vomiting were very common.

Higher frequency in some solicited systemic reactions was observed when Prevenar 13 was 
administered concomitantly with trivalent inactivated influenza vaccine (TIV) compared to TIV given 
alone (headache, chills, rash, decreased appetite, arthralgia, and myalgia) or Prevenar 13 given alone 
(headache, fatigue, chills, decreased appetite, and arthralgia). 

Adverse reactions from Prevenar 13 postmarketing experience
The following are considered adverse drug reactions for Prevenar 13; because these reactions were 
derived from spontaneous reports, the frequencies could not be determined and are thus considered as 
not known.

Blood and lymphatic system disorders:
Lymphadenopathy (localised to the region of the vaccination-site)



61

Immune system disorders:
Anaphylactic/anaphylactoid reaction including shock; angioedema

Skin and subcutaneous tissue disorders:
Erythema multiforme

General disorders and administration site conditions:
Vaccination-site urticaria; vaccination-site dermatitis; vaccination-site 
pruritus; flushing

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

In infants and children there have been reports of overdose with Prevenar 13 defined as subsequent 
doses administered closer than recommended to the previous dose. In general, adverse events reported 
with overdose are consistent with those that have been reported with doses given in the recommended 
paediatric schedules of Prevenar 13.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: vaccines, pneumococcal vaccines; ATC code: J07AL02

Prevenar 13 contains the 7 pneumococcal capsular polysaccharides that are in Prevenar (4, 6B, 9V, 
14, 18C, 19F, 23F) plus 6 additional polysaccharides (1, 3, 5, 6A, 7F, 19A) all conjugated to CRM197

carrier protein. 

Burden of disease

Infants and children aged 6 weeks to 5 years

Based on serotype surveillance in Europe performed before the introduction of Prevenar, Prevenar 13 
is estimated to cover 73-100% (depending on the country) of serotypes causing invasive 
pneumococcal disease (IPD) in children less than 5 years of age. In this age group, serotypes 1, 3, 5, 
6A, 7F, and 19A account for 15.6% to 59.7% of invasive disease, depending on the country, the time
period studied, and the use of Prevenar.

Acute otitis media (AOM) is a common childhood disease with different aetiologies. Bacteria can be 
responsible for 60-70% of clinical episodes of AOM. S. pneumoniae is one of the most common 
causes of bacterial AOM worldwide.

Prevenar 13 is estimated to cover over 90% of serotypes causing antimicrobial-resistant IPD. 

Children and adolescents aged 6 to 17 years

In children and adolescents aged 6 to 17 years, the incidence of pneumococcal disease is low, 
however, there is an increased risk of morbidity and mortality in those with underlying comorbidities.



62

Adults ≥ 18 years and the elderly

Pneumonia is the most common clinical presentation of pneumococcal disease in adults.

The reported incidence of community-acquired pneumonia (CAP) and IPD in Europe varies by 
country, increases with age from 50 years and is highest in individuals aged ≥ 65 years. S. pneumoniae
is the most frequent cause of CAP, and is estimated to be responsible for approximately 30% of all 
CAP cases requiring hospitalisation in adults in developed countries.

Bacteraemic pneumonia (approximately 80% of IPD in adults), bacteraemia without a focus, and 
meningitis are the most common manifestations of IPD in adults. Based on surveillance data following 
the introduction of Prevenar but before the introduction of Prevenar 13 in childhood vaccination 
programmes, the pneumococcal serotypes in Prevenar 13 may be responsible for at least 50 – 76% 
(depending on country) of IPD in adults.

The risk for CAP and IPD in adults also increases with chronic underlying medical conditions, 
specifically, anatomical or functional asplenia, diabetes mellitus, asthma, chronic cardiovascular, 
pulmonary, kidney or liver disease, and it is highest in those who are immune-suppressed such as 
those with malignant haematological diseases or HIV infection. 

Prevenar 13 immunogenicity clinical studies in infants, children and adolescents

The protective efficacy of Prevenar 13 against IPD has not been studied. As recommended by the 
World Health Organization (WHO) the assessment of potential efficacy against IPD in infants and 
young children has been based on a comparison of immune responses to the seven common serotypes 
shared between Prevenar 13 and Prevenar, for which protective efficacy has been proven (for 
Prevenar (7-valent) efficacy in infants and children, see below). Immune responses to the additional 
6 serotypes were also measured.

Study of Prevenar 13 containing the preservative 2-phenoxyethanol (2-PE):

Safety and immunogenicity of Prevenar 13 containing the preservative 2-PE (presented in a multidose 
container) given to healthy infants at 8, 12 and 16 weeks of age were compared to those of 
Prevenar 13 without added preservative (250 infants per group).

Pneumococcal immune responses were compared using non-inferiority criteria, including the 
percentage of subjects with serum anti-polysaccharide serotype-specific IgG concentration 
≥0.35 μg/ml and the comparison of IgG GMCs one month after the infant series. In addition, OPA 
GMTs between subjects receiving Prevenar 13 with or without 2-PE were compared.

Non-inferiority for the proportion of subjects achieving an IgG concentration 0.35 μg/ml was 
demonstrated for all 13 serotypes (lower bound of the 97.5% confidence interval (CI) for the 
difference in percentage of responders at 0.35 µg/ml between groups was >-10%). Additionally, all 
13 serotypes met the pre-defined non-inferiority criterion for IgG GMCs (lower bound of the 97.5% 
CI of GMC ratio [GMR] was greater than 0.5).

Correspondingly, OPA GMTs were similar in both groups, except for serotype 3, which was lower, 
and serotype 18C, which was higher, in the group that received Prevenar 13 with 2-PE. 

Studies of Prevenar 13 not containing the preservative 2-PE

Immune responses following a three-dose primary infant series

Clinical studies have been conducted in a number of European countries and the US using a range of 
vaccination schedules, including two randomised non-inferiority studies (Germany using a 2, 3, 
4 month primary series [006] and US using a 2, 4, 6 month primary series [004]). In these two studies 



63

pneumococcal immune responses were compared using a set of non-inferiority criteria including the 
percentage of subjects with serum anti-polysaccharide serotype-specific IgG ≥ 0.35 μg/ml one month 
after the primary series and the comparison of IgG geometric mean concentrations (ELISA GMCs); in 
addition, functional antibody titres (OPA) between subjects receiving Prevenar 13 and Prevenar were 
compared. For the six additional serotypes, these values were compared with the lowest response 
among all of the seven common serotypes in the Prevenar recipients.

The non-inferiority immune response comparisons for study 006, based on the proportion of infants 
achieving anti-polysaccharide IgG concentrations ≥ 0.35 μg/ml, are shown in Table 1. Results for 
study 004 were similar. Prevenar 13 non-inferiority (lower bound of the 95% CI for the difference in 
percentage of responders at 0.35 µg/ml between groups was >-10%) was demonstrated for all 
7 common serotypes, except for serotype 6B in study 006 and serotypes 6B and 9V in study 004, 
which missed by a small margin. All seven common serotypes met pre-defined non-inferiority criteria 
for IgG ELISA GMCs. Prevenar 13 elicited comparable, although slightly lower, antibody levels than 
Prevenar for the 7 common serotypes. The clinical relevance of these differences is not known.

Non-inferiority was met for the 6 additional serotypes based on the proportion of infants achieving 
antibody concentrations ≥ 0.35 μg/ml and comparison of IgG ELISA GMCs in study 006 and was met 
for 5 out of the 6 serotypes, with the exception of serotype 3 for study 004. For serotype 3, the 
percentages of Prevenar 13 recipients with serum IgG ≥ 0.35 μg/ml were 98.2% (study 006) and 
63.5% (study 004).

Table 1: Comparison of the proportion of subjects achieving a pneumococcal anti-polysaccharide IgG 
antibody concentration ≥ 0.35 μg/ml after dose 3 of the infant series – study 006

Serotypes

Prevenar 13 
%

(N=282-285)

7-valent Prevenar
%

(N=277-279)
Difference
(95 % CI)

7-valent Prevenar serotypes
4 98.2 98.2 0.0 (-2.5, 2.6)

6B 77.5 87.1 -9.6 (-16.0, -3.3)
9V 98.6 96.4 2.2 (-0.4, 5.2)
14 98.9 97.5 1.5 (-0.9, 4.1)

18C 97.2 98.6 -1.4 (-4.2, 1.2)
19F 95.8 96.0 -0.3 (-3.8, 3.3)
23F 88.7 89.5 -0.8 (-6.0, 4.5)

Additional serotypes in Prevenar 13
1 96.1 87.1* 9.1 (4.5, 13.9)
3 98.2 87.1 11.2 (7.0, 15.8)
5 93.0 87.1 5.9 (0.8, 11.1)

6A 91.9 87.1 4.8 (-0.3, 10.1)
7F 98.6 87.1 11.5 (7.4, 16.1)

19A 99.3 87.1 12.2 (8.3, 16.8)
* The serotype in Prevenar with the lowest percent response rate was 6B in study 006 (87.1 %).

Prevenar 13 elicited functional antibodies to all 13 vaccine serotypes in studies 004 and 006. For the 
7 common serotypes there were no differences between groups in the proportion of subjects with OPA 
titres ≥ 1:8. For each of the seven common serotypes, > 96% and > 90% of the Prevenar 13 recipients 
reached an OPA titre ≥ 1:8 one month after the primary series in studies 006 and 004, respectively.

For each of the 6 additional serotypes, Prevenar 13 elicited OPA titres ≥ 1:8 in 91.4% to 100% of 
vaccinees one month after the primary series in studies 004/006. The functional antibody (OPA) 
geometric mean titres for serotypes 1, 3 and 5 were lower than the titres for each of the other 
additional serotypes; the clinical relevance of this observation for protective efficacy is unknown. 

Immune responses following a two-dose primary infant series



64

The immunogenicity after two doses in infants has been documented in four studies. The proportion 
of infants achieving a pneumococcal anti-capsular polysaccharide IgG concentration ≥ 0.35 g/ml one 
month after the second dose ranged from 79.6% to 98.5% across 11 of the 13 vaccine serotypes. 
Smaller proportions of infants achieved this antibody concentration threshold for serotype 6B (27.9% 
to 57.3%) and 23F (55.8% to 68.1%) for all studies using a 2, 4 month regimen, compared to 58.4% 
for serotype 6B and 68.6% for 23F for a study using a 3, 5 month regimen. After the booster dose, all 
vaccine serotypes including 6B and 23F had immune responses consistent with adequate priming with 
a two-dose primary series. In a UK study, the functional antibody (OPA) responses were comparable 
for all serotypes including 6B and 23F in the Prevenar and Prevenar 13 arms after the primary series 
at two and four months of age and after the booster dose at 12 months of age. For Prevenar 13 
recipients, the proportion of responders with an OPA titre  1:8 was at least 87% following the infant 
series, and at least 93% following the booster dose. The OPA geometric mean titres for serotypes 1, 3 
and 5 were lower than the titres for each of the other additional serotypes; the clinical relevance of 
this observation is unknown.

Booster responses following two-dose and three-dose primary infant series

Following the booster dose, antibody concentrations increased from the pre-booster level for all 
13 serotypes. Post-booster antibody concentrations were higher for 12 serotypes than those achieved 
after the infant primary series. These observations are consistent with adequate priming (the induction 
of immunologic memory). The immune response for serotype 3 following the booster dose was not 
increased above the levels seen after the infant vaccination series; the clinical relevance of this 
observation regarding the induction of serotype 3 immune memory is unknown.

Antibody responses to booster doses following two-dose or three-dose infant primary series were 
comparable for all 13 vaccine serotypes.

For children aged from 7 months to 5 years, age appropriate catch-up immunisation schedules (as 
described in section 4.2) result in levels of anti-capsular polysaccharide IgG antibody responses to 
each of the 13 serotypes that are at least comparable to those of a three-dose primary series in infants.

Antibody persistence and immunological memory were evaluated in a study in healthy children who 
received a single dose of Prevenar 13 at least 2 years after they had been previously immunised with 
either 4 doses of Prevenar, a 3-dose infant series of Prevenar followed by Prevenar 13 at 12 months of 
age, or 4 doses of Prevenar 13. 

The single dose of Prevenar 13, in children approximately 3.4 years of age regardless of previous 
vaccination history with Prevenar or Prevenar 13, induced a robust antibody response for both the 
7 common serotypes and the 6 additional serotypes in Prevenar 13.

Since the introduction of 7-valent Prevenar in 2000, pneumococcal disease surveillance data have not 
shown that the immunity elicited by Prevenar in infancy has waned over time. 

Preterm Infants

Safety and immunogenicity of Prevenar 13 given at 2, 3, 4 and 12 months was assessed in 
approximately 100 prematurely born infants (mean Estimated Gestational Age [EGA], 31 weeks; 
range, 26 to 36 weeks) and compared with approximately 100 infants born at term (mean EGA, 
39 weeks; range, 37 to 42 weeks).

Immune responses in preterm and term infants were compared using the proportion of subjects 
achieving a pneumococcal polysaccharide IgG binding antibody concentration ≥0.35 μg/ml 1 month 
after the infant series, the approach used for immunogenicity comparisons of Prevenar 13 to Prevenar 
based on WHO guidelines.



65

More than 85% achieved a pneumococcal polysaccharide IgG binding antibody concentration 
≥0.35 µg/ml 1 month after the infant series, except for serotypes 5 (71.7%), 6A (82.7%), and 6B 
(72.7%) in the preterm group. For these 3 serotypes, the proportion of responders among preterm 
infants was significantly lower than among term infants. Approximately one month after the toddler 
dose, the proportion of subjects in each group achieving this same antibody concentration threshold 
was >97%, except for serotype 3 (71% in preterm infants and 79% in term infants). It is unknown 
whether immunological memory to all serotypes is induced in pre-term infants. In general, 
serotype-specific IgG GMCs were lower for preterm infants than term infants.

After the infant series, OPA GMTs were similar in preterm infants compared to term infants except 
for serotype 5, which was lower in preterm infants. OPA GMTs after the toddler dose relative to those 
after the infant series were similar or lower for 4 serotypes (4, 14, 18C, and 19F) and were statistically 
significantly higher for 6 of 13 serotypes (1, 3, 5, 7F, 9V, and 19A) in preterm infants compared to 10 
of 13 serotypes (1, 3, 4, 5, 6A, 7F, 9V, 18C, 19A, and 23F) in term infants.

Children (12-59 months) completely immunised with Prevenar (7-valent)

Following administration of a single dose of Prevenar 13 to children (12-59 months) who are 
considered completely immunised with Prevenar (7-valent) (either 2 or 3 dose primary series plus 
booster), the proportion achieving serum IgG levels ≥0.35 µg/ml and OPA titres ≥1:8 was at least 
90%. However, 3 (serotypes 1, 5 and 6A) of the 6 additional serotypes showed lower IgG GMC and 
OPA GMT when compared with children who had received at least one previous vaccination with 

Prevenar 13. The clinical relevance of the lower GMCs and GMTs is currently unknown.

Unvaccinated Children (12-23 months)

Studies in unvaccinated children (12 -23 months) with Prevenar (7-valent) demonstrated that 2 doses 
were required to achieve serum IgG concentrations for 6B and 23F similar to those induced by a 
3-dose infant series.

Children and Adolescents 5 to 17 years of age

In an open-label study in 592 healthy children and adolescents including those with asthma (17.4%) 
who may be predisposed to pneumococcal infection, Prevenar 13 elicited immune responses to all 
13 serotypes. A single dose of Prevenar 13 was given to children 5 to 10 years of age previously 
vaccinated with at least 1 dose of Prevenar, and children and adolescents 10 to 17 years of age who 
had never received a pneumococcal vaccine.

In both the children 5 to 10 years of age and children and adolescents aged 10 to 17 years, the immune
response to Prevenar 13 was non inferior to Prevenar for the 7 common serotypes and to Prevenar 13 
for the 6 additional serotypes compared to the immune response after the fourth dose in infants 
vaccinated at 2, 4, 6 and 12-15 months of age as measured by serum IgG.

In children and adolescents aged 10 to 17 years of age OPA GMTs 1 month after vaccination were 
noninferior to OPA GMTs in the 5 to 10 year old age group for 12 of the 13 serotypes (except 
serotype 3). 

Immune responses after subcutaneous administration

Subcutaneous administration of Prevenar 13 was evaluated in a non-comparative study in 185 healthy 
Japanese infants and children who received 4 doses at 2, 4, 6 and 12-15 months of age. The study 
demonstrated that safety and immunogenicity were generally comparable with observations made in 
studies of intramuscular administration.



66

Prevenar 13 Effectiveness

Invasive Pneumococcal Disease
Data published by Public Health England showed that, four years after the introduction of Prevenar as 
a two dose primary infant series with booster dose in the second year of life and with a 94% vaccine 
uptake, there was a 98% (95% CI 95; 99) reduction in disease caused by the 7 vaccine serotypes in 
England and Wales. Subsequently, four years following the switch to Prevenar 13, the additional
reduction in incidence of IPD due to the 7 serotypes in Prevenar ranged from 76% in children less 
than 2 years of age to 91% in children 5-14 years of age. The serotype specific reductions for each of 
the 5 additional serotypes in Prevenar 13 (no cases of serotype 5 IPD were observed) by age group are 
shown in Table 2 and ranged from 68% (serotype 3) to 100% (serotype 6A) for children less than 
5 years of age. Significant incidence reductions were also observed in older age groups who had not 
been vaccinated with Prevenar 13 (indirect effect).

Table 2: Serotype specific number of cases and incidence reductions of IPD in 2013/14 compared to 
2008/09-2009/10 (2008/10) by age in England and Wales

<5 years of age 5 to 64 years of age ≥65 years of age

2008-
10§

2013/
14§

% Incidence 
reduction 
(95% CI*)

2008-
10§

2013/
14§

% 
Incidence 
reduction 
(95% CI*)

2008-
10§

2013/
14§

% Incidence 
reduction 
(95% CI*)

Additional serotypes covered by Prevenar 13

1 59 (54) 5 (5) 91%

(98%; 
68%)**

458 
(382)

77 
(71)

83%

(88%; 
74%)**

102 
(89)

13 
(13)

87%

(94%; 
72%)**

3 26 (24) 8 (8) 68%

(89%; 6%)

178 
(148)

73 
(68)

59%

(72%; 
38%)**

256 
(224)

143 
(146)

44%

(57%; 
27%)**

6A 10 (9) 0 (0) 100%

(100%; 
62%)**

53 (44) 5 (5) 90%

(97%; 
56%)**

94 (82) 5 (5) 95%

(99%; 
81%)**

7F 90 (82) 8 (8) 91%

(97%; 
74%)**

430 
(361)

160
(148)

63%

(71%; 
50%)**

173 
(152)

75 
(77)

56%

(70%; 
37%)**

19A 85 (77) 7 (7) 91%

(97%; 
75%)**

225 
(191)

104 
(97)

54%

(65%; 
32%)**

279 
(246)

97 
(99)

65%

(75%; 
53%)**

§ Corrected for proportion of samples serotyped, missing age, denominator compared with 2009/10, and 
for the trend in total invasive pneumococcal disease up to 2009/10 (after which no trend correction was 
applied).

* 95% CI inflated from a Poisson interval based on over-dispersion of 2.1 seen from modelling of 
2000-06 pre-Prevenar all IPD data.

** p<0.005 to cover 6A where p=0.002



67

Otitis media (OM)
In a published study performed in Israel, using a 2-dose primary series plus booster dose in the second 
year of life, the impact of Prevenar 13 on OM was documented in a population-based 
active-surveillance system with tympanocentesis culturing of middle ear fluid in Israeli children less 
than 2 years of age with OM. 

Following the introduction of Prevenar and subsequently Prevenar 13 there was a decline in incidence 
from 2.1 to 0.1 cases per 1000 children (95%) for the Prevenar serotypes plus serotype 6A and a 
decline in incidence from 0.9 to 0.1 cases per 1000 children (89%) for the additional serotypes 1, 3, 5, 
7F, and 19A in Prevenar 13. The annual overall pneumococcal incidence of OM declined from 9.6 to 
2.1 cases per 1000 children (78%) between July 2004 (prior to the introduction of Prevenar) and June 
2013 (post Prevenar 13 introduction).

Pneumonia
In a multicenter observational study in France comparing the periods before and after the switch from 
Prevenar to Prevenar 13, there was 16% (2060 to 1725 cases) reduction in all community acquired 
pneumonia (CAP) cases in emergency departments in children 1 month to 15 years of age. Reductions 
were 53% (167 to 79 cases) (p<0.001) for CAP cases with pleural effusion and 63% (64 to 24 cases) 
(p<0.001) for microbiologically confirmed pneumococcal CAP cases. In the second year after the 
introduction of Prevenar 13 the total number of CAP cases due to the 6 additional vaccine serotypes in 
Prevenar 13 was reduced from 27 to 7 isolates (74%).

The decrease in all cause pneumonia cases was most pronounced in the younger vaccinated age 
groups with a decrease of 31.8% (757 to 516 cases) and 16.6% (833 to 695 cases) in the age groups 
<2 years and 2 to 5 years, respectively. The incidence in older, predominantly non-vaccinated children 
(>5 years) did not change over the duration of the study.

In an ongoing surveillance system (2004 to 2013) to document the impact of Prevenar and 
subsequently Prevenar 13 on CAP in children less than 5 years in Southern Israel using a 2 dose 
primary series with a booster dose in the second year of life, there was a reduction of 68% 
(95% CI 73; 61) in outpatient visits and 32% (95% CI 39; 22) in hospitalizations for alveolar CAP 
following the introduction of Prevenar 13 when compared to the period before the introduction of 
Prevenar.

Effect on nasopharyngeal carriage 

In a surveillance study in France in children presenting with acute otitis media, changes in 
nasopharyngeal (NP) carriage of pneumococcal serotypes were evaluated following the introduction 
of Prevenar (7-valent) and subsequently Prevenar 13. Prevenar 13 significantly reduced NP carriage of 
the 6 additional serotypes (and serotype 6C) combined and individual serotypes 6C, 7F, 19A when 
compared with Prevenar. A reduction in carriage was also seen for serotype 3 (2.5% vs 1.1%; p=0.1). 
There was no carriage of serotypes 1 and 5 observed.

The effect of pneumococcal conjugate vaccination on nasopharyngeal carriage was studied in a 
randomised double-blind study in which infants received either Prevenar 13 or Prevenar (7-valent) at 
2, 4, 6 and 12 months of age in Israel. Prevenar 13 significantly reduced newly identified NP 
acquisition of the 6 additional serotypes (and serotype 6C) combined and of individual serotypes 1, 
6A, 6C, 7F, 19A when compared with Prevenar. There was no reduction seen in serotype 3 and for 
serotype 5 the colonization was too infrequent to assess impact. For 6 of the remaining 7 common 
serotypes, similar rates of NP acquisition were observed in both vaccine groups; for serotype 19F a 
significant reduction was observed.

In this study, reductions of S. pneumoniae serotypes 19A, 19F, and 6A not susceptible to a number of 
antibiotics were documented. The reductions ranged between 34% and 62% depending on serotype 
and antibiotic.



68

Prevenar (7-valent vaccine) protective efficacy in infants and children

The efficacy of 7-valent Prevenar was evaluated in two major studies – the Northern California Kaiser 
Permanente (NCKP) study and the Finnish Otitis Media (FinOM) study. Both studies were 
randomised, double-blind, active-control studies in which infants were randomised to receive either 
Prevenar or control vaccine (NCKP, meningococcal serogroup C CRM-conjugate [MnCC] vaccine; 
FinOM, hepatitis B vaccine) in a four-dose series at 2, 4, 6, and 12-15 months of age. The efficacy 
results from these studies (for invasive pneumococcal disease, pneumonia, and acute otitis media) are 
presented below (Table 3).

Table 3: Summary of efficacy of 7-valent Prevenar1

Test N VE2 95% CI

NCKP: Vaccine-serotype IPD3 30,258 97% 85, 100

NCKP: Clinical pneumonia with abnormal chest X-ray 23,746 35% 4, 56

NCKP: Acute Otitis Media (AOM)4 23,746

Total episodes 7% 4, 10

Recurrent AOM (3 episodes in 6 months, or 4 episodes in 1 year) 9% 3, 15
Recurrent AOM (5 episodes in 6 months, or 6 episodes in 1 year) 23% 7, 36
Tympanostomy tube placement 20% 2, 35

FinOM: AOM 1,662

Total episodes 6% -4, 16

All pneumococcal AOM 34% 21, 45
Vaccine-serotype AOM 57% 44, 67

1Per protocol
2Vaccine efficacy
3October 1995 to April 20, 1999
4October 1995 to April 30, 1998

Prevenar (7-valent) effectiveness

The effectiveness (both direct and indirect effect) of 7-valent Prevenar against pneumococcal disease 
has been evaluated in both three-dose and two-dose primary infant series immunisation programmes, 
each with booster doses (Table 4). Following the widespread use of Prevenar, the incidence of IPD 
has been consistently and substantially reduced.

Using the screening method, serotype-specific effectiveness estimates for 2 doses under the age of 
1 year in the UK were 66 % (-29, 91 %) and 100 % (25, 100 %) for serotype 6B and 23F, respectively.



69

Table 4: Summary of effectiveness of 7-valent Prevenar for invasive pneumococcal disease
Country

(year of introduction)
Recommended schedule Disease reduction, % 95% CI

UK (England & Wales)1 (2006) 2, 4, + 13 months Vaccine serotypes:
Two doses under age 1: 85%

49, 95%

USA (2000)

Children < 52

Persons ≥ 653

2, 4, 6, + 12-15 months

Vaccine serotypes: 98%
All serotypes: 77%

Vaccine serotypes: 76%
All serotypes: 38%

97, 99%
73, 79%

NA
NA

Canada (Quebec)4

(2004)
2, 4, + 12 months All serotypes: 73%

Vaccine serotypes:
2-dose infant series: 99%
Completed schedule:100%

NA

92, 100%
82, 100%

1Children < 2 years of age. Calculated vaccine effectiveness as of June 2008 (Broome method).
22005 data.
32004 data.
4Children < 5 years of age. January 2005 to December 2007. Complete effectiveness for routine 2+1 schedule not 
yet available.

Acute Otitis Media
Effectiveness of Prevenar in a 3+1 schedule has also been observed against acute otitis media and 
pneumonia since its introduction in a national immunisation programme. In a retrospective evaluation 
of a large US insurance database, AOM visits were reduced by 42.7 % (95 % CI, 42.4-43.1 %), and 
prescriptions for AOM by 41.9 % in children younger than 2 years of age, compared with a 
pre-licensure baseline (2004 vs. 1997-99). In a similar analysis, hospitalisations and ambulatory visits 
for all-cause pneumonia were reduced by 52.4 % and 41.1 %, respectively. For those events 
specifically identified as pneumococcal pneumonia, the observed reductions in hospitalisations and 
ambulatory visits were 57.6 % and 46.9 %, respectively, in children younger than 2 years of age, 
compared with a pre-licensure baseline (2004 vs. 1997-99). While direct cause-and-effect cannot be 
inferred from observational analyses of this type, these findings suggest that Prevenar plays an 
important role in reducing the burden of mucosal disease (AOM and pneumonia) in the target 
population.

Efficacy study in adults 65 years and older

Efficacy against vaccine-type (VT) pneumococcal CAP and IPD was assessed in a large-scale 
randomised double-blind, placebo-controlled study (Community-Acquired Pneumonia Immunization 
Trial in Adults–CAPiTA) in the Netherlands. 84,496 subjects, 65 years and older received a single 
vaccination of either Prevenar 13 or placebo in a 1:1 randomisation.

The CAPiTA study enrolled volunteers ≥ 65 years of age whose demographic and health 
characteristics may differ from those seeking vaccination.

A first episode of hospitalised, chest X-ray confirmed pneumonia was identified in about 2% of this 
population (n=1,814 subjects) of which 329 cases were confirmed pneumococcal CAP and 182 cases 
were VT pneumococcal CAP in the per protocol and modified intent to treat (mITT) populations.

Efficacy was demonstrated for the primary and secondary endpoints in the per protocol population
(Table 5).



70

Table 5: Vaccine efficacy (VE) for the primary and secondary endpoints of the CAPiTA study (per 
protocol population)

Efficacy endpoint

Cases

VE (%)
(95.2% CI)

p-value
Total

Prevenar 13
group

Placebo
group

Primary endpoint

First episode of confirmed VT
pneumococcal CAP

139 49 90
45.56

(21.82, 62.49)
0.0006

Secondary endpoints

First episode of confirmed NB/NI1

vaccine type pneumococcal CAP
93 33 60

45.00
(14.21, 65.31)

0.0067

First episode of VT-IPD2 35 7 28
75.00

(41.06, 90.87)
0.0005

1NB/NI – non-bacteraemic/non-invasive
2VT-IPD – vaccine-type invasive pneumococcal disease

The duration of protective efficacy against a first episode of VT pneumococcal CAP, 
NB/NI VT pneumococcal CAP, and VT-IPD extended throughout the 4-year study.

The study was not designed to demonstrate efficacy in subgroups, and the number of subjects 
≥ 85 years of age was not sufficient to demonstrate efficacy in this age group.

A post-hoc analysis was used to estimate the following public health outcomes against clinical CAP 
(as defined in the CAPiTA study, and based on clinical findings regardless of radiologic infiltrate or 
etiologic confirmation): vaccine efficacy (VE), incidence rate reduction (IRR), and number needed to 
vaccinate (NNV) (Table 6).

IRR, also referred to as vaccine preventable disease incidence, is the number of cases of vaccine 
preventable disease per 100,000 person-years of observation.

In Table 6, NNV is a measure that quantifies the number of people that need to be vaccinated in order 
to prevent one clinical CAP case.

Table 6: Vaccine efficacy (VE) against clinical CAP*

Episodes Vaccine efficacy1 % 
(95% CI)

(1-sided p-value)

Incidence per 
100,000 person-

years of observation 
(PYO)

Incidence 
rate 

reduction2

(95% CI)

Number 
needed to 
vaccinate3

Prevenar
13

Placebo Prevenar 
13

Placebo

All 
episodes 
analysis

1375 1495 8.1 

(-0.6, 16.1) 

(0.034)

819.1 891.2 72.2 
(-5.3, 149.6)

277

First 
episode 
analysis

1126 1214 7.3

(-0.4, 14.4)

(0.031)

670.7 723.7 53.0
(-2.7, 108.7)

378

* Patients with at least 2 of the following: Cough; purulent sputum, temperature >38°C or <36.1°C; pneumonia 
(auscultatory findings); leukocytosis; C-reactive protein value >3 times the upper limit of normal; hypoxemia with 
a partial oxygen pressure <60 mm Hg while breathing room air.
1 A Poisson regression model with random effects was used to calculate VE.
2 Per 100,000 person-years of observation. IRR is calculated as the incidence in the placebo group minus the 
incidence in the vaccine group, and was mathematically equivalent to VE × the incidence in the placebo group.
3 Based on a 5-year duration of protection. NNV is not a rate but instead indicates the number of cases prevented 
for a given number of persons vaccinated. NNV also incorporates the length of the trial or duration of protection



71

and is calculated as 1 divided by the product of the IRR and duration of protection (or length of trial) (=1/(IRR ×
duration).

Immunogenicity studies in adults ≥18 years and the elderly

In adults, an antibody threshold of serotype-specific pneumococcal polysaccharide IgG binding 
antibody concentration associated with protection has not been defined. For all pivotal clinical trials, a 
serotype-specific opsonophagocytosis assay (OPA) was used as a surrogate to assess potential
efficacy against invasive pneumococcal disease and pneumonia. OPA geometric mean titers (GMTs) 
measured 1-month after each vaccination were calculated. OPA titres are expressed as the reciprocal 
of the highest serum dilution that reduces survival of the pneumococci by at least 50 %.

Pivotal trials for Prevenar 13 were designed to show that functional OPA antibody responses for the 
13 serotypes are non-inferior, and for some serotypes superior, to the 12 serotypes in common with 

the licensed 23-valent pneumococcal polysaccharide vaccine [1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 
19F, 23F] one month after vaccine administration. The response to serotype 6A, which is unique to 
Prevenar 13, was assessed by demonstration of a 4-fold increase in the specific OPA titer above 
pre-immunised levels.

Five clinical studies were conducted in Europe and the USA evaluating the immunogenicity of 
Prevenar 13 in different age groups ranging from 18-95 years of age. Clinical studies with Prevenar 13 
currently provide immunogenicity data in adults aged 18 years and older, including adults aged 65 and 
older previously vaccinated with one or more doses of 23-valent pneumococcal polysaccharide 
vaccine, 5 years prior to enrollment. Each study included healthy adults and immuno-competent adults 
with stable underlying conditions known to predispose individuals to pneumococcal infection (i.e., 
chronic cardiovascular disease, chronic pulmonary disease including asthma, renal disorders and 
diabetes mellitus, chronic liver disease including alcoholic liver disease), and adults with risk factors 
such as smoking and alcohol abuse.

Immunogenicity and safety of Prevenar 13 has been demonstrated in adults aged 18 years and older 
including those previously vaccinated with a pneumococcal polysaccharide vaccine.

Adults not previously vaccinated with 23-valent pneumococcal polysaccharide vaccine
In a head-to-head, comparative trial conducted in adults aged 60-64 years, subjects received a single 
dose of either Prevenar 13 or 23-valent pneumococcal polysaccharide vaccine. In the same study 
another group of adults aged 50-59 years and another group of adults aged 18-49 years received a 
single dose of Prevenar 13.

Table 7 compares the OPA GMTs, 1-month post-dose, in 60-64 year olds given either a single dose of 
Prevenar 13 or 23-valent pneumococcal polysaccharide vaccine, and in 50-59 year olds given a single 
dose of Prevenar 13.



72

Table 7: OPA GMTs in adults aged 60-64 years given Prevenar 13 or 23-valent pneumococcal 
polysaccharide vaccine (PPSV23) and in adults aged 50-59 years given Prevenar 13a,b,c

Prevenar 13 Prevenar 13 PPSV23 Prevenar 13
50-59 Relative to

60-64 Years

Prevenar 13 Relative
to PPSV23,
60-64 Years

50-59 Years 
N=350-384

60-64 Years 
N=359-404

60-64 Years 
N=367-402

Serotype GMT GMT GMT GMR (95% CI) GMR (95% CI)
1 200 146 104 1.4 (1.08, 1.73) 1.4 (1.10, 1.78)
3 91 93 85 1.0 (0.81, 1.19) 1.1 (0.90, 1.32)
4 2833 2062 1295 1.4 (1.07, 1.77) 1.6 (1.19, 2.13)
5 269 199 162 1.4 (1.01, 1.80) 1.2 (0.93, 1.62)

6A† 4328 2593 213 1.7 (1.30, 2.15) 12.1 (8.63, 17.08)
6B 3212 1984 788 1.6 (1.24, 2.12) 2.5 (1.82, 3.48)
7F 1520 1120 405 1.4 (1.03, 1.79) 2.8 (1.98, 3.87)
9V 1726 1164 407 1.5 (1.11, 1.98) 2.9 (2.00, 4.08)
14 957 612 692 1.6 (1.16, 2.12) 0.9 (0.64, 1.21)

18C 1939 1726 925 1.1 (0.86, 1.47) 1.9 (1.39, 2.51)
19A 956 682 352 1.4 (1.16, 1.69) 1.9 (1.56, 2.41)
19F 599 517 539 1.2 (0.87, 1.54) 1.0 (0.72, 1.28)
23F 494 375 72 1.3 (0.94, 1.84) 5.2 (3.67, 7.33)

a Non-inferiority was defined as the lower limit of the 2-sided 95% CI for GMR was greater than 0.5. 
b Statistically significantly greater response was defined as the lower bound of the 2-sided 95% CI for the GMR 
was greater than 1. 
c For serotype 6A†, which is unique to Prevenar 13, a statistically significantly greater response was defined as 
the lower bound of the 2-sided 95% CI for the GMR being greater than 2.

In adults aged 60-64 years, OPA GMTs to Prevenar 13 were non-inferior to the OPA GMTs elicited to 
the 23-valent pneumococcal polysaccharide vaccine for the twelve serotypes common to both 
vaccines. For 9 serotypes, the OPA titers were shown to be statistically significantly greater in 
Prevenar 13 recipients. 

In adults aged 50-59 years, OPA GMTs to all 13 serotypes in Prevenar 13 were non-inferior to the 
Prevenar 13 responses in adults aged 60-64 years. For 9 serotypes, immune responses were related to 
age, with adults in the 50-59 years group showing statistically significantly greater responses than 
adults aged 60-64 years.

In all adults ≥ 50 years who received a single dose of Prevenar 13, the OPA titers to serotype 6A were 
significantly greater than in adults ≥ 60 years who received a single dose of 23-valent pneumococcal 
polysaccharide vaccine.

One year after vaccination with Prevenar 13 OPA titers had declined compared to one month after 
vaccination, however, OPA titers for all serotypes remained higher than levels at baseline:

OPA GMT levels at baseline OPA GMT levels one year after 
Prevenar 13

Adults 50-59 years not previously 
vaccinated with 23-valent 
pneumococcal polysaccharide vaccine

5 to 45 20 to 1234

Adults 60-64 years not previously 
vaccinated with 23-valent 
pneumococcal polysaccharide vaccine

5 to 37 19 to 733



73

Table 8 shows OPA GMTs 1-month after a single dose of Prevenar 13 in 18-49 year olds compared to 
60-64 year olds.

Table 8: OPA GMTs in adults aged 18-49 years and 60-64 years given Prevenar 13a,b

18-49 Years
N=836-866

60-64 Years
N=359-404

18-49 Years 
Relative to 

60-64 Years 
Serotype GMTb GMTb GMR (95% CIc)

1 353 146 2.4 (2.03, 2.87)
3 91 93 1.0 (0.84, 1.13)
4 4747 2062 2.3 (1.92, 2.76)
5 386 199 1.9 (1.55, 2.42)

6A 5746 2593 2.2 (1.84, 2.67)
6B 9813 1984 4.9 (4.13, 5.93)
7F 3249 1120 2.9 (2.41, 3.49)
9V 3339 1164 2.9 (2.34, 3.52)
14 2983 612 4.9 (4.01, 5.93)

18C 3989 1726 2.3 (1.91, 2.79)
19A 1580 682 2.3 (2.02, 2.66)
19F 1533 517 3.0 (2.44, 3.60)
23F 1570 375 4.2 (3.31, 5.31)

a Non-inferiority was defined as the lower limit of the 2-sided 95% CI for GMR was greater than 0.5. 
b Statistically significantly greater response was defined as the lower bound of the 2-sided 95% CI for the GMR 
was greater than 1.

c c Confidence intervals (CIs) for the ratio are back transformations of a confidence interval based on the Student t 
distribution for the mean difference of the logarithms of the measures.

In adults aged 18-49 years, OPA GMTs to all 13 serotypes in Prevenar 13 were non-inferior to the 
Prevenar 13 responses in adults aged 60-64 years. 

One year after vaccination with Prevenar 13 OPA titers had declined compared to one month after 
vaccination, however OPA titers for all serotypes remained higher than levels at baseline.

OPA GMT levels at baseline OPA GMT levels one year after 
Prevenar 13

Adults 18-49 years not previously 
vaccinated with 23-valent 
pneumococcal polysaccharide vaccine

5 to 186 23 to 2948

Adults previously vaccinated with 23-valent pneumococcal polysaccharide vaccine
Immune responses to Prevenar 13 and 23-valent pneumococcal polysaccharide vaccine were 
compared in a head to head trial in adults aged ≥ 70 years, who had received a single dose of 
pneumococcal polysaccharide vaccine at least 5 years before study vaccination.

Table 9 compares the OPA GMTs, 1-month post-dose, in pneumococcal polysaccharide vaccinated 
adults aged ≥ 70 years given a single dose of either Prevenar 13 or 23-valent pneumococcal 
polysaccharide vaccine.



74

Table 9: OPA GMTs in pneumococcal polysaccharide vaccinated adults aged 
≥ 70 years given either Prevenar 13 or 23-valent pneumococcal polysaccharide vaccine (PPSV23)a,b,c

Prevenar 13
N=400-426

PPSV23
N=395-445

Prevenar OPA GMT 
Relative to PPSV23

Serotype OPA GMT OPA GMT GMR (95% CI)
1 81 55 1.5 (1.17, 1.88)
3 55 49 1.1 (0.91, 1.35)
4 545 203 2.7 (1.93, 3.74)
5 72 36 2.0 (1.55, 2.63)

6A† 903 94 9.6 (7.00, 13.26)
6B 1261 417 3.0 (2.21, 4.13)
7F 245 160 1.5 (1.07, 2.18)
9V 181 90 2.0 (1.36, 2.97)
14 280 285 1.0 (0.73, 1.33)

18C 907 481 1.9 (1.42, 2.50)
19A 354 200 1.8 (1.43, 2.20)
19F 333 214 1.6 (1.17, 2.06)
23F 158 43 3.7 (2.69, 5.09)

a Non-inferiority was defined as the lower limit of the 2-sided 95% CI for GMR was greater than 0.5. 
b Statistically significantly greater response was defined as the lower bound of the 2-sided 95% CI for the GMR 
was greater than 1. 
c For serotype 6A†, which is unique to Prevenar 13, a statistically significantly greater response was defined as the 
lower bound of the 2-sided 95% CI for the GMR greater than 2.

In adults vaccinated with pneumococcal polysaccharide vaccine at least 5 years prior to the clinical 
study, OPA GMTs to Prevenar 13 were non-inferior to the 23-valent pneumococcal polysaccharide 
vaccine responses for the 12 serotypes in common. Furthermore, in this study statistically significantly 
greater OPA GMTs were demonstrated for 10 of the 12 serotypes in common. Immune responses to 
serotype 6A were statistically significantly greater following vaccination with Prevenar 13 than after 
23-valent pneumococcal polysaccharide vaccine.

One year after vaccination with Prevenar 13 in adults aged 70 years and over who were vaccinated 
with 23-valent pneumococcal polysaccharide vaccine, at least 5 years prior to study entry, OPA titers 
had declined compared to one month after vaccination, however, OPA titers for all serotypes 
remained higher than levels at baseline:

Immune responses in Special Populations

Individuals with the conditions described below have an increased risk of pneumococcal disease. The 
clinical relevance of the antibody levels elicited by Prevenar 13 in these special populations is 
unknown.

Sickle cell disease
An open label single arm study in France, Italy, UK, US, Lebanon, Egypt and Saudi Arabia with 
2 doses of Prevenar 13 given 6 months apart was conducted in 158 children and adolescents ≥ 6 to 
< 18 years of age with sickle cell disease who were previously vaccinated with one or more doses of 
23-valent pneumococcal polysaccharide vaccine at least 6 months prior to enrollment. After the first 
vaccination, Prevenar 13 elicited antibody levels measured by both IgG GMCs and OPA GMTs that 
were statistically significantly higher when compared to levels prior to vaccination. After the second 

OPA GMT levels at baseline OPA GMT levels one year after 
Prevenar 13

Adults ≥ 70 years vaccinated with 
23-valent pneumococcal 
polysaccharide vaccine at least 5 
years prior

9 to 122 18 to 381



75

dose immune responses were comparable to those after the first dose. One year after the second dose, 
antibody levels measured by both IgG GMCs and OPA GMTs were higher than levels prior to the first 
dose of Prevenar 13, except for the IgG GMCs for serotypes 3 and 5 that were numerically similar.

Additional Prevenar (7-valent) immunogenicity data: children with sickle cell disease
The immunogenicity of Prevenar has been investigated in an open-label, multicentre study in 
49 infants with sickle cell disease. Children were vaccinated with Prevenar (3 doses one month apart 
from the age of 2 months), 46 of these children also received a 23-valent pneumococcal 
polysaccharide vaccine at the age of 15-18 months. After primary immunisation, 95.6 % of the 
subjects had antibody levels of at least 0.35 μg/ml for all seven serotypes found in Prevenar. 
A significant increase was seen in the concentrations of antibodies against the seven serotypes after 
the polysaccharide vaccination, suggesting that immunological memory was well established.

HIV infection

Children and adults not previously vaccinated with a pneumococcal vaccine
HIV-infected children and adults with CD4 ≥ 200 cells/µL (mean 717.0 cells/μL), viral load 
< 50,000 copies/ml (mean 2090.0 copies/ml), free of active AIDS-related illness and not previously 
vaccinated with a pneumococcal vaccine received 3 doses of Prevenar 13. As per general 
recommendations, a single dose of 23-valent pneumococcal polysaccharide vaccine was subsequently 
administered. Vaccines were administered at 1 month intervals. Immune responses were assessed in 
259-270 evaluable subjects approximately 1 month after each dose of vaccine. After the first dose, 
Prevenar 13 elicited antibody levels, measured by both IgG GMCs and OPA GMTs that were 
statistically significantly higher when compared to levels prior to vaccination. After the second and 
third dose of Prevenar 13, immune responses were similar or higher than those after the first dose.

Adults previously vaccinated with 23-valent pneumococcal polysaccharide vaccine
HIV-infected adults ≥ 18 years of age with CD4 ≥ 200 cells/µL (mean 609.1 cells/µL) and viral load 
< 50,000 copies/ml (mean 330.6 copies/ml), who were free of active AIDS-related illness and were 
previously vaccinated with 23-valent pneumococcal polysaccharide vaccine administered at least 
6 months prior to enrollment, received 3 doses of Prevenar 13, at enrollment, 6 months, and 
12 months after the first dose of Prevenar 13. Immune responses were assessed in 231-255 evaluable 
subjects approximately 1 month after each dose of Prevenar 13. After the first dose, Prevenar 13 
elicited antibody levels measured by both IgG GMCs and OPA GMTs that were statistically 
significantly higher when compared to levels prior to vaccination. After the second and third dose of 
Prevenar 13, immune responses were comparable or higher than those after the first dose. In the study 
162 subjects had received one prior dose of 23-valent pneumococcal polysaccharide vaccine, 
143 subjects 2 prior doses and 26 subjects more than 2 prior doses of 23-valent polysaccharide 
vaccine. Subjects who received two or more previous doses of 23-valent pneumococcal 
polysaccharide vaccine showed a similar immune response compared with subjects who received a 
single previous dose.

Haematopoietic stem cell transplant
Children and adults with an allogeneic haematopoietic stem cell transplant (HSCT) at ≥ 2 years of age 
with complete haematologic remission of underlying disease or with very good partial remission in the 
case of lymphoma and myeloma received three doses of Prevenar 13 with an interval of at least 
1 month between doses. The first dose was administered at 3 to 6 months after HSCT. A fourth 
(booster) dose of Prevenar 13 was administered 6 months after the third dose. As per general 
recommendations, a single dose of 23-valent pneumococcal polysaccharide vaccine was administered 
1 month after the fourth dose of Prevenar 13. Immune responses as measured by IgG GMCs were 
assessed in 168-211 evaluable subjects approximately 1 month after vaccination. Prevenar 13 elicited 
increased antibody levels after each dose of Prevenar 13. Immune responses after the fourth dose of 
Prevenar 13 were significantly increased for all serotypes compared with after the third dose.
Functional antibody titers (OPA titers) were not measured in this study.



76

5.2 Pharmacokinetic properties

Not applicable.

5.3 Preclinical safety data

Non-clinical data revealed no special hazard for humans based on conventional studies of safety 
pharmacology, single and repeated dose toxicity, local tolerance, and reproduction and developmental 
toxicity.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sodium chloride
Succinic acid
Polysorbate 80
2-phenoxyethanol
Water for injections

For adjuvant, see section 2.

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products.

6.3 Shelf life

3 years

After first use:

Once opened, the product may be stored for a maximum of 28 days at 2-8 oC. Other in-use storage 
times and conditions are the responsibility of the user.

6.4 Special precautions for storage

Store in a refrigerator (2C–8C). Do not freeze.

For storage conditions after first opening of the medicinal product, see section 6.3.

6.5 Nature and contents of container

2 ml (4 x 0.5 ml doses) suspension for injection in a container (Type I glass) with a latex-free grey 
chlorobutyl rubber stopper and sealed with an aluminum flip-off seal and a polypropylene flip-off 
cap.

Pack sizes of 1, 5, 10, 25 and 50.

Not all pack sizes may be marketed.



77

6.6 Special precautions for disposal and other handling

During storage, a white deposit and clear supernatant can be observed. This does not constitute a sign 
of deterioration.

The vaccine should be shaken well to obtain a homogeneous white suspension and should be 
inspected visually for any particulate matter and/or variation of physical aspect prior to 
administration. Do not use if the content appears otherwise. 

No special requirements for disposal.

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.

7. MARKETING AUTHORISATION HOLDER

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/09/590/012
EU/1/09/590/013
EU/1/09/590/014
EU/1/09/590/015
EU/1/09/590/016

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 09 December 2009
Date of latest renewal: 18 September 2014

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.



78

ANNEX II

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

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION

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



79

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

Name and address of the manufacturers of the biological active substance

Wyeth BioPharma Division of Wyeth Pharmaceuticals LLC
One Burtt Road
Andover, MA 01810
USA

Pfizer Ireland Pharmaceuticals
Grange Castle Business Park
Clondalkin
Dublin 22
Ireland

Wyeth Pharmaceutical Division of Wyeth Holdings LLC
4300 Oak Park
Sanford, NC 27330
USA

Name and address of the manufacturer responsible for batch release

Pfizer Manufacturing Belgium N.V.
Rijksweg 12
B-2870 Puurs
Belgium

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to medical prescription.

 Official batch release

In accordance with Article 114 Directive 2001/83/EC, the official batch release will be undertaken by 
a state laboratory or a laboratory designated for that purpose.

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION

 Periodic safety update reports (PSURs)

The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 
subsequent updates published on the European medicines web-portal.



80

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

 Risk management plan (RMP) 

The marketing authorization holder (MAH) shall perform the required pharmacovigilance activities 
and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing 
authorisation and any agreed subsequent updates of the RMP. 

An updated RMP should be submitted: 
 At the request of the European Medicines Agency; 

 Whenever the risk management system is modified, especially as the result of new 
information being received that may lead to a significant change to the benefit/risk profile or 
as the result of an important (pharmacovigilance or risk minimisation) milestone being 
reached. 



81

ANNEX III

LABELLING AND PACKAGE LEAFLET



82

A. LABELLING



83

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON

Pack of 1, 10 and 50 pre-filled syringe, with or without needle – WITH BLUE BOX

1. NAME OF THE MEDICINAL PRODUCT

Prevenar 13 suspension for injection 
pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed)

2. STATEMENT OF ACTIVE SUBSTANCE(S)

1 dose (0.5 ml) contains 2.2 µg of polysaccharide for serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 
19F, 23F and 4.4 µg for serotype 6B conjugated to CRM197 carrier protein, adsorbed on aluminium 
phosphate. 1 dose (0.5 ml) contains 0.125 mg aluminium. 

3. LIST OF EXCIPIENTS

Sodium chloride, succinic acid, polysorbate 80 and water for injections

4. PHARMACEUTICAL FORM AND CONTENTS

Suspension for injection
1 single-dose (0.5 ml) pre-filled syringe with separate needle
1 single-dose (0.5 ml) pre-filled syringe without needle
10 single-dose (0.5 ml) pre-filled syringes with separate needles
10 single-dose (0.5 ml) pre-filled syringes without needle
50 single-dose (0.5 ml) pre-filled syringes with separate needles
50 single-dose (0.5 ml) pre-filled syringes without needle

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Intramuscular use.
Shake well before use.
Read the package leaflet before use. 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY



84

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator.
Do not freeze.
Prevenar 13 is stable at temperatures up to 25°C for four days. At the end of this period Prevenar 13 
should be used or discarded.

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

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/09/590/002 – pack of 1 with separate needle
EU/1/09/590/001 – pack of 1 without needle
EU/1/09/590/004 – pack of 10 with separate needles
EU/1/09/590/003 – pack of 10 without needle
EU/1/09/590/006 – pack of 50 with separate needles
EU/1/09/590/005 – 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



85

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN



86

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

Pre-filled syringe

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Prevenar 13 suspension for injection
IM

2. METHOD OF ADMINISTRATION

Shake well before use.

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

1 dose (0.5 ml)

6. OTHER



87

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON

1, 5, 10, 25, 50 single dose vials

1. NAME OF THE MEDICINAL PRODUCT

Prevenar 13 suspension for injection in single dose vial
pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed)

2. STATEMENT OF ACTIVE SUBSTANCE(S)

1 dose (0.5 ml) contains 2.2 µg of polysaccharide for serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 
19F, 23F and 4.4 µg for serotype 6B conjugated to CRM197 carrier protein, adsorbed on aluminium 
phosphate. 1 dose (0.5 ml) contains 0.125 mg aluminium. 

3. LIST OF EXCIPIENTS

Sodium chloride, succinic acid, polysorbate 80 and water for injections

4. PHARMACEUTICAL FORM AND CONTENTS

Suspension for injection
1 single-dose (0.5 ml) vial
5 single-dose (0.5 ml) vials
10 single-dose (0.5 ml) vials
25 single-dose (0.5 ml) vials
50 single-dose (0.5 ml) vials

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Intramuscular use.
Shake well before use.
Read the package leaflet before use. 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY



88

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator.
Do not freeze.

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

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/09/590/007 – pack of 1 vial
EU/1/09/590/008 – pack of 5 vials
EU/1/09/590/009 – pack of 10 vials
EU/1/09/590/010 – pack of 25 vials
EU/1/09/590/011 – pack of 50 vials

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Justification for not including Braille accepted



89

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN



90

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

Single Dose Vial Label

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Prevenar 13 suspension for injection in single dose vial
IM

2. METHOD OF ADMINISTRATION

Shake well before use.

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

1 dose (0.5 ml)

6. OTHER



91

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
OUTER CARTON

1, 5, 10, 25, 50 multidose containers

1. NAME OF THE MEDICINAL PRODUCT

Prevenar 13 suspension for injection in multidose container
pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed)

2. STATEMENT OF ACTIVE SUBSTANCE(S)

1 dose (0.5 ml) contains 2.2 µg of polysaccharide for serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 
19F, 23F and 4.4 µg for serotype 6B conjugated to CRM197 carrier protein, adsorbed on aluminium 
phosphate. 1 dose (0.5 ml) contains 0.125 mg aluminium. 

3. LIST OF EXCIPIENTS

Sodium chloride, succinic acid, polysorbate 80, 2-phenoxyethanol and water for injections

4. PHARMACEUTICAL FORM AND CONTENTS

Suspension for injection in multidose container
1 multidose container (4 x 0.5 ml doses)
5 multidose containers (4 x 0.5 ml doses per containers)
10 multidose containers (4 x 0.5 ml doses per containers)
25 multidose containers (4 x 0.5 ml doses per containers)
50 multidose containers (4 x 0.5 ml doses per containers)

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Intramuscular use.
Shake well before use.
Read the package leaflet before use. 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY



92

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator.
Do not freeze.
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

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/09/590/012 – pack of 1 multidose container
EU/1/09/590/013– pack of 5 multidose containers
EU/1/09/590/014– pack of 10 multidose containers
EU/1/09/590/015 – pack of 25 multidose containers
EU/1/09/590/016– pack of 50 multidose containers

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.



93

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN



94

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

Multidose Container Label

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Prevenar 13 suspension for injection in multidose container
IM

2. METHOD OF ADMINISTRATION

Shake well before use.

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

4 x 0.5 ml doses

6. OTHER



95

B. PACKAGE LEAFLET



96

Package Leaflet: Information for the user

Prevenar 13 suspension for injection
pneumococcal polysaccharide conjugate vaccine (13 valent, adsorbed)

Read all of this leaflet carefully before you or 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, pharmacist or nurse.
- This vaccine has been prescribed for you or your child only. Do not pass it on to others.
- If you or your child get any side effects, talk to your doctor, pharmacist or nurse. This includes 

any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Prevenar 13 is and what it is used for
2. What you need to know before you or your child receives Prevenar 13
3. How Prevenar 13 is given
4. Possible side effects
5. How to store Prevenar 13
6. Contents of the pack and other information

1. What Prevenar 13 is and what it is used for

Prevenar 13 is a pneumococcal vaccine given to:

 children from 6 weeks to 17 years to help protect against diseases such as: meningitis 
(inflammation around the brain), sepsis or bacteraemia (bacteria in the blood stream), pneumonia 
(lung infection) and ear infections

 adults aged 18 years and older to help prevent disease such as: pneumonia (lung infection), 
sepsis or bacteraemia (bacteria in the blood stream) and meningitis (inflammation around the 
brain),

caused by 13 types of the bacteria Streptococcus pneumoniae.

Prevenar 13, provides protection against 13 types of Streptococcus pneumoniae bacteria, and replaces 
Prevenar, which provided protection against 7 types.

The vaccine works by helping the body to make its own antibodies, which protect you or your child 
against these diseases.

2. What you need to know before you or your child receives Prevenar 13

Prevenar 13 should not be given

• if you or your child is allergic (hypersensitive) to the active substances or to any of the other 
ingredients in this medicine (listed in section 6) or to any other vaccine that contains diphtheria 
toxoid.

 if you or your child has a severe infection with a high temperature (over 38°C). If this applies to 
you or your child, then the vaccination will be postponed until you or your child is feeling better. 
A minor infection, such as a cold, should not be a problem. However, talk to your doctor, 
pharmacist, or nurse first.



97

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before the vaccination if you or your child:
 has any present or past medical problems after any dose of Prevenar or Prevenar 13 such as an 

allergic reaction or problems with breathing.
 has any bleeding problems or bruises easily.
 has a weakened immune system (such as due to HIV infection), you/she/he may not get the full

benefit from Prevenar 13.
 has experienced seizures as medicines to lower fever may need to be taken before Prevenar 13 is 

given. If your child should become unresponsive or experience seizures (fits) after the 
vaccination, please contact your doctor immediately. See also section 4.

Talk to your doctor, pharmacist, or nurse before the vaccination if your child was born very 
prematurely (at or before 28 weeks of gestation), as longer gaps than normal between breaths may 
occur for 2-3 days after vaccination. See also section 4.

As with any vaccine, Prevenar 13 will not protect all persons who are vaccinated.

Prevenar 13 will only protect against ear infections in children caused by the types of Streptococcus 
pneumoniae for which the vaccine has been developed. It will not protect against other infectious 
agents that can cause ear infections.

Other medicines/vaccines and Prevenar 13

Your doctor may ask you to give your child paracetamol or other medicines that lower fever before
Prevenar 13 is given. This will help to lower some of the side effects of Prevenar 13.

Tell your doctor, pharmacist or nurse if you or your child is taking, has recently taken or might take 
any other medicines, or has recently received any other vaccine.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before receiving this medicine.

Driving and using machines

Prevenar 13 has no or negligible influence on the ability to drive and use machines. However, some of
the effects mentioned under section 4 “Possible side effects” may temporarily affect the ability to 
drive or use machines.

Prevenar 13 contains sodium

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially 
‘sodium-free’.

3. How Prevenar 13 is given

The doctor or nurse will inject the recommended dose (0.5 ml) of the vaccine into your arm or 
your child's arm or leg muscle.



98

Infants aged 6 weeks to 6 months of age

Typically, your child should receive an initial course of three injections of the vaccine followed by a 
booster dose.

 The first injection may be given from the age of six weeks. 
 Each injection will be given at least one month apart. 
 A fourth injection (booster) will be given between 11 and 15 months of age. 
 You will be told when your child should come back for the next injection.

According to official recommendations in your country, an alternative schedule may be used by your 
healthcare provider. Please speak to your doctor, pharmacist, or nurse for more information.

Premature infants 

Your child will receive an initial course of three injections. The first injection may be given as early 
as six weeks of age with at least one month between doses. Between 11 and 15 months of age, your 
child will receive a fourth injection (booster).

Unvaccinated infants, children, and adolescents over 7 months of age

Infants aged 7 to 11 months should receive two injections. Each injection will be given at least one 
month apart. A third injection will be given in the second year of life.

Children aged 12 to 23 months should receive two injections. Each injection will be given at least 
two months apart.

Children aged 2 to 17 years should receive one injection.

Infants, children, and adolescents previously vaccinated with Prevenar

Infants and children who have previously received Prevenar may receive Prevenar 13 to complete the 
course of injections.

For children 1 to 5 years of age previously vaccinated with Prevenar, your doctor or nurse will 
recommend how many injections of Prevenar 13 are required.

Children and adolescents 6 to 17 years of age should receive one injection.

It is important to follow the instructions from the doctor, pharmacist, or nurse so that your child
completes the course of injections.

If you forget to go back at the scheduled time, ask the doctor, pharmacist, or nurse for advice.

Adults

Adults should receive one injection.

Tell your doctor, pharmacist or nurse if you have been given a pneumococcal vaccine before.

If you have any further questions on the use of Prevenar 13, ask your doctor, pharmacist, or nurse.



99

Special Populations

Individuals considered to be at a higher risk of pneumococcal infection (such as those with sickle cell 
disease or HIV infection), including those previously vaccinated with the 23-valent pneumococcal 
polysaccharide vaccine, may receive at least one dose of Prevenar 13.

Individuals with a blood-forming stem cell transplant may receive three injections, with the first given 
at 3 to 6 months after the transplant and with an interval of at least 1 month between doses. A fourth 
injection (booster) is recommended 6 months after the third injection.

4. Possible side effects

Like all vaccines, Prevenar 13 can cause side effects, although not everybody gets them.

The following side effects include those reported for Prevenar 13 in infants and children 
(6 weeks to 5 years of age):

The most common side effects (these may occur with more than 1 in 10 doses of the vaccine) are:

 Decreased appetite
 Fever; irritability; pain, tenderness, redness, swelling or hardness at the vaccination-site; 

drowsiness; restless sleep
 Redness, hardness, swelling at the vaccination-site of 2.5 cm -7.0 cm (after the booster dose and 

in older children [aged 2 to 5 years])

Common side effects (these may occur with up to 1 in 10 doses of the vaccine) are:

 Vomiting; diarrhoea 
 Fever of more than 39°C; tenderness at the vaccination-site interfering with movement, redness, 

hardness, swelling at the vaccination-site of 2.5 cm -7.0 cm (after the initial course of injections)
 Rash 

Uncommon side effects (these may occur with up to 1 in 100 doses of the vaccine) are:

 Seizures (or fits), including those caused by a high temperature
 Hives (urticaria or urticaria-like rash) 
 Redness, swelling, or hardness at the vaccination-site of more than 7 cm; crying

Rare side effects (these may occur with up to 1 in 1,000 doses of the vaccine) are:

 Collapse or shock-like state (hypotonic-hyporesponsive episode)
 Allergic (hypersensitivity) reaction, including swelling of the face and/or lips, difficulty in 

breathing

The following side effects include those reported for Prevenar 13 in children and adolescents 
(6 to 17 years of age):

The most common side effects (these may occur with more than 1 in 10 doses of the vaccine) are:

 Decreased appetite
 Irritability; pain, tenderness, redness, swelling or hardness at the vaccination-site; drowsiness; 

restless sleep; tenderness at the vaccination-site interfering with movement



100

Common side effects (these may occur with up to 1 in 10 doses of the vaccine) are:

 Headaches
 Vomiting; diarrhoea
 Rash; hives (urticaria or urticaria-like rash)
 Fever

Children and adolescents with either HIV infection, sickle cell disease or a blood-forming stem cell 
transplant had similar side effects however the frequencies of headaches, vomiting, diarrhoea, fever, 
fatigue, joint and muscle pain were very common.

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.

The following side effects include those reported for Prevenar 13 in adults:

The most common side effects (these may occur with more than 1 in 10 doses of the vaccine) are:

 Decreased appetite; headaches; diarrhoea; vomiting (for those 18 to 49 years of age)
 Chills; tiredness; rash; pain, redness, swelling hardness or tenderness at the vaccination-site, 

interfering with arm movement (severe pain or tenderness at vaccination-site for those 18-39 years 
of age and severe limitation of arm movements for those 18 to 39 years of age)

 Worsening or new pain in your joints, worsening or new pain in your muscles
 Fever (for those 18 to 29 years of age)

Common side effects (these may occur with up to 1 in 10 doses of the vaccine) are:

 Vomiting (for those 50 years and older); fever (for those 30 years and older)

Uncommon side effects (these may occur with up to 1 in 100 doses of the vaccine) are:

 Nausea
 Allergic (hypersensitivity) reaction, including swelling of the face and/or lips, difficulty in 

breathing
 Enlarged lymph nodes or glands (lymphadenopathy) near the vaccination-site, such as under the 

arm

Adults with HIV infection had similar side effects however the frequencies were very common for 
fever, vomiting and common for nausea.

Adults with a blood-forming stem cell transplant had similar side effects however the frequencies 
were very common for fever and vomiting.

The following additional side effects have been seen with Prevenar 13 in postmarketing 
experience 

 Severe allergic reaction including shock (cardiovascular collapse); angioedema (swelling of lips, 
face or throat)

 Hives (urticaria), redness and irritation (dermatitis) and itching (pruritus) at the vaccination-site; 
flushing

 Enlarged lymph nodes or glands (lymphadenopathy) near the vaccination-site, such as under the 
arm or in the groin

 A rash causing itchy red blotches (erythema multiforme) 



101

Reporting of side effects

If you or your child get any side effects, talk to your doctor, pharmacist, or nurse. This includes any 
possible side effects not listed in this leaflet. You can also report side effects directly via the national 
reporting system listed in Appendix V. By reporting side effects you can help provide more 
information on the safety of this medicine.

5. How to store Prevenar 13 

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 and label after EXP. The 
expiry date refers to the last day of that month.

Store in a refrigerator (2C – 8C).

Do not freeze.
Prevenar 13 is stable at temperatures up to 25°C for four days. At the end of this period Prevenar 13 
should be used or discarded. These data are intended to guide health care professionals in case of 
temporary temperature excursions.

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 Prevenar 13 contains

The active substances are polysaccharide CRM197 conjugates consisting of:
 2.2 µg of polysaccharide for serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F and 23F
 4.4 µg of polysaccharide for serotype 6B

1 dose (0.5 ml) contains approximately 32 µg CRM197 carrier protein, adsorbed on aluminium 
phosphate (0.125 mg aluminium).

The other ingredients are sodium chloride, succinic acid, polysorbate 80 and water for injections.

What Prevenar 13 looks like and contents of the pack

The vaccine is a white suspension for injection, provided in a single-dose, pre-filled syringe (0.5 ml). 
Pack sizes of 1, 10 and 50, with or without needle. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder: 
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

Manufacturer responsible for batch release:
Pfizer Manufacturing Belgium N.V.
Rijksweg 12
B-2870 Puurs
Belgium



102

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder:

België/Belgique/Belgien
Luxembourg/Luxemburg
Pfizer S.A./N.V.
Tél/Tel: + 32 (0)2 554 62 11

Lietuva
Pfizer Luxembourg SARL filialas Lietuvoje
Tel. + 370 52 51 4000

България
Пфайзер Люксембург САРЛ, Клон 
България
Teл: +359 2 970 4333

Magyarország
Pfizer Kft
Tel: +36 1 488 3700

Česká Republika
Pfizer, spol. s r.o.
Tel: +420 283 004 111

Malta
Vivian Corporation Ltd.
Tel: + 35621 344610

Danmark
Pfizer ApS
Tlf: + 45 44 201 100

Nederland
Pfizer BV
Tel: +31 (0)10 406 43 01

Deutschland
Pfizer Pharma GmbH
Tel: + 49 (0)30 550055-51000

Norge
Pfizer AS
Tlf: +47 67 52 61 00

Eesti
Pfizer Luxembourg SARL Eesti filiaal
Tel: +372 666 7500

Österreich
Pfizer Corporation Austria Ges.m.b.H
Tel: + 43 (0)1 521 15-0

Ελλάδα
Pfizer Ελλάς A.E.
Τηλ.: +30 210 6785 800

Polska
Pfizer Polska Sp. z o.o.
Tel.: +48 22 335 61 00

España
Pfizer, S.L.
Télf:+34914909900

Portugal
Laboratórios Pfizer, Lda.
Tel: +351 21 423 5500

France
Pfizer
Tél +33 1 58 07 34 40

România
Pfizer Romania S.R.L
Tel: +40 (0) 21 207 28 00

Hrvatska 
Pfizer Croatia d.o.o.
Tel: + 385 1 3908 777

Slovenija
Pfizer Luxembourg SARL
Pfizer, podružnica za svetovanje s področja
farmacevtske dejavnosti, Ljubljana
Tel.: + 386 (0) 1 52 11 400

Ireland
Pfizer Healthcare Ireland
Tel: 1800 633 363 (toll free)
+44 (0)1304 616161

Slovenská republika
Pfizer Luxembourg SARL,
organizačná zložka
Tel: + 421 2 3355 5500



103

Ísland
Icepharma hf
Simi: + 354 540 8000

Suomi/Finland
Pfizer Oy
Puh/Tel: +358 (0)9 430 040

Italia
Pfizer S.r.l. 
Tel: +39 06 33 18 21

Sverige
Pfizer AB
Tel: +46 (0)8 550 520 00

Kύπρος
Pfizer Ελλάς Α.Ε. (Cyprus Branch) 
Tηλ: +357 22 817690

United Kingdom
Pfizer Limited
Tel: +44 (0) 1304 616161

Latvija
Pfizer Luxembourg SARL filiāle Latvijā
Tel.: + 371 670 35 775

This leaflet was last revised in

Other sources of information

Detailed information on this product is available on the European Medicines Agency website:
http://www.ema.europa.eu.
----------------------------------------------------------------------------------------------------------------------------
The following information is intended for healthcare professionals only:

During storage, a white deposit and clear supernatant may be observed. This does not constitute a sign 
of deterioration.

Inspect visually for any foreign particulate matter and/or abnormal physical appearance; do not use if 
either are found.

Prior to expelling air from the syringe, shake well to obtain a homogeneous white suspension.

Administer the entire dose.

Prevenar 13 is for intramuscular use only. Do not administer intravascularly. 

Prevenar 13 must not be mixed with any other vaccines in the same syringe.

Prevenar 13 can be given at the same time as other childhood vaccines; in this case, different 
vaccination sites should be used. 

Prevenar 13 may be given to adults aged 50 years and older at the same time as the trivalent or 
quadrivalent inactivated influenza vaccine.

Any unused product or waste material should be disposed of in accordance with local requirements.



104

Package Leaflet: Information for the user

Prevenar 13 suspension for injection in single dose vial
pneumococcal polysaccharide conjugate vaccine (13 valent, adsorbed)

Read all of this leaflet carefully before you or 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, pharmacist or nurse.
- This vaccine has been prescribed for you or your child only. Do not pass it on to others.
- If you or your child get any side effects, talk to your doctor, pharmacist or nurse. This includes 

any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Prevenar 13 is and what it is used for
2. What you need to know before you or your child receives Prevenar 13
3. How Prevenar 13 is given
4. Possible side effects
5. How to store Prevenar 13
6. Contents of the pack and other information

1. What Prevenar 13 is and what it is used for

Prevenar 13 is a pneumococcal vaccine given to:

 children from 6 weeks to 17 years to help protect against diseases such as: meningitis 
(inflammation around the brain), sepsis or bacteraemia (bacteria in the blood stream), pneumonia 
(lung infection) and ear infections

 adults aged 18 years and older to help prevent disease such as: pneumonia (lung infection),
sepsis or bacteraemia (bacteria in the blood stream) and meningitis (inflammation around the 
brain),

caused by 13 types of the bacteria Streptococcus pneumoniae.

Prevenar 13, provides protection against 13 types of Streptococcus pneumoniae bacteria, and replaces 
Prevenar, which provided protection against 7 types.

The vaccine works by helping the body to make its own antibodies, which protect you or your child 
against these diseases.

2. What you need to know before you or your child receives Prevenar 13

Prevenar 13 should not be given

• if you or your child is allergic (hypersensitive) to the active substances or to any of the other 
ingredients in this medicine (listed in section 6) or to any other vaccine that contains diphtheria 
toxoid.

 if you or your child has a severe infection with a high temperature (over 38°C). If this applies to 
you or your child, then the vaccination will be postponed until you or your child is feeling better. 
A minor infection, such as a cold, should not be a problem. However, talk to your doctor, 
pharmacist, or nurse first.



105

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before the vaccination if you or your child:
 has any present or past medical problems after any dose of Prevenar or Prevenar 13 such as an 

allergic reaction or problems with breathing.
 has any bleeding problems or bruises easily.
 has a weakened immune system (such as due to HIV infection), you/she/he may not get the full 

benefit from Prevenar 13.
 has experienced seizures as medicines to lower fever may need to be taken before Prevenar 13 is 

given. If your child should become unresponsive or experience seizures (fits) after the 
vaccination, please contact your doctor immediately. See also section 4.

Talk to your doctor, pharmacist, or nurse before the vaccination if your child was born very 
prematurely (at or before 28 weeks of gestation), as longer gaps than normal between breaths may 
occur for 2-3 days after vaccination. See also section 4.

As with any vaccine, Prevenar 13 will not protect all persons who are vaccinated.

Prevenar 13 will only protect against ear infections in children caused by the types of Streptococcus 
pneumoniae for which the vaccine has been developed. It will not protect against other infectious 
agents that can cause ear infections.

Other medicines/vaccines and Prevenar 13

Your doctor may ask you to give your child paracetamol or other medicines that lower fever before
Prevenar 13 is given. This will help to lower some of the side effects of Prevenar 13.

Tell your doctor, pharmacist or nurse if you or your child is taking, has recently taken or might take 
any other medicines, or has recently received any other vaccine.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before receiving this medicine.

Driving and using machines

Prevenar 13 has no or negligible influence on the ability to drive and use machines. However, some of 
the effects mentioned under section 4 “Possible side effects” may temporarily affect the ability to
drive or use machines.

Prevenar 13 contains sodium

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially 
‘sodium-free’.

3. How Prevenar 13 is given

The doctor or nurse will inject the recommended dose (0.5 ml) of the vaccine into your arm or 
your child's arm or leg muscle.



106

Infants aged 6 weeks to 6 months of age

Typically, your child should receive an initial course of three injections of the vaccine followed by a 
booster dose.

 The first injection may be given from the age of six weeks. 
 Each injection will be given at least one month apart. 
 A fourth injection (booster) will be given between 11 and 15 months of age. 
 You will be told when your child should come back for the next injection.

According to official recommendations in your country, an alternative schedule may be used by your 
healthcare provider. Please speak to your doctor, pharmacist, or nurse for more information.

Premature infants 

Your child will receive an initial course of three injections. The first injection may be given as early 
as six weeks of age with at least one month between doses. Between 11 and 15 months of age, your 
child will receive a fourth injection (booster).

Unvaccinated infants, children, and adolescents over 7 months of age

Infants aged 7 to 11 months should receive two injections. Each injection will be given at least one 
month apart. A third injection will be given in the second year of life.

Children aged 12 to 23 months should receive two injections. Each injection will be given at least 
two months apart.

Children aged 2 to 17 years should receive one injection.

Infants, children, and adolescents previously vaccinated with Prevenar

Infants and children who have previously received Prevenar may receive Prevenar 13 to complete the 
course of injections.

For children 1 to 5 years of age previously vaccinated with Prevenar, your doctor or nurse will 
recommend how many injections of Prevenar 13 are required.

Children and adolescents 6 to 17 years of age should receive one injection.

It is important to follow the instructions from the doctor, pharmacist, or nurse so that your child 
completes the course of injections.

If you forget to go back at the scheduled time, ask the doctor, pharmacist, or nurse for advice.

Adults

Adults should receive one injection.

Tell your doctor, pharmacist or nurse if you have been given a pneumococcal vaccine before.

If you have any further questions on the use of Prevenar 13, ask your doctor, pharmacist, or nurse.



107

Special Populations

Individuals considered to be at a higher risk of pneumococcal infection (such as those with sickle cell 
disease or HIV infection), including those previously vaccinated with the 23-valent pneumococcal 
polysaccharide vaccine, may receive at least one dose of Prevenar 13.

Individuals with a blood-forming stem cell transplant may receive three injections, with the first given 
at 3 to 6 months after the transplant and with an interval of at least 1 month between doses. A fourth 
injection (booster) is recommended 6 months after the third injection.

4. Possible side effects

Like all vaccines, Prevenar 13 can cause side effects, although not everybody gets them.

The following side effects include those reported for Prevenar 13 in infants and children 
(6 weeks to 5 years of age):

The most common side effects (these may occur with more than 1 in 10 doses of the vaccine) are:

 Decreased appetite
 Fever; irritability; pain, tenderness, redness, swelling or hardness at the vaccination-site; 

drowsiness; restless sleep
 Redness, hardness, swelling at the vaccination-site of 2.5 cm -7.0 cm (after the booster dose and 

in older children [aged 2 to 5 years])

Common side effects (these may occur with up to 1 in 10 doses of the vaccine) are:

 Vomiting; diarrhoea
 Fever of more than 39°C; tenderness at the vaccination-site interfering with movement, redness, 

hardness, swelling at the vaccination-site of 2.5 cm -7.0 cm (after the initial course of injections)
 Rash

Uncommon side effects (these may occur with up to 1 in 100 doses of the vaccine) are:

 Seizures (or fits), including those caused by a high temperature
 Hives (urticaria or urticaria-like rash) 
 Redness, swelling, or hardness at the vaccination-site of more than 7 cm; crying

Rare side effects (these may occur with up to 1 in 1,000 doses of the vaccine) are:

 Collapse or shock-like state (hypotonic-hyporesponsive episode)
 Allergic (hypersensitivity) reaction, including swelling of the face and/or lips, difficulty in 

breathing

The following side effects include those reported for Prevenar 13 in children and adolescents 
(6 to 17 years of age):

The most common side effects (these may occur with more than 1 in 10 doses of the vaccine) are:

 Decreased appetite
 Irritability; pain, tenderness, redness, swelling or hardness at the vaccination-site; drowsiness; 

restless sleep; tenderness at the vaccination-site interfering with movement



108

Common side effects (these may occur with up to 1 in 10 doses of the vaccine) are:

 Headaches
 Vomiting; diarrhoea
 Rash; hives (urticaria or urticaria-like rash)
 Fever

Children and adolescents with either HIV infection, sickle cell disease or a blood-forming stem cell 
transplant had similar side effects however the frequencies of headaches, vomiting, diarrhoea, fever, 
fatigue, joint and muscle pain were very common.

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.

The following side effects include those reported for Prevenar 13 in adults:

The most common side effects (these may occur with more than 1 in 10 doses of the vaccine) are:

 Decreased appetite; headaches; diarrhoea; vomiting (for those 18 to 49 years of age)
 Chills; tiredness; rash; pain, redness, swelling hardness or tenderness at the vaccination-site, 

interfering with arm movement (severe pain or tenderness at vaccination-site for those 18-39 years 
of age and severe limitation of arm movements for those 18 to 39 years of age)

 Worsening or new pain in your joints, worsening or new pain in your muscles
 Fever (for those 18 to 29 years of age)

Common side effects (these may occur with up to 1 in 10 doses of the vaccine) are:

 Vomiting (for those 50 years and older); fever (for those 30 years and older)

Uncommon side effects (these may occur with up to 1 in 100 doses of the vaccine) are:

 Nausea
 Allergic (hypersensitivity) reaction, including swelling of the face and/or lips, difficulty in 

breathing
 Enlarged lymph nodes or glands (lymphadenopathy) near the vaccination-site, such as under the 

arm

Adults with HIV infection had similar side effects however the frequencies were very common for
fever, vomiting and common for nausea.

Adults with a blood-forming stem cell transplant had similar side effects however the frequencies 
were very common for fever and vomiting. 

The following additional side effects have been seen with Prevenar 13 in postmarketing 
experience 

 Severe allergic reaction including shock (cardiovascular collapse); angioedema (swelling of lips,
face or throat)

 Hives (urticaria), redness and irritation (dermatitis) and itching (pruritus) at the vaccination-site; 
flushing

 Enlarged lymph nodes or glands (lymphadenopathy) near the vaccination-site, such as under the 
arm or in the groin

 A rash causing itchy red blotches (erythema multiforme) 



109

Reporting of side effects

If you or your child get any side effects, talk to your doctor, pharmacist, or nurse. This includes any 
possible side effects not listed in this leaflet. You can also report side effects directly via the national 
reporting system listed in Appendix V. By reporting side effects you can help provide more 
information on the safety of this medicine.

5. How to store Prevenar 13 

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 and label after EXP. The 
expiry date refers to the last day of that month.

Store in a refrigerator (2C – 8C).

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 Prevenar 13 contains

The active substances are polysaccharide CRM197 conjugates consisting of:
 2.2 µg of polysaccharide for serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F and 23F
 4.4 µg of polysaccharide for serotype 6B

1 dose (0.5 ml) contains approximately 32 µg CRM197 carrier protein, adsorbed on aluminium 
phosphate (0.125 mg aluminium).

The other ingredients are sodium chloride, succinic acid, polysorbate 80 and water for injections.

What Prevenar 13 looks like and contents of the pack

The vaccine is a white suspension for injection, provided in a single-dose vial (0.5 ml). Pack sizes of 
1, 5, 10, 25 and 50 vials. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder: 
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

Manufacturer responsible for batch release:
Pfizer Manufacturing Belgium N.V.
Rijksweg 12
B-2870 Puurs
Belgium



110

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder:

België/Belgique/Belgien
Luxembourg/Luxemburg
Pfizer S.A./N.V.
Tél/Tel: + 32 (0)2 554 62 11

Lietuva
Pfizer Luxembourg SARL filialas Lietuvoje
Tel. + 370 52 51 4000

България
Пфайзер Люксембург САРЛ, Клон 
България
Teл: +359 2 970 4333

Magyarország
Pfizer Kft
Tel: +36 1 488 3700

Česká Republika
Pfizer, spol. s r.o. 
Tel: +420 283 004 111

Malta
Vivian Corporation Ltd.
Tel: + 35621 344610

Danmark
Pfizer ApS
Tlf: + 45 44 201 100

Nederland
Pfizer BV
Tel: +31 (0)10 406 43 01

Deutschland
Pfizer Pharma GmbH
Tel: + 49 (0)30 550055-51000

Norge
Pfizer AS
Tlf: +47 67 52 61 00

Eesti
Pfizer Luxembourg SARL Eesti filiaal
Tel: +372 666 7500

Österreich
Pfizer Corporation Austria Ges.m.b.H
Tel: + 43 (0)1 521 15-0

Ελλάδα
Pfizer Ελλάς A.E.
Τηλ.: +30 210 6785 800

Polska
Pfizer Polska Sp. z o.o.
Tel.: +48 22 335 61 00

España
Pfizer, S.L.
Télf:+34914909900

Portugal
Laboratórios Pfizer, Lda.
Tel: +351 21 423 5500

France
Pfizer
Tél +33 1 58 07 34 40

România
Pfizer Romania S.R.L
Tel: +40 (0) 21 207 28 00

Hrvatska 
Pfizer Croatia d.o.o.
Tel: + 385 1 3908 777

Slovenija
Pfizer Luxembourg SARL
Pfizer, podružnica za svetovanje s področja
farmacevtske dejavnosti, Ljubljana
Tel.: + 386 (0) 1 52 11 400

Ireland
Pfizer Healthcare Ireland
Tel: 1800 633 363 (toll free)
+44 (0)1304 616161

Slovenská republika
Pfizer Luxembourg SARL,
organizačná zložka
Tel: + 421 2 3355 5500



111

Ísland
Icepharma hf
Simi: + 354 540 8000

Suomi/Finland
Pfizer Oy
Puh/Tel: +358 (0)9 430 040

Italia
Pfizer S.r.l. 
Tel: +39 06 33 18 21

Sverige
Pfizer AB
Tel: +46 (0)8 550 520 00

Kύπρος
Pfizer Ελλάς Α.Ε. (Cyprus Branch) 
Tηλ: +357 22 817690

United Kingdom
Pfizer Limited
Tel: +44 (0) 1304 616161

Latvija
Pfizer Luxembourg SARL filiāle Latvijā
Tel.: + 371 670 35 775

This leaflet was last revised in

Other sources of information

Detailed information on this product is available on the European Medicines Agency website:
http://www.ema.europa.eu.
----------------------------------------------------------------------------------------------------------------------------
The following information is intended for healthcare professionals only:

During storage, a white deposit and clear supernatant may be observed. This does not constitute a sign 
of deterioration.

Inspect visually for any foreign particulate matter and/or abnormal physical appearance; do not use if 
either are found.

Shake well prior to use to obtain a homogeneous white suspension.

Administer the entire dose.

Prevenar 13 is for intramuscular use only. Do not administer intravascularly. 

Prevenar 13 must not be mixed with any other vaccines in the same syringe.

Prevenar 13 can be given at the same time as other childhood vaccines; in this case, different 
vaccination sites should be used. 

Prevenar 13 may be given to adults aged 50 years and older at the same time as the trivalent or 
quadrivalent inactivated influenza vaccine.

Any unused product or waste material should be disposed of in accordance with local requirements.



112

Package Leaflet: Information for the user

Prevenar 13 suspension for injection in multidose container
pneumococcal polysaccharide conjugate vaccine (13 valent, adsorbed)

Read all of this leaflet carefully before you or 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, pharmacist or nurse.
- This vaccine has been prescribed for you or your child only. Do not pass it on to others.
- If you or your child get any side effects, talk to your doctor, pharmacist or nurse. This includes 

any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Prevenar 13 is and what it is used for
2. What you need to know before you or your child receives Prevenar 13
3. How Prevenar 13 is given
4. Possible side effects
5. How to store Prevenar 13
6. Contents of the pack and other information

1. What Prevenar 13 is and what it is used for

Prevenar 13 is a pneumococcal vaccine given to:

 children from 6 weeks to 17 years to help protect against diseases such as: meningitis 
(inflammation around the brain), sepsis or bacteraemia (bacteria in the blood stream), pneumonia 
(lung infection) and ear infections

 adults aged 18 years and older to help prevent disease such as: pneumonia (lung infection),
sepsis or bacteraemia (bacteria in the blood stream) and meningitis (inflammation around the 
brain),

caused by 13 types of the bacteria Streptococcus pneumoniae.

Prevenar 13, provides protection against 13 types of Streptococcus pneumoniae bacteria, and replaces 
Prevenar, which provided protection against 7 types.

The vaccine works by helping the body to make its own antibodies, which protect you or your child 
against these diseases.

2. What you need to know before you or your child receives Prevenar 13

Prevenar 13 should not be given

• if you or your child is allergic (hypersensitive) to the active substances or to any of the other 
ingredients in this medicine (listed in section 6) or to any other vaccine that contains diphtheria 
toxoid.

 if you or your child has a severe infection with a high temperature (over 38°C). If this applies to 
you or your child, then the vaccination will be postponed until you or your child is feeling better. 
A minor infection, such as a cold, should not be a problem. However, talk to your doctor, 
pharmacist, or nurse first.



113

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before the vaccination if you or your child:
 has any present or past medical problems after any dose of Prevenar or Prevenar 13 such as an 

allergic reaction or problems with breathing.
 has any bleeding problems or bruises easily.
 has a weakened immune system (such as due to HIV infection), you/she/he may not get the full 

benefit from Prevenar 13.
 has experienced seizures as medicines to lower fever may need to be taken before Prevenar 13 is 

given. If your child should become unresponsive or experience seizures (fits) after the 
vaccination, please contact your doctor immediately. See also section 4.

Talk to your doctor, pharmacist, or nurse before the vaccination if your child was born very 
prematurely (at or before 28 weeks of gestation), as longer gaps than normal between breaths may 
occur for 2-3 days after vaccination. See also section 4.

As with any vaccine, Prevenar 13 will not protect all persons who are vaccinated.

Prevenar 13 will only protect against ear infections in children caused by the types of Streptococcus 
pneumoniae for which the vaccine has been developed. It will not protect against other infectious 
agents that can cause ear infections.

Other medicines/vaccines and Prevenar 13

Your doctor may ask you to give your child paracetamol or other medicines that lower fever before
Prevenar 13 is given. This will help to lower some of the side effects of Prevenar 13.

Tell your doctor, pharmacist or nurse if you or your child is taking, has recently taken or might take 
any other medicines, or has recently received any other vaccine.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before receiving this medicine.

Driving and using machines

Prevenar 13 has no or negligible influence on the ability to drive and use machines. However, some of 
the effects mentioned under section 4 “Possible side effects” may temporarily affect the ability to
drive or use machines.

Prevenar 13 contains sodium

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially 
‘sodium-free’.

3. How Prevenar 13 is given

The doctor or nurse will inject the recommended dose (0.5 ml) of the vaccine into your arm or 
your child's arm or leg muscle.



114

Infants aged 6 weeks to 6 months of age

Typically, your child should receive an initial course of three injections of the vaccine followed by a 
booster dose.

 The first injection may be given from the age of six weeks. 
 Each injection will be given at least one month apart. 
 A fourth injection (booster) will be given between 11 and 15 months of age. 
 You will be told when your child should come back for the next injection.

According to official recommendations in your country, an alternative schedule may be used by your 
healthcare provider. Please speak to your doctor, pharmacist, or nurse for more information.

Premature infants 

Your child will receive an initial course of three injections. The first injection may be given as early 
as six weeks of age with at least one month between doses. Between 11 and 15 months of age, your 
child will receive a fourth injection (booster).

Unvaccinated infants, children, and adolescents over 7 months of age

Infants aged 7 to 11 months should receive two injections. Each injection will be given at least one 
month apart. A third injection will be given in the second year of life.

Children aged 12 to 23 months should receive two injections. Each injection will be given at least 
two months apart.

Children aged 2 to 17 years should receive one injection.

Infants, children, and adolescents previously vaccinated with Prevenar

Infants and children who have previously received Prevenar may receive Prevenar 13 to complete the 
course of injections.

For children 1 to 5 years of age previously vaccinated with Prevenar, your doctor or nurse will 
recommend how many injections of Prevenar 13 are required.

Children and adolescents 6 to 17 years of age should receive one injection.

It is important to follow the instructions from the doctor, pharmacist, or nurse so that your child 
completes the course of injections.

If you forget to go back at the scheduled time, ask the doctor, pharmacist, or nurse for advice.

Adults

Adults should receive one injection.

Tell your doctor, pharmacist or nurse if you have been given a pneumococcal vaccine before.

If you have any further questions on the use of Prevenar 13, ask your doctor, pharmacist, or nurse.



115

Special Populations

Individuals considered to be at a higher risk of pneumococcal infection (such as those with sickle cell 
disease or HIV infection), including those previously vaccinated with the 23-valent pneumococcal 
polysaccharide vaccine, may receive at least one dose of Prevenar 13.

Individuals with a blood-forming stem cell transplant may receive three injections, with the first given 
at 3 to 6 months after the transplant and with an interval of at least 1 month between doses. A fourth 
injection (booster) is recommended 6 months after the third injection.

4. Possible side effects

Like all vaccines, Prevenar 13 can cause side effects, although not everybody gets them.

The following side effects include those reported for Prevenar 13 in infants and children 
(6 weeks to 5 years of age):

The most common side effects (these may occur with more than 1 in 10 doses of the vaccine) are:

 Decreased appetite
 Fever; irritability; pain, tenderness, redness, swelling or hardness at the vaccination-site; 

drowsiness; restless sleep
 Redness, hardness, swelling at the vaccination-site of 2.5 cm -7.0 cm (after the booster dose and 

in older children [aged 2 to 5 years])

Common side effects (these may occur with up to 1 in 10 doses of the vaccine) are:

 Vomiting; diarrhoea
 Fever of more than 39°C; tenderness at the vaccination-site interfering with movement, redness, 

hardness, swelling at the vaccination-site of 2.5 cm -7.0 cm (after the initial course of injections)
 Rash

Uncommon side effects (these may occur with up to 1 in 100 doses of the vaccine) are:

 Seizures (or fits), including those caused by a high temperature
 Hives (urticaria or urticaria-like rash)
 Redness, swelling, or hardness at the vaccination-site of more than 7 cm; crying

Rare side effects (these may occur with up to 1 in 1,000 doses of the vaccine) are:

 Collapse or shock-like state (hypotonic-hyporesponsive episode)
 Allergic (hypersensitivity) reaction, including swelling of the face and/or lips, difficulty in 

breathing

The following side effects include those reported for Prevenar 13 in children and adolescents 
(6 to 17 years of age):

The most common side effects (these may occur with more than 1 in 10 doses of the vaccine) are:

 Decreased appetite
 Irritability; pain, tenderness, redness, swelling or hardness at the vaccination-site; drowsiness; 

restless sleep; tenderness at the vaccination-site interfering with movement



116

Common side effects (these may occur with up to 1 in 10 doses of the vaccine) are:

 Headaches
 Vomiting; diarrhoea
 Rash; hives (urticaria or urticaria-like rash)
 Fever

Children and adolescents with either HIV infection, sickle cell disease or a blood-forming stem cell 
transplant had similar side effects however the frequencies of headaches, vomiting, diarrhoea, fever, 
fatigue, joint and muscle pain were very common.

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.

The following side effects include those reported for Prevenar 13 in adults:

The most common side effects (these may occur with more than 1 in 10 doses of the vaccine) are:

 Decreased appetite; headaches; diarrhoea; vomiting (for those 18 to 49 years of age)
 Chills; tiredness; rash; pain, redness, swelling hardness or tenderness at the vaccination-site, 

interfering with arm movement (severe pain or tenderness at vaccination-site for those 18-39 years 
of age and severe limitation of arm movements for those 18 to 39 years of age)

 Worsening or new pain in your joints, worsening or new pain in your muscles
 Fever (for those 18 to 29 years of age)

Common side effects (these may occur with up to 1 in 10 doses of the vaccine) are:

 Vomiting (for those 50 years and older); fever (for those 30 years and older)

Uncommon side effects (these may occur with up to 1 in 100 doses of the vaccine) are:

 Nausea
 Allergic (hypersensitivity) reaction, including swelling of the face and/or lips, difficulty in 

breathing
 Enlarged lymph nodes or glands (lymphadenopathy) near the vaccination-site, such as under the

arm

Adults with HIV infection had similar side effects however the frequencies were very common for
fever, vomiting and common for nausea.

Adults with a blood-forming stem cell transplant had similar side effects however the frequencies 
were very common for fever and vomiting. 

The following additional side effects have been seen with Prevenar 13 in postmarketing 
experience 

 Severe allergic reaction including shock (cardiovascular collapse); angioedema (swelling of lips, 
face or throat)

 Hives (urticaria), redness and irritation (dermatitis) and itching (pruritus) at the vaccination-site; 
flushing

 Enlarged lymph nodes or glands (lymphadenopathy) near the vaccination-site, such as under the 
arm or in the groin

 A rash causing itchy red blotches (erythema multiforme) 



117

Reporting of side effects

If you or your child get any side effects, talk to your doctor, pharmacist, or nurse. This includes any 
possible side effects not listed in this leaflet. You can also report side effects directly via the national 
reporting system listed in Appendix V. By reporting side effects you can help provide more 
information on the safety of this medicine.

5. How to store Prevenar 13 

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 and label after EXP. The 
expiry date refers to the last day of that month.

Store in a refrigerator (2C – 8C).
Do not freeze.
After first use, the product may be stored in a refrigerator for a maximum of 28 days.

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 Prevenar 13 contains

The active substances are polysaccharide CRM197 conjugates consisting of:
 2.2 µg of polysaccharide for serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F and 23F
 4.4 µg of polysaccharide for serotype 6B

1 dose (0.5 ml) contains approximately 32 µg CRM197 carrier protein, adsorbed on aluminium 
phosphate (0.125 mg aluminium).

The other ingredients are sodium chloride, succinic acid, polysorbate 80, 2- phenoxyethanol and water 
for injections.

What Prevenar 13 looks like and contents of the pack

The vaccine is a white suspension for injection, provided in a multidose container (4 x 0.5 ml doses). 
Pack sizes of 1, 5, 10, 25 and 50 vials. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder: 
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

Manufacturer responsible for batch release:
Pfizer Manufacturing Belgium N.V.
Rijksweg 12
B-2870 Puurs
Belgium



118

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder:

België/Belgique/Belgien
Luxembourg/Luxemburg
Pfizer S.A./N.V.
Tél/Tel: + 32 (0)2 554 62 11

Lietuva
Pfizer Luxembourg SARL filialas Lietuvoje
Tel. + 370 52 51 4000

България
Пфайзер Люксембург САРЛ, Клон 
България
Teл: +359 2 970 4333

Magyarország
Pfizer Kft
Tel: +36 1 488 3700

Česká Republika
Pfizer, spol. s r.o.
Tel: +420 283 004 111

Malta
Vivian Corporation Ltd.
Tel: + 35621 344610

Danmark
Pfizer ApS
Tlf: + 45 44 201 100

Nederland
Pfizer BV
Tel: +31 (0)10 406 43 01

Deutschland
Pfizer Pharma GmbH
Tel: + 49 (0)30 550055-51000

Norge
Pfizer AS
Tlf: +47 67 52 61 00

Eesti
Pfizer Luxembourg SARL Eesti filiaal
Tel: +372 666 7500

Österreich
Pfizer Corporation Austria Ges.m.b.H
Tel: + 43 (0)1 521 15-0

Ελλάδα
Pfizer Ελλάς A.E.
Τηλ.: +30 210 6785 800

Polska
Pfizer Polska Sp. z o.o.
Tel.: +48 22 335 61 00

España
Pfizer, S.L.
Télf:+34914909900

Portugal
Laboratórios Pfizer, Lda.
Tel: +351 21 423 5500

France
Pfizer
Tél +33 1 58 07 34 40

România
Pfizer Romania S.R.L
Tel: +40 (0) 21 207 28 00

Hrvatska 
Pfizer Croatia d.o.o.
Tel: + 385 1 3908 777

Slovenija
Pfizer Luxembourg SARL
Pfizer, podružnica za svetovanje s področja
farmacevtske dejavnosti, Ljubljana
Tel.: + 386 (0) 1 52 11 400

Ireland
Pfizer Healthcare Ireland
Tel: 1800 633 363 (toll free)
+44 (0)1304 616161

Slovenská republika
Pfizer Luxembourg SARL,
organizačná zložka
Tel: + 421 2 3355 5500



119

Ísland
Icepharma hf
Simi: + 354 540 8000

Suomi/Finland
Pfizer Oy
Puh/Tel: +358 (0)9 430 040

Italia
Pfizer S.r.l. 
Tel: +39 06 33 18 21

Sverige
Pfizer AB
Tel: +46 (0)8 550 520 00

Kύπρος
Pfizer Ελλάς Α.Ε. (Cyprus Branch) 
Tηλ: +357 22 817690

United Kingdom
Pfizer Limited
Tel: +44 (0) 1304 616161

Latvija
Pfizer Luxembourg SARL filiāle Latvijā
Tel.: + 371 670 35 775

This leaflet was last revised in

Other sources of information

Detailed information on this product is available on the European Medicines Agency website:
http://www.ema.europa.eu.
----------------------------------------------------------------------------------------------------------------------------
The following information is intended for healthcare professionals only:

During storage, a white deposit and clear supernatant may be observed. This does not constitute a sign 
of deterioration.

Inspect visually for any foreign particulate matter and/or abnormal physical appearance; do not use if 
either are found.

Shake well prior to use to obtain a homogeneous white suspension.

Administer the entire dose.

Prevenar 13 is for intramuscular use only. Do not administer intravascularly. 

Prevenar 13 must not be mixed with any other vaccines in the same syringe.

Prevenar 13 can be given at the same time as other childhood vaccines; in this case, different 
vaccination sites should be used. 

Prevenar 13 may be given to adults aged 50 years and older at the same time as the trivalent or 
quadrivalent inactivated influenza vaccine.

After first use, the product may be stored in a refrigerator for a maximum of 28 days.

Any unused product or waste material should be disposed of in accordance with local requirements.



120

Annex IV

Scientific conclusions and grounds for the variation to the terms of the marketing 

authorisation(s)



121

Scientific conclusions

Taking into account the PRAC Assessment Report on the PSUR(s) for pneumococcal 

polysaccharide conjugate vaccine (adsorbed) - 13 valent, the scientific conclusions of CHMP are as 

follows: 

In view of available data on spontaneous reports, including close temporal relationship, and in 

view of a plausible mechanism of action, the PRAC considers a causal relationship between 

pneumococcal polysaccharide conjugate vaccine (adsorbed) - 13 valent and anaphylaxis in

children above the age of 5 years and adults is at least a reasonable possibility. Consequently the 

PRAC has updated section 4.8 of the SmPC to add the adverse reaction anaphylaxis with a 

frequency not known to the group of children above 5 years of age and adults.

The CHMP agrees with the scientific conclusions made by the PRAC.

Grounds for the variation to the terms of the marketing authorisation(s)

On the basis of the scientific conclusions for pneumococcal polysaccharide conjugate vaccine 

(adsorbed) - 13 valent the CHMP is of the opinion that the benefit-risk balance of the medicinal 

product(s) containing pneumococcal polysaccharide conjugate vaccine (adsorbed) - 13 valent is 

unchanged subject to the proposed changes to the product information.

The CHMP recommends that the terms of the marketing authorisation(s) should be varied.


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCES ANDMANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETINGAUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE ANDEFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET
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hiv infection), you/she/he may not get the full benefit from prevenar 13. has experienced seizures as medicines to lower fever may need to be taken before prevenar 13 is given. if your child should become unresponsive or experience seizures (fits) after the vaccination, please contact your doctor immediately. see also section 4. talk to your doctor, pharmacist, or nurse before the vaccination if your child was born very prematurely (at or before 28 weeks of gestation), as longer gaps than normal between breaths may occur for 2-3 days after vaccination. see also section 4. as with any vaccine, prevenar 13 will not protect all persons who are vaccinated. prevenar 13 will only protect against ear infections in children caused by the types of streptococcus pneumoniae for which the vaccine has been developed. it will not protect against other infectious agents that can cause ear infections. other medicines/vaccines and prevenar 13 your doctor may ask you to give your child paracetamol or other medicines that lower fever before prevenar 13 is given. this will help to lower some of the side effects of prevenar 13. tell your doctor, pharmacist or nurse if you or your child is taking, has recently taken or might take any other medicines, or has recently received any other vaccine. pregnancy and breast-feeding if you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before receiving this medicine. driving and using machines prevenar 13 has no or negligible influence on the ability to drive and use machines. however, some of the effects mentioned under section 4 "possible side effects" may temporarily affect the ability to drive or use machines. prevenar 13 contains sodium this medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially \'sodium-free\'.', 'Entity_Recognition': [{'Text': 'prevenar 13', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 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{'Title': '3 3. how prevenar 13 is given', 'Section_Content': "the doctor or nurse will inject the recommended dose (0.5 ml) of the vaccine into your arm or your child's arm or leg muscle. infants aged 6 weeks to 6 months of age typically, your child should receive an initial course of three injections of the vaccine followed by a booster dose. the first injection may be given from the age of six weeks. each injection will be given at least one month apart. a fourth injection (booster) will be given between 11 and 15 months of age. you will be told when your child should come back for the next injection. according to official recommendations in your country, an alternative schedule may be used by your healthcare provider. please speak to your doctor, pharmacist, or nurse for more information. premature infants your child will receive an initial course of three injections. the first injection may be given as early as six weeks of age with at least one month between doses. between 11 and 15 months of age, your child will receive a fourth injection (booster). unvaccinated infants, children, and adolescents over 7 months of age infants aged 7 to 11 months should receive two injections. each injection will be given at least one month apart. a third injection will be given in the second year of life. children aged 12 to 23 months should receive two injections. each injection will be given at least two months apart. children aged 2 to 17 years should receive one injection. infants, children, and adolescents previously vaccinated with prevenar infants and children who have previously received prevenar may receive prevenar 13 to complete the course of injections. for children 1 to 5 years of age previously vaccinated with prevenar, your doctor or nurse will recommend how many injections of prevenar 13 are required. children and adolescents 6 to 17 years of age should receive one injection. it is important to follow the instructions from the doctor, pharmacist, or nurse so that your child completes the course of injections. if you forget to go back at the scheduled time, ask the doctor, pharmacist, or nurse for advice. adults adults should receive one injection. tell your doctor, pharmacist or nurse if you have been given a pneumococcal vaccine before. if you have any further questions on the use of prevenar 13, ask your doctor, pharmacist, or nurse. special populations individuals considered to be at a higher risk of pneumococcal infection (such as those with sickle cell disease or hiv infection), including those previously vaccinated with the 23-valent pneumococcal polysaccharide vaccine, may receive at least one dose of prevenar 13. individuals with a blood-forming stem cell transplant may receive three injections, with the first given at 3 to 6 months after the transplant and with an interval of at least 1 month between doses. a fourth injection (booster) is recommended 6 months after the third injection.", 'Entity_Recognition': [{'Text': 'prevenar 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{'Title': '4. possible side effects', 'Section_Content': 'like all vaccines, prevenar 13 can cause side effects, although not everybody gets them. the following side effects include those reported for prevenar 13 in infants and children (6 weeks to 5 years of age): the most common side effects (these may occur with more than 1 in 10 doses of the vaccine) are: decreased appetite fever; irritability; pain, tenderness, redness, swelling or hardness at the vaccination-site; drowsiness; restless sleep redness, hardness, swelling at the vaccination-site of 2.5 cm -7.0 cm (after the booster dose and in older children [aged 2 to 5 years]) common side effects (these may occur with up to 1 in 10 doses of the vaccine) are: vomiting; diarrhoea fever of more than 39; tenderness at the vaccination-site interfering with movement, redness, hardness, swelling at the vaccination-site of 2.5 cm -7.0 cm (after the initial course of injections) rash uncommon side effects (these may occur with up to 1 in 100 doses of the vaccine) are: seizures (or fits), including those caused by a high temperature hives (urticaria or urticaria-like rash) redness, swelling, or hardness at the vaccination-site of more than 7 cm; crying rare side effects (these may occur with up to 1 in 1,000 doses of the vaccine) are: collapse or shock-like state (hypotonic-hyporesponsive episode) allergic (hypersensitivity) reaction, including swelling of the face and/or lips, difficulty in breathing the following side effects include those reported for prevenar 13 in children and adolescents (6 to 17 years of age): the most common side effects (these may occur with more than 1 in 10 doses of the vaccine) are: decreased appetite irritability; pain, tenderness, redness, swelling or hardness at the vaccination-site; drowsiness; restless sleep; tenderness at the vaccination-site interfering with movement 100 common side effects (these may occur with up to 1 in 10 doses of the vaccine) are: headaches vomiting; diarrhoea rash; hives (urticaria or urticaria-like rash) fever children and adolescents with either hiv infection, sickle cell disease or a blood-forming stem cell transplant had similar side effects however the frequencies of headaches, vomiting, diarrhoea, fever, fatigue, joint and muscle pain were very common. 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. the following side effects include those reported for prevenar 13 in adults: the most common side effects (these may occur with more than 1 in 10 doses of the vaccine) are: decreased appetite; headaches; diarrhoea; vomiting (for those 18 to 49 years of age) chills; tiredness; rash; pain, redness, swelling hardness or tenderness at the vaccination-site, interfering with arm movement (severe pain or tenderness at vaccination-site for those 18-39 years of age and severe limitation of arm movements for those 18 to 39 years of age) worsening or new pain in your joints, worsening or new pain in your muscles fever (for those 18 to 29 years of age) common side effects (these may occur with up to 1 in 10 doses of the vaccine) are: vomiting (for those 50 years and older); fever (for those 30 years and older) uncommon side effects (these may occur with up to 1 in 100 doses of the vaccine) are: nausea allergic (hypersensitivity) reaction, including swelling of the face and/or lips, difficulty in breathing enlarged lymph nodes or glands (lymphadenopathy) near the vaccination-site, such as under the arm adults with hiv infection had similar side effects however the frequencies were very common for fever, vomiting and common for nausea. adults with a blood-forming stem cell transplant had similar side effects however the frequencies were very common for fever and vomiting. the following additional side effects have been seen with prevenar 13 in postmarketing experience severe allergic reaction including shock (cardiovascular collapse); angioedema (swelling of lips, face or throat) hives (urticaria), redness and irritation (dermatitis) and itching (pruritus) at the vaccination-site; flushing enlarged lymph nodes or glands (lymphadenopathy) near the vaccination-site, such as under the arm or in the groin a rash causing itchy red blotches (erythema multiforme) 101 reporting of side effects if you or your child get any side effects, talk to your doctor, pharmacist, or nurse. this includes any possible side effects not listed in this leaflet. you can also report side effects directly via the national reporting system listed in appendix v. by reporting side effects you can help provide more information on the safety of this medicine.', 'Entity_Recognition': [{'Text': 'prevenar 13', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'all vaccines', 'Type': 'TREATMENT', 'BeginOffset': 5, 'EndOffset': 17}, {'Text': '13', 'Type': 'NUMBER', 'BeginOffset': 28, 'EndOffset': 30}, {'Id': 7, 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