ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
1.
Prevenar 13 suspension for injection
Pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed)
2.
1 dose (0.5 ml) contains:
Pneumococcal polysaccharide serotype 3
1
1
2.2 µg
Pneumococcal polysaccharide serotype 4
1
2.2 µg
Pneumococcal polysaccharide serotype 5
Pneumococcal polysaccharide serotype 6A
1
2.2 µg
2.2 µg
Pneumococcal polysaccharide serotype 6B
1
4.4 µg
Pneumococcal polysaccharide serotype 7F
1
2.2 µg
Pneumococcal polysaccharide serotype 9V
1
2.2 µg
Pneumococcal polysaccharide serotype 14
Pneumococcal polysaccharide serotype 18C
1
1
2.2 µg
2.2 µg
Pneumococcal polysaccharide serotype 19A
1
2.2 µg
Pneumococcal polysaccharide serotype 19F
1
2.2 µg
2.2 µg
1
Conjugated to CRM
197
carrier protein and adsorbed on aluminium phosphate (0.125 mg aluminium).
For a full list of excipients, see section 6.1.
3.
Suspension for injection.
The vaccine is a homogeneous white suspension.
4.
4.1
Active immunisation for the prevention of invasive disease, pneumonia and acute otitis media caused
by
Streptococcus pneumoniae
in infants and children from 6 weeks to 5 years of age. 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 impact of invasive disease in different age groups as well as the variability of
serotype epidemiology in different geographical areas.
4.2
Posology
The immunisation schedules for Prevenar 13 should be based on official recommendations.
It is recommended that infants who receive a first dose of Prevenar 13 complete the vaccination course
with Prevenar 13.
2
Pneumococcal polysaccharide serotype 1
1
2.2 µg
Pneumococcal polysaccharide serotype 23F
1
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).
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.
Children aged 2-5 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
CRM
197
. Infants and children who have begun immunisation with Prevenar may switch to Prevenar 13
at any point in the schedule.
Children aged 12-23 months
Children who have not received two doses of Prevenar 13 during the infant series should receive two
doses of the vaccine (with an interval of at least 2 months between doses) to complete the
immunisation series for the six additional serotypes. Alternatively, complete the immunisation series
according to official recommendations.
Children aged 2-5 years
One single dose.
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 young
children.
4.3
Hypersensitivity to the active substances, to any of the excipients (see 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
3
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.
This vaccine should not be given as an intramuscular injection to infants or children 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.
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).
Children with impaired immune responsiveness, whether due to the use of immunosuppressive
therapy, a genetic defect, HIV infection, or other causes, may have reduced antibody response to
active immunisation.
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). Safety and immunogenicity data are not yet
available for children in other specific high-risk groups for invasive pneumococcal disease (e.g.,
children with another congenital or acquired splenic dysfunction, HIV infected, malignancy, nephrotic
syndrome). Vaccination in high-risk groups should be considered on an individual basis. Specific data
are not yet available for Prevenar 13.
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 immunocompromised)
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 48-72h should be considered
when administering the primary immunisation series to very premature infants (born ≤ 28 weeks of
gestation), and particularly for those with a previous history of respiratory immaturity. As the benefit
of vaccination is high in this group of infants, vaccination should not be withheld or delayed.
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).
4
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
Prevenar 13 can be given 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, meningococcal serogroup C, measles, mumps, rubella
and varicella. Clinical studies demonstrated that the immune responses and the safety profiles of the
administered vaccines were unaffected.
In clinical studies, where there was concomitant administration of Prevenar 13 and rotavirus vaccine,
no change in the safety profiles of these vaccines was observed.
Different injectable vaccines should always be given at different injection sites.
4.6
Prevenar 13 is not intended for use in adults. Human data on the use during pregnancy or lactation and
animal reproduction studies are not available.
4.7
Not relevant.
4.8
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 were injection-site reactions, fever,
irritability,
decreased appetite, and increased and/or decreased sleep.
An increase in injection 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 reported in clinical studies or from the post-marketing experience are listed in the
following table per body system and per frequency, and this is for all age groups. 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).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
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 as related to vaccination in Prevenar 13 clinical studies:
Immune system disorders:
Hypersensitivity
reaction including face oedema, dyspnoea, bronchospasm
5
Rare:
Nervous system disorders:
Rare:
Convulsions (including febrile convulsions), hypotonic-hyporesponsive
episode
Gastrointestinal disorders:
Very common:
Vomiting; diarrhoea
Skin and subcutaneous tissue disorders:
Rare:
Rash; urticaria or urticaria-like rash
General disorders and administration site conditions:
Very common:
Pyrexia; irritability; any injection-site erythema, induration/swelling or
pain/tenderness; somnolence; poor quality sleep
Injection-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; injection-site movement impairment (due to pain);
injection-site erythema or induration/swelling 2.5 cm–7.0 cm (after infant
series)
Uncommon:
Injection-site erythema, induration/swelling > 7.0 cm; crying
Adverse reactions from Prevenar postmarketing experience
Although the following adverse drug reactions were not observed in the Prevenar 13 clinical studies,
the following are considered adverse drug reactions for Prevenar and are considered adverse drug
reactions for Prevenar 13 as well. These frequencies are based on spontaneous reporting rates for
Prevenar.
Blood and lymphatic system disorders:
Very rare:
Lymphadenopathy (localised to the region of the injection site)
Immune system disorders:
Rare:
Anaphylactic/anaphylactoid reaction including shock; angioedema
Skin and subcutaneous tissue disorders:
Very rare:
Erythema multiforme
General disorders and administration site conditions:
Rare:
Injection-site urticaria; injection-site dermatitis; injection-site pruritus;
flushing
Additional information in special populations:
Apnoea in very premature infants (≤ 28 weeks of gestation) (see section 4.4).
4.9
Overdose with Prevenar 13 is unlikely due to its presentation as a pre-filled syringe. However, 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 schedules of Prevenar 13.
5.
5.1
Pharmacodynamic properties
Pharmacotherapeutic group: vaccines, pneumococcal vaccines; ATC code: J07AL02
6
Uncommon:
Decreased appetite
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 CRM
197
carrier protein.
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 antibiotic-resistant IPD.
Prevenar 13 Immunogenicity Clinical Studies
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 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. 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
percentage of Prevenar 13 recipients with serum IgG ≥ 0.35 μg/ml were 98.2 % (study 006) and 63.5
% (study 004).
7
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
Prevenar 13
7-valent Prevenar
Serotypes
%
%
Difference
(95 % CI)
(N=282-285)
(N=277-279)
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 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 μg/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 series
8
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.
Long-term persistence of antibodies has not been investigated after administration of Prevenar 13 as
either a primary series in infants plus booster or after administration of a single priming dose in older
children. Since the introduction of 7-valent Prevenar in 2000, pneumococcal disease surveillance data
have not shown that the immunity elicited by Prevenar in infancy have waned over time.
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 (7-valent vaccine) protective efficacy
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 2).
Table 2: Summary of efficacy of 7-valent Prevenar
1
Test
N
VE
2
95% CI
NCKP: Vaccine-serotype IPD
3
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
1
Per protocol
2
Vaccine efficacy
3
October 1995 to April 20, 1999
4
October 1995 to April 30, 1998
9
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 3). Following the widespread use of Prevenar, the incidence of IPD has
been consistently and substantially reduced. An increase in the incidence of IPD cases caused by
serotypes not contained in Prevenar, such as 1, 7F and 19A, has been reported in some countries.
Surveillance will continue with Prevenar 13, and as countries update their surveillance data,
information in this table may change.
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 3: Summary of effectiveness of 7-valent Prevenar for invasive pneumococcal disease
Country
Recommended schedule
Disease reduction, %
95% CI
(year of introduction)
1
UK (England & Wales)
2, 4, + 13 months
Vaccine serotypes
:
49, 95%
(2006)
Two doses under age 1:
85%
USA (2000)
2, 4, 6, + 12-15 months
Children < 5
2
Vaccine serotypes: 98%
97, 99%
All serotypes: 77%
73, 79%
Persons ≥ 65
3
Vaccine serotypes: 76%
NA
All serotypes: 38%
NA
2, 4, + 12 months All serotypes: 73% NA
(2004)
Vaccine serotypes
:
2-dose infant series: 99% 92, 100%
Completed schedule:100% 82, 100%
1
Children < 2 years of age. Calculated vaccine effectiveness as of June 2008 (Broome method).
2
2005 data.
3
2004 data.
4
Children < 5 years of age. January 2005 to December 2007. Complete effectiveness for routine 2+1
schedule not yet available.
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.
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), and 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
10
Canada (Quebec)
4
in the concentrations of antibodies against the seven serotypes after the polysaccharide vaccination,
suggesting that immunological memory was well established.
5.2
Pharmacokinetic properties
Evaluation of pharmacokinetic properties is not available for vaccines.
5.3
Preclinical safety data
Studies with a vaccine formulation representative of Prevenar 13 revealed no special hazard for
humans based on conventional studies of safety pharmacology, repeated dose toxicity, juvenile
toxicity and local tolerance.
6.
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 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 and 10, with or without needle, and a multipack of 5 packs, each containing 10
pre-filled syringes, 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.
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.
11
Any unused product or waste material should be disposed of in accordance with local requirements.
7.
Wyeth Lederle Vaccines S.A.
Rue du Bosquet, 15
B-1348 Louvain-la-Neuve
Belgium
8.
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.
09/12/2009
10.
Detailed information on this medicinal product is available on the website of the European Medicines
Agency (EMEA) http://www.emea.europa.eu
12
ANNEX II
A.
MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE
SUBSTANCE(S) AND MANUFACTURING
AUTHORISATION HOLDER(S) RESPONSIBLE FOR
BATCH RELEASE
B.
CONDITIONS OF THE MARKETING AUTHORISATION
13
A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND
MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCH
RELEASE
Name and address of the manufacturers of the biological active substance
Wyeth Biotech
One Burtt Road
Andover, MA 01810
USA
Wyeth Medica Ireland
Grange Castle International Business Park
Clondalkin
Dublin 22
Ireland
Wyeth Pharmaceuticals, Division of Wyeth Holdings Corporation
4300 Oak Park
Sanford, NC 27330
USA
Wyeth Pharmaceuticals, Division of Wyeth Holdings Corporation
401 N. Middletown Road
Pearl River, NY 10965
USA
Name and address of the manufacturer responsible for batch release
John Wyeth & Brother Ltd. (Trading as Wyeth Pharmaceuticals)
New Lane
Havant
Hampshire PO9 2NG
United Kingdom
B. CONDITIONS OF THE MARKETING AUTHORISATION
Medicinal product subject to medical prescription.
•
CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND
EFFECTIVE USE OF THE MEDICINAL PRODUCT
The MAH should inform health care professionals about the differentiating characteristics of 13vPnC
and 7vPnC vaccines, i.e. differences in packaging, the product label and different colour of syringe
and tip cap and how to transition to 13vPnC for children who started a vaccination schedule with
7vPnC.
In order to ensure that potential adverse event reports can be unambiguously linked to the type of
vaccine administered, the MAH shall ensure that the two vaccines have different batch numbers,
different colour of the plunger and tip cap of the syringe, and different carton packaging and label.
14
•
OTHER CONDITIONS
Pharmacovigilance system
The MAH must ensure that the system of pharmacovigilance, as described in version 3.0 presented in
Module 1.8.1. of the Marketing Authorisation Application, is in place and functioning before and
whilst the product is on the market.
Risk Management Plan
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in
the Pharmacovigilance Plan, as agreed in version 3.2 of the Risk Management Plan (RMP) presented
in Module 1.8.2. of the Marketing Authorisation Application and any subsequent updates of the RMP
agreed by the CHMP.
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the
updated RMP should be submitted at the same time as the next Periodic Safety Update Report (PSUR).
In addition, an updated RMP should be submitted
•
When new information is received that may impact on the current Safety Specification,
Pharmacovigilance Plan or risk minimisation activities
•
Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being
reached
•
At the request of the EMEA
Official batch release: in accordance with Article 114 Directive 2001/83/EC as amended, the official
batch release will be undertaken by a state laboratory or a laboratory designated for that purpose.
15
ANNEX III
LABELLING AND PACKAGE LEAFLET
16
A. LABELLING
17
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON TEXT
Pre-filled syringe, with or without needle, pack of 1 or 10
1.
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.
3.
LIST OF EXCIPIENTS
Sodium chloride, succinic acid, polysorbate 80 and water for injections
4.
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
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 REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
18
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
Wyeth Lederle Vaccines S.A.
Rue du Bosquet, 15
B-1348 Louvain-la-Neuve
Belgium
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
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Justification for not including Braille accepted
19
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON TEXT
Pre-filled syringe, with or without needle, pack of 10 for multipack of 50 (5 x 10) (without blue
box)
1.
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.
3.
LIST OF EXCIPIENTS
Sodium chloride, succinic acid, polysorbate 80 and water for injections.
4.
Suspension for injection
Component of a multipack comprising 5 packs, each containing 10 single-dose (0.5 ml) pre-filled
syringes with separate needles.
Component of a multipack comprising 5 packs, each containing 10 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 REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
20
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
Wyeth Lederle Vaccines S.A.
Rue du Bosquet, 15
B-1348 Louvain-la-Neuve
Belgium
EU/1/09/590/006 – pack of 50 (5 x 10) with separate needles
EU/1/09/590/005 – pack of 50 (5 x 10) without needle
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Justification for not including Braille accepted
21
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON TEXT
Pre-filled syringe, with or without needle, multipack of 50 (5 x 10) (outer wrapper label to be
applied on transparent foil, including blue box)
1.
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.
3.
LIST OF EXCIPIENTS
Sodium chloride, succinic acid, polysorbate 80 and water for injections.
4.
Suspension for injection
Multipack comprising 5 packs, each containing 10 single-dose (0.5 ml) pre-filled syringes with
separate needles.
Multipack comprising 5 packs, each containing 10 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 REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
22
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
Wyeth Lederle Vaccines S.A.
Rue du Bosquet, 15
B-1348 Louvain-la-Neuve
Belgium
EU/1/09/590/006 – pack of 50 (5 x 10) with separate needles
EU/1/09/590/005 – pack of 50 (5 x 10) without needle
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Justification for not including Braille accepted
23
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
Pre-filled syringe
1.
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
24
B. PACKAGE LEAFLET
25
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 your child receives this vaccine.
-
Keep this leaflet. You may need to read it again.
-
If you have any further questions, ask your doctor, pharmacist, or nurse.
-
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor, pharmacist, or nurse.
In this leaflet:
1.
What Prevenar 13 is and what it is used for
2.
Before your child receives Prevenar 13
3.
How Prevenar 13 is given
4.
How to store Prevenar 13
6.
Further information
1.
WHAT PREVENAR 13 IS AND WHAT IT IS USED FOR
Prevenar 13 is a pneumococcal vaccine. Prevenar 13 is given to children from 6 weeks to 5 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 caused by 13
types of the bacteria
Streptococcus pneumoniae.
The vaccine works by helping the body to make its own antibodies, which protect your child against
these diseases.
2.
BEFORE YOUR CHILD RECEIVES PREVENAR 13
Prevenar 13 should not be given:
•
if your child is allergic (hypersensitive) to the active substances, to any other ingredients or to any
other vaccine that contains diphtheria toxoid. The active substances and other ingredients are listed
under “What Prevenar 13 contains” in section 6.
•
if your child has a severe infection with a high temperature (over 38°C). If this applies to your
child, then the vaccination will be postponed until your child is feeling better. A minor infection,
such as a cold, should not be a problem. However, talk to your doctor, pharmacist, or nurse first.
Take special care with Prevenar 13
Tell the doctor, pharmacist, or nurse before the vaccination:
•
if 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.
•
if your child has any bleeding problems or bruises easily.
•
if your child has a weakened immune system (such as due to HIV infection), she/he may not get
the full benefit from Prevenar 13.
As with any vaccine, Prevenar 13 will not protect 100 % of those who receive the vaccine.
Prevenar 13 will only protect against ear infections 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.
26
-
This vaccine has been prescribed for your child. Do not pass it on to others.
5.
Possible side effects
Using other medicines/vaccines:
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.
Please tell your doctor, pharmacist or nurse if your child is taking, has recently taken any other
medicines, including medicines obtained without prescription, or has recently received any other
vaccine.
3.
HOW PREVENAR 13 IS GIVEN
The doctor or nurse will inject the recommended dose (0.5 ml) of the vaccine into
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.
Unvaccinated infants and children 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 5 years
should receive one injection.
Infants and children 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.
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.
If you have any further questions on the use of Prevenar 13, ask your doctor, pharmacist, or nurse.
27
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:
The most common side effects
(these may occur with more than 1 in 10 doses of the vaccine) are:
•
Decreased appetite
•
Fever; irritability; any pain, tenderness, redness, swelling or hardness at the injection-site;
drowsiness; restless sleep
Common side effects
(these may occur with up to 1 in 10 doses of the vaccine) are:
•
Fever of more than 39°C
Uncommon side effects
(these may occur with up to 1 in 100 doses of the vaccine) are:
•
Vomiting; diarrhoea
•
Redness, swelling, or hardness at the injection-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:
•
Seizures (or fits), including those caused by a high temperature
•
Hypotonic-hyporesponsive episode (collapse or shock-like state)
Hypersensitivity reaction, including swelling of the face and/or lips, difficulty in breathing
•
•
Flushing
Rash; urticaria or urticaria-like rash (hives)
Prevenar 13, which provides protection against 13 types of
Streptococcus pneumoniae
bacteria,
replaces Prevenar, which provided protection against 7 types.
The following additional side effects have been seen with Prevenar because it has been available
for a longer period of time. These side effects may be reported in the future with Prevenar 13:
Rare side effects
(these may occur with up to 1 in 1,000 doses of the vaccine) are:
Anaphylactic/anaphylactoid reaction including shock (cardiovascular collapse); angioedema
(swelling of lips, face or throat)
•
Urticaria (hives), dermatitis (redness and irritation) and pruritus (itching) at the injection-site
Very rare side effects
(these may occur with up to 1 in 10,000 doses of the vaccine) are:
•
Enlarged lymph nodes or glands (lymphadenopathy) near the injection site, such as under the arm
or in the groin
•
Erythema multiforme (a rash causing itchy red blotches)
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.
Please speak with your doctor, pharmacist, or nurse should you have any questions or concerns. If any
of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your
doctor, pharmacist, or nurse.
5.
HOW TO STORE PREVENAR 13
Keep out of the reach and sight of children.
Do not use Prevenar 13 after the expiry date stated on the carton and label. The expiry date refers to
the last day of that month.
28
•
•
Store in a refrigerator (2°C – 8°C).
Do not freeze.
Medicines should not be disposed of via wastewater or household waste. Ask your doctor, pharmacist,
or nurse how to dispose of medicines no longer required. These measures will help to protect the
environment.
6.
FURTHER INFORMATION
What Prevenar 13 contains
The active substances are:
•
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
Conjugated to CRM
197
carrier protein and 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 and 10, with or without needle, and a multipack each containing 5 packs of 10
pre-filled syringes, with or without needle.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Manufacturing Authorisation Holder responsible
for batch release:
Wyeth Lederle Vaccines S.A.
Rue du Bosquet, 15
B-1348 Louvain-la-Neuve
Wyeth Pharmaceuticals
Belgium
Hampshire, PO9 2NG
United Kingdom
For any information about this medicinal product, please contact the local representative of the
Marketing Authorisation Holder:
België/Belgique/Belgien
Latvija
Pfizer S.A. / N.V.
Wyeth Whitehall Export GmbH
Tél/Tel: +32 (0)2 554 62 11
Tãlr.: + 43 1 89 1140
България
Lietuva
Wyeth Whitehall Export GmbH
Wyeth Whitehall Export GmbH
Tel: + 43 1 89 1140
Teл: + 43 1 89 1140
Česká Republika
Malta
Pfizer s.r.o.
Vivian Corporation Ltd.
Tel: +420-283-004-111
Tel: + 35621 344610
Pfizer ApS
Wyeth Pharmaceuticals B.V.
Tlf: +45 44 201 100
Tel: + 31 23 5672567
29
New Lane
Havant
Danmark
Nederland
Deutschland
Norge
Pfizer Pharma GmbH
Pfizer AS
Tel: +49 (0)30 550055-51000
Tlf: +47 67 526 100
Eesti
Österreich
Wyeth Whitehall Export GmbH
Pfizer Corporation Austria Ges.m.b.H.
Tel: + 43 1 89 1140
Tel: +43 (0)1 521 15-0
Ελλάδα
Polska
Pfizer Hellas A.E.
Τηλ.: +30 210 6785 800
Pfizer Polska Sp. z o.o.
Tel.: +48 22 335 61 00
Pfizer, S.A.
Laboratórios Pfizer, Lda.
Télf:+34914909900
Tel: (+351) 21 423 55 00
France
România
Pfizer Romania S.R.L
Tél +33 1 58 07 30 00
Tel: +40 (0) 21 207 28 00
Ireland
Slovenská Republika
Tel: + 353 1 449 3500
Pfizer Luxembourg SARL, organiza
č
ná
zložka
Tel: + 421 2 3355 5500
Ísland
Slovenija
Icepharma hf.
Tel: + 354 540 8000
Wyeth Whitehall Export GmbH
Tel: + 43 1 89 1140
Italia
Suomi/Finland
Wyeth Lederle S.p.A.
Pfizer Oy
Puh/Tel: +358 (0)9 430 040
Kύπρος
Sverige
Wyeth Hellas (Cyprus Branch) AEBE
Tel: +46 (0)8 550 520 00
Luxembourg/Luxemburg
United Kingdom
Pfizer S.A. / N.V.
Wyeth Vaccines
Tél/Tel: +32 (0)2 554 62 11
Tel: +44 845 367 0098
Magyarország
Pfizer Kft.
Tel: +36 1 488 3700
This leaflet was last approved in
{MM/YYYY}.
Detailed information on this medicine is available on the European Medicines Agency (EMA) website
http://www.ema.europa.eu/home
----------------------------------------------------------------------------------------------------------------------------
The following information is intended for medical or healthcare professionals only:
During storage, a white deposit and clear supernatant may be observed.
30
España
Portugal
Pfizer
Wyeth Vaccines
Tel: + 39 06 927151
Tηλ: +357 22 817690
Pfizer AB
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 injection
sites should be used.
Any unused product or waste material should be disposed of in accordance with local requirements.
31
Source: European Medicines Agency
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