Prevenar 13 suspension for injection

Pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed)

1 dose (0.5 ml) contains:

For a full list of excipients, see section 6.1.

Suspension for injection.

The vaccine is a homogeneous white suspension.

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.

Active immunisation for the prevention of invasive disease caused by Streptococcus pneumoniae in adults aged 50 years and older.

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.

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).

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 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 CRM₁₉₇.

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

Young Children (12-59 months) completely immunized 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).

Adults aged 50 years and older

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 polysaccharide vaccine is considered appropriate, Prevenar 13 should be given first (see sections 4.5 and 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.

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.

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 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.

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 immunization.

Safety and immunogenicity data for Prevenar 13 are not available for individuals in specific immuno-compromised groups (e.g., congenital or acquired splenic dysfunction, HIV infected, malignancy, haematopoietic stem cell transplant, nephrotic syndrome) and vaccination should be considered on an individual basis.

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 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).

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.

Infants and children aged 6 weeks to 5 years

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.

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. The clinical significance of this is unknown.

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

Fertility and pregnancy

There are no data from the use of pneumococcal 13-valent conjugate in pregnant women.

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

Lactation

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

Not relevant.

Adverse reactions reported in clinical studies or from the post-marketing 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).

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 were vaccination-site reactions, fever, irritability, decreased appetite, and increased and/or decreased sleep.

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 as related to vaccination in Prevenar 13 clinical studies:

Adverse reactions from Prevenar 13 postmarketing experience

Although the following adverse drug reactions were not observed in the Prevenar 13 clinical studies in infants and children, the following are considered adverse drug reactions for Prevenar 13 as they were reported in the postmarketing experience. Because these reactions were derived from spontaneous reports, the frequencies could not be determined and are thus considered as not known.

Additional information in special populations:

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

Adults aged 50 years and older

Safety was assessed in 6 clinical studies including 6,198 adults ranging in age from 50 to 95 years. Prevenar 13 was administered to 5,667 adults; 2,616 (46.2 %) aged 50 to 64 years, and 3,051 (53.8 %) aged 65 years and older. 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 3,751 were 23-valent polysaccharide vaccine unvaccinated. Subjects older than 65 years of age reported fewer adverse reactions than younger adults, regardless of prior pneumococcal vaccination status. Overall, the frequency categories were similar for both age groups.

Adverse reactions from clinical studies

Local reactions and systemic events were solicited daily for 14 days after each vaccination in all the clinical studies. The following frequencies are based on adverse reactions assessed as related to vaccination with Prevenar 13 in adults:

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.

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).

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.

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

Mechanism of action

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 in 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 antibiotic-resistant IPD.

Burden of disease in adults aged 50 years and older

The incidence of invasive pneumococcal disease (IPD) in adults increases with age from 50 years, risk factors (smoking status or alcohol use), and underlying co-morbidities (chronic cardiovascular disease, chronic pulmonary disease including asthma, renal disorders, diabetes mellitus, and chronic liver disease including alcoholic liver disease). Bacteraemic pneumonia, bacteraemia without a focus, and meningitis are the most common manifestations of IPD in adults aged 50 years or older. Based on surveillance data, the pneumococcal serotypes in Prevenar 13 may be responsible for at least 50 - 76% (depending on country) of IPD in adults aged over 50 years. Approximately 80% of IPD in adults is bacteraemic pneumonia.

Prevenar 13 immunogenicity clinical studies in infants and children

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. 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).

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 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 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.

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 0.35μg/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.

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.

The European Medicines Agency has deferred the obligation to submit the results of studies with Prevenar 13 in one or more subsets of the paediatric population in Pneumococcal disease (see section 4.2 for information on paediatric use).

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 Per protocol (Table 2).

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.

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 in the concentrations of antibodies against the seven serotypes after the polysaccharide vaccination, suggesting that immunological memory was well established.

Immunogenicity studies in adults 50 years and older

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 50-95 years of age. Clinical studies with Prevenar 13 currently provide immunogenicity data in adults aged 50 years and older, including adults aged 65 and older previously vaccinated with one or more doses of 23-valent 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 50 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 polysaccharide vaccine. In the same study another group of adults aged 50-59 years received a single dose of Prevenar 13.

Table 4 compares the OPA GMTs, 1-month post-dose, in 60-64 year olds given either a single dose of Prevenar 13 or 23-valent polysaccharide vaccine, and in 50-59 year olds given a single dose of Prevenar 13.

In adults aged 60-64 years, OPA GMTs to Prevenar 13 were non-inferior to the OPA GMTs elicited to the 23-valent 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 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:

Adults previously vaccinated with 23-valent pneumococcal polysaccharide vaccine

Immune responses to Prevenar 13 and 23-valent 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 5 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 polysaccharide vaccine.

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 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 polysaccharide vaccine.

One year after vaccination with Prevenar 13 in adults aged 70 years and over who were vaccinated with 23-valent 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:

Evaluation of pharmacokinetic properties is not required for vaccines.

Non-clinical data for Prevenar 13 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.

Sodium chloride

Succinic acid

Polysorbate 80

Water for injections

For adjuvant, see section 2.

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

3 years

Store in a refrigerator (2°C-8°C).

Do not freeze.

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.

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.

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

Wyeth Lederle Vaccines S.A.

Pleinlaan 17 Boulevard de la Plaine

1050 Brussel - Bruxelles

Belgium

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

09/12/2009

March 2012

Detailed information on this product is available on the website of the European Medicines Agency (EMA) http://www.ema.europa.eu

Ref: PN 3_0 UK