Prevenar 13 - Package Leaflet

Rare: rash; hives or urticarial rash

General disorders and administration site conditions:

Very common: fever, irritability, any erythema at the vaccination site, induration / swelling or pain / tenderness; drowsiness, restless sleep. Erythema at the vaccination site or induration / swelling of 2.5 cm-7.0 cm (after the booster dose and in older children [2-5 years of age])

Common: fever> 39 ° C; difficulty moving at the vaccination site (due to pain), erythema at the vaccination site or induration / swelling of 2.5cm-7.0cm (after infant series)

Uncommon: vaccination site erythema, induration / swelling> 7.0 cm; cry

Adverse reactions following post-marketing experience with Prevenar 13

Although the following adverse reactions were not observed during clinical trials of Prevenar 13 in infants and children, they are considered as adverse reactions for Prevenar 13 because they were reported in post-marketing experience. Since these reactions are derived from spontaneous reporting, the frequencies are not they can be determined and are therefore regarded as unknown.

Disorders of the blood and lymphatic system:

lymphadenopathy (localized in the region of the vaccination site)

Disorders of the immune system:

anaphylactic / anaphylactoid reaction, including shock; angioedema

Skin and subcutaneous tissue disorders:

erythema multiforme

General disorders and administration site conditions:

vaccination site hives, vaccination site dermatitis, vaccination site pruritus, flushing

Additional information for special populations:

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

Children and adolescents between the ages of 6 and 17

Safety was assessed in 592 children aged 6 to 17 years, 294 children aged 5 to 10 years previously immunized with at least one dose of Prevenar, and 298 children aged 10 to 17 years who did not a pneumococcal vaccine had been administered. The most common adverse events in children and adolescents aged 6-17 years were:

Nervous system disorders:

Common: headache

Gastrointestinal disorders:

Very common: decreased appetite

Common: vomiting, diarrhea

Skin and subcutaneous tissue disorders:

Common: rash, urticaria or urticarial rash

General disorders and administration site conditions:

Very common: irritability, any erythema at the vaccination site, induration / swelling or pain / tenderness, somnolence, poor sleep quality, tenderness at the vaccination site (including impaired movement)

Common: fever

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

Adults aged ≥ 18 years and the elderly

The safety of the vaccine was evaluated in 6 clinical studies which included 7,097 adults aged 18 to 95 years.Prevenar 13 was administered to 5,667 adults; 2,616 (46.2%) aged between 50 and 64, and 3,051 (53.8%) adults aged 65 or over. Among patients treated with Prevenar 13, 1,916 adults had previously been vaccinated with 23-valent pneumococcal polysaccharide vaccine at least 3 years prior to study initiation and 3,751 were not vaccinated with 23-valent pneumococcal polysaccharide vaccine. One of the six studies included a group of adults (n = 899) aged 18 to 49 who had received Prevenar 13 and had not previously been vaccinated with 23-valent pneumococcal polysaccharide vaccine.

A trend towards a lower frequency of adverse reactions was associated with older age; adults aged> 65 years (regardless of previous pneumococcal vaccination status) reported fewer adverse reactions than younger adults, with adverse reactions generally more common in younger adults aged 18-29 years.

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

Adverse reactions observed in clinical studies

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

Metabolism and nutrition disorders:

Very common: decreased appetite

Nervous system disorders:

Very common: headache

Gastrointestinal disorders:

Very common: diarrhea; vomiting (in adults aged 18 to 49 years)

Common: vomiting (in adults aged 50 and over)

Uncommon: nausea

Disorders of the immune system:

Uncommon: hypersensitivity reactions including face edema, dyspnoea, bronchospasm

Skin and subcutaneous tissue disorders:

Very common: rash

General disorders and administration site conditions:

Very common: chills, fatigue, erythema at the vaccination site, induration / swelling at the vaccination site or pain / tenderness at the vaccination site (severe pain / tenderness at the vaccination site in adults aged 18 to 39 years), limitation in arm movement (severe limitation in arm movement very common in adults aged 18 to 39 years)

Common: fever (very common in adults aged 18-29 years)

Uncommon: localized lymphadenopathy in the region of the vaccination site

Musculoskeletal and connective tissue disorders

Very common: arthralgia, myalgia

Overall, there were no significant differences in the frequency of adverse reactions when Prevenar 13 was administered in adults previously vaccinated with pneumococcal polysaccharide vaccine.

A higher frequency in some systemic reactions was observed when Prevenar 13 was co-administered with the inactivated trivalent influenza vaccine (TIV) compared to when TIV was administered alone (headache, chills, rash, decreased appetite, arthralgia and myalgia ) or Prevenar 13 was administered alone (headache, chills, fatigue, decreased appetite and arthralgia)

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous 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. in "Annex V.

04.9 Overdose

An overdose with Prevenar 13 is unlikely as it comes as a pre-filled syringe.

However, cases of overdose with Prevenar 13 have been reported in infants and children due to subsequent doses given shorter than recommended than the previous dose.

In general, adverse events reported with overdose are consistent with those reported with administrations of Prevenar 13 according to the recommended pediatric vaccination schedule.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

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

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

Burden of disease in infants and children aged 6 weeks to 5 years.

Based on serotype surveillance in Europe, conducted prior to the introduction of Prevenar, Prevenar 13 has been estimated to cover 73-100% (depending on country) of the serotypes causing invasive pneumococcal disease (IPD). ) in children under the age of 5. In this age group, serotypes 1, 3, 5, 6A, 7F and 19A are responsible for 15.6% -59.7% of invasive disease, depending on the country. the period studied and the use of Prevenar. Acute otitis media (AOM) is a common childhood disease with different etiologies. Bacteria can be responsible for 60-70% of clinical episodes of AOM. S. pneumoniae it is one of the most common causes of bacterial AOM worldwide.

Prevenar 13 is estimated to cover more than 90% of the serotypes causing antibiotic-resistant invasive pneumococcal disease.

Burden of disease in children and adolescents aged 6 to 17 years

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

Burden of disease in adults ≥ 18 years of age and the elderly.

Adults with underlying comorbidities are at increased risk for invasive pneumococcal disease (IPD). Furthermore, the incidence of invasive pneumococcal disease (IPD) in adults increases with age starting from 50 years.

Based on surveillance data following the introduction of Prevenar but prior to the introduction of Prevenar 13 in childhood vaccination programs, pneumococcal serotypes present in Prevenar 13 may be responsible for at least 50 - 76% (depending on the country) of IPD in adults over 50 years of age.

Bacteremic pneumonia, unfocused bacteraemia and meningitis are the most common manifestations of IPD in adults and approximately 80% of IPD in adults is bacteremic pneumonia.

Clinical Immunogenicity Studies with Prevenar 13 in Infants, Children and Adolescents

The protective efficacy of Prevenar 13 against IPD has not been analyzed. As recommended by the World Health Organization (WHO), the evaluation of the potential efficacy against IPD in infants and young children was based on a comparison of immune responses. the seven serotypes common to Prevenar 13 and Prevenar, whose protective efficacy was demonstrated, and immune responses to the 6 additional serotypes were also evaluated.

Immune response following the three-dose infantile primary series

Clinical trials were conducted in several European countries and in the United States with a series of vaccination programs, including two randomized non-inferiority studies (in Germany with a primary series at 2, 3, 4 months [006] and in the United States with a primary series at 2, 4, 6 months [004]).

In these two studies, pneumococcal immune responses were compared using a set of non-inferiority criteria, including the percentage of subjects who had serotype-specific serotype-specific anti-polysaccharide IgG ≥ 0.35 μg / ml one month after the primary series and the comparison of geometric mean concentrations of IgG (ELISA GMC "s); in addition, functional antibody titers (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 7 common serotypes in those who received Prevenar.

Comparisons on non-inferiority of immune response in study 006, based on the proportion of infants achieving an IgG anti-polysaccharide concentration ≥ 0.35 mcg / mL, are shown in Table 1. The results from study 004 were similar. Non-inferiority of Prevenar 13 (lower limit of 95% CI for the percentage difference, between subjects of the two groups responding to 0.35 mcg / ml, greater than -10%) was demonstrated for all 7 common serotypes. , with the exception of serotype 6B in study 006 and serotypes 6B and 9V in study 004, which narrowly missed the margin. All 7 common serotypes met the pre-established non-inferiority criteria for IgG ELISA GMC "s. Prevenar 13 elicited antibody levels comparable, albeit slightly lower, to those of Prevenar for the 7 common serotypes. Clinical relevance of these differences is not known.

Non-inferiority was demonstrated in study 006 for the 6 additional serotypes, based on the number of neonates achieving an antibody concentration ≥ 0.35 μg / mL and in comparison of IgG ELISA GMCs, and was demonstrated for 5 of the 6 serotypes, with the exception of serotype 3 in study 004. For serotype 3, the percentages of Prevenar 13 recipients with serum IgG ≥ 0.35 mcg / ml were 98.2% (study 006) and 63 , 5% (study 004).

Prevenar 13 in studies 004 and 006 elicited functional antibodies for all 13 serotypes contained in the vaccine. For the 7 common serotypes, there were no differences in the percentages between subjects with OPA titers ≥ 1: 8. For each of the seven common serotypes, more than 96% and more than 90% of those who received Prevenar 13 achieved an OPA titre ≥ 1: 8 in studies 006 and 004, respectively, one month after the primary series.

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

Immune response following the two-dose primary series in neonates

Immunogenicity after two doses in neonates was demonstrated in four studies.

The percentage of children who achieved an IgG anticapsular pneumococcal polysaccharide concentration ≥ 0.35 mcg / ml, one month after the second dose, ranged between 79.6% and 98.5% in 11 of the 13 serotypes present in the vaccine. . Lower percentages of children reached the threshold of this antibody concentration for serotypes 6B (between 27.9% and 57.3%) and 23F (between 55.8% and 68.1%) in all 2- and 4-month dosing studies, compared to 58.4% for serotype 6B and 68.6% for serotype 23F in a 3- and 5-month dosing study. After the booster dose all vaccine serotypes, including 6B and 23F, had an immune response consistent with adequate stimulation with a two-dose primary series. In a study in the UK, functional antibody responses were comparable for all serotypes, including 6B and 23F in the Prevenar and Prevenar 13 groups after the primary series at two and four months of age and after the booster dose at 12 months of age. For those who received Prevenar 13, the percentage of those who responded with OPA titre ≥ 1: 8 was at least 87% after the primary series and at least 97% after the booster dose. The geometric mean OPA titers for serotypes 1,3 and 5 were lower than those of each of the other additional serotypes; the clinical relevance of this observation is unknown.

Responses after the booster dose following the two-dose and three-dose primary series in neonates.

For all 13 serotypes, after the booster dose, the antibody concentration increased from the pre-booster level. For 12 serotypes the antibody concentrations after the booster dose were higher than those achieved after the primary infant series. These observations are consistent with adequate stimulation (induction of an immunological memory).

The immune response after the booster dose for serotype 3 did not increase beyond the levels observed after the infant vaccination series; the clinical relevance of this observation regarding the induction of immune memory for serotype 3 is unknown.

Antibody responses following the booster dose after the primary infant series, both of two and three doses, were comparable to those achieved for all 13 vaccine serotypes.

For children aged 7 months to 5 years an "appropriate recovery vaccination schedule (as described in section 4.2) leads to anti-capsular polysaccharide IgG response levels for each of the 13 serotypes, at least comparable to those of the series three-dose primary in children.

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

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

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

Infants (12 - 59 months) fully immunized with Prevenar (7-valent)

Following a single dose administration of Prevenar 13 to children (12 - 59 months) who are considered to be fully immunized with Prevenar (7-valent) (2- or 3-dose primary series plus booster dose), the proportion reaching serum IgG levels ≥0.35mcg / 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 GMC and GMT is 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 serotypes 6B and 23F, similar to those induced by a three-dose infant series .

Children and adolescents between the ages of 5 and 17

In an open-label study of 592 healthy children and adolescents, including some with asthma (17.4%) who may be predisposed to pneumococcal infection, Prevenar 13 induced immune responses to all 13 serotypes. A single dose of Prevenar 13 It has been given to children aged 5 to 10 who have previously been vaccinated with at least 1 dose of Prevenar, and to children and adolescents aged 10 to 17 who have never been given a pneumococcal vaccine.

In both children aged 5 to 10 years 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 additional 6 serotypes compared to the immune response measured in terms of serum IgG after the fourth dose in vaccinated infants at 2, 4, 6 and 12-15 months of age.

In children and adolescents aged 10-17 years, the OPA GMTs 1 month after vaccination were not lower than the OPA GMTs in the age group 5 to 10 years for 12 of the 13 serotypes (except serotype 3).

Immune response following subcutaneous administration

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

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

Effect on the state of the nasopharyngeal carrier

In a surveillance study in France in children with acute otitis media, changes in nasopharyngeal carrier status of pneumococcal serotypes after the introduction of Prevenar (7-valent) and subsequently Prevenar 13 were evaluated. reduced carrier status of the 6 additional serotypes combined (and serotype 6C) and individual serotypes 6C, 7F, 19A when compared with Prevenar. A reduction was also noted for serotype 3 (2.5% vs 1.1% ; p = 0.1) Carrier status of serotypes 1 and 5 was not observed.

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

Protective efficacy of Prevenar (7-valent vaccine) 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 randomized, double-blind, active-controlled, in which children were randomized to receive Prevenar or the control vaccine (NCKP, meningococcal serogroup C CRM-conjugated vaccine [MnCC]; FinOM, hepatitis B vaccine) in a four-dose series at 2, 4, 6 and 12-15 months d "age. The efficacy results obtained from these studies (for invasive pneumococcal disease, pneumonia and acute otitis media) are listed below (table 2).

The protective efficacy of Prevenar (7-valent vaccine)

The efficacy (direct and indirect effect) of 7-valent Prevenar against pneumococcal disease was evaluated during both three-dose and two-dose primary infant series immunization programs, each with a booster dose (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 villages. Surveillance will continue with Prevenar 13, and as countries update their surveillance data, the information in this table may change.

Using the screening method, serotype-specific efficacy assessed for 2 doses administered under 1 year of age in the UK was 66% (-29.91%) and 100% (25.100%) for serotypes 6B and 23F, respectively.

The efficacy of Prevenar in the 3 + 1 immunization series has also been observed against acute otitis media and pneumonia since its introduction into the national immunization program. for children under 2 years of age, visits for AOM were reduced by 42.7% (95% CI, 42.4-43.1%) and prescriptions for AOM reduced by 41.9%, compared to the baseline prior to the introduction of Prevenar (2004 vs 1997-99). In a similar analysis, hospitalization and outpatient visits for pneumonia of any origin were reduced by 52.4% and 41.1%,

respectively. For the events specifically identified as pneumococcal pneumonia, the observed reduction in hospitalization and frequency of outpatient visits were 57.6% and 46.9%, respectively, in children less than 2 years of age, from the pre-baseline value. "introduction of Prevenar (2004 vs 1997-99). While the direct cause-effect relationship cannot be extrapolated from observational analyzes of this type, these results suggest that Prevenar plays an important role in reducing mucosal pathology (AOM and pneumonia) in the defined population.

Further data on the immunogenicity of 7-valent Prevenar: children with sickle cell anemia

The immunogenicity of Prevenar was analyzed in an open-label multicenter study of 49 infants with sickle cell anemia. Children were vaccinated with Prevenar (starting at two months of age, 3 doses with an interval of one month between dose and other) and 46 of these children were also vaccinated with a 23-valent pneumococcal polysaccharide vaccine at the age of 15-18 months. After primary immunization, 95.6% of subjects had antibody levels of at least 0, 35 mcg / ml for all seven serotypes present in Prevenar. After polysaccharide vaccination, a significant increase was observed in antibody concentrations against the seven serotypes, suggesting that immunological memory was well established.

Immunogenicity studies in adults ≥ 18 years of age and the elderly

In adults, an IgG binding antibody concentration threshold has not been defined for the antibody-specific pneumococcal polysaccharide that is associated with protection. In all pivotal clinical trials, the serotype specific opsonophagocytosis (OPA) titer was used as a surrogate to determine potential efficacy against invasive pneumococcal disease and pneumonia.

The geometric mean of OPA titers (GMTs) measured 1 month after each vaccination was calculated. The OPA titers are expressed as the reciprocal of the highest serum dilution that reduces pneumococcal survival by at least 50%.

Pivotal studies for Prevenar 13 were designed to demonstrate that functional OPA antibody responses for the 13 serotypes are not lower, and for some serotypes higher, than the 12 serotypes shared with the licensed 23-valent pneumococcal polysaccharide vaccine [1, 3 , 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F] one month after the administration of the vaccine. The response to serotype 6A, which is unique to Prevenar 13, was assessed by demonstrating a 4-fold increase in specific OPA titer above pre-immunization levels.

Five clinical studies have been conducted in Europe and the USA to evaluate the immunogenicity of Prevenar 13 in different age groups ranging from 18 to 95 years. Clinical studies with Prevenar 13 currently provide immunogenicity data in adults aged 18 and over. beyond, including adults aged 65 years previously vaccinated with one or more doses of the 23-valent pneumococcal polysaccharide vaccine, 5 years prior to enrollment. Each study includes healthy adults and immunocompetent adults with stable underlying conditions known to predispose individuals to pneumococcal infections (eg, chronic cardiovascular disease, chronic lung disease including asthma, kidney disorders, diabetes mellitus, chronic liver disease including liver disease alcohol), and adults with risk factors such as smoking and alcohol abuse.

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

Adults not previously vaccinated with 23-valent pneumococcal polysaccharide vaccine

In a comparative head-to-head study in adults aged 60 to 64 years, patients received a single dose of Prevenar 13 or 23-valent pneumococcal polysaccharide vaccine. In the same study, another group of adults between the ages of 50 and 59 and another group of adults between the ages of 18 and 49 received a single dose of Prevenar 13. Table 4 compares the OPA GMTs, 1 month after dosing, in the 60-64 year age group given a single dose of Prevenar 13 or 23-valent pneumococcal polysaccharide vaccine, and in the 50-59 year age group a single dose of Prevenar 13 was administered.

In adults aged 60 to 64 years, the OPA GMTs of Prevenar 13 were non-inferior to the OPA GMTs derived from the 23-valent pneumococcal polysaccharide vaccine for the twelve serotypes common to both vaccines. For 9 serotypes, OPA titers were shown to be higher with statistical significance in patients treated with Prevenar 13.

In adults 50 to 59 years of age, OPA GMTs for all 13 Prevenar 13 serotypes were non-inferior to responses in adults 60 to 64 years of age.

For 9 serotypes, the immune response was age-related, with the group of adults aged 50-59 showing greater responses with statistical significance than adults aged 60-64.

In all adults 50 years of age and older who received a single dose of Prevenar 13, OPA titers for serotype 6A were significantly higher than adults 60 years of age or older who received a single dose. of 23-valent pneumococcal polysaccharide vaccine.

One year after vaccination with Prevenar 13 OPA titers decreased compared to one month after vaccination, however, OPA titers for all serotypes remained above baseline levels:

Table 5 shows OPA GMT 1 month after a single dose of Prevenar 13 in patients aged 18 to 49 years compared to patients aged 60 to 64 years.

In adults 18 to 49 years of age OPA GMTs for all 13 Prevenar 13 serotypes were non-inferior to the responses to Prevenar 13 seen in adults 60 to 64 years of age.

OPA titers decreased one year after vaccination with Prevenar 13 compared with one month after vaccination, however they remained higher for all serotypes than baseline levels.

Adults previously vaccinated with 23-valent pneumococcal polysaccharide vaccine

Immune responses with Prevenar 13 and 23-valent pneumococcal polysaccharide vaccine were compared in a head-to-head study in adults aged 70 years or older who received a single dose of pneumococcal polysaccharide vaccine at least 5 years prior to the study. vaccination.

Table 6 compares the OPA GMTs, 1 month after administration, in adults aged 70 years or older, vaccinated with a single dose of Prevenar 13 or 23-valent pneumococcal polysaccharide vaccine.

In adults vaccinated with pneumococcal polysaccharide vaccine at least 5 years prior to the clinical study, OPA GMTs of Prevenar 13 were non-inferior to responses to 23-valent pneumococcal polysaccharide vaccine for twelve serotypes in common. Furthermore, OPAs of 10 out of 12 common serotypes were shown to be greater with statistical significance in this study.

The immune response to serotype 6A was statistically significantly greater following vaccination with Prevenar 13 than with 23-valent pneumococcal polysaccharide vaccine. One year after vaccination with Prevenar 13 in adults 70 years of age and older vaccinated with 23-valent pneumococcal polysaccharide vaccine, at least 5 years before starting the study, OPA titers were lower than one month after vaccination, however, OPA titers for all serotypes remained above baseline levels:

05.2 "Pharmacokinetic properties

Evaluation of pharmacokinetic properties is not required for vaccines.

05.3 Preclinical safety data

Non-clinical data for Prevenar 13 revealed no particular risk for humans, based on conventional studies of safety pharmacology, single or repeated dose toxicity, local tolerability, developmental and reproductive toxicity.

06.0 PHARMACEUTICAL INFORMATION

06.1 Excipients

Sodium chloride

Succinic acid

Polysorbate 80

Water for injections

For the adjuvant, see section 2.

06.2 Incompatibility

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

06.3 Period of validity

3 years

06.4 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 must be used or discarded. These data are intended to provide guidance to healthcare professionals in the event of temporary temperature excursions.

06.5 Nature of the immediate packaging and contents of the package

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

Packs of 1 and 10, with or without needle, and multipack comprising 5 packs of 10 pre-filled syringes without needle.

Not all pack sizes may be marketed.

06.6 Instructions for use and handling

During storage, a white deposit and a clear supernatant can be observed. The vaccine should be shaken thoroughly until a homogeneous white suspension is obtained before expelling air from the syringe, and should be visually inspected for any corpuscular elements and / or changes in physical appearance prior to administration. Do not use if the contents appear different.

No special instructions for disposal.

Unused medicine and discarded waste derived from this medicine must be disposed of in accordance with local regulations.

07.0 MARKETING AUTHORIZATION HOLDER

Pfizer Limited

Ramsgate Road

Sandwich

Kent CT13 9NJ

UK

08.0 MARKETING AUTHORIZATION NUMBER

EU / 1/09/590/001

039550013

EU / 1/09/590/002

039550025

EU / 1/09/590/003

039550037

EU / 1/09/590/004

039550049

EU / 1/09/590/005

039550052

EU / 1/09/590/006

039550064

09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION

Date of first authorization: 9 December 2009

10.0 DATE OF REVISION OF THE TEXT

July 2013

11.0 FOR RADIO DRUGS, COMPLETE DATA ON THE INTERNAL RADIATION DOSIMETRY

12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON EXEMPORARY PREPARATION AND QUALITY CONTROL