- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
|Pneumococcal polysaccharide serotype 11,2 Pneumococcal polysaccharide serotype 41,2 Pneumococcal polysaccharide serotype 51,2 Pneumococcal polysaccharide serotype 6B1,2 Pneumococcal polysaccharide serotype 7F1,2 Pneumococcal polysaccharide serotype 9V1,2 Pneumococcal polysaccharide serotype 141,2 Pneumococcal polysaccharide serotype 18C1,3 Pneumococcal polysaccharide serotype 19F1,4 Pneumococcal polysaccharide serotype 23F1,2||1 microgram 3 micrograms 1 microgram 1 microgram 1 microgram 1 microgram 1 microgram 3 micrograms 3 micrograms 1 microgram|
|1 adsorbed on aluminium phosphate 2 conjugated to protein D (derived from non-typeable Haemophilus influenzae) carrier protein 3 conjugated to tetanus toxoid carrier protein 4 conjugated to diphtheria toxoid carrier protein||0.5 milligram Al3+ 9-16 micrograms 5-10 micrograms 3-6 micrograms|
PosologyThe immunisation schedules for Synflorix should be based on official recommendations.
Infants from 6 weeks to 6 months of age
Three-dose primary seriesThe recommended immunisation series to ensure optimal protection consists of four doses, each of 0.5 ml. The primary infant series consists of three doses with the first dose usually given at 2 months of age and with an interval of at least 1 month between doses. The first dose may be given as early as six weeks of age. A booster (fourth) dose is recommended at least 6 months after the last priming dose and preferably between 12 and 15 months of age (see sections 4.4 and 5.1).
Two-dose primary seriesAlternatively, when Synflorix is given as part of a routine infant immunisation programme, a series consisting of three doses, each of 0.5 ml may be given. The first dose may be administered from the age of 2 months, with a second dose 2 months later. A booster (third) dose is recommended at least 6 months after the last primary dose (see section 5.1).
Preterm newborn infants (born between 27-36 weeks gestation)In preterm infants born after at least 27 weeks of gestational age, the recommended immunisation series consists of four doses, each of 0.5ml. The primary infant series consists of three doses with the first dose given at 2 months of age and with an interval of at least 1 month between doses. A booster (fourth) dose is recommended at least 6 months after the last primary dose (see sections 4.4 and 5.1).
Unvaccinated infants and children ≥ 7 months of age- infants aged 7-11 months: The vaccination schedule consists of two primary doses of 0.5 ml with an interval of at least 1 month between doses. A booster (third) dose is recommended in the second year of life with an interval of at least 2 months after the last primary dose.- children aged 12 months - 5 years: The vaccination schedule consists of two doses of 0.5 ml with an interval of at least 2 months between doses. It is recommended that subjects who receive a first dose of Synflorix complete the full vaccination course with Synflorix.
Paediatric populationThe safety and efficacy of Synflorix in children over 5 years of age have not been established.
Method of administrationThe vaccine should be given by intramuscular injection. The preferred sites are anterolateral aspect of the thigh in infants or the deltoid muscle of the upper arm in young children.
Use with other vaccinesSynflorix can be given concomitantly with any of the following monovalent or combination vaccines [including DTPa-HBV-IPV/Hib and DTPw-HBV/Hib]: diphtheria-tetanus-acellular pertussis vaccine (DTPa), hepatitis B vaccine (HBV), inactivated polio vaccine (IPV), Haemophilus influenzae type b vaccine (Hib), diphtheria-tetanus-whole cell pertussis vaccine (DTPw), measles-mumps-rubella vaccine (MMR), varicella vaccine (V), meningococcal serogroup C conjugate vaccine (CRM197 and TT conjugates), meningococcal serogroups A, C, W-135 and Y conjugate vaccine (TT conjugate), oral polio vaccine (OPV) and oral rotavirus vaccine. Different injectable vaccines should always be given at different injection sites.Clinical studies demonstrated that the immune responses and the safety profiles of the co-administered vaccines were unaffected, with the exception of the inactivated poliovirus type 2 response, for which inconsistent results were observed across studies (seroprotection ranging from 78% to 100%). In addition when the meningococcal serogroups A, C, W-135 and Y vaccine (TT conjugate) was co-administered with a booster dose of Synflorix during the second year of life in children primed with 3 doses of Synflorix, lower antibody geometric mean concentration (GMC) and opsonophagocytic assay geometric mean titre (OPA GMT) were observed for one pneumococcal serotype (18 C). There was no impact of co-administration on the other nine pneumococcal serotypes. Enhancement of antibody response to Hib-TT conjugate, diphtheria and tetanus antigens was observed. The clinical relevance of the above observations is unknown.
Use with systemic immunosuppressive medicinal productsAs with other vaccines, it may be expected that in patients receiving immunosuppressive treatment an adequate response may not be elicited.
Use with prophylactic administration of antipyreticsSee section 4.4.
Summary of the safety profileSafety assessment of Synflorix was based on clinical trials involving the administration of 63,905 doses of Synflorix to 22,429 healthy children and 137 preterm infants as primary vaccination. Furthermore, 19,466 children and 116 preterm infants received a booster dose of Synflorix in the second year of life.Safety was also assessed in 435 previously unvaccinated children from 2 to 5 years old of which 285 subjects received 2 doses of Synflorix.In all trials, Synflorix was administered concurrently with the recommended childhood vaccines.In infants, the most common adverse reactions observed after primary vaccination were redness at the injection site and irritability which occurred after approximately 41% and 55% of all doses respectively. Following booster vaccination, the most common adverse reactions were pain at the injection site and irritability, which occurred at approximately 51% and 53% respectively. The majority of these reactions were of mild to moderate severity and were not long lasting.No increase in the incidence or severity of the adverse reactions was seen with subsequent doses of the primary vaccination series.Local reactogenicity of primary vaccination course was similar in infants < 12 months of age and in children > 12 months of age except for injection site pain for which the incidence increased with increasing age: pain was reported by more than 39% of the infants < 12 months of age and by more than 58% of the children > 12 months of age.Following booster vaccination, children > 12 months of age are more likely to experience injection site reactions compared to the rates observed in infants during the primary series with Synflorix.Following catch-up vaccination in children 12 to 23 months of age, urticaria was reported more frequently (uncommon) compared to the rates observed in infants during primary and booster vaccination.Reactogenicity was higher in children receiving whole cell pertussis vaccines concomitantly. In a clinical study children received either Synflorix (N=603) or 7-valent Prevenar (N=203) concomitantly with a DTPw containing vaccine. After the primary vaccination course, fever ≥38°C and >39°C was reported respectively in 86.1% and 14.7% of children receiving Synflorix and in 82.9% and 11.6% of children vaccinated with 7-valent Prevenar.In comparative clinical studies, the incidence of local and general adverse events reported within 4 days after each vaccination dose was within the same range as after vaccination with 7-valent Prevenar.
Tabulated list of adverse reactionsAdverse reactions (for all age groups) considered as being at least possibly related to vaccination have been categorised by frequency.Frequencies are reported as:
|Very common: Common: Uncommon: Rare: Very rare:||(≥ 1/10) (≥1/100 to <1/10) (≥1/1,000 to <1/100) (≥1/10,000 to <1/1,000) (<1/10,000)|
|System Organ Class||Frequency||Adverse reactions|
|Immune system disorders||Rare||Allergic reactions (such as allergic dermatitis, atopic dermatitis, eczema)|
|Metabolism and nutrition disorders||Very common||Appetite lost|
|Psychiatric disorders||Very common||Irritability|
|Nervous system disorders||Very common||Drowsiness|
|Rare||Convulsions (including febrile convulsions)|
|Vascular disorders||Very rare||Kawasaki disease|
|Respiratory, thoracic and mediastinal disorders||Uncommon||Apnoea in very premature infants (≤28 weeks of gestation) (see section 4.4)|
|Gastrointestinal disorders||Uncommon||Diarrhoea, vomiting|
|Skin and subcutaneous tissue disorders||Uncommon||Rash|
|General disorders and administration site conditions||Very common||Pain, redness, swelling at the injection site, fever ≥38°C rectally (age < 2 years)|
|Common||Injection site reactions like injection site induration, fever >39°C rectally (age < 2 years)|
|Uncommon||Injection site reactions like injection site haematoma, haemorrhage and nodule|
|Adverse reactions additionally reported after booster vaccination of primary series and/or catch-up vaccination:|
|Nervous system disorders||Uncommon||Headache (age 2 to 5 years)|
|Gastrointestinal disorders||Uncommon||Nausea (age 2 to 5 years)|
|General disorders and administration site conditions||Common||Fever ≥38°C rectally (age 2 to 5 years)|
|Uncommon||Injection site reactions like pruritus, fever > 40°C rectally (age < 2 years), fever >39°C rectally (age 2 to 5 years), diffuse swelling of the injected limb, sometimes involving the adjacent joint|
|Immune system disorders||Very rare||Anaphylaxis|
|Nervous system disorders||Rare||Hypotonic-hyporesponsive episode|
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via:
IrelandHPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; e-mail: firstname.lastname@example.org
United Kingdomthe Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
1. Epidemiological dataThe 10 pneumococcal serotypes included in this vaccine represent the major disease-causing serotypes in Europe covering approximately 56% to 90% of invasive pneumococcal disease (IPD) in children <5 years of age. In this age group, serotypes 1, 5 and 7F account for 3.3% to 24.1% of IPD depending on the country and time period studied.Pneumonia of different aetiologies is a leading cause of childhood morbidity and mortality globally. In prospective studies, Streptococcus pneumoniae was estimated to be responsible for 30-50% of pneumonia cases.Acute otitis media (AOM) is a common childhood disease with different aetiologies. Bacteria can be responsible for 60-70% of clinical episodes of AOM. Streptococcus pneumoniae and Non-Typeable Haemophilus influenzae (NTHi) are the most common causes of bacterial AOM worldwide.
2. Efficacy and effectiveness in clinical trialsIn a large-scale phase III/IV, double-blind, cluster-randomized, controlled, clinical trial in Finland (FinIP), children were randomised into 4 groups according to the two infant vaccination schedules [2-dose (3, 5 months of age) or 3-dose (3, 4, 5 months of age) primary schedule followed by a booster dose as of 11 months of age] to receive either Synflorix (2/3rd of clusters) or hepatitis vaccines as control (1/3rd of clusters). In the catch-up cohorts, children between 7-11 months of age at first vaccine dose received Synflorix or hepatitis B control vaccine according to a 2-dose primary schedule followed by a booster dose and children between 12-18 months of age at first vaccine dose received 2 doses of either Synflorix or hepatitis A control vaccine. Average follow-up, from first vaccination, was 24 to 28 months for invasive disease and hospital-diagnosed pneumonia. In a nested study, infants were followed up till approximately 21 months of age to assess impact on nasopharyngeal carriage and physician-diagnosed AOM reported by parents.In a large-scale phase III, randomized, double-blind clinical trial (Clinical Otitis Media and Pneumonia Study - COMPAS) conducted in Argentina, Panama and Colombia, healthy infants aged 6 to 16 weeks received either Synflorix or hepatitis B control vaccine at 2, 4 and 6 months of age followed respectively by either Synflorix or hepatitis A control vaccine at 15 to 18 months of age.
2.1. Invasive pneumococcal disease (which includes sepsis, meningitis, bacteraemic pneumonia and bacteraemia)
Effectiveness/efficacy in infant cohort below 7 months of age at enrolmentVaccine effectiveness or efficacy (VE) was demonstrated in preventing culture-confirmed IPD due to vaccine pneumococcal serotypes when Synflorix was given to infants in either 2+1 or 3+1 schedules in FinIP or 3+1 schedule in COMPAS (see Table 1).Table 1: Number of vaccine serotype IPD cases and vaccine effectiveness (FinIP) or efficacy (COMPAS) in infants below 7 months of age at enrolment receiving at least one vaccine dose (Infant total vaccinated cohort)
|Type of IPD||FinIP||COMPAS|
|No. of IPD cases||VE (95% CI)||No. of IPD cases||VE (95% CI)|
|Synflorix 3+1 schedule||Synflorix 2+1 schedule||Control(2)||3+1 schedule||2+1 schedule||Synflorix 3+1 schedule||Control||3+1 schedule|
|N 10,273||N 10,054||N 10,200||N 11,798||N 11,799|
|Vaccine serotype IPD(1)||0||1||12||100%(3) (82.8; 100)||91.8%(4) (58.3; 99.6)||0||18||100%(5) (77.3; 100)|
|Serotype 6B IPD||0||0||5||100% (54.9; 100)||100% (54.5; 100)||0||2||-|
|Serotype 14 IPD||0||0||4||100% (39.6; 100)||100% (43.3; 100)||0||9||100% (49.5; 100)|
Effectiveness following catch-up immunisationAmong the 15,447 children in the catch-up vaccinated cohorts, there were no culture-confirmed IPD cases in the Synflorix groups while 5 vaccine serotype IPD cases were observed in the control groups (serotypes 4, 6B, 7F, 14 and 19F).
2.2 PneumoniaEfficacy against pneumonia was assessed in COMPAS. The mean duration follow-up from 2 weeks post-dose 3 in the ATP cohort was 23 months (range from 0 to 34 months) for the interim analysis (IA) and 30 months (range from 0 to 44 months) for the end-of-study analysis. At the end of this IA or end-of-study ATP follow-up period, the mean age was 29 months (range from 4 to 41 months) and 36 months (range from 4 to 50 months), respectively. The proportion of subjects who received the booster dose in the ATP cohort was 92.3% in both analyses.Efficacy of Synflorix against first episodes of likely bacterial Community Acquired Pneumonia (CAP) occurring from 2 weeks after the administration of the 3rd dose was demonstrated in the ATP cohort (P value ≤ 0.002) in the interim analysis (event-driven; primary objective). Likely bacterial CAP (B-CAP) is defined as radiologically confirmed CAP cases with either alveolar consolidation/pleural effusion on the chest X-ray, or with non alveolar infiltrates but with C reactive protein (CRP) ≥ 40 mg/L.The vaccine efficacy against B-CAP observed at the interim analysis is presented below (table 2).
Table 2: Numbers and percentages of subjects with first episodes of B-CAP occurring from 2 weeks after the administration of the 3rd dose of Synflorix or control vaccine and vaccine efficacy (ATP cohort)
|Synflorix N=10,295||Control vaccine N=10,201||Vaccine efficacy|
|n||% (n/N)||n||% (n/N)|
|240||2.3%||304||3.0%||22.0% (95% CI: 7.7; 34.2)|
2.3. Acute Otitis Media (AOM)Two efficacy studies, COMPAS and POET (Pneumococcal Otitis Media Efficacy Trial), were conducted with pneumococcal conjugate vaccines containing protein D: Synflorix and an investigational 11-valent conjugate vaccine (which in addition contained serotype 3), respectively.In COMPAS, 7,214 subjects [Total Vaccinated cohort (TVC)] were included in the AOM efficacy analysis of which 5,989 subjects were in the ATP cohort (Table 3). Table 3: Vaccine efficacy against AOM(1) in COMPAS
|Type or cause of AOM||Vaccine efficacy (95% CI)|
|Clinical AOM||16.1% (-1.1; 30.4)(3)|
|Any pneumococcal serotype||56.1% (13.4; 77.8)|
|10 pneumococcal vaccine serotypes||67.1% (17.0; 86.9)|
|Non-typeable Haemophilus influenzae (NTHi)||15.0%(4) (-83.8; 60.7)|
2.4 Impact on nasopharyngeal carriage (NPC)The effect of Synflorix on nasopharyngeal carriage was studied in 2 double-blind randomised studies using an inactive control: in the nested study of FinIP in Finland (5,023 subjects) and in COMPAS (1,700 subjects).In both COMPAS and the nested Finnish study, Synflorix reduced vaccine type carriage with an apparent increase in non-vaccine (excluding vaccine-related) serotypes observed after booster. The results were not statistically significant across all analyses in COMPAS. However, taken together there was a trend for decrease in overall pneumococcal carriage.In both studies there were significant decrease of individual serotypes 6B and 19F. In the nested Finnish study, a significant reduction was also observed for individual serotypes 14, 23F and, in the 3 dose primary schedule, for the cross-reactive serotype 19A.
3. Effectiveness in post-marketing surveillanceIn Brazil, Synflorix was introduced into the national immunisation programme (NIP) using a 3+1 schedule in infants (2, 4, 6 months of age and a booster dose at 12 months) with a catch-up campaign in children up to 2 years of age. Based on almost 3 years of surveillance following Synflorix introduction, a matched case-control study reported a significant decrease in culture or PCR confirmed IPD due to any vaccine serotype, and IPD due to individual serotypes 6B, 14 and 19A.
Table 4: Summary of effectiveness of Synflorix for IPD in Brazil
|Types of IPD(1)||Adjusted Effectiveness(2) % (95% CI)|
|Any vaccine serotype IPD(3) - Invasive pneumonia or bacteraemia - Meningitis||83.8% (65.9;92.3) 81.3% (46.9;93.4) 87.7% (61.4;96.1)|
|IPD due to individual serotypes(4) - 6B - 14 - 19A||82.8% (23.8;96.1) 87.7% (60.8;96.1) 82.2% (10.7;96.4)|
Table 5: Rates of IPD and the corresponding rate reductions in Finland
|IPD||Incidence per 100,000 person years||Relative rate reduction(1) % (95% CI)|
|Before NIP||After NIP|
|Any culture confirmed||62.9||12.9||80% (72;85)|
|Any vaccine serotype(2)||49.1||4.2||92% (86;95)|
|Serotype 19A||5.5||2.1||62% (20;85)|
4. Immunogenicity data
4.1 Immunologic non-inferiority to 7-valent PrevenarThe assessment of potential efficacy against IPD pre-licensure was based on a comparison of immune responses to the seven serotypes shared between Synflorix and another pneumococcal conjugate vaccine for which protective efficacy was evaluated previously (i.e. 7-valent Prevenar), as recommended by the WHO. Immune responses to the extra three serotypes in Synflorix were also measured.In a head-to-head comparative trial with 7-valent Prevenar, non-inferiority of the immune response to Synflorix measured by ELISA was demonstrated for all serotypes, except for 6B and 23F (upper limit of the 96.5% CI around the difference between groups >10%) (Table 6). For serotypes 6B and 23F, respectively, 65.9% and 81.4% of infants vaccinated at 2, 3 and 4 months reached the antibody threshold (i.e. 0.20 µg/ml) one month after the third dose of Synflorix versus 79.0% and 94.1% respectively, after three doses of 7-valent Prevenar. The clinical relevance of these differences is unclear, as Synflorix was observed to be effective against IPD caused by serotype 6B in a double-blind, cluster-randomized clinical study (see Table 1).The percentage of vaccinees reaching the threshold for the three additional serotypes in Synflorix (1, 5 and 7F) was respectively 97.3%, 99.0% and 99.5% and was at least as good as the aggregate 7-valent Prevenar response against the 7 common serotypes (95.8%). Table 6: Comparative analysis between 7-valent Prevenar and Synflorix in percentage of subjects with antibody concentrations ≥ 0.20 µg/ml one month post-dose 3
|Antibody||Synflorix||7-valent Prevenar||Difference in % ≥ 0.20μg/ml (7-valent Prevenar minus Synflorix)|
4.2 Additional immunogenicity data
Infants from 6 weeks to 6 months of age
3-dose primary scheduleIn total eight studies, conducted in various countries across Europe, in Chile and in the Philippines, have evaluated the immunogenicity of Synflorix after a three-dose primary series (N=3,089) according to different vaccination schedules (6-10-14 weeks, 2-3-4, 3-4-5 or 2-4-6 months of age). A fourth (booster) dose was given in six clinical studies to 1,976 subjects. In general, comparable vaccine responses were observed for the different schedules, although somewhat higher immune responses were noted for the 2-4-6 month schedule.
2-dose primary scheduleThe immunogenicity of Synflorix following a 2-dose or 3-dose primary vaccination schedule in subjects less than 6 months of age was evaluated in a clinical study. Although there was no significant difference between the two groups in the percentages of subjects with antibody concentration ≥ 0.20 μg/mL (ELISA), the percentages of subjects for serotypes 6B and 23F were lower than for the other vaccine serotypes (Table 7 and Table 8). The percentage of subjects with OPA titres ≥ 8 in 2-dose primed subjects compared to 3-dose primed subjects were lower for serotypes 6B, 18C and 23F (74.4%, 82.8%, 86.3% respectively for the 2-dose schedule and 88.9%, 96.2%, 97.7% respectively for the 3-dose schedule). Overall, the persistence of the immune response until the booster at 11 months of age was lower in the 2-dose primed subjects. In both schedules, a booster response indicative of immunological priming was observed for each vaccine serotype (Table 7 and Table 8). After the booster dose a lower percentage of subjects with OPA titres ≥ 8 was observed in the 2-dose schedule for serotypes 5 (87.2% versus 97.5% for the 3-dose primed subjects) and 6B (81.1% versus 90.3%), all other responses were comparable.
Table 7: Percentage of 2-dose primed subjects with antibody concentrations ≥ 0.20 µg/ml one month post-primary and one month post-booster
|Antibody||≥ 0.2μg/mL (ELISA)|
|%||95% CI||%||95% CI|
Table 8: Percentage of 3-dose primed subjects with antibody concentrations ≥ 0.20 µg/ml one month post-primary and one month post-booster
|Antibody||≥ 0.2μg/mL (ELISA)|
|%||95% CI||%||95% CI|
Immune memoryIn the follow-up of the study evaluating the 2-dose and 3-dose primary vaccination schedules, the persistence of antibodies at 36-46 months of age was demonstrated in subjects that had received a 2-dose primary series followed by a booster dose with at least 83.7% of subjects remaining seropositive for vaccine serotypes and the cross-reactive serotype 19A. In subjects that had received a 3-dose primary series followed by a booster dose, at least 96.5% of the subjects remained seropositive for vaccine serotypes and 86.4% for serotype 19A. After a single dose of Synflorix, administered during the 4th year of life, as a challenge dose, the fold increase in ELISA antibody GMCs and OPA GMTs, pre to post vaccination, was similar in 2-dose primed subjects to that in 3-dose primed subjects. These results are indicative of immunological memory in primed subjects for all vaccine serotypes and the cross-reactive serotype 19A.
Unvaccinated infants and children ≥ 7 months of ageThe immune responses elicited by Synflorix in previously unvaccinated older children were evaluated in three clinical studies.The first clinical study evaluated the immune responses for vaccine serotypes and the cross-reactive serotype 19A in children aged 7-11 months, 12-23 months and 2 to 5 years:• Children aged 7-11 months received 2 primary doses followed by a booster dose in the second year of life. The immune responses after the booster dose in this age group were generally similar to those observed after the booster dose in infants who had been primed with 3 doses below 6 months of age.• In children aged 12-23 months, the immune responses elicited after two doses were comparable to the responses elicited after three doses in infants below 6 months of age, except for vaccine serotypes 18C and 19F as well as serotype 19A for which responses were higher in the 12-23 months children. • In children aged 2 to 5 years that received 1 dose, the ELISA antibody GMCs were similar for 6 vaccine serotypes as well as serotype 19A than those achieved following a 3-dose vaccination schedule in infants below 6 months of age while they were lower for 4 vaccine serotypes (serotypes 1, 5, 14 and 23F). The OPA GMTs were similar or higher following a single dose than a 3 dose primary course in infants below 6 months of age, except for serotype 5.In the second clinical study, a single dose administered four months after two catch-up doses at 12-20 months of age elicited a marked increase of ELISA GMCs and OPA GMTs (when comparing the responses pre and post the last dose), indicating that two catch-up doses provide adequate priming.The third clinical study showed that the administration of 2 doses with a 2 month interval starting at 36-46 months of age resulted in higher ELISA antibody GMCs and OPA GMTs than those observed one month after a 3 dose primary vaccination for each vaccine serotype and the cross-reactive serotype 19A. The proportion of subjects with an ELISA antibody concentration ≥ 0.20 µg/mL or an OPA titre ≥ 8 for each vaccine serotype was comparable or higher in the catch-up group than in the 3-dose primed infants.Long-term persistence of antibodies has not been investigated after administration of a primary series in infants plus booster or after a two-dose priming in older children.In a clinical study, it has been demonstrated that Synflorix can be safely administered as a booster dose in the second year of life to children who had received 3 primary doses of 7-valent Prevenar. This study has shown that the immune responses against the 7 common serotypes were comparable to those elicited by a booster dose of 7-valent Prevenar. However, children who received 7-valent Prevenar for the primary series would not be primed against the additional serotypes contained in Synflorix (1, 5, 7F). Therefore the degree and duration of protection against invasive pneumococcal disease and otitis media due to these three serotypes in children of this age group following a single dose of Synflorix cannot be predicted.
4.3. Immunogenicity data in preterm infantsImmunogenicity of Synflorix in very preterm (gestation period of 27-30 weeks) (N=42), preterm (gestation period of 31-36 weeks) (N=82) and full term (gestation period > 36 weeks) (N=132) infants was evaluated following a 3 dose primary vaccination course at 2, 4, 6 months of age. Immunogenicity following a fourth dose (booster dose) at 15 to 18 months of age was evaluated in 44 very preterm, 69 preterm and 127 full term infants.One month after primary vaccination (i.e. after the third dose), for each vaccine serotype at least 92.7% of subjects achieved ELISA antibody concentrations ≥ 0.2 µg/ml and at least 81.7% achieved OPA titres ≥ 8 except serotype 1 (at least 58.8% with OPA titres ≥ 8). Similar antibody GMCs and OPA GMTs were observed for all infants except lower antibody GMCs for serotypes 4, 5, 9V and the cross-reactive serotype 19A in very preterms and serotype 9V in preterms and lower OPA GMT for serotype 5 in very preterms. The clinical relevance of these differences is not known.One month after the booster dose increases of ELISA antibody GMCs and OPA GMTs were seen for each vaccine serotype and the cross-reactive serotype 19A, indicative of immunological memory. Similar antibody GMCs and OPA GMTs were observed for all infants except a lower OPA GMT for serotype 5 in very preterm infants. Overall, for each vaccine serotype at least 97.6% of subjects achieved ELISA antibody concentrations ≥ 0.2µg/ml and at least 91.9% achieved OPA titres ≥ 8.The European Medicines Agency has deferred the obligation to submit the results of studies with Synflorix in one or more subsets of the paediatric population in diseases caused by Streptococcus pneumoniae and in acute otitis media caused by Haemophilus influenzae (see section 4.2 for information on paediatric use).
Instructions for administration of the vaccine
|1. Holding the syringe barrel in one hand (avoid holding the syringe plunger), unscrew the syringe cap by twisting it anticlockwise. 2. To attach the needle to the syringe, twist the needle clockwise into the syringe until you feel it lock. 3. Remove the needle protector, which on occasion can be a little stiff.|
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