Suspension for injection (injection). The vaccine is a turbid white suspension.

Active immunisation against invasive disease and acute otitis media caused by Streptococcus pneumoniae in infants and children from 6 weeks up to 2 years of age. The use of Synflorix 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.

Method of administration

The 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.

Posology

The immunisation schedules for Synflorix should be based on official recommendations.

Infants from 6 weeks to 6 months of age

The primary vaccination schedule consists of three doses of 0.5 ml with an interval of at least 1 month between doses.

A booster dose is recommended at least 6 months after the last priming dose and preferably between 12 and 15 months of age.

Previously unvaccinated older infants and children

- infants aged 7-11 months: The vaccination schedule consists of two doses 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 with an interval of at least 2 months between doses.

- children aged 12-23 months: The vaccination schedule consists of two doses of 0.5 ml with an interval of at least 2 months between doses. The need for a booster dose after this immunisation schedule has not been established.

It is recommended that subjects who receive a first dose of Synflorix complete the full vaccination course with Synflorix.

Hypersensitivity to the active substances or to any of the excipients, or to any of the carrier proteins.

As with other vaccines, the administration of Synflorix 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.

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

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.

Synflorix should under no circumstances be administered intravascularly or intradermally. No data are available on subcutaneous administration of Synflorix.

As for other vaccines administered intramuscularly, Synflorix should be given with caution to individuals with thrombocytopenia or any coagulation disorder since bleeding may occur following an intramuscular administration to these subjects.

Official recommendations for the immunisation against diphtheria, tetanus and Haemophilus influenzae type b should also be followed.

There is insufficient evidence that Synflorix provides protection against pneumococcal serotypes not contained in the vaccine or against non-typeable Haemophilus influenzae. Synflorix does not provide protection against other micro-organisms.

As with any vaccine, Synflorix may not protect all vaccinated individuals against invasive pneumococcal disease or otitis media caused by the serotypes in the vaccine. Protection against otitis media caused by pneumococcal serotypes in the vaccine is expected to be substantially lower than protection against invasive disease. In addition, as otitis media is caused by many micro-organisms other than the Streptococcus pneumoniae serotypes represented in the vaccine, the overall protection against otitis media is expected to be limited.

In clinical trials Synflorix elicited an immune response to all ten serotypes included in the vaccine, but the magnitude of the responses varied between serotypes. The functional immune response to serotypes 1 and 5 was lower in magnitude than the response against all other vaccine serotypes. It is not known whether this lower functional immune response against serotypes 1 and 5 will result in lower protective efficacy against invasive disease or otitis media caused by these serotypes.

Synflorix is indicated for use in children aged from 6 weeks up to 2 years. Children should receive the dose regimen of Synflorix that is appropriate to their age at the time of commencing the vaccination series. Safety and immunogenicity data are not yet available in children above 2 years of age.

The immune response elicited after two doses of Synflorix in children 12-23 months of age is comparable to the response elicited after three doses in infants. The immune response to a booster dose after two doses in children aged 12-23 months has not been evaluated, but a booster dose may be needed to ensure optimal individual protection.

However, a 2-dose schedule in children aged 12-23 months with high risk of pneumococcal disease (such as children with sickle-cell disease, asplenia, HIV infection, chronic illness or who are immunocompromised) may not be sufficient to provide optimal protection. In these children, a 23-valent pneumococcal polysaccharide vaccine should be given 2 years of age, whenever recommended. The interval between the pneumococcal conjugate vaccine (Synflorix) 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 pneumococcal polysaccharide vaccine to Synflorix primed children may result in hyporesponsiveness to further doses of pneumococcal polysaccharide or to pneumococcal conjugate vaccine.

Safety and immunogenicity data in children with increased risk for pneumococcal infections (sickle cell disease, congenital and acquired splenic dysfunction, HIV-infected, malignancy, nephrotic syndrome) are not available.

Children with impaired immune responsiveness, whether due to the use of immunosuppressive therapy, a genetic defect, HIV infection, or other causes, may have reduced antibody response to vaccination.

Prophylactic administration of antipyretics before or immediately after vaccine administration can reduce the incidence and intensity of post-vaccination febrile reactions. However, data suggest that the prophylactic use of paracetamol might reduce the immune response to Synflorix. The clinical relevance of this observation, as well as the impact of antipyretics other than paracetamol on the immune response to Synflorix remains unknown.

The use of prophylactic antipyretic medicinal products is recommended:

- for all children receiving Synflorix simultaneously with vaccines containing whole cell pertussis because of higher rate of febrile reactions.

- for children with seizure disorders or with a prior history of febrile seizures.

Antipyretic treatment should be initiated according to local treatment guidelines.

Use with other vaccines

Synflorix 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), 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%). The clinical relevance of this observation is not known. No negative interference was observed with meningococcal conjugate vaccines irrespective of the carrier protein (CRM197 and TT conjugates). Enhancement of antibody response to Hib-TT conjugate, diphtheria and tetanus antigens was observed.

Use with systemic immunosuppressive medicinal products

As with other vaccines, it may be expected that in patients receiving immunosuppressive treatment an adequate response may not be elicited.

Clinical trials involved the administration of 12,879 doses of Synflorix to 4,595 healthy children as primary vaccination. Furthermore, 3,870 children received a booster dose of Synflorix in the second year of life. In all trials, Synflorix was administered concurrently with the recommended childhood vaccines.

The most common adverse reactions observed after primary vaccination were redness at the injection site and irritability which occurred after 38.3% and 52.3% of all doses respectively. Following booster vaccination, these adverse reactions occurred at 52.6% and 55.4% 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.

An increase in reactogenicity was reported after booster vaccination compared to the doses of the primary course with Synflorix.

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.

Adverse reactions (following primary immunisation or booster dose) considered as being at least possibly related to vaccination have been categorised by frequency.

Frequencies are reported as:

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Nervous system disorders

Very common: drowsiness

Rare: febrile and non-febrile convulsions

Respiratory, thoracic and mediastinal disorders

Uncommon: apnoea in very premature infants (28 weeks of gestation) 

Gastro-intestinal disorders

Uncommon: diarrhoea, vomiting

Skin and subcutaneous tissue disorders

Rare: rash, urticaria

Metabolism and nutrition disorders

Very common: appetite lost

General disorders and administration site conditions

Very common: pain, redness, swelling at the injection site, fever (38°C rectally)

Common: injection site induration, fever (>39°C rectally)

Uncommon: injection site haematoma, haemorrhage and nodule, fever (>40°C rectally)*

Immune system disorders

Rare: allergic reactions (such as allergic dermatitis, atopic dermatitis, eczema)

Psychiatric disorders

Very common: irritability

Uncommon: crying abnormal

*reported following booster vaccination

GlaxoSmithKline UK

POM – Prescription Only Medicine