Synflorix 0,5 mL FC tablets.

Active immunisation of infants and children from 6 weeks up to 5 years of age against disease caused by Streptococcus pneumoniae vaccine serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, 23F and cross-reactive serotype 19A (including sepsis, meningitis, pneumonia, bacteraemia and acute otitis media) and against acute otitis media caused by Non-Typeable Haemophilus influenzae.

Official recommendations should be taken into account when immunising with SYNFLORIX.

Posology:

Infants from 6 weeks to 6 months of age:

• Three-dose primary series: The 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 an interval of at least 1 month between doses. The first dose may be given as early as six weeks of age. A booster dose is recommended at least 6 months after the last primary dose and may be given from the age of 9 months onwards (see section 5.1).
• Two-dose primary series: Alternatively, 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 given as early as six weeks of age, with a second dose administered 2 months later. A booster dose is recommended at least 6 months after the last primary dose and may be given from the age of 9 months onwards (see section 5.1).

Preterm infants born after at least 27 weeks of gestational age: 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. A booster dose is recommended at least 6 months after the last primary dose (see section 5.1).

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.
• children aged 12 months to 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.

Special populations:

In individuals who have underlying conditions predisposing them to invasive pneumococcal disease (such as Human Immunodeficiency Virus (HIV) infection, sickle cell disease (SCD) or splenic dysfunction), SYNFLORIX may be given according to the above mentioned schedules, except that a 3-dose schedule should be given as primary vaccination in infants, starting vaccination from 6 weeks to 6 months of age (see sections 4.4 and 5.1).

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 children.

Use and handling:

A fine white deposit with a clear colourless supernatant may be observed upon storage of the syringe/vial. This does not constitute a sign of deterioration. The content of the syringe/vial should be inspected visually both before and after shaking for any foreign particulate matter and/or abnormal physical appearance prior to administration. In the event of either being observed, discard the vaccine. The vaccine should be well shaken before use.

Instructions for the pre-filled syringe: Hold the syringe by the barrel, not by the plunger. Unscrew the syringe cap by twisting it anticlockwise. To attach the needle, connect the hub to the Luer Lock Adaptor and rotate a quarter turn clockwise until you feel it lock. Do not pull the syringe plunger out of the barrel. If it happens, do not administer the vaccine.

SYNFLORIX should not be administered to subjects with known hypersensitivity to any component of the vaccine.

It is good clinical practice to precede vaccination by a review of the medical history (especially with regard to previous vaccination and possible occurrence of undesirable events) and a clinical examination. 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.

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.

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

Syncope (fainting) can occur following, or even before, any vaccination as a psychogenic response to the needle injection. It is important that procedures are in place to avoid injury from faints.

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.

Safety and immunogenicity data are available for HIV infected infants, children with sickle cell disease and children with splenic dysfunction (see sections 4.8 and 5.1). Safety and immunogenicity data for SYNFLORIX are not available for individuals in other specific immunocompromised groups and vaccination should be considered on an individual basis.

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

For children at high-risk for pneumococcal disease (such as children with sickle cell disease, asplenia, HIV infection, chronic illness or those who have other immunocompromising conditions):

• the appropriate for age SYNFLORIX vaccination series should be given (see section 4.2)
• The use of pneumococcal conjugate vaccine does not replace the use of 23-valent pneumococcal polysaccharide vaccines which should be given according to local recommendations in those children.

The potential risk of apnoea and the need for respiratory monitoring for 48-72 hours should be considered when administering the primary immunisation series to very premature infants (born u2264 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 will not protect against pneumococcal serogroups other than those included in the vaccine. Although antibody response to diphtheria toxoid, tetanus toxoid and Protein D (protein D is highly conserved in all Haemophilus influenzae strains including NTHi) occurs, immunisation with SYNFLORIX does not substitute routine immunisation with diphtheria, tetanus or Haemophilus influenzae type b vaccines. Official recommendations for the immunisations against diphtheria, tetanus and Haemophilus influenzae type b should also be followed.

As with any vaccine, a protective immune response may not be elicited in all vaccinees.

Prophylactic administration of antipyretics before or immediately after vaccines administration can reduce the incidence and intensity of post-vaccination febrile reactions. Data however, suggest that the use of prophylactic paracetamol might reduce the immune response to pneumococcal vaccines. The clinical relevance of this observation remains unknown.

Sodium content: This medicine contains less than 1 mmol sodium (23 mg) per dose, essentially u2018sodium freeu2019.

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, meningococcal serogroup C conjugate vaccine (CRM 197 and TT conjugates), meningococcal serogroups A, C, W-135 and Y conjugate vaccine (TT conjugate), oral polio vaccine (OPV) and rotavirus vaccine. Different injectable vaccines should always be given at different injections 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 this observation is unknown.

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

As SYNFLORIX is not intended for use in adults, adequate human data on use during pregnancy and lactation and adequate animal reproduction studies are not available.

Not applicable.

Summary of the safety profile: Safety assessment of SYNFLORIX was based on clinical trials involving the administration of approximately 64 000 doses of SYNFLORIX to approximately 22 500 healthy children and 137 preterm infants as primary vaccination. Furthermore, approximately 19 500 children and 116 preterm infants received a booster dose of SYNFLORIX in the second year of life. Safety was also assessed in approximately 400 children from 2 to 5 years of age. In all trials, SYNFLORIX was administered concurrently with the recommended childhood vaccines.

No increase in the incidence or severity of the adverse reactions was seen with subsequent doses of the primary vaccination series. Reactogenicity was higher in children receiving whole cell pertussis vaccines concomitantly. 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.

Adverse reactions reported (for all age groups) are listed according to the following frequency:

Very common: u2265 1/10
Common: u2265 1/100 to < 1/10
Uncommon: u2265 1/1 000 to < 1/100
Rare: u2265 1/10 000 to < 1/1 000
Very rare: < 1/10 000.

System organ class Frequency Adverse reactions

Immune system disorders Rare allergic reactions (such as allergic dermatitis, atopic dermatitis, eczema) Very rare angioedema

Metabolism and nutrition disorders Very common appetite loss

Psychiatric disorders Very common irritability Uncommon crying abnormal

Nervous system disorders Very common drowsiness Rare convulsions (including febrile convulsions)

Vascular disorders Very rare Kawasaki disease

System organ class Frequency Adverse reactions

Respiratory, thoracic and mediastinal disorders Uncommon apnoea (see section 4.4 for apnoea in very premature infants (u2264 28 weeks of gestation))

Gastro-intestinal disorders Uncommon diarrhoea, vomiting

Skin and subcutaneous tissue disorders Uncommon rash Rare urticaria

General disorders and administration site conditions Very common pain, redness, swelling at the injection site, fever u2265 38 u221eC rectally (age 39 u221eC 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)

Gastro-intestinal disorders Uncommon nausea (age 2 to 5 years)

General disorders and administration site conditions Common fever u2265 38 u221eC rectally (age 2 to 5 years) Uncommon injection site reactions like pruritus, fever > 40 u221eC rectally (age 39 u221eC rectally (age 2 to 5 years), diffuse swelling of the injected limb, sometimes involving the adjacent joint

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.

Special populations: Safety of SYNFLORIX was assessed in 83 HIV positive (HIV+/+) infants, 101 HIV negative infants born from an HIV positive mother (HIV+/-) and 50 infants with sickle cell disease (SCD), receiving primary vaccination. Of these, 76, 96 and 49 infants, respectively, received a booster dose. Safety of SYNFLORIX was also assessed in 50 children with SCD starting vaccination at 7-11 months of age, all of them receiving the booster vaccination, and in 50 children with SCD starting vaccination at 12-23 months of age. Results suggest comparable reactogenicity and safety profile of SYNFLORIX between these high-risk groups and healthy children.

Post-marketing data: Immune system disorders: Very rare: anaphylaxis Nervous system disorders: Rare: hypotonic-hyporesponsive episode.

Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of a medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are asked to report any suspected adverse reactions to SAHPRA via theu2019 6.04 Adverse Drug Reactions Reporting form,u2019 found under SAHPRA publications: https:/www.sahpra.org.za/Publications/Index/8.

Insufficient data are available.