4.1. Therapeutic indications

Active immunisation for the prevention of invasive disease, pneumonia and acute otitis media caused by Streptococcus pneumoniae in infants, children and adolescents from 6 weeks to 17 years of age.

Active immunisation for the prevention of invasive disease and pneumonia caused by Streptococcus pneumoniae in adults ≥18 years of age and the elderly.

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 risk of invasive disease and pneumonia in different age groups, underlying comorbidities as well as the variability of serotype epidemiology in different geographical areas.

4.2. Posology and method of administration

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).

Preterm infants (< 37 weeks gestation)

In preterm infants, 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 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 (see sections 4.4 and 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 and adolescents aged 2-17 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 immunised 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).

Children and adolescents 5–17 years

Children 5 to 17 years of age may receive a single dose of Prevenar 13 if they have been previously vaccinated with one or more doses of Prevenar. 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 ≥18 years of age, and the elderly

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 pneumococcal polysaccharide vaccine is considered appropriate, Prevenar 13 should be given first (see sections 4.5 and 5.1).

Special Populations

Individuals who have underlying conditions predisposing them to invasive pneumococcal disease (such as sickle cell disease or HIV infection) including those previously vaccinated with one or more doses of 23-valent pneumococcal polysaccharide vaccine may receive at least one dose of Prevenar 13 (see section 5.1).

In individuals with an haematopoietic stem cell transplant (HSCT), the recommended immunisation series consists of four doses of Prevenar 13, each of 0.5 ml. The primary series consists of three doses, with the first dose given at 3 to 6 months after HSCT and with an interval of at least 1 month between doses. A fourth (booster) dose is recommended 6 months after the third dose (see section 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.

4.3. Contraindications

Hypersensitivity to the active substances, to any of the excipients listed in 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.

4.4. Special warnings and precautions for use

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. For the most recent epidemiological information in your country you should consult with the relevant national organisation.

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 immunisation.

Safety and immunogenicity data are available for a limited number of individuals with sickle cell disease, HIV infection, or with an haematopoietic stem cell transplant (see section 5.1). Safety and immunogenicity data for Prevenar 13 are not available for individuals in other specific immuno-compromised groups (e.g., malignancy or nephrotic syndrome) and vaccination should be considered on an individual basis.

Excipients

This medicinal product contains polysorbate 80 (see section 2). Polysorbate 80 may cause hypersensitivity reactions.

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially 'sodium-free'.

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 immuno-compromised) 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).

When Prevenar 13 is administered concomitantly with Infanrix hexa (DTPa-HBV-IPV/Hib), the rates of febrile reactions are similar to those seen with concomitant administration of Prevenar (7-valent) and Infanrix hexa (see section 4.8). Increased reporting rates of convulsions (with or without fever) and hypotonic hyporesponsive episode (HHE) were observed with concomitant administration of Prevenar 13 and Infanrix hexa (see section 4.8).

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.

4.5. Interaction with other medicinal products and other forms of interaction

Infants and children aged 6 weeks to 5 years

Prevenar 13 can be given concomitantly 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 (see section 4.4 for guidance on Infanrix hexa), meningococcal serogroup C, measles, mumps, rubella, varicella and rotavirus vaccine.

Prevenar 13 can also be given concomitantly between 12-23 months with the tetanus toxoid conjugated meningococcal polysaccharide serogroups A, C, W and Y vaccine to children who have been adequately primed with Prevenar 13 (as per local recommendations).

Data from a postmarketing clinical study evaluating the impact of prophylactic use of antipyretics (ibuprofen and paracetamol) on the immune response to Prevenar 13 suggest that administration of paracetamol concomitantly or within the same day of vaccination may reduce the immune response to Prevenar 13 after the infant series. Responses to the booster dose administered at 12 months were unaffected. The clinical significance of this observation is unknown.

Children and adolescents 6 to 17 years of age

No data are currently available regarding concomitant use with other vaccines.

Adults 18 to 49 years of age

No data are available regarding concomitant use with other vaccines.

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, however, there was no long-term impact on circulating antibody levels.

In a third study in adults aged 50-93 years, it was demonstrated that Prevenar 13 may be given concomitantly with the seasonal quadrivalent inactivated influenza vaccine (QIV). The immune responses to all four QIV strains were noninferior when Prevenar 13 was given concomitantly with QIV compared to when QIV was given alone.

The immune responses to Prevenar 13 were noninferior when Prevenar 13 was given concomitantly with QIV compared to when Prevenar 13 was given alone. As with concomitant administration with trivalent vaccines, immune responses to some pneumococcal serotypes were lower when both vaccines were given concomitantly.

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

4.6. Fertility, pregnancy and lactation

Pregnancy

There are no data from the use of pneumococcal 13-valent conjugate vaccine in pregnant women. Therefore the use of Prevenar 13 should be avoided during pregnancy.

Breast-feeding

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

Fertility

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

4.7. Effects on ability to drive and use machines

Prevenar 13 has no or negligible influence on the ability to drive and use machines. However, some of the effects mentioned under section 4.8 “Undesirable effects” may temporarily affect the ability to drive or use machines.

4.8. Undesirable effects

Analysis of postmarketing reporting rates suggests a potential increased risk of convulsions, with or without fever, and HHE when comparing groups which reported use of Prevenar 13 with Infanrix hexa to those which reported use of Prevenar 13 alone.

Adverse reactions reported in clinical studies or from the postmarketing 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 in children 6 weeks to 5 years of age were vaccination-site reactions, fever, irritability, decreased appetite, and increased and/or decreased sleep.

In a clinical study in infants vaccinated at 2, 3, and 4 months of age, fever ≥ 38°C was reported at higher rates among infants who received Prevenar (7-valent) concomitantly with Infanrix hexa (28.3% to 42.3%) than in infants receiving Infanrix hexa alone (15.6% to 23.1%). After a booster dose at 12 to 15 months of age, fever ≥ 38°C was reported in 50.0% of infants who received Prevenar (7-valent) and Infanrix hexa at the same time as compared to 33.6% of infants receiving Infanrix hexa alone. These reactions were mostly moderate (less than or equal to 39°C) and transient.

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 in Prevenar 13 clinical studies:

Immune system disorders:

Rare:

Hypersensitivity reaction including face oedema, dyspnoea, bronchospasm

Nervous system disorders:

Uncommon:

Convulsions (including febrile convulsions)

Rare:

Hypotonic-hyporesponsive episode

Gastrointestinal disorders:

Very common:

Decreased appetite

Common:

Vomiting; diarrhoea

Skin and subcutaneous tissue disorders:

Common:

Rash

Uncommon:

Urticaria or urticaria-like rash

General disorders and administration site conditions:

Very common:

Pyrexia; irritability; any vaccination-site erythema, induration/swelling or pain/tenderness; somnolence; poor quality sleep

Vaccination-site erythema or induration/swelling 2.5 cm–7.0 cm (after the booster dose and in older children [age 2 to 5 years])

Common:

Pyrexia > 39°C; vaccination-site movement impairment (due to pain); vaccination-site erythema or induration/swelling 2.5 cm–7.0 cm (after infant series)

Uncommon:

Vaccination-site erythema, induration/swelling > 7.0 cm; crying

Additional information in special populations:

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

Children and adolescents aged 6 to 17 years of age

Safety was evaluated in 592 children (294 children aged 5 to 10 years previously immunised with at least one dose of Prevenar and 298 children aged 10 to 17 years who had not received a pneumococcal vaccine).

The most common adverse events in children and adolescents 6 to 17 years of age were:

Nervous system disorders:

Common:

Headaches

Gastrointestinal disorders:

Very common:

Decreased appetite

Common:

Vomiting; diarrhoea

Skin and subcutaneous tissue disorders:

Common:

Rash; urticaria or urticaria-like rash

General disorders and administration site conditions:

Very common:

Irritability; any vaccination-site erythema; induration/swelling or pain/tenderness; somnolence; poor quality sleep; vaccination-site tenderness (including impaired movement)

Common:

Pyrexia

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

Additional information in special populations

Children and adolescents with sickle cell disease, HIV infection, or an haematopoietic stem cell transplant have similar frequencies of adverse reactions, except that headaches, vomiting, diarrhoea, pyrexia, fatigue, arthralgia, and myalgia were very common.

Adults ≥ 18 years and the elderly

Safety was assessed in 7 clinical studies including 91,593 adults ranging in age from 18 to 101 years. Prevenar 13 was administered to 48,806 adults; 2,616 (5.4%) aged 50 to 64 years, and 45,291 (92.8%) aged 65 years and older. One of the 7 studies included a group of adults (n=899) ranging from 18 to 49 years who received Prevenar 13 and who were not previously vaccinated with 23-valent pneumococcal polysaccharide vaccine. 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 46,890 were 23-valent pneumococcal polysaccharide vaccine unvaccinated.

A trend to lower frequency of adverse reactions was associated with greater age; adults > 65 years of age (regardless of prior pneumococcal vaccination status) reported fewer adverse reactions than younger adults, with adverse reactions generally most common in the youngest adults, 18 to 29 years of age.

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 < 1/10) in all other age groups, and pyrexia was very common in adults aged 18 to 29 years and common in all other age groups. Severe vaccination-site pain/tenderness and severe limitation of arm movement was very common in adults 18 to 39 years and common in all other age groups.

Adverse reactions from clinical studies

Local reactions and systemic events were solicited daily after each vaccination for 14 days in 6 studies and 7 days in the remaining study. The following frequencies are based on adverse reactions assessed in Prevenar 13 clinical studies in adults:

Metabolism and nutrition disorders:

Very common:

Decreased appetite

Nervous system disorders:

Very common:

Headaches

Gastrointestinal disorders:

Very common:

Diarrhoea; vomiting (in adults aged 18 to 49 years)

Common:

Vomiting (in adults aged 50 years and over)

Uncommon:

Nausea

Immune system disorders:

Uncommon:

Hypersensitivity reaction including face oedema, dyspnoea, bronchospasm

Skin and subcutaneous tissue disorders:

Very common:

Rash

General disorders and administration site conditions:

Very common:

Chills; fatigue; vaccination-site erythema; vaccination-site induration/swelling; vaccination-site pain/tenderness (severe vaccination-site pain/tenderness very common in adults aged 18 to 39 years); limitation of arm movement (severe limitation of arm movements very common in adults aged 18 to 39 years)

Common:

Pyrexia (very common in adults aged 18 to 29 years)

Uncommon:

Lymphadenopathy localized to the region of the vaccination-site

Musculoskeletal and connective tissue disorders:

Very common:

Arthralgia; myalgia

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.

Additional information in special populations

Adults with HIV infection have similar frequencies of adverse reactions, except that pyrexia and vomiting were very common and nausea common.

Adults with an haematopoietic stem cell transplant have similar frequencies of adverse reactions, except that pyrexia and vomiting were very common.

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).

Adverse reactions from Prevenar 13 postmarketing experience

The following are considered adverse drug reactions for Prevenar 13; because these reactions were derived from spontaneous reports, the frequencies could not be determined and are thus considered as not known.

Blood and lymphatic system disorders:

Lymphadenopathy (localised to the region of the vaccination-site)

Immune system disorders:

Anaphylactic/anaphylactoid reaction including shock; angioedema

Skin and subcutaneous tissue disorders:

Erythema multiforme

General disorders and administration site conditions:

Vaccination-site urticaria; vaccination-site dermatitis; vaccination-site pruritus; flushing

Reporting of suspected adverse reactions

Reporting 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 the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

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.