4.1. Therapeutic indications

Active immunisation for the prevention of pneumococcal disease caused by Streptococcus pneumoniae in individuals from 6 weeks of age and older.

See sections 4.4 and 5.1 for information on protection against specific pneumococcal serotypes.

Prevenar 20 should be used in accordance with official recommendations.

4.2. Posology and method of administration

Posology

It is recommended that infants who receive a first dose of Prevenar 20 complete the vaccination course with Prevenar 20.

Vaccination schedule in infants and children 6 weeks to 15 months of age

3-dose series (two-dose primary series followed by a booster dose)

Three doses, each of 0.5 mL. The first dose is usually given at 2 months of age, with a second dose 2 months later. The first dose may be given as early as 6 weeks of age. The third (booster) dose is recommended between 11 and 15 months of age (see section 5.1).

4-dose series (three-dose primary series followed by a booster dose)

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 4 weeks between doses. The first dose may be given as early as 6 weeks of age. The fourth (booster) dose is recommended between 11 and 15 months of age (see section 5.1).

Preterm infants (less than 37 weeks of gestation)a

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 4 weeks between doses. The first dose may be given as early as 6 weeks of age. The fourth (booster) dose is recommended between 11 and 15 months of age (see sections 4.4 and 5.1).

Vaccination schedule for infants and children less than 15 months of age transitioning from another pneumococcal conjugate vaccineb

Prior vaccination with another pneumococcal conjugate vaccine

Infants and children who have begun immunisation with another pneumococcal conjugate vaccine may complete immunisation by transitioning to Prevenar 20 at any point in the schedule.

Catch-up vaccination schedule for infants and children 7 months to less than 18 years of age

Unvaccinated infants 7 to less than 12 months of agea

Two doses, each of 0.5 mL, with an interval of at least 4 weeks between doses. A third dose is recommended in the second year of life.

Unvaccinated children 12 to less than 24 months of agea

Two doses, each of 0.5 mL, with an interval of at least 8 weeks between doses.

Unvaccinated children 2 to less than 5 years of agea

One single dose of 0.5 mL.

Children 15 months to less than 5 years of age previously vaccinated with a pneumococcal conjugate vaccine

1 dose (0.5 mL).

If a previous pneumococcal conjugate vaccine was administered, at least 8 weeks should elapse before administering Prevenar 20 (see section 5.1).

Children 5 to less than 18 years of age regardless of prior pneumococcal conjugate vaccination

1 dose (0.5 mL).

If a previous pneumococcal conjugate vaccine was administered, at least 8 weeks should elapse before administering Prevenar 20 (see section 5.1).

Vaccination schedule for individuals 18 years of age and older

Individuals 18 years of age and older

Prevenar 20 is to be administered as a single dose to individuals 18 years of age and older.

The need for revaccination with a subsequent dose of Prevenar 20 has not been established.

No data on sequential vaccination with other pneumococcal vaccines or a booster dose are available for Prevenar 20. Based on the clinical experience with Prevenar 13 (a pneumococcal conjugate vaccine consisting of 13 polysaccharide conjugates that are also in Prevenar 20), if the use of 23-valent pneumococcal polysaccharide vaccine (Pneumovax 23 [PPSV23]) is considered appropriate, Prevenar 20 should be given first (see section 5.1).

a. In preterm and unvaccinated infants and children 7 months to less than 5 years of age, Prevenar 20 is expected to perform similarly to Prevenar 13, a pneumococcal conjugate vaccine consisting of 13 polysaccharide conjugates that are also in Prevenar 20.

b. The safety and immunogenicity of Prevenar 20 administered to infants and children less than 15 months of age who have begun vaccination with another pneumococcal conjugate vaccine have not been established. However, safety and immunogenicity studies with a transition from a lower valent to higher valent pneumococcal conjugate vaccine are relevant to Prevenar 20. Based on clinical experience and relevant randomised controlled trials, the recommended transition from a lower to a higher valent pneumococcal conjugate vaccine may be considered in guiding vaccination with Prevenar 20 for infants and children who have not yet completed the infant vaccination series.

Paediatric population

The safety and efficacy of Prevenar 20 in infants below 6 weeks of age have not been established. No data are available.

Special populations

There are no data with Prevenar 20 in special populations. The use of Prevenar 20 should be guided by official recommendations.

Experience from clinical studies with Prevenar 13 (a pneumococcal conjugate vaccine consisting of 13 polysaccharide conjugates that are also in Prevenar 20) are available in adults and children at higher risk of pneumococcal infection including immunocompromised adults and children with human immunodeficiency virus (HIV) infection or haematopoietic stem cell transplant (HSCT), and children with sickle cell disease (SCD) (see sections 4.4 and 5.1).

Based on these data the following posology was recommended for Prevenar 13:

- Individuals at higher risk of pneumococcal infection (e.g., individuals with SCD or HIV infection), including those previously vaccinated with 1 or more doses of PPSV23, were recommended to receive at least 1 dose of Prevenar 13.

- In individuals with a HSCT, the recommended immunisation series with Prevenar 13 consisted of 4 doses of 0.5 mL each. The primary series consisted of 3 doses, with the first dose given 3 to 6 months after HSCT and with an interval of at least 4 weeks between doses. A booster dose was recommended 6 months after the third dose (see section 5.1).

The recommended dosing of Prevenar 13 may be considered in guiding vaccination with Prevenar 20 in higher risk populations. For immune responses to pneumococcal vaccines in immunocompromised individuals, please also refer to sections 4.4. and 5.1.

Method of administration

For intramuscular use only.

One dose (0.5 mL) of Prevenar 20 should be administered intramuscularly, preferably in the anterolateral aspect of the thigh (vastus lateralis muscle) in infants or the deltoid muscle of the upper arm in children and adults, with care to avoid injection into or near nerves and blood vessels.

For instructions on the handling of the vaccine before administration, see section 6.6.

4.3. Contraindications

Hypersensitivity to the active substances, to any of the excipients listed in section 6.1, or to diphtheria toxoid.

4.4. Special warnings and precautions for use

Do not inject Prevenar 20 intravascularly.

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Hypersensitivity

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

Concurrent illness

Vaccination should be postponed in individuals 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.

Thrombocytopenia and coagulation disorders

The vaccine must be administered with caution to individuals with thrombocytopenia or a bleeding disorder since bleeding may occur following an intramuscular administration.

The risk of bleeding in patients with coagulation disorders needs to be carefully evaluated before intramuscular administration of any vaccine, and subcutaneous administration should be considered if the potential benefit clearly outweighs the risks.

Protection against pneumococcal disease

Prevenar 20 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 (OM). As with any vaccine, Prevenar 20 may not protect all individuals receiving the vaccine from pneumococcal invasive disease, OM or pneumonia. For the most recent epidemiological information in your country, you should consult with the relevant national organisation.

Immunocompromised individuals

Safety and immunogenicity data on Prevenar 20 are not available for individuals in immunocompromised groups. Vaccination should be considered on an individual basis.

Based on experience with pneumococcal vaccines, some individuals with altered immunocompetence may have reduced immune responses to Prevenar 20.

Individuals with impaired immune response, whether due to the use of immunosuppressive therapy, a genetic defect, HIV infection, or other causes, may have reduced antibody response to active immunisation. The clinical relevance of this is unknown.

Safety and immunogenicity data with Prevenar 13 (a pneumococcal conjugate vaccine consisting of 13 polysaccharide conjugates that are also in Prevenar 20) are available for a limited number of individuals with HIV infection, SCD or with a HSCT (see sections 4.8 and 5.1).

In adults across all studied age groups, formal non-inferiority criteria were met although numerically lower opsonophagocytic activity (OPA) geometric mean titres were observed with Prevenar 20 for most of the serotypes compared to Prevenar 13 (see section 5.1). In children, numerically lower immunoglobulin G (IgG) geometric mean concentrations (GMCs) were observed for all shared serotypes compared with Prevenar 13 (see section 5.1). The clinical relevance of these observations for immunocompromised individuals is unknown.

Paediatric population

The potential risk of apnoea and the need for respiratory monitoring for 48 to 72 h should be considered when administering the primary immunisation series to very premature infants (born less than or equal to 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.

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, that is to say essentially 'sodium-free'.

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

Different injectable vaccines should always be administered at different vaccination sites.

Do not mix Prevenar 20 with other vaccines/medicinal products in the same syringe.

Paediatric population

In infants and children, 6 weeks to less than 5 years of age, Prevenar 20 can be administered concomitantly with any of the following vaccine antigens, either as monovalent or combination vaccines: diphtheria, tetanus, acellular pertussis, hepatitis B, Haemophilus influenzae type b, inactivated poliomyelitis, measles, mumps, rubella, and varicella vaccines. The vaccine has been safely administered with influenza and rotavirus vaccines.

Individuals 18 years of age and older

Prevenar 20 can be administered concomitantly with seasonal influenza vaccine (surface antigen, inactivated, adjuvanted). In subjects with underlying conditions associated with a high risk of developing life-threatening pneumococcal disease, consideration may be given to separating administrations of seasonal influenza vaccine and Prevenar 20 (e.g., by approximately 4 weeks). In a double-blind, randomised study (B7471004) in adults 65 years of age and older, the immune response was formally non-inferior, however numerically lower titres were observed for all pneumococcal serotypes included in Prevenar 20 when given concomitantly with a quadrivalent seasonal influenza vaccine (surface antigen, inactivated, adjuvanted) compared to when Prevenar 20 was given alone. The clinical relevance of this finding is unknown.

Prevenar 20 can be administered concomitantly with COVID-19 mRNA vaccine (nucleoside modified).

There are no data on the concomitant administration of Prevenar 20 with other vaccines.

4.6. Fertility, pregnancy and lactation

Pregnancy

There are no data on the use of Prevenar 20 in pregnant women.

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.

Administration of Prevenar 20 in pregnancy should only be considered when the potential benefits outweigh any potential risks for the mother and fetus.

Breast-feeding

It is unknown whether Prevenar 20 is excreted in human milk.

Fertility

No human data on the effect of Prevenar 20 on fertility are available. Animal studies do not indicate direct or indirect harmful effects with respect to female fertility (see section 5.3).

4.7. Effects on ability to drive and use machines

Prevenar 20 has no or negligible influence on the ability to drive and use machines. However, some of the effects mentioned under section 4.8 may temporarily affect the ability to drive or use machines.

4.8. Undesirable effects

Summary of the safety profile

Paediatric population

The safety of Prevenar 20 was evaluated in 5,987 participants 6 weeks of age to less than 18 years of age in four randomised double-blind, active-controlled, clinical trials and one single-arm clinical trial (one Phase 2 and four Phase 3); 3,664 participants received at least 1 dose of Prevenar 20, and 2,323 participants received Prevenar 13 (control vaccine).

Participants 6 weeks to less than 15 months of age

In four infant trials, 5,156 participants received at least 1 dose of vaccine: 2,833 received Prevenar 20 and 2,323 received Prevenar 13. Prevenar 20 was well tolerated when administered in a 3-dose or 4-dose series, with low rates of severe local and systemic reactions, and most reactions resolving within 1 to 3 days. The most frequently reported reactions after any dose of Prevenar 20 were irritability, drowsiness, and pain at injection site. In these studies, Prevenar 20 was co-administered or permitted to be administered with certain routine paediatric vaccines (see section 4.5).

In a 3-dose series study, 601 healthy infants, 2 months (≥ 42 to ≤ 112 days) of age and born at > 36 weeks of gestation, received Prevenar 20. The most frequently reported adverse reactions (> 10%) after any dose were irritability (71.0% to 71.9%), drowsiness/increased sleep (50.9% to 61.2%), pain at injection site (22.8% to 42.4%), decreased appetite (24.7% to 39.3%), redness at the injection site (25.3% to 36.9%), swelling at the injection site (21.4% to 29.8%), and fever ≥ 38.0°C (8.9% to 24.3%). Most adverse reactions occurred within 1 to 2 days following vaccination and were mild or moderate in severity and of short duration (1 to 2 days).

Three other studies included 2,232 healthy infants vaccinated with Prevenar 20 in a 4-dose series. The most frequently reported adverse reactions (> 10%) observed after any dose were irritability (58.5% to 70.6%), drowsiness/increased sleep (37.7% to 66.2%), pain at injection site (32.8% to 45.5%), decreased appetite (23.0% to 26.4%), redness at the injection site (22.6% to 24.5%) and swelling at the injection site (15.1% to 17.6%). Most adverse reactions were mild or moderate following vaccination and severe reactions were reported infrequently. The local and systemic reactions in a preterm subgroup (111 infants born at 34 to less than 37 weeks of gestation) were similar to or lower than in the term infants of the study.

The frequency and severity of the adverse reactions in all infant clinical trials were generally similar in the Prevenar 20 and Prevenar 13 groups.

Participants aged 15 months to less than 18 years of age

In one study, 831 participants who received a single dose of Prevenar 20 were included in four age groups: 209 participants 15 to less than 24 months of age; 216 participants 2 years to less than 5 years of age; 201 participants 5 years to less than 10 years age; and 205 participants 10 years to less than 18 years of age. The participants less than 5 years of age had received at least 3 prior doses of Prevenar 13.

The most frequently reported adverse reactions (> 10%) observed after any dose in participants less than 2 years of age were irritability (61.8%), pain at the injection site (52.5%), drowsiness/increased sleep (41.7%), redness at the injection site (37.7%), decreased appetite (25.0%), swelling at the injection site (22.1%) and fever ≥ 38.0 °C (11.8%). In participants aged 2 years and older, the most frequently reported adverse reactions were pain at the injection site (66.0% to 82.9%), muscle pain (26.5% to 48.3%), redness at the injection site (15.1% to 39.1%), fatigue (27.8% to 37.2%), headache (5.6% to 29.3%), and swelling at the injection site (15.6% to 27.1%).

Adult population

The safety of Prevenar 20 was evaluated in 4,552 participants 18 years of age and older in six clinical trials (two Phase 1, one Phase 2, and three Phase 3), with 2,496 participants in the control groups.

In the Phase 3 trials, 4,263 participants received Prevenar 20. This included 1,798 participants 18 through 49 years of age, 334 participants 50 through 59 years of age, and 2,131 participants 60 years of age and older (1,138 were 65 years of age and older). Overall, 3,639 subjects were naïve to pneumococcal vaccines, 253 had previously received a pneumococcal polysaccharide vaccine ([23-valent]; PPSV23) (≥ 1 to ≤ 5 years prior to enrolment), 246 had previously received Prevenar 13 only (≥ 6 months prior to enrolment), and 125 had previously received Prevenar 13 followed by PPSV23 (the dose of PPSV23 ≥ 1 year prior to enrolment).

In participants 18 to 49 years of age, the most frequently reported adverse reactions were pain at injection site (79.2%), muscle pain (62.9%), fatigue (46.7%), headache (36.7%), and joint pain (16.2%). In participants 50 to 59 years of age, the most frequently reported adverse reactions were pain at injection site (72.5%), muscle pain (49.8%), fatigue (39.3%), headache (32.3%), and joint pain (15.4%). In participants ≥ 60 years of age, the most frequently reported adverse reactions were pain at injection site (55.4%), muscle pain (39.1%), fatigue (30.2%), headache (21.5%), and joint pain (12.6%). These were usually mild or moderate in intensity and resolved within a few days after vaccination.

In a study that evaluated Prevenar 20 in participants ≥ 65 years of age with varying prior pneumococcal status (prior PPSV23, prior Prevenar 13 or prior Prevenar 13 followed by PPSV23), the most frequently reported adverse reactions were similar in frequency to those described for participants ≥ 60 years of age, with slightly higher injection site pain (61.2%) in participants with prior Prevenar 13, and joint pain (16.8%) in participants with prior Prevenar 13 followed by PPSV23.

Tabulated list of adverse reactions

Tabulated lists of adverse reactions in paediatric and adult clinical trials, and postmarketing experience are presented below.

Adverse reactions from clinical trials

As Prevenar 20 contains the same 13 serotype-specific capsular polysaccharide conjugates and the same vaccine excipients as Prevenar 13, the adverse reactions already identified for Prevenar 13 have been adopted for Prevenar 20. Table 1 presents adverse reactions reported in clinical trials based on the highest frequency reported after vaccination in a Prevenar 20 group or integrated dataset. The data from clinical trials in infants reflect Prevenar 20 administered simultaneously with other routine childhood vaccines. In the case of adverse reactions reported in clinical trials of Prevenar 13, but not reported in Prevenar 20 trials, the frequency indicated in the table is the frequency of the adverse reaction in Prevenar 13 trials.

In clinical trials, the safety profile of Prevenar 20 was similar to that of Prevenar 13 and no new adverse reactions were identified as compared to Prevenar 13.

Adverse reactions are listed by 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).

Table 1: Tabulated Adverse Reactions From Prevenar 20 Clinical Trials

System Organ Class

Adverse Reactions

Frequency

Infants/Children/Adolescents

Adults

6 weeks to less than 5 years of age

5 years to less than 18 years of age

Immune System Disorders

Hypersensitivity reaction including face oedema, dyspnoea, bronchospasm

Rarea

-

Uncommon

Metabolism and Nutrition Disorders

Decreased appetite

Very common

Very commona

Very commona

Psychiatric Disorders

Irritability

Very common

Very commona

-

Crying

Uncommona

-

-

Nervous System Disorders

Drowsiness/increased sleep

Very common

Very commona

-

Seizures (including febrile seizures)

Uncommon

-

-

Hypotonic-hyporesponsive episode

Rarea

-

-

Restless sleep/decreased sleep

Very commona

Very commona

-

Headache

-

Very common

Very common

Gastrointestinal Disorders

Diarrhoea

Common

Commona

Uncommonb

Nausea

-

-

Uncommon

Vomiting

Common

Commona

Uncommonb

Skin and Subcutaneous Tissue Disorders

Rash

Common

Commona

Uncommonb

Angioedema

-

-

Uncommon

Urticaria or urticaria-like rash

Uncommon

Uncommon

-

Musculoskeletaland connective tissue Disorders

Muscle pain

-

Very common

Very common

Joint pain

-

Common

Very common

General Disorders and Administration Site Conditions

Fever (pyrexia)

Very common

Uncommon

Common

Fever greater than 38.9 °C

Common

-

-

Fatigue

-

Very common

Very common

Vaccination-site erythema

Very common

Very common

Commonb

Vaccination-site induration/swelling

Very common

Very common

Commonb

Vaccination-site erythema or induration/swelling (> 2.0-7.0 cm)

Very common (after toddler dose and in older children [age 2 to < 5 years])

-

-

Common (after infant series)

-

-

Vaccination-site erythema or induration/swelling (> 7.0 cm)

Uncommon

-

-

Vaccination-site pain/tenderness

Very common

Very common

Very common

Vaccination-site pain/tenderness causing limitation of limb movement

Common

Common

Very commona

Vaccination-site pruritus

-

-

Uncommon

Lymphadenopathy

-

-

Uncommon

Vaccination-site urticaria

-

-

Uncommon

Chills

-

-

Uncommonb

Vaccination-site hypersensitivity

Rarec

-

-

a. These frequencies are based on adverse reactions (ARs) reported in clinical trials with Prevenar 13 as these ARs were not reported in Prevenar 20 trials.

b. Event reported with very common frequency (≥ 1/10) in clinical trials with Prevenar 13.

c. AR not reported for Prevenar 13, although injection-site urticaria, injection-site pruritus, and injection-site dermatitis were reported in Prevenar 13 postmarketing experience.

Safety with concomitant vaccine administration in adults

When Prevenar 20 was administered to adults aged ≥ 65 years together with the third (booster) dose of a COVID-19 mRNA vaccine (nucleoside modified), the tolerability profile generally resembled that of the COVID-19 mRNA vaccine (nucleoside modified) administered alone. There were a few differences in the safety profile when compared to administration of Prevenar 20 alone: pyrexia (13.0%) and chills (26.5%) were reported as “very common” with co-administration. There was also one report of dizziness (0.5%) in the co-administration group.

Adverse reactions from postmarketing experience

Table 2 includes adverse experiences that have been spontaneously reported during the postmarketing use of Prevenar 13 in paediatric and adult populations, which may also occur with Prevenar 20. The postmarketing safety experience with Prevenar 13 is relevant to Prevenar 20, as Prevenar 20 contains all components (polysaccharide conjugates and excipients) of Prevenar 13. These events were reported voluntarily from a population of uncertain size. Therefore, it is not possible to reliably estimate their frequency or to establish, for all events, a causal relationship to vaccine exposure.

Table 2. Adverse Reactions From Prevenar 13 Postmarketing Experience

System Organ Class

Frequency Not Known

Blood and lymphatic system disorders

Lymphadenopathy localised to the region of the vaccination site

Immune system disorders

Anaphylactic/anaphylactoid reaction, including shock

Skin and subcutaneous tissue disorders

Angioedema, erythema multiforme

General disorders and administration site conditions

Vaccination-site dermatitis, vaccination-site urticaria, vaccination-site pruritus

Additional information in special populations in studies with Prevenar 13

Participants 6 to < 18 years of age with HIV infection have similar frequencies of adverse reactions in Table 1, except fever (11% to 19%), joint pain (24% to 42%), and vomiting (8% to 18%) which were very common. Participants ≥ 18 years of age with HIV infection have similar frequencies of adverse reactions in Table 1, except for pyrexia (5% to 18%) and vomiting (8% to 12%) which were very common and nausea (< 1% to 3%) which was common.

Participants 2 to < 18 years of age with HSCT have similar frequencies of adverse reactions in Table 1, except vaccination-site pain causing limitation of limb movement (5% to 15%), vomiting (6% to 21%), diarrhoea (15% to 32%), and joint pain (25% to 32%) which were very common. Participants ≥ 18 years of age with an HSCT have similar frequencies of adverse reactions in Table 1, except for pyrexia (4% to 15%), vomiting (6% to 21%), and diarrhoea (25% to 36%) which were very common.

Participants 6 to < 18 years of age with SCD have similar frequencies of adverse reactions in Table 1, except vaccination-site pain causing limitation of limb movement (11% to 16%), fever (21% to 22%), vomiting (13% to 15%), diarrhoea (13% to 25%), and joint pain (40% to 45%) which were very common.

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 20 is unlikely due to its presentation as a pre-filled syringe.