4.1. Therapeutic indications

Vaxneuvance is indicated for 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 less than 18 years of age.

Vaxneuvance is indicated for active immunisation for the prevention of invasive disease and pneumonia caused by Streptococcus pneumoniae in individuals 18 years of age and older.

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

The use of Vaxneuvance should be in accordance with official recommendations.

4.2. Posology and method of administration

Posology

Routine vaccination schedule in infants and children aged 6 weeks to less than 2 years

Two-dose primary series followed by a booster dose

The recommended immunisation regimen consists of 3 doses of Vaxneuvance, each of 0.5 mL. The first dose is given as early as 6 weeks of age, with a second dose administered 8 weeks later. The third (booster) dose is recommended between 11 through 15 months of age.

Three-dose primary series followed by a booster dose

An immunisation regimen consisting of 4 doses of Vaxneuvance, each of 0.5 mL, may be given. This primary series consists of 3 doses, with the first dose given as early as 6 weeks of age, with an interval of 4 to 8 weeks between doses in the primary series. The fourth (booster) dose is recommended between 11 through 15 months of age and at least 2 months after the third dose.

Preterm infants (<37 weeks gestation at birth)

The recommended immunisation regimen consists of a three-dose primary series of Vaxneuvance followed by a fourth (booster) dose, each of 0.5 mL, as per three-dose primary series followed by a booster dose posology (see sections 4.4 and 5.1).

Prior vaccination with another pneumococcal conjugate vaccine

Infants and children who have begun immunisation with another pneumococcal conjugate vaccine may switch to Vaxneuvance at any point in the schedule (see section 5.1).

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

Unvaccinated infants 7 to less than 12 months of age

3 doses, each of 0.5 mL, with the first two doses given at least 4 weeks apart. A third (booster) dose is recommended after 12 months of age, separated from the second dose by at least 2 months.

Unvaccinated children 12 months to less than 2 years of age

2 doses, each of 0.5 mL, with an interval of 2 months between doses.

Unvaccinated or not fully vaccinated children and adolescents 2 to less than 18 years of age

1 dose (0.5 mL).

If a previous pneumococcal conjugate vaccine was administered, at least 2 months should elapse before administering Vaxneuvance.

Vaccination schedule for individuals 18 years of age and older

Individuals 18 years of age and older

1 dose (0.5 mL).

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

Special populations

One or more doses of Vaxneuvance may be given to individuals who have one or more underlying conditions predisposing them to an increased risk of pneumococcal disease (such as individuals with sickle cell disease or living with human immunodeficiency virus (HIV) infection or recipients of haematopoietic stem cell transplant (HSCT) or immunocompetent individuals 18 to 49 years of age with risk factors for pneumococcal disease; see section 5.1).

Method of administration

The vaccine should be administered by intramuscular injection. The preferred site is the anterolateral aspect of the thigh in infants or the deltoid muscle of the upper arm in children and adults.

No data are available for administration via the intradermal route.

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 any diphtheria toxoid‑containing vaccine.

4.4. Special warnings and precautions for use

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.

Precaution related to route of administration

Vaxneuvance must not be administered intravascularly.

Anaphylaxis

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.

Concurrent illness

Vaccination should be postponed in individuals suffering from acute severe febrile illness or acute infection. The presence of a minor infection and/or low-grade fever should not delay vaccination.

Thrombocytopenia and coagulation disorders

As with other intramuscular injections, the vaccine should be given with caution to individuals receiving anticoagulant therapy, or to those with thrombocytopenia or any coagulation disorder such as haemophilia. Bleeding or bruising may occur following an intramuscular administration in these individuals. Vaxneuvance may be given subcutaneously if the potential benefit clearly outweighs the risks (see section 5.1).

Apnoea in premature infants

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 ≤ 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 generally should not be withheld or delayed.

Immunocompromised individuals

Immunocompromised individuals, whether due to the use of immuno-suppressive therapy, a genetic defect, HIV infection, or other causes, may have reduced antibody response to active immunisation.

Safety and immunogenicity data for Vaxneuvance are available for individuals with sickle cell disease or living with HIV infection or with a haematopoietic stem cell transplant (see section 5.1). Safety and immunogenicity data for Vaxneuvance are not available for individuals in other specific immunocompromised groups and vaccination should be considered on an individual basis.

Protection

As with any vaccine, vaccination with Vaxneuvance may not protect all vaccine recipients. Vaxneuvance will only protect against Streptococcus pneumoniae serotypes included in the vaccine (see sections 2 and 5.1).

Excipients with known effect

Sodium

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

Polysorbate 20

This medicinal product contains 1 mg of polysorbate 20 in each 0.5 mL dose. Polysorbates may cause allergic reactions.

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

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

Immunosuppressive therapies may reduce the immune responses to vaccines.

Infants and children aged 6 weeks to less than 2 years

Vaxneuvance can be given concomitantly with any of the following vaccine antigens, either as monovalent or combination vaccines: diphtheria, tetanus, pertussis, poliomyelitis (serotypes 1, 2 and 3), hepatitis A, hepatitis B, Haemophilus influenzae type b, measles, mumps, rubella, varicella and rotavirus vaccine.

Children and adolescents 2 to less than 18 years of age

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

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

Adults

Vaxneuvance can be administered concomitantly with seasonal quadrivalent influenza vaccine (split virion, inactivated). There are no data on the concomitant administration of Vaxneuvance with other vaccines.

4.6. Fertility, pregnancy, and lactation

Pregnancy

There is limited experience with the use of Vaxneuvance in pregnant women.

Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryo/foetal development, parturition or post-natal development (see section 5.3).

Administration of Vaxneuvance in pregnancy should only be considered when the potential benefits outweigh any potential risks for the mother and the foetus.

Breast‑feeding

It is unknown whether Vaxneuvance is excreted in human milk.

Fertility

No human data on the effect of Vaxneuvance on fertility are available. Animal studies in female rats do not indicate harmful effects (see section 5.3).

4.7. Effects on ability to drive and use machines

Vaxneuvance 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

Summary of the safety profile

Paediatric population

Infants and children aged 6 weeks to less than 2 years

The safety of Vaxneuvance in healthy infants, including preterm infants (from 6 weeks of age at first vaccination) and children (11 through 15 months of age) was assessed as a 3 dose or 4 dose regimen in 5 clinical studies with a total of 7,229 participants.

All 5 studies evaluated the safety of Vaxneuvance when administered concomitantly with other routine paediatric vaccines. In these studies, 4,286 participants received a complete regimen of Vaxneuvance, 2,405 participants received a complete regimen of the 13-valent pneumococcal conjugate vaccine (PCV) and 538 participants received Vaxneuvance when used to complete a regimen initiated with the 13-valent PCV (mixed dose regimen).

The most frequent adverse reactions were pyrexia ≥38 °C (75.2%), irritability (74.5%), somnolence (55.0%), injection-site pain (44.4%), injection-site erythema (41.7%), decreased appetite (38.2%), injection-site induration (28.3%) and injection-site swelling (28.2%) based on results in 3,589 participants (Table 1), excluding participants who received a mixed dose regimen. The majority of solicited adverse reactions were mild to moderate (based on intensity or size) and of short duration (≤3 days). Severe reactions (defined as being extremely distressed or unable to do usual activities or size of injection site reaction >7.6 cm) occurred in ≤3.5% of infants and children following any dose, with the exception of irritability which occurred in 11.4% of participants.

Children and adolescents 2 to less than 18 years of age

The safety of Vaxneuvance in healthy children and adolescents was assessed in a study that included 352 participants 2 to less than 18 years of age, of whom 177 received a single dose of Vaxneuvance. In this age cohort, 42.9% of all participants had a history of previous vaccination with a lower valency pneumococcal conjugate vaccine.

The most frequent adverse reactions were injection-site pain (54.8%), myalgia (23.7%), injection-site swelling (20.9%), injection-site erythema (19.2%), fatigue (15.8%), headache (11.9%), injection-site induration (6.8%), and pyrexia ≥38 °C (5.6%) (Table 1). The majority of solicited adverse reactions were mild to moderate (based on intensity or size) and of short duration (≤3 days); severe reactions (defined as being extremely distressed or unable to do usual activities or size of injection site reaction >7.6 cm) occurred in ≤4.5% of children and adolescents.

Adults 18 years of age and older

The safety of Vaxneuvance in healthy and immunocompetent adults was assessed in 6 clinical studies in 7,136 adults ≥18 years of age. An additional clinical study assessed 302 adults ≥18 years of age living with HIV. Vaxneuvance was administered to 5,630 adults; 1,241 were 18 to 49 years of age, 1,911 were 50 to 64 years of age, and 2,478 were 65 years of age and older. Of those who received Vaxneuvance, 1,134 were immunocompetent adults 18 to 49 years of age who had no (n=285), 1 (n=620) or ≥ 2 (n=229) risk factors for pneumococcal disease and 152 were adults ≥18 years of age living with HIV. In addition, 5,253 adults were pneumococcal vaccine‑naïve and 377 adults were previously vaccinated with 23‑valent pneumococcal polysaccharide vaccine (PPV23) at least 1 year prior to enrollment.

The most frequently reported adverse reactions following vaccination with Vaxneuvance were solicited. In the pooled analysis of the 7 studies, the most frequent adverse reactions were injection-site pain (64.6%), fatigue (23.4%), myalgia (20.7%), headache (17.3%), injection-site swelling (16.1%), injection-site erythema (11.3%) and arthralgia (7.9%) (Table 1). The majority of solicited adverse reactions were mild (based on intensity or size) and of short duration (≤3 days); severe reactions (defined as an event that prevents normal daily activity or size of injection site reaction >10 cm) occurred in ≤1.5% of adults across the clinical program.

Older adults reported fewer adverse reactions than younger adults.

Tabulated list of adverse reactions

In clinical studies of adults, local and systemic adverse reactions were solicited daily after vaccination for 5 and 14 days, respectively and in infants, children and adolescents up to 14 days after vaccination. In all populations, unsolicited adverse reactions were reported for 14 days after vaccination.

Adverse reactions reported 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 the available data).

Table 1: Tabulated list of adverse reactions

System Organ Class

Adverse Reactions

Frequency

Infants/Children/Adolescents

Adults

6W to <2Y

2 to <18Y§

Metabolism and nutrition disorders

Decreased appetite

Very common

Common

-

Psychiatric disorders

Irritability

Very common

Common

-

Immune system disorders

Hypersensitivity reaction including tongue oedema, flushing, and throat tightness

-

-

Rare

Nervous system disorders

Somnolence

Very common

Common

-

Headache

-

Very common

Very common

Dizziness

-

-

Uncommon†

Skin and subcutaneous tissue disorders

Urticaria

Common

Common

Rare

Rash

Common

Not known ‡

Uncommon

Gastrointestinal disorders

Nausea

-

Common

Uncommon†

Vomiting

Common

Uncommon

Uncommon

Musculoskeletal and connective tissue disorders

Myalgia

-

Very common

Very common

Arthralgia

-

-

Common*

General disorders and administration site conditions

Pyrexia⸸

Very common

Common

Uncommon†

≥39°C

Very common

-

-

≥40 °C

Common

-

-

Injection‑site pain

Very common

Very common

Very common

Injection-site erythema

Very common

Very common

Very common

Injection-site swelling

Very common

Very common

Very common

Injection-site induration

Very common

Common

-

Injection-site urticaria

Uncommon

-

-

Fatigue

-

Very common

Very common

Injection‑site pruritus

-

-

Common

Injection-site warmth

-

-

Uncommon

Injection-site bruising/haematoma

Common

Common

Uncommon

Chills

-

-

Uncommon†

§Different systemic adverse events were solicited for participants 2 to <3 years of age, than for participants ≥3 to less than 18 years of age. For participants <3 years of age (Vaxneuvance N=32, 13-valent PCV N=28), decreased appetite, irritability, somnolence and urticaria were solicited from Day 1 through Day 14 following vaccination. For participants ≥3 to less than 18 years of age, fatigue, headache, myalgia, and urticaria were solicited from Day 1 through Day 14 following vaccination.

†common in adults 18 to 49 years of age

‡In clinical trials, no events were observed following Vaxneuvance in healthy children and adolescents and two events were observed in special populations (sickle cell disease and HIV).

*very common in adults 18 to 49 years of age

⸸defined as temperature ≥38 °C

Additional information for other dosing regimens, vaccination schedules and special populations

Mixed dose regimen of different pneumococcal conjugate vaccines

The safety profiles of mixed 4-dose regimens of Vaxneuvance and the 13-valent PCV in healthy infants and children were generally comparable to those of complete 4-dose regimens of either Vaxneuvance or the 13-valent PCV (see section 5.1).

Catch-up vaccination schedule

Safety was also assessed as a catch-up vaccination schedule in 126 healthy infants and children from 7 months to less than 2 years of age who received 2 or 3 doses of Vaxneuvance based on age at enrollment. The safety profile of the catch-up vaccination schedule was generally consistent with the safety profile of the routine vaccination schedule initiated from 6 weeks of age (see section 5.1).

Children and adolescents with sickle cell disease or living with HIV

Safety was also assessed in 69 children and adolescents 5 to less than 18 years of age with sickle cell disease and in 203 children and adolescents 6 to less than 18 years of age living with HIV, all of whom received a single dose of Vaxneuvance. The safety profile of Vaxneuvance in children with these conditions was generally consistent with the safety profile in healthy children (see section 5.1).

Children and adults receiving Haematopoietic Stem Cell Transplant

Safety was also assessed in 131 adults and 8 children ≥3 years of age who had received an allogeneic haematopoietic stem cell transplant (allo-HSCT) 3 to 6 months prior to enrollment, all of whom received between 1 and 4 doses of Vaxneuvance. The safety profile of Vaxneuvance in recipients of allo-HSCT was generally consistent with the safety profile in a healthy population.

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

There are no data with regard to overdose.