4.1. Therapeutic indications

MenQuadfi is indicated for active immunisation of individuals from the age of 12 months and older against invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, W, and Y.

The use of this vaccine should be in accordance with available official recommendations.

4.2. Posology and method of administration

Posology

Primary vaccination:

• Individuals 12 months of age and older: One single dose (0.5 mL).

Booster vaccination:

• A single 0.5 mL dose of MenQuadfi may be used to boost subjects who have previously received a meningococcal vaccine containing the same serogroups (see section 5.1).

• Long-term antibody persistence data following vaccination with MenQuadfi are available up to 7 years after vaccination (see sections 4.4 and 5.1).

• There are no data available to indicate the need for or timing of a booster dose of MenQuadfi (see section 5.1).

Other paediatric population

The safety and immunogenicity of MenQuadfi in individuals under 12 months of age have not yet been established.

Method of administration

For intramuscular injection only, preferably in the deltoid region or anterolateral thigh depending on the recipient's age and muscle mass.

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

4.3. Contraindications

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1 or after previous administration of the vaccine or a vaccine containing the same components.

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.

MenQuadfi should not be administered subcutaneously, intravascularly or intradermally.

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 effects) and a clinical examination.

Hypersensitivity

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

Intercurrent illness

Vaccination should be postponed in individuals suffering from an acute severe febrile illness. However, the presence of a minor infection, such as cold, should not result in the deferral of vaccination.

Syncope

Syncope (fainting) and other anxiety‐related reactions can occur following or even before any vaccination as a psychogenic response to the needle injection. Procedures should be in place to prevent falling or injury and to manage syncope.

Thrombocytopenia and coagulation disorders

MenQuadfi should be given with caution to individuals with thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injection, unless the potential benefit clearly outweighs the risk of administration.

Protection

MenQuadfi will only protect against Neisseria meningitidis groups A, C, W, and Y. The vaccine will not protect against any other Neisseria meningitidis groups.

As with any vaccine, vaccination with MenQuadfi may not protect all vaccine recipients.

Waning of serum bactericidal antibody titres against serogroup A when using human complement in the assay (hSBA) has been reported for MenQuadfi and other quadrivalent meningococcal vaccines. The clinical relevance of this observation is unknown. However, if an individual is expected to be at particular risk of exposure to serogroup A and received a dose of MenQuadfi more than approximately one year previously, consideration may be given to administering a booster dose.

Lower hSBA geometric mean titres (GMTs) against serogroup A have been observed after a single dose of MenQuadfi was administered to toddlers who previously received serogroup C meningococcal conjugate vaccine (MenC-CRM) during infancy. Nevertheless, seroprotection rates were comparable between treatment groups (see section 5.1). The clinical relevance of this observation is unknown. This aspect might be considered for individuals at high risk for MenA infection who received MenC-CRM vaccine in their first year of life.

Immunodeficiency

It may be expected that in patients receiving immunosuppressive treatment or patients with immunodeficiency, an adequate immune response may not be elicited (see section 4.5). Persons with familial complement deficiencies (for example, C5 or C3 deficiencies) and persons receiving treatments that inhibit terminal complement activation (for example, eculizumab) are at increased risk of invasive disease caused by Neisseria meningitidis groups A, C, W, and Y, even if they develop antibodies following vaccination with MenQuadfi. No data on immunocompromised patients are available.

Tetanus immunisation

Immunisation with MenQuadfi vaccine does not substitute for routine tetanus immunisation.

Co-administration of MenQuadfi with a tetanus toxoid-containing vaccine does not impair the response to tetanus toxoid or impact the safety.

Sodium content

This medicine 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

Use with other vaccines

Injection sites on separate limbs and separate syringes must be used in the case of concomitant administration.

For ages 12‑23 months, MenQuadfi can be co-administered with the measles-mumps-rubella vaccine (MMR) + varicella vaccine (V), combined diphtheria - tetanus - acellular pertussis (DTaP) vaccines, including combination DTaP vaccines with hepatitis B (HBV), inactivated poliovirus (IPV) or Haemophilus influenzae type b (Hib) such as DTaP-IPV-HB-Hib (Hib conjugated to tetanus toxoid) vaccine and 13-valent pneumococcal polysaccharide conjugated vaccine (PCV-13).

There was no impact on the immune response to MenQuadfi when a meningococcal serogroup B vaccine was co-administered.

MenQuadfi can be administered concomitantly with PCV-13. Lower hSBA GMTs on day 30 post-dose for serogroup A have been observed when given concomitantly. The clinical relevance of this observation is unknown. As a precaution in children 12‑23 months of age at high risk for serogroup A disease, consideration might be given for administration of MenQuadfi and PCV-13 vaccines separately.

For ages 10-17 years, MenQuadfi can be co-administered with diphtheria, tetanus, pertussis (acellular, component) vaccine (adsorbed, reduced antigen(s) content) (Tdap), or Tdap and inactivated poliovirus vaccine (Tdap-IPV), and 4-valent human papillomavirus vaccine (recombinant, adsorbed) (4vHPV) or 9-valent HPV vaccine (9vHPV). However, the antibody responses to some of the antigens might be affected by the co-administration.

Meningococcal vaccine naïve children and adolescents aged 10-17 years had non inferior response for PT and lower antibody responses to FHA, PRN and FIM when Tdap vaccine was administered concomitantly with MenQuadfi and 4vHPV compared to co-administration with 4vHPV vaccine alone (immune response assessed after the full series of HPV was completed). The clinical implications of the observed pertussis antigen responses also observed with other quadrivalent meningococcal conjugate vaccines are unknown.

The co-administration of MenQuadfi with Tdap-IPV and 9vHPV in children and adolescents aged 10-17 years resulted in lower GMTs and seroresponse rates for serogroup A, lower GMTs for serogroup W, lower responses to inactivated polio types 1 and 3, diphtheria, and anti-HPV types 6 and 58 (immune response assessed after the first dose of 9vHPV) compared to when MenQuadfi was given sequentially with Tdap-IPV and 9vHPV. The clinical implication of the observed reduced titre responses is unclear. Consideration might be given for sequential administration of MenQuadfi with Tdap-IPV and 9vHPV (e.g. for children and adolescents at higher risk).

Concomitant vaccines should always be administered at separate injection sites and preferably contralateral.

Concomitant administration of MenQuadfi and other vaccines than those listed above has not been studied.

Use with systemic immunosuppressive medicinal products

It may be expected that in patients receiving immunosuppressive treatment an adequate immune response may not be elicited (see also section 4.4).

4.6. Fertility, pregnancy and lactation

Pregnancy

There is limited amount of data on the use of MenQuadfi in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). MenQuadfi should be used during pregnancy only if the expected benefits for the mother outweigh the potential risks, including those for the foetus.

Breast-feeding

It is unknown whether MenQuadfi is excreted in human milk. MenQuadfi should only be used during breast-feeding when the possible advantages outweigh the potential risks.

Fertility

A developmental and reproductive toxicity study was performed in female rabbits. There were no effects on mating performances or female fertility. No study was conducted on male fertility (see section 5.3).

4.7. Effects on ability to drive and use machines

MenQuadfi has no or negligible influence on the ability to drive and use machines.

However, some of the adverse reactions 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

The safety of a single dose of MenQuadfi in individuals 12 months of age and older was evaluated in clinical trials where 6 308 subjects received either a primary dose (N = 5 906) or a booster dose (N = 402) of MenQuadfi. This included 1 389 toddlers aged 12 through 23 months of age, 498 children aged 2 through 9 years, 2 289 children and adolescents aged 10 through 17 years, 1 684 adults aged 18 through 55 years, 199 older adults aged 56 through 64 years, and 249 elderly aged 65 years and older. Of these, 392 adolescents received MenQuadfi co-administered with Tdap and 4vHPV, and 589 toddlers received MenQuadfi co-administered with MMR+V (N = 189), DTaP-IPV-HB-Hib (N = 200) or PCV-13 (N = 200).

The most frequently reported adverse reactions within 7 days after vaccination with a single dose of MenQuadfi alone in toddlers 12 through 23 months of age were irritability (36.7%) and injection site tenderness (30.6%) and in ages 2 years and above were injection site pain (38.7%) and myalgia (30.5%). These adverse reactions were mostly mild or moderate in intensity.

Rates of adverse reactions after a booster dose of MenQuadfi in adolescents and adults at least 15 years of age were comparable to those seen in adolescents and adults who received a primary dose of MenQuadfi.

Rates of adverse reactions within 7 days following vaccination among toddlers were comparable when MMR+V were given concomitantly with or without MenQuadfi, and when DTaP-IPV-HB-Hib was given with or without MenQuadfi. Overall, the rates of adverse reactions were higher in toddlers who received PCV-13 given concomitantly with MenQuadfi (36.5%) than in toddlers who received PCV-13 alone (17.2%).

Children and adolescents aged 10-17 years of age were given either MenQuadfi alone (N = 171) or MenQuadfi concomitantly with Tdap-IPV and the first dose of 9vHPV (N = 116). The rates of injection site pain at the 9vHPV injection site were higher when given concomitantly with Tdap-IPV and MenQuadfi (83.6%) compared to when Tdap-IPV and 9vHPV were given without MenQuadfi (67.3%). Overall, rates and intensity of adverse reactions were comparable between these two groups.

Adolescents and adults 13-26 years of age primed with MenQuadfi 3-6 years previously received MenQuadfi co-administered with meningococcal serogroup B vaccine (MenB), MenB (recombinant, adsorbed) (N = 93) or MenB (rDNA, component, adsorbed) (N = 92). Rates and intensity of systemic adverse reactions within 7 days following vaccination tended to be higher when MenQuadfi was given concomitantly with MenB vaccine than when MenQuadfi was given alone. The most common solicited systemic adverse reaction was myalgia, of mild intensity, which was experienced more frequently in adolescents and adults who received MenQuadfi and MenB vaccine concomitantly (MenB [recombinant, adsorbed], 65.2%; or MenB [rDNA, component, adsorbed], 63%) compared to those who received MenQuadfi alone (32.8%).

Tabulated list of adverse reactions

The following adverse reactions, as listed below, have been identified from clinical trials conducted with MenQuadfi when given alone to subjects 2 years of age and older and post-marketing surveillance. The safety profile observed in toddlers aged 12 through 23 months is presented in the paediatric population section.

The adverse reactions are listed by MedDRA system organ class and by frequency according to the following frequency categories:

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).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 1: Adverse reactions following administration of MenQuadfi from clinical trials and post-marketing surveillance in subjects 2 years of age and above

MedDRA system organ class

Frequency

Adverse reactions

Blood and lymphatic system disorders

Rare

Lymphadenopathy

Immune system disorders

Very rare

Anaphylaxis

Not known

Hypersensitivity

Nervous system disorders

Very common

Headache

Uncommon

Dizziness

Not known

Febrile convulsions, seizures

Gastrointestinal disorders

Uncommon

Vomiting, nausea

Rare

Diarrhoea, stomach pain

Skin and subcutaneous tissue disorders

Rare

Urticaria, pruritus, rash

Musculoskeletal and connective tissue disorders

Very common

Myalgia

Rare

Pain in extremity

General disorders and administration site conditions

Very common

Malaise

Injection site pain

Common

Fever

At the injection site: swelling, erythema

Uncommon

Fatigue

At the injection site: pruritus, warmth, bruising, rash

Rare

Chills, axillary pain

At the injection site: induration

Paediatric population

The safety profile of MenQuadfi in children and adolescents 2 through 17 years of age was generally comparable to that in adults. Injection site erythema and swelling at the MenQuadfi injection site were reported more frequently in children 2 through 9 years of age (very common) than in the older age groups.

In toddlers 12 through 23 months of age, injection site erythema and swelling (very common) at the MenQuadfi injection site, vomiting (common) and diarrhoea (common), were reported more frequently than in the older age groups. The following additional reactions, as listed below in Table 2, have been reported following administration of MenQuadfi in toddlers during clinical trials and post-marketing surveillance:

Table 2: Adverse reactions following administration of MenQuadfi from clinical trials and post-marketing surveillance in subjects 12 months through 23 months

MedDRA system organ class

Frequency

Adverse reactions

Immune system disorders

Very rare

Anaphylaxis

Not known

Hypersensitivity

Metabolic and nutrition disorders

Very common

Appetite lost

Psychiatric disorders

Very common

Irritability

Uncommon

Insomnia

Nervous system disorders

Very common

Drowsiness

Not known

Febrile convulsions, seizures

Gastrointestinal disorders

Common

Vomiting, diarrhoea

Skin and subcutaneous tissue disorders

Uncommon

Urticaria

General disorders and administration site conditions

Very common

Abnormal crying

At the injection site: tenderness/pain, erythema, swelling

Common

Fever

Uncommon

At the injection site: pruritus, induration, bruising, rash

Older population

Overall, within 7 days after vaccination with a single dose of MenQuadfi, the same injection site and systemic adverse reactions were observed in older (≥ 56 years of age) and younger adults (18 through 55 years old) but at lower frequencies; except for injection site pruritus, which was more frequent (common) in older adults. These adverse reactions mostly were mild or moderate in intensity.

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 Medicines and Healthcare products Regulatory Agency (MHRA), 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 MenQuadfi is unlikely due to its presentation as a single dose vial. In the event of overdose, monitoring of vital functions and possible symptomatic treatment is recommended.