4.1. Therapeutic indications

Nimenrix is indicated for active immunisation of individuals from the age of 6 weeks against invasive meningococcal disease caused by Neisseria meningitidis groups A, C, W-135, and Y.

4.2. Posology and method of administration

Posology

Nimenrix should be used in accordance with available official recommendations.

Primary immunisation

Infants from 6 weeks to less than 6 months of age: two doses, each of 0.5 ml, should be administered with an interval of 2 months between doses.

Infants from 6 months of age, children, adolescents and adults: a single 0.5 mL dose should be administered.

An additional primary dose of Nimenrix may be considered appropriate for some individuals (see section 4.4).

Booster doses

Long-term antibody persistence data following vaccination with Nimenrix are available up to 10 years after vaccination (see sections 4.4 and 5.1).

After completion of the primary immunisation course in infants 6 weeks to less than 12 months of age, a booster dose should be given at 12 months of age with an interval of at least 2 months after the last Nimenrix vaccination (see section 5.1).

In previously vaccinated individuals 12 months of age and older, Nimenrix may be given as a booster dose if they have received primary vaccination with a conjugated or plain polysaccharide meningococcal vaccine (see sections 4.4 and 5.1).

Method of administration

Immunisation should be carried out by intramuscular injection only.

In infants, the recommended injection site is the anterolateral aspect of the thigh. In individuals from 1 year of age, the recommended injection site is the anterolateral aspect of the thigh or the deltoid muscle (see sections 4.4 and 4.5).

For instructions on reconstitution of the medicinal product 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.

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.

Nimenrix should under no circumstances be administered intravascularly, intradermally or subcutaneously.

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.

Appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic event following the administration of the vaccine.

Intercurrent illness

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

Syncope

Syncope (fainting) can occur following, or even before, any vaccination especially in adolescents as a psychogenic response to the needle injection. This can be accompanied by several neurological signs such as transient visual disturbance, paraesthesia and tonic-clonic limb movements during recovery. It is important that procedures are in place to avoid injury from faints.

Thrombocytopenia and coagulation disorders

Nimenrix should be given with caution to individuals with thrombocytopenia or any coagulation disorder since bleeding may occur following an intramuscular administration to these subjects.

Immunodeficiency

It may be expected that in patients receiving immunosuppressive treatment or patients with immunodeficiency, an adequate immune response may not be elicited.

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 for invasive disease caused by Neisseria meningitidis groups A, C, W-135 and Y, even if they develop antibodies following vaccination with Nimenrix.

Protection against meningococcal disease

Nimenrix will only confer protection against Neisseria meningitidis groups A, C, W-135 and Y. The vaccine will not protect against any other Neisseria meningitidis groups.

A protective immune response may not be elicited in all vaccinees.

Effect of prior vaccination with plain polysaccharide meningococcal vaccine

Subjects previously vaccinated with a plain polysaccharide meningococcal vaccine and vaccinated with Nimenrix 30 to 42 months later had lower Geometric Mean Titres (GMTs) measured with a serum bactericidal assay using rabbit complement (rSBA) than subjects who had not been vaccinated with any meningococcal vaccine in the preceding 10 years (see section 5.1). The clinical relevance of this observation is unknown.

Effect of pre-vaccination antibody to tetanus toxoid

The safety and immunogenicity of Nimenrix was evaluated when it was sequentially administered or co-administered with a vaccine containing, diphtheria and tetanus toxoids, acellular pertussis, inactivated polioviruses (1, 2 and 3), hepatitis B surface antigen and Haemophilus influenzae type b polyribosyl ribose phosphate conjugated to tetanus toxoid (DTaP-HBV-IPV/Hib) in the second year of life. The administration of Nimenrix one month after the DTaP-HBV-IPV/Hib vaccine resulted in lower rSBA GMTs against groups A, C and W-135 compared with co-administration (see section 4.5). The clinical relevance of this observation is unknown.

Immune response in infants aged 6 months to less than 12 months

A single dose administered at 6 months was associated with lower human complement serum bactericidal assay (hSBA) titres to groups W-135 and Y compared with three doses administered at 2, 4, and 6 months (see section 5.1). The clinical relevance of this observation is unknown. If an infant aged 6 months to less than 12 months is expected to be at particular risk of invasive meningococcal disease due to exposure to groups W-135 and/or Y, consideration may be given to administering a second primary dose of Nimenrix after an interval of 2 months.

Immune responses in toddlers aged 12-14 months

Toddlers aged 12-14 months had similar rSBA titres to groups A, C, W-135 and Y at one month after one dose of Nimenrix or at one month after two doses of Nimenrix given two months apart.

A single dose was associated with lower hSBA titres to groups W-135 and Y compared with two doses given two months apart. Similar responses to groups A and C were observed after one or two doses (see section 5.1). The clinical relevance of this observation is unknown. If a toddler is expected to be at particular risk of invasive meningococcal disease due to exposure to groups W-135 and/or Y, consideration may be given to administering a second dose of Nimenrix after an interval of 2 months. Regarding waning of antibody against group A or group C after a first dose of Nimenrix in children aged 12-23 months, see under Persistence of serum bactericidal antibody titres.

Persistence of serum bactericidal antibody titres

Following administration of Nimenrix there is a waning of serum bactericidal antibody titres against group A when using hSBA (see section 5.1). The clinical relevance of this observation is unknown. However, if an individual is expected to be at particular risk of exposure to group A and received a dose of Nimenrix more than approximately one year previously, consideration may be given to administering a booster dose.

A decline in antibody titres over time has been observed for groups A, C, W-135 and Y. The clinical relevance of this observation is unknown. A booster dose might be considered in individuals vaccinated at toddler age remaining at high risk of exposure to meningococcal disease caused by groups A, C, W-135 or Y (see section 5.1).

Effect of Nimenrix on anti-tetanus antibody concentrations

Although an increase of the anti-tetanus toxoid (TT) antibody concentrations was observed following vaccination with Nimenrix, Nimenrix does not substitute for tetanus immunisation.

Giving Nimenrix with or one month before a TT-containing vaccine in the second year of life does not impair the response to TT or significantly affect safety. No data are available beyond the age of 2 years.

Sodium content

This vaccine 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

In infants, Nimenrix can be given concomitantly with combined DTaP-HBV-IPV/Hib vaccines and with 10-valent pneumococcal conjugate vaccine.

From age 1 year and above, Nimenrix can be given concomitantly with any of the following vaccines: hepatitis A (HAV) and hepatitis B (HBV) vaccines, measles - mumps - rubella (MMR) vaccine, measles - mumps - rubella - varicella (MMRV) vaccine, 10-valent pneumococcal conjugate vaccine or unadjuvanted seasonal influenza vaccine.

In the second year of life, Nimenrix can also be given concomitantly with combined diphtheria - tetanus - acellular pertussis (DTaP) vaccines, including combination DTaP vaccines with hepatitis B, inactivated poliovirus or Haemophilus influenzae type b (HBV, IPV or Hib) such as DTaP-HBV-IPV/Hib vaccine, and 13-valent pneumococcal conjugate vaccine.

In individuals aged 9 to 25 years, Nimenrix can be given concomitantly with human papillomavirus bivalent [Type 16 and 18] vaccine, recombinant (HPV2).

Whenever possible, Nimenrix and a TT-containing vaccine, such as DTaP-HBV-IPV/Hib vaccine, should be co-administered or Nimenrix should be administered at least one month before the TT-containing vaccine.

One month after co-administration with a 10-valent pneumococcal conjugate vaccine, lower Geometric Mean antibody Concentrations (GMCs) and opsonophagocytic assay (OPA) antibody GMTs were observed for one pneumococcal serotype (18C conjugated to tetanus toxoid carrier protein). The clinical relevance of this observation is unknown. There was no impact of co-administration on immune responses to the other nine pneumococcal serotypes.

One month after co-administration with a combined tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine, adsorbed (Tdap) in subjects aged 9 to 25 years, lower GMCs were observed to each pertussis antigen (pertussis toxoid [PT], filamentous haemagglutinin [FHA] and pertactin [PRN]). More than 98% of subjects had anti-PT, FHA or PRN concentrations above the assay cut-off thresholds. The clinical relevance of these observations is unknown. There was no impact of co-administration on immune responses to Nimenrix or the tetanus or diphtheria antigens included in Tdap.

If Nimenrix is to be given at the same time as another injectable vaccine, the vaccines should always be administered at different injection sites.

It may be expected that in patients receiving immunosuppressive treatment, an adequate response may not be elicited.

4.6. Fertility, pregnancy and lactation

Pregnancy

There is limited experience with use of Nimenrix 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).

Nimenrix should be used during pregnancy only when clearly needed, and the possible advantages outweigh the potential risks for the foetus.

Breast-feeding

It is unknown whether Nimenrix is excreted in human milk.

Nimenrix should only be used during breast-feeding when the possible advantages outweigh the potential risks.

Fertility

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

4.7. Effects on ability to drive and use machines

No studies on the effects of Nimenrix on the ability to drive and use machines have been performed.

However, some of the effects mentioned under section 4.8 “Undesirable effects” may affect the ability to drive or use machines.

4.8. Undesirable effects

Summary of the safety profile

The safety of Nimenrix presented in the table below is based on two clinical study datasets as follows:

• A pooled analysis of data from 9,621 subjects administered a single dose of Nimenrix. This total included 3,079 toddlers (12 months to 23 months), 909 children between 2 and 5 years of age, 990 children between 6 and 10 years of age, 2,317 adolescents (11 to 17 years) and 2,326 adults (18 to 55 years).

• Data from a study in infants aged 6 to 12 weeks at the time of the first dose (Study MenACWY-TT-083), 1,052 subjects received at least one dose of a primary series of 2 or 3 doses of Nimenrix and 1,008 received a booster dose at approximately 12 months of age.

Safety data have also been evaluated in a separate study, in which a single dose of Nimenrix was administered to 274 individuals aged 56 years and older.

Local and general adverse reactions

In the 6-12 weeks and in the 12-14 months age groups who received 2 doses of Nimenrix given 2 months apart, the first and second doses were associated with similar local and systemic reactogenicity.

The local and general adverse reaction profile of a booster dose of Nimenrix given to subjects from 12 months through 30 years of age after primary vaccination with Nimenrix or other conjugated or plain polysaccharide meningococcal vaccines, was similar to the local and general adverse reaction profile observed after primary vaccination with Nimenrix, except for gastrointestinal symptoms (including diarrhoea, vomiting, and nausea), which were very common among subjects 6 years of age and older.

Tabulated list of adverse reactions

Adverse reactions reported are listed 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 available data)

Table 1 shows the adverse reactions reported from the studies in subjects aged from 6 weeks up to 55 years of age and post-marketing experience. Adverse reactions reported in subjects aged >55 years were similar to those observed in younger adults.

Table 1: Tabulated summary of adverse reactions by system organ class

System Organ Class

Frequency

Adverse reactions

Blood and lymphatic system disorders

Not known***

Lymphadenopathy

Immune system disorders

Uncommon

Hypersensitivity***

Not known

Anaphylaxis***

Metabolism and nutrition disorders

Very common

Appetite lost

Psychiatric disorders

Very common

Irritability

Uncommon

Insomnia

Crying

Nervous system disorders

Very common

Drowsiness

Headache

Uncommon

Hypoaesthesia

Dizziness

Rare

Febrile convulsion

Gastrointestinal disorders

Common

Diarrhoea

Vomiting

Nausea*

Skin and subcutaneous tissue disorders

Uncommon

Pruritus

Urticaria

Rash**

Musculoskeletal and connective tissue disorders

Uncommon

Myalgia

Pain in extremity

General disorders and administration site conditions

Very common

Fever

Swelling at injection site

Pain at injection site

Redness at injection site

Fatigue

Common

Injection site haematoma*

Uncommon

Malaise

Injection site induration

Injection site pruritus

Injection site warmth

Injection site anaesthesia

Not known***

Extensive limb swelling at the injection site, frequently associated with erythema, sometimes involving the adjacent joint or swelling of the entire injected limb

*Nausea and Injection site haematoma occurred at a frequency of Uncommon in infants

**Rash occurred at a frequency of Common in infants

***ADR identified post-marketing

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 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

No case of overdose has been reported.