Nimenrix

Meningococcal polysaccharide groups A, C, W-135 and Y conjugate vaccine.

After reconstitution, 1 dose (0.5 ml) contains 5 micrograms of polysaccharide for Neisseria meningitidis groups A*, C*, W-135* and Y*.
*conjugated to tetanus toxoid carrier protein 44 micrograms.
Excipients/Inactive Ingredients: Powder: sucrose, trometamol.
Solvent: sodium chloride, water for injections.

Pharmacotherapeutic group: bacterial vaccines. ATC code: J07AH08.
Pharmacology: Pharmacodynamics: Mechanism of Action: Anti-capsular meningococcal antibodies protect against meningococcal disease via complement mediated bactericidal killing. Nimenrix induces the production of bactericidal antibodies against capsular polysaccharides of Neisseria meningitidis groups A, C, W-135 and Y when measured by assays using either rSBA or hSBA. By conjugating capsular polysaccharide to a protein carrier that contains T-cell epitopes, meningococcal conjugate vaccines like Nimenrix change the nature of immune response to capsular polysaccharide from T-cell independent to T-cell dependent.
Vaccine efficacy was inferred from the demonstration of immunologic non inferiority (based mainly on comparing proportions with rSBA titres at least 1:8) to licensed meningococcal vaccines. Immunogenicity was measured by using rSBA or hSBA which are biomarkers for protective efficacy against meningococcal groups A, C, W-135 and Y.
Immunogenicity in infants: In Study MenACWY-TT-083, the immunogenicity of a 2-dose primary vaccination schedule administered at 2 and 4 months of age was evaluated. Routinely used infant vaccines DTaP/IPV/Hib/HepB and a 10-valent pneumococcal vaccine were co-administered. For group C, rSBA and hSBA titres elicited by Nimenrix were compared to a 2-dose priming with licensed monovalent meningococcal conjugate group C vaccines, MenC-CRM and MenC-TT vaccines. Nimenrix elicited rSBA and hSBA titres against the four meningococcal groups. The response against group C was non-inferior to the one elicited by the licensed MenC-CRM and MenC-TT vaccines in terms of the percentage of subjects with rSBA titres ≥8 at 1 month after the second dose.
For subjects initially vaccinated in infancy with Nimenrix at 2 and 4 months of age and receiving a Nimenrix booster dose at 12 months of age, the increase in rSBA and hSBA titres 1 month post-booster dose ranged between 15 and 80-fold for all groups and more than 99.0% of all infants achieved post-booster titres above 8 for both assays. The observed booster response for group C was similar to that observed in subjects primed and boosted with a monovalent MenC conjugate vaccine (TT or CRM conjugated). Results are shown in Table 1. (See Table 1.)

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In Study MenACWY-TT-087, infants received either a single primary dose at 6 months followed by a booster dose at 15-18 months or three primary doses at 2, 4, and 6 months followed by a booster dose at 15-18 months. All subjects also received DTaP-IPV/Hib and 10-valent pneumococcal conjugate vaccines at all time points. A single primary dose administered at 6 months of age elicited robust rSBA titres to the four meningococcal groups, as measured by the percentage of subjects with rSBA titres ≥8, that were comparable to responses after the last dose of a three-dose primary series. A booster dose produced robust responses, comparable between the two dosing groups, against all four meningococcal groups. Results are shown in Table 2. (See Table 2.)

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Measurement of hSBA titres was a secondary endpoint in Study MenACWY-TT-087. Although similar responses to groups A and C were observed with both dosing schedules, a single primary dose in infants at 6 months was associated with lower hSBA titres to groups W-135 and Y as measured by the percentage of subjects with hSBA titres ≥8 [87.2% (95% CI: 74.3; 95.2) and 92.3% (95% CI: 81.5; 97.9), respectively] compared with three primary doses at 2, 4, and 6 months of age [100% (95% CI: 96.6; 100) and 100% (95% CI: 97.1; 100), respectively] (see Precautions). After a booster dose, hSBA titres to all four meningococcal groups were comparable between the two dosing schedules (Table 2).
Immunogenicity in toddlers aged 12-23 months: In clinical studies MenACWY-TT-039 and MenACWY-TT-040, a single dose of Nimenrix elicited SBA titres against the four meningococcal groups, with group C rSBA titres that were comparable to those elicited by a licensed MenC-CRM vaccine in terms of the percentage of subjects with rSBA titres ≥8. In Study MenACWY-TT-039, hSBA was also measured as a secondary endpoint. Results are shown in Table 3. (See Table 3.)

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Long term immunogenicity in toddlers: Study MenACWY-TT-104 evaluated the immunogenicity after 1 month and the persistence of the response up to 5 years following 1 or 2 doses (given 2 months apart) of Nimenrix in toddlers aged 12 to 14 months. One month following one or two doses administered 2 months apart Nimenrix elicited rSBA titres against all four meningococcal groups that were similar in terms of the percentage of subjects with rSBA titre ≥8 and GMT. As a secondary endpoint hSBA titres were measured. In terms of the percentage of subjects with hSBA titres ≥8, at 1 month post vaccination, hSBA titres against groups W-135 and Y were higher after two doses of Nimenrix than after one dose, while the hSBA titres against groups A and C were similar in the two dose groups. At Year 5 only a small difference in antibody persistence between one and two doses was observed, in terms of percentages of subjects with hSBA titres ≥8 against all groups. Antibody persistence was observed at Year 5 against groups C, W-135 and Y. After one and two doses the percentages of subjects with hSBA titres ≥8 for group C were 60.7% and 67.8%, group W-135 were 58.9% and 63.6% and group Y were 61.5% and 54.2%, respectively. For group A, 27.9% and 17.9% of subjects receiving one or two doses, respectively, had hSBA titres ≥8. (See Table 4.)

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In children vaccinated at toddler age, the persistence of rSBA and hSBA titres was evaluated up to 4 years in Study MenACWY-TT-048. Results are shown in Table 5. (See Table 5.)

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rSBA and hSBA titres were determined over a period of 10 years in children initially vaccinated with one dose of Nimenrix or MenC-CRM at 12 to 23 months of age in Study MenACWY-TT-027. Persistence of SBA titres was evaluated in two extension studies: MenACWY-TT-032 (up to 5 years) and MenACWY-TT-100 (up to 10 years). Study MenACWY-TT-100 also evaluated the response to a single booster dose of Nimenrix administered 10 years following the initial vaccination with Nimenrix or MenC-CRM. Results are shown in Table 6 (see Precautions). (See Table 6.)

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Persistence of booster response: Study MenACWY-TT-102 evaluated the persistence of SBA titres up to 6 years after a booster dose of Nimenrix or MenC-CRM₁₉₇ administered in Study MenACWY-TT-048 to children who initially received the same vaccine at 12 to 23 months of age in Study MenACWY-TT-039. A single booster dose was administered 4 years after the initial vaccination. Results are shown in Table 7 (see Precautions). (See Table 7.)

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Immune memory: In Study MenACWY-TT-014, the induction of immune memory was assessed 1 month after the administration of a fifth of the dose of ACWY-PS vaccine (10 µg of each polysaccharide) to children in the third year of life initially vaccinated in Study MenACWY-TT-013 with Nimenrix or a licensed MenC-CRM vaccine at the age of 12 to 14 months.
One month after the challenge dose, the GMTs elicited by the initial vaccination with Nimenrix increased by 6.5 to 8 fold for groups A, C, W-135, and Y, indicating that Nimenrix induces immune memory to all four meningococcal groups. The post-challenge rSBA-MenC GMT was similar in both study groups, indicating that Nimenrix induces an analogous immune memory to group C as the licensed MenC-CRM vaccine. Results are shown in Table 8. (See Table 8.)

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Immunogenicity in children aged 2-10 years: In two comparative studies conducted in subjects aged 2-10 years, one group of subjects received a dose of Nimenrix and a second group a dose of either a licensed MenC-CRM vaccine (Study MenACWY-TT-081) or the licensed ACWY-PS vaccine (Study MenACWY-TT-038) as comparator.
In Study MenACWY-TT-038, a single dose of Nimenrix was demonstrated to be non-inferior to the licensed ACWY-PS vaccine in terms of vaccine response to the four meningococcal groups as shown in Table 9. (See Table 9.)

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In Study MenACWY-TT-081, a single dose of Nimenrix (N = 268) was demonstrated to be non-inferior to another licensed MenC-CRM vaccine (N = 92) in terms of vaccine response to group C [94.8% (95% CI: 91.4; 97.1) and 95.7% (95% CI: 89.2; 98.8), respectively]. GMTs were lower for the Nimenrix group [2795 (95% CI: 2393; 3263)] versus the MenC-CRM vaccine [5292 (95% CI: 3815; 7340)].
In Study MenACWY-TT-088, the persistence of SBA titres was evaluated up to 68 months after vaccination in children 2-10 years of age initially vaccinated in Study MenACWY-TT-081. Results are shown in Table 10 (see Precautions). (See Table 10.)

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In Study MenACWY-TT-028, the persistence of hSBA titres was evaluated 1 year after vaccination in children aged 6-10 years who were initially vaccinated in Study MenACWY-TT-027. Results are shown in Table 11. (See Table 11.)

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SBA titres were determined over a period of 10 years in children initially vaccinated with one dose of Nimenrix or ACWY-PS at 2 to 10 years of age in Study MenACWY-TT-027. Persistence of SBA titres was evaluated in two extension studies: MenACWY-TT-032 (up to 5 years) and MenACWY-TT-100 (up to 10 years).
Study MenACWY-TT-100 also evaluated the response to a single booster dose of Nimenrix administered 10 years following the initial vaccination with Nimenrix or ACWY-PS. Results are shown in Table 12 (see Precautions). (See Table 12.)

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Immunogenicity in adolescents aged 11-17 years and adults aged ≥18 years: In two clinical studies, conducted in adolescents aged 11-17 years (Study MenACWY-TT-036) and in adults aged 18-55 years (Study MenACWY-TT-035), either one dose of Nimenrix or one dose of the ACWY-PS vaccine was administered.
In both adolescents and adults, Nimenrix was demonstrated to be immunologically non-inferior to the ACWY-PS vaccine in terms of vaccine response. rSBA titres to the four meningococcal groups elicited by Nimenrix were either similar to or higher than those elicited by the ACWY-PS vaccine as shown in Table 13. (See Table 13.)

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rSBA titres were determined over a period of 10 years in subjects initially vaccinated with one dose of Nimenrix or ACWY-PS at 11 to 17 years of age in Study MenACWY-TT-036. Persistence of rSBA titres was evaluated in two extension studies: MenACWY-TT-043 (up to 5 years) and MenACWY-TT-101 (at 10 years). Study MenACWY-TT-101 also evaluated the response to a single booster dose of Nimenrix administered 10 years following the initial vaccination with Nimenrix or ACWY-PS. Results are shown in Table 14. (See Table 14.)

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In Study MenACWY-TT-059, hSBA persistence was evaluated up to 5 years after vaccination in adolescents and adults aged 11-25 years initially vaccinated in Study MenACWY-TT-052.
For all meningococcal groups, the persistence of hSBA titres elicited by Nimenrix was similar to or higher than those induced by the licensed quadrivalent meningococcal diphtheria toxoid (DT) conjugate (ACWY-DT) vaccine as shown in Table 15. (See Table 15.)

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rSBA titres were determined over a period of 10 years in subjects initially vaccinated with one dose of Nimenrix or ACWY-PS at 11 to 55 years of age in Study MenACWY-TT-015. Persistence of rSBA titres was evaluated in two extension studies: MenACWY-TT-020 (up to 5 years) and MenACWY-TT-099 (up to 10 years). Study MenACWY-TT-099 also evaluated the response to a single booster dose of Nimenrix administered 10 years following the initial vaccination with Nimenrix or ACWY-PS. Results are shown in Table 16. (See Table 16.)

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In a descriptive study conducted in 194 adults aged 56 years and older (Study MenACWY-TT-085), Nimenrix was immunogenic, with a vaccine response rate ≥63.4% and with ≥97.4% of subjects with rSBA titres ≥8 against all four meningococcal groups. Moreover, at least 93.2% of subjects achieved the more conservative threshold of protection of rSBA titres ≥128.
Booster response for subjects previously vaccinated with a conjugate meningococcal vaccine against Neisseria meningitidis: Nimenrix booster vaccination in subjects previously primed with a monovalent (MenC-CRM) or a quadrivalent conjugate meningococcal vaccine (MenACWY-TT) was studied in subjects from 12 months of age onwards who received a booster vaccination. Robust anamnestic responses to the antigen(s) in the priming vaccine were observed (see Tables 6, 7, 12, 14, and 16).
Response to Nimenrix in subjects previously vaccinated with a plain polysaccharide meningococcal vaccine against Neisseria meningitidis: In Study MenACWY-TT-021 conducted in subjects aged 4.5-34 years, the immunogenicity of Nimenrix administered between 30 and 42 months after vaccination with a ACWY-PS vaccine was compared to the immunogenicity of Nimenrix administered to age-matched subjects who had not been vaccinated with any meningococcal vaccine in the preceding 10 years. The rSBA GMTs were significantly lower in the subjects who had received a dose of ACWY-PS vaccine 30-42 months prior to Nimenrix. The clinical relevance of this observation is unknown since all subjects achieved rSBA titres ≥8 for all four meningococcal groups. Results are shown in Table 17. (See Table 17.)

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Immunogenicity in children aged 2-17 years with anatomical or functional asplenia: Study MenACWY-TT-084 evaluated the immunogenicity of one and two doses of Nimenrix given 2 months apart in 43 at-risk subjects aged 2-17 years (at increased risk for meningococcal disease, i.e., asplenic subjects, and hyposplenic subjects) compared to 43 healthy age-matched subjects.
One month after the first vaccine dose, vaccine response rates (rSBA titre ≥1:32 or a ≥4-fold increase in rSBA titre from baseline) for groups A, C, W-135, and Y, respectively, were 100%, 92.5%, 100% and 97.5% in the at-risk group and were 97.5%, 97.5%, 97.5%, and 100% for healthy subjects. After the second vaccine dose, vaccine response rates in both at-risk and healthy subjects were 100% for each of the four meningococcal groups.
One month after Vaccination 1, hSBA response rates for groups A, C, W-135, and Y, respectively, were 69.7%, 77.1%, 55.6%, and 60.5% in the at-risk group and were 69.7%, 60.6%, 65.5%, and 76.3%, in the healthy group. One month after Vaccination 2, hSBA response rates were 84.8%, 100%, 80.6% and 73.0%, in the at-risk group and 75.0%, 85.3%, 77.4%, and 73.0% in the healthy group.
Impact of a single dose of Nimenrix: The Netherlands introduced Nimenrix into the national immunization program in 2018 as a single dose at 14 months of age. A catch-up campaign for individuals 14-18 years of age initiated in 2018 and in 2020 a single dose of Nimenrix at 14 years of age became routine, resulting in a toddler and adolescent national immunization program. Within two years, the incidence of meningococcal disease caused by groups C, W, and Y was significantly reduced by 100% (95% CI: 14, 100) in individuals 14-18 years of age, 85% (95% CI: 32, 97) in all vaccine eligible ages (direct effect), and 50% (95% CI: 28, 65) in non-vaccine eligible ages (indirect effect). In children 15 to 36 months, there were only 3 cases during the pre-vaccination period and 2 cases in the post-vaccination period, resulting in an IRR of 33% (95% CI: -302, 89). The low number of cases among this age group, does not allow for a reliable assessment of vaccine impact as indicated by the wide 95% CIs.
Pharmacokinetics: Not relevant for vaccines.
Toxicology: Preclinical Safety Data: Non-clinical data reveal no special hazard for humans based on local tolerance, acute toxicity, repeated dose toxicity, developmental/reproductive toxicity and fertility studies.

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

Posology: Nimenrix should be used in accordance with available official recommendations. (See Table 18.)

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Previously vaccinated children from 12 months of age, adolescents and adults: Nimenrix may be given as a booster dose to individuals who have previously received primary vaccination with a conjugated or plain polysaccharide meningococcal vaccine (see Pharmacology: Pharmacodynamics under Actions).
Special populations: Individuals who have underlying conditions predisposing them to meningococcal infection due to anatomic or functional asplenia (such as sickle cell disease) may receive at least one dose of Nimenrix (see Adverse Reactions and Pharmacology: Pharmacodynamics under Actions).
Method of administration: Immunization 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 Precautions and Interactions).
For instructions on reconstitution of the medicinal product before administration, see Special Precautions for Disposal and Other Handling under Cautions for Usage.

No cases of overdose have been reported.

Nimenrix should not be administered to subjects with hypersensitivity to the active substances or to any of the excipients contained in the vaccine (see Description).

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.
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.
Intercurrent illness: As with other vaccines, 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 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.
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 rabbit complement serum bactericidal assay (rSBA) than subjects who had not been vaccinated with any meningococcal vaccine in the preceding 10 years. Clinical relevance of this observation is unknown.
Thrombocytopenia and coagulation disorders: As with other vaccines administered intramuscularly, 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 certain complement deficiencies and persons receiving treatment that inhibits 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.
Special populations: Limited data are available on the safety and immunogenicity in individuals with increased susceptibility to meningococcal infection due to anatomic or functional asplenia (such as sickle cell disease) (see Dosage & Administration, Adverse Reactions and Pharmacology: Pharmacodynamics under Actions).
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 other Neisseria meningitidis groups.
As with any vaccine, a protective immune response may not be elicited in all vaccinees.
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 Pharmacology: Pharmacodynamics under Actions). The clinical relevance of this observation is unknown. If an infant aged 6 months to less than 12 months is expected to be at immediate 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: At 1 month post vaccination, toddlers aged 12-14 months had similar rSBA titres to groups A, C, W-135, and Y following one dose of Nimenrix or two doses of Nimenrix given 2 months apart. At 1 year post vaccination, the rSBA titres to groups A, C, W-135 and Y were similar in both the one and the two dose groups (see Pharmacology: Pharmacodynamics under Actions).
Measured with a serum bactericidal assay using hSBA, 1 month post vaccination, responses to groups W-135 and Y were lower after a single dose than after 2 doses given 2 months apart, while responses to groups A and C were similar in the two groups (see Pharmacology: Pharmacodynamics under Actions). The clinical relevance of these observations is unknown. If a toddler is expected to be at immediate risk of invasive meningococcal disease due to the exposure to groups W-135 and/or Y, consideration may be given to administering a second primary dose after an interval of 2 months. At 1 year post vaccination, the hSBA responses for groups A, C, W-135 and Y were similar in both the one and the two dose groups (see Pharmacology: Pharmacodynamics under Actions). 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: Persistence of antibodies has been evaluated up to 10 years after vaccination. The persistence studies with Nimenrix have shown a waning of serum bactericidal antibody titres against group A when using human complement in the assay (hSBA) (see Pharmacology: Pharmacodynamics under Actions). 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 1 year previously, consideration may be given to administering a booster dose.
A decline in antibody titres over time has been observed. The clinical relevance of this observation is unknown. A booster dose might be considered in individuals remaining at high risk of exposure to meningococcal disease caused by groups A, C, W-135 and Y (see Pharmacology: Pharmacodynamics under Actions).
Although Nimenrix contains tetanus toxoid, this vaccine does not substitute for tetanus immunization.
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.

Pregnancy: There is limited experience with use of Nimenrix in pregnant women.
Animal studies with Nimenrix do not indicate direct or indirect harmful effects with respect to fertility, pregnancy, embryo/foetal development, parturition or post-natal development (see Pharmacology: Toxicology: Preclinical Safety Data under Actions).
Nimenrix should be used during pregnancy only when clearly needed, and the possible advantages outweigh the potential risks for the foetus.
Lactation: The safety of Nimenrix when administered to breast-feeding women has not been evaluated. It is unknown whether Nimenrix is excreted in human breast milk.
Nimenrix should only be used during breast-feeding when the possible advantages outweigh the potential risks.

The safety profile presented in Table 19 is based on two data sets: A pooled analysis in more than 9,000 subjects from the age of 1 year on, who have been vaccinated with 1 dose of Nimenrix in clinical studies.
Data from approximately 1,000 infants (6 weeks to 12 months of age) who have been primed and boosted with Nimenrix. (See Table 19.)

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In a separate study a single dose of Nimenrix was administered to 274 individuals aged 56 years and older. All adverse reactions reported in this study were already observed in younger age groups.
Local and general adverse reactions: In all age groups, the local adverse reactions of pain, redness and swelling at the injection site were reported at a very common frequency after vaccination.
In the infant and toddler groups, the general adverse reactions of drowsiness, fever, irritability/fussiness and loss of appetite were reported at a very common frequency after vaccination.
In a separate infant study, 554 infants were primed with one or three doses of Nimenrix and 508 received booster doses in the second year of life. Local and general adverse reactions in this study were similar in frequency to the larger infant study.
In the 12-14 months age group who received two doses of Nimenrix given two months apart, the first and second doses were associated with similar local and systemic reactogenicity.
In an additional clinical study of age-matched subjects who were either healthy or at increased risk of meningococcal disease due to anatomical or functional asplenia (such as sickle cell disease), the safety profile of Nimenrix in at-risk children and adolescents was generally similar to that observed in the non-asplenic population (see Pharmacology: Pharmacodynamics under Actions).
The 2-5 year group reported general adverse reactions at a frequency ranging from common (irritability, loss of appetite and fever) to very common (drowsiness).
In the 6-10, 11-17 and ≥18 years age groups, the general adverse reactions were reported at a frequency ranging from common (gastrointestinal symptoms and fever) to very common (headache and fatigue).
In a clinical study of 11 to 25 year old subjects co-administered Nimenrix and Tdap or given the vaccines separately, the local reactions (injection site pain, redness, and swelling) and general reactions (fatigue and headache) occurred at a similar frequency in both groups and in the subjects in the pooled analysis (very common). The general reactions gastrointestinal events (nausea, vomiting, diarrhoea, abdominal pain) occurred more frequently (very common) and fever occurred less frequently (common) compared to subjects in the pooled analysis, but occurred at a similar frequency in subjects co-administered the vaccines and subjects given the vaccines separately in the study.
In a clinical study of female subjects 9 to 25 years old, the local reactions (pain, redness, and swelling at the Nimenrix injection site) and general reactions (headache, fever, and fatigue) occurred at a similar frequency in subjects co-administered Nimenrix, Tdap and HPV2 and in subjects given Nimenrix alone, as they did in subjects in the pooled analysis (very common). The general reactions gastrointestinal events (nausea, vomiting, diarrhoea, abdominal pain) and myalgia occurred at a similar frequency in the two groups but more frequently than in the pooled analysis (very common), as did the general reaction rash (common).
The local and general adverse reaction profile of a booster dose of Nimenrix given to subjects from 12 months 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 gastrointestinal symptoms (including diarrhoea, vomiting, and nausea) which ranged from common to very common among subjects 6 years of age and older (versus common after primary vaccination).

In infants, Nimenrix can be given concomitantly with combined diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus and Haemophilus influenzae type b vaccines (DTaP/IPV/Hib/HepB), as well as 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.
Nimenrix can also be given concomitantly with combined diphtheria - tetanus - acellular pertussis vaccines, including combination DTaP vaccines with hepatitis B, inactivated poliovirus or Haemophilus influenzae type b, such as DTaP/IPV/Hib/HepB vaccine and 13-valent pneumococcal conjugate vaccine in the second year of life.
Safety and immunogenicity of Nimenrix was evaluated when sequentially administered or co-administered with a DTaP/IPV/Hib/HepB vaccine in the second year of life. The administration of Nimenrix 1 month after the DTaP/IPV/Hib/HepB vaccine resulted in lower MenA, MenC and MenW-135 GMTs as measured with a serum bactericidal assay using rSBA. The clinical relevance of this observation is unknown, since at least 99.4% of subjects (N=178) had rSBA titres ≥8 for each group (A, C, W-135, and Y). Whenever possible, Nimenrix and a tetanus toxoid (TT) containing vaccine, such as DTaP/IPV/Hib/HepB vaccine, should be co-administered or Nimenrix should be administered at least 1 month before the TT-containing vaccine.
One month after co-administration with a 10-valent pneumococcal conjugate vaccine in toddlers aged 12-23 months, 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 the other nine pneumococcal serotypes.
In individuals aged 9 to 25 years, Nimenrix can be given concomitantly with human papillomavirus bivalent [Type 16 and 18] vaccine, recombinant (HPV2).
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.
As with other vaccines, it may be expected that in patients receiving immunosuppressive treatment an adequate response may not be elicited.

Incompatibilities: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Special Precautions for Disposal and Other Handling: Before reconstitution: Instructions for reconstitution of the vaccine with solvent presented in ampoules: Nimenrix must be reconstituted by adding the entire content of the ampoule of solvent to the vial containing the powder. To do so, break the top of the ampoule, draw up the solvent with a syringe and add the solvent to the powder. The mixture should be well shaken until the powder is completely dissolved in the solvent.
Instructions for reconstitution of the vaccine with the solvent presented in pre-filled syringe: Nimenrix must be reconstituted by adding the entire content of the pre-filled syringe of solvent to the vial containing the powder.
To attach the needle to the syringe: 1. Holding the syringe barrel in one hand (avoid holding the syringe plunger), unscrew the syringe cap by twisting it anticlockwise.
2. To attach the needle to the syringe, twist the needle clockwise into the syringe until the patient feels it lock.
3. Remove the needle protector, which on occasion can be a little stiff.
Add the solvent to the powder. After the addition of the solvent to the powder, the mixture should be well shaken until the powder is completely dissolved in the solvent.
After reconstitution: The reconstituted vaccine is a clear colourless solution.
The reconstituted vaccine should be inspected visually for any foreign particulate matter and/or variation of physical aspect prior to administration. In the event of either being observed, discard the vaccine.
After reconstitution, the vaccine should be used promptly. Although delay is not recommended, stability has been demonstrated for 8 hours at 30°C after reconstitution. If not used within 8 hours, do not administer the vaccine.
A new needle should be used to administer the vaccine.
Any unused product or waste material should be disposed of in accordance with local requirements.

Store in a refrigerator (2°C - 8°C).
The solvent may also be stored at ambient temperature (25°C).
Do not freeze.
Protect from light.

Vaccines, Antisera & Immunologicals

J07AH08 - meningococcus A,C,Y,W-135, tetravalent purified polysaccharides antigen conjugated ; Belongs to the class of meningococcal bacterial vaccines.

POM