Nimenrix

Nimenrix

vaccine, meningococcal

Manufacturer:

Pfizer

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Meningococcal polysaccharide serogroups A, C, W-135 and Y conjugate vaccine.
Description
After reconstitution, 1 dose (0.5 mL) contains 5 micrograms of polysaccharide for Neisseria meningitidis serogroups 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.
Action
Pharmacotherapeutic Group: Bacterial Vaccines. ATC Code: J07AH08.
Pharmacology: Pharmacodynamics: Mechanism of Action: Anti-capsular meningococcal antibodies protect against meningococcal diseases via complement mediated bactericidal killing. Nimenrix induces the production of bactericidal antibodies against capsular polysaccharides of serogroups 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.
Pharmacodynamic Effects: Immunogenicity: The immunogenicity of one dose of Nimenrix has been evaluated in more than 8,000 subjects aged ≥12 months and in approximately 1,000 subjects below 12 months of age.
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.
Persistence of immune response: The persistence of the immune response elicited by Nimenrix was evaluated up to 5 years after vaccination in subjects aged 12 months to 55 years.
The antibodies elicited by Nimenrix were similar or higher than those induced by the licensed meningococcal vaccines (Tables 7, 8, 11, 12, 14 and 15).
In contrast to the observed rSBA-MenA persistence, across age groups, there was a more rapid waning (as measured at 12 months post-dose onwards) of serum bactericidal antibody titres against MenA than against other groups (C, W-135, Y) when using human complement in the assay (Tables 7, 8, 11, 12 and 15). This rapid waning of hSBA-MenA antibodies has also been observed with other meningococcal vaccines. The clinical relevance of the rapid waning of hSBA-MenA antibody titres is unknown (see Precautions).
The vaccine response was defined in subjects aged ≥2 years as the proportion of subjects with: rSBA titres ≥32 for initially seronegative subjects (i.e., pre-vaccination rSBA titre <8); at least a 4-fold increase in rSBA titres from pre- to post-vaccination for initially seropositive subjects (i.e., pre-vaccination rSBA titre ≥8).
Vaccine immunogenicity: Booster response: In 5 clinical trials, the use of Nimenrix as a booster following primary vaccination with Nimenrix or other meningococcal vaccines (quadrivalent meningococcal A, C, W-135 and Y-DT conjugate vaccine or monovalent MenC conjugate vaccines) was evaluated. A robust Nimenrix booster response was observed for all groups in all age ranges assessed.
Infants: Immunogenicity in infants: Two clinical studies have been conducted in infants, MenACWY-TT-083 and MenACWY-TT-087. In MenACWY-TT-083, the immunogenicity of a 2-dose primary vaccination schedule administered at 2 and 4 months of age was evaluated (Table 1). Routinely used infant vaccines DTPa-HBV-IPV/Hib and a 10-valent pneumococcal vaccine were co-administered. For group C, the immune response elicited by Nimenrix was compared to a 2-dose priming with licensed monovalent meningococcal conjugate group C vaccines, C-CRM197 conjugate (MenC-CRM) and C-TT conjugate (MenC-TT) vaccines. Nimenrix elicited a bactericidal antibody response against the four groups. The response against group C was non-inferior to the one elicited by the licensed MenC-CRM and MenC-TT vaccines in term of rSBA titres ≥8.
For subjects primed 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 one 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 (Table 1). The observed booster response for MenC was similar to that observed in subjects primed and boosted with a monovalent MenC conjugate vaccine (TT or CRM conjugated). (See Table 1.)

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In 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 DTPa-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 responses to groups A, C, W-135 and Y, 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 (see Table 2).

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Serum bactericidal activity was also measured using hSBA as a secondary endpoint. 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 responses 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, the hSBA titres to all four serogroups were comparable between the two dosing schedules.
Toddlers: Immunogenicity in toddlers aged 12-23 months: In clinical studies MenACWY-TT-039 and MenACWY-TT-040 a single dose of Nimenrix elicited rSBA responses against the four meningococcal groups, with a response against group C that was comparable to the one elicited by the licensed MenC-CRM vaccine in term of percentages with rSBA titres ≥8 (see Table 3).

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In study MenACWY-TT-039, serum bactericidal activity was also measured using human serum as the source of complement (hSBA) as a secondary endpoint (see Table 4).

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In Study Men ACWY-TT-104, the immune response following one or two doses of Nimenrix given 2 months apart was evaluated 1 month and 1 year after the last vaccination. Nimenrix elicited bactericidal responses against all four groups that were similar in terms of % with rSBA titre ≥8 and GMT after one or two doses (see Table 5).

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In the study MenACWY-TT-104, the serum bactericidal activity was also measured using hSBA as a secondary endpoint. In terms of % with hSBA titre ≥8, at one month post vaccination, responses against groups W-135 and Y were higher after two doses of Nimenrix than after one dose, while responses against groups A and C were similar in the two groups. At one year post vaccination, the % responses with hSBA titre ≥1:8 for groups A, C, W-135 and Y were similar in both the one and two dose groups (see Table 6).

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Persistence of immune response in toddlers aged 12-23 months: In children vaccinated at toddler age, the persistence of the immune response was evaluated by rSBA and hSBA up to 4 years in study MenACWY-TT-048 (Table 7) and up to 5 years in study MenACWY-TT-032 (Table 8). (See Tables 7 and 8.)

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Immune memory: In study MenACWY-TT-014, the induction of immune memory was assessed one 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 previously primed in the 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 subjects primed with Nimenrix increased by 6.5 to 8 fold for groups A, C, W-135 and Y and indicate that Nimenrix induces immune memory to groups A, W-135 and Y. 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 (see Table 9).

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Children: 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 GlaxoSmithKline Biologicals' plain polysaccharide meningococcal group A, C, W-135, Y (ACWY-PS) vaccine (study MenACWY-TT-038) as comparator.
In the MenACWY-TT-038 study, Nimenrix was demonstrated to be non-inferior to the licensed ACWY-PS vaccine in terms of vaccine response to the four groups (A, C, W-135 and Y) (see Table 10).

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In the MenACWY-TT-081 study, Nimenrix (N = 268) was demonstrated to be non-inferior to another licensed MenC-CRM vaccine (N = 92) in terms of vaccine response to the Men C group [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)].
Persistence of immune response in children: Persistence of immune response in children aged 2-10 years: In study MenACWY-TT-088, the persistence of the immune response was evaluated up to 68 months after vaccination in children 2-10 years of age primed in study MenACWY-TT-081 (see Table 11).

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Persistence of immune response in children aged 6-10 years: In study MenACWY-TT-028, the persistence of the immune response was evaluated by hSBA 1 year after vaccination in children 6-10 years of age primed in study MenACWY-TT-027 (see Table 12).

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

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In a descriptive study (study MenACWY-TT-085), a single dose of Nimenrix was administered to 194 Lebanese adults 56 years of age and older (including 133 aged 56-65 years and 61 aged >65 years), Nimenrix was immunogenic, with a vaccine response rate ≥63.4% and with ≥97.4% of subjects with rSBA titres ≥8 against all four serogroups. Moreover, at least 93.2% of subjects achieved the more conservative threshold of protection of rSBA titres ≥128.
Persistence of immune response in adolescents aged 11-17 years of age: In study MenACWY-TT-043, the persistence of the immune response was evaluated up to 5 years after vaccination in adolescents primed in study MenACWY-TT-036 (Table 14). See Table 4 for primary results in this study. (See Table 14.)

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Persistence of immune response in adolescents and adults aged 11-25 years evaluated by hSBA: In study MenACWY-TT-059, the persistence of the immune response was evaluated by hSBA up to 5 years after vaccination in adolescents and adults 11-25 years of age primed in study MenACWY-TT-052.
For all groups (A, C, W-135, Y), the persistence of the antibodies elicited by Nimenrix was similar or higher than those induced by the licensed quadrivalent meningococcal diphtheria toxoid (DT) conjugate (ACWY-DT) vaccine (see Table 15).

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Nimenrix booster vaccination after priming in toddlers, children, adolescents and adults: For subjects primed with Nimenrix aged 1 year and above and boosted with Nimenrix 4 or 5 years later, more than 99.0% of all subjects achieved post-booster SBA titres ≥1:8 for both assays (studies MenACWY-TT-062, 048, 059, 088). One month after the booster vaccination, the GMTs elicited were significantly higher than those elicited by age matched naïve control groups, indicating that Nimenrix induces immune memory to groups A, C, W-135, and Y.
The observed MenC booster response with Nimenrix was similar to that observed in subjects primed and boosted with a monovalent MenC-CRM conjugate vaccine (study MenACWY-TT-048). One year after Nimenrix booster, SBA titres ≥1:8 persisted in at least 95.5% of subjects (study MenACWY-TT-048, 12 to 23 months of age at primary vaccination).
When Nimenrix was used as a booster following primary vaccination with a MenACWY-DT conjugate vaccine or a monovalent MenC conjugate vaccine (study MenACWY-TT-059, 10 to 25 years of age at primary vaccination and study MenACWY-TT-088, 2 to 10 years of age at primary vaccination), the titres increased by 48-340 fold for all groups and 100% of the subjects reached SBA titres ≥1:8.
Immunogenicity in subjects previously vaccinated with a plain polysaccharide meningococcal vaccine: 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 the 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 (Table 16). Clinical relevance of this observation is unknown since all subjects achieved rSBA titres ≥8 for each group (A, C, W-135, Y). (See Table 16.)

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Immunogenicity in children aged 2-17 years with anatomical or functional asplenia: Study MenACWY-TT-084 evaluated the immunogenicity of 1 and 2 doses of Nimenrix given two 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 4 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.
Clinical Studies: See Pharmacodynamics as previously mentioned.
Pharmacokinetics: Not relevant for vaccines.
Toxicology: Non-Clinical Information: Non-clinical data reveal no special hazard for humans based on local tolerance, acute toxicity, repeated dose toxicity, developmental/reproductive toxicity and fertility studies.
Indications/Uses
Nimenrix is indicated for active immunization of individuals from 6 weeks of age against invasive meningococcal diseases caused by Neisseria meningitidis serogroups A, C, W-135 and Y.
Dosage/Direction for Use
Posology: (See Table 17.)

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Nimenrix should be used in accordance with available official recommendations.
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 Precautions and Pharmacology: Pharmacodynamics: Pharmacodynamic Effects 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: Pharmacodynamic Effects 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 Instructions for Use/Handling under Cautions for Usage.
Overdosage
No cases of overdose have been reported.
Contraindications
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.)
Special Precautions
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 Meningococcal polysaccharide serogroups A, C, W-135 and Y even if they develop antibodies following vaccination with Nimenrix.
Special populations: Safety and immunogenicity data are available for a limited number of 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: Pharmacodynamic Effects under Actions).
Protection against meningococcal disease: Nimenrix will only confer protection against Neisseria meningitidis serogroups 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 vaccines.
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: Pharmacodynamic Effects under Actions). The clinical relevance of this finding 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 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 one month post vaccination, toddlers aged 12-14 months had similar rSBA responses to groups A, C, W-135 and Y following one dose of Nimenrix or two doses of Nimenrix given two months apart. At one year post vaccination, the rSBA responses for groups A, C, W-135 and Y were similar in both the one and the two dose groups (see Pharmacology: Pharmacodynamics: Pharmacodynamic Effects 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 two months apart, while responses to groups A and C were similar in the two groups (see Pharmacology: Pharmacodynamics: Pharmacodynamic Effects under Actions). The clinical relevance of these findings 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 Y, consideration may be given to administering a second primary dose after an interval of 2 months. At one 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: Pharmacodynamic Effects under Actions). Regarding waning of antibody against MenA or MenC 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 5 years after vaccination. The persistence studies with Nimenrix have shown a waning of serum bactericidal antibody titres against MenA when using human complement in the assay (hSBA) (see Pharmacology: Pharmacodynamics: Pharmacodynamic Effects under Actions). The clinical relevance of the waning of hSBA MenA antibody titres is unknown. Currently there is limited information available on the safety of a booster dose. However, if an individual is expected to be at particular risk of exposure to MenA 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 the waning antibody titres 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: Pharmacodynamic Effects under Actions).
Although Nimenrix contains tetanus toxoid, this vaccine does not substitute for tetanus immunisation.
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.
Use In Pregnancy & Lactation
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: Non-Clinical Information 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.
Adverse Reactions
The safety profile presented in the table as follows 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.
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 1 or 3 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 2 doses of Nimenrix given 2 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: Pharmacodynamic Effects 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 2 groups but more frequently than in the pooled analysis (very common), as did the general reaction rash (common).
Adverse reactions reported are listed according to the following frequency: Very common ≥1/10; Common ≥1/100 to <1/10; Uncommon ≥1/1000 to <1/100; Rare ≥1/10000 to <1/1000; Very rare <1/10000; Not known (cannot be estimated from the available data). (See Table 18.)

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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.
Drug Interactions
In infants, Nimenrix can be given concomitantly with combined diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus and Haemophilus influenzae type b vaccines, 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-HBV-IPV/Hib 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-HBV-IPV/Hib vaccine in the second year of life. The administration of Nimenrix one month after the DTaP-HBV-IPV/Hib vaccine resulted in lower MenA, MenC and MenW-135 GMTs as measured with a serum bactericidal assay using rSBA. 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, Y). Whenever possible, Nimenrix and a tetanus toxoid (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 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). 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.
Caution For Usage
Instructions for Use/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, refer to the instructions as follows.
Holding the syringe barrel in one hand (avoid holding the syringe plunger), unscrew the syringe cap by twisting it anticlockwise.
To attach the needle to the syringe, twist the needle clockwise into the syringe until it feels lock.
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.
Incompatibilities: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Storage
Store in a refrigerator (2°C - 8°C).
The solvent may be stored at ambient temperature (25°C).
Do not freeze.
Protect from light.
ATC Classification
J07AH08 - meningococcus A,C,Y,W-135, tetravalent purified polysaccharides antigen conjugated ; Belongs to the class of meningococcal bacterial vaccines.
Presentation/Packing
Vaccine (inj) [vial (white powder) and pre-filled syringe (clear, colourless)] 5 mcg/0.5 mL x 1's.
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