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
Each 0.5 mL of the reconstituted Nimenrix (1 dose) contains Neisseria meningitidis polysaccharide serogroups A, C, W-135 and Y 5 mcg (conjugated to tetanus toxoid carrier protein 44 mcg). It also contains the following excipients: Powder: Sucrose and trometamol. Solvent: Sodium chloride and water for injection.
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 rabbit complement (rSBA) or human complement (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: The immunogenicity of 1 dose of Nimenrix has been evaluated in >8000 subjects aged ≥12 months.
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.
The vaccine response was defined in subjects aged ≥2 years as the proportion of subjects with: rSBA titres ≥32 for initially seronegative subjects (ie, pre-vaccination rSBA titre <8), at least a 4-fold increase in rSBA titres from pre- to post-vaccination for initially seropositive subjects (ie, pre-vaccination rSBA titre ≥8).
Vaccine Immunogenicity: Immunogenicity in Toddlers Aged 12-23 Months: In clinical studies MenACWY-TT-039 and MenACWY-TT-040, the immune response to vaccination with either Nimenrix or a licensed meningococcal C-CRM197 conjugate (MenC-CRM) vaccine was evaluated.
Nimenrix elicited a bactericidal antibody response against the 4 groups, with a response against group C that was comparable to the one elicited by the licensed MenC-CRM vaccine in term of rSBA titres ≥8 (see Table 1).

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In the study MenACWY-TT-039, the serum bactericidal activity was also measured using human serum as the source of complement (hSBA) as a secondary endpoint (see Table 2).

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Immunogenicity in Children Aged 2-10 years: In 2 comparative studies conducted in subjects aged 2-10 years, 1 group of subjects received a dose of Nimenrix, and a 2nd 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 4 groups (A, C, W-135 and Y) (see Table 3).

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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% and 95.7%, respectively), geometric mean titres (GMTs) were lower for the Nimenrix group (2794.8) versus the MenC-CRM vaccine (5291.6).
Immunogenicity in Adolescents Aged 11-17 Years and Adults ≥18 Years: In 2 clinical studies, conducted in adolescents 11-17 years (study MenACWY-TT-036) and in adults 18-55 years (study MenACWY-TT-035), either 1 dose of Nimenrix or 1 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 4 meningococcal groups elicited by Nimenrix was either similar or higher than the one elicited by the ACWY-PS vaccine (see Table 4).

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In a descriptive study conducted in 194 adults ≥56 years (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 4 serogroups. Moreover, at least 93.2% of subjects achieved the more conservative threshold of protection of rSBA titres ≥128.
Persistence of Immune Response: The persistence of the immune response elicited by Nimenrix was evaluated up to 48 months after vaccination in subjects 12 months to 55 years.
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 meningococcal vaccines [ie, MenC-CRM vaccine in subjects 12-23 months, licensed quadrivalent meningococcal diphtheria toxoid (DT) conjugate (ACWY-DT) vaccine in subjects 11-25 years and ACWY-PS vaccine in subjects >2 years].
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 (see Tables 5, 6 and 8). 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).
Persistence of Immune Response in Toddlers Aged 12-23 Months: In study MenACWY-TT-048, the persistence of the immune response was evaluated by rSBA and hSBA up to 4 years after vaccination in toddlers primed in study MenACWY-TT-039 (see Table 5).

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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 primed in study MenACWY-TT-027 (see Table 6).

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Persistence of Immune Response in Adolescents Aged 11-17 Years: In study MenACWY-TT-043, the persistence of the immune response was evaluated up to 4 years after vaccination in adolescents primed in study MenACWY-TT-036 (see Table 7). Refer to Table 4 for primary results in this study.

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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 1 and 3 years after vaccination in adolescents and adults 11-25 years 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 ACWY-DT vaccine (see Table 8).

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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 5th of the dose of ACWY-PS vaccine (10 mcg of each polysaccharide) to children in the 3rd year of life previously primed in the study MenACWY-TT-013 with Nimenrix or a licensed MenC-CRM vaccine at the age of 12-14 months.
One (1) 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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Booster Response: In study MenACWY-TT-048, a booster response was evaluated in children vaccinated 4 years earlier (at toddler age) in study MenACWY-TT-039 (see Table 2). Children were primed and boosted with the same vaccine: Either Nimenrix or a MenC-CRM vaccine. A robust increase in rSBA and hSBA GMTs was observed from pre-booster dose to 1 month post-booster dose of Nimenrix (see Table 10).

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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 months 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 (see Table 11). Clinical relevance of this observation is unknown since all subjects achieved rSBA titres ≥8 for each group (A, C, W-135, Y). (See Table 11.)

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Clinical Studies: See Pharmacodynamics in previous text.
Pharmacokinetics: Not relevant for vaccines.
Toxicology: Preclinical Safety Data: Nonclinical data reveal no special hazard for humans based on local tolerance, acute toxicity, repeated-dose toxicity, developmental/reproductive toxicity and fertility studies.
Indications/Uses
Active immunization of individuals from 12 months of age against invasive meningococcal diseases caused by Neisseria meningitidis serogroups A, C, W-135 and Y. (see Pharmacology: Pharmacodynamics under Actions).
Dosage/Direction for Use
Primary Vaccination: Single 0.5-mL dose of the reconstituted vaccine is used for immunization.
Booster Vaccination: May be given in subjects who have previously been vaccinated with a plain polysaccharide meningococcal vaccine.
There are no data available in subjects previously vaccinated with a meningococcal C conjugate vaccine.
The need for a booster dose in subjects primed with Nimenrix has not been established.
Nimenrix should be used in accordance with available official recommendations.
Administration: For IM injection only, preferably in the deltoid muscle. In children 12-23 months, Nimenrix may also be administered in the anterolateral part of the thigh (see Precautions and Interactions).
Overdosage
No cases of overdosage have been reported.
Contraindications
Hypersensitivity to meningococcal polysaccharide serogroups A, C, W-135 and Y or to any of the excipients of Nimenrix (see Descriptions).
Special Precautions
Nimenrix should under no circumstances be administered intravascularly, intradermally or subcutaneously.
It is a good clinical practice to precede vaccination by a review of the medical history (especially with regard to previous vaccination and possible occurrence of adverse 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 Nimenrix.
As with other vaccines, vaccination with Nimenrix should be postponed in patients suffering from an acute severe febrile illness. The presence of a minor infection eg, cold, should not result in the deferral of vaccination.
Syncope (fainting) can occur following or even before, any vaccination as a psychogenic response to the needle injection. It is important that procedures are in place to avoid injury from faints.
As with other vaccines administered IM, Nimenrix should be given with caution to individuals with thrombocytopenia or any coagulation disorder since bleeding may occur following an IM administration to these subjects.
Nimenrix will only confer protection against Neisseria meningitidis serogroups A, C, W-135 and Y. The vaccine will not protect against other N. meningitidis serogroups.
As with any vaccine, a protective immune response may not be elicited in all vaccinees.
It may be expected that in patients receiving immunosuppressive treatment or patients with immunodeficiency, an adequate immune response may not be elicited.
Safety and immunogenicity have not been assessed in patients with increased susceptibility to meningococcal infection due to conditions eg, terminal complement deficiencies and anatomic or functional asplenia. In these individuals, an adequate immune response may not be elicited.
Although Nimenrix contains tetanus toxoid, this vaccine does not substitute for tetanus immunisation.
A more rapid waning of serum bactericidal antibody titres against MenA than for other groups (C, W-135, Y), has been observed when using human complement in the assay (see Pharmacology: Pharmacodynamics: Pharmacodynamic Effects under Actions). In individuals expected to be at particular risk of exposure to MenA and who received a 1st dose of Nimenrix >1 year earlier, consideration may be given to administering a 2nd dose of Nimenrix. Available data indicate that a 2nd dose will elicit an anamnestic immune response to all 4 meningococcal types in the vaccine. Currently, there is very limited information available on the safety of a 2nd dose of Nimenrix.
Effects of the Ability to Drive or Operate Machinery: No studies on the effects of Nimenrix on the ability to drive and use machines have been performed.
Use in pregnancy & lactation: There is limited experience with the 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 fetus.
The safety of Nimenrix when administered to breastfeeding women has not been evaluated. It is unknown whether Nimenrix is excreted in human breast milk. Nimenrix should only be used during breastfeeding when the possible advantages outweigh the potential risks.
Use In Pregnancy & Lactation
There is limited experience with the 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 fetus.
The safety of Nimenrix when administered to breastfeeding women has not been evaluated. It is unknown whether Nimenrix is excreted in human breast milk. Nimenrix should only be used during breastfeeding when the possible advantages outweigh the potential risks.
Adverse Reactions
The safety profile presented as follows is based on a pooled analysis on 8108 subjects who have been vaccinated with 1 dose of Nimenrix in clinical studies.
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 ≥1/10,000 to <1/1000; very rare <1/10,000; not known (cannot be estimated from the available data).
Metabolism and Nutrition Disorders: Very Common: Loss of appetite.
Psychiatric Disorder: Very Common: Irritability. Uncommon: Insomnia, crying.
Nervous System Disorder: Very Common: Drowsiness, headache. Uncommon: Hypoaesthesia, dizziness.
Gastrointestinal Disorder: Common: Gastrointestinal symptoms (including diarrheoa, vomiting and nausea).
Skin and Subcutaneous Tissue Disorder: Uncommon: Pruritus, rash.
Musculoskeletal and Connective Tissue Disorder: Uncommon: Myalgia, pain in extremity.
General Disorders and Administration Site Conditions: Very Common: Fever, swelling, pain and redness at injection site, fatigue. Common: Injection site haematoma. Uncommon: Malaise, injection site reaction (including induration, pruritus, warmth, anesthesia).
Drug Interactions
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 in the 2nd year of life, including combination DTaP vaccines with hepatitis B, inactivated polio or Haemophilus influenzae type b eg, DTaP-HBV-IPV/Hib vaccine.
Safety and immunogenicity of Nimenrix was evaluated when sequentially administered or co-administered with a DTaP-HBV-IPV/Hib vaccine in the 2nd year of life. The administration of Nimenrix 1 month after the DTaP-HBV-IPV/Hib vaccine resulted in lower MenA, MenC and MenW-135 GMTs as measured with rabbit complement serum bactericidal assay (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 eg, DTaP-HBV-IPV/Hib vaccine, should be co-administered or Nimenrix should be administered at least 1 month before the TT-containing vaccine.
One (1) 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 1 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 9 pneumococcal serotypes.
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 and Disposal: Instructions for Reconstitution 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.
1. Holding the syringe barrel in 1 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 an lock is felt.
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.
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 Nimenrix.
After reconstitution, Nimenrix should be used immediately. However, chemical and physical in-use stability has been demonstrated for 24 hrs at 30°C.
A new needle should be used to administer Nimenrix.
Any unused product or waste material should be disposed of in accordance with local requirements.
Incompatibilities: In the absence of compatibility studies, Nimenrix must not be mixed with other medicinal products.
Storage
Store in a refrigerator (2°-8°C). 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 for inj) & pre-filled syringe (clear, colorless soln for inj)] 5 mcg/0.5 mL x 1's.
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