NIMENRIX

NIMENRIX (meningococcal polysaccharide groups A, C, W-135 and Y conjugate vaccine) is indicated for the active immunization of individuals from 6 weeks to 55 years of age against invasive meningococcal diseases caused by Neisseria meningitidis groups A, C, W-135 and Y.

1.1 Pediatrics

Pediatrics (≥ 6 weeks of age): The safety and efficacy of NIMENRIX in pediatric subjects 6 weeks of age and older have been established (see 4.2 Recommended Dose and Dose Adjustment, 8 ADVERSE REACTIONS and 14 CLINICAL TRIALS).

1.2 Geriatrics 

Geriatrics (≥ 65 years of age): Limited safety and immunogenicity data are available in subjects 56 years of age and older (see 8 ADVERSE REACTIONS and 14 CLINICAL TRIALS).

NIMENRIX should not be administered to subjects with known hypersensitivity to any component of the vaccine. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.

4.1 Dosing Considerations

NIMENRIX should be used in accordance with available official recommendations.

4.2 Recommended Dose and Dosage Adjustment

Long-term antibody persistence data following vaccination with NIMENRIX are available up to 10 years after vaccination (see 7 WARNINGS AND PRECAUTIONS – Immune: Protection Against Meningococcal Disease and 14 CLINICAL TRIALS).  [M1.6.2: CDS pg. 3]

NIMENRIX may be given as a booster dose to individuals who have previously received primary vaccination with NIMENRIX or other conjugated or plain polysaccharide meningococcal vaccines (see 7 WARNINGS AND PRECAUTIONS – Immune: Protection Against Meningococcal Disease: Persistence of serum bactericidal antibody titres and 14 CLINICAL TRIALS). 

4.3 Reconstitution

Parenteral Products: 

In the absence of compatibility studies, NIMENRIX must not be mixed with other medicinal products.

Instructions for reconstitution of the vaccine with the diluent presented in pre-filled syringe

NIMENRIX must be reconstituted by adding the entire content of the pre-filled syringe of diluent to the vial containing the powder.

To attach the needle to the syringe, refer to the below drawing. 

Note: However, the syringe provided with NIMENRIX might be slightly different (without screw thread) than the syringe described in the drawing. In that case, the needle should be attached without screwing.

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 you feel it lock (see drawing).

3. Remove the needle protector, which on occasion can be a little stiff.

4. Add the diluent to the powder. After the addition of the diluent to the powder, the mixture should be well shaken until the powder is completely dissolved in the diluent.

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.

4.4 Administration

NIMENRIX is for 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 deltoid muscle (see 7 WARNINGS AND PRECAUTIONS and 9 DRUG INTERACTIONS).

For instructions on reconstitution of the vaccine before administration, see 4.3 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.

Any unused product or waste material should be disposed of in accordance with local requirements.

NIMENRIX is supplied as a sterile lyophilized white powder or cake in a single dose vial.

The diluent (sodium chloride and water for injections) is a sterile clear and colourless liquid supplied separately in a prefilled syringe.

The vaccine does not contain any preservatives or adjuvants.

NIMENRIX is available as a single dose vial packaged with pre-filled syringe of diluent with or without needles in pack sizes of 1 and 10.

Table 1 Dosage Forms, Strengths, Composition and Packaging

Traceability

To help ensure the traceability of vaccines for patient immunization record-keeping as well as safety monitoring, health professionals should record the time and date of administration, quantity of administered dose (if applicable), anatomical site and route of administration, brand name and generic name of the vaccine, the product lot number and expiry date.

General

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.

Although NIMENRIX contains tetanus toxoid, this vaccine does not substitute for tetanus immunization.

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. It is important that procedures are in place to avoid injury from faints.

Hematologic

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.

Immune 

Immunodeficiency

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

Individuals with certain complement deficiencies and individuals 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.

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 14.4 Immunogenicity: Immunogenicity in infants). 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 rabbit complement serum bactericidal assay (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 one year post vaccination, the percentage of subjects  achieving rSBA titres ≥1:8  for groups A, C, W-135 and Y were:  63.5%, 49.1%, 65.3% and 73.1% in the one dose group, and 70.6%, 55.2%, 77.6% and 79.7% in the two doses group (see 14.4 Immunogenicity: Immunogenicity in toddlers aged 12-23 months).  

One month post-vaccination, a single dose vaccination was associated with lower human complement serum bactericidal assay (hSBA) titres to groups W-135 and Y compared with two doses given 2 months apart, while responses to groups A and C were higher in the two groups. The clinical relevance of these observations 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 primary dose after an interval of 2 months. At one year post-vaccination, the percentage of subjects achieving hSBA responses ≥1:8 for groups A, C, W-135 and Y were 35.7%, 80.3%, 95.8% and 91.9% in the one dose group, and 35.5%, 90.5%, 98.5% and 87.9% in the two doses group. Regarding waning of antibody against group A or group C after a first dose of NIMENRIX in children aged 12-23 months, see 7 WARNINGS AND PRECAUTIONS - 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 14.4 Immunogenicity). 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.

Similar to the monovalent Men C comparator, 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 14.4 Immunogenicity).

Reproductive Health: Female and Male Potential

See 7.1.1 Pregnant Women.

7.1 Special Populations

7.1.1 Pregnant Women 

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/fetal development, parturition or post-natal development (see 16 NON-CLINICAL TOXICOLOGY).

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

7.1.2 Breast-feeding

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.

7.1.3 Pediatrics

Pediatrics (≥ 6 weeks of age): The safety and efficacy of NIMENRIX in pediatric subjects 6 weeks of age and older have been established. 

7.1.4 Geriatrics

Geriatrics (≥ 65 years of age): Limited safety and immunogenicity data are available in subjects 56 years of age and older (see 8 ADVERSE REACTIONS and 14 CLINICAL TRIALS).

8.1 Adverse Reaction Overview

The safety profile is based on two data sets:

• A pooled analysis on 9,621 subjects who have been vaccinated with one dose of NIMENRIX in clinical studies. The pooled analysis includes data for 3,079 toddlers 12 months to 23 months), 1,899 children (2 to 10 years), 2,317 adolescents (11 to 17 years) and 2,326 adults (18 – 55 years). In addition, a descriptive study provides safety data from 274 individuals aged 56 years and older and who have been vaccinated with one dose of NIMENRIX.
• Data from approximately 1000 infants (6 weeks to 12 months of age) who have been primed and boosted with NIMENRIX.

8.2 Clinical Trial Adverse Reactions

Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials, therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use.

Solicited Adverse Reactions:

Infants 6 weeks to 12 months old
In Study MenACWY-TT-083, healthy infants received a primary series of two doses (at 2 and 4 months of age) of NIMENRIX or control vaccine (meningococcal group C CRM₁₉₇-conjugate vaccine [MenC-CRM] or meningococcal group C tetanus toxoid conjugate vaccine [MenC-TT]), with the first dose administered between 6 and 12 weeks of age, followed by a booster dose at 12 months of age. Routinely used infant vaccines DTaP/IPV/Hib/HepB and a 10-valent pneumococcal vaccine (PCV10) were coadministered. Table 2 presents the rates of solicited symptoms reported during the 4-day post-vaccination period.

Toddlers 12 to 23 months old
In Study MenACWY-TT-039, healthy children 12 through 23 months of age were administered one dose of NIMENRIX either alone or co-administered with a first dose of PRIORIX-TETRA®, 1 dose of PRIORIX-TETRA or 1 dose of a licensed MenC-CRM₁₉₇ (MenC-CRM) vaccine.

Table 3 presents the rates of solicited symptoms reported during the 4-day post-vaccination period in the Co-administered (Co-ad), NIMENRIX, PRIORIX-TETRA and MenC-CRM groups.

Redness was the most frequently reported solicited local symptom in each group after each vaccination (38.7% in the PRIORIX-TETRA group, 35.5% in the Co-ad group, 37.1% in the NIMENRIX group and 31.7% in the MenC-CRM group).

Irritability was the most frequently reported solicited general symptom in the 4 groups (50.7% in the Co-ad group, 40.9% in the NIMENRIX group, 38.7% in the PRIORIX-TETRA group and 43.5% in the MenC-CRM group).

In Study Men ACWY-TT-104, toddlers 12-14 months of age were vaccinated with either a single dose of NIMENRIX or two NIMENRIX doses administered 2 months apart. In the group who received two doses, the first and second doses were associated with similar local and systemic reactogenicity.

Children (2-10 years old), Adolescents (10-25 years old), and Adults (18-55 years old)

Children (2-5 years old)
In Study MenACWY-TT-081, healthy children 2 through 10 years of age were administered 1 dose of NIMENRIX or 1 dose of a licensed MenC-CRM vaccine.

Table 4 presents the percentage of subjects (2 through 5 years of age) with solicited adverse reactions during the 4-day post vaccination period in the NIMENRIX and MenC-CRM groups.

Redness was the most frequently reported solicited local symptom in each group (35.2% and 39.6% of the subjects in the NIMENRIX group and MenC-CRM group, respectively).

Irritability was the most frequently reported solicited general symptom in each group (15.4% and 11.3% of the subjects in the NIMENRIX group and MenC-CRM group, respectively). Drowsiness was also reported by 11.3% of the subjects in the MenC-CRM group, as compared to 14.2% of the subjects in the NIMENRIX group. Fever ≥ 37.5°C was reported by 5.6% of the subjects in the NIMENRIX group and 5.7% of the subjects in the MenC-CRM. The majority of fevers were measured by the rectal route (66.7% in the NIMENRIX group and 100% in the MenC-CRM group).

Children (6-10 years old)
Table 5 includes the percentage of subjects (6 through 10 years of age) with solicited adverse reactions during the 4-day post vaccination period in the NIMENRIX and MenC-CRM groups.

Pain was the most frequently reported solicited local symptom in each group (43.9% and 54.0% of the subjects in the NIMENRIX group and MenC-CRM group, respectively).

Fatigue was the most frequently reported solicited general symptom in each group (22.3% and 22.0% of the subjects in the NIMENRIX group and MenC-CRM group, respectively). Fever ≥ 37.5°C was reported in 6.8% of the subjects in the NIMENRIX group and 2.0% of the subjects in the MenC-CRM group.

Adolescents (10-25 years old)
In Study MenACWY-TT-071, healthy subjects 10 through 25 years of age were administered 1 dose of NIMENRIX or 1 dose of MENACTRA® (ACWY-DT vaccine).

Table 5 includes the percentage of subjects (10 through 25 years of age) with solicited adverse reactions during the 4-day post vaccination period in the NIMENRIX and MENACTRA groups.

The most common solicited local symptom during the 4-day post-vaccination period was pain at the injection site, reported by 51.4% and 55.4% of subjects in the NIMENRIX and MENACTRA groups, respectively. A much smaller percentage of these subjects reported pain with grade 3 intensity, ranging between 0.6% and 2.4% across all vaccine groups.

The incidence of redness at the injection site was 25.8% and 20.3% of subjects in the NIMENRIX and MENACTRA groups, respectively. The incidence of swelling was 19.1% and 13.5% of subjects, respectively. The majority of these events were grade 1 in intensity. Grade 3 events of redness (i.e. > 50 mm in diameter) were reported by 3 and 6 subjects in the NIMENRIX and MENACTRA groups, respectively. Grade 3 events of swelling (i.e. > 50 mm in diameter) were reported by 3 subjects each of the two vaccine groups.

The most common solicited general symptom was fatigue with an incidence of 27.3% to 29.2% across the two vaccine groups. Headache was reported by 25.5% to 26.4% and gastrointestinal symptoms by 13.1% to 13.5% of subjects across the two vaccine groups.

Coadministration with other vaccines (Tdap and HPV2) has not been associated with increased local or systemic reactions in clinical studies.

Adults (18-55 years old)
In Study MenACWY-TT-035, healthy adults 18 through 55 years of age were administered either 1 dose of NIMENRIX, 1 dose of a licensed ACWY-PS (polysaccharide) vaccine, or 1 dose of NIMENRIX co-administered with a licensed influenza vaccine, FLUARIX®.

Table 5 includes the percentage of subjects (18 through 55 years of age) with solicited adverse reactions during the 4-day post vaccination period in the NIMENRIX, ACWY-PS and Co-administered groups.

Pain was the most frequently reported solicited local symptom in each group (19.4% in the NIMENRIX group, 21.9% in the Co-administered group and 13.5% in the ACWY-PS group). Headache was the most frequently reported solicited general symptom in each group (16.3% in the NIMENRIX group, 14.2% in the ACWY-PS group, and 13.3% in the Co-administered group).

Adults > 55 years old

In a descriptive study a single dose of NIMENRIX was administered to 274 individuals aged 56 years and older. The adverse reactions reported in this study were already observed in younger age groups.

Common and Uncommon Clinical Trial Adverse Drug Reactions:

Additional adverse reactions reported during clinical studies included in the safety pooled analysis:
Common (≥ 1% to < 10%)*: Injection site hematoma, gastrointestinal symptoms (including diarrhea, vomiting and nausea)

Uncommon (≥ 0.1% to < 1%)**: insomnia, crying, hypoesthesia, dizziness, pruritus, rash, urticaria, myalgia, pain in extremity, malaise, and injection site reaction (including induration, pruritus, warmth, anesthesia).

*

Nausea and injection site hematoma occurred at a frequency of Uncommon in infants.

**

Rash occurred at a frequency of Common in infants. The adverse reactions hypoesthesia, dizziness, pruritus, urticaria, myalgia and pain in extremity were not reported in the infant clinical study (N= 524). Urticaria was not reported in the clinical studies of children 6-10 years old (N=990) and adolescents 11-17 years old (N=2317).

Booster Dose in Subjects from 12 Months of Age:

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 that gastrointestinal symptoms (including diarrhea, vomiting, and nausea) ranged from common to very common among subjects 6 years of age and older (versus common after primary vaccination). 

8.5 Post-Market Adverse Drug Reactions

General disorders and administration site conditions

Unknown: extensive limb swelling at the injection site, frequently associated with erythema, sometimes involving the adjacent joint or swelling of the entire injected limb.

9.4 Drug-Drug Interactions

Use with Other Vaccines

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 (PCV10).

From age 1 year and above, NIMENRIX can be given concomitantly with any of the following vaccines: hepatitis A and hepatitis B vaccines (HAV and HBV), measles-mumps-rubella vaccine (MMR), measles-mumps-rubella-varicella vaccine (MMRV), 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 (PCV13) in the second year of life.

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

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 rSBA Geometric Mean Titres (GMTs). The clinical relevance of this observation is unknown, since at least 99.4% of subjects (N=178) had rSBA titres ≥ 1:8 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, 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.

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.

Use with Systemic Immunosuppressive Medications

As with other vaccines, it may be expected that in patients receiving immunosuppressive treatment, an adequate response may not be elicited.

9.5 Drug-Food Interactions

Interactions with food have not been established.

9.6 Drug-Herb Interactions

Interactions with herbal products have not been established.

9.7 Drug-Laboratory Test Interactions

Interactions with laboratory tests have not been established.

10.1 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 Neisseria meningitidis groups 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.

Canadian epidemiological data is available on the Public Health Agency of Canada website:  http://www.phac-aspc.gc.ca/im/vpd-mev/meningococcal-eng.php.

Store in a refrigerator (2°C – 8°C). The diluent may also be stored at ambient temperature (25°C).

Do not freeze. Protect from light.

For shelf-life after reconstitution of the vaccine, see 4.3 Reconstitution.

There are no special handing instructions for this drug product. For information on reconstitution of the vaccine with the diluent, please see 4.3 Reconstitution.

Control #: 266087
December 9, 2022