Menactra®, Meningococcal (Groups A,C,Y and W-135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine is indicated for active primary and booster immunization for prevention of invasive disease caused by N meningitides serogroups A, C, Y and W-135. Menactra® vaccine is indicated for use in individuals from 9 months through 55 years of age.
The use of Menactra vaccine should be determined on the basis of local recommendations.

Menactra®
Confidential/ Proprietary Information
Page 2 of 35
Menactra vaccine is not to be used for treatment of meningococcal infections.
Meningococcal vaccination is also recommended for use in control of meningococcal outbreaks.
Menactra vaccine can be used to boost the serogroup C antibody response in subjects primed with a monovalent C conjugate vaccine.

Menactra vaccine should be administered as a 0.5 mL dose by intramuscular route.
Primary Vaccination
• In children 9 through 23 months of age, Menactra vaccine is given as a 2-dose series at least three months apart.
• Individuals 2 through 55 years of age receive a single dose.
Menactra vaccine should be administered as a single 0.5 mL injection by the intramuscular route,
preferably in the anterolateral thigh or deltoid region depending on the recipient's age and muscle mass.
Do not administer by intravascular injection (see section 6.6 on instruction for preparation).
Avoid injecting the vaccine intradermally or subcutaneously since clinical studies have not been done to establish safety and efficacy of the vaccine using these routes of administration.

Protection
Menactra vaccine will only protect against N meningitides A, C, Y and W-135 serogroups and will not protect against any other microorganisms.
As with any vaccine, vaccination with Menactra vaccine may not protect 100% of individuals against vaccine serogroups.
Individuals with functional or anatomical asplenia may produce an immune response to Menactra vaccine however; the degree of protection that would be afforded is unknown.

an antibody response to diphtheria toxoid may occur, Menactra vaccine should not be considered as an immunizing agent against diphtheria. No changes in the schedule for administering routine vaccines containing diphtheria toxoid are recommended.
Special patient groups
 Thrombocytopenia or bleeding disorders
Menactra vaccine has not been evaluated in persons with thrombocytopenia or bleeding disorders. As with any other vaccine administered intramuscularly, the vaccine risk versus benefit for persons at risk of haemorrhage following intramuscular injection must be evaluated. If the decision is made to administer any product by intramuscular injection to such persons, it should be given with caution, with steps taken to avoid the risk of hematoma formation following injection.
 Immunosuppression
The immunogenicity of Menactra vaccine could be reduced by immunosuppressive treatment. In such cases it is recommended to postpone the vaccination until the end of the immunosuppression.
Menactra vaccine has been evaluated in persons infected with human immunodeficiency virus (HIV). One dose of Menactra vaccine was safe and immunogenic in HIV-infected persons 11–24 years of age; a 2-dose series was safe and immunogenic in HIV-infected persons 2–10 years of age.
 Guillain-Barré Syndrome (GBS)
Persons previously diagnosed with Guillain-Barré syndrome (GBS) may be at increased risk of GBS following receipt of Menactra vaccine. The decision to give Menactra vaccine should take into account the potential benefits and risks.
GBS has been reported in temporal relationship following administration of Menactra vaccine. The risk of GBS following Menactra vaccine vaccination was evaluated in a post-marketing retrospective cohort study.
Administration route-related precautions
 Administration of Menactra vaccine and DTaP vaccine
In cases where Menactra vaccine and DTaP vaccine are to be administered at 4 through 6 years of age, preference should be given to simultaneous administration of the 2 vaccines or administration of Menactra vaccine prior to DTaP vaccine.
Do not administer by intravascular injection: ensure that the needle does not penetrate a blood vessel.
Serious and severe adverse events related precautions
 Anaphylactic reaction or serious adverse event
Prior to administration of any dose of Menactr vaccine, the parent or guardian of the recipient or the adult recipient himself must be asked about his personal history, family history, and recent health status, including immunization history, current health status and any adverse event after previous immunizations. In subjects who have a history of serious or severe reaction within 48 hours of a previous injection with a vaccine containing similar components, the decision to vaccinate must be carefully considered.
Before the injection of any biological, the person responsible for administration must take all precautions known for the prevention of allergic or any other reactions. As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic event following administration of the vaccine.
As a precautionary measure, epinephrine injection (1:1000) must be immediately available in case of unexpected anaphylactic or serious allergic reactions.
 Pregnancy
Refer to section 4.6
 Syncope
Syncope (fainting) has been reported following vaccination with Menactra vaccine Procedures
should be in place to prevent falling injury and manage syncopal reactions.

Concomitant administration with other vaccines
PCV7, MMR, V, MMRV, HepA, Hib
In clinical trials conducted in children younger than 2 years of age, Pneumococcal 7-valent Conjugate Vaccine (PCV), Measles, Mumps, and Rubella Virus Vaccine (MMR), Varicella Virus Vaccine Live (V), Measles, Mumps, Rubella and Varicella Virus Vaccine Live (MMRV), Hepatitis A Vaccine (HepA) or Haemophilus influenzae type b Vaccine (Hib) were co-administered with the second dose of Menactra vaccine at 12 months of age. Menactra vaccine and all these vaccines had similar safety profiles when administered concomitantly or separately at 12 months of age. The immunogenicity profiles of Menactra vaccine and MMRV, MMR+V, or Hib were also similar when these vaccines were given concomitantly or separately.
When Menacra vaccine was administered concomitantly with PCV, antibody responses to 3 of the 7 serotypes in PCV and to serogroup W-135 of Menactra vaccine did not meet the non-inferiority criteria. Given the high antibody response rates to all PCV serotypes when assessed by either ELISA or OPA, and considering that >81% of subjects achieved SBA-HC antibody titers ≥1:8 for all 4 serogroups of Menactra vaccine, it is unlikely that there will be any impact on the clinical efficacy of either of these vaccines when administered concomitantly.
DTaP
Data are not available to assess the safety and immunogenicity of Menactra vaccine and DTaP containing vaccines when administered concomitantly in the second year of life.
In one clinical trial conducted in children 4-6 years of age, Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTaP) (DAPTACEL/TRIPACEL/TRIACEL) and Menactr vaccine had similar safety profiles and were well tolerated when administered concomitantly or separately. Antibody responses to meningococcal serogroups A, C, and W-135 after concomitant administration were non-inferior to those observed when Menactra vaccine was administered separately (1 month before DTaP). The non-inferiority criterion was not met for serogroup Y. It is unlikely there will be any impact on clinical efficacy given that in both groups >80% of the subjects had SBA-HC antibody titers ≥1:8 for serogroup Y. With the exception of antibodies to the pertussis antigens fimbriae types 2 and 3 (FIM), antibody responses to pertussis, tetanus and diphtheria antigens following Menactra vaccine and DTaP concomitant administration were noninferior to those observed when each vaccine was administered separately. Because there are no widely accepted serological correlates of protection for pertussis, the clinical significance of this lower response to FIM is unknown.
Significantly lower antibody responses to all 4 meningococcal serogroups were observed when Menactra vaccine was administered 1 month after DTaP (DAPTACEL/TRIPACEL/TRIACEL). As a measure of precaution, in cases where Menctra vaccine and DTaP vaccine are to be administered at 4 through 6 years of age, preference should be given to simultaneous administration of the 2 vaccines or administration of Menactra vaccine prior to DTaP vaccine.
Tdap
In a clinical trial conducted in adolescents 11 to 17 years of age, Tetanus Toxoid, reduce Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Tdap) and Menactra vaccine had similar safety profiles and were well tolerated when administered concomitantly or separately. The concomitant administration of Tdap and Menactra vaccine induced antibody responses to all 4 meningococcal serogroups A, C, Y, and W-135 that were non-inferior to those observed when Menactra vaccine was administered separately.
Geometric mean concentrations (GMCs) of antibodies to the pertussis antigens pertactin (PRN) and fimbriae types 2 and 3 (FIM) were lower when Tdap was administered concomitantly with Menactra vaccine than when Tdap was administered alone. Given the strong response to all pertussis antigens across the treatment groups and since there are no widely accepted serological correlates of protection for pertussis, the clinical significance of certain lower pertussis antibody responses is unknown.
Td
In adolescents, Menactra vaccine can be administered concomitantly with Tetanus and Diphtheria Toxoids Adsorbed, For Adult Use (Td) vaccine. The immune responses to Td and Menactra vaccine antigens when Td and Menactra vaccine were given concomitantly were non-inferior to the responses obtained when the two products were administered separately. Concomitant administration of Menactra vaccine with Td was safe and well tolerated.
HPV
Menactra vaccine can be administered with bivalent or quadrivalent human papillomavirus vaccines (HPV2 or HPV4), with or without Tdap. Concomitant administration of Menactra vaccine with HPV vaccines has been evaluated in two studies. In one study, Menactra vaccine was coadministered with human papillomavirus bivalent (Types 16 and 18) AS04-adjuvanted vaccine (HPV2) alone and with Tdap to females 11 – 18 years of age. In another study, Menactra vaccine was coadministered with both human papillomavirus quadrivalent (Types 6, 11, 16 and 18) vaccine (HPV4) and Tdap to females and males 10 – 17 years of age. (44) In both studies, the safety profiles of the vaccines following concomitant administration were similar to those observed when the vaccines were given separately. Concomitant administration of Menactra vaccine and Tdap with HPV did not interfere with the immune responses to any antigens in these vaccines.
Typhim Vi
In adults, Menactra vaccine can be administered concomitantly with Typhoid Vi Polysaccharide vaccine Typhim Vi® vaccine. The immunogenic response to Typhim Vi vaccine when given concomitantly with Menactra vaccine is non-inferior to the response when Typhim Vi vaccine was given alone. Concomitant administration of Menactra vaccine with Typhim Vi was safe and well tolerated.
Menactra vaccine must not be mixed with any vaccine in the same syringe. Separate injection sites should be used in case of concomitant administration.
Vaccine-drug and / or vaccine-vaccine interactions
 Immunosuppressive therapy
If the vaccine is used in persons under immunosuppressive therapy, the expected immune response may not be obtained.

Animal reproduction studies have not demonstrated a risk with respect to effects on pregnancy and embryo-fetal development, parturition and postnatal development. However, no studies have been performed in pregnant women and spontaneously reported post-marketing data on the use of this vaccine in pregnant women are limited. Menactra vaccine should be given to a pregnant woman only if clearly needed, such as during an outbreak or prior to travel to an endemic area, and only following an assessment of the risks and benefits.
Given the severity of the meningococcal disease, pregnancy should not preclude vaccination when the benefit/risk ratio of administering Menactra vaccine is considered favourable.
Sanofi Pasteur maintains a Menactra vaccine pregnancy registry to prospectively collect data from healthcare providers of patients who received Menactra vaccine during pregnancy. The objective of this pregnancy registry is to collect and analyse the outcome of exposure to Menactra vaccine during pregnancy and monitor for any potential safety signals that may arise in this population. To date, no safety concern for maternal or infant’s health has been identified from this passive pregnancy surveillance system. The experience with Menactra vaccine exposure during pregnancy, however, remains limited.
It is not known whether the active substances included in the vaccine are excreted in human milk, but antibodies to the polysaccharides have been found to be transferred to the suckling offspring of mice.
Animal studies conducted in mice have not shown any harmful effect on the postnatal development of offspring exposed through breastfeeding to Menactra vaccine-induced maternal antibodies. However, the effect on breast-fed infants of the administration of Menactra vaccine to their mothers has not been studied. The risks and benefits of vaccination should be assessed before making the decision to immunize a nursing woman.

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

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine and may not reflect the rates observed in practice.
The safety profile of Menactra vaccine comes from approximately 3700 infants (9 months through 18 months of age) enrolled in four clinical trials. (30) (29) (31) (47)
Safety was evaluated within the first 7 days, 30 days and 6 months after the last vaccination.
Two doses of Menactra vaccine are safe and well tolerated by infants and toddlers when given alone or with concomitant vaccines (refer to Table for a list of concomitant vaccines). (16)
The majority of the solicited local reactions reported within 7 days after vaccination were of Grade 1 or Grade 2 intensity and of short duration (≤3 days). (16) The majority of the solicited systemic reactions were of Grade 1 intensity and of short duration (≤3 days). (16) (See Table and Table2.)
Metabolism and nutrition disorders
 Very common:
o Appetite lost
Nervous system disorders
 Very common:
o Drowsiness
Gastrointestinal disorders
 Common to very common:
o Vomiting
General disorders and administration site disorders
 Very common:
o Injection site tenderness, injection site erythema, injection site swelling
Irritability, crying abnormal, fever

b Intensity scale for fever: Any (>100.4°F) and Grade 3 (>103.1°F).
The primary safety study was a controlled trial that enrolled 1256 children who received Menactra vaccine at 9 and 12 months of age. At 12 months of age these children also received MMRV (or MMR + V), PCV7 and HepA. The most frequently reported solicited injection site and systemic adverse reactions within 7 days following vaccination in children 9 months and 12 months of age were injection site tenderness and irritability. (See Table .)
Metabolism and nutrition disorders
 Very common:
o Appetite lost
Nervous system disorders
 Very common:
o Drowsiness
Gastrointestinal disorders
 Very common:
o Vomiting
General disorders and administration site disorders
 Very common:
o Injection site tenderness, injection site erythema, injection site swelling
o Irritability, crying abnormal, fever

e Grade 2: cries and protests when injection site is touched, Grade 3: cries when injected limb is moved, or the movement of the injected limb is reduced.
f Grade 2: ≥1.0 inches to <2.0 inches, Grade 3: ≥2.0 inches.
g Grade 2: requires increased attention, Grade 3: inconsolable.
h Grade 2: 1 to 3 hours, Grade 3: >3 hours.
i Grade 2: not interested in surroundings or did not wake up for a feed/meal, Grade 3: sleeping most of the time or difficult to wake up.
j Grade 2: missed 1 or 2 feeds/meals completely, Grade 3: refuses 3 feeds/meals or refuses most feeds/meals.
k Grade 2: 2 to 5 episodes per 24 hours, Grade 3: ≥6 episodes per 24 hours or requiring parenteral hydration.
l Grade 2: >38.5°C to ≤39.5°C, Grade 3: >39.5°C.
Studies conducted in subjects 2 through 10 years of age
The safety profile of Menactra vaccine was evaluated in over 2400 children ages 2 through 10 years enrolled in three clinical trials. Two of the studies documented the safety profile of Menactra vaccine in meningococcal vaccination naïve population. (26) (50)The third study documented the safety profile of Menactra vaccine used as a meningococcal (re) vaccination in children already vaccinated with a meningococcal C conjugated vaccine (non-naïve population) (27). The safety profile of Menactra vaccine is reported separate for these two populations.
Safety was evaluated within the first 7 days, 28 days and 6 months after vaccination.
Menactra vaccine was generally safe and well tolerated among children.
The majority of the solicited local and systemic reactions reported within 7 days after vaccination were mild, with a mean duration of no more than 3 days for the local reactions and less than 4 days for the systemic reactions (26) (50).
 Safety profile of Menactra vaccine when used in meningococcal vaccination naïve population.
The most commonly reported solicited adverse reaction was pain at the injection site (40% to 48% of the participants) (26) (50) (See Table 4).
Metabolism and nutrition disorders
 Common to very common:
o Decreased appetite (anorexia)
Nervous system disorders
 Common to very common:
o Drowsiness
Gastrointestinal disorders
 Very common:
o Diarrhea
 Common:
o Vomiting
Skin and subcutaneous tissue disorders
 Common:
o Rash

o Hives
Musculoskeletal and connective tissue disorders
 Common:
o Arthralgia
General disorders and administration site disorders
 Very common:
o Injection site pain
o Injection site induration
 Common to very common:
o Irritability
o Injection site redness
o Injection site swelling
o Fever

a N = The total number of participants with data.
b Irritability was collected in Study 1 under Fussiness
The most frequently reported solicited injection site and systemic adverse reactions in US children aged 2 years through 10 years of age were injection site pain and irritability, respectively. Injection site redness, induration or swelling, diarrhea, and drowsiness were also very common. (See Table .)
Metabolism and nutrition disorders
 Common:
o Decreased appetite (anorexia)
Nervous system disorders
 Very common:
o Drowsiness
Gastrointestinal disorders
 Very common:
o Diarrhea
 Common:
o Vomiting
Skin and subcutaneous tissue disorders
 Common:
o Rash
Musculoskeletal and connective tissue disorders
 Common:
o Arthralgia
General disorders and administration site disorders
 Very common:
o Injection site pain, injection site redness, injection site induration, injection site swelling
o Irritability
 Common:
o Fever

Studies conducted in subjects 11 through 55 years of age
The safety profile of Menactra vaccine was assessed in over 7,000 adolescents and adults (11 through 55 years old) enrolled in seven clinical trials (19) (20) (21) (22) (23) (24) (25).
Safety was evaluated within the first 7 days, 28 days and 6 months after vaccination.
Menactra vaccine was generally safe and well tolerated among adolescents and adults (51).
The majority of the solicited local and systemic reactions reported within 7 days after vaccination were mild, with a mean duration of 2 days for the local reactions and less than 5 days for the systemic reactions (51).
The most commonly reported solicited adverse reactions were pain at the injection site and headache (respectively 55% and 37% in the whole population) (See Table ) (51).
Metabolism and nutrition disorders
 Common to very common:
o Decreased appetite (anorexia)
Nervous system disorders
 Very common:
o Headache
Gastrointestinal disorders
 Common to very common:
o Diarrhea
 Common:
o Vomiting
Skin and subcutaneous tissue disorders
 Common:
o Rash
Musculoskeletal and connective tissue disorders
 Very common:
o Arthralgia
General disorders and administration site disorders
 Very common:
o Injection site pain, injection site induration, injection site redness, injection site swelling
o Fatigue, malaise
 Common:
o Chills, fever

Menactra vaccine was well tolerated in persons who had high pre-existing titers for any serogroup in this vaccine (51).
The overall safety profile was similar when evaluated by age, gender and race (51).
The overall safety profile for Menactra vaccine was comparable to the safety profile of the quadrivalent polysaccharide vaccine Menomune® - A/C/Y/W-135. However, local solicited reactions were more frequently reported for Menactra vaccine (See Table and Table 1) (51).
Metabolism and nutrition disorders
 Very common:
o Decreased appetite (anorexia)
Nervous system disorders
 Very common:
o Headache
Gastrointestinal disorders
 Very common:
o Diarrhea
 Common:
o Vomiting
Skin and subcutaneous tissue disorders
 Common:
o Rash
Musculoskeletal and connective tissue disorders
 Very common:
o Arthralgia
General disorders and administration site disorders
 Very common:
o Injection site pain, injection site induration, injection site redness, injection site swelling
o Fatigue, malaise
 Common:
o Chills, fever

 Safety Profile of a Single Dose of Menactra vaccine 4-6 Years After a Prior dose of Menactra vaccine (Booster Vaccination) (52)
In an open-label, multi-center trial conducted in the US, 834 participants were enrolled to receive a single dose of Menactra vaccine 4-6 years after a primary dose. The mean age of participants was 17.8 years (range: 15.0-53.7 years). A total of 48.0% (400/834) were male and 52.0% (434/834) were female.
Booster vaccination with Menactra vaccine was generally safe and well tolerated among adolescents and adults.
Overall rates of solicited injection-site reactions and solicited systemic reactions were similar to those observed in clinical trials that evaluated primary vaccination in adolescents and adults. The majority of solicited reactions were Grade 1 or 2 and resolved within 3 days. The most common solicited injection-site and systemic reactions following booster vaccination were pain and myalgia.
 Safety Profile of Menactra vaccine when used in meningococcal vaccination non-naïve population.
A clinical study (27) performed in the UK documented the safety profile of Menactra vaccine compared to Haemophilus Influenzae Type b (Hib) vaccine Hiberix®, a lyophilized vaccine of purified polyribosyl-ribitol-phosphate (PRP) capsular polysaccharide of Hib, covalently bound to tetanus toxoid when used in children (mean age 3 years) already vaccinated with a meningococcal protein-conjugated monovalent C vaccine.
The majority of the solicited injection site (local) and systemic reactions reported within 7 days after vaccination were mild, with a mean duration of 3 days.
The most commonly reported solicited adverse reaction was irritability (reported by 57% of the participants) (See Table .)

Data from Post-marketing surveillance
Based on spontaneous reporting, the following additional adverse events have been reported after commercial use of Menactra vaccine. These events have been very rarely reported, however exact incidence rates cannot be calculated precisely, their frequency is qualified as “Not known”.
Immune System disorders
Hypersensitivity reactions such as anaphylaxis/anaphylactic reaction, wheezing, difficulty breathing, upper airway swelling, urticaria, erythema, pruritus, hypotension
Nervous system disorders
Guillain-Barré syndrome, paraesthesia, vasovagal syncope, dizziness, convulsion, facial palsy, acute disseminated encephalomyelitis, transverse myelitis
Musculoskeletal and connective tissue disorders
Myalgia
Post-marketing Safety Study
The risk of GBS following receipt of Menactra Vaccine was evaluated in a US retrospective cohort study using healthcare claims data from 9,578,688 individuals 11 through 18 years of age, of whom 1,431,906 (15%) received Menactra vaccine. Of 72 medical chart-confirmed GBS cases, none had received Menactra vaccine within 42 days prior to symptom onset. An additional 129 potential cases of GBS could not be confirmed or excluded due to absent or insufficient medical chart information. In an analysis that took into account the missing data, estimates of the attributable risk of GBS in individuals 11 through 18 years of age ranged from 0 to 5 additional cases of GBS per 1,000,000 vaccinees within the 6 week period following vaccination.
To report any side effect(s):
• Saudi Arabia:
- National Pharmacovigilance Center (NPC):
o Fax: +966-11-205-7662
o Call NPC at :
+966-11-2038222 Exts: 2317-2356-2353-2354-2334-2340
o Toll free phone: 8002490000
o E-mail: npc.drug@sfda.gov.sa
o Website: www.sfda.gov.sa/npc

Not applicable.

Pharmacotherapeutic group: meningococcal vaccine, ATC code: J07AH08
Mechanism of action
The presence of bactericidal anti-capsular meningococcal antibodies has been associated with
protection from invasive meningococcal disease. Menactra vaccine induces the production of bactericidal antibodies specific to the capsular polysaccharides of serogroups A, C, Y and W-135.
Pharmacodynamic effects
Meningococcal disease including meningitis and septicemia is caused by the bacterium N
meningitidis from which several serogroups have been identified. Menactra vaccine can provide
protection against infections caused by serogroups A, C, Y and W-135.
Immunogenicity
The immunogenicity of Menactra vaccine has been studied in three clinical trials in infants 9through 18 months of age (29) (30) (47), in four clinical trials among children 2 through 10 years of age (26) (27) (28) (50), and in six clinical trials among adolescents and adults 11 through 55 years of age (19) (20) (22) (23) (24) (25).
Menactra vaccine induces the production of antibodies specific to the capsular polysaccharides of all vaccine serogroups (A, C, Y and W-135), which are capable of killing the corresponding bacteria. Immunogenicity was assessed by measuring these functional antibodies in a serum bactericidal assay (SBA) using baby rabbit (SBA-BR) or human (SBA-HC) serum as the complement source (53).
Immunogenicity in the population 9 months through 23 months of age
The immunogenicity of Menactra vaccine has been studied in three clinical trials in approximately 2250 infants 9 through 18 months of age where one or two doses were administered either alone or with concomitant paediatric vaccine(s) (MMRV or PCV). A subset of the participants in these trials received Menactra vaccine concomitantly with MMRV + Hib vaccine (29), (30) (47)
In a primary study, the majority of the participants in groups that received the second dose of
Menactra vaccine alone or with concomitant paediatric vaccine(s), achieved SBA-HC titers ≥1:8 for all serogroups. Groups that received the second dose of Menactra vaccine alone had ≥ 91% of subjects achieving an SBA-HC titer ≥1:8 for serogroups A, C, and Y, and ≥86% for serogroup W-135 ( Table 2). When the second dose of Menactra vaccine was given concomitantly with MMRV (or MMRV+Hib) or with PCV, the percentages of subjects with SBA-HC titers ≥1:8 were high (>90% for serogroups A, C and Y, and >81% for serogroup W-135). SBA-HC GMTs were high for all serogroups. (29)

Administration of Menactra vaccine to toddlers at 12 months and 15 months of age (N=65) was evaluated in a US study. Prior to the first dose, 33.3% of participants had an SBA-HC titer ≥1:8 to serogroup A, and 0-2% to serogroups C, Y and W135. After the second dose, percentages of participants with an SBA-HC titer ≥1:8 were: 85.2%, serogroup A; 100.0%, serogroup C; 96.3%, serogroup Y; 96.2%, serogroup W-135. (47)
In the same study, a group of infants received Menactra vaccine at 9 months and 15 months of age (N=65). Prior to the first dose 43.9% of participants had an SBA-HC titer ≥1:8 to serogroup A, and 0-2.2% to serogroups C, Y and W-135. After the second dose, percentages of participants with an SBA-HC titer ≥1:8 were: 89.4%, serogroup A; 100.0%, serogroup C; 94.0%, serogroup Y; 92.0%, serogroup W-135. (47)
Immunogenicity in the population of meningococcal vaccinated naïve children 2 through 10 years of age
The immunogenicity profile was demonstrated in a subset of 2 clinical trials (26) (50) with more
than 750 children 2 through 10 years of age. Immunogenicity was assessed immediately before
and 28 days after administration of a single dose of Menactra vaccine. Participants demonstrated a large increase in serum bactericidal antibodies resulting in a significant increase in SBA geometric

mean titers (GMTs) from baseline values, for all four serogroups included in the vaccine, when measured 28 days post vaccination (See Table 3 and Table 5).
For all vaccine serogroups, 86% to 100% of participants with undetectable SBA titers (<1:8) at
baseline seroconverted to achieve ≥ 4-fold rise in Day 28 SBA titers (See Table 4).

Immune responses induced by Menactra vaccine in monovalent C conjugate-vaccinated children (non-naïve population)
The capacity of Menactra vaccine to induce a booster response to serogroup C polysaccharide and to prime for serogroups A, Y, and W-135 polysaccharides was documented by vaccinating children aged 3 to 5 years immunized during infancy with monovalent C conjugate meningococcal vaccines (27).
The immune responses against all four serogroups were of high magnitude, with high proportions of children developing a ≥4-fold rise in their SBA-BR titers. In particular, responses against the serogroup C were strong with 93.2% of children developing a ≥4-fold rise in their SBA-BR titers.
The data confirmed the lack of hyporesponsiveness induction by meningococcal conjugated vaccines.
(See Table 6)

Immunogenicity in the population adolescents 11 through 18 years of age
The immunogenicity profile was demonstrated in a subset of 2 clinical trials (20) (24) with approximately 1400 adolescents 11 through 18 years of age.
Results from a clinical trial conducted in adolescents 11 through 18 years of age (20), demonstrated a strong immune response to a single dose of Menactra vaccine. SBA GMTs were significantly higher 28 days after vaccination than at baseline (See Table 8).
In addition, 98% to 100% of adolescents with undetectable SBA titer (<1:8) at baseline achieved a ≥4-fold rise in Day 28 SBA titers to all vaccine serogroups (20). (See Table 8). These results indicate that the vaccine is highly immunogenic in adolescents.

d Menactra vaccine was non-inferior to Menomune – A/C/Y/W-135 vaccine. Non-inferiority was assessed by the proportion of participants with a 4-fold or greater rise in SBA-BR titer for N meningitidis serogroups A, C, Y and W-135 using a 10% non-inferiority margin and a one-sided Type I error rate of 0.05.
Immunogenicity in Adolescents and Adults Following Booster Vaccination
For a description of the study design and number of participants, please refer to 4.8 Undesirable effects .The rapidity and magnitude of the anti-meningococcal antibody increases following booster vaccination with Menactra vaccine suggested these were anamnestic responses. Among the randomly chosen subset of trial participants for whom immune responses at Day 6 were assessed (n=112), 86.6%, 91.1%, 94.6%, and 92.0% achieved ≥4-fold rises in SBA-H antibody titers for Serogroups A, C, Y, and W-135, respectively. The proportions of participants (n=781) who achieved ≥4-fold rises in SBA-H antibody titers by Day 28 were 95.0%, 95.3%, 97.1%, and 96% for Serogroups A, C, Y, and W-135, respectively. The proportions of participants who achieved an SBA-H titer ≥1:8 by Day 28 were >99% for each serogroup.
Immunogenicity in the population 18 through 55 years of age
The immunogenicity profile was demonstrated in a subset of three clinical trials (23) (22) and (25) with more than 3,000 adolescents and adults. Immunogenicity was assessed immediately before and 28 days after administration of a single dose of Menactra vaccine. Participants demonstrated a large increase in serum bactericidal antibodies resulting in a significant increase in SBA geometric mean titers (GMTs) from baseline values, for all four serogroups included in the
vaccine, when measured 28 days post vaccination (See Table 9).
For all vaccine serogroups, 93% to 100% of participants with undetectable SBA titers (<1:8) at
baseline achieved a ≥ 4-fold rise in Day 28 SBA titers (See Table 9).

In these three clinical trials (23) (22) (25), the immunogenicity profile induced by Menactra vaccine was similar when evaluated according to age, race, or gender.
When evaluated in comparison to the meningococcal polysaccharide vaccine Menomune® - A/C/Y/W-135 vaccine, the immune response to Menactra vaccinewas shown to be similar to the immune response to Menomune - A/C/Y/W-135 vaccine for all serogroups (23) (22).
Clinical efficacy
Clinical efficacy trials have not been performed as the induction of serum bactericidal antibodies has been established as a marker of efficacy for meningococcal vaccines.
Data obtained during the vaccination campaign conducted in 1999-2000 in the UK, with three meningococcal serogroup C conjugates, have shown that a SBA titer of ≥1:8, using baby rabbit serum as source of complement, correlates with protection. However, for other serogroups, the minimum protective SBA titer against meningococcal disease has not been determined.
Evidence that complement-mediated bactericidal antibody provides protection against invasive meningococcal disease (IMD) was observed in studies conducted by the Walter Reed Army Institute of Research. Goldschneider et al. provided evidence that there was a strong correlation between bactericidal antibody titers (SBA using human complement) ≥1:4 and protection from serogroup C meningococcal disease. In the studies of Menactra vaccine in infants and toddlers, a serum bactericidal assay using human complement (SBA-HC) was applied to evaluate antibody responses for all 4 serogroups. A more conservative titer of 1:8 was the serological endpoint used to evaluate the antibody responses.
Studies conducted with the Meningococcal Polysaccharide Vaccine, Groups A, C, Y and W-135 Combined, Menomune® - A/C/Y/W-135, demonstrated that a 4-fold increase in bactericidal antibodies is indicative of protection in adults.

Menactra vaccine has been evaluated by assessing the production of specific functional antibodies according to the same serological criteria considered to be surrogate markers of protection.

No pharmacokinetic studies have been performed.

No pharmacokinetic studies have been performed.

Physiological Saline, 0.85%
Sodium Chloride, Granular, USP* 8.7 g/L
Phosphate Buffered Saline, 0.5 M
Sodium Chloride, Granular, USP* 8.5 g/L
Dibasic Sodium Phosphate Anhydrous* 34.8 g/L
Sodium Phosphate, Monobasic, USP* 35.2 g/L
* These purchased commodities are added to Water for Injection at the above concentrations to achieve the required batch size.
USP: United States Pharmacopoeia
Menactra vaccine is preservative-free.
No adjuvant is added.

This vaccine must not be mixed with other vaccine or medicinal products in the same syringe.

Store at 2°C to 8°C (35°F to 46°F) (i.e. in a refrigerator).
Do not freeze.
Protect from light.

The vaccine is manufactured as a single dose unit, containing 0.5 mL of solution.
Containers and devices Container element Nature
Single dose vial type I borosilicate glass (not made with natural rubber latex)
Seal fitted with a flip off button (Crimped aluminium cap)

The vaccine should be inspected visually for any particulate matter and/or variation of physical aspect prior to administration. Do not use if the content appears otherwise.
Keep in the refrigerator until use.

Remove the flip cap and using a suitable syringe and needle, withdraw 0.5 mL of product, ensuring no air bubbles are present before injection.
After use, any remaining vaccine and container must be disposed of safely, preferably by heat inactivation or incineration, according to locally agreed procedures.