Consumer medicine information

Menactra

Neisseria meningitidis vaccine

BRAND INFORMATION

Brand name

Menactra Solution for injection

Active ingredient

Neisseria meningitidis vaccine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Menactra.

What is in this leaflet

Read all of this leaflet carefully before you are vaccinated.

  • Keep this leaflet. You may need to read it again.
  • If you have any further questions, ask your doctor or pharmacist.
  • This vaccine has been prescribed for you. Do not pass it on to others.
  • If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

  • What Menactra vaccine is and what it is used for
  • Before you are given Menactra vaccine
  • How Menactra vaccine is given
  • Possible side effects
  • Storing Menactra vaccine
  • Further information

What Menactra vaccine is and what it is used for

Menactra is a vaccine.

Vaccines are used to protect you against infectious diseases.

Menactra vaccine is given to protect persons 2 through 55 years of age against meningococcal disease caused by four groups of Neisseria meningitidis (A, C, Y and W-135). The use of this vaccine should be in accordance with official recommendations. It allows the body to produce enough antibodies to provide a defence against the bacteria that cause meningococcal disease. However, as with all vaccines, 100% protection cannot be guaranteed.

Menactra vaccine will not prevent meningitis (an infection of the brain and spinal cord coverings) caused by other groups of Neisseria meningitidis or meningitis caused by different kinds of microbes.

Before you are given Menactra vaccine

When you must not be given it

  • Do not have Menactra vaccine if you are allergic (hypersensitive) to the active substance or any of the other ingredients of Menactra vaccine listed in the FURTHER INFORMATION section
  • If you have an illness with febrile or acute infection, the vaccination shall be postponed until after you have recovered
  • If you have been previously diagnosed with Guillain-Barre syndrome
  • Children younger than 2 years of age or adults older than 55 years of age

Take special care with Menactra vaccine

  • Tell your doctor if you have been previously diagnosed with Guillain-Barre syndrome or any brain disorder
  • Tell your doctor if you are pregnant or nursing

If you become aware that you were pregnant when you received Menactra vaccine, please discuss this with your doctor or contact sanofi pasteur at 1800 829 468 (in Australia) or 0800727 838 (in New Zealand) for more information.

  • Tell your doctor if you have an immune deficiency condition

Your doctor should make sure the benefits of vaccination outweigh the risks when recommending Menactra vaccine.

Taking other medicines

  • Medicines that may reduce your immune response: such as corticosteroids (for example prednisone), medicines used to treat cancer (chemotherapy), radiotherapy or other medicines affecting the immune system. Tell your doctor if you have been treated with such medicines.

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without prescription.

Having other vaccines

  • Your doctor will advise you if Menactra vaccine is to be given with another vaccine. Menactra vaccine may be given at the same time as typhoid vaccines and Td (tetanus and diphtheria) vaccines using separate syringes and into separate limbs.

How Menactra vaccine is given

Menactra vaccine is administered to you by your doctor or your nurse.

A single dose of Menactra vaccine (0.5 mL) is injected into the muscle of the upper arm (preferably) of persons 2 through 55 years of age.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

Possible side effects

Like all medicines, Menactra vaccine can cause side effects, although not everybody gets them.

The most common local side effects with Menactra vaccine include:

  • pain, tenderness, redness, hardness and swelling at the injection site

Systemic side effect include:

  • headache, tiredness (fatigue), feeling unwell (malaise)
  • joint pain (arthralgia)
  • fever, chills
  • loss of appetite, diarrhoea, vomiting
  • rash
  • irritability, drowsiness (in children)

These side effects usually clear up within a few days. If events continue or become severe, please tell your doctor or pharmacist.

Other side effects that have been reported very rarely include:

  • hypersensitivity reactions such as wheezing, difficulty breathing, upper airway swelling, low blood pressure (hypotension), skin reactions for which symptoms may include itchiness of the skin (urticaria, pruritus) and redness of the skin (erythema)
  • sudden severe allergic reaction, for which symptoms may include rash, itching or hives on the skin, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or trouble breathing (anaphylactic/anaphylactoid reaction)
  • neurological disorders that may result in confusion, numbness or tingling, pain and weakness of the limbs, loss of balance, loss of reflexes, paralysis of part or all the body (Guillain-Barre syndrome, acute disseminated encephalomyelitis, transverse myelitis)
  • dizziness
  • fainting
  • convulsion
  • drooping eyelid and sagging muscles on one side of the face (facial palsy)
  • tingling or numbness of the hands or feet (paraesthesia)
  • sore, aching muscles (myalgia)

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

After using Menactra Vaccine

Storage

Menactra vaccine is usually stored in the doctor's surgery or clinic, or at the pharmacy. However, if you need to store Menactra vaccine

  • Keep out of reach and sight of children.
  • Keep Menactra vaccine in the original pack until it is time for it to be given.
  • Keep it in the refrigerator, store at 2°C to 8°C. Do not freeze Menactra vaccine.

Do not use Menactra vaccine after the expiry date which is stated on the carton after EXP.

Do not have Menactra vaccine if the packaging is torn or shows signs of tampering.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Product description

What Menactra vaccine contains

The active substance is 4 µg of each polysaccharide per serogroup A, C, Y and W-135 conjugated to approximately 48 µg diphtheria toxoid.

The other ingredients are excipients: sodium chloride, sodium phosphate - dibasic anhydrous and sodium phosphate - monobasic.

No adjuvant or preservative is added.

What Menactra vaccine looks like and contents of the pack

Each pack of Menactra vaccine contains

1 vial containing a single dose (0.5 mL) of a clear to slightly turbid liquid

Name and Address of Australian Sponsor

sanofi-aventis australia pty ltd
Talavera Corporate Centre - Building D
12-24 Talavera Road
Macquarie Park NSW 2113
Australia
Tel: 1800 829 468 (1800 Vaxin8)

Name and Address of New Zealand Sponsor

Sanofi-Aventis New Zealand Pty Ltd
Level 8, James & Wells Tower
56 Cawley St
Ellerslie
Auckland
New Zealand
Tel: 0800 727 838

AUST R number
AUST R 168403

Date of preparation
11 May 2012

Menactra is a registered trademark of sanofi pasteur and its subsidiaries.

BRAND INFORMATION

Brand name

Menactra Solution for injection

Active ingredient

Neisseria meningitidis vaccine

Schedule

S4

 

1 Name of Medicine

Meningococcal (Groups A, C, Y and W-135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine.

2 Qualitative and Quantitative Composition

Each 0.5 mL dose of vaccine contains:
Active ingredients:
Meningococcal polysaccharide* Group A: 4.0 mcg/dose;
Meningococcal polysaccharide* Group C: 4.0 mcg/dose;
Meningococcal polysaccharide* Group Y: 4.0 mcg/dose;
Meningococcal polysaccharide* Group W-135: 4.0 mcg/dose;
Diphtheria toxoid protein: Approximately 48 mcg/dose.
*Each of the four polysaccharides is conjugated to diphtheria toxoid.
Menactra is a sterile, clear to slightly turbid solution of Neisseria meningitidis purified capsular polysaccharides of groups A, C, Y and W-135, individually conjugated to a carrier protein. The protein is a purified Corynebacterium diphtheriae toxoid, formalin-detoxified. Each 0.5 mL dose of vaccine is formulated in sodium phosphate buffered isotonic sodium chloride solution. No preservative or adjuvant is added.
There is no latex in any component of the vial.

3 Pharmaceutical Form

Solution for injection.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

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 induces the production of bactericidal antibodies specific to the capsular polysaccharides of serogroups A, C, Y and W-135.

Clinical trials.

Immunogenicity.

The immunogenicity of Menactra has been studied in three clinical trials in infants 9 through 18 months of age, in four clinical trials among children 2 through 10 years of age, and in six clinical trials among adolescents and adults 11 through 55 years of age.
Menactra 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.
The response to vaccination following one or two doses of vaccine administered to children 9 through 18 months of age and following one dose of vaccine administered to children 2 through 10 years of age was evaluated by the proportion of subjects having an SBA-HC antibody titre of 1:8 or greater, for each serogroup. In adolescents and adults, the response to vaccination was evaluated by the proportion of subjects with a 4-fold or greater increase in bactericidal antibody to each serogroup as measured by SBA-BR.
Immunogenicity of Menactra 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) (Measles, Mumps, Rubella and Varicella Virus vaccine Live [MMRV] or Pneumococcal 7-valent Conjugate (Diphtheria CRM197 Protein) vaccine [PCV7]). A subset of the participants in these trials received Menactra concomitantly with MMRV + Haemophilus Influenza type b vaccine [Hib].
Immunogenicity was evaluated in three comparative, randomised, US, multi-centre, active controlled clinical trials that enrolled children (2-10 years old), adolescents (11-18 years old), and adults (18-55 years old). Participants received a dose of Menactra (N=2526) or Menomune-A/C/Y/W-135 (N=2317). For all age groups studied, sera were obtained before and approximately 28 days after vaccination.
In each of the trials, there were no substantive differences in demographic characteristics between the vaccine groups, between immunogenicity subsets or the overall study population.

Immunogenicity in children 9 through 23 months of age.

In a primary study (MTA44), the majority of the participants in groups that received the second dose of Menactra alone or with concomitant paediatric vaccines achieved SBA-HC titres ≥ 1:8 for all serogroups. Groups that received the second dose of Menactra alone had ≥ 91% of subjects achieving an SBA-HC titre ≥ 1:8 for serogroups A, C, and Y, and ≥ 86% for serogroup W 135 (Table 5). When the second dose of Menactra was given concomitantly with MMRV (or MMRV+Hib) or with PCV7, the percentages of subjects with SBA-HC titres ≥ 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.
Administration of Menactra 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 titre ≥ 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 titre ≥ 1:8 were: 85.2%, serogroup A; 100.0%, serogroup C; 96.3%, serogroup Y; 96.2%, serogroup W-135.
In the same study, a group of infants received Menactra at 9 months and 15 months of age (N=65). Prior to the first dose 43.9% of participants had an SBA-HC titre ≥ 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 titre ≥ 1:8 were: 89.4%, serogroup A; 100.0%, serogroup C; 94.0%, serogroup Y; 92.0%, serogroup W-135.
In MTA26, a Phase II, dose schedule-optimisation study, after a first dose of Menactra given at 9 or 12 months of age in Groups 1, 2 and 3, the percentage of subjects achieving SBA-HC titres ≥ 8 ranged from 51.9% to 75.8% for serogroup A, from 82.9% to 85.4% for serogroup C, from 20.6% to 34.6% for serogroup Y, and from 17.6% to 26.7% for serogroup W-135.
After the second dose of Menactra given at 12 or 15 months, the percentage of subjects in each group achieving titres ≥ 8 ranged from 85.2% (for serogroup A) to 100% (for serogroup C) (Table 6).
This study also evaluated a single dose of Menactra at 15 months or 18 months of age. After a single dose of Menactra at 15 or 18 months, responses for serogroups A and C were similar to those in Groups 1, 2 and 3 after the first dose of Menactra. Responses after the single dose of Menactra at 15 or 18 months for serogroups Y and W-135 were higher than those after a single dose of Menactra at 9 months. However, overall the results confirmed that 2 doses of Menactra are preferred to elicit a high immune response for all 4 serogroups in subjects aged 9 through 15 months.

Immunogenicity in children 2 through 10 years of age.

Of 1408 enrolled children 2-10 years old, immune responses evaluated in a subset of Menactra participants (2-3 years old, n=52; 4-10 years old, n=84) and Menomune-A/C/Y/W-135 participants (2-3 years old, n=53; 4-10 years old, n=84) were comparable for all four serogroups (Table 7 and Table 8).
In the subset of participants 2-3 years of age with undetectable pre-vaccination titres (i.e. < 4 at Day 0), seroconversion rates (defined as ≥ 8 at Day 28) were similar between the Menactra and Menomune-A/C/Y/W-135 recipients. Menactra participants achieved seroconversion rates of: 57%, serogroup A (n=12/21); 62%, serogroup C (n=29/47); 84%, serogroup Y (n=26/31); 53%, serogroup W-135 (n=20/38). The seroconversion rates for Menomune-A/C/Y/W-135 recipients were 55%, serogroup A (n=16/29); 30%, serogroup C (n=13/43); 57%, serogroup Y (n=17/30); 26%, serogroup W-135 (n=11/43).
In the subset of participants 4-10 years of age, percentages of participants that achieved seroconversion were similar between the Menactra and Menomune-A/C/Y/W-135 recipients. Menactra participants achieved seroconversion rates of: 69%, serogroup A (n=11/16); 81%, serogroup C (n=50/62); 98%, serogroup Y (n=45/46); 69%, serogroup W-135 (n=27/39). The seroconversion rates for Menomune-A/C/Y/W-135 recipients were 48%, serogroup A (n=10/21); 38%, serogroup C (n=19/50); 84%, serogroup Y (n=38/45); 68%, serogroup W-135 (n=26/38).

Immunogenicity in adolescents 11 through 18 years of age.

Results from the comparative clinical trial conducted in 881 adolescents aged 11-18 years showed that the immune responses to Menactra and Menomune-A/C/Y/W-135 were similar for all four serogroups (Table 9).
In participants with undetectable pre-vaccination titres (i.e. less than 8 at Day 0), seroconversion rates (defined as a ≥ 4-fold rise in Day 28 SBA titres) were similar between the Menactra and Menomune-A/C/Y/W-135 recipients. Menactra participants achieved seroconversion rates of: 100%, serogroup A (n=81/81); 99%, serogroup C (n=153/155); 98%, serogroup Y (n=60/61); 99%, serogroup W-135 (n=161/164). The seroconversion rates for Menomune-A/C/Y/W-135 recipients were 100%, serogroup A (n=93/93); 99%, serogroup C (n=151/152); 100%, serogroup Y (n=47/47); 99%, serogroup W-135 (n=138/139).

Immunogenicity in adolescents and adults following booster vaccination.

In an open-label, multi-centre trial conducted in the US (MTA77), 834 participants < 56 years of age were enrolled to receive a single dose of Menactra 4-6 years after a primary dose at ≥ 11 years of age. The mean age of subjects was 17.8 years. The rapidity and magnitude of the anti-meningococcal antibody increases following booster vaccination with Menactra 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 titres for Serogroups A, C, Y, and W-135, respectively. The proportions of participants (n=781) who achieved ≥ 4-fold rises in SBA-H antibody titres 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 titre ≥ 1:8 by Day 28 were > 99% for each serogroup.

Immunogenicity in adults 18 through 55 years of age.

Results from the comparative clinical trial conducted in 2554 adults aged 18-55 years showed that the immune responses to Menactra and Menomune-A/C/Y/W-135 were similar for all four serogroups (Table 10).
In participants with undetectable pre-vaccination titres (i.e. less than 8 at Day 0), seroconversion rates (defined as a ≥ 4-fold rise in Day 28 SBA titres) were similar between the Menactra and Menomune-A/C/Y/W-135 recipients. Menactra participants achieved seroconversion rates of: 100%, serogroup A (n=156/156); 99%, serogroup C (n=343/345); 91%, serogroup Y (n=253/279); 97%, serogroup W-135 (n=360/373). The seroconversion rates for Menomune-A/C/Y/W-135 recipients were 99%, serogroup A (n=143/144); 98%, serogroup C (n=297/304); 97%, serogroup Y (n=221/228); 99%, serogroup W-135 (n=325/328).

Concomitant vaccine administration.

PCV7, MMR, V, MMRV, HepA, Hib.

In clinical trials conducted in children younger than 2 years of age, Pneumococcal 7-valent Conjugate Vaccine (PCV7), 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 at 12 months of age. Menactra and all these vaccines had similar safety profiles when administered concomitantly or separately at 12 months of age. The immunogenicity profiles of Menactra and MMRV, MMR+V, or Hib were also similar when these vaccines were given concomitantly or separately.
When Menactra was administered concomitantly with PCV, antibody responses to 3 of the 7 serotypes in PCV (MTA37) and to serogroup W-135 (MTA44) of Menactra 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 titres ≥ 1:8 for all 4 serogroups of Menactra, it is unlikely that there will be any impact on the clinical efficacy of either of these vaccines when administered concomitantly.

Diphtheria, tetanus and acellular pertussis.

The concomitant use of Menactra and Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTPa) was evaluated in a double-blind, randomised clinical trial (MTA43) conducted in 881 participants aged 4-6 years.
When Menactra as administered 30 days after DTPa (and Inactivated Polio Vaccine (IPV)) [Group 1], significantly lower SBA-HC GMTs to all 4 meningococcal serogroups were observed compared to Menactra (and IPV) administered 30 days prior to DTPa [Group 3]. When Menactra was administered concomitantly with DTPa [Group 2], SBA-HC GMTs to meningococcal serogroups A, C, and W-135 were non-inferior to those observed after Menactra (and IPV) [Group 3]. The non-inferiority criterion was marginally missed for meningococcal serogroup Y. Non-inferiority of SBA-HC GMTs following concomitant administration of Menactra and DTPa compared to those after concomitant Menactra and IPV was concluded if the upper limit of the 2-sided 95% CI of (GMTGroupC divided by GMTGroupB) computed separately for each of the serogroup was < 2. (See Table 11)
Significantly lower antibody responses to all 4 meningococcal serogroups were observed when Menactra was administered 1 month after DTPa. As a measure of precaution, in cases where Menactra and DTPa 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 prior to DTPa vaccine.

Tetanus, reduced diphtheria and acellular pertussis.

The concomitant use of Menactra and Tetanus Toxoid, reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (dTpa) and Menactra was evaluated in a clinical trial conducted in adolescents 11 to 17 years of age. The concomitant administration of dTpa and Menactra induced antibody responses to all 4 meningococcal serogroups A, C, Y, and W-135 that were non-inferior to those observed when Menactra was administered separately.

Tetanus and diphtheria.

The concomitant use of Menactra and Tetanus and Diphtheria Toxoids Adsorbed, For Adult Use (Td, manufactured by Sanofi Pasteur Inc.) was evaluated in a double-blind, randomised, controlled clinical trial conducted in 1021 participants aged 11-17 years. For meningococcal serogroups C, Y and W-135, the proportion of participants with a 4-fold or greater rise in SBA titre was higher when Menactra was given concomitantly with Td than when Menactra was given one month following Td. The clinical relevance of this finding has not been fully evaluated. No interference was observed in the immune response to the tetanus and diphtheria components following concomitant vaccination.

Human papillomavirus.

Concomitant administration of Menactra with HPV vaccines has been evaluated in two studies. In one study, Menactra was co-administered 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 was co-administered with both human papillomavirus quadrivalent (Types 6, 11, 16 and 18) vaccine (HPV4) and dTpa to females and males 10 - 17 years of age. Concomitant administration of Menactra and dTpa with HPV did not interfere with the immune responses to any antigens in these vaccines.

Typhoid Vi polysaccharide vaccine, Typhim Vi.

The concomitant use of Menactra and Typhim Vi (recommended for certain travellers) was evaluated in a double-blind, randomised, controlled clinical trial conducted in 945 participants aged 18-55 years. The immune response to Menactra and to Typhim Vi when given concurrently was comparable to the immune response when Menactra or Typhim Vi was given alone.

5.2 Pharmacokinetic Properties

No pharmacokinetic studies have been performed.

5.3 Preclinical Safety Data

Genotoxicity.

No genotoxicity studies have been conducted with Menactra.

Carcinogenicity.

No carcinogenicity studies have been conducted with Menactra.

4 Clinical Particulars

4.1 Therapeutic Indications

Menactra is indicated for active immunisation of individuals 9 months through 55 years of age for the prevention of invasive meningococcal disease caused by N. meningitidis serogroups A, C, Y and W-135.
Menactra is not indicated for the prevention of meningitis caused by other microorganisms or for the prevention of invasive meningococcal disease caused by N. meningitidis serogroup B.
Menactra is not indicated for treatment of meningococcal infections.
Menactra is not indicated for immunisation against diphtheria.

4.3 Contraindications

Known hypersensitivity to any component of Menactra including diphtheria toxoid, or a life threatening reaction after previous administration of a vaccine containing similar components, are contraindications to vaccine administration.

4.4 Special Warnings and Precautions for Use

Do not administer by intravascular injection: ensure that the needle does not penetrate a blood vessel.

Guillain-Barré syndrome.

Persons previously diagnosed with Guillain-Barré syndrome (GBS) may be at increased risk of GBS following receipt of Menactra. The decision to give Menactra should take into account the potential benefits and risks.
GBS has been reported in temporal relationship following administration of Menactra. The risk of GBS following Menactra vaccination was evaluated in a post-marketing retrospective cohort study (see Section 4.8).

Prior to vaccination.

Febrile or acute disease.

Vaccination must be postponed in case of acute severe febrile disease. However, a minor febrile or non-febrile illness (e.g. a cold) is not usually a reason to postpone immunisation.

Anaphylaxis.

As with all injectable vaccines, appropriate medical treatment and supervision should be readily available for immediate use in case of a rare anaphylactic reaction following the administration of vaccine. As a precautionary measure, adrenaline (epinephrine) injection (1:1,000) must be immediately available in case of unexpected anaphylactic or serious allergic reactions.

Individual history.

Before administration, all appropriate precautions should be taken to prevent adverse reactions. This includes a review of the patient's previous immunisation history, the presence of any contraindications to immunisation, the current health status, and history concerning possible sensitivity to the vaccine or similar vaccine.
Syncope has been reported following vaccination with Menactra. Procedures should be in place to prevent falling injury and manage syncopal reactions.

Special patient groups.

Thrombocytopenia or bleeding disorders.

Menactra has not been evaluated in individuals with thrombocytopenia or bleeding disorders. As with any other vaccine administered intramuscularly, the vaccine risk versus benefit for individuals at risk of haemorrhage following intramuscular injection must be evaluated. If the decision is made to administer any product by intramuscular injection to such individuals, it should be given with caution, with steps taken to avoid the risk of haematoma formation following injection.

Immunosuppression.

The immunogenicity of Menactra could be reduced by immunosuppressive treatment. In such cases it is recommended to postpone the vaccination until the end of the immunosuppression.
Menactra has been evaluated in about 300 Human Immunodeficiency Virus (HIV)-infected subjects. Menactra was safe and immunogenic in this population.

Protection.

Menactra may not protect 100% of individuals.
Menactra will only protect against N. meningitidis A, C, Y and W-135 serogroups and will not protect against N. meningitidis serogroup B disease or any other microorganisms.
Although an antibody response to diphtheria toxoid may occur, Menactra should not be considered as an immunising agent against diphtheria. No changes in the schedule for administering routine vaccines containing diphtheria toxoid are recommended.

Use in the elderly.

Safety and effectiveness of Menactra in adults older than 55 years have not been established.

Paediatric use.

Menactra is approved for use in children from 9 months of age.

Effects on laboratory tests.

Interference of Menactra with laboratory tests has not been studied.

4.5 Interactions with Other Medicines and Other Forms of Interactions

For information regarding concomitant administration of Menactra with other vaccines, see Section 4.8 and Section 5.1.
If the vaccine is used in individuals under immunosuppressive therapy, the expected immune response may not be obtained.
Menactra must not be mixed with any vaccine in the same syringe. Separate injection sites should be used in case of concomitant administration.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There were no effects on the mating performance or fertility of female mice intramuscularly injected with Menactra (at one fifth of the clinical dose) two weeks prior to mating. The effect of Menactra on male fertility has not been evaluated (see also Use in pregnancy).
(Category B1)
In female mice intramuscularly injected with Menactra vaccine (one fifth of the clinical dose per animal or at least 60 times the clinical dose on a mg/kg body weight basis) two weeks prior to mating and on gestation days 6 and 18, no maternal toxicity or effects on embryofetal and postnatal development were observed. However, no Sanofi Pasteur sponsored clinical trials with the primary objective of evaluating Menactra vaccine in pregnant women have been performed and spontaneously reported post-marketing data on the use of this vaccine in pregnant women are limited. The vaccine should be used during pregnancy only when clearly needed, such as during an outbreak or prior to necessary travel to an endemic area, and only following an assessment of the risks and benefits.
Sanofi Pasteur maintains a Menactra pregnancy registry to prospectively collect data from healthcare providers of patients who received Menactra during pregnancy. The objective of this pregnancy registry is to collect and analyse the outcome of exposure to Menactra 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 surveillance system. The experience with Menactra exposure during pregnancy, however, remains limited.
Healthcare providers are encouraged to inform Sanofi Pasteur of any pregnant women who receive Menactra for their inclusion in the vaccination pregnancy registry by calling 1800 818 806 (in Australia) or 0800 283 684 (in New Zealand).
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-induced maternal antibodies. However, the effect on breast-fed infants of the administration of Menactra to their mothers has not been studied. The potential benefits to the mother and risks to the infant should be considered before administering Menactra to a nursing woman.

4.8 Adverse Effects (Undesirable Effects)

Clinical trials experience.

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 adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to vaccine use and for approximating rates of those events.

Children 9 through 18 months of age.

The safety of Menactra was evaluated in 4 clinical studies that enrolled approximately 3,700 infants 9-18 months of age. At 12 months of age these children also received one or more other recommended vaccines [MMRV or MMR and Varicella Virus Vaccine Live (V), PCV7, Hepatitis A Vaccine (HepA)]. A control group of 997 children was enrolled at 12 months of age and received two or more childhood vaccines [MMRV (or MMR + V), PCV7, HepA] at 12 months of age (Section 5.1).
The primary safety study was a controlled trial that enrolled 1256 children who received Menactra at 9 and 12 months of age. At 12 months of age these children received MMRV (or MMR + V), PCV7 and HepA.

Individuals 2 through 55 years of age.

The safety of Menactra was evaluated in 8 clinical studies that enrolled 10,057 participants aged 2-55 years who received Menactra and 5266 participants who received Menomune-A/C/Y/W-135. The three primary safety studies were randomised, active-controlled trials that enrolled participants 2-10, 11-18 and 18-55 years of age, respectively.

Solicited adverse events in the primary safety studies.

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 (Table 1) were injection site tenderness and irritability.
The most frequently reported solicited local and systemic adverse reactions in children aged 2-10 years (Table 2) were injection site pain and irritability, respectively. Injection site redness, induration or swelling, diarrhoea, and drowsiness were also very common. In adolescents, ages 11-18 years (Table 3), and adults, ages 18-55 years (Table 4), the most commonly reported were injection site pain, headache and fatigue. Except for redness in adults, local reactions were more frequently reported after Menactra vaccination than after Menomune-A/C/Y/W-135 vaccination.

Booster vaccination.

The safety of a booster dose of Menactra was evaluated in an open-label, multi-centre trial that enrolled 834 participants to receive a single dose of Menactra 4-6 years after a primary dose. The mean age of participants was 17.8 years (range: 15.0-53.7 years).
Booster vaccination with Menactra was generally safe and well tolerated among adolescents and young 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 most common solicited injection-site and systemic reactions following booster vaccination were pain and myalgia.

Adverse events in concomitant vaccine studies.

Local and systemic reactions when given with routine paediatric vaccines.

In the primary safety study, 1378 US children were enrolled to receive Menactra alone at 9 months of age and Menactra plus one or more other routinely administered vaccines (MMRV, PCV7 and HepA) at 12 months of age (N=961). Another group of children received two or more routinely administered vaccines (MMRV, PCV7 and HepA vaccines) (control group, n=321) at 12 months of age. The frequency of occurrence of solicited adverse events is presented in Table 1.

Local and systemic reactions when given with DTPa vaccine.

In a clinical trial conducted in children 4 to 6 years of age, rates of local and systemic reactions were evaluated after administration of Menactra and DTPa. Menactra and DTPa had similar safety profiles and were well tolerated when administered concomitantly or separately.

Local and systemic reactions when given with dTpa vaccine.

In a clinical trial conducted in adolescents 11 to 17 years of age, Tetanus Toxoid, reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (dTpa) and Menactra had similar safety profiles and were well tolerated when administered concomitantly or separately.

Local and systemic reactions when given with Td vaccine.

The two vaccine groups reported similar frequencies of pain, induration, redness and swelling at the Menactra injection site, as well as, at the Td injection site. Pain was the most frequent local reaction reported at both the Menactra and Td injection sites.
The overall rate of systemic adverse events was higher when Menactra and Td vaccines were given concomitantly than when Menactra was administered 28 days after Td. In both groups, the most common reactions were headache and fatigue.

Local and systemic reactions when given with HPV vaccine.

Concomitant administration of Menactra with HPV vaccines has been evaluated in two studies. In both studies, the safety profiles of the vaccines following concomitant administration were similar to those observed when the vaccines were given separately.

Local and systemic reactions when given with Typhim Vi vaccine.

The two vaccine groups reported similar frequencies of pain, induration, redness and swelling at the Menactra injection site, as well as, at the Typhim Vi injection site. Pain was the most frequent local reaction reported at both the Menactra and Typhim Vi injection sites. More participants experienced pain after Typhim Vi vaccination than after Menactra vaccination (76% versus 47%). The majority (70%-77%) of local solicited reactions for both groups at either injection site were reported as mild and resolved within 3 days post-vaccination. In both groups, the most common systemic reaction was headache and fatigue.

Adverse reactions from post-marketing surveillance.

Based on spontaneous reporting, the following additional adverse events have been reported during the commercial use of Menactra. These events have been very rarely reported, however exact incidence rates cannot be calculated precisely, their frequency is qualified as "Not known".

Blood and lymphatic system disorders.

Lymphadenopathy.

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.

General disorders and administrative site conditions.

Large injection site reactions, including extensive limb swelling have been reported. These reactions may be associated with erythema, warmth, tenderness or pain at the injection site.

Post-marketing safety study.

The risk of GBS following receipt of Menactra 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. Of 72 medical chart-confirmed GBS cases, none had received Menactra 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 ranged from 0 to 5 additional cases of GBS per 1,000,000 vaccinees within the 6 week period following vaccination.
Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems (Australia) or https://nzphvc.otago.ac.nz/reporting/ (New Zealand).

4.2 Dose and Method of Administration

Menactra should be administered as a 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.

Primary vaccination.

In children 9 through 23 months of age, Menactra is given as a 2-dose series 3 months apart.
Individuals 2 through 55 years of age receive a single dose.

Booster vaccination.

Menactra can also be used for booster vaccination in accordance with the national recommendation. For further information, refer to the current Immunisation Handbook.
Do not administer by intravascular injection.
Avoid injecting the vaccine intradermally or subcutaneously since clinical studies have not been conducted to establish safety and efficacy of the vaccine using these routes of administration.
For further information, refer to the current Immunisation Handbook.
Parenteral drug products should be inspected visually for container integrity, particulate matter and discoloration prior to administration, whenever solution and container permit.
Menactra must not be mixed with any vaccine in the same syringe. Therefore, separate injection sites and different syringes should be used in case of concomitant administration.
Product is for single use in one patient only. Discard any residue.

4.7 Effects on Ability to Drive and Use Machines

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

4.9 Overdose

No case of overdose has been reported.
For general advice on overdose management, contact the Poisons Information Centre, telephone number 13 11 26 (Australia) or the National Poisons Centre, 0800 POISON or 0800 764 766 (New Zealand).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sodium chloride 4.35 mg (within 0.85% Physiological Saline+ and 0.5 M Phosphate Buffered Saline*, pH 6.8).
Dibasic sodium phosphate 0.348 mg (within 0.5 M Phosphate Buffered Saline*, pH 6.8).
Monobasic sodium phosphate 0.352 mg (within 0.5 M Phosphate Buffered Saline*, pH 6.8).
+0.85% Physiological Saline is composed of sodium chloride in Water for Injections.
*0.5 M Phosphate Buffered Saline is composed of sodium chloride, dibasic sodium phosphate and monobasic sodium phosphate in Water for Injections.

6.2 Incompatibilities

Menactra must not be mixed with any vaccine in the same syringe.

6.3 Shelf Life

24 months.

6.4 Special Precautions for Storage

Store at 2°C to 8°C (Refrigerate. Do not freeze). Product that has been exposed to freezing should not be used. Do not use after expiration date.
Protect from light.

6.5 Nature and Contents of Container

Vial, 1 Dose.
Packs of 1 vial (marketed) or 5 vials (not marketed).

6.6 Special Precautions for Disposal

After use, any remaining vaccine and container must be disposed of safely, according to locally acceptable procedures.

Summary Table of Changes