Sanofi Pasteur MSD Limited

MENJUGATE KIT 10 micrograms powder and solvent for suspension for injection.

Meningococcal group C conjugate vaccine.

One dose (0.5 ml of the reconstituted vaccine) contains:

Conjugated to

For a full list of excipients, see section 6.1.

Powder and solvent for suspension for injection.

Powder (vial): white to off-white

Suspension (syringe): white opalescent

Active immunisation of children from 2 months of age, adolescents and adults, for the prevention of invasive disease caused by Neisseria meningitidis group C.

The use of Menjugate Kit should be determined on the basis of official recommendations.

Posology

There are no data on the use of different Meningococcal group C conjugate vaccines within the primary series or for boosting. Whenever possible, the same vaccine should be used throughout.

Primary immunisation

Infants from 2 months of age up to 12 months: two doses, each of 0.5 ml, should be given with an interval of at least 2 months. (See section 4.5 regarding co-administration of Menjugate Kit with other vaccines).

Children over the age of 12 months, adolescents and adults: a single dose of 0.5 ml.

Booster doses

It is recommended that a booster dose should be given after completion of the primary immunisation series in infants. The timing of this dose should be in accordance with available official recommendations. Information on responses to booster doses and on co-administration with other childhood vaccines is given in sections 5.1 and 4.5, respectively.

The need for booster doses in subjects primed with a single dose (i.e. aged 12 months or more when first immunised) has not yet been established (see section 5.1).

Method of Administration

Intramuscular injection. The vaccine (0.5 ml) is intended for deep intramuscular injection, preferably in the anterolateral thigh in infants and in the deltoid region in older children, adolescents and adults.

The vaccine must not be injected intravenously, subcutaneously or intradermally.

Menjugate Kit must not be mixed with other vaccines in the same syringe. Separate injection sites must be used if more than one vaccine is being administered.

Hypersensitivity to the active substance(s) or to any of the excipients of the vaccine, including diphtheria toxoid.

Persons who have shown signs of hypersensitivity after previous administration of Menjugate Kit.

As with other vaccines, administration of Menjugate Kit must be postponed in subjects with an acute severe febrile illness.

Before the injection of any vaccine, 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 must always be readily available in case of a rare anaphylactic event following administration of the vaccine.

Prior to administration of any dose of Menjugate Kit, the parent or guardian must be asked about the personal history, family history, and recent health status of the vaccine recipient, including immunisation history, current health status and any adverse event after previous immunisations.

The benefits of vaccination with meningococcal group C conjugate vaccine must be reviewed in light of the incidence of N. meningitidis group C infection in a given population before the institution of a widespread immunisation campaign.

Menjugate Kit will not protect against meningococcal diseases caused by any of the other types of meningococcal bacteria (A, B, 29-E, H, I, K, L, W-135, X, Y, or Z, including non-typed). Complete protection against meningococcal group C infection cannot be guaranteed.

No data on the applicability of the vaccine for post-exposure outbreak control are as yet available.

In individuals deficient in producing antibodies, vaccination may not result in an appropriate protective antibody response. While HIV infection is not a contraindication, Menjugate Kit has not been specifically evaluated in the immunocompromised. Individuals with complement deficiencies and individuals with functional or anatomical asplenia may mount an immune response to meningococcal group C conjugate vaccines; however, the degree of protection that would be afforded is unknown.

Although symptoms of meningism such as neck pain/stiffness or photophobia have been reported there is no evidence that the vaccine causes meningococcal C meningitis.

Clinical alertness to the possibility of co-incidental meningitis must therefore be maintained.

Conjugate vaccines containing Cross Reacting Material 197 (CRM197) should not be considered as immunising agents against diphtheria. No changes in the schedule for administering vaccines containing Diphtheria Toxoid are recommended.

Any acute infection or febrile illness is reason for delaying the use of Menjugate Kit except when, in the opinion of the physician, withholding the vaccine entails a greater risk. A minor afebrile illness, such as a mild upper respiratory infection, is not usually reason to defer immunisation.

The potential risk of apnoea and the need for respiratory monitoring for 48-72 hours should be considered when administering the primary immunisation series to very premature infants (born 28 weeks of gestation) and particularly for those with a previous history of respiratory immaturity. As the benefit of vaccination is high in this group of infants, vaccination should not be withheld or delayed.

The vaccine must not be injected intravenously, subcutaneously or intradermally.

Menjugate Kit has not been evaluated in persons with thrombocytopenia or bleeding disorders.

The risk versus benefit for persons at risk of haemorrhage following intramuscular injection must be evaluated.

Parents must be informed of the immunisation schedule for this vaccine. Precautions such as useful antipyretic measures for this vaccine must be relayed to the parent or guardian and the need to report any adverse event must be stressed.

The tip cap of the syringe contains 10% Dry Natural Rubber. Although the risk for developing allergic latex reactions is very small, healthcare professionals are encouraged to consider the benefit risk prior to administering this vaccine to patients with known history of hypersensitivity to latex.

There are no data in adults aged 65 years and older (see section 5.1)

Menjugate Kit must not be mixed with other vaccines in the same syringe. Separate injection sites must be used if more than one vaccine is being administered.

Administration of Menjugate Kit at the same time as (but, for injected vaccines, at a different injection site) the following vaccines in clinical studies did not reduce the immunological response to any of these other antigens:

- Polio (inactivated polio vaccine [IPV] and oral polio vaccine);

- Diphtheria [D] and Tetanus [T] toxoids alone or in combination with whole cell or acellular Pertussis [aP];

- Haemophilus Influenzae type B [Hib] conjugate vaccine;

- Hepatitis B [HBV] vaccine administered alone or at the same time as combined vaccine containing D, T, Hib, IPV and aP;

- Combined measles, mumps and rubella vaccine;

- 7-valent pneumococcal conjugate vaccine (Prevenar). The effect of concomitant administration of Menjugate with 7-valent pneumococcal conjugate vaccine (Prevenar) and a hexavalent vaccine [DTaP-HBV-IPV-Hib] on immune responses was assessed in infants vaccinated at median ages of approximately 2, 4.5 and 6.5 months. The potential for immune interference has not been assessed at other primary immunisation schedules.

Minor variations in GMT antibody titres were observed between studies; however, the clinical significance, if any, of these observations is not established.

In various studies with different vaccines, concomitant administration of meningococcal group C conjugates with combinations containing aP components (with or without IPV, hepatitis B surface antigen or Hib conjugates) has been shown to result in lower SBA GMTs compared to separate administrations or to coadministration with whole cell pertussis vaccines. The proportions reaching SBA titres of at least 1:8 or 1:128 are not affected. At present, the potential implications of these observations for the duration of protection are not known.

Pregnancy

There are no data on the use of this vaccine in pregnant women. Animal studies in rabbit at different stages of gestation have not demonstrated a risk to the foetus following administration of Menjugate Kit. Nevertheless, considering the severity of meningococcal group C disease pregnancy should not preclude vaccination when the risk of exposure is clearly defined.

Lactation

Information on the safety of the vaccine during lactation is not available. The benefit-risk ratio must be examined before making the decision as to whether to immunise during lactation.

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

Dizziness has been very rarely reported following vaccination. This may temporarily affect the ability to drive or use machines.

The following descriptions of frequency have been defined: Very common (10%); common (1% and<10%); uncommon (0.1% and <1%); rare (0.01% and <0.1%); very rare (<0.01%).

Adverse Reactions from clinical trials

Adverse reactions reported across all age groups are provided below. Adverse reactions were collected on the day of vaccination and each day following for at least 3 and up to 6 days. The majority of reactions were self-limiting and resolved within the follow-up period.

In all age groups injection site reactions (including redness, swelling and tenderness/pain) were very common (ranging from 1 in 3 older children to 1 in 10 pre-school children). However, these were not usually clinically significant. Redness or swelling of at least 3cm and tenderness interfering with movement for more than 48 hours was infrequent where studied.

Fever of at least 38.0°C is common (ranging from 1 in 20 in infants and toddlers to 1 in 10 in pre-school children), but does not usually exceed 39.1°C, particularly in older age groups.

In infants and toddlers symptoms including crying and vomiting (toddlers) were common after vaccination. Irritability, drowsiness, impaired sleeping, anorexia, diarrhoea and vomiting (infants) were very common after vaccination. There was no evidence that these were related to Menjugate Kit rather than concomitant vaccines, particularly DTP.

Very commonly reported adverse events include myalgia and arthralgia in adults. Drowsiness was commonly reported in younger children. Headache was very common in secondary school children and common in primary school children.

Adverse reactions reported across all age groups

General disorders and administration site conditions

Additional reactions reported in infants (first year of life) and toddlers (second year of life)

Gastrointestinal disorders

General disorders and administration site conditions

Additional reactions reported in older children and adults

Gastrointestinal disorders

Musculoskeletal and connective tissue disorders

General disorders and administration site conditions

Adverse Reactions from Post Marketing Surveillance (for all age groups)

The most commonly reported suspected reactions in post marketing surveillance include dizziness, pyrexia, headache, nausea, vomiting and faints.

The frequencies given below are based on spontaneous reporting rates, for this and other Meningococcal group C conjugate vaccines and have been calculated using the number of reports received as the numerator and the total number of doses distributed as the denominator.

Nervous system disorders

There have been very rare reports of seizures following Menjugate Kit vaccination; individuals have usually rapidly recovered. Some of the reported seizures may have been faints. The reporting rate of seizures was below the background rate of epilepsy in children. In infants seizures were usually associated with fever and were likely to be febrile convulsions.

There have been very rare reports of visual disturbances and photophobia following vaccination with Meningococcal group C conjugate vaccines, usually in conjunction with other neurological symptoms like headache and dizziness.

Respiratory, thoracic and mediastinal disorders

Apnoea in very premature infants ( 28 weeks of gestation) (see section 4.4)

Gastrointestinal disorders

Skin and subcutaneous tissue disorders

Musculoskeletal and connective tissue disorders

Immune system disorders

Relapse of nephrotic syndrome has been reported in association with Meningococcal group C conjugate vaccines.

No case of overdose has been reported. Since each injection is a single dose of 0.5 millilitres, overdose is unlikely.

Pharmacotherapeutic group: Meningococcal vaccines, ATC code: J07A H.

Immunogenicity

No prospective efficacy trials have been performed.

The serum bactericidal assay (BCA) referenced in the text below used human serum as a source of complement. Serum bactericidal assay (BCA) results achieved with human serum as a source of complement are not directly comparable with those achieved with rabbit serum as a source of complement.

Data on the use of a 2-dose primary immunisation series are available from a clinical trial that compared a 2, 3, 4 month vaccination schedule to a 2, 4 month vaccination schedule in 241 infants. One month after completion of the primary series nearly all subjects had attained hBCA titres 1:8 (100% and 98% in respective groups). At 28 days after a challenge dose of unconjugated MenC vaccine at 12 months of age, all of 50 subjects primed with three doses and 54/56 (96%) primed with two doses achieved hBCA titres 1:8.

Compared to licensed unconjugated meningococcal polysaccharide vaccines in clinical studies, the immune response induced by Menjugate Kit was shown to be superior in toddlers, children and adolescents, and was comparable in adults (see table).

Additionally, unlike unconjugated polysaccharide vaccines, Menjugate Kit induces immunologic memory after vaccination, although the duration of protection is not yet established.

There are no data in adults aged 65 years or older.

MenPS = licensed unconjugated Meningococcal polysaccharide vaccine.

(1) = groups A, C, W-135 and Y, containing 50μg of group C per dose.

(2) = groups A and C, containing 50μg of group C per dose.

No pharmacodynamic studies have been conducted with Menjugate Kit, in accordance with its status as a vaccine.

Post-marketing surveillance following an immunisation campaign in the UK

Estimates of vaccine effectiveness from the UK's routine immunisation programme (using various quantities of three meningococcal group C conjugate vaccines) covering the period from introduction at the end of 1999 to March 2004 demonstrated the need for a booster dose after completion of the primary series (three doses administered at 2, 3 and 4 months). Within one year of completion of the primary series, vaccine effectiveness in the infant cohort was estimated at 93% (95% confidence intervals 67, 99). However, more than one year after completion of the primary series, there was clear evidence of waning protection.

Up to 2007 the overall estimates of effectiveness in age cohorts from 1-18 years that received a single dose of meningococcal group C conjugate vaccine during the initial catch-up vaccination programme in the UK fall between 83 and 100%. The data show no significant fall in effectiveness within these age cohorts when comparing time periods less than a year or one year or more since immunisation.

No pharmacokinetic studies have been conducted with Menjugate Kit, in accordance with its status as a vaccine.

Non-clinical data reveal no special hazard for humans based on conventional studies of repeated dose toxicity and toxicity to reproduction (embryofetal studies).

Vial containing MenC-CRM197 Conjugate

- Mannitol

- Sodium dihydrogen phosphate monohydrate

- Disodium phosphate – heptahydrate

Syringe containing aluminium hydroxide

- Sodium chloride

- Water for injections.

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

3 years

Following reconstitution, the product should be used immediately.

The two components of the product may have different expiry dates. The outer carton bears the earlier of the two dates and this date must be respected. The carton and ALL its contents must be discarded on reaching this outer carton expiry date.

Store in a refrigerator (2^oC – 8^oC).

Do not freeze.

Keep the vial and the syringe in the outer carton in order to protect from light.

Menjugate Kit is presented as a vial of powder (type I glass), with a stopper (bromobutyl rubber) and 0.6 ml of solvent in a syringe (type I glass) with a stopper (bromobutyl rubber) and a tip cap (chlorobutyl rubber)- pack size of 1,5 or 10 single doses.

Not all pack sizes may be marketed.

The lyophilised vaccine will require preparation by reconstitution with aluminium hydroxide solvent.

Gently agitate the syringe containing the aluminium hydroxide solvent. Remove the tip cap from the syringe and attach a suitable needle. Use the whole content of the syringe (0.6 mL of suspension) to reconstitute the Meningococcal group C conjugate vaccine vial.

Gently shake the reconstituted vial until the vaccine is dissolved (this will ensure the antigen is bound to the adjuvant). Taking care not to withdraw the plunger completely out of the barrel of the syringe, withdraw the full contents of the vial into the syringe.

Please note that it is normal for a small residual amount of liquid to remain in the vial following withdrawal of the dose. Please ensure that no air bubbles are present in the syringe before injecting the vaccine.

Following reconstitution the vaccine is a slightly opaque, colourless to light yellow suspension, free from visible foreign particles. In the event of any foreign particulate matter and/or variation of physical aspect being observed, discard the vaccine.

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

Novartis Vaccines and Diagnostics S.r.l.,

Via Fiorentina 1,

53100 Siena,

Italy.

PA919/4/2

22nd April 2005/1st March 2005

May 2009