Data Sheet

MeNZB

Suspension for Injection, Meningococcal group B Outer Membrane Vesicle (OMV) vaccine.

QUALITATIVE AND QUANTITATIVE COMPOSITION

1 dose (0.5 ml) contains:

Outer membrane vesicles from Neisseria meningitidis group B (strain NZ 98/254)

measured as amount of total protein* .......................................................25 microgram

* Adsorbed on aluminium hydroxide (1.65 milligram)

For excipients, see List of excipients.

PHARMACEUTICAL FORM

Suspension for injection.

Off-white, opalescent suspension.

Clinical particulars

Therapeutic indications

MeNZB is indicated for primary immunisation against group B meningococci with the P1.7-b,4* PorA protein ("New Zealand strain"). The population at risk should be vaccinated with MeNZB to prevent serious systemic disease (septicaemia and meningitis) caused by New Zealand strain serogroup B meningococci.

This vaccine is for use in individuals aged 6 months or older.

* According to new classification terminology: P1.7-2,4

Posology and method of administration

This vaccine is for use in individuals aged 6 months or older.

Posology

Three doses, each of 0.5 ml, with an interval of 6 weeks between doses.

Currently the necessity for a booster dose has not been established but is under evaluation (see Pharmacodynamic Properties).

Method of Administration

Intramuscular injection.

The vaccine (0.5 ml) is intended for deep intramuscular injection, preferably in the anterolateral thigh in infants/toddlers and in the deltoid region of the non dominant arm in toddlers, older children, adolescents and adults.

The vaccine must not be injected intravenously, subcutaneously, or intradermally and must not be mixed with other vaccines in the same syringe.

Contraindications

Persons having shown signs of hypersensitivity to any component of the vaccine or persons having shown signs of hypersensitivity after previous administration of MeNZB.

As with other vaccines, administration of MeNZB should usually be postponed in persons with an acute febrile illness (fever > 38,5°C).

Warning and Precautions

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

In the event of any foreign particulate matter and/or variation of the normal physical aspect (off-white, opalescent suspension) being observed, the vaccine should not be used.

Data of concomitant use of other vaccines are not yet available. Separate injection sites must be used if other vaccines are administered at the same time (see Interaction with other medicinal products and other forms of interaction).

MeNZB has not been evaluated in persons with thrombocytopenia or bleeding disorders. For such individuals the risk of haemorrhage following intramuscularly injection must be evaluated against the benefit of vaccination.

Protection against invasive meningococcal diseases caused by any of the other serogroups of meningococcal bacteria has not been proven for MeNZB. The same holds true for N. meningitidis serogroup B other than the New Zealand strain.

Therefore it cannot be assumed that MeNZB will protect against meningococcal diseases caused by any of the other types of meningococcal bacteria (A, C, 29-E, H, I, K, L, W-135, X, Y, or Z, including non-typeable). Furthermore, protection should not be assumed against N. meningitidis serogroup B other than the New Zealand strain. Complete protection against infection caused by the New Zealand strain cannot be guaranteed.

Before the injection of any vaccine, the person responsible for administration should 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 the rare case of an anaphylactic event following administration of a vaccine.

Prior to administration of any dose of MeNZB, the patient, parent or guardian should 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.

In individuals deficient in producing antibodies or taking medication with an immunosuppressive effect, vaccination may not result in an appropriate protective antibody response. While HIV infection is not a contraindication, MeNZB 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 MeNZB; however, the degree of protection that would be afforded is unknown.

Any acute infection and febrile illness is reason for delaying the use of MeNZB except when, in the opinion of the physician, withholding the vaccine entails a greater risk. A minor illness with a temperature of = 38,5°C, such as a mild upper respiratory infection, is not usually reason to postpone immunisation.

Patients, parents or guardians should be informed of the immunisation schedule for this vaccine. Precautions such as the use of antipyretic measures following receipt of this vaccine should be relayed to the parent or guardian and the need to report any adverse event stressed.

Interaction with other medicinal products and other forms of interaction

There are no known interactions with any medications.

MeNZB must not be mixed with other vaccines in the same syringe.

Separate injection sites must be used if other vaccines are administered at the same time (see Warnings and Precautions). Concomitant use of MeNZB with other vaccines should only be considered if medically important and not on a routine basis.

Pregnancy and lactation

Pregnancy

There are no adequate data from the use of MeNZB in pregnant women.

Animal studies are insufficient with respect to effects on pregnancy, and/or embryonal/foetal development, and/or parturition, and/or postnatal development (see Preclinical Safety Data). The potential risk for humans is unknown.

Lactation

Information on the safety of the vaccine during lactation is not available.

Effects on ability to drive and use machines

The vaccine is unlikely to produce an effect on the ability to drive or use machines.

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

Undesirable effects

Adverse Reactions from Clinical Studies with MeNZB

Adverse reactions reported across all age groups are provided below. The age groups are Infants (700 doses) , toddlers (772 doses), children (1606 doses) and adults (173 doses ). Note the following descriptions of frequency have been defined as: Very common (=10%); common (=1% and <10%); uncommon (=0.1% and <1%); rare (=0.01% and <0.1%); very rare (<0.01%). Adverse reactions were collected on the day of vaccination and each day following for up to 7 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 induration) were very common. Tenderness/pain was the most common injection site reaction. However, these were not usually clinically significant. Severe injection site reactions persisting for more than 7 day were uncommon.

Crying (infants), irritability, sleepiness, change in eating habits, diarrhoea and vomiting (toddlers), and headache were very common after vaccination. These occurred at a similar rate in the control vaccine groups, where studied.

Very commonly reported adverse events include headache, myalgia, and arthralgia in adults. Irritability, sleepiness, change in eating habits, vomiting, and fever of at least 38.5 °C was very common in toddlers and infants.

There have been very rare reports of febrile convulsion following MeNZB vaccination; individuals have usually rapidly recovered.

Adverse Reactions from Clinical Studies with the Norwegian parent vaccine, MenBvac, an OMV vaccine manufactured with a strain from a different sero-(sub)type (B:15:P1.7,16)

For MenBvac further adverse events were reported including anaphylactic reactions, flu-like symptoms, haematuria, Guillain-Barré syndrome, myalgic encephalomyelitis/chronic fatigue syndrome. All these reactions were very rare and occured in adolescents and/or adults.

Additional information:

Although MenBvac is the parent vaccine of MeNZB the above mentioned adverse events of MenBvac may not necessarily be expected to happen with MeNZB.

Overdose

Vaccine formulations of MeNZB containing the double amount of the active ingredient (50 microgram per dose) but the same adjuvant content have been administered in clinical trials with similar reactogenicity to the 25 microgram formulations.

PHARMACOLOGICAL PROPERTIES

Pharmacodynamic properties

Pharmacotherapeutic group: Meningococcal vaccines, ATC code: J07A H06

Mechanism of action:

A vaccination schedule of 3 doses MeNZB given with an interval of 6 weeks between doses induces a humoral immune response against the New Zealand strain. The degree and quality of the cellular immune response is not yet established. An immune response against common antigens on other N. meningitidis serogroup B sero-subtypes may be elicited.

The duration of protection is not yet established.

Pharmacodynamic effects:

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

Clinical efficacy:

No prospective efficacy trials have been performed with MeNZB.

Standardised serological correlates for protection have not been definitively established for OMV meningococcal B vaccines; these are under study. The serum bactericidal assay (SBA) provides however a good indication of a probable protection. The SBA referenced in the text below used human serum as a source of complement and has been validated.

Data from trials using a vaccination schedule of 3 doses MeNZB given with an interval of 6 weeks demonstrate that 74% infants, 75% toddlers, 74% children, and 91% adults developed a 4-fold rise (compared with pre-vaccination values) in serum bactericidal antibody titres 4-6 weeks after the third dose. The necessity for a booster dose has not been established but is under evaluation.

Pharmacokinetic properties

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

Preclinical safety data

Preclinical data reveal no special hazard for humans based on conventional studies of single and repeated dose toxicity.

PHARMACEUTICAL PARTICULARS

List of excipients

Sodium chloride

Histidine buffer

For adjuvant see Qualitative and quantitative composition.

Incompatibilities

This vaccine must not be mixed with other medicinal products.

Shelf life

MenNZB has a shelf life of 18 months.

Special precautions for storage

Store at +2°C to +8°C (in a refrigerator). Do not freeze. Protect from light.

Nature and contents of container

MeNZB is presented as a 0.5 ml suspension for injection in a colourless single dose Type I glass vial closed with bromobutyl rubber stoppers.

MeNZB is supplied in packs containing ten single dose vials.

Instructions for use, handling and disposal

The vaccine (0.5 ml) is intended for deep intramuscular injection. Care must be taken to ensure that the vaccine is not injected into a blood vessel. Shake before use.

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

Further information.

Provisional Consent for the distribution of MeNZB has been granted under Section 23 of the Medicines Act 1981. This consent is valid for 2 years from 8 July 2004. This vaccine is for use in individuals aged 6 months or older.

Medicine Classification

Prescription Medicine

Name and Address

Sponsor in New Zealand:

Multichem NZ Ltd
8 Apollo Drive
Mairangi Bay
Auckland
New Zealand

Date of Preparation

August 2004