Sanofi Pasteur MSD Limited

Rabies Vaccine BP 2.5 IU/ml, Powder and solvent for suspension for injection

After reconstitution, 1 dose (1ml) contains:

Rabies virus* (inactivated, strain PM/WI 38 1503-3M)……..2.5 IU

*produced in human diploid MRC-5 cells

For a full list of excipients, see section 6.1

Powder and solvent for suspension for injection

The powder is pinkish beige to orangey yellow.

The solvent is a clear, colourless solution.

For prophylactic immunisation against rabies. Treatment of patients following suspected rabies contact.

Administer by intramuscular injection. The vaccine should be administered into the deltoid region. For instructions on the reconstitution of the vaccine before administration, see section 6.6.

Adults, Elderly and Children

Prophylaxis:

Three injections each of 1 millilitre given on days 0, 7 and 28. A single reinforcing dose should be given at two or three year intervals to those at continued risk.

If, for whatever reason, it has not been possible to give a full course of three injections, it is probable that, in the majority of subjects, two doses may be adequate to confer protection, provided these were given four weeks apart. Subjects receiving only two injections who remain at continued risk should receive a reinforcing dose 6-12 months later, with further reinforcing doses given at two to three year intervals.

Treatment

(i) In persons known to have adequate prophylaxis:

(II) In persons with no, or possibly inadequate, prophylaxis:

Pre Exposure

Known systemic hypersensitivity reaction to any component of Rabies Vaccine BP or after previous administration of the vaccine or a vaccine containing the same components as Rabies Vaccine BP.

Vaccination must be postponed in case of febrile and/or acute disease.

Post Exposure

Since declared rabies infection generally results in death, there are no contraindications to post exposure vaccination.

In subjects with a history of allergy there may be an increased risk of side-effects and this possibility should be taken into account.

As with all vaccines, appropriate facilities and medication such as epinephrine (adrenaline) should be readily available for immediate use in case of anaphylaxis or hypersensitivity following injection.

The vaccine may contain traces of neomycin and betapropiolactone which are used during the manufacturing process. Caution must be exercised when the vaccine is administered to subjects with hypersensitivity to betapropiolactone, neomycin, and other antibiotics of the same class

Rabies Vaccine BP should not be administered to patients with bleeding disorders such as haemophilia or thrombocytopenia, or to persons on anticoagulant therapy unless the potential benefit clearly outweighs the risk of administration. If the decision is taken to administer Rabies Vaccine BP in such persons, it should be given with caution with steps taken to avoid the risk of haematoma formation following injection.

The potential risk of apnoea and the need for respiratory monitoring for 48-72 h 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.

Corticosteroids and immunosuppressive treatments may interfere with antibody production and cause the failure of the vaccination. It is therefore advisable to perform a neutralising antibody assay 2 – 4 weeks after the last injection.

Administration of an additional dose should be considered if the antibody titre is less than 0.5 IU/ml (using an RFFIT analysis – Rapid Fluorescent Focus Inhibition Test).

Data on limited number of exposed pregnancies do not allow a conclusion on the potential risk of Rabies HDCV for pregnancy or for the health of the foetus/newborn child. Due to the severity of disease, pregnancy is not considered a contraindication to post exposure prophylaxis. If there is substantial risk of exposure to rabies, pre-exposure prophylaxis may also be indicated during pregnancy.

Due to the severity of the disease, breast feeding is not considered a contraindication and treatment must not be discontinued. It is not known whether this vaccine is excreted in human breast milk, thus no recommendation on continuation/discontinuation of breastfeeding can be made.

No adverse effects reported.

Adverse reaction information is derived from clinical trials and worldwide post- marketing experience.

Two randomised controlled trials where Rabies Vaccine BP has been studied in both children (n=199) using pre-exposure schedule (3 doses, IM) and adults (n=124) using the post exposure schedule (5 doses, IM) have been selected to represent safety clinical data.

Within each system organ class the adverse reactions are ranked under headings of frequency, using the following convention:

Very common (>1/10)

Common (>1/100, <1/10)

Uncommon (>1/1000, <1/100)

Not known (cannot be estimated from the available data because only reported post marketing and not in clinical trials)

The most frequent adverse reactions are injection site pain and headache.

• Blood and lymphatic system disorders

• Immune system disorders

These reactions have been associated with the presence of betapropiolactone-altered human albumin (including the production of IgE antibodies in the vaccine).

Allergic reactions occurred more frequently among persons receiving booster than primary vaccination. Further information on allergic reactions see section 4.4.

• Nervous system disorders

• Gastrointestinal disorders

• Musculoskeletal and connective tissue disorders

• General disorders and administration site conditions

Additional information on special populations:

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

Not applicable.

The vaccine is a lyophilised, stabilised suspension of inactivated Wistar rabies virus strain PM/WI 38-1503-3M, cultured in human diploid cells (MRC₅) and inactivated by beta-propiolactone.

Not applicable.

None stated.

Human Albumin Solution.

Solvent: Water for Injections (1 millilitre).

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

3 years

Once reconstituted, the vaccine must be used immediately.

Store between +2°C and +8°C in a refrigerator. Do not freeze.

Powder:

Single dose (Ph Eur type 1 glass) vial with elastomeric stopper (chlorobutyl) and aluminium overcap.

Solvent:

1.0 ml disposable syringe (type 1 glass) with a plunger-stopper (halobutyl) without needle and with a tip- cap (chlorobromobutyl or styrene butadiene rubber). Up to two separate needles (for each syringe) may be included in the pack.

1.0 ml disposable syringe (type I glass) with a plunger-stopper (halobutyl) with attached needle and needle shield (chlorobromobutyl or synthetic polyisoprene rubber).

Pack of 1 vial and 1 prefilled syringe.

Not all pack presentations may be marketed

For needle free syringes, the needle should be pushed firmly on to the end of the prefilled syringe and rotated through 90 degrees.

Reconstitute the freeze-dried vaccine by introducing the solvent provided in the pre-filled syringe into the vial of powder. Shake carefully until complete suspension of the powder is obtained. Following reconstitution, the suspension will be a pinkish colour and free from particles. Withdraw the suspension from the vial into the syringe prior to intramuscular injection.

Shake well immediately before use.

Use immediately after reconstitution.

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

Sanofi Pasteur MSD Limited

Block A, Second Floor

Cookstown Court

Old Belgard Road

Tallaght

Dublin 24

Ireland

PA 544/14/1

Date of first authorisation: 12^th December 1994

Date of last renewal: 11^th November 2008

11/2010