Sanofi Pasteur MSD Limited

REVAXIS

Suspension for injection in pre-filled syringe

Diphtheria, tetanus and poliomyelitis (inactivated) vaccine (adsorbed, reduced antigen(s) content)

Each dose (0.5 ml) contains:

Active ingredients:

Purified diphtheria toxoid ............ not less than 2 IU* (5 Lf)

Purified tetanus toxoid ............ not less than 20 IU* (10 Lf)

Inactivated poliomyelitis virus type 1**....................... 40 D antigen units***

Inactivated poliomyelitis virus type 2**………………..……………... 8 D antigen units***

Inactivated poliomyelitis virus type 3**…………………………….…32 D antigen units***

aluminium hydroxide as adsorbant…………………………………… 0.35 mg (as aluminium)

For a full list of excipients, see section 6.1

* As lower confidence limit (p = 0.95) of activity measured according to the assay described in the European Pharmacopoeia.

** Produced in Vero cells.

*** Or equivalent antigenic quantity determined by a suitable immunochemical method

Suspension for injection in pre-filled syringe.

The vaccine has a cloudy white appearance.

REVAXIS is indicated for active immunisation against diphtheria, tetanus and poliomyelitis in children from six years of age, adolescents and adults as a booster following primary vaccination.

REVAXIS is not intended for primary immunisation.

Posology

The dose for children from the age of six years, adolescents and adults is 0.5 ml.

REVAXIS should be administered in accordance with official recommendations and/or local practice regarding the use of vaccines that provide reduced dose diphtheria toxoid plus tetanus toxoid in combination with inactivated poliomyelitis viruses.

REVAXIS may be used as a booster following primary immunisation with inactivated or oral poliomyelitis vaccines (IPV or OPV). There are no clinical data available regarding the use of REVAXIS in individuals with an incomplete, or no, history of a primary series of diphtheria and tetanus toxoids or of vaccinations against poliomyelitis.

Although REVAXIS has not been studied in subjects with tetanus-prone injuries, studies have shown that it induces similar tetanus antitoxin titres to Td vaccine. REVAXIS may therefore be used in subjects with tetanus-prone injuries if concomitant vaccination against diphtheria and poliomyelitis is desirable.

Method of Administration

REVAXIS is for intramuscular injection only. The recommended injection site is the deltoid region.

REVAXIS must not be administered by intradermal or intravascular routes.

Under certain conditions (e.g. bleeding disorders) REVAXIS may be administered as a deep subcutaneous injection.

For further instructions for use see section 6.6.

Hypersensitivity to diphtheria, tetanus or poliomyelitis vaccines or to any other ingredient of the vaccine.

Hypersensitivity to neomycin, streptomycin or polymyxin B. These are used during production and traces may remain in the vaccine.

Acute severe febrile illness. The presence of a minor infection is not a contraindication.

Neurological complications following an earlier immunisation against diphtheria and/or tetanus.

As for all vaccines, appropriate medical treatment should be readily available for immediate use in case of an anaphylactic reaction following vaccination.

REVAXIS should under no circumstances be administered intravascularly. The intradermal route must not be used either.

The immunogenicity of the vaccine could be reduced in immunosuppressed subjects. Where possible, vaccination should be postponed until immune function has recovered. However, vaccination of subjects with chronic immunodeficiency, such as AIDS, is recommended even if the antibody response might be limited.

REVAXIS must be administered with caution to subjects with thrombocytopenia or a bleeding disorder since bleeding may occur following an intramuscular administration to such subjects.

In order to minimise the risk of adverse events, REVAXIS should not be administered to subjects who completed a primary vaccination course or received a booster of a vaccine containing diphtheria or tetanus toxoids within the previous five years.

If Guillain-Barré syndrome or brachial neuritis has occurred following receipt of prior vaccine containing tetanus toxoid, the decision to give any vaccine containing tetanus toxoid should be based on careful consideration of the potential benefits and possible risks.

REVAXIS may be administered at the same time as other vaccines or immunoglobulins provided that the injections are made at separate site.

Subjects who are taking immunosuppressive agents may not respond to REVAXIS (see section 4.4).

The effect of REVAXIS on embryo-foetal development has not been assessed in animals. No teratogenic effect of vaccines containing diphtheria or tetanus toxoids, or inactivated poliovirus has been observed following use in pregnant women. However, this vaccine should not be administered to pregnant women unless it is considered urgent to boost immunity.

REVAXIS may be administered to breastfeeding women.

Vertigo has been reported following vaccination.

The adverse events are ranked under headings of frequency using the following convention:

Very common: (1/10)

Common: (1/100 to <1/10)

Uncommon: (1/1,000 to <1/100)

Rare: (1/10,000 to <1/1,000)

Very rare: (<1/10,000), not known (cannot be estimated from the available data)

Data from pre-approval clinical studies

In clinical studies, the most common events occurring after vaccine administration were local injection site reactions (pain, erythema, induration and oedema) reported by 65 to 80% of subjects in each trial. These usually had their onset within the 48 hours following vaccination and persisted for 1 to 2 days. These reactions are sometimes accompanied by injection site nodules.

Blood and lymphatic system disorders:

Uncommon: lymphadenopathy

Nervous system disorders

Common: headache

Ear and labyrinth disorders

Common: vertigo

Gastrointestinal disorders

Common: nausea / vomiting

Musculoskeletal and connective tissue disorders

Uncommon:myalgia

Rare: arthralgia

General disorders and administration site conditions

Very common: local reactions (injection site pain, injection site erythema, injection site induration, injection site oedema and injection site nodule)

Common: pyrexia

Uncommon:malaise

Data from post-marketing surveillance:

Based on spontaneous reporting, the following additional adverse events have been reported during the commercial use of REVAXIS.

These events have been very rarely reported, however exact incidence rates cannot precisely be calculated.

Nervous system disorders

Gastrointestinal disorders

Abdominal pain, diarrhoea

Skin and subcutaneous tissue disorders

allergic-type reactions such as urticaria, various types of rash, and face oedema

Musculskelettal and connective tissue disorders

General disorders and administration site conditions

Large injection site reaction (>50 mm), including extensive limb swelling from the injection site beyond one or both joints have been reported. These reactions start within 24-72 hours after vaccination, may be associated with erythema, warmth, tenderness or pain at the injection site and resolve spontaneously within 3-5 days.

Pallor, asthenia, usually occurring and resolving within a few days, chills, influenza-like symptoms, mostly the same day as the vaccination

Immune system disorder:

systemic allergic / anaphylactic reactions including shock

Not documented.

Pharmacotherapeutic group: Vaccine against diphtheria, tetanus and poliomyelitis

ATC code: J07CA01

During clinical studies, the immunogenicity of REVAXIS was evaluated in 661 healthy subjects aged six to 78 years. In subjects vaccinated within ten years of a previous dose of diphtheria/tetanus/poliomyelitis vaccine, more than 99% achieved protective antibody levels for diphtheria, tetanus and poliomyelitis (types 1, 2 and 3) one month after receiving REVAXIS .

In a clinical study carried out in 113 healthy subjects aged 40 to 78 years who received their last vaccination against diphtheria, tetanus and poliomyelitis more than ten years ago, REVAXIS elicited a satisfactory booster response.

Antibody persistence over a two-year period was assessed in 113 healthy adults. Two years after receiving a dose of REVAXIS the proportions of subjects with protective titres against diphtheria, tetanus and poliomyelitis (types 1, 2 and 3) were 100%, 94.7% and 100% respectively. In a clinical study in 151 healthy children aged six to nine years, antibody titres at one month after a dose of REVAXIS were approximately three-fold higher than those seen in the healthy adults at two years post-dose. Therefore, it may be anticipated that antibody levels in children would be at least as good as those observed in adults at two years post-dose.

Evaluation of pharmacokinetic properties is not required for vaccines.

Preclinical data reveal no special hazard for humans based on conventional studies of safety, specific toxicity and compatibility of ingredients.

Phenoxyethanol

Formaldehyde

Medium 199*

Water for injections

* Medium 199 is a complex medium of amino acids, mineral salts, vitamins, polysorbate 80 and other substances diluted in water for injections.

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

3 years

Store in a refrigerator (2°C to 8°C).

Do not freeze. Discard the vaccine if it has been frozen.

0.5 ml of suspension in pre-filled syringe (0.5 ml, type I glass) with a plunger-stopper (chlorobromobutyl elastomer) and attached needle and needle-guard (natural rubber or polyisoprene elastomer).

0.5 ml of suspension in pre-filled syringe (0.5 ml, type I glass) with a plunger-stopper (chlorobromobutyl elastomer) and tip-cap (chlorobromobutyl elastomer), without needle.

Packs of 1, 10 and 20 syringes.

0.5 ml of suspension in pre-filled syringe (0.5 ml, type I glass) with a plunger-stopper (chlorobromobutyl elastomer) and tip-cap (chlorobromobutyl elastomer), with 1 or 2 separate needles (for each syringe).

Packs of 1 and 10 syringes.

Not all pack sizes and presentations may be marketed.

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

The vaccine's normal appearance is a cloudy white suspension that may sediment during storage. Shake the pre-filled syringe well to distribute uniformly the suspension before administering the vaccine.

Parenteral biological products should be inspected visually for extraneous particulate matter and/or discolouration prior to administration. In the event of either being observed, discard the vaccine.

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

PA 544/35/1

3^rd June 2003/4^th April 2008

April 2008