Havrix® Monodose® Vaccine

Each vial or syringe contains 1440 ELISA units/1 ml dose of hepatitis A virus antigen.

For a full list of excipients, see section 6.1.

Vaccine suspension for injection.

Active immunisation against infections caused by hepatitis A virus. The vaccine is particularly indicated for those at increased risk of infection or transmission. For example immunisation should be considered for the following risk groups:

travellers visiting areas of medium or high endemicity, i.e. anywhere outside northern or western Europe, Australia, North America and New Zealand.

military and diplomatic personnel, haemophiliacs and patients, intravenous drug abusers, homosexual men, laboratory workers working directly with the hepatitis A virus, sanitation workers in contact with untreated sewage.

patients with chronic liver disease (including alcoholic cirrhosis, chronic hepatitis B, chronic hepatitis C, autoimmune hepatitis, primary biliary cirrhosis).

close contacts of hepatitis A cases.

Since virus shedding from infected persons may occur for a prolonged period, active immunisation of close contacts may be considered.

Under certain circumstances additional groups could be at increased risk of infection or transmission. Immunisation of such groups should be considered in the light of local circumstances. Such groups might include:

staff and inmates of residential institutions for the mentally handicapped and other institutions where standards of personal hygiene are poor.

staff working in day care centres and other settings with children who are not yet toilet trained.

food packagers or handlers.

In addition there may be other groups at risk or specific circumstances such as an outbreak of hepatitis A infection when immunisation should be given.

Adults (16 years and over)

Primary immunisation consists of a single dose of Havrix Monodose vaccine (1440 ELISA units/ml) given intramuscularly. This provides anti-HAV antibodies for at least one year.

Havrix Monodose confers protection against hepatitis A within 2-4 weeks.

In order to obtain more persistent immunity, a booster dose is recommended between 6 and 12 months after primary immunisation.

Although a booster should be given within 6 – 12 months of the initial vaccination with Havrix Monodose, it has been shown that immunocompetent subjects given a booster up to 3 years after the initial vaccination can develop similar antibody levels to subjects given a booster within the recommended time period. Subjects given a booster up to 5 years after initial vaccination can also show a satisfactory antibody response but approximately 30% of individuals receiving a delayed booster have no detectable anti-HAV antibodies prior to booster dosing.

It is unnecessary to restart the primary vaccination schedule of Havrix Monodose if the booster is administered within 5 years of the primary vaccination.

Current recommendations do not support the need for further booster vaccination among immunocompetent subjects after a 2 dose vaccination course.

The results described above should be considered to apply only to immunocompetent adults.

Havrix Monodose can be used as a booster in subjects previously immunised with any inactivated hepatitis A vaccine.

In the event of a subject being exposed to a high risk of contracting hepatitis A within 2 weeks of the primary immunisation dose human normal immunoglobulin may be given simultaneously with Havrix Monodose at different injection sites.

Children/adolescents (1-15 years)

Havrix Monodose is not recommended (Havrix Junior Monodose should be used).

Method of administration

Havrix Monodose vaccine should be injected intramuscularly in the deltoid region.

The vaccine should never be administered intravenously.

Hypersensitivity to any component of the vaccine. Severe febrile illness.

As for all vaccinations, appropriate medication e.g. epinephrine (adrenaline) should be readily available for immediate use in case of anaphylaxis. Havrix Monodose may contain traces of the antibiotic neomycin B sulphate.

It is possible that subjects may be in the incubation period of a hepatitis A infection at the time of immunisation. It is not known whether Havrix Monodose will prevent hepatitis A in such cases.

In haemodialysis patients and in subjects with an impaired immune system, adequate anti-HAV antibody titres may not be obtained after the primary immunisation and such patients may therefore require administration of additional doses of vaccine.

Syncope (fainting) can occur following, or even before, any vaccination especially in adolescents as a psychogenic response to the needle injection. This can be accompanied by several neurological signs such as transient visual disturbance, paraesthesia and tonic-clonic limb movements during recovery. It is important that procedures are in place to avoid injury from faints.

Simultaneous administration of Havrix at a dose of 720 ELISA units/ml with ISG does not influence the seroconversion rate to Havrix, however, it may result in a lower antibody titre. A similar effect could be observed with Havrix Monodose.

Preliminary data on the concomitant administration of Havrix at a dose of 720 ELISA units/ml, with recombinant hepatitis B virus vaccine suggest that there is no interference in the immune response to either antigen. On this basis and since it is an inactivated vaccine interference with immune response is unlikely to occur when Havrix Monodose is administered with other inactivated or live vaccines. When concomitant administration is considered necessary the vaccines must be given at different injection sites.

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

The effect of Havrix Monodose on foetal development has not been assessed.

However, as with all inactivated viral vaccines the risks to the foetus are considered negligible. Havrix Monodose should be used during pregnancy only when clearly needed.

The effect on breast fed infants of the administration of Havrix Monodose to their mothers has not been evaluated in clinical studies. Havrix Monodose should therefore be used with caution in breast feeding women.

Not applicable.

The safety profile presented below is based on data from more than 5300 subjects that participated in clinical trials, plus reactions observed through post-marketing surveillance. It should be noted that it was not possible to calculate the frequency of reactions from the post-marketing data, therefore the frequency is noted as “Not known”.

The most frequently reported reactions are pain and redness at site of injection (Havrix Monodose reports in over 50% of doses, Havrix Junior Monodose reports in 18.2% of doses overall). Swelling at the site of injection was the next most frequently reported reactions.

Frequencies per dose are defined as follows:

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness

* refers to adverse reaction reported only for Havrix Monodose (1ml adult dose)

** refers to adverse reactions reported only for Havrix Junior Monodose (0.5ml children's dose)

# this adverse reaction was identified through post-marketing surveillance but was not observed in randomised controlled clinical trials. The frequency category of rare was estimated from a statistical calculation based on the total number of paediatric patients exposed to Havrix in randomised controlled clinical trials (n=4574).

Cases of overdose have been reported during post-marketing surveillance. Adverse events reported following overdosage were similar to those reported with normal vaccine administration.

Havrix confers immunisation against HAV by stimulating specific immune responses evidenced by the induction of antibodies against HAV.

In clinical studies, 99% of vaccinees seroconverted 30 days after the first dose. In a subset of clinical studies where the kinetics of the immune response was studied, early and rapid seroconversion was demonstrated following administration of a single dose of Havrix in 79% of vaccinees at day 13, 86.3% at day 15, 95.2% at day 17 and 100% at day 19, which is shorter than the average incubation period of hepatitis A (4 weeks).

The efficacy of Havrix was evaluated in different community outbreaks. These studies indicated that administration of a single dose of Havrix contributed to termination of the outbreaks. In one study, vaccine coverage in excess of 80% was followed by termination of the outbreak within 4 to 8 weeks.

In order to ensure long term protection, a booster dose should be given between 6 and 12 months after the primary dose of Havrix Monodose. In clinical trials, virtually all vaccinees were seropositive one month after the booster dose.

Long term persistence of hepatitis A antibody titres following 2 doses of Havrix given 6 to 12 months apart has been evaluated. Data available after 10 years allows prediction that at least 97% of subjects will remain seropositive (>20 mIU/ml) 25 years after vaccination.

Not applicable to vaccine products.

Not applicable to vaccine products.

Aluminium hydroxide gel (3% w/w)

Polysorbate 20

Amino acids for injection

Disodium phosphate

Monopotassium phosphate

Sodium chloride

Potassium chloride

Water for injections.

Not applicable.

36 months.

Store at 2°C - 8°C in a refrigerator. Keep in outer container. Do not freeze.

Colourless glass vials (Type I, Ph Eur) with grey butyl rubber stoppers and aluminium overcaps fitted with avocado coloured flip-off tops containing 1 ml of suspension in packs of one and 10.

1 ml of suspension in prefilled syringe (type I glass) with a plunger stopper (rubber butyl) with or without needles - pack size of 1 or 10.

Not all pack sizes may be marketed.

The vaccine should be inspected visually for any foreign particulate matter and/or variation of physical aspect prior to administration. Before use, the vaccine should be well shaken to obtain a slightly opaque white suspension. Discard the vaccine if the content appears otherwise.

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

SmithKline Beecham plc

Great West Road, Brentford, Middlesex TW8 9GS

Trading as:

GlaxoSmithKline UK

Stockley Park West

Uxbridge

Middlesex

UB11 1BT

PL 10592/0037

18 May 1999

16 April 2012

POM