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.

Persons for whom Hepatitis A is an occupational hazard or for whom there is an increased risk of transmission. These include employees in day care centres, nursing, medical and paramedical personnel in hospitals and institutions, especially gastroenterology and paediatric units, sewage workers and food packagers or handlers.

Haemophiliacs.

Intravenouse drug abusers.

Homosexual men.

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

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

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.

Posology

Adults (16 years and over)

Primary immunisation consists of a single dose given intramuscularly. This provides anti-HAV antibodies for at least one year.

This vaccine 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, 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 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 (see section 5.1).

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 this vaccine at different injection sites.

Children/adolescents (1-15 years)

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

Method of administration

The vaccine should be injected intramuscularly in the deltoid region. The vaccine should not be administered in the gluteal region.

The vaccine should never be administered intravascularly.

The vaccine should not be administered subcutaneously/intradermally since administration by these routes may result in a less than optimal anti-HAV antibody response. In subjects with a bleeding disorder who are at risk of haemorrhage following intramuscular injection (e.g. haemophiliacs), this vaccine may be administered by deep subcutaneous injection as per local guidance. Firm pressure should be applied to the injection site (without rubbing) for at least two minutes.

Hypersensitivity to the active substance, to any of the excipients listed in section 6.1, or to neomycin (present at traces).

Immunisation should be postponed in subjects suffering from an acute severe febrile illness. The presence of a minor infection, such as a cold, should not result in the deferral of vaccination.

As for all vaccinations, appropriate medication e.g. epinephrine (adrenaline) should be readily available for immediate use in case of anaphylaxis.

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.

Excipients

This vaccine contains 166 micrograms phenylalanine in each dose. Phenylalanine may be harmful to patients that have phenylketonuria (PKU).

This medicine contains potassium, less than 1 mmol (39 mg) per 1 mL dose, i.e. essentially 'potassium- free'.

This medicinal product contains less than 1 mmol sodium (23 mg) per 1 mL dose, that is to say essentially 'sodium- free'.

Simultaneous administration of Havrix at a dose of 720 ELISA units/mL with normal immunoglobulin 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. Havrix Monodose can be given concomitantly with monovalent and combination vaccines comprised of measles, mumps, rubella and varicella. 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.

Pregnancy

There are limited amount of data from the use of this vaccine in pregnant women. Animal studies are insufficient with respect to reproductive toxicity. However, as with all inactivated viral vaccines, the risks to the foetus are considered negligible. The use of this vaccine may be considered during pregnancy, if necessary.

Breast-feeding

It is unknown whether this vaccine is excreted in human milk.

A decision must be made whether to discontinue breast-feeding or to abstain from vaccination taking into account the benefit of breast feeding for the child and the benefit of vaccination for the woman.

Fertility

No fertility data are available.

No studies on the effects of Havrix Monodose on the ability to drive and use machines have been performed. However, some of the effects mentioned under section 4.8 “ Undesirable effects” may temporarily affect the ability to drive or use machines.

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).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

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

Pharmacotherapeutic group: Hepatitis A vaccine, ATC code J07BC02.

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

Immune response

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).

Persistence of the immune response

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

Long term persistence of hepatitis A antibody titres has been evaluated following 2 doses of Havrix given 6 to 12 months apart to healthy immunocompetent subjects aged 17 to 40 years. Data available after 17 years allow prediction that at least 95% and 90% of subjects will remain seropositive (> 15 mIU/mL) 30 and 40 years after vaccination, respectively.

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

Efficacy of Havrix for outbreak control

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.

Impact of mass vaccination on disease incidence

A reduction in the incidence of hepatitis A was observed in countries where a two-dose Havrix immunization programme was implemented for children in their second year of life:

• In Israel, a retrospective database study showed up to 95 % reduction in hepatitis A incidence in the general population 8 years after the implementation of the vaccination program. Data from the National Surveillance also showed a 95% reduction in hepatitis A incidence as compared to the pre-vaccination era.

• In Panama, a retrospective database study showed a 90% reduction in reported hepatitis A incidence in the vaccinated population, and 87% in the general population, 3 years after implementation of the vaccination programme.

The observed reduction in hepatitis A incidence in the general population (vaccinated and non-vaccinated) in both countries are consistent with herd immunity.

Not applicable to vaccine products.

Not applicable to vaccine products.

Polysorbate 20

Amino acids for injection (containing phenylalanine)

Disodium phosphate

Monopotassium phosphate

Sodium chloride

Potassium chloride

Water for injections

For adsorbent, see section 2

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

36 months.

Store at 2 ° C - 8 ° C in a refrigerator.

Store in the original package in order to protect from light.

Do not freeze.

Stability data indicate that Havrix is stable at temperatures up to 25° C for 3 days. These data are intended to guide healthcare professionals in case of temporary temperature excursion only.

1 mL of suspension in a pre-filled syringe (type I glass) with a plunger stopper (butyl rubber) and with a rubber tip cap or 1 mL of suspension in a vial (type I glass) with stopper (butyl rubber) with or without needles - pack size of 1 or 10.

The tip cap and rubber plunger stopper of the pre-filled syringe and the stopper of the vial are made with synthetic rubber.

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.

Instructions for the pre-filled syringe

Disposal

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