Havrix 1440 Adult is indicated for active immunisation against hepatitis A virus
(HAV) infection in subjects at risk of exposure to HAV.
Havrix 1440 Adult will not prevent hepatitis infection caused by other agents such
as hepatitis B virus, hepatitis C virus, hepatitis E virus or other pathogens known to
infect the liver.
In areas of low to intermediate prevalence of hepatitis A, immunisation with
Havrix 1440 Adult is particularly recommended in subjects who are, or will be, at
increased risk of infection such as:
Travellers. Persons travelling to areas where the prevalence of hepatitis A is high.
These areas include Africa, Asia, the Mediterranean basin, the Middle East,
Central and South America.
Armed Forces. Armed Forces personnel who travel to higher endemicity areas or
to areas where hygiene is poor have an increased risk of HAV infection. Active
immunisation is indicated for these individuals.
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 centers, nursing, medical and paramedical
personnel in hospitals and institutions, especially gastroenterology and paediatric
units, sewage workers, food handlers, among others.

Persons at increased risk due to their sexual behaviour. Homosexuals, persons with
multiple sexual partners.
Haemophiliacs.
Abusers of Injectable Drugs.
Contacts of Infected Persons.
Since virus shedding of infected persons may occur for a prolonged period, active
immunisation of close contacts is recommended.
Persons who require protection as part of hepatitis A outbreak control or because of
regionally elevated morbidity.
Specific population groups known to have a higher incidence of hepatitis A. For
example, American Indians, Eskimos, recognised community-wide HAV
epidemics.
Subjects with chronic liver disease or who are at risk of developing chronic liver
disease (e.g. Hepatitis B (HB) and Hepatitis C (HC) chronic carriers and alcohol
abusers).
In areas of intermediate to high prevalence of hepatitis A (eg Africa, Asia, the
Mediterranean basin, the Middle East, Central and South America) susceptible
individuals may be considered for active immunisation.

Posology
Primary vaccination
- Adults from age 16 years and onwards
A single dose of Havrix 1440 Adult (1.0 ml suspension) is used for primary
immunisation.
Booster vaccination
After primary vaccination with Havrix 1440 Adult, a booster dose is
recommended in order to ensure long term protection. This booster dose should be
given at any time between 6 months and 5 years, but preferably between 6 and
12 months after the primary dose (see Pharmacodynamics).
Method of administration
Havrix 1440 Adult is for intramuscular administration. The vaccine should be injected
in the deltoid region in adults and children, in the antero-lateral part of the thigh in young
children.
The vaccine should not be administered in the gluteal region.
The vaccine should not be administered subcutaneously/intradermally since
administration by these routes may result in a less than optimal anti-HAV antibody
response.
Havrix 1440 Adult should under no circumstances be administered
intravascularly.
Havrix 1440 Adult should be administered with caution to subjects with
thrombocytopenia or a bleeding disorder since bleeding may occur following an
intramuscular administration to these subjects. Firm pressure should be applied to the
injection site (without rubbing) for at least two minutes.

As with other vaccines, the administration of Havrix 1440 Adult should be postponed in
subjects suffering from acute severe febrile illness. The presence of a minor infection,
however, is not a contraindication for vaccination.
It is possible that subjects may be in the incubation period of a hepatitis A infection at the
time of vaccination. It is not known whether Havrix 1440 Adult 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 a single dose of Havrix 1440
Adult and such patients may therefore require administration of additional doses of
vaccine.
As with all injectable vaccines, appropriate medical treatment and supervision should
always be readily available in case of a rare anaphylactic event following the
administration of the vaccine.
Syncope (fainting) can occur following, or even before, any vaccination as a
psychogenic response to the needle injection. It is important that procedures are in place
to avoid injury from faints.
Havrix 1440 Adult can be given to HIV-infected persons.
Seropositivity against hepatitis A is not a contraindication.

Since Havrix 1440 Adult is an inactivated vaccine its concomitant use with other
inactivated vaccines is unlikely to result in interference with the immune responses.
Havrix 1440 Adult can be given concomitantly with any of the following vaccines:
typhoid, yellow fever, cholera (injectable), tetanus, or with monovalent and
combination vaccines comprised of measles, mumps, rubella and varicella.
Concomitant administration of immunoglobulines does not impact the protective effect
of the vaccine.
When concomitant administration of other vaccines or of immunoglobulins is
considered necessary, the products must be given with different syringes and needles and
at different injection sites.

Pregnancy
Adequate human data on use during pregnancy and adequate animal reproduction
studies are not available. However, as with all inactivated viral vaccines the risks to the
foetus are considered to be negligible. Havrix 1440 Adult should be used during
pregnancy only when clearly needed.
Lactation
Adequate human data on use during lactation and adequate animal reproduction studies
are not available. Although the risk can be considered as negligible, Havrix 1440
Adult should be used during lactation only when clearly needed.

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

The safety profile presented below is based on data from more than 5300 subjects.

Frequencies per dose are defined as follows:

Very common:  ³ 10%

Common:          ³ 1% and < 10%

Uncommon:      ³ 0.1% and < 1%

Rare:                  ³ 0.01% and < 0.1%

Very rare:          < 0.01%

To report any side effect(s):

National Pharmacovigilance centre (NPC)

·         Fax: +966-11-205-7662

·         Call NPC at +966-11-208222, Ext: 2317-2356-2353-2354-2334-2340

·         Toll-free: 8002490000

·         E-mail: npc.drug@sfda.gov.sa

·         Website: www.sfda.gov.sa/npc

-GlaxoSmithKline - Head Office, Jeddah

• Tel:  00966(012)6536666
• Fax: 00966(012)6536660
• P.O Box 55850, Jeddah 21544, Saudi Arabia.

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

Pharmaco-therapeutic group: Hepatitis A vaccines, 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 were 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) (see also Pre-clinical Safety Data).

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 of Havrix™ 1440 Adult or Havrix™ 720 Junior. In clinical trials, virtually, all vaccinees were seropositive one month after the booster dose.

However, if the booster dose has not been given between 6 and 12 months after the primary dose, the administration of this booster dose can be delayed up to 5 years. In a comparative trial, a booster dose given up to 5 years after the primary dose has been shown to induce similar antibody levels as a booster dose given between 6 and 12 months after the primary 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 17 years allows prediction that at least 95% and 90% of subjects will remain seropositive (≥15 mIU/ml) 30 and 40 years after vaccination, respectively (see Table 1).

Table 1: Predicted proportion with anti-HAV level ≥15 mIU/ml and 95% confidence intervals for studies HAV-112 and HAV-123.

Current data do not support the need for 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-wide outbreaks (Alaska, Slovakia, USA, UK, Israel and Italy). These studies demonstrated that vaccination with Havrix™ led to termination of the outbreaks. A vaccine coverage of 80% led to termination of the outbreaks 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™ immunisation programme was implemented for children in their second year of life:

•      In Israel, two retrospective database studies showed 88% and 95% reduction in hepatitis A incidence in the general population 5 and 8 years after the implementation of the vaccination program, respectively. Data from 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. In paediatric hospitals in Panama City, confirmed acute hepatitis A cases were no longer diagnosed 4 years after implementation of the vaccination programme.

•      The observed reductions in hepatitis A incidence in the general population (vaccinated and non-vaccinated) in both countries demonstrate herd immunity.

NA

Appropriate safety tests have been performed.
In an experiment in 8 non-human primates, the animals were exposed to an heterologous
hepatitis A strain and vaccinated 2 days after exposure. This post exposure vaccination
resulted in protection of all animals.

Amino acids for injections, disodium phosphate, monopotassium phosphate, polysorbate 20, potassium chloride, sodium chloride, water for injections.

Neomycin sulphate is present as residual from the manufacturing process

Havrix™ should not be mixed with other vaccines or immunoglobulins in the same syringe.

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

Havrix™ should be stored at +2°C to +8°C.

Do not freeze; discard if vaccine has been frozen.

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.

Havrix™ is presented in a glass vial or pre-filled glass syringe.

The vials and syringes are made of neutral glass type I, which conforms to European Pharmacopoeia Requirements.

Not all presentations are available in every country.

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

Havrix is a trademark of the GSK group of companies.