1 dose (1 ml) contains:

Inactivated Hepatitis A virus (HM175 strain)* 1440 ELISA Units

Vi polysaccharide of Salmonella typhi (Ty2 strain) 25 micrograms

adsorbed on aluminium hydroxide (adjuvant) Total: 0.5 milligrams Al³⁺

* propagated on MRC-5 human diploid cells

For excipients, see 6.1.

Active immunisation against hepatitis A virus infection and typhoid fever for adults and adolescents 15 years of age and older.

Hepatyrix should be given in accordance with official recommendations.

Posology

Primary vaccination

A single dose of 1.0 ml is recommended for both adults and adolescents aged 15 years and older.

The vaccine should be given at least two weeks prior to risk of exposure to typhoid and hepatitis A (see section 5.1 for immunogenicity data).

Booster vaccination

In order to provide long term protection against infection caused by hepatitis A virus, a booster dose of an inactivated hepatitis A vaccine is recommended at any time between 6 and 12 months after a single dose of Hepatyrix.

Hepatyrix may also be given as a single dose of 1.0 ml for booster vaccination between 6 and 12 months following primary immunisation with an inactivated hepatitis A vaccine to subjects who also require protection against typhoid fever.

Subjects who remain at risk of typhoid fever should be revaccinated using a single dose of Vi polysaccharide vaccine every 3 years, unless it is also appropriate to administer a booster of hepatitis A vaccine, in which case Hepatyrix may be used.

As Hepatyrix has not been studied in subjects under 15 years of age, it is not recommended for use in this age group.

Method of Administration

Hepatyrix is for intramuscular administration in the deltoid region.

The vaccine should not be administered in the gluteal region.

Hepatyrix should under no circumstances be administered intravascularly.

Hepatyrix should not be administered subcutaneously/intradermally since administration by these routes may result in a suboptimal response to the vaccine.

In exceptional circumstances, Hepatyrix may be administered subcutaneously to subjects with thrombocytopenia or bleeding disorders 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 after the injection.

Hepatyrix should not be administered to subjects who have had a hypersensitivity reaction to a previous dose of Hepatyrix or a dose of either of the monovalent vaccines Havrix™ and Typherix™.

Hepatyrix should not be administered to subjects who are known to be hypersensitive to any component of the vaccine.

Hepatyrix contains traces of neomycin. The vaccine should not be used in subjects with known hypersensitivity to neomycin.

As with other vaccines, the administration of Hepatyrix should be postponed in subjects suffering from acute severe febrile illness. The presence of a minor infection, however, is not a contra-indication for vaccination.

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.

In subjects with an impaired immune system, adequate anti-HAV and anti-Vi antibody titres may not be obtained after a single dose of Hepatyrix and such patients may therefore require administration of additional doses of vaccine. If possible, vaccination should be delayed until the completion of any immunosuppressive treatment. Subjects with chronic immunodeficiency such as HIV infection may be vaccinated if the underlying immunodeficiency allows the induction of an antibody response, even if limited.

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 Hepatyrix will prevent clinically apparent hepatitis A infections in such cases.

Hepatyrix will not prevent infection caused by other hepatitis-causing agents such as hepatitis B virus, hepatitis C virus, hepatitis E virus or other pathogens known to infect the liver.

Hepatyrix protects only against typhoid fever caused by Salmonella enterica serotype Typhi. Protection is not conferred against paratyphoid fever or infections with any other serotypes of S. enterica.

As with any vaccine, a protective immune response may not be elicited in all vaccinees.

Hepatyrix must not be mixed with any other vaccine in the same syringe.

If Hepatyrix is to be given at the same time as (an)other injectable vaccine(s), the vaccines should always be administered at different injection sites.

Hepatyrix contains purified inactivated hepatitis A antigen and purified Vi capsular polysaccharide. Although concomitant use with other inactivated vaccines has not specifically been studied, it is anticipated that no interaction will be observed.

Concomitant administration of yellow fever vaccine with Hepatyrix has not been specifically assessed. However, based on data obtained from the concomitant administration of various monovalent vaccines (purified Vi polysaccharide typhoid vaccine or inactivated hepatitis A vaccine) with yellow fever vaccine, no interference with the immune responses to any of these antigens would be expected.

The effect of concomitant administration of immunoglobulins on the immunogenicity of Hepatyrix has not been assessed. Therefore, interference with the immune response cannot be ruled out.

Pregnancy

Adequate human data on use during pregnancy and adequate animal reproduction studies are not available. Hepatyrix should only be used after careful consideration of the risk-benefit relationship.

Lactation

Adequate data on the administration of Hepatyrix to women who are breast-feeding their infants are not available. Hepatyrix should be used during breast-feeding only when clearly needed.

Some of the effects mentioned under section 4.8 “Undesirable effects” may affect the ability to drive or operate machinery.

In controlled clinical studies, the most commonly reported reactions after administration of Hepatyrix were those at the site of injection. All local and general symptoms resolved without any sequelae.

Frequencies are reported as:

Very common: 10%

Common: 1% and < 10%

Uncommon: 0.1% and < 1%

Rare: 0.01% and < 0.1%

Very rare: < 0.01%

Application site:

Very common: pain, erythema

Common: swelling

Systemic adverse events with at least a suspected causal relationship to vaccination are listed below:

Body as a whole:

Common: malaise, headache, general aches, fever

Gastro-intestinal system:

Common: nausea

Skin and appendages:

Common: itching

During postmarketing surveillance, the following undesirable events have been reported in temporal association with Hepatyrix vaccination:

Body as a whole:

Very rare: allergic reactions, including anaphylaxis and anaphylactoid reactions

Cardiovascular general:

Very rare: syncope

Skin and appendages:

Very rare: skin rashes

In controlled clinical studies with the GlaxoSmithKline monovalent hepatitis A vaccine, systemic adverse events such as vomiting and loss of appetite have been reported.

During postmarketing surveillance, the following undesirable effects have been reported very rarely with the GlaxoSmithKline monovalent hepatitis A vaccine : convulsions, arthralgia, myalgia, neurological manifestations, including transverse myelitis, Guillain-Barre syndrome and neuralgic amyotrophy.

Pharmaco-therapeutic group: Bacterial and viral vaccines combined, ATC code JO7C (combined)/P03 (typhoid)/C02 (Hepatitis A)

Hepatyrix confers immunity against typhoid fever and HAV infection by inducing specific anti-Vi and anti-HAV antibodies.

In clinical studies involving 462 subjects of 15-50 years of age, seropositivity rates for anti-HAV and anti-Vi antibodies were 89.8% and 97.5% respectively two weeks after primary immunisation. At month 1, seropositivity rates for anti-HAV and anti-Vi antibodies were 99.0% and 95.7% respectively.

In a clinical study where a group of 99 subjects received a booster dose of hepatitis A vaccine 12 months following the initial dose of Hepatyrix, all subjects were seropositive for anti-HAV antibodies one month later (i.e. at month 13).

When Hepatyrix was given 12 months following primary vaccination with the hepatitis A vaccine in a cohort of 97 subjects, the seropositivity rates for anti-Vi and anti-HAV antibodies were 88.2% and 100% respectively one month later (i.e. at month 13).

In a long term clinical study, the persistence of antibodies has been evaluated in 118 subjects up to 36 months after vaccination with Hepatyrix and a booster dose of Havrix™ 1440 administered six months later. At month 36, 53% were still seropositive with respect to anti-Vi antibody and 100% for anti-HAV antibodies. These seropositivity rates are similar to those seen in subjects in other clinical trials who were followed up for a similar period after vaccination with either of the licensed monovalent Vi polysaccharide vaccines or a licensed hepatitis A vaccine.

With respect to the hepatitis A component, based on data generated after administration of a booster dose of a monovalent hepatitis A vaccine between six and twelve months following the initial dose of the monovalent hepatitis A vaccine, it is predicted that anti-HAV antibodies persist for many years (at least 10 years).

Sodium chloride

2-phenoxyethanol (preservative)

Water for injections.

For adjuvants, see section 2.

Store at 2°C – 8°C (in a refrigerator).

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

Do not freeze. Discard if vaccine has been frozen.

1 ml of suspension in prefilled syringe (type I glass) with a plunger stopper (butyl rubber) with or without needles. Packs of 1 and 10 (with needles). Packs of 1, 10, 20 and 50 (without needles).

Not all packs may be marketed.

The vaccine's normal appearance is a cloudy white suspension, which may sediment during storage. Shake the container well to distribute the suspension uniformly before administering the vaccine.

The vaccine should be inspected visually for extraneous particulate matter and/or discolouration prior to administration. Any unused vaccine or waste material should be disposed of safely in accordance with local regulations.

Administrative Data

SmithKline Beecham plc

Trading as:

GlaxoSmithKline UK,

Stockley Park West,

Uxbridge,

Middlesex, UB11 1BT8.