EPAXAL®
Vaccine for active immunisation against hepatitis A

Qualitative and quantitative composition
1 vaccine dose (0.5 ml) contains at least 24 IU of inactivated hepatitis A virus (strain RG-SB), propagated in human diploid cell cultures.
The virus particles are adsorbed in virosomes, as an immunoadjuvant system consisting of highly purified surface antigens of the Influenza virus
(10 micrograms) strain A/Singapore/6/86 (H1N1), phospholipids lecithin (80 micrograms) and cephalin (20 micrograms).

The other ingredients are referred in: Excipients.

Pharmaceutical form
Emulsion for injection in prefilled syringe.

Pharmacotherapeutic class
EPAXAL is a vaccine against hepatitis A, which contains hepatitis A virus, strain RG-SB, it is propagated in MRC-5 human diploid cells and inactivated with formaldehyde.

Market Authorisation Holder
Istituto Sieroterapico Berna S.r.l. Via Bellinzona 39
I-22100 Como
Itália

Representative in Portugal:
ANGELINI FARMACÊUTICA, LDA. Rua João Chagas 53, Piso 3,
1495-072 Algés

Indications
Active immunisation against hepatitis A in children from 1 year of age, and adults.

Contraindications and most frequent side effects
Hypersensitivity to any of the vaccine’s components.
Hypersensitivity to eggs and chicken protein or formaldehyde.
In cases of acute infectious disease with fever, vaccination with Epaxal should be postponed.

The possible undesirable effects are mild and of short duration. The frequencies of adverse events provided were base on clinical studies. The most common adverse reactions fatigue, local pain and headache, were registered at frequencies of 6 to 32%, 5 to 25% and 6 to 25% respectively.

Very common (=1/10)
Nervous system disorders: Headache
General disorders and administration site conditions:
Local pain, fatigue

Common (=1/100 and <1/10)
Metabolism and nutrition disorders:
Anorexia
Gastrointestinal disorders:
Mild and transient diarrhoea, nausea
General disorders and administration site conditions:
Injection site reactions (induration, redness, swelling), malaise, fever

Uncommon (=1/1000 and <1/100):
Nervous system disorders:
Dizziness
Skin and subcutaneous tissue disorders:
Skin rash/pruritus
Gastrointestinal disorders:
Vomiting
Musculoskeletal, connective tissue and bone disorders:
Arthralgia

The degree of dizziness is not more pronounced as compared to other vaccines in comparative trials.

A transient and mild rise in levels of liver enzymes was observed on single occasions at the time of vaccination.

As observed with other vaccines, occasional inflammatory diseases of the central and peripheral nervous system may occur, including ascending paralysis up to respiratory paralysis, e.g. Guillain-Barré Syndrome.

Drug interactions and other forms of interactions
A prospectively planned interaction study was performed with yellow fever vaccine in 55 subjects. In addition, concomitant vaccination against yellow fever, typhoid fever, poliomyelitis, diphtheria, tetanus, meningococci A + C, as well as concomitant malaria prophylaxis was studied as part of a travel prophylaxis program in 38 subjects.

A prospectively planned interaction study was performed with concomitant whole influenza virus vaccine in 163 subjects. The concomitant administration does neither impair immunogenicity against hepatitis A nor influenza. In addition, immunogenicity against hepatitis A is independent of the level of influenza pre-immunisation titres.

These results indicate that Epaxal can be administered simultaneously with the above vaccines but in separate syringes, as well as with malaria prophylaxis.

Special precautions for use
Influenza hemagglutinin contained in Epaxal does not provide an alternative for influenza vaccination.
Immunodeficiency disorders may impair immune response. In splenectomised patients, the booster vaccination should be administered 1 to 6 months after primary immunisation, owing to the lower titres achieved in these subjects. This also applies to other categories of immunocompromised patients.

Experience of the vaccination of children under 1 year of age and adults over 60 years of age is limited.

Effects on pregnant women, breast-feeding women, children, elderly patients and patients with special pathologies
There is no adequate data on the use of Epaxal in pregnant women. The effect of Epaxal on the development of the foetus has not been determined. Like with other inactivated vaccines, lesions in the foetus are not expected. The vaccine should not be given to pregnant women, unless the risk of infection by hepatitis A is increased.

Whether the vaccine passes into the milk of a lactating mother is unknown. Breast-feeding women should use Epaxal with caution.

As it was previously referred, in patients with coagulation disorders the vaccine may be administered by subcutaneous route in the arm.

It was also referred that experience of the vaccination of children under 1 year of age and adults over 60 years of age is limited.

Effects on the ability to drive and use machines
There is no evidence of any vaccine-related reduction in reaction times.

However, the occasional occurrence of dizziness or headache, as also observed occasionally with other vaccines, needs to be considered.

Excipients
0.5 ml of EPAXAL contains sodium chloride and water for injectables.

Posology and method of administration
1 dose of 0.5 ml, injected intramuscularly.
To ensure optimal immune response, the vaccine should be injected into the deltoid muscle. As it was previously referred, in patients with coagulation disorders the vaccine may be administered by subcutaneous route in the arm.

For long-term protection a booster vaccination of 0.05 ml should be administered, preferably 6 to 12 months after the first dose, but it can be administered up to 4 years afterwards, based on the experience with adult travellers.

Epaxal may be alternated with other inactivated hepatitis A vaccines for the first and second booster doses.

Effect duration
Primary vaccination with 0.5 ml Epaxal results in protective antibody titres (min. 20 mIU/ml) in 78-100% of vaccinated subjects for at least 12 months. Booster vaccination with 0.5 ml Epaxal is estimated to prolong the protective efficacy to at least 20 years for at least 95% of the vaccinated subjects. This estimate is based on mathematical modelling and extrapolation of 3-6 years follow up data from subjects in the age range of 16 to 45 years.

Simultaneous active and passive immunisation
If immediate protection against hepatitis A is necessary, Epaxal can be administered concomitantly with human gamma globulin at separate injection sites.

Measures to be adopted in case of overdosage
There are no reports of overdosage. Inadvertent administration of a second dose of 0.5 ml Epaxal has no adverse effects.

Report of undesirable effects
You should inform your doctor or pharmacist about any undesirable effects detected.

Shelf life
2 years.
Check the expiry term stated on the package or in the container’s label.

Special precautions for storage
Store in the refrigerator at 2–8 ºC, protected from light. Do not freeze.

Date of the last revision of the leaflet
March 2005

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