4.1. Therapeutic indications

AVAXIM is indicated for active immunisation against infection caused by hepatitis A virus in susceptible adults and adolescents of 16 years of age and above.

The use of AVAXIM should be based on official recommendations.

4.2. Posology and method of administration

Posology

The recommended dosage for subjects of at least 16 years of age is 0.5 millilitres for each injection.

Initial protection is achieved with one single dose of vaccine. Protective levels of antibody may not be reached until 14 days after administration of the vaccine.

In order to provide long-term protection, a second dose (booster) of an inactivated hepatitis A vaccine should be given. The second dose is preferably given between 6 and 12 months but may be administered up to 36 months after the first dose (see section 5.1). It is predicted that HAV antibodies persist for many years (beyond 10 years) after the second dose.

The vaccine may be used to provide the second dose (booster) in subjects from 16 years of age who received another inactivated hepatitis A vaccine (monovalent or with purified Vi polysaccharide typhoid) 6 months to up to 36 months previously.

Paediatric population

AVAXIM is not recommended for use in children of less than or equal to 15 years of age due to insufficient data on safety and efficacy.

Method of administration

AVAXIM should be administered by intramuscular injection in the deltoid region. AVAXIM must not be administered intradermally or intravascularly.

The vaccine should not be administered into the buttocks, due to the varying amount of fatty tissue in this region, contributing to variability in effectiveness of the vaccine.

In exceptional circumstances (e.g. in patients with thrombocytopenia or in patients at risk of haemorrhage), the vaccine may be injected by the subcutaneous route.

Precautions to be taken before handling or administering the medicinal product.

For instructions on preparation of the medicinal product before administration, see section 6.6.

4.3. Contraindications

• Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1 or to neomycin, which may be present in the vaccine in trace amounts.

• Hypersensitivity following a previous injection of this vaccine.

• Vaccination should be delayed in subjects with an acute severe febrile illness.

4.4. Special warnings and precautions for use

As with all vaccines, appropriate medical treatment and supervision should be readily available for immediate use in case of rare anaphylactic reaction following vaccination. AVAXIM should only be given by a physician or health care worker trained in the administration of vaccines.

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.

AVAXIM has not been studied in patients with impaired immunity. The immune response to AVAXIM could be impaired by immunosuppressive treatment or in immunodeficiency states. In such cases, it is recommended to measure the antibody response to be sure of protection and, if possible, to wait for the end of any suppressive treatment before vaccination. Nevertheless, vaccination of subjects with chronic immunodeficiency such as HIV infection is recommended although the antibody response may be limited.

Because of the incubation period of hepatitis A, infection may be present but not clinically apparent at the time of vaccination. The effect of AVAXIM on individuals late in the incubation period of hepatitis A has not been documented.

Individuals having grown up in areas of high endemicity and/or with a history of jaundice may be immune to hepatitis A, in which case the vaccine is unnecessary. Testing for antibodies to hepatitis A prior to a decision on immunisation should be considered in such situations. If not, seropositivity against hepatitis A is not a contraindication. AVAXIM is as well tolerated in seropositive as in seronegative subjects (see Section 4.8).

AVAXIM does not provide protection against infection caused by hepatitis B virus, hepatitis C virus, hepatitis E virus or by other liver pathogens.

As no studies have been performed with AVAXIM in subjects with liver disease, the use of this vaccine in such subjects should be considered with care.

As with any vaccine, vaccination may not result in a protective response in all susceptible vaccinees.

AVAXIM contains ethanol, phenylalanine, potassium and sodium

AVAXIM contains 2 mg of alcohol (ethanol) in each 0.5 ml dose. The small amount of alcohol in this medicine will not have any noticeable effects

AVAXIM contains 10 microgram phenylalanine in each 0.5 ml dose which is equivalent to 0.17 microgram/kg for a 60 kg person. Phenylalanine may be harmful for people with phenylketonuria (PKU), a rare genetic disorder in which phenylalanine builds up because the body cannot remove it properly.

AVAXIM contains less than 1mmol of potassium (39 mg) and sodium (23 mg) per dose, that is to say essentially 'potassium-free' and 'sodium-free'.

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

4.5. Interaction with other medicinal products and other forms of interaction

No clinical data on concomitant administration of AVAXIM with other inactivated vaccine(s) or recombinant hepatitis B virus vaccine have been generated. When concurrent administration is considered necessary, AVAXIM must not be mixed with other vaccines in the same syringe, and other vaccines should be administered at different sites with different syringes and needles.

Seroconversion rates were not modified when AVAXIM was given at the same time as but at a different injection site to a Vi polysaccharide typhoid vaccine or a yellow fever vaccine reconstituted with a Vi polysaccharide typhoid vaccine.

Concomitant administration of immunoglobulin and AVAXIM at two separate sites may be performed. Seroconversion rates are not modified, but antibody titres could be lower than after vaccination with AVAXIM alone. Therefore, consideration should be given to whether or not the subject is likely to be at long-term risk of exposure.

No interaction with other medicinal products is currently known.

4.6. Fertility, pregnancy and lactation

Pregnancy

There are no adequate data from the use of hepatitis A vaccine (inactivated, adsorbed) in pregnant women. Animal studies are insufficient with respect to effects on pregnancy, embryonal/foetal development, parturition or postnatal development. The potential risk for humans is unknown.

AVAXIM should not be used during pregnancy unless clearly necessary and following an assessment of the risks and benefits.

Breast-feeding

The use of this vaccine is possible during breast-feeding.

4.7. Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed.

4.8. Undesirable effects

Summary of the safety profile

In clinical trials, adverse reactions were usually mild and confined to the first few days after vaccination with spontaneous recovery.

Reactions were less frequently reported after the booster dose than after the first dose.

In subjects seropositive against hepatitis A virus, AVAXIM was as well tolerated as in seronegative subjects.

Tabulated list of adverse reactions

Adverse reaction data are derived from clinical trials and worldwide post-marketing experience.

Within each system organ class, the adverse reactions are ranked under headings of frequency, most frequent reactions first, using the following convention:

• Very common (≥1/10),

• Common (≥1/100 to <1/10),

• Uncommon (≥1/1000 to <1/100),

• Rare (≥1/10000 to <1/1000),

• Very rare (<1/10000),

• Not known (cannot be estimated from available data): the adverse reactions have been reported following commercial use of AVAXIM based on spontaneous reporting. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency.

Adverse reactions

Frequency

Blood and lymphatic system disorders

Lymphadenopathy

Not known

Immune system disorders

Anaphylactic reaction

Not known

Nervous system disorders

Headache

Common

Vasovagal syncope in response to injection

Not known

Gastrointestinal disorders

Nausea

Common

Vomiting

Common

Decreased appetite

Common

Diarrhoea

Common

Abdominal pain

Common

Skin and subcutaneous tissue disorders

Urticaria

Not known

Rashes associated or not with pruritus

Not known

Musculoskeletal and connective tissue disorders

Myalgia

Common

Arthralgia

Common

General disorders and administration site conditions

Asthenia

Very common

Mild fever

Common

Mild injection site pain

Very common

Injection site erythema

Uncommon

Injection site nodule

Rare

Investigations

Transaminases increased (mild and reversible)

Rare

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.

4.9. Overdose

A few cases of overdose have been reported with AVAXIM, without specific adverse event.