Consumer medicine information

Avaxim

Hepatitis A vaccine

BRAND INFORMATION

Brand name

Avaxim

Active ingredient

Hepatitis A vaccine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Avaxim.

What is in this leaflet

This leaflet answers some common questions about AVAXIM It does not contain all the available information.

It does not take the place of talking to your doctor.

All medicines, including vaccines, have risks and benefits. Your doctor has weighed the risks of you having AVAXIM against the benefits they expect it will have for you.

If you have any concerns about this vaccine, ask your doctor, nurse or pharmacist.

Keep this leaflet. You may need to read it again.

What AVAXIM is used for

AVAXIM is a vaccine used to help prevent Hepatitis A infection.

Hepatitis A is an infection caused by a virus which is usually transmitted in unclean food or drink. It may also be transmitted by sharing needles and some sexual practices.

The vaccine contains inactivated virus and is injected into the body. The body then produces its own protection by making disease-fighting substances (antibodies) to fight the virus. The vaccine cannot cause the infection. If a vaccinated person comes into contact with live virus the body is usually ready to destroy it. However, as with all vaccines, 100% protection against hepatitis A cannot be guaranteed. Avaxim will not protect against hepatitis caused by other agents or viruses (such as hepatitis B, hepatitis C, or hepatitis E).

As with most vaccines, AVAXIM may not protect every person.

AVAXIM is recommended in adults and children aged 2 years and older.

Before you are given AVAXIM

When you must not be given it

You have had a severe reaction to a previous injection of this vaccine.

Do not have AVAXIM if you have an allergy to:

  • AVAXIM or any of the ingredients listed at the end of this leaflet

Symptoms of an allergic reaction may include:

  • Shortness of breath, wheezing or difficulty breathing
  • Swelling of the face, lips, tongue or other parts of the body
  • Skin rash, itching or hives

Do not give AVAXIM to children under 2 years of age. The safety and efficacy of AVAXIM in these children has not been established.

Do not have AVAXIM after the expiry date printed on the pack. If the vaccine is used after the expiry date has passed, it may not work.

Do not have AVAXIM if the packaging is torn or shows signs of tampering.

Talk to your doctor or pharmacist if you are not sure whether you should have AVAXIM.

Before you are given it

Tell your doctor if you have ever had a serious allergic reaction to a vaccine.

Tell your doctor if you have an illness with a high temperature or any acute illness Your doctor may decide to delay vaccination until the illness has passed. A mild illness, such as a cold, is not usually a reason to delay vaccination.

Tell your doctor if you have, or have had, any medical conditions, especially the following:

  • Lowered immunity due to diseases such as some blood disorders, leukaemia, malaria, kidney disease requiring dialysis, HIV/AIDS or cancer
  • Lowered immunity due to treatment with medicines such as corticosteroids, cyclosporin or other medicines used to treat cancer (including radiation therapy)

If you have lowered immunity then the vaccine may not work as well as it would in healthy individuals.

Tell your doctor if you have allergies to:

  • Neomycin
  • Any other medicines
  • Any other substances, such as foods, preservatives or dyes

Tell your doctor if you are pregnant or intend to become pregnant. AVAXIM is not recommended for use during pregnancy. If there is a need to consider AVAXIM during your pregnancy, your doctor will discuss with you the benefits and risks of having it.

Tell your doctor if you are breast-feeding. Your doctor will discuss the possible risks and benefits of having AVAXIM during breastfeeding.

Having other vaccines

As AVAXIM does not contain any live bacteria or viruses, it can generally be given at the same time as other inactivated vaccines, but at a different injection site.

AVAXIM can be given at the same time as yellow fever vaccine or polysaccharide typhoid vaccine at different injection sites.

Other medicines should be taken as usual after the vaccination.

How AVAXIM is given

AVAXIM is given as an injection into your upper arm muscle by a doctor or nurse.

For some people with bleeding disorders, the dose may need to be given under the skin.

AVAXIM should not be injected directly into the veins or into the buttocks.

The dose is the same for adults and children, 0.5 mL of vaccine. The first injection is followed by a second injection 6 to 36 months later in order to give long-term protection. AVAXIM may be given as a second injection to those who have previously been vaccinated with another inactivated hepatitis A vaccine.

It is important to return at the scheduled date for the second dose. If you miss a scheduled dose, talk to your doctor and arrange another visit as soon as possible.

Because hepatitis A infection can go undetected for a long period of time, it is possible that an individual may already be infected at the time the vaccine is given. The vaccine may not prevent hepatitis A in these individuals.

How much is injected

Your doctor will usually give you one injection, followed by another injection 6 to 36 months later.

After having AVAXIM

Things you must do

  • Keep an updated record of your vaccinations
  • Attend any other appointments made by your doctor or nurse
  • Report any side effects to your doctor.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well after having AVAXIM

AVAXIM may have unwanted side effects in a few people. All medicines, including vaccines, can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • Local reaction around the injection site such as pain sometimes associated with redness. The appearance of a nodule at the injection site has been observed in very rare cases
  • Bruising
  • Mild fever
  • Headaches
  • Unusual weakness
  • Aching muscles, muscle tenderness or weakness (not caused by exercise)
  • Painful, swollen joints
  • Stomach upsets such as nausea, diarrhoea, vomiting or abdominal pain
  • Fainting

These are the more common side effects of AVAXIM. Mostly these are mild and short-lived.

Less common side effects include rash sometimes associated with itchiness of skin, or pinkish, itchy swelling on the skin. Very rarely some patients experience a mild reversible rise in liver enzyme but this can only be found when your doctor does tests.

Hence tell your doctor as soon as possible if you notice anything that is making you feel unwell after you have been given AVAXIM.

Other side effects not listed above may also occur in some people.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

Storing AVAXIM

AVAXIM is usually stored in the doctor's surgery or clinic, or at the pharmacy. However, if you need to store AVAXIM

  • Keep it where children cannot reach it.
  • Keep AVAXIM in the original pack until it is time for it to be given.
  • Keep it in the refrigerator, between 2C and 8C. Do not freeze AVAXIM.

Freezing destroys the vaccine.

Product description

What it looks like

Each pack of AVAXIM contains one syringe filled with inactivated Hepatitis A vaccine.

Ingredients

Active ingredients:

  • 160 antigen units hepatitis A virus (inactivated, adsorbed)

Other ingredients:

  • Aluminium hydroxide hydrate
  • Phenoxyethanol
  • Ethanol absolute
  • Formaldehyde
  • Medium 199 (Hanks) supplemented with Polysorbate 80
  • Neomycin (trace)
  • Bovine serum albumin (trace)

The hepatitis A virus that this vaccine contains was grown in a cell line derived from human embryonic lung in the 1960s.

The manufacture of this product includes exposure to bovine derived materials. No evidence exists that any case of vCJD (considered to be the human form of bovine spongiform encephalopathy) has resulted from the administration of any vaccine product.

Name and Address of Sponsor

Australia:

sanofi-aventis australia pty ltd
12-24 Talavera Road
Macquarie Park NSW 2113
Australia
Tel: 1800 818 806

New Zealand:

sanofi-aventis new zealand limited
Level 8,
56 Cawley St
Ellerslie
Auckland
New Zealand
Tel: 0800 283 684

AUST R number

Aust R 73452

Aust R 194815

Date of preparation

11 July 2019

avaxim-ccdsv9-cmiv3-11jul19

Published by MIMS September 2019

BRAND INFORMATION

Brand name

Avaxim

Active ingredient

Hepatitis A vaccine

Schedule

S4

 

1 Name of Medicine

Hepatitis A virus (inactivated, adsorbed).

6.7 Physicochemical Properties

CAS number.

No data available.

2 Qualitative and Quantitative Composition

Avaxim is a sterile suspension for injection containing formaldehyde-inactivated hepatitis A virus (GBM strain) adsorbed onto aluminium hydroxide hydrate.
Each 0.5 mL dose contains:

Active ingredient.

Hepatitis A virus* 160 antigen units**.
* GBM strain cultured on MRC-5 human diploid cells. MRC-5 is a cell line that was derived from human embryonic lung tissue in the 1960s.
** In the absence of an international standardised reference, the antigen content is expressed using an in-house reference.
The manufacture of this product includes exposure to bovine derived materials. No evidence exists that any case of vCJD (considered to be the human form of bovine spongiform encephalopathy) has resulted from the administration of any vaccine product.
Contains phenylalanine and residual neomycin.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Suspension for injection.
Avaxim is a cloudy, whitish suspension.

5 Pharmacological Properties

ATC code: J: Anti-infectives for systemic use; J07 (vaccines) B (Viral vaccines) C (Hepatitis vaccines) 02 (Hepatitis A, inactivated, whole virus).

5.1 Pharmacodynamic Properties

Mechanism of action.

Hepatitis A is generally transmitted by the faecal-oral route through contaminated water or food. Blood and sexual (oral-anal relations) transmission has been demonstrated.
Avaxim confers immunity against hepatitis A virus by inducing antibodies. The measured antibody titres are greater than those obtained after passive immunisation with immunoglobulin. They are comparable to antibody titres obtained after vaccination with other inactivated hepatitis A vaccines with proven protective efficacy. The efficacy of this vaccine has not been demonstrated in field studies.
14 days after vaccination more than 90% of immunocompetent individuals are protected. One month after the first injection 100% of individuals are protected. Immunity persists for at least 36 months and is reinforced after a booster injection.
Primary immunisation should be given at least two weeks prior to anticipated exposure to the hepatitis A virus.
Data relative to long-term persistence of hepatitis A virus antibodies (anti-HAV) following vaccination with Avaxim are not currently available. Based on antibody kinetic modelling, it is predicted that anti-HAV antibody would persist for at least 10 years after the completion of the two dose vaccination schedule.

Clinical trials.

The efficacy of Avaxim has been determined by the comparison of the antibody titres produced by Avaxim with that of a control hepatitis A vaccine that had previously been demonstrated to confer protective efficacy in a controlled trial of healthy children in Thailand. Seroprotection was defined as anti-HAV > 20 mIU/mL. The protective effect of Avaxim against infection with hepatitis A has not been assessed. In total 4,220 subjects received Avaxim in 9 studies in adults and 3 studies in children during the course of the clinical development program.
The pivotal studies were two multicentre, open, randomised controlled studies. In the first, 840 adults were enrolled; 420 who received Avaxim and 420 who received the control hepatitis A vaccine. In the second study 423 adults were enrolled; 212 who were inoculated with Avaxim and 211 who received the control vaccine.
In the first pivotal study Avaxim immunogenicity was assessed at 8 weeks after the primary injection (in the subjects that were HAV seronegative (< 20 mIU/mL) at inclusion) with 99.3% of subjects achieving seropositive titres (95% CI 97.5-99.9%). The Geometric Mean Titre (GMT) was 138.4 mIU/mL (95% CI 124.5-153.9). The seroconversion rate 4 weeks post the last dose (week 28) was 100% (95% CI 99.0-100) with GMT of 4,189.6 mIU/mL (95% CI 3,792.3-4,628.6 mIU/mL). Additional analyses were made one, two and three years postbooster. All subjects tested were still seropositive. See Table 3.
In the second pivotal study 100% of subjects were seropositive 8 weeks after the primary injection (95% CI 97.7-100%) with the GMT being 114 mIU/mL (95% CI 102-127). Four weeks after the booster injection the GMT had risen to 3,557 mIU/mL (95% CI 2,985-4,239).
Three studies have determined the immunogenicity of Avaxim in children aged between 2 and 17 years. Study 1 was conducted in haemophiliac males in France, with the other two studies being conducted in school children in Venezuela and Taiwan. Seroprotection was defined as > 20 mIU/mL. See Table 4.
Long-term persistence of vaccine induced anti-HAV was evaluated in a study designed to determine the antibody (anti-HAV and anti-Vi) persistence 1, 2 and 3 years after primary dose of the combined purified Vi polysaccharide typhoid and inactivated hepatitis A vaccine (Vivaxim) or of the simultaneous individual vaccines (purified Vi polysaccharide vaccine (Typhim Vi) and inactivated hepatitis A vaccine (Avaxim)). This study was an open label, randomised trial which included 360 adult subjects; 179 in the Vivaxim group and 181 in the Avaxim and Typhim Vi group (see Table 5).
At year 3, a subset of the original subjects underwent revaccination with the combined vaccine (Vivaxim) and the antibody response was recorded 28 days later (see Table 6).
Three years after primary vaccination with Avaxim, the hepatitis A seroprotection rate (percent ≥ 20 mIU/mL) was 99%. Three years after primary vaccination with Avaxim, the seroprotection rate for hepatitis A increased to 100% 28 days after a booster vaccination with Vivaxim, demonstrating anamnestic immune response against hepatitis A.
Noninferior immunogenicity of Avaxim when used as a booster following the primary dose of Vivaxim was demonstrated in a study designed to demonstrate that either of the two hepatitis A vaccines (Avaxim and Vaqta) could be used as a booster following primary vaccination with Vivaxim. This study was an open label, randomised trial which included 120 adult subjects. The results showed that one month after the booster injection, the immunogenicity elicited by vaccination with Vivaxim and booster Avaxim was noninferior to that of Avaxim and booster Avaxim in terms of GMT of anti-HAV antibody; and similarly that the immunogenicity elicited by vaccination with Vivaxim and booster Vaqta was noninferior to that of Avaxim and booster Avaxim (see Table 7).

5.2 Pharmacokinetic Properties

No data available.

5.3 Preclinical Safety Data

Genotoxicity.

Avaxim has not been evaluated for the genotoxic potential.

Carcinogenicity.

Avaxim has not been evaluated for the carcinogenic potential.

4 Clinical Particulars

4.1 Therapeutic Indications

Avaxim is indicated for active immunisation against hepatitis A infection in adults and children 2 years and over.
Vaccination against viral hepatitis A is recommended for individuals who are or will be at increased risk of infection, e.g. travellers to areas of moderate or high endemicity for hepatitis A; visitors to rural and remote indigenous communities; child daycare and preschool personnel; the intellectually disabled and their carers; healthcare providers; sewerage workers; men who have sex with men; injecting drug users; patients with chronic liver disease and haemophiliacs who may receive pooled plasma concentrates.

4.3 Contraindications

Avaxim should not be administered to anyone with a history of severe allergic reaction to any component of the vaccine (see Section 2 Qualitative and Quantitative Composition) or after previous administration of the vaccine or vaccine containing the same components or constituents.
Vaccination must be postponed in case of febrile or acute disease.

4.4 Special Warnings and Precautions for Use

As each dose contains formaldehyde, caution should be exercised when the vaccine is administered to individuals with hypersensitivity to this product.
As the vaccine may contain undetectable traces of neomycin, which is used during vaccine production, caution should be exercised when the vaccine is administered to individuals with hypersensitivity to this antibiotic (and other antibiotics of the same class).
This vaccine contains polysorbate which may cause local skin reactions.
As with other injectable vaccines, appropriate medical treatment and supervision should always be available in case of anaphylactic reactions. Adrenaline should always be readily available whenever the injection is given.
Immunogenicity of the vaccine could be impaired by immunosuppressive treatment or in immunodeficiency. In such cases, it is recommended to postpone the vaccination until the end of the treatment and/or the resolution of the disease. Nevertheless, vaccination of individuals with chronic immunodeficiency such as HIV infection is recommended even if the antibody response might be limited.
Because of the incubation period of the disease, infection may be present but not clinically apparent at the time of vaccination. In this case, the vaccination may have no effect on the development of hepatitis A.
The vaccine does not provide protection against infection caused by hepatitis B virus, hepatitis C virus, hepatitis E virus or by other liver pathogens.
As with any vaccine, vaccination with Avaxim may not protect 100% of susceptible individuals.
Do not administer by intravascular injection: ensure that the needle does not penetrate a blood vessel.
As with all injectable vaccines, the vaccine must be administered with caution to individuals with thrombocytopenia or a bleeding disorder since bleeding may occur following an intramuscular administration to these individuals.
In exceptional circumstances, the vaccine may be administered by the subcutaneous route in individuals suffering from thrombocytopenia or in individuals at risk of haemorrhage.
Syncope (fainting) can occur following, or even before, any vaccination as a psychogenic response to the needle injection. Procedures should be in place to prevent falling injury and manage syncopal reactions.

Use in the elderly.

Immunogenicity and clinical experience with Avaxim in the elderly is limited.

Paediatric use.

Safety and effectiveness of Avaxim below the age of 2 years have not been established.

Effects on laboratory tests.

Interference of Avaxim with laboratory tests has not been studied.

4.5 Interactions with Other Medicines and Other Forms of Interactions

For individuals requiring immediate and longer-term protection, such as travellers departing on short notice to endemic areas or contacts of infected individuals requiring longer term postexposure prophylaxis, Avaxim may be administered concomitantly with immunoglobulin. The vaccine may be administered concurrently with immunoglobulin providing different injection sites are used. Seroconversion rates are unaffected although antibody titres may be lower than those obtained with vaccine alone.
Information on the concomitant use of Avaxim and other vaccines is limited. There is evidence for concurrent administration of Typhim Vi (typhoid Vi polysaccharide vaccine) or live yellow fever vaccine without any interference with the immune response.
Separate injection sites and separate syringes must be used in case of concomitant administration with other medicinal products.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Avaxim has not been evaluated for the effects on fertility.
(Category B2)
Animal reproduction studies have not been conducted with this vaccine. Data on the use of this vaccine in pregnant women are limited. Therefore, the administration of the vaccine during pregnancy is not recommended. Avaxim should be given to pregnant women only if clearly needed, and following an assessment of the risks and benefit.
It is not known whether this vaccine is excreted in human milk. Caution must be exercised when Avaxim is administered to a nursing mother.

4.8 Adverse Effects (Undesirable Effects)

Clinical trial experience.

The adverse reactions reported during clinical trials were generally mild, short-term and resolved without treatment.

Local reactions at the injection site.

This was most frequently a local pain sometimes associated with erythema. The appearance of a nodule at the injection site was observed in very rare cases.

Systemic reactions.

Mild fever, asthenia, headache, myalgia or arthralgia and gastrointestinal disorder were most frequently reported.
Mild reversible elevation of serum transaminase has been observed on rare occasions.
Reactions were less frequently reported after the booster injection than after the first dose.
In individuals seropositive against hepatitis A virus, this vaccine was as well tolerated as in seronegative individuals.

Adults.

The reactogenicity of Avaxim was assessed using the same methodology in all the clinical development trials undertaken, making it possible to consolidate the results. A total of 2,204 adults received at least one dose of the final formulation of Avaxim by the intramuscular route.
Local reactions were observed in 13.2% of vaccine recipients after the first dose and 9.9% after the booster dose. General symptoms were reported in 27.3% of vaccine recipients after the first dose and 13.6% after the booster dose.
Two comparative studies compared the reactogenicity of Avaxim with a commercially available hepatitis A vaccine. The first study showed no statistical difference in the reactogenicity for seronegative patients. In the second study there was a significantly lower incidence of local reactions with Avaxim than with the comparator, both after the first and booster doses (p < 0.5). This study was randomised but not blinded. See Table 1.

Children.

In the combined clinical trials a total of 261 children received the first dose and 135 received the booster dose of Avaxim. See Table 2.

Post-marketing experience.

Based on spontaneous reporting, the following additional adverse events have been reported during the commercial use of Avaxim. These events have been very rarely (< 0.01%) reported; however as exact incidence of rates cannot be calculated precisely, their frequency is qualified as not known.

Nervous system disorders.

Headache, vasovagal syncope.

Gastrointestinal disorders.

Nausea, diarrhoea, vomiting, abdominal pain.

Skin and subcutaneous tissue disorder.

Urticaria, rashes associated or not with pruritus.

Musculoskeletal and connective tissue disorders.

Arthralgia, myalgia.

General disorders and administration site condition.

Injection site pain, injection site rash, injection site nodule, pyrexia, asthenia.

Investigation.

Transaminases increased (mild and reversible).

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems (Australia) or https://nzphvc.otago.ac.nz/reporting/ (New Zealand).

4.2 Dose and Method of Administration

The dose is 0.5 mL for each injection. The dose is the same for adults and children.
The primary vaccination is performed with one single dose of vaccine. The booster injection can be given 6 to 36 months after the primary vaccination.
Avaxim may be used as a booster in individuals previously vaccinated with another inactivated hepatitis A vaccine.
The combined purified Vi polysaccharide typhoid and inactivated hepatitis A vaccine (Vivaxim) may be given as a booster injection 6 to 36 months after primary vaccination with Avaxim, in individuals over 16 years travelling to areas where hepatitis A and typhoid are endemic.
Avaxim may be used as a booster injection 6 to 36 months after a primary vaccination performed by the combined purified Vi polysaccharide typhoid and inactivated hepatitis A vaccine (Vivaxim) to ensure long-term protection against infection with hepatitis A virus.
As the vaccine is adsorbed, it must be injected by the intramuscular route in order to minimise local reactions. The recommended injection site is the deltoid region.
Do not administer by intradermal or intravenous injection. Ensure that the needle does not enter a blood vessel.
Shake the prefilled syringe before injection to obtain a homogenous suspension.
This vaccine must not be mixed with other vaccines in the same syringe.
The prefilled syringe is for single use only and any residue must be discarded.

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.

4.9 Overdose

Cases of administration of more than the recommended dose (overdose) have been reported with Avaxim. The adverse events reported in these cases did not differ in nature to those described, see Section 4.8 Adverse Effects (Undesirable Effects).
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia) or 0800 POISON (New Zealand).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Aluminium hydroxide hydrate (quantity expressed as aluminium) 0.3 mg, phenoxyethanol (preservative) 2.5 microL, ethanol absolute (preservative) 2.5 microL, formaldehyde (preservative) 12.5 microgram, Medium 199 (Hanks)*** up to 0.5 mL.
*** Medium 199 Hanks (without phenol red) is a complex mixture of amino acids (including phenylalanine), mineral salts, vitamins and other substances, diluted in water for injection, supplemented with polysorbate 80 and with a pH adjusted with hydrochloric acid or sodium hydroxide.
Neomycin (≤ 2.5 microgram) and bovine serum albumin (< 50 nanogram) may be present as residual traces.

6.2 Incompatibilities

This vaccine must not be mixed with other vaccines or medicinal products.

6.3 Shelf Life

36 months.

6.4 Special Precautions for Storage

Store at 2°C to 8°C. (Refrigerate. Do not freeze.)
Store protected from light.

6.5 Nature and Contents of Container

Single dose prefilled syringe, 0.5 mL.

6.6 Special Precautions for Disposal

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

Summary Table of Changes