1. Name Of The Medicinal Product
AVAXIM, suspension for injection in a pre-filled syringe.
Hepatitis A vaccine (inactivated, adsorbed).
2. Qualitative And Quantitative Composition
One 0.5 millilitre dose contains:
Hepatitis A virus, GBM strain (inactivated)1, 2……160 U3
1 produced in human diploid (MRC-5) cells
2 adsorbed on aluminium hydroxide, hydrated (0.3 milligrams Al)
3 In the absence of an international standardised reference, the antigen content is expressed using an in- house reference
Excipient(s):
For a full list of excipients, see section 6.1.
3. Pharmaceutical Form
Suspension for injection in a pre-filled syringe.
Hepatitis A vaccine (inactivated, adsorbed) is a cloudy and white suspension.
4. Clinical Particulars
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 millilitre 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.
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.
See section 6.6 for instructions for preparation.
4.3 Contraindications
• Hypersensitivity to the active substance(s) or to any of the excipients.
• Hypersensitivity following a previous injection of this vaccine.
• Systemic hypersensitivity to neomycin, which may be present in the vaccine in trace amounts.
• 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.
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.
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 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
Lactation
There are no data on the effect of administration of AVAXIM during lactation. AVAXIM is therefore not recommended during lactation.
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
Adverse event data are derived from clinical trials and worldwide post-marketing experience.
Within each system organ class, the adverse events are ranked under headings of frequency, most frequent reactions first, using the following convention:
Very common (
Clinical Studies
In clinical trials, adverse reactions were usually mild and confined to the first few days after vaccination with spontaneous recovery. The adverse reactions observed with AVAXIM were:
Nervous system disorders
Common: headache
Gastrointestinal disorders
Common: nausea, vomiting, decreased appetite, diarrhoea, abdominal pain
Musculoskeletal and connective tissue disorders
Common: myalgia/arthralgia
General disorders and administration site conditions
Very common: asthenia, mild injection site pain
Common: mild fever
Uncommon: injection site erythema
Rare: injection site nodule
Investigations
Rare: transaminases increased (mild and reversible)
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.
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 reported, however exact incidence rates are not known (cannot be estimated from the available data).
Skin and subcutaneous tissue disorders
urticaria, rashes associated or not with pruritus
4.9 Overdose
A few cases of overdose have been reported with AVAXIM, without specific adverse event.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Pharmacotherapeutic group: Viral vaccine, ATC Code: J07BC02
AVAXIM confers immunity against hepatitis A virus by inducing antibody titres greater than those obtained after passive immunisation with immunoglobulin. Antibody appears shortly after the first injection and 14 days after vaccination more than 90% of immunocompetent subjects are seroprotected (titre above 20 mIU/millilitre).
One month after the first injection, almost 100% of subjects have antibody titres above 20mIU/millilitre. Serological data show continuing protection against hepatitis A for up to 36 months in subjects who responded to the first dose. In a study of 103 healthy adults who were followed serologically for three years after the first injection of AVAXIM, 99% still had at least 20 mIU/ml anti-HAV antibody at month 36.
The long-term persistence of protective antibody levels to hepatitis A virus after a second dose (booster) of AVAXIM has not been fully evaluated. Nevertheless, available data (antibody titres obtained two years after the second dose) suggest that anti-HAV antibodies persist beyond 10 years after the second dose in healthy individuals.
5.2 Pharmacokinetic Properties
Not applicable.
5.3 Preclinical Safety Data
Non-clinical data reveal no special hazard for humans based on conventional studies of acute toxicity, repeated dose toxicity, local tolerance and hypersensitivity.
6. Pharmaceutical Particulars
6.1 List Of Excipients
2-phenoxyethanol
Formaldehyde
Medium 199 Hanks *
Water for injections
Hydrochloric acid and sodium hydroxide for pH adjustment
*Medium 199 Hanks is a complex mixture of amino acids (including phenylalanine), mineral salts, vitamins and other components.
6.2 Incompatibilities
In the absence of compatibility studies, the vaccine must not be mixed with other medicinal products.
6.3 Shelf Life
3 years.
6.4 Special Precautions For Storage
Store in a refrigerator (2°C - 8°C).
Do not freeze. If frozen, the vaccine should be discarded.
6.5 Nature And Contents Of Container
0.5 ml of suspension in pre-filled syringe (type I glass) with a plunger-stopper (chlorobromobutyl or chlorobutyl) and attached needle and needle-shield (natural rubber or polyisoprene).
0.5 ml of suspension in pre-filled syringe (type I glass) with a plunger-stopper (chlorobromobutyl or chlorobutyl) and tip-cap (chlorobromobutyl), without needle.
Packs of 1, 5, 10 and 20 syringes.
0.5 ml of suspension in pre-filled syringe (type I glass) with a plunger-stopper (chlorobromobutyl or chlorobutyl) and tip-cap (chlorobromobutyl), with 1 or 2 separate needles (for each syringe).
Packs of 1 and 10 syringes.
Not all pack sizes and presentations may be marketed.
6.6 Special Precautions For Disposal And Other Handling
For needle free syringes, the needle should be pushed firmly on to the end of the pre-filled syringe and rotated through 90 degrees.
Shake before injection to obtain a homogeneous suspension. The vaccine should be visually inspected before administration for any foreign particulate matter.
Any unused product or waste material should be disposed of in accordance with local requirements.
7. Marketing Authorisation Holder
Sanofi Pasteur MSD Limited
Mallards Reach
Bridge Avenue
Maidenhead
Berkshire
SL6 1QP
8. Marketing Authorisation Number(S)
PL 6745/0070
9. Date Of First Authorisation/Renewal Of The Authorisation
30th April 2001/28th April 2006
10. Date Of Revision Of The Text
March 2011
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