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AVAXIM 160 U, suspension for injection in a prefilled syringe
Hepatitis A vaccine (inactivated, adsorbed)
1. NAME OF THE MEDICINAL PRODUCT
AVAXIM 160 U, suspension for injection in prefilled syringe
Hepatitis A vaccine (inactivated, adsorbed)
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
One dose (0.5 mL) contains:
Hepatitis A virus, GBM strain* (inactivated) ** .................................160 ELISA units***
* Cultured on MRC-5 human diploid cells
** Adsorbed on hydrated aluminium hydroxide (0.3 milligrams of Al
3+
)
*** In the absence of an international standardised reference, the antigen content is
expressed using an in-house reference.
Excipient(s) with known effect:
Less than 1 mmol of sodium and less than 1 mmol of potassium per dose
Ethanol........................................................................................................... 2.5 microlitres
Phenylalanine ............................................................................................... 10 micrograms
Per 0.5 mL dose
For the full list of excipients, see Section 6.1.
3. PHARMACEUTICAL FORM
Suspension for injection in a prefilled syringe.
The hepatitis A vaccine (inactivated, adsorbed) is a turbid and whitish suspension.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
This vaccine is indicated for active immunisation against infection caused by the hepatitis
A virus in adolescents from 16 years of age and in adults.
This vaccine should be administered in accordance with official recommendations.
4.2 Posology and method of administration
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Posology
The recommended dosage for subjects from 16 years of age is 0.5 mL.
The initial protection is obtained after one single injection.
In order to obtain a long-term protection against infections caused by the Hepatitis A
virus, in adolescents from 16 years of age and in adults, a second dose (booster) should
be administered, preferably between 6 and 12 months after the first vaccination and can
be administered up to 36 months after the first vaccination (see Section 5.1). It is
estimated that anti-VHA antibodies persist several years (beyond 10 years) after the
second dose (booster). This recommendation is based on mathematical modelling with
persistence data available for 3-5 years.
This vaccine can also be administered as a booster dose of the hepatitis A vaccination in
subjects from 16 years of age who received a first injection with the combined typhoid
fever (Vi purified polysaccharide) and hepatitis A (inactivated) vaccine between 6 and 36
months earlier.
Method of administration
• This vaccine must be administered by the intramuscular route (IM). The
recommended injection site is the deltoid region.
• In exceptional cases, the vaccine may be administered by the subcutaneous route in
patients with thrombocytopenia or in patients at risk of haemorrhage.
• The vaccine should not be administered into the buttocks because of the varying
amount of fat tissue in this region, that may contribute to variability in effectiveness
of the vaccine.
• Do not inject by the intravascular route: ensure that the needle does not penetrate a
blood vessel.
• Do not inject by the intradermal route.
• See section 6.6 for the instructions on preparation.
4.3 Contraindications
• Hypersensitivity to the active substance or to any of the excipients or to neomycin
(that may be present as traces in each dose due to its use during the manufacturing
process).
• Hypersensitivity following a previous injection of this vaccine.
• Vaccination should be postponed in case of severe acute febrile illness.
4.4 Special warnings and precautions for use
• As with all injectable vaccines, available appropriate medical treatment and subject
monitoring are recommended in case of an anaphylactic reaction after vaccine
administration.
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• AVAXIM 160 U has not been studied in patients with impaired immunity.
• Syncope (fainting) can occur following, or even before, any vaccination as a
psychogenic response to the needle injection, especially in adolescents. This may be
accompanied by several neurological signs such as transient sight disorders,
paraesthesia and tonic-clonic limb movements during the recovery phase. It is
important that procedures be in place to avoid any injury from faints.
• Immunosuppressive treatment or immunodeficiency may induce a decrease in the
immune response to the vaccine.
It is then recommended to wait until the end of treatment before vaccinating or to
make sure the subject is well protected. Nevertheless, vaccination of subjects with
chronic immunodeficiency such as HIV infection is recommended even though the
antibody response might be limited.
• Because of the incubation period of hepatitis A, infection may already be present,
although asymptomatic, at the time of vaccination. The effect of administering
AVAXIM 160 U during the incubation period of hepatitis A has not been
documented. In such a case, vaccination may have no effect on the development of
hepatitis A.
• The use of this vaccine in subjects with liver disease should be considered with
caution, as no studies have been performed in such subjects.
• As with all vaccines, a protective immune response may not be obtained in all
vaccinees.
• The vaccine does not protect against infection caused by hepatitis B, hepatitis C or
hepatitis E viruses, or by other known liver pathogens.
• AVAXIM 160 U contains ethanol, phenylalanine, potassium and sodium
o AVAXIM 160 U contains 2 mg of alcohol (ethanol) in each 0.5 mL dose. The
small amount of alcohol in this medicinal product will not have any noticeable
effects.
o AVAXIM 160 U contains 10 micrograms of phenylalanine in each 0.5 mL dose,
which is equivalent to 0.17 micrograms/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.
o AVAXIM 160 U contains less than 1 mmol potassium (39 mg) and less than 1
mmol 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
Concomitant administration of immunoglobulins and this vaccine in two separate sites
may be performed. Seroprotection rates are not modified but antibody titres may be lower
than those obtained when the vaccine is administered alone.
When concomitant administration is deemed necessary, AVAXIM 160 U must not be
mixed with other vaccines in a same syringe: the other vaccines must be administered in
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separate sites using separate syringes and needles.
As the vaccine is inactivated, association with other inactivated vaccine(s) in a separate
injection site does not generally result in any interaction.
This vaccine can be administered simultaneously, but in two separate sites, with a
typhoid polysaccharide vaccine (Typhim Vi) without modification of the immune
response to either antigen.
This vaccine can be administered simultaneously, but in two separate sites, with the live
yellow fever vaccine.
This vaccine can be used as a booster dose in subjects who have received primary
vaccination with another inactivated hepatitis A vaccine.
4.6 Fertility, pregnancy and lactation
Pregnancy
No reliable data are available on teratogenesis in animals.
To date, there are no sufficiently relevant clinical data available to assess a potential
vaccine-related malformation or fetotoxic effect of the hepatitis A vaccine, when it is
administered during pregnancy. As a precautionary measure, it is preferable not to use
this vaccine during pregnancy except in case of a major contamination risk.
Breast-feeding
The use of this vaccine is possible during breast-feeding.
4.7 Effects on ability to drive and use machines
The effects on the ability to drive and use machines have not been studied.
4.8 Undesirable effects
Summary of tolerance profile
During clinical studies, adverse reactions were generally moderate and limited to the first days
following vaccination with spontaneous regression.
The reactions were less frequently reported after administration of 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 reaction
The adverse reactions are derived from clinical studies and worldwide post-marketing
experience. The adverse reactions are ranked under headings of frequency using the
following convention:
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Very common (≥ 1/10)
Common (≥ 1/100 to < 1/10)
Uncommon (≥ 1/1,000 to < 1/100)
Rare (≥ 1/10,000 to < 1/1,000)
Very rare (< 1/10,000)
Not known: (cannot be estimated from available data): ): adverse reactions were
spontaneously reported after the marketing of Avaxim 160 U. Given that these reactions
were reported voluntarily by a population of unknown size, it is not possible to accurately
estimate their frequency.
Adverse reactions Frequency
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
Decrease in appetite Common
Diarrhoea Common
Abdominal pain Common
Skin and subcutaneous tissue disorders
Urticaria Not known
Rash 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
Slight fever Common
Mild injection site pain Very common
Injection site erythema Uncommon
Injection site nodule Rare
Investigations
Increased serum transaminases (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 national reporting system.
4.9 Overdose
A few cases of overdose have been reported with AVAXIM 160 U, with no specific
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adverse reactions.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Vaccine Against Hepatitis A, ATC code: J07BC02.
This vaccine is prepared from hepatitis A virus cultured, purified and then inactivated by
formaldehyde. It confers immunity against hepatitis A virus by inducing a higher
antibody response than that obtained after passive immunisation with immunoglobulins.
The antibodies appear soon after the first injection, and 14 days after vaccination, more
than 90% of immunocompetent subjects are seroprotected (titres above 20 mIU/ml).
One month after the first injection, almost 100% of subjects have titres higher than 20
mIU/ml. Immunity may persist up to the 36
th
month. In a study with 103 healthy subjects
whose serology levels were monitored for 3 years after the first injection of AVAXIM
160 U, 99% still had, by the 36
th
month, antibody titres of at least 20 mIU/ml against the
hepatitis A virus.
Long-term persistence of a protective antibody level against the hepatitis A virus after a
second dose (booster) of AVAXIM 160 U is not currently established. However, the
available data suggest that the antibodies against the hepatitis A virus persist beyond 10
years after the second dose in healthy people.
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, ethanol, formaldehyde, and Hanks 199 medium*, water for injections,
polysorbate 80, hydrochloric acid and sodium hydroxide for pH adjustment.
*Hanks 199 medium (without phenol red) is a complex mixture of amino acids (including
phenylalanine), mineral salts, vitamins, and other components, including potassium.
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with
other medicinal products.
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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 must be discarded.
Keep in the original packaging, protected from light.
6.5 Nature and contents of container
0.5 mL of suspension in prefilled syringe (type I glass) with a plunger-stopper
(chlorobutyl or bromobutyl) and attached needle and needle-shield (natural rubber or
polyisoprene).
0.5 mL of suspension in prefilled syringe (type I glass) with a plunger-stopper
(chlorobutyl or bromobutyl), without needle
Packs of 1, 5, 10 and 20 syringes.
0.5 mL of suspension in prefilled syringe (type-I glass) with a plunger-stopper
(chlorobutyl or bromobutyl), 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
Shake before injection, until a homogenous suspension is obtained.
For the syringes without attached needles, the separate needle must be fitted firmly to the
syringe, rotating it by one quarter turn.
The vaccine must be visually inspected before administration to verify the absence of
foreign particles.
Any unused medicinal product or waste material should be disposed of in accordance
with local requirements.
7. MARKETING AUTHORISATION HOLDER
SANOFI PASTEUR
14 Espace Henry Vallée
69007 Lyon
France
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8. DATE OF REVISION OF THE TEXT
Feb 2023 (CCDS v10)