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AVAXIM SUSPENSION FOR INJECTION IN A PRE-FILLED SYRINGE

Active substance(s): HEPATITIS A VIRUS INACTIVATED / HEPATITIS A VIRUS INACTIVATED / HEPATITIS A VIRUS INACTIVATED

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SUMMARY OF PRODUCT CHARACTERISTICS

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.
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 Section4.8).
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 postmarketing 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 (≥1/10), Common (≥1/100, <1/10), Uncommon (≥1/1000,
<1/100), Rare (≥1/10000, <1/1000), Very rare (<1/10000) including isolated
reports.
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).
Nervous system disorders
vasovagal syncope in response to injection
Skin and subcutaneous tissue disorders
urticaria, rashes associated or not with pruritus
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:
https://yellowcard.mhra.gov.uk/.

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
(bromochlorobutyl or chlorobutyl or bromobutyl) and attached needle and needleshield (natural rubber or polyisoprene).
0.5 ml of suspension in pre-filled syringe (type I glass) with a plunger-stopper
(bromochlorobutyl or chlorobutyl or bromobutyl) 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
(bromochlorobutyl or chlorobutyl or bromobutyl) 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
For needle free syringes, the needle should be pushed firmly on to the end of the prefilled 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 Europe
2 Avenue Pont Pasteur
69007 Lyon
FRANCE
Distributed in the UK by:
Sanofi
One Onslow Street

Guildford
Surrey
GU1 4YS

8

MARKETING AUTHORISATION NUMBER(S)
PL 46602/0001

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
28/04/2006

10

DATE OF REVISION OF THE TEXT
10/02/2017

Expand Transcript

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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