AVAXIM 80 U PEDIATRIC
1. NAME OF THE MEDICINAL PRODUCT
AVAXIM 80 U PEDIATRIC, suspension for injection in prefilled syringe
Inactivated Hepatitis A vaccine, adsorbed
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Hepatitis A virus, GBM strain*, (inactivated)**…………………80 ELISA units***
for one dose of 0.5 mL.
* Cultured on MRC5 human diploid cells
** Adsorbed on hydrated aluminium hydroxide (0.15 milligrams of Al3+)
*** 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 prefilled syringe.
The hepatitis A vaccine (inactivated, adsorbed) is a turbid and whitish suspension.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
AVAXIM 80 U PEDIATRIC is indicated for active immunization against infection caused
by hepatitis A virus in children aged from 12 months to 15 years.
The vaccine should be administered in accordance with official recommendations.
4.2 Posology and method of administration
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Posology
Paediatric population
? Primary-vaccination :
Primary vaccination is achieved with one vaccine dose of 0.5 mL..
? Booster
One booster dose of 0.5 mL is recommended in order to provide long-term protection. This
booster dose will preferably be administered 6 to 36 months following the primary
vaccination dose, but administration will be possible until 7 years after this primary
vaccination.
Available data on vaccination with AVAXIM 80 U PEDIATRIC show that after the two
doses of the initial vaccination schedule, no other booster vaccination is necessary in
immunocompetent individuals, which is in agreement with the official recommendations.
Method of administration
This vaccine must be administered by the intramuscular route.
The recommended injection site is the deltoid region.
In exceptional cases, the vaccine may be administered by the subcutaneous route in patients
suffering from thrombocytopaenia 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.
4.3 Contra-indications
? Hypersensitivity to the active substance, to one of the excipients, 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 special precaution 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.
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
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limb movements during the recovery phase. It is important that procedures be in place to
avoid any injury from faints.
AVAXIM 80 U PEDIATRIC has not been studied in patients with impaired immunity.
The immune response to the vaccine may be impaired by immunosuppressive treatment or
immunodeficiency. In such cases it is recommended to wait for 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 80 U PEDIATRIC 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, vaccination may not induce a protective response in some vaccinees.
This vaccine does not protect against infection caused by hepatitis B virus, hepatitis C virus,
hepatitis E virus or by other known liver pathogens.
AVAXIM 80 U PEDIATRIC, suspension for injection in prefilled syringe contains
ethanol, phenylalanine, potassium and sodium
o AVAXIM 80 U PEDIATRIC contains small amounts of ethanol (alcohol), less than
100 mg per dose.
o AVAXIM 80 U PEDIATRIC 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 80 U PEDIATRIC contains less than 1 mmol of potassium (39 mg) and
sodium (23 mg) per dose, that is to say essentially “potassium-free” and “sodiumfree”.
4.5 Interaction with other medicinal products and other forms of interaction
The simultaneous administration of immunoglobulins with this vaccine in two different
injection sites may be performed. The seroprotection rates are not modified, but the antibody
titres may be lower than those obtained when the vaccine is administered alone.
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In case of simultaneous administration, this vaccine must not be mixed with other vaccines in
the same syringe. The vaccine may be administered simultaneously, in two different
injection sites, with the routine booster vaccine of the child during the second year of life, i.e.
various vaccines containing one or more of following valences: diphtheria, tetanus, pertussis
(acellular or whole cells), Haemophilus influenzae of type b and inactivated or oral
poliomyelitis.
This vaccine can be administered simultaneously, but at two different injection sites, with a
vaccine against measles, mumps and rubella.
This vaccine can be used as a booster in subjects previously vaccinated with another
inactivated Hepatitis A vaccine.
4.6 Pregnancy and lactation
Pregnancy
No relevant teratogenic data on animal are available.
In humans, up to now, the data is inadequate to assess teratogenic or foetotoxic risk of the
vaccine against Hepatitis A when 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.
Breastfeeding
The excretion of AVAXIM 80U PEDIATRIC in maternal milk is unknown. The excretion of
AVAXIM 80U PEDIATRIC in milk has not been studied in animals. The decision to
continue/discontinue lactation or whether to administer AVAXIM 80U PEDIATRIC or not
should be made taking into account the benefit of breast-feeding for the child and the benefit
of AVAXIM 80U PEDIATRIC for the woman.
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
a. Summary of the safety profile
More than 6200 children aged from 12 months to 15 years (around 7000 administered doses)
were vaccinated with AVAXIM 80 U PEDIATRIC during clinical trials.
All undesirable effects were moderate and limited to the first few days following vaccination
with spontaneous recovery. Reactions were more rarely reported after the booster dose than
after the first dose.
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However, as with all pharmaceuticals, expanded commercial use of the vaccine might reveal
rarer undesirable effects.
b. Tabulated list of adverse reactions
The undesirable effects are derived from clinical studies and worldwide post-marketing
experience.
In each System Organ Class, the undesirable effects are ranked under headings of frequency,
the most common reactions coming first, using the following convention:
Very common (? 1/10)
Common (? 1/100, < 1/10)
Uncommon (? 1/1 000, < 1/100)
Rare (? 1/10 000, < 1/1000)
Very rare (< 1/10 000)
Not known: cannot be estimated from the available data.
The table below summarize the frequencies of the adverse reactions that were recorded after
the first dose, after the booster dose or after any dose of AVAXIM 80 U PEDIATRIC.
Adverse reactions Frequency
after the
primary dose
Frequency
after the
booster dose
Frequency
after any dose
Metabolism and nutrition
disorders
Appetite decrease Common Common Common
Psychiatric disorders
Abnormal crying
Irritability
Insomnia
Very common
Common
Common
Uncommon
Common
Common
Very common
Common
Common
Nervous system disorders
Cephalalgia
Vasovagal syncope in response to
injection
Common
Not known
Common
Not known
Very common
Not known
Gastrointestinal disorders
Abdominal pain
Diarrhoea
Nausea
Vomiting
Common
Common
Common
Common
Common
Common
Common
Common
Common
Common
Common
Common
Skin and subcutaneous tissue
disorders
Rash
Urticaria
NR*
Uncommon
Uncommon
NR*
Uncommon
Uncommon
Musculoskeletal and connective
tissue disorders
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Adverse reactions Frequency
after the
primary dose
Frequency
after the
booster dose
Frequency
after any dose
Arthralgia
Myalgia
Common
Common
Uncommon
Common
Common
Common
General disorders and
administration site conditions
Local reactions
Pain at the injection site
Redness at the injection site
Induration or oedema at the
injection site
Haematoma at the injection site
Systemic reactions
Malaise
Fever
Asthenia or somnolence
Very common
Common
Common
Common
Common
Common
Common
Common
Common
Common
Uncommon
Common
Common
Common
Very common
Common
Common
Common
Very common
Common
Common
* Not reported during clinical studies
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
An overdose is unlikely to provoke any harmful effects.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Viral vaccine, ATC code: J07BC02
This vaccine is prepared from hepatitis A virus cultured, harvested and then inactivated by
formaldehyde.
It confers immunity against hepatitis A virus (HAV) by inducing anti-HAV antibody titres
longer lasting and higher than those obtained after passive immunization with
immunoglobulins. This vaccine has been demonstrated to elicit protective anti-HAV
antibody titres (?20mIU/mL) within two weeks following the injection in over 95% of
individuals and in 100% of individuals before the booster dose administered 6 months after
the first dose.
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A study conducted in Argentina (an area of intermediate endemicity for hepatis A) enabled
the evaluation of long term persistence of anti-HAV antibodies in children aged 12 months to
47 months vaccinated with 2 doses of Avaxim 80 U Pediatric 6 months apart. The results
show a persistence of the antibodies until 14-15 years at levels considered as protective and
do not suggest the need for new administration of the vaccine.
A mathematical model using the available data from this study until 14-15 years after
administration of the 2 doses of Avaxim 80 U Pediatric predicts a persistence of the
protective anti-HAV antibodies for at least 30 years in 87.5% (CI 95%: 74.1; 94.8) of these
children.
Duration of Effect
A descriptive, prospective, mono-centre, antibody persistence study conducted in 546
Argentinean children provided long-term antibody persistence data on two groups; one group
who received a single dose of AVAXIMR - Pediatric and another group who received the
standard two-dose schedule. It was shown 7 years after vaccination that the group who
received a single dose of AVAXIMR - Pediatric (N=204) had a similar seroprotective level of
anti-HAV antibodies as the group who received two doses (N=53).
5.2 Pharmacokinetic properties
Not applicable.
5.3 Preclinical safety data
Non-clinical data revealed no special hazard for humans based on conventional acute
toxicity, repeat dose toxicity, local tolerance and hypersensitivity studies.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipient(s)
2-Phenoxyethanol, ethanol, formaldehyde and Hanks Medium 199*,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 pharmaceutical product must not be mixed with
other medicinal products.
6.3 Shelf-life
3 years
6.4 Special precautions for storage
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Single dose presentation
Store between +2°C and +8°C. Keep in the original packaging,protected from light. Do not
freeze.
6.5 Nature and contents of container
Single dose presentation
0.5ml of suspension in prefilled syringe (type I glass) with a plunger-stopper
(bromochlorobutyl or chlorobutyl or bromobutyl), with attached needle, without needle or
with two separate needles. Box of 1, 10 or 20.
Not all presentations may be available.
6.6 Instruction for use and handling
Shake before injection, until a homogenous suspension is obtained.
The vaccine must be visually inspected before administration to verify the absence of foreign
particles.
Any unused product or waste material should be disposed of in accordance with local
requirement.
7. MARKETING AUTHORISATION HOLDER
SANOFI PASTEUR SA
14 Espace Henry Vallee
69007 Lyon,
France.
8. DATE OF REVISION OF TEXT
Jun 2020
(CCDS V11,12,13)