Inactivated adsorbed hepatitis A vaccine (GBM strain).
One dose (0.5 ml) contains: Hepatitis A virus, GBM strain* (inactivated)** 160 units***.
*Cultured on MRC-5 human diploid cells.
**Adsorbed on hydrated aluminium hydroxide (0.3 milligrams of Al).
***In the absence of an international standardised reference, the antigen content is expressed using an in-house reference.
Excipients/Inactive Ingredients: 2-Phenoxyethanol, formaldehyde, and Hanks 199 medium* (without phenol red) supplemented with polysorbate 80.
*Hanks 199 medium is a complex mixture of amino acids (including phenylalanine), mineral salts, vitamins, and other components, diluted in water for injections and with a pH that has been adjusted with hydrochloric acid or sodium hydroxide.
Pharmacotherapeutic Group: Vaccine against Hepatitis A. ATC code: J07BC02.
Pharmacology: Pharmacodynamics: 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 36th 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 36th 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. This recommendation is based on mathematical modelling with persistence data available for 3-5 years.
Pharmacokinetics: Not applicable.
Toxicology: 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.
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.
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 Pharmacology: Pharmacodynamics under Actions). 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 Cautions for Usage for the instructions on preparation.
A few cases of overdose have been reported with AVAXIM 160 U, with no specific undesirable effects.
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.
As with all injectable vaccines, available appropriate medical treatment and subject monitoring are recommended in case of an anaphylactic reaction after vaccine administration.
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 vaccines.
The vaccine does not protect against infection caused by hepatitis B, hepatitis C or hepatitis E viruses, or by other known liver pathogens.
Effects on ability to drive and use machines: The effects on the ability to drive and use machines have not been studied.
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 foetotoxic 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 excretion of Avaxim in maternal milk is unknown. The excretion of Avaxim in milk has not been studied in animals. The decision to continue/discontinue lactation or whether to administer Avaxim or not should be made taking into account the benefit of breast-feeding for the child and the benefit of Avaxim for the woman.
The undesirable effects are derived from clinical studies and worldwide post-marketing experience.
The undesirable effects are ranked under headings of frequency using the following convention: Very common (≥ 1/10); Common (≥ 1/100 and < 1/10); Uncommon (≥ 1/1,000 and < 1/100); Rare (≥ 1/10,000 and < 1/1,000); Very rare (< 1/10,000), including isolated cases; Not known: cannot be estimated from available data.
Nervous system disorders:
Common: cephalalgia. Not known: vasovagal syncope in response to injection.
Common: nausea, vomiting, appetite decrease, diarrhoea, abdominal pain.
Skin and subcutaneous tissue disorders:
Not known: urticaria, rash associated or not with pruritus.
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.
Rare: increase in serum transaminases (mild and transient).
The reactions were less frequently reported after the booster injection than after the first dose. In subjects seropositive against hepatitis A virus, this vaccine was as well tolerated as in seronegative subjects.
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.
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 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.
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 should be fitted firmly to the syringe, rotating it by 1 quarter turn.
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 requirements.
Incompatibilities: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Store in refrigerator (2°C-8°C).
Do not freeze.
If frozen, the vaccine should be discarded.
Shelf life: 3 years.
J07BC02 - hepatitis A, inactivated, whole virus ; Belongs to the class of hepatitis viral vaccines.
Vaccine inj (pre-filled syringe) 160 antigen units/0.5 mL.