Avaxim

Inactivated hepatitis A vaccine.

The hepatitis A vaccine (inactivated, adsorbed) is a turbid and whitish suspension.
Avaxim 80 U Pediatric: Hepatitis A virus, GBM strain* (inactivated) ** 80 ELISA unit*** for one dose of 0.5 mL.
* Cultured on MRC5 human diploid cells.
** Adsorbed on hydrated aluminium hydroxide (0.15 milligrams of Al³⁺).
Excipient(s) with known effect (see Precautions): Phenylalanine 10 micrograms; Per 0.5 mL dose.
*** In the absence of an international standardised reference, the antigen content is expressed using an in-house reference.
Avaxim 160 U: 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 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.
Excipients/Inactive Ingredients: 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.

Pharmacotherapeutic group: Avaxim 80 U Pediatric: Viral vaccine. Avaxim 160 U: VACCINE AGAINST HEPATITIS A. ATC code: J07B C02.
Pharmacology: Pharmacodynamics: Avaxim 80 U Pediatric: This vaccine is prepared from hepatitis A virus cultured, harvested, purified and then inactivated by formaldehyde.
It confers immunity against hepatitis A virus ( H A V ) by inducing antibody titres longer lasting and higher than those obtained after passive immunisation with immunoglobulins. This vaccine has been demonstrated to elicit protective anti-HAV antibody titres (≥ 20 mIU/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.
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.
Avaxim 160 U: 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.
Pharmacokinetics: Not applicable.
Toxicology: 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.

Avaxim 80 U Pediatric: AVAXIM 80 U PEDIATRIC is indicated for active immunisation against infection caused by hepatitis A virus in children aged from 12 months to 15 years inclusive, who are at risk either of contaminating or spreading infection or of a life-threatening disease if infected.
Transmission of the hepatitis A virus usually occurs through the consumption of contaminated water or food. Persons in contact with contaminated subjects are usually infected through oro-fecal routes.
The possibility of transmission through the blood or by sexual contacts (oral-anal relations) has also been proven.
Potential candidates for the vaccine are: travellers to countries where hepatitis A is endemic, especially when travel involves rural or primitive conditions; residents of communities with high endemic rates or recurrent outbreaks of HAV; members of the armed forces, emergency relief workers and others likely to be posted abroad at short notice to areas with high rates of HAV infection; residents and staff of institutions for the developmentally challenged where there is an ongoing problem with HAV transmission; inmates of correctional facilities in which there is an ongoing problem with HAV infection; people with life-style determined risks of infection, including those engaging in oral or intravenous illicit drug use in unsanitary conditions; men who have sex with men; people with chronic liver disease who may not be at increased risk of infection but are at increased risk of fulminant hepatitis A; patients with hemophilia A or B receiving plasma-derived replacement clotting factors; zoo-keepers, veterinarians and researchers who handle non-human primates; certain workers involved in research on hepatitis A virus or production of hepatitis A vaccine.
Avaxim 160 U: This medicinal product is recommended for the prevention of infection caused by hepatitis A virus in adolescents from 16 years of age and in adults. Vaccination against viral hepatitis A is recommended for subjects at risks of exposure to hepatitis A virus including: Non-immunised adolescents from 16 years of age and adults travelling in endemic areas; Adults at risk of contamination through their work: nursery personnel, personnel in residential institutions and homes for handicapped children and young people, sewage and water treatment personnel, food industry and catering personnel; Adolescents from 16 years of age and adults exposed to specific risk: haemophilia, multiple transfusion, IV drug dependency, homosexual practices; Adolescents from 16 years of age and adults chronically infected by Hepatitis B virus.
It does not protect against infection due to other types of hepatitis virus or to other known pathogens of the liver.

Posology: Avaxim 80 U Pediatric: 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.
Avaxim 160 U: 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-HAV antibodies persist several years (beyond 10 years) after the second dose (booster).
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.
Avaxim 160 U: See Special precautions for disposal and other handling under Cautions for Usage for the instructions on preparation.

Avaxim 80 U Pediatric: An overdose is unlikely to provoke any harmful effects.
Avaxim 160 U: 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.
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.
AVAXIM 80 U PEDIATRIC and AVAXIM 160 U has not been studied in patients with impaired immunity.
Immunosupressive 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 80 U PEDIATRIC and 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, vaccination may not induce a protective response in some vaccinees.
The 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 and 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.
AVAXIM 80 U PEDIATRIC and AVAXIM 160 U contains less than 1 mmol (39 mg) of potassium and less than 1 mmol (23 mg) of sodium per dose, that is to say essentially "potassium-free" and "sodium-free".
AVAXIM 80 U PEDIATRIC and AVAXIM 160 U, AVAXIM 80 U PEDIATRIC contains 2 mg of alcohol (ethanol) per dose of 0.5 mL. The quantity for 1 dose of this medicinal product is equivalent to less than 0.1 mL of beer or less than 0.1 mL of wine. The small quantity of alcohol contained in this medicinal product is not likely to cause any notable effects.
Effects on ability to drive and use machines: The effects on the ability to drive and use machines have not been studied.

Pregnancy: Avaxim 80 U Pediatric: 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.
Avaxim 160 U: 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: Avaxim 80 U Pediatric: The effect of administration of AVAXIM 80U Pediatric during lactation has not been assessed. As AVAXIM 80U Pediatric is inactivated, any risk to the mother or the infant is improbable. The benefits versus the risks of administering AVAXIM 80U Pediatric during lactation should carefully be evaluated.
Avaxim 160 U: The effect of administering this vaccine during breast feeding has not been studied and its use during breast feeding is therefore not recommended.

AVAXIM 80 U PEDIATRIC: Summary of the safety profile: More than 6200 children aged from 12 months to 15 years were vaccinated with AVAXIM 80 U PEDIATRIC during clinical trials.
Most 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.
However, as with all pharmaceuticals, expanded commercial use of the vaccine might reveal rarer undesirable effects.
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 as follows 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. (See table.)

Click on icon to see table/diagram/image

AVAXIM 160 U: 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.
Gastrointestinal disorders: 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.
Investigations: 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: AVAXIM 80 U Pediatric and AVAXIM 160 U: 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.

Avaxim 80 U Pediatric: 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.
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.
Avaxim 160 U: 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.

Incompatibilities: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Special precautions for disposal and other 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 requirements.
Avaxim 160 U: For the syringes without attached needles, the separate needle should be fitted firmly to the syringe, rotating it by one quarter turn.

Store in a refrigerator (2°C - 8°C). Do not freeze.
If frozen, the vaccine should be discarded.
Keep in the original packaging, protected from light.
Shelf-life:3 years.

Vaccines, Antisera & Immunologicals

J07BC02 - hepatitis A, inactivated, whole virus ; Belongs to the class of hepatitis viral vaccines.

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