Sanofi Pasteur MSD Limited

In section 6.5 (nature and contents of container), added 'or chlorobutyl' after chlorobromobutyl to extend the nature of the plunger stopper

Addition of information related to the long term protectin provided by Avaxim

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.

 
In section 4.2: clarification of the section and move part of the information in section 5.1

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.  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 Section 4.8). 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.

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. There are serological data to show that there should be continuing protection against hepatitis A for up to 36 months after a first dose in subjects who responded to the initial vaccination.

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 after the primary immunisation but may be administered up to 36 months after the primary immunisation first dose (see section 5.1). It is predicted that HAV antibodies persist for many years (beyond 10 years) after the booster vaccination second dose.

Current recommendations do not support the need for further booster vaccinations for immunocompetent individuals after the initial two-dose vaccination course.

In the event that the second dose (booster) has been delayed after 36 months, there may be a decreased anti-hepatitis A antibody response. If long-term protection is required, the serum anti-hepatitis A antibody titre should be determined after AVAXIM administration of the second dose.

The vaccine may be used as a 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.

 
Addition of a precaution in section 4.4

4.4     Special warnings and precautions for use

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 Section 4.8).

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) dose of AVAXIM is not currently available has not been fully evaluated. Nevertheless, available data (antibody titres obtained two years after the second dose) suggests that anti-HAV antibodies persist beyond 10 years after the booster vaccination second dose in healthy individuals.

Change to section 2 - qualitative and quantitative composition

Changed mL to millilitre in line with current guidelines.  Added ‘Excipient(s)’ as per QRD template.

Change to section 4.1 - therapeutic indications

Wording at end of 1^st paragraph changed to improve clarity.

Change to section 4.2 - Posology and method of administration

Added heading ‘Posology’ to aid navigation, information moved into more appropriate sections, cross-reference to other sections to meet QRD template.

Change to section 4.3 - Contra-indications

Re-worded contraindication on hypersensitivity as per QRD template.

Change to section 4.4 - Special warnings & precautions for use

Information moved into more appropriate sections and re-ordered as per SPC guideline.

Change to section 4.5 - Interactions with other medicaments

Re-worded to improve clarity.

Change to section 4.6 - Pregnancy and lactation

Headings added to aid navigation and text on pregnancy re-worded in line with QRD template.

Change to section 4.7 - Effects on ability to drive and use machines

Re-worded in line with QRD template.

Change to section 4.8 - Undesirable effects

Section re-organised in line with QRD template.

Change to section 4.9 - Overdose

Amended to state whether any cases of overdose have been reported.

Change to section 5.1 - Pharmacodynamic properties

Pharmacotherapeutic group has been added, as per SPC guidelines.

Change to section 5.2 - Pharmacokinetic properties

Re-worded to improve clarity.

Change to section 5.3 - Preclinical safety data

Re-worded as per QRD template.

Change to section 6.1 - List of excipients

Re-formatted to improve clarity.  Mention of phenylalanine, as per guideline on excipients.

Change to section 6.4 – Special precautions for storage

Re-worded according to QRD template.

Change to section 6.6. – Instructions for use/handling

Added sentences as per the guideline ‘Pharmaceutical aspects of the product information for human vaccines’ and as per QRD template.

Change to section 10 – Date of partial revision of the text.