Sanofi Pasteur MSD Limited

HBVAXPRO 40 micrograms, suspension for injection

Hepatitis B vaccine (rDNA)

One dose (1 ml) contains:

Hepatitis B virus surface antigen, recombinant (HBsAg) *.................. 40 micrograms

Adsorbed on amorphous aluminium hydroxyphosphate sulfate (0.50 milligram Al⁺)

* produced in Saccharomyces cerevisiae (strain 2150-2-3) yeast by recombinant DNA technology.

The vaccine may contain traces of formaldehyde and potassium thiocyanate which are used during the manufacturing process. See sections 4.3, 4.4 and 4.8.

For a full list of excipients, see section 6.1.

Suspension for injection

Slightly opaque white suspension.

HBVAXPRO is indicated for the active immunisation against hepatitis B virus infection caused by all known subtypes in predialysis and dialysis adult patients.

It can be expected that hepatitis D will also be prevented by immunisation with HBVAXPRO as hepatitis D (caused by the delta agent) does not occur in the absence of hepatitis B infection.

Posology

Predialysis and dialysis adult patients: 1 dose (1 ml) at each injection.

Primary vaccination:

A course of vaccination should include three injections:

Schedule 0, 1, 6 months: two injections with an interval of one month; a third injection 6 months after the first administration.

Booster:

A booster dose must be considered in these vaccinees if the antibody level against hepatitis B virus surface antigen (anti-HBsAg) after primary series is less than 10 IU/l.

In accordance with standard medical practice for hepatitis B vaccine administration, regular antibody testing should be done in hemodialysis patients. A booster dose should be given when antibody levels decline below 10 IU/l.

Special dosage recommendations for known or presumed exposure to hepatitis B virus (e.g needlestick with contaminated needle):

- Hepatitis B immunoglobulin should be given as soon as possible after exposure (within 24 hours).

- The first dose of the vaccine should be given within 7 days of exposure and can be administered simultaneously with hepatitis B immunoglobulin but at a separate injection site.

- Serologic testing is also recommended, with the administration of subsequent doses of vaccine, if necessary, (i.e according to the serologic status of the patient) for short and long term protection.

- In the case of unvaccinated or incompletely vaccinated individuals, additional doses should be given as in the recommended immunisation schedule.

Method of administration

This vaccine should be administered intramuscularly.

The deltoid muscle is the preferred site for injection in adults.

Do not inject intravascularly.

Exceptionally, the vaccine may be administered subcutaneously in patients with thrombocytopoenia or bleeding disorders.

Precautions to be taken before handling or administering the product: see section 6.6.

- History of hypersensitivity to the active substance, or to any of the excipients, or trace residuals (e.g. formaldehyde and potassium thiocyanate) (see sections 6.1 and 2)

- Vaccination should be postponed in individuals with a severe febrile illness or acute infection.

As with all injectable vaccines, appropriate medical treatment should always be readily available in case of rare anaphylactic reactions following the administration of the vaccine (see section 4.8).

This vaccine may contain traces of formaldehyde and potassium thiocyanate which are used during the manufacturing process. Therefore, hypersensitivity reactions may occur (see sections 2 and 4.8).

Use caution when vaccinating latex-sensitive individuals since the vial stopper contains dry natural latex rubber that may cause allergic reactions.

A number of factors have been observed to reduce the immune response to hepatitis B vaccines. These factors include older age, male gender, obesity, smoking, route of administration and some chronic underlying diseases. Consideration should be given to serological testing of those subjects who may be at risk of not achieving seroprotection following a complete course of HBVAXPRO. Additional doses may need to be considered for persons who do not respond or have a sub-optimal response to a course of vaccinations.

Because of the long incubation period of hepatitis B, it is possible for unrecognised hepatitis B infection to be present at the time of vaccination. The vaccine may not prevent hepatitis B infection in such cases.

The vaccine will not prevent infection caused by other agents such as hepatitis A, hepatitis C and hepatitis E and other pathogens known to infect the liver.

Caution should be exercised when prescribing to pregnant or breast-feeding women. (see section 4.6).

This vaccine can be administered:

- with hepatitis B immunoglobulin, at a separate injection site.

- to complete a primary immunisation course or as a booster dose in subjects who have previously received another hepatitis B vaccine.

- concomitantly with other vaccines, using separate sites and syringes.

Fertility:

HBVAXPRO has not been evaluated in fertility studies.

Pregnancy:

There is no clinical data on the use of HBVAXPRO on pregnant women.

The vaccine should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.

Breast-feeding:

There is no clinical data on the use of HBVAXPRO on breast-feeding women.

No studies on the effects on the ability to drive and use machines have been performed. However, HBVAXPRO is expected to have no or negligible influence on the ability to drive and use machines.

a. Summary of the safety profile

The most common side effects seen are injection-site reactions: transient soreness, erythema, induration.

b. Tabulated summary of adverse reactions

The following undesirable effects have been reported following the widespread use of the vaccine.

As with other hepatitis B vaccines, in many instances, the causal relationship to the vaccine has not been established.

There have been reports of administration of higher than recommended doses of HBVAXPRO.

In general, the adverse event profile reported with overdose was comparable to that observed with the recommended dose of HBVAXPRO.

Pharmacotherapeutic group: anti-infectious, ATC code: J07BC01

The vaccine induces specific humoral antibodies against hepatitis B virus surface antigen (anti-HBsAg). Development of an antibody titre against hepatitis B virus surface antigen (anti-HBsAg) equal to or greater than 10 IU/l measured 1 to 2 months after the last injection correlates with protection to hepatitis B virus infection.

In clinical trials, 96 % of 1,497 healthy infants, children, adolescents and adults given a 3 dose course of a previous formulation of Merck's recombinant hepatitis B vaccine developed a protective level of antibodies against hepatitis B virus surface antigen ( 10 IU/l).

Although the duration of the protective effect of a previous formulation of Merck's recombinant hepatitis B vaccine in healthy vaccinees is unknown, follow-up over 5-9 years of approximately 3,000 high-risk subjects given a similar plasma-derived vaccine has revealed no cases of clinically apparent hepatitis B infection.

In addition, persistence of vaccine-induced immunologic memory for hepatitis B virus surface antigen (HBsAg) has been demonstrated through an anamnestic antibody response to a booster dose of a previous formulation of Merck's recombinant hepatitis B vaccine in healthy adults.

In accordance with standard medical practice for hepatitis B vaccine administration, regular antibody testing should be done in hemodialysis patients. A booster dose should be given when antibody levels decline below 10 IU/l. In subjects in whom insufficient antibody titres are achieved after boosting, the use of alternative hepatitis B vaccines should be considered.

Reduced risk of Hepatocellular Carcinoma

Hepatocellular carcinoma is a serious complication of hepatitis B virus infection. Studies have demonstrated the link between chronic hepatitis B infection and hepatocellular carcinoma and 80 % of hepatocellular carcinomas are caused by hepatitis B virus infection. Hepatitis B vaccine has been recognized as the first anti-cancer vaccine because it can prevent primary liver cancer.

Not applicable.

Animal reproduction studies have not been conducted.

Sodium chloride

Borax

Water for injections.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

3 years.

Store in a refrigerator (2 °C – 8 °C).

Do not freeze.

1 ml of suspension in vial (glass) with stopper (gray butyl rubber) and aluminum seals with plastic flip caps. Pack size of 1.

The vaccine should be inspected visually in order to detect any appearance of precipitate or discolouring of the content prior to administration. If these conditions exist, the product should not be administered.

Before use, the vial should be well shaken.

Once the vial has been penetrated, the withdrawn vaccine should be used promptly, and the vial must be discarded.

Any unused product or waste material should be disposed of in accordance with local requirements.

SANOFI PASTEUR MSD SNC

8, rue Jonas Salk

F-69007 Lyon

France

EU/1/01/183/015

Date of first authorisation: 27/04/2001

Date of last renewal: 27/04/2011

08/2011

Detailed information on this product is available on the website of the European Medicines Agency http://www.ema.europa.eu