Genetically derived surface antigens (vaccines).

Hepatitis B

Engerix B® 20 micrograms/1 ml Suspension for injection Hepatitis B recombinant vaccine, adsorbed

Suspension for injection.

Engerix B is indicated for active immunisation against hepatitis B virus infection (HBV) caused by all known subtypes in non immune subjects. The categories within the population to be immunised are determined on the basis of official recommendations. It can be expected that hepatitis D will also be prevented by immunisation with Engerix B as hepatitis D (caused by the delta agent) does not occur in the absence of hepatitis B infection.

Posology

Dosage

The 20 μg dose vaccine in 1.0 ml suspension is intended for use in subjects 16 years of age and above.

The 10 μg dose vaccine in 0.5 ml suspension is intended for use in subjects up to and including 15 years of age, including neonates.

However, the 20 μg vaccine can also be used in subjects from 11 years up to and including 15 years of age as a 2-dose schedule in situations when there is a low risk of hepatitis B infection during the vaccination course, and when compliance with the complete vaccination course can be assured.

Primary Immunisation schedules

Subjects up to and including 15 years of age:

Two primary immunisation schedules can be recommended:

A 0, 1, 6 months schedule which gives optimal protection at month 7 and produces high antibody titres.

An accelerated schedule, with immunisation at 0, 1 and 2 months, which will confer protection more quickly and is expected to provide better patient compliance. With this schedule, a fourth dose should be administered at 12 months to assure long term protection as titres after the third dose are lower than those obtained after the 0, 1, 6 months schedule. In infants this schedule will allow for simultaneous administration of hepatitis B with other childhood vaccines.

- Patients with renal insufficiency including patients undergoing haemodialysis:

Patients with renal insufficiency, including patients undergoing haemodialysis, have a reduced immune response to hepatitis B vaccines. Either the 0, 1, 2 and 12 months or the 0, 1, 6 months schedule of Engerix B (10 μg) can be used. Based on adult experience, vaccination with a higher dosage of antigen may improve the immune response. Consideration should be given to serological testing following vaccination. Additional doses of vaccine may be needed to ensure a protective anti-HBs level of > 10 IU/l.

- Neonates born of mothers who are HBV carriers:

The immunisation with Engerix B (10 μg) of these neonates should start at birth, and two immunisation schedules have been followed. Either the 0, 1, 2 and 12 months or the 0, 1 and 6 months schedule can be used; however, the former schedule provides a more rapid immune response. When available, hepatitis B immune globulins (HBIg) should be given simultaneously with Engerix B at a separate injection site as this may increase the protective efficacy.

Subjects from 11 years up to and including 15 years of age:

The 20 μg vaccine may be administered in subjects from 11 years up to and including 15 years of age according to a 0, 6 months schedule. However, in this case, protection against hepatitis B infections may not be obtained until after the second dose (see section 5.1). Therefore, this schedule should be used only when there is a low risk of hepatitis B infection during the vaccination course and when completion of the two-dose vaccination course can be assured. If both conditions cannot be assured (for instance patients undergoing haemodialysis, travellers to endemic regions and close contacts of infected subjects), the three dose or the accelerated schedule of the 10 μg vaccine should be used.

Subjects 16 years of age and above:

Two primary immunisation schedules can be recommended:

A 0, 1, 6 months schedule which gives optimal protection at month 7 and produces high antibody titres.

An accelerated schedule, with immunisation at 0, 1 and 2 months, which will confer protection more quickly and is expected to provide better patient compliance. With this schedule, a fourth dose should be administered at 12 months to assure long term protection as titres after the third dose are lower than those obtained with the 0, 1, 6 months schedule.

Subjects 18 years of age and above:

In exceptional circumstances in adults, where an even more rapid induction of protection is required, e.g. persons travelling to areas of high endemicity and who commence a course of vaccination against hepatitis B within one month prior to departure, a schedule of three intramuscular injections given at 0, 7 and 21 days may be used. When this schedule is applied, a fourth dose is recommended 12 months after the first dose.

- Patients with renal insufficiency including patients undergoing haemodialysis, 16 years of age and above:

The primary immunisation schedule for patients, with renal insufficiency including patients undergoing haemodialysis is four double doses (2 x 20 μg) at elected date, 1 month, 2 months and 6 months from the date of the first dose. The immunisation schedule should be adapted in order to ensure that the anti-HBs antibody titre remains equal to or higher than the accepted protective level of 10 IU/l.

- Known or presumed exposure to HBV:

In circumstances where exposure to HBV has recently occurred (eg needlestick with contaminated needle) the first dose of Engerix B can be administered simultaneously with HBIg which, however, must be given at a separate injection site. The 0, 1, 2-12 months immunisation schedule should be advised.

These immunisation schedules may be adjusted to accommodate local immunisation practices.

Booster dose

Current data do not support the need for booster vaccination among immunocompetent subjects who have responded to a full primary vaccination course (Lancet 2000, 355:561).

However, in immunocompromised subjects (eg subjects with chronic renal failure, haemodialysis patients, HIV positive subjects), boosters should be administered to maintain anti-HBs antibody titre equal or higher than the accepted protective level of 10 IU/l. For these immunocompromised subjects, post-vaccination testing every 6-12 months is advised.

National recommendations on booster vaccination should be considered.

Method of Administration

Engerix B should be injected intramuscularly in the deltoid region in adults and children or in the anterolateral thigh in neonates, infants and young children.

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

12 years and under: 0 .5 mL by intramuscular injection into the antero-lateral aspect of thigh (infants) or deltoid, repeated 1 month and 6 months later. Rapid immunisation, 0 .5 mL by intramuscular injection, repeated 1 month, 2 months and 12 months later.

Engerix B should not be administered to subjects with known hypersensitivity to any component of the vaccine, or to subjects having shown signs of hypersensitivity after previous Engerix B administration.

As with other vaccines, the administration of Engerix B should be postponed in subjects suffering from acute severe febrile illness. The presence of a minor infection, however, is not a contra-indication for immunisation.

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

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

As with any vaccine, a protective immune response may not be elicited in all vaccinees.

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 Engerix B. Additional doses may need to be considered for persons who do not respond or have a sub-optimal response to a course of vaccinations.

Patients with chronic liver disease or with HIV infection or hepatitis C carriers should not be precluded from vaccination against hepatitis B. The vaccine could be advised since HBV infection can be severe in these patients: the HB vaccination should thus be considered on a case by case basis by the physician. In HIV infected patients, as also in patients with renal insufficiency including patients undergoing haemodialysis and persons with an impaired immune system, adequate anti-HBs antibody titres may not be obtained after the primary immunisation course and such patients may therefore require administration of additional doses of vaccine.

Engerix B should not be administered in the buttock or intradermally since this may result in a lower immune response.

Engerix B should under no circumstances be administered intravenously.

Thiomersal (an organomercuric compound) has been used in the manufacturing process of this medicinal product and residues of it are present in the final product. Therefore, sensitisation reactions may occur.

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.

The simultaneous administration of Engerix B and a standard dose of HBIg does not result in lower anti-HBs antibody titres provided that they are administered at separate injection sites.

Engerix B can be given concomitantly with Haemophilus influenzae b, BCG, hepatitis A, polio, measles, mumps, rubella, diphtheria, tetanus and pertussis vaccines.

Different injectable vaccines should always be administered at different injection sites.

Engerix B may be used to complete a primary immunisation course started either with plasma-derived or with other genetically-engineered hepatitis B vaccines, or, if it is desired to administer a booster dose, it may be administered to subjects who have previously received a primary immunisation course with plasma-derived or with other genetically-engineered hepatitis B vaccines.

Engerix B is generally well tolerated.

The following undesirable events 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.

Blood and lymphatic system disorders

Very rare: thrombocytopenia

Immune system disorders

Very rare: anaphylaxis, serum sickness, lymphadenopathy

Nervous system disorders

Rare: dizziness, headache, paraesthesia

Very rare: syncope, paralysis, neuropathy, neuritis (including Guillain-Barré syndrome, optic neuritis and multiple sclerosis), encephalitis, encephalophy, meningitis, convulsions

Vascular disorders

Very rare: hypotension, vasculitis

Respiratory, thoracic and mediastinal disorders

Very rare: bronchospasm

Gastrointestinal disorders

Rare: nausea, vomiting, diarrhoea, abdominal pain

Hepatobiliary disorders

Rare: hepatic function abnormal

Skin and subcutaneous tissue disorders

Rare: rash, pruritus, urticaria

Very rare: angioneurotic oedema, erythema multiforme

Musculoskeletal and connective tissue disorders

Rare: athralgia, myalgia

Very rare: arthritis

General disorders and administration site conditions

Common: injection site pain, injection site erythema, injection site induration

Rare: fatigue, fever, malaise, influenza-like symptoms

The booster dose is as well tolerated as the primary vaccination.

In a comparative trial in subjects from 11 years up to and including 15 years of age, the incidence of local and general solicited symptoms reported after a two-dose regimen of Engerix B 20 μg was similar overall to that reported after the standard three-dose regimen of Engerix B 10 μg.

GlaxoSmithKline(GSK)

(POM)

25 June 2009