4.1. Therapeutic indications

Engerix B is indicated for in neonates, infants, children and adolescents up to and including 15 years of age for active immunisation against hepatitis B virus infection (HBV) caused by all known subtypes in non immune subjects. 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. 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.

4.2. Posology and method of administration

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 (see below and section 5.1).

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 concentrations.

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 antibody concentrations 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, up to and including 15 years of age:

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 ≥ 10 m IU/ml.

- 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/1 ml 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/0.5 ml 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 concentrations.

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 antibody concentrations 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 concentrations remain 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 (see section 4.5). The 0, 1, 2-12 months immunisation schedule should be advised.

Subjects up to and including 15 years of age: These immunisation schedules may be adjusted to accommodate local immunisation practices with regard to the recommended age of administration of other childhood vaccines.

Subjects 16 years of age and above: 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.

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

National recommendations on booster vaccination should be considered.

Interchangeability of hepatitis B vaccines

See section 4.5.

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.

4.3. Contraindications

Engerix B should not be administered to subjects with known hypersensitivity to the active substances or to any of the excipients listed in section 6.1, 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.

4.4. Special warnings and precautions for use

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Precautions for use

Syncope (fainting) can occur following, or even before any vaccination especially in adolescents as a psychogenic response to the needle injection. This can be accompanied by several neurological signs such as transient visual disturbance, paraesthesia and tonic-clonic limb movements during recovery. It is important that procedures are in place to avoid injury from faints.

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

ENGERIX B Junior should under no circumstances be administered intravascularly.

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.

Protection

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.

Special population

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 concentrations may not be obtained after the primary immunisation course and such patients may therefore require administration of additional doses of vaccine.

Preterm infants

The potential risk of apnoea and the need for respiratory monitoring for 48-72h should be considered when administering the primary immunization series to very premature infants born ≤ 28 weeks of gestation) and particularly for those with a previous history of respiratory immaturity. As the benefit of vaccination is high in this group of infants, vaccination should not be withheld or delayed.

Sodium content

This vaccine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 'sodium free'.

4.5. Interaction with other medicinal products and other forms of interaction

The simultaneous administration of Engerix B and a standard dose of HBIg does not result in lower anti-HBs antibody concentrations 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.

Engerix B can be given concomitantly with Human Papillomavirus (HPV) vaccine. Administration of Engerix B at the same time as Cervarix (HPV vaccine) has shown no clinically relevant interference in the antibody response to the HPV antigens. Anti-HBs geometric mean antibody concentrations were lower on co-administration, but the clinical significance of this observation is not known since the seroprotection rates remain unaffected. The proportion of subjects reaching anti-HBs ≥ 10mIU/ml was 97.9% for concomitant vaccination and 100% for Engerix B alone.

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.

It may be expected that in patients receiving immunosuppressive treatment or patients with immunodeficiency, an adequate immune response may not be elicited (see section 4.4).

4.6. Fertility, pregnancy and lactation

Pregnancy

The effect of the HBsAg on foetal development has not been assessed.

However, as with all inactivated viral vaccines one does not expect harm for the foetus. Engerix B should be used during pregnancy only when clearly needed, and the possible advantages outweigh the possible risks for the foetus.

Breast-feeding

The effect on breastfed infants of the administration of Engerix B to their mothers has not been evaluated in clinical studies, as information concerning the excretion into the breast milk is not available.

No contraindication has been established.

Fertility

Engerix B has not been evaluated in fertility studies.

4.7. Effects on ability to drive and use machines

Engerix B has no or negligible influence on the ability to drive and use machines.

4.8. Undesirable effects

Summary of the safety profile

The safety profile presented below is based on data from 5329 subjects followed in 23 studies.

The current formulation of Engerix B does not contain thiomersal (an organomercuric compound). The following undesirable effects have been reported following the use of the thiomersal containing formulations as well as the thiomersal free formulation.

In one clinical study conducted in adults with the current formulation (thiomersal free formulation), the incidence of pain, redness, swelling, fatigue, gastro-enteritis, headache and fever was comparable to the incidence observed in the clinical studies conducted with former thiomersal containing vaccine formulations.

In one clinical study conducted in children with the current formulation (thiomersal free formulation), the incidence of pain, redness, swelling, drowsiness, irritability, loss of appetite and fever was comparable to the incidence observed in the clinical studies conducted with former thiomersal containing vaccine formulations.

Tabulated summary of adverse reactions

Frequencies per dose are defined as follows:

Very common:

Common:

Uncommon:

Rare;

Very rare:

≥1/10

≥1/100 to <1/10

≥1/1000 to <1/100

≥1/10,000 to <1/1000

<1/10,000

System Organ Class

Frequency

Adverse reactions

Clinical trials

Blood and lymphatic system disorders

Rare

Lymphadenopathy

Metabolism and nutrition disorders

Common

Appetite lost

Psychiatric disorders

Very common

Irritability

Nervous system disorders

Very common

Headache (paediatric use)

Common

Drowsiness, headache (adult use)

Uncommon

Dizziness

Rare

Paraesthesia

Gastrointestinal disorders

Common

Gastrointestinal symptoms (such as nausea, vomiting, diarrhoea, abdominal pain)

Skin and subcutaneous tissue disorders

Rare

Urticaria, pruritus, rash

Musculoskeletal and connective tissue disorders

Uncommon

Myalgia

Rare

Arthralgia

General disorders and administration site conditions

Very common

Pain and redness at injection site, fatigue

Common

Fever (≥37.5°C), malaise, swelling at injection site, injection site reaction (such as induration)

Uncommon

Influenza-like illness

Post-marketing surveillance

Infections and infestations

Not known (cannot be estimated from the available data)

Meningitis

Blood and lymphatic system disorders

Not known (cannot be estimated from the available data)

Thrombocytopenia

Immune system disorders

Not known (cannot be estimated from the available data)

Anaphylaxis, allergic reactions including anaphylactoid reactions and mimicking serum sickness, polyarteritis nodosa

Nervous system disorders

Not known (cannot be estimated from the available data)

Encephalitis, encephalopathy, convulsions, paralysis, neuritis (including Guillain-Barré syndrome, optic neuritis and multiple sclerosis), neuropathy, hypoaesthesia

Vascular disorders

Not known (cannot be estimated from the available data)

Vasculitis, hypotension

Respiratory thoracic and mediastinal disorders

Not known (cannot be estimated from the available data)

Apnoea in very premature infants (≤ 28 weeks of gestation) (see section 4.4)

Skin and subcutaneous tissue disorders

Not known (cannot be estimated from the available data)

Erythema multiforme, angioneurotic oedema, lichen planus

Musculoskeletal and connective tissue disorders

Not known (cannot be estimated from the available data)

Arthritis, muscular weakness

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/1 ml was similar overall to that reported after the standard three-dose regimen of Engerix B 10 µg/0.5 ml.

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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Cases of overdose have been reported during post-marketing surveillance. Adverse events reported following overdosage were similar to those reported with normal vaccine administration.