4.1. Therapeutic indications

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.

4.2. Posology and method of administration

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 haemodialysis 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 thrombocytopaenia or bleeding disorders.

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

4.3. Contraindications

- 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 6.2.

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

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.

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).

Excipient(s) with known effect:

This medicinal product contains less than 1mmol sodium (23 mg) per dose, and is considered to be essentially sodium free.

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

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.

4.6. Fertility, pregnancy and lactation

Fertility:

HBVAXPRO has not been evaluated in fertility studies.

Pregnancy:

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

4.7. Effects on ability to drive and use machines

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.

4.8. Undesirable effects

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.

Adverse reactions

Frequency

General disorders and administration site conditions

Local reactions (injection site): Transient soreness, Erythema, Induration

Common (≥1/100 to, <1/10)

Fatigue, Fever, Malaise, Influenza-like symptoms

Very rare (<1/10,000)

Blood and the lymphatic system disorders

Thrombocytopaenia, Lymphadenopathy

Very rare (<1/10,000)

Immune system disorders

Serum sickness, Anaphylaxis, Polyarteritis nodosa

Very rare (<1/10,000)

Nervous system disorders

Paresthesia, Paralysis (including Bell's palsy, facial paralysis), Peripheral neuropathies (polyradiculoneuritis, Guillain Barre Syndrome), Neuritis (including optical neuritis), Myelitis (including transverse Myelitis), Encephalitis, Demyelinating disease of the central nervous system, Exacerbation of multiple sclerosis, Multiple sclerosis, Seizure, Headache, Dizziness, Syncope

Very rare (<1/10,000)

Eye disorders

Uveitis

Very rare (<1/10,000)

Vascular disorders

Hypotension, Vasculitis

Very rare (<1/10,000)

Respiratory, thoracic and mediastinal disorders

Bronchospasm-like symptoms

Very rare (<1/10,000)

Gastrointestinal disorders

Vomiting, Nausea, Diarrhoea, Abdominal pain

Very rare (<1/10,000)

Skin and subcutaneous tissue disorders

Rash, Alopecia, Pruritus, Urticaria, Erythema multiforme, Angioedema, Eczema

Very rare (<1/10,000)

Musculoskeletal, connective tissue and bone disorders

Arthralgia, Arthritis, Myalgia, Pain in extremity

Very rare (<1/10,000)

Investigations

Elevation of liver enzymes

Very rare (<1/10,000)

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 the 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

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.