4.1. Therapeutic indications

HBVAXPRO is indicated for active immunisation against hepatitis B virus infection caused by all known subtypes in individuals from birth through 15 years of age considered at risk of exposure to hepatitis B virus.

The specific at risk categories to be immunised are to be determined on the basis of the official recommendations.

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

Individuals from birth through 15 years of age: 1 dose (0.5 mL) at each injection.

Primary vaccination:

A course of vaccination should include at least three injections.

Two primary immunisation schedules can be recommended:

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

0, 1, 2, 12 months: three injections with an interval of one month; a fourth dose should be administered at 12 months.

It is recommended that the vaccine be administered in the schedules indicated. Infants receiving the compressed regimen (0, 1, 2 months dosing schedule) must receive the 12 month booster to induce higher antibody titres.

Booster:

Immunocompetent vaccinees

The need for a booster dose in healthy individuals who have received a full primary vaccination course has not been established. However, some local vaccination schedules currently include a recommendation for a booster dose and these should be respected.

Immunocompromised vaccinees (e.g. dialysis patients, transplant patients, AIDS Patients)

In vaccinees with an impaired immune system, administration of additional doses of vaccine should be considered if the antibody level against hepatitis B virus surface antigen (anti-HBsAg) is less than 10 IU/l.

Revaccination of nonresponders

When persons who do not respond to the primary vaccine series are revaccinated, 15-25 % produce an adequate antibody response after one additional dose and 30-50 % after three additional doses. However, because data are insufficient concerning the safety of hepatitis B vaccine when additional doses in excess of the recommended series are administered, revaccination following completion of the primary series is not routinely recommended. Revaccination should be considered for high-risk individuals, after weighing the benefits of vaccination against the potential risk of experiencing increased local or systemic adverse reactions.

Special dosage recommendations:

Dosage recommendations for neonates born to mothers who are hepatitis B virus carriers

- At birth, one dose of hepatitis B immunoglobulin (within 24 hours).

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

- Subsequent doses of vaccine should be given according to the locally recommended vaccination schedule.

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. The accelerated schedule including the 12 month booster dose can be proposed.

Method of administration

This vaccine should be administered intramuscularly.

The anterolateral thigh is the preferred site for injection in neonates and infants. The deltoid muscle is the preferred site for injection in children and adolescents.

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, the syringe plunger stopper and tip cap contain dry natural latex rubber that may cause allergic reactions.

For clinical or laboratory monitoring regarding immunocompromised individuals or individuals with known or presumed exposure to hepatitis B virus, see section 4.2.

The potential risk of apnoea and the need for respiratory monitoring for 48 to 72 hours should be considered when administering the primary immunisation series to very premature infants (born ≤ 28 weeks of gestation) and particularly for those with a previous history of respiratory immaturity (see section 4.8). As the benefit of vaccination is high in this group of infants, vaccination should not be withheld or delayed.

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.

The concomitant administration of pneumococcal conjugate vaccine (PREVENAR) given with hepatitis B vaccine using the 0, 1 and 6 and 0, 1, 2 and 12 month schedules has not been sufficiently studied.

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 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.

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)

c. Other special population

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

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.