This information is intended for use by health professionals

1. Name of the medicinal product

HBVAXPRO® 10 micrograms, suspension for injection in pre-filled syringe

Hepatitis B vaccine (recombinant DNA)

2. Qualitative and quantitative composition

One dose (1 ml) contains:

Hepatitis B virus surface antigen, recombinant (HBsAg) *………… 10 micrograms

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

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

This 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.

Excipient(s) with known effect:

Sodium less than 1mmol (23 mg) per dose.

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Suspension for injection in pre-filled syringe

Slightly opaque white suspension.

4. Clinical particulars
4.1 Therapeutic indications

HBVAXPRO is indicated for active immunisation against hepatitis B virus infection caused by all known subtypes in individuals 16 years of age or more 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


Individuals 16 years of age or more: 1 dose (1 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. Those receiving the compressed regimen (0, 1, 2 months dosing schedule) must receive the 12 month booster to induce higher antibody titres.


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 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 vaccinates individuals, additional doses should be given as in the recommended immunisation schedules. The accelerated schedule including the 12 month booster dose can be proposed.

Individuals less than 16 years of age:

HBVAXPRO 10 micrograms is not indicated in this subset of paediatric population.

The appropriate strength for administration to individuals from birth through 15 years of age is HBVAXPRO 5 micrograms.

Method of administration

This vaccine should be administered intramuscularly.

The deltoid muscle is the preferred site for injection in adults 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 2.

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

4.4 Special warnings and precautions for use


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 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.

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


HBVAXPRO has not been evaluated in fertility studies.


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.


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


General disorders and administration site conditions

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


(≥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


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)


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 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.

5. Pharmacological properties
5.1 Pharmacodynamic properties

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). In two trials conducted in older adolescents and adults, 95.6-97.5 % of vaccinees developed a protective level of antibodies, with geometric mean titres in these trials ranging from 535 – 793 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. As with other hepatitis B vaccines, the duration of the protective effect in healthy vaccinees is unknown at present. The need for a booster dose of HBVAXPRO is not yet defined beyond the 12 month booster dose required for the 0, 1, 2 compressed schedule.

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.

5.2 Pharmacokinetic properties

Not applicable.

5.3 Preclinical safety data

Animal reproduction studies have not been conducted.

6. Pharmaceutical particulars
6.1 List of excipients

Sodium chloride


Water for injections

6.2 Incompatibilities

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

6.3 Shelf life

3 years.

6.4 Special precautions for storage

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

Do not freeze. Store in the original package in order to protect from light.

HBVAXPRO should be administered as soon as possible after being removed from refrigeration. HBVAXPRO can be administered provided total (cumulative multiple excursion) time out of refrigeration (at temperatures between 8°C and 25°C) does not exceed 72 hours. Cumulative multiple excursions between 0°C and 2°C are also permitted as long as the total time between 0°C and 2°C does not exceed 72 hours. These are not, however, recommendations for storage.

6.5 Nature and contents of container

1 ml of suspension in pre-filled syringe (glass) without needle with a plunger stopper (gray chlorobutyl or bromobutyl). Pack size of 1, 10

1 ml of suspension in pre-filled syringe (glass) with 1 separate needle with a plunger stopper (gray chlorobutyl or bromobutyl). Pack size of 1, 10

1 ml of suspension in pre-filled syringe (glass) with 2 separate needles with a plunger stopper (gray chlorobutyl or bromobutyl). Pack size of 1, 10, 20

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

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 syringe should be well shaken.

Hold the syringe barrel and attach the needle by twisting in clockwise direction, until the needle fits securely on the syringe.

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

7. Marketing authorisation holder


162 avenue Jean Jaurès

69007 Lyon


8. Marketing authorisation number(s)








9. Date of first authorisation/renewal of the authorisation

Date of first authorisation: 27/04/2001

Date of last renewal: 17/03/2011

10. Date of revision of the text

29 April 2021

Detailed information on this product is available on the website of the European Medicines Agency

© Merck Sharp & Dohme (UK) Limited, 2021. All rights reserved.