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HBvaxPRO

HBVAXPRO® 10 micrograms suspension for injection

Manufacturer
Merck Sharp & Dohme (UK) Limited
Label last updated
03 Jan 2023
Source
Official SmPC ↗

Recombinant hepatitis B vaccine for people aged 16 and over at risk of exposure. The 10 microgram strength is not indicated for under-16s, who need the 5 microgram version.

42 findings, each with the section of the label it comes from.

Ingredients and materials

  • Hepatitis B virus surface antigen, recombinant (HBsAg), 10 micrograms per 1 ml doses.2
  • Produced in Saccharomyces cerevisiae (strain 2150-2-3) yeast by recombinant DNA technologys.2
  • Adsorbed on amorphous aluminium hydroxyphosphate sulfate, 0.50 mg aluminium, present as an adjuvants.2
  • May contain traces of formaldehyde and potassium thiocyanate used during manufacture; hypersensitivity to these trace residuals is a contraindications.2, 4.3, 4.4
  • Excipients: sodium chloride, borax, water for injectionss.6.1
  • The vial stopper, syringe plunger stopper and tip cap contain dry natural latex rubber, so caution is advised in latex-sensitive individualss.4.4
  • Declared essentially sodium free, less than 1 mmol (23 mg) sodium per doses.2, 4.4

Manufacture, storage and handling

  • Shelf life 3 yearss.6.3
  • Store at 2C to 8C, do not freeze, store in the original package to protect from lights.6.4
  • Total cumulative time out of refrigeration between 8C and 25C must not exceed 72 hours; cumulative excursions between 0C and 2C are also permitted up to 72 hours. These are not storage recommendationss.6.4
  • Intramuscular injection, deltoid preferred in adults and adolescents; do not inject intravascularlys.4.2
  • Exceptionally may be given subcutaneously in patients with thrombocytopenia or bleeding disorderss.4.2
  • Must be inspected for precipitate or discolouration; do not administer if either is present. Shake well before uses.6.6
  • Once a vial has been penetrated, the withdrawn vaccine must be used promptly and the vial discardeds.6.6
  • Must not be mixed with other medicinal products; no compatibility studies exists.6.2

Safety findings

  • Indicated from 16 years of age only; the 10 microgram strength is not indicated in the paediatric population, which needs the 5 microgram strengths.4.1, 4.2
  • Contraindicated with a history of hypersensitivity to the active substance, excipients, or trace residuals such as formaldehyde and potassium thiocyanates.4.3
  • Vaccination should be postponed in severe febrile illness or acute infections.4.3
  • Factors observed to reduce the immune response include older age, male gender, obesity, smoking, route of administration and some chronic underlying diseasess.4.4
  • Serological testing should be considered for those at risk of not achieving seroprotection; additional doses may be needed for non-responders or sub-optimal responderss.4.4
  • Because of the long incubation period of hepatitis B, an unrecognised infection may already be present at the time of vaccination, and the vaccine may not prevent infection in that cases.4.4
  • The vaccine does not prevent infection from hepatitis A, C or E, or other liver pathogenss.4.4
  • Pregnancy: there is no clinical data on use in pregnant women; use only if the potential benefit justifies the potential risk to the foetuss.4.6
  • Breastfeeding: there is no clinical data on use in breastfeeding womens.4.6
  • Fertility: the vaccine has not been evaluated in fertility studiess.4.6
  • Most common side effects are injection-site reactions: transient soreness, erythema and induration, listed as commons.4.8
  • A very large list of adverse reactions is listed as very rare: thrombocytopenia, lymphadenopathy, serum sickness, anaphylaxis, polyarteritis nodosa, paresthesia, paralysis including Bell's palsy and facial paralysis, peripheral neuropathies including polyradiculoneuritis and 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, uveitis, hypotension, vasculitis, bronchospasm-like symptoms, erythema multiforme, angioedema, arthritis, elevation of liver enzymess.4.8
  • Many of the reported effects are from widespread use of the vaccine and in many instances the causal relationship to the vaccine 'has not been established's.4.8
  • Overdose has been reported rarely and the adverse event profile was comparable to the recommended doses.4.9

Evidence and claims

  • An antibody titre of 10 IU/l or more measured 1 to 2 months after the last injection 'correlates with protection' - a surrogate measure, not observed cases of diseases.5.1
  • In clinical trials, 96 per cent 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 antibody levels.5.1
  • In two trials in older adolescents and adults, 95.6 to 97.5 per cent developed a protective level, with geometric mean titres of 535 to 793 IU/ls.5.1
  • The duration of protection of that previous formulation in healthy vaccinees is unknown; follow-up over 5 to 9 years of about 3,000 high-risk subjects given a similar plasma-derived vaccine revealed no cases of clinically apparent hepatitis B infections.5.1
  • The need for a booster beyond the 12-month dose required for the compressed schedule 'is not yet defined's.4.2, 5.1
  • Revaccination of non-responders: 15 to 25 per cent produce an adequate response after one extra dose and 30 to 50 per cent after three. Because data are insufficient on the safety of extra doses, routine revaccination is not recommendeds.4.2
  • The need for a booster in healthy individuals who completed a full primary course 'has not been established's.4.2
  • Hepatitis B vaccine is described as the first anti-cancer vaccine because it can prevent primary liver cancers.5.1
  • Preclinical: animal reproduction studies have not been conducteds.5.3

Document and licensing

  • Marketing authorisation holder: Merck Sharp & Dohme (UK) Limited, Londons.7
  • First authorised 1 January 2021s.9
  • Text last revised 15 December 2022; the document carries a 2022 copyright notice for Merck & Co., Rahway, New Jerseys.10
  • Suspected reactions are reported through the MHRA Yellow Card schemes.4.8

Every line above is a summary of a statement in the manufacturer's own label, with the section number it comes from. Nothing has been added from any other source. The full list of flagged sentences is below, as it came out of the document.

Listed ingredients

Section 2 - qualitative and quantitative composition source ↗

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.

What these are, in plain English

  • recombinant - Made by genetic engineering: the gene for one piece of the germ is put into a laboratory cell or bacterium, which then makes that piece.
  • aluminium - An aluminium salt. It is an adjuvant: it makes the immune system respond more strongly to the vaccine. Aluminium in vaccines has been used since the 1930s.
  • yeast - Used in the laboratory to produce proteins. Traces can remain, which is why a yeast allergy can be a problem.
  • formaldehyde - A chemical used to inactivate (kill) viruses or bacteria during manufacture. It is then removed, and only trace amounts can remain.

Other ingredients (excipients)

Section 6.1 source ↗

  • Sodium chlorideSalt. Used to keep the liquid at the same saltiness as the body.
  • BoraxAlso called sodium tetraborate (E285), a mineral salt used to hold the acidity steady.
  • Water for injectionsPurified water to the standard used for injected medicines. It is the liquid the other ingredients are dissolved in.
Audit trail: every flagged sentence in the document (16)

These are the sentences the mechanical filter pulled out, in the document's own words, grouped by section. They are what the briefing above was built from, kept here so you can check nothing was left out. Some are fragments and some are technical, which is why the briefing exists.

4.2 Posology and method of administration

  1. The need for a booster dose in healthy individuals who have received a full primary vaccination course has not been established.

    Section 4.2 Posology and method of administration source ↗

    In plain English

    • not been established - There is not yet enough evidence to state a conclusion.

    No data / not studied matched: not been established

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

    Section 4.2 Posology and method of administration source ↗

    In plain English

    • immunocompromised - Having a weakened immune system, from illness or from medicines such as chemotherapy.

    Immune system, shedding and transmission matched: immunocompromised

  3. 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.

    Section 4.2 Posology and method of administration source ↗

    In plain English

    • insufficient - Not enough to draw a conclusion from.

    Limited, insufficient or inconclusive matched: insufficient

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

    Section 4.2 Posology and method of administration source ↗

    Not recommended, contraindicated or restricted matched: is not indicated

4.3 Contraindications

  1. - 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.

    Section 4.3 Contraindications source ↗

    In plain English

    • hypersensitivity - An allergic-type reaction, from a mild rash up to a severe reaction.

    Trace residues and process chemicals matched: formaldehyde

4.4 Special warnings and precautions for use

  1. This vaccine may contain traces of formaldehyde and potassium thiocyanate which are used during the manufacturing process.

    Section 4.4 Special warnings and precautions for use source ↗

    Trace residues and process chemicals matched: formaldehyde

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

    Section 4.4 Special warnings and precautions for use source ↗

    In plain English

    • immunocompromised - Having a weakened immune system, from illness or from medicines such as chemotherapy.

    Immune system, shedding and transmission matched: immunocompromised

  3. A number of factors have been observed to reduce the immune response to hepatitis B vaccines.

    Section 4.4 Special warnings and precautions for use source ↗

    Efficacy, effectiveness and endpoints matched: immune response

4.6 Fertility, pregnancy and lactation

  1. HBVAXPRO has not been evaluated in fertility studies.

    Section 4.6 Fertility, pregnancy and lactation source ↗

    In plain English

    • has not been evaluated - It has not been tested or measured in this group or situation.

    No data / not studied matched: has not been evaluated

4.8 Undesirable effects

  1. As with other hepatitis B vaccines, in many instances, the causal relationship to the vaccine has not been established.

    Section 4.8 Undesirable effects source ↗

    In plain English

    • not been established - There is not yet enough evidence to state a conclusion.

    No data / not studied matched: not been established

  2. 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

    Section 4.8 Undesirable effects source ↗

    In plain English

    • encephalitis - Inflammation of the brain.

    Rare or very rare serious events matched: bell's palsy

5.1 Pharmacodynamic properties

  1. 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).

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • recombinant - Made by genetic engineering: the gene for one piece of a germ is put into a lab cell or bacterium, which then makes that piece.
    • antigen - The part of a germ that the immune system recognises and remembers.

    Genetic engineering, vectors and GMOs matched: recombinant

  2. 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.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • geometric mean - An average used for antibody levels, because those vary over a huge range.

    Efficacy, effectiveness and endpoints matched: geometric mean

  3. 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.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • recombinant - Made by genetic engineering: the gene for one piece of a germ is put into a lab cell or bacterium, which then makes that piece.

    Animal, human or cell-line derived materialGenetic engineering, vectors and GMOsNo data / not studied matched: is unknown, plasma, recombinant

  4. 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.

    Section 5.1 Pharmacodynamic properties source ↗

    In plain English

    • recombinant - Made by genetic engineering: the gene for one piece of a germ is put into a lab cell or bacterium, which then makes that piece.
    • antigen - The part of a germ that the immune system recognises and remembers.

    Genetic engineering, vectors and GMOs matched: recombinant

  5. The duration of the protective effect in healthy vaccinees is unknown.

    Section 5.1 Pharmacodynamic properties source ↗

    No data / not studied matched: is unknown

Read the whole document at the source ↗