Engerix^® B (Suspension) Instructions for Use

ATC Code

J07BC01 (Hepatitis B virus purified antigen)

Active Substance

Hepatitis B vaccine (rDNA) (Ph.Eur. European Pharmacopoeia)

Clinical-Pharmacological Group

Vaccine for the prevention of hepatitis B

Pharmacotherapeutic Group

MIBP-vaccine

Pharmacological Action

Hepatitis B vaccine. Promotes the development of immunity against the hepatitis B virus. It is a purified major surface antigen of the hepatitis B virus (HBsAg), produced using recombinant DNA technology and adsorbed onto aluminum hydroxide.

The antigen is produced by a culture of yeast cells (Saccharomyces cerevisiae), obtained by genetic engineering and having a gene encoding the major surface antigen of the hepatitis B virus. HBsAg is purified from yeast cells using several sequentially applied physicochemical methods.

HBsAg spontaneously transforms into spherical particles 20 nm in diameter, containing non-glycosylated HBsAg polypeptides and a lipid matrix consisting mainly of phospholipids. Studies have shown that these particles possess properties characteristic of natural HBsAg.

Prophylactic efficacy in risk groups ranges from 95% to 100% in newborns, children, and adults at risk.

Engerix B induces the formation of specific HBs antibodies, which at a titer of 10 IU/L protect against hepatitis B.

In newborns from HBsAg-positive mothers immunized according to the 0, 1, 2, 12 months or 0, 1, 6 months schedule without simultaneous or subsequent administration of hepatitis B immunoglobulin (HBIg) at birth, the prophylactic efficacy of vaccination is 95%, while simultaneous administration of the vaccine and HBIg at birth increases the efficacy of prophylaxis to 98%.

Prophylactic efficacy in healthy individuals when using the 0, 1, 6 months vaccination schedule: in more than 96% of vaccinated individuals, a protective level of antibodies is determined 7 months after the first dose. If vaccination is carried out according to the 0, 1, 2, 12 months schedule, then 15% and 89% of vaccinated individuals have a protective level of antibodies 1 month after the first dose and 1 month after the third dose, respectively. One month after the fourth dose, a protective antibody titer is determined in 95.8% of vaccinated individuals.

When vaccination is carried out according to the 0, 7, 21 days schedule, 1 and 5 weeks after the third dose, a protective antibody titer is determined in 65.2% and 76% of vaccinated individuals, respectively. One month after the fourth dose, administered one year after immunization, a protective level of antibodies is determined in 98.6% of vaccinated individuals.

As a result of universal vaccination of children aged 6 to 14 years against hepatitis B, a significant decrease in the incidence of hepatocellular carcinoma was observed, as well as the persistence of the hepatitis B antigen, which is an important factor in the development of liver cancer.

For patients with renal failure, seroprotective levels (calculated as the percentage of patients who achieved the target antibody titer > 10 IU/L), determined during clinical trials, are given in the table.

The vaccine undergoes a high degree of purification and meets WHO requirements for recombinant hepatitis B vaccines. No substances derived from human body materials are used in the production of the vaccine.

Engerix B can also prevent hepatitis D infection in case of co-infection with the delta agent.

Pharmacokinetics

Data on the pharmacokinetics of the Engerix B vaccine are not provided.

Indications

Specific prophylaxis of viral hepatitis B in children, adolescents, and adults.

In accordance with the National Immunization Schedule and the Immunization Schedule for Epidemic Indications, vaccination against viral hepatitis B for all population groups not previously vaccinated.

Vaccination against viral hepatitis B in risk groups, including:

• Personnel of medical and dental institutions, including employees of clinical and serological laboratories;
• Patients who are undergoing or planning transfusion of blood and its components; planned surgical interventions; invasive therapeutic and diagnostic procedures; organ transplantation;
• Children born to mothers who are carriers of the hepatitis B virus;
• Individuals whose increased risk of disease is associated with their sexual behavior;
• Individuals who use injectable drugs;
• Individuals traveling to regions endemic for hepatitis B;
• Individuals who have lived in regions endemic for hepatitis B;
• Patients with sickle cell anemia;
• Patients with chronic liver disease, or individuals at risk of developing liver diseases (including patients with chronic hepatitis C and carriers of the hepatitis C virus, alcohol abusers);
• Individuals who have close contact with patients with acute or chronic hepatitis B; as well as, in accordance with the immunization schedule for epidemic indications
• Children from orphanages, children’s homes, and boarding schools;
• Individuals employed in the production of immunobiological preparations from donor and placental blood;
• Students of medical institutes and students of secondary medical educational institutions (primarily graduates).

In areas with moderate or high incidence of hepatitis B, where there is a risk of infection for the entire population, in addition to all the above groups, vaccination is also necessary for all children, including newborns, as well as adolescents and young people.

ICD codes

Dosage Regimen

Suspension

The vaccine dose depends on the patient’s age.

For individuals aged 16 years and older, the dose is 20 mcg/1 ml.

For individuals under 16 years of age, including newborns, the dose is 10 mcg/0.5 ml.

Primary vaccination

Standard vaccination is carried out according to the 0, 1, and 6 months schedule, with optimal protection provided at the 7th month.

Accelerated vaccination is carried out according to the 0, 1, and 2 months schedule with revaccination 12 months after the first vaccination, which provides a faster immune response and greater adherence to vaccination.

Individuals aged 16 years and older. In exceptional circumstances requiring rapid development of a prophylactic response to immunization, for example, travel to a hyperendemic area one month after the first vaccination, an emergency vaccination schedule of 0, 7, 21 days may be used. When using this schedule, the fourth vaccination should be given 12 months after the first.

Patients aged 16 years and older with renal impairment on hemodialysis. Primary vaccination of patients on hemodialysis includes four double doses (40 mcg) on a chosen day, and at 1, 2, and 6 months after the first double dose. Consideration should be given to performing serological tests after vaccination. The vaccination schedule can be adequately adjusted to ensure an antibody titer above and equal to the acceptable protective level of 10 IU/L.

Patients under 16 years of age, including newborns, with renal impairment on hemodialysis. Both standard and accelerated vaccination schedules can be used at a dose of 10 mcg/0.5 ml. Consideration should be given to performing serological tests after vaccination. According to data obtained in adults, the use of a double dose improves the immune response. The vaccination schedule can be adequately adjusted to ensure an antibody titer above and equal to the acceptable protective level of 10 IU/L.

Individuals accidentally exposed to the risk of infection

In case of recent possible infection with the hepatitis B virus (e.g., a needle stick with a contaminated needle), an accelerated vaccination schedule of 0, 1, 2 + 12 months is recommended. The first dose of the vaccine is administered simultaneously with hepatitis B immunoglobulin; in this case, injections are given at different sites on the body.

Newborns born to mothers who are carriers of the hepatitis B virus or who had hepatitis B in the third trimester of pregnancy

The first vaccine administration is recommended within the first 12 hours after birth, then an accelerated vaccination schedule is used, taking into account that the accelerated schedule allows for a faster immune response. If necessary, hepatitis B immunoglobulin is administered to enhance the protective function; injections of Engerix B and immunoglobulin are administered at different sites. These vaccination schedules can be adjusted if necessary.

Revaccination

The tolerability of revaccination is comparable to that of primary vaccination. The need for revaccination in healthy individuals who have received a full course of primary vaccination has not been established.

The need for revaccination in patients with a reduced immune response and patients on hemodialysis is determined by the results of serological tests.

Rules for administration of Engerix B vaccine

The vaccine is administered deep intramuscularly to adults and older children in the deltoid muscle region, and to newborns and young children in the anterolateral region of the thigh. As an exception, the vaccine can be administered subcutaneously to patients with thrombocytopenia or other blood clotting disorders.

It is not recommended to administer the vaccine intramuscularly into the gluteal region, or subcutaneously or intradermally, as this will not achieve an adequate immune response.

The vaccine must never be administered intravenously under any circumstances.

Immediately before use, the vial should be shaken until a slightly opaque whitish suspension free of foreign particles is obtained. If the vaccine looks different, it should not be administered. When using a vial containing multiple doses, each dose should be withdrawn and administered with a sterile disposable syringe and a sterile disposable needle. The vaccine from an opened multidose vial should be used within the working day.

The vaccine should be drawn into the syringe under strict aseptic conditions and with precautions aimed at preventing contamination of the contents.

Adverse Reactions

Definition of frequency of adverse reactions: very common – >10%, common – from >1% to ≤10%, uncommon – from >0.1% to ≤1%, rare – from ≥0.01% to <0.1%, very rare, including isolated reports - <0.01%.

Local reactions: common – redness, pain, swelling.

Systemic reactions: rare – weakness, fever, malaise, flu-like syndrome.

Allergic reactions rare – rash, itching, urticaria; very rare – limited acute angioedema, erythema multiforme, very rare – anaphylactic and anaphylactoid reactions, serum sickness-like drug allergy syndrome.

Cardiovascular system: very rare – syncope, hypotension, vasculitis.

Central and peripheral nervous system: rare – dizziness, headache, paresthesia; very rare – paralysis, neuropathy, neuritis (including Guillain-Barré syndrome, optic neuritis and multiple sclerosis), encephalitis, encephalopathy, meningitis, convulsions.

Digestive system: rare – nausea, vomiting, diarrhea, abdominal pain, changes in liver function tests.

Hematopoietic system: very rare – thrombocytopenia, lymphadenopathy.

Musculoskeletal system: rare – arthralgia, myalgia; very rare – arthritis.

Respiratory system: very rare – symptoms resembling bronchospasm.

As with other hepatitis B vaccines, a causal relationship with the administration of the Engerix^® B vaccine has not been established.

Contraindications

• Hypersensitivity reactions after previous administration of hepatitis B vaccines;
• Hypersensitivity to any component of the vaccine (including baker’s yeast).

Use in Pregnancy and Lactation

No controlled studies have been conducted on the use of the Engerix^® B vaccine during pregnancy and lactation (breastfeeding), nor have experimental studies been conducted on the effect on reproductive function in animals. Nevertheless, as with the use of other inactivated viral vaccines, the risk to the fetus is minimal.

Use in Renal Impairment

Patients aged 16 years and older with renal impairment on hemodialysis. Primary vaccination of patients on hemodialysis includes four double doses (40 mcg) on a chosen day, and at 1, 2, and 6 months after the first double dose. Consideration should be given to performing serological tests after vaccination. The vaccination schedule can be adequately adjusted to ensure an antibody titer above and equal to the acceptable protective level of 10 IU/L.

Patients under 16 years of age, including newborns, with renal impairment on hemodialysis. Both standard and accelerated vaccination schedules can be used at a dose of 10 mcg/0.5 ml. Consideration should be given to performing serological tests after vaccination. According to data obtained in adults, the use of a double dose improves the immune response. The vaccination schedule can be adequately adjusted to ensure an antibody titer above and equal to the acceptable protective level of 10 IU/L.

Special Precautions

Vaccination should be postponed in individuals with an acute febrile condition, including exacerbation of chronic diseases.

Vaccination is carried out 1 month after recovery (onset of remission).

In the presence of an infectious disease occurring in a mild form, vaccination can be carried out immediately after the temperature normalizes.

Due to the long incubation period of hepatitis B, a latent hepatitis B virus infection may be present during the vaccination course. In such cases, the use of the vaccine cannot prevent hepatitis B disease.

The vaccine does not prevent infections caused by other pathogens, such as hepatitis A, hepatitis C and hepatitis E, as well as pathogens that cause other liver diseases.

Since the development of an immune response to vaccination is associated with various concomitant factors, individuals for whom vaccination was not sufficiently effective may require an additional dose of the vaccine.

In patients on hemodialysis, in HIV-infected patients, and in individuals with other immune disorders, an adequate titer of HBs antibodies may not be achieved after the main course of immunization, so additional vaccine administration may be required.

When administering Engerix B, it is necessary to have available the means that may be required in case of anaphylactic reactions. Allergic reactions may develop immediately after vaccine administration, therefore vaccinated patients should be under medical supervision for 30 minutes.

Effect on ability to drive vehicles and operate machinery

It is unlikely that the Engerix^® B vaccine affects the ability to drive vehicles and operate machinery.

Overdose

No cases of overdose of the Engerix B vaccine have been reported to date.

Drug Interactions

Simultaneous administration of Engerix B with hepatitis B immunoglobulin is not accompanied by a decrease in anti-HBs antibody titer, provided they are administered at different injection sites.

Engerix B can be used simultaneously with other vaccines from the National Immunization Schedule and inactivated vaccines from the Immunization Schedule for Epidemic Indications.

Vaccines should be administered with different syringes at different sites on the body.

Engerix B can be used to complete a vaccination course started with other hepatitis B vaccines, as well as for revaccination if necessary.

Storage Conditions

The vaccine should be stored and transported at a temperature from 2°C (35.6°F) to 8°C (46.4°F), in a place inaccessible to children. Do not freeze.

Shelf Life

Shelf life – 3 years.

Dispensing Status

The vaccine is dispensed by prescription.

Multidose packages are intended for medical and preventive institutions.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.