Consumer medicine information

Engerix-B

Hepatitis B child vaccine

BRAND INFORMATION

Brand name

Engerix-B Vaccine

Active ingredient

Hepatitis B child vaccine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Engerix-B.

WHAT IS IN THIS LEAFLET

This leaflet answers some of the common questions about ENGERIX-B vaccine. It does not contain all the available information. It does not take the place of talking to your doctor, nurse or pharmacist.

All medicines and vaccines have risks and benefits. Your doctor has weighed the possible risks of you having ENGERIX-B against the expected benefits.

If you have any concerns about receiving ENGERIX-B talk to your doctor, nurse or pharmacist.

Keep this leaflet with this vaccine. You may need to read it again.

WHAT ENGERIX-B IS USED FOR

ENGERIX-B is a vaccine used to protect you or your child against hepatitis B infection. The vaccine works by causing your body to produce its own protection (antibodies) against this disease. ENGERIX-B can be given to adults, adolescents, children and infants.

Hepatitis B is an infectious disease, which causes the liver to become swollen (inflamed). It is caused by a virus (hepatitis B virus). The virus is found in body fluids such as blood, semen, vaginal secretions, or saliva of infected people. You can catch the virus if it can enter your bloodstream. Ways this can happen are through:

  • injection (e.g. needlestick injury, or sharing needles for IV drug use)
  • sexual intercourse
  • sores, cuts or tiny wounds coming into contact with infected fluids (e.g. from a human bite, sharing razors or toothbrushes, or working with human blood or body fluids)
  • an infected mother passing the virus onto her baby during or shortly after birth.

Some people infected with hepatitis B may not look or feel sick. But others will get symptoms, which may not be seen for 6 weeks to 6 months after infection. Sometimes people will only have mild flu-like symptoms, but other people can become very ill. They may be extremely tired, and have dark urine, pale faeces, yellowish skin and/or eyes (jaundice), and other symptoms possibly requiring hospitalisation.

Most adults fully recover from the disease. But some people, particularly children, who may not have had symptoms can remain infected. They are called hepatitis B virus carriers. Hepatitis B carriers can infect others throughout their lives.

Babies infected with hepatitis B at birth almost always become carriers. Often they do not show symptoms, and seem healthy for many years. However, after 30, 40 or 50 years they can become sick and develop symptoms.

For all chronic hepatitis B carriers there is a risk of serious liver disease, such as cirrhosis (liver scarring) and liver cancer.

There is no specific treatment for hepatitis B. Therefore vaccination is the best way to help protect against infection and possible serious long-term disease.

ENGERIX-B will not protect against hepatitis caused by other agents or viruses (such as hepatitis A, hepatitis C, hepatitis E). If a person is already infected with the hepatitis B virus at the time of vaccination, ENGERIX-B may not prevent the disease in these people.

BEFORE RECEIVING ENGERIX-B

DO NOT HAVE ENGERIX-B IF :

  • you have had an allergic reaction to ENGERIX-B, or any ingredient listed at the end of this leaflet.
Signs of an allergic reaction may include skin rash, itchiness, shortness of breath, or swelling of the face, neck or tongue.
If you had ENGERIX-B before and became unwell, tell your doctor, nurse or pharmacist before receiving the next dose.
  • you have had an allergic reaction to H-B-Vax II, or another hepatitis B vaccine.
  • you have a severe infection with a high temperature. A minor infection such as a cold should not be a problem, but talk to your doctor about this before being vaccinated.
  • the expiry date printed on the pack has passed.
  • the packaging is torn or shows signs of tampering.

If you are not sure whether you should have ENGERIX-B, talk to your doctor, nurse or pharmacist. Do not give this vaccine to anyone else; your doctor has prescribed it specifically for you.

BEFORE YOU HAVE ENGERIX-B TELL YOUR DOCTOR IF:

  • you have an allergy to yeast
  • you are or think you may be pregnant, or if you intend to become pregnant. Your doctor will discuss with you the possible risks and benefits of receiving ENGERIX-B during pregnancy.
  • you are breastfeeding. It is not known if ENGERIX-B passes into breast milk, but as it can safely be given to infants, it is not expected to cause problems in nursing babies. However, the infant should be checked for any reactions.
  • you have any medical conditions, such as
    - severe heart or lung disease
    - a bleeding disorder
    - a liver or kidney problem
    - an immune deficiency condition (e.g. are HIV positive)
    - or a nervous system illness.

Fainting can occur following, or even before, any needle injection, therefore tell the doctor or nurse if you/your child fainted with a previous injection.

If your child has breathing difficulties, please contact your doctor. This may be more common in the first three days following vaccination if your child is born prematurely (before or at 28 weeks of pregnancy).

Sometimes ENGERIX-B may need to be given differently (e.g. people with bleeding problems) or a higher dose used (e.g. dialysis patients, or HIV positive people).

  • you have allergies to any other medicines or substances, such as dyes, foods or preservatives.
  • you have received another vaccine, or are taking any prescription or OTC (over-the-counter) medicines. In particular mention if you are taking medicines which suppress the immune system, such as steroids or cyclosporin. You may need a higher dose of ENGERIX-B than normal.

Some vaccines may be affected by other vaccines or medicines. Your doctor, nurse or pharmacist will be able to tell you what to do if ENGERIX-B is to be given with another vaccine or medicine.

USE IN CHILDREN

ENGERIX-B can be given to newborns, infants and children of all ages.

HOW ENGERIX-B IS GIVEN

The doctor or nurse will give ENGERIX-B as an injection. If you have any concerns about this, talk to your doctor, nurse or pharmacist.

HOW MUCH IS GIVEN

Usually, for adults and adolescents over 19 years of age: 1mL (20 microgram) is given. For adolescents aged 10 up to and including 19 years of age: 0.5mL (10 microgram) is given. Where compliance cannot be assured a 1mL dose (20 microgram) should be given. For babies and children under 10 years of age: 0.5mL (10 microgram) is given.

People with some conditions may need to have higher dosages.

HOW IS IT GIVEN

ENGERIX-B will be injected into your upper arm muscle. For babies, the vaccine may be given in the upper thigh muscle. For some people with bleeding problems, the dose may need to be given under the skin (subcutaneously).

The vaccine should not be given directly into the veins (intravenously).

WHEN IS IT GIVEN

ENGERIX-B is generally given as a total of three doses over 6 months. Each dose is given at a separate visit. The first dose will be given on an elected date. The remaining two doses will be given one month, and six months after the first dose.

  • First dose: at an elected date
  • Second dose: 1 month later
  • Third dose: 6 months after the first dose

It is important to return at the recommended times for follow up doses.

For babies born to mothers infected with hepatitis B, the first dose of ENGERIX-B should be given at birth or shortly afterwards. Hepatitis B immunoglobulin can also be given at this time.

ENGERIX-B can also be given as a total of three doses over 3 months. This schedule may be given to people needing rapid protection (e.g. overseas travellers). The first dose will be given on an elected date. The remaining two doses will be given one month and two months after the first dose. A booster dose is recommended at 12 months.

For adults, ENGERIX-B can also be given as a total of three doses over 3 weeks (a 0, 7, 21 day schedule). However, the body’s immune response to this rapid schedule may be reduced compared to the above two schedules. Therefore, this rapid schedule should only be used under special circumstances (e.g. travellers wanting to be vaccinated within one month of departure). A booster dose is recommended at 12 months.

For adolescents aged from 11 to 15 years, ENGERIX-B can also be given as a total of two adult (1 mL) doses 6 months apart. However, as protection against hepatitis B is only achieved after the second dose is given, this schedule should only be used when there is a relatively low risk of hepatitis B infection during the vaccination course and when it can be anticipated that the complete course is given.

Your doctor will advise on the possible need for extra doses, and future booster dosing.

IF YOU MISS A DOSE

If you miss a scheduled dose, talk to your doctor and arrange another visit as soon as possible.

WHILE YOU ARE USING ENGERIX-B

THINGS YOU MUST DO:

Keep your follow up visits with the doctor or clinic. It is important the 2 follow-up doses of ENGERIX-B are given at the correct times. This will ensure the best effect of the vaccine in protecting you or your child against hepatitis B.

THINGS TO BE CAREFUL OF:

Be careful driving or operating machinery until you know how ENGERIX-B affects you. ENGERIX-B should not normally interfere with your ability to drive a car or operate machinery. But in some people vaccination can cause dizziness or lightheadedness. Make sure you know how you react to ENGERIX-B before you drive a car or operate machinery, or do anything that could be dangerous if you are dizzy or lightheaded.

SIDE EFFECTS

Tell your doctor, nurse or pharmacist as soon as possible if you do not feel well during or after having had a dose of ENGERIX-B.

ENGERIX-B helps protect most people from hepatitis B, but it may have unwanted side effects in a few people. All medicines and vaccines can have side effects. Sometimes they are serious; most of the time they are not. Some side effects may need medical treatment.

Ask your doctor, nurse or pharmacist to answer any questions you may have.

Most unwanted effects with ENGERIX-B are mild and usually clear up within a few days. These effects, as with other vaccines, generally occur around the injection site. Events reported following ENGERIX-B which may have been related to the vaccine are listed below.

MILD EVENTS

  • Tell your doctor if you notice any of the following that are troublesome or ongoing:
    - pain, redness, swelling, a hard lump, bruising or itching around the injection site
    - headache, unusual tiredness, drowsiness, dizziness or feeling generally unwell
    - vomiting or feeling sick, stomach pains, loss of appetite or diarrhoea
    - muscle aches and pains, back pain or neck stiffness
    - coughing, sore throat, runny nose, mild fever, swollen glands in armpit or neck, fainting, sweating, flushing or chills
    - disturbed sleep, irritability in your child.

MORE SERIOUS EVENTS

  • Tell your doctor immediately if you notice any of the following:
    - breathing difficulties in your child
    - difficulty in walking, numbness, weakness and/or fatigue in limbs, tingling in fingers or toes, pain, blurred vision or other visual changes
    - drooping eyelid or sagging muscles on one side of the face, also called Bell’s palsy
    - aches or pains in joints, mild skin rash
    - swelling with fluid in tissues
    - difficulty in passing urine
    - fever
    - reddening of the skin, red swellings over the skin or in the mouth and on the lips, or other skin problems.
    - bleeding or bruising more easily than normal
  • As with all vaccines given by injection there is a very small risk of serious allergic reaction. Contact your doctor immediately or go to the casualty department of your nearest hospital if you notice any of the following:
    - swelling of limbs, face, eyes, inside of nose, mouth or throat
    - shortness of breath, breathing or swallowing difficulties
    - hives, itching (especially of the hands or feet), reddening of skin (especially around the ears), or severe skin reactions
    - unusual tiredness or weakness that is sudden and severe.
Allergy to ENGERIX-B is rare. Any such severe reactions will usually occur within the first few hours of vaccination.
  • Other rare events that have been reported with ENGERIX-B include:
    - blood disorders or low blood pressure
    - narrowing or blockage of blood vessels
    - changes in liver function tests
    - Guillain-Barre Syndrome (an inflammatory illness affecting nerves, resulting in weakness of muscles)
    - Disease of the brain including infection and swelling
    - Convulsions
    - Swollen glands in neck, armpit or groin

Other side effects not listed above, can also occur during or soon after a dose of ENGERIX-B. Check with your doctor if you notice any other effects.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

STORAGE

ENGERIX-B is usually stored at the doctor’s clinic or surgery, or at the pharmacy. But if you need to store ENGERIX-B always:

  • Keep ENGERIX-B in the refrigerator stored between +2°C and +8°C. THE PACK SHOULD NEVER BE FROZEN. FREEZING DESTROYS THE VACCINE.
  • Keep the vaccine out of the reach of children.

Keep ENGERIX-B in the original pack until it is time for it to be given.

Ask your pharmacist what to do with any left over ENGERIX-B that has expired or has not been used.

PRODUCT DESCRIPTION

WHAT IT LOOKS LIKE

ENGERIX-B comes in glass prefilled syringes or vials, as a white, slightly milky liquid. Two different vaccine dosages are available:

  • 20 microgram in 1mL of liquid
  • 10 microgram in 0.5mL of liquid

INGREDIENTS:

The active ingredient of ENGERIX-B is the surface protein of the hepatitis B virus, derived from genetically engineered yeast cells. The vaccine is not infectious, and will not give you the hepatitis B virus.

Inactive ingredients in the vaccine are: aluminium hydroxide hydrate, dibasic sodium phosphate dihydrate, monobasic sodium phosphate, sodium chloride (salt), and water. ENGERIX-B contains no thiomersal.

ENGERIX-B is made without any human blood or blood products, or any other substances of human origin.

The manufacture of this product includes exposure to bovine derived materials. No evidence exists that any case of vCJD (considered to be the human form of bovine spongiform encephalopathy) has resulted from the administration of any vaccine product.

FURTHER INFORMATION

ENGERIX-B is only available if prescribed by a doctor.

ENGERIX-B comes in the following packs:

20 microgram/1mL - Monodose prefilled syringe in packs of 1 and 10 (AUST R 123713)

20 microgram/1mL - Monodose vial in packs of 1 and 10 (AUST R 123709)

10 microgram/0.5mL - Monodose prefilled syringes in packs of 1 and 10 (AUST R 123712)

10 microgram/0.5mL - Monodose vial in packs of 1 and 10 (AUST R 123710)

Not all presentations and packs maybe available.

DISTRIBUTED BY:

GlaxoSmithKline Australia Pty Ltd
Level 4, 436 Johnston Street
Abbotsford Victoria 3067

Leaflet prepared:
24 December 2019

Version 4.0

Trade marks are owned by or licensed to the GSK group of companies.

© 2020 GSK group of companies or its licensor.

Published by MIMS May 2020

BRAND INFORMATION

Brand name

Engerix-B Vaccine

Active ingredient

Hepatitis B child vaccine

Schedule

S4

 

1 Name of Medicine

Hepatitis B surface antigen recombinant (yeast).

6.7 Physicochemical Properties

Not relevant to vaccines.

2 Qualitative and Quantitative Composition

Engerix-B Paediatric Dose: 10 microgram dose vaccine.

1 dose (0.5 mL) contains:
hepatitis B surface antigen1,2 10 microgram.
1Adsorbed on aluminium hydroxide hydrate, total: 0.25 milligram Al3+.
2Produced in yeast cells (Saccharomyces cerevisiae) by recombinant DNA technology.

Engerix-B: 20 microgram dose vaccine.

1 dose (1 mL) contains:
hepatitis B surface antigen1,2 20 microgram.
1Adsorbed on aluminium hydroxide hydrate, total: 0.50 milligram Al3+.
2Produced in yeast cells (Saccharomyces cerevisiae) by recombinant DNA technology.
For the full list of excipients, see Section 6.1 List of Excipients.
The manufacture of this product includes exposure to bovine derived materials. No evidence exists that any case of vCJD (considered to be the human form of bovine spongiform encephalopathy) has resulted from the administration of any vaccine product.
Engerix-B is highly purified, and meets the WHO requirements for recombinant hepatitis B vaccines. No substances of human origin are used in its manufacture.

3 Pharmaceutical Form

Suspension for injection.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Engerix-B induces the production of specific humoral antibodies (anti-HBs), which confer immunity against hepatitis B. A peak anti-HBs antibody concentration of ≥ 10 IU/L correlates with long-term protection against hepatitis B virus (HBV) infection (seroprotection (SP)).
Seroconversion (SC) is defined as the appearance of antibodies ≥ 1 IU/L in a previously seronegative participant.

Clinical trials.

Protective efficacy.

Clinical trials demonstrated SC rates of greater than or equal to 97% (seroprotection (SP) rates of greater than or equal to 96%) in normal immunocompetent adults and children following a 0, 1 and 6 months schedule, and SC rates of > 90% in neonates following injections at 0, 1 and 2 months.
In healthy adults administered vaccine doses according to a 0, 1, 2 month primary schedule with a 12 month booster, seroprotective rates of 15% and 89% were achieved one month after the first and third doses, respectively. One month after the 12 month booster dose, 95.8% of vaccinees achieved seroprotective antibody levels. In healthy adults administered a 0, 7, 21 day primary schedule with a 12 month booster, seroprotective rates of 65.2% and 76.4% were achieved one week and one month, respectively following the third vaccine dose. One month after the 12 month booster dose, 98.6% of vaccinees achieved seroprotective antibody levels.
In healthy adolescents (from 11 years up to and including 15 years of age) administered doses of 20 microgram at 0 and 6 months, SP rates were 11.3% at month 2, 26.4% at month 6 and 96.7% at month 7. Immunogenicity in this study was measured by the development of antibody to HBsAg as detected by enzyme immunoassay (seropositivity cutoff: 3.3 mIU/mL), using a titre of greater than or equal to 10 IU/L as indicative of seroprotection.
The seroprotection rates (SP) obtained with the two different dosages and schedules recommended in participants from 11 years up to and including 15 years of age were evaluated up to 66 months after the first dose of the primary vaccination and are presented in Table 5.
These data show that a primary vaccination with Engerix-B vaccine induces circulating anti-HBs antibodies that persist for at least 66 months. From one month after completion of the primary course through to 66 months, i.e. month 7 to month 66, the seroprotection rates were comparable between the 2 groups but tended to be lower in the 20 microgram group (0, 6 months schedule) compared to the 10 microgram group (0, 1, 6 month schedule) at all timepoints. The seroprotection rates at month 66 were 79.5% (95% CI 71.7%, 86.1%) and 91.4% (95% CI 82.3%, 96.8%) in the 20 microgram group and 10 microgram group respectively. All participants in both vaccine groups (including participants with anti-HBs antibody concentrations < 10 IU/L) received a challenge dose 72 to 78 months after primary vaccination. One month after the challenge dose, all participants mounted an anamnestic response to the challenge dose and were shown to be seroprotected (i.e. anti-HBs antibody concentrations ≥ 10 IU/L). These data suggest that protection against hepatitis B may still be conferred through immune memory in all participants who responded to primary vaccination but lost seroprotection level of anti-HBs antibodies.

Rechallenge in healthy participants.

In a clinical study conducted in Germany, healthy participants (N=284) aged 12 to 13 years vaccinated during infancy with 3 doses of Engerix-B received a challenge dose of Engerix-B. One month later, 98.9% of participants were shown to be seroprotected.

At risk groups.

In clinical studies performed in Thailand twenty years after primary vaccination during infancy, participants born to mothers who were HBV carriers, received a challenge dose of Engerix-B. One month later, at least 93% of participants (N=75) mounted an anamnestic response i.e. at least (greater than or equal to) a 4-fold rise in post-challenge dose anti-HB's antibody concentrations in subjects seropositive at the previous available long-term time-point, demonstrating immune memory.
Following a 0, 1, 6 month schedule, SC rates of 96.6% and 99% (corresponding to SP rates of 92.3% and 93%) were obtained in intellectually impaired individuals and male homosexuals respectively. In a clinical trial where thalassaemic patients received three doses of 20 microgram at 0, 1, 6 months, SC rates as well as SP rates were 100% (17 participants tested).

Patients with renal insufficiency.

In patients 16 years of age and above with impaired renal function, including patients undergoing haemodialysis administered 40 microgram (2 x 20 microgram) doses at 0, 1, 2 and 6 months, SP rates were 55.4% at month 3 and 87.1% at month 7. See Table 6.
Immunogenicity was measured by the development of antibody to HBsAg as detected by enzyme immunoassay (seropositivity cutoff: 3.3 mIU/mL), using a titre of greater than or equal to 10 IU/L as indicative of seroprotection.

Patients with type II diabetes.

The seroprotection rates in subjects 20 years of age and above with type II diabetes were evaluated one month after the last dose of the primary vaccination and are presented in Table 7.

Reduction in the incidence of hepatocellular carcinoma in children.

A significant reduction in the incidence of hepatocellular carcinoma was observed in Taiwanese children aged 6-14 years, following a nationwide hepatitis B vaccination program.

Interchangeability of hepatitis B vaccines.

Although no clinical data have been submitted, there is no reason to believe that the use of a different formulation of hepatitis B vaccine used either during a primary vaccination course or during booster dosing will not be satisfactory.

5.2 Pharmacokinetic Properties

Not relevant to vaccines.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

4 Clinical Particulars

4.1 Therapeutic Indications

Engerix-B is indicated for active immunisation against hepatitis B virus infection. The use of the vaccine should be in accordance with official recommendations.
As hepatitis D (caused by the delta agent) does not occur in the absence of hepatitis B infection, it can be expected that hepatitis D will also be prevented by vaccination with Engerix-B. The vaccine will not protect against infection caused by hepatitis A, hepatitis C and hepatitis E viruses, and other pathogens known to infect the liver.

4.3 Contraindications

Engerix-B should not be administered to participants with known hypersensitivity to any component of the vaccine, or to participants having shown signs of hypersensitivity after previous Engerix-B administration.
As for any vaccine, Engerix-B should not be administered to participants with severe febrile infections. However, the presence of minor infection without fever does not contraindicate vaccination.
HIV infection is not considered a contraindication to hepatitis B vaccination.

4.4 Special Warnings and Precautions for Use

The vaccine should never be administered intravenously.
As with all injectable vaccines, appropriate medical treatment (i.e. adrenaline) and supervision should always be readily available in case of anaphylactic reactions following the administration of the vaccine.
It is good clinical practice that any vaccination be preceded by a review of medical history (especially with regard to previous vaccinations and possible adverse events) and a clinical examination.
Engerix-B should not be administered in the gluteal region or intradermally/ subcutaneously since these routes of administration may not result in an optimum immune response. Exceptionally, in patients with thrombocytopenia or severe bleeding disorders (e.g. haemophiliacs), the vaccine may be administered subcutaneously, since bleeding after intramuscular injection may occur in these patients (see Section 4.2 Dose and Method of Administration).
The immune response to hepatitis B vaccines is related to a number of factors including route of administration, age (more than 40 years of age), male gender, obesity and smoking habits. As individuals in these groups may respond less optimally to hepatitis B vaccines, the administration of additional vaccine doses may be considered.
In dialysis patients, HIV infected patients and participants who have impairment of the immune system, adequate antibody concentrations may not be obtained after the recommended primary vaccination course. The need for monitoring antibody levels in such patients should be considered (see Section 4.2 Dose and Method of Administration, Chronic adult haemodialysis patients/ patients with impaired renal function (creatinine clearance < 30 mL/minute) 16 years of age and above).
Caution should be exercised in administering the vaccine to patients in whom a systemic reaction due to the vaccine may pose a significant risk, e.g. in patients with severely compromised cardiopulmonary function.
Syncope (fainting) can occur following, or even before, any vaccination as a psychogenic response to the needle injection. It is important that procedures are in place to avoid injury from faints.
Because of the long incubation period of hepatitis B, it is possible for unrecognised infection to be present at the time of vaccination. The vaccine may not prevent hepatitis B in such cases.
The vaccine may not prevent infection in individuals who do not achieve protective antibody titres.
The vaccine will not protect against infection caused by hepatitis A, hepatitis C and hepatitis E viruses and other pathogens known to infect the liver.
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. As the benefit of vaccination is high in this group of infants, vaccination should not be withheld or delayed.

Use in hepatic impairment.

No data available.

Use in renal impairment.

See Section 4.4 Special Warnings and Precautions for Use, for use in haemodialysis patients.

Use in the elderly.

No data available.

Paediatric use.

See Section 4.2 Dose and Method of Administration.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Engerix-B should not be mixed in the same syringe with other vaccines.
Engerix-B may be administered concomitantly with the following vaccines: diphtheria tetanus pertussis (DTP), diphtheria tetanus (DT), poliomyelitis (oral or injectable), measles mumps rubella, Haemophilus influenzae type b (Hib) and hepatitis A, providing separate syringes and separate injection sites are used.
Engerix-B can be given concomitantly with human papillomavirus (HPV) vaccine (Cervarix). Administration of Engerix-B at the same time as Cervarix (HPV vaccine) has shown no clinically relevant interference in the antibody response to the HPV antigens. Anti-HBs geometric mean antibody concentrations were lower on coadministration, but the clinical significance of this observation is not known since the seroprotection rates remain unaffected. The proportion of participants reaching anti-HBs ≥ 10 mIU/mL was 97.9% for concomitant vaccination and 100% for Engerix-B alone.
The simultaneous administration of Engerix-B and hepatitis B immunoglobulin (HBIG) does not result in reduced anti-HBs antibody titres provided separate injection sites are used.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B2)
Adequate human data on use during pregnancy and adequate animal reproduction studies are not available. Therefore, vaccination of pregnant women cannot be recommended, unless expected benefits outweigh potential risks, as might occur in high risk situations.
Adequate human data on use during lactation and adequate animal reproduction studies are not available.

4.8 Adverse Effects (Undesirable Effects)

Engerix-B is generally well tolerated.

Clinical trials experience.

Based on clinical trial symptom sheet data, the incidence of local side effects is 24% and of systemic side effects 8%. Both local and systemic side effects occurred in approximately 13% of participants. The incidence of local and systemic reactions was comparable to those of plasma derived hepatitis B vaccines.
In a comparative trial in participants from 11 years up to and including 15 years of age, the incidence of local and general solicited symptoms reported after a two dose regimen of Engerix-B 20 microgram was overall similar to that reported after the standard three dose regimen of Engerix-B 10 microgram.
Adverse effects data from patients who received a challenge dose of Engerix-B 10 microgram (preservative free) at 72 to 78 months after primary vaccination is shown in Table 4. The group 1 participants had received 2 doses of thiomersal free Engerix-B (20 microgram) at 0 and 6 months, with placebo at month 1. The group 2 participants had received 3 doses of preservative free Engerix-B (10 microgram) at 0, 1 and 6 months.
The safety profile presented below is based on data from more than 5,300 participants. Events are listed within body systems and categorised by frequency according to the following definitions.
Frequencies are reported as very common: ≥ 1/10; common: ≥ 1/100, < 1/10; uncommon: ≥ 1/1,000, < 1/100; rare: ≥ 1/10,000, < 1/1,000; very rare: < 1/10,000 including isolated reports.

Blood and lymphatic system disorders.

Rare: lymphadenopathy.

Metabolism and nutrition disorders.

Common: appetite lost.

Psychiatric disorders.

Very common: irritability.

Nervous system disorders.

Common: headache (very common with 10 microgram formulation), drowsiness. Uncommon: dizziness. Rare: paraesthesia.

Gastrointestinal disorders.

Common: gastrointestinal symptoms (such as nausea, vomiting, diarrhoea, abdominal pain).

Skin and subcutaneous tissue disorders.

Rare: rash, pruritus, urticaria.

Musculoskeletal and connective tissue disorders.

Uncommon: myalgia. Rare: arthralgia.

General disorders and administration site conditions.

Very common: pain and redness at injection site, fatigue.
Common: swelling at injection site, malaise, injection site reaction (such as induration), fever (≥ 37.5°C). Uncommon: influenza-like illness.

Postmarketing data.

The following adverse events have been reported following widespread use of the vaccine. As with other hepatitis B vaccines, in many instances the causal relationship to the vaccine has not been established.

Autonomic nervous system.

Rare: flushing, sweating.

Body as a whole.

Rare: fever, fatigue, malaise, chills.
Very rare: anaphylaxis, delayed hypersensitivity reactions, mimicking serum sickness.
Unknown frequency: allergic reactions including anaphylactoid reactions.

Cardiovascular.

Very rare: syncope, hypotension.

Central and peripheral nervous system.

Rare: paraesthesia, dizziness, headache.
Very rare: paralysis, neuropathy (including Guillain-Barre syndrome, facial paralysis, optic neuritis (visual disturbance) and multiple sclerosis), encephalitis, encephalopathy, meningitis, neck stiffness, neuritis, vertigo and convulsions.
Unknown frequency: hypoaesthesia.

Gastrointestinal system.

Rare: nausea, vomiting, diarrhoea, abdominal pain.
Very rare: anorexia.

Hearing and vestibular.

Very rare: tinnitus.

Liver and biliary system.

Rare: abnormal liver function tests.

Local reactions.

Common: transient soreness, pain, induration, erythema and swelling at the injection site have been reported. These reactions are usually mild and subside within two days.
Very rare: ecchymosis at the injection site.

Musculoskeletal system.

Rare: arthralgia, myalgia.
Very rare: arthritis.
Unknown frequency: muscular weakness.

Platelet bleeding and clotting.

Very rare: thrombocytopenia.

Psychiatric.

Very rare: disturbed sleep.

Respiratory system.

Very rare: bronchospasm-like symptoms, pharyngitis or other upper respiratory infection, cough.

Skin and appendages.

Rare: urticaria, rash, pruritus.
Very rare: severe skin disorders such as erythema multiforme, angioedema.
Unknown frequency: lichen planus.

Urinary system.

Very rare: dysuria.

Vascular extracardiac.

Very rare: vasculitis.

White cell and reticuloendothelial system.

Very rare: lymphadenopathy.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

Dosage.

The vaccine can be administered at any age from birth onwards. Vaccination of individuals who have antibodies against hepatitis B virus from a previous infection is not necessary.

Adults and adolescents older than 19 years.

A dose of 20 microgram of antigen protein in 1 mL is recommended in a 0, 1, 6 month schedule.

Adolescents.

In adolescents from the age of 10 years, up to and including 19 years, a 10 microgram dose is recommended provided the immunisation is carried out in the 0, 1, 6 month schedule in circumstances which will ensure compliance to the full vaccination course. If compliance cannot be assured, then a 20 microgram dose should be used to increase the proportion of participants protected after the first and second doses.
The 20 microgram vaccine can also be used in participants from 11 years up to and including 15 years of age in a 0 and 6 month schedule in situations when there is a relatively low risk of hepatitis B infection during the vaccination course and when compliance with the complete vaccination course can be anticipated.
Adolescent vaccination is not necessary for children who have received a primary course of hepatitis B vaccine.

Neonates, infants and children below 10 years of age.

A dose of 10 microgram of antigen protein in 0.5 mL suspension is recommended in a 0, 1, 6 month schedule. For details on the recommended vaccination schedule, including use in preterm babies, refer to the Australian Immunisation Handbook.
In neonates and infants, maternally transferred antibodies do not interfere with the active immune response to the vaccine.

Vaccination schedules.

For primary vaccination of adults, adolescents and children not previously exposed to the hepatitis B virus the schedules are shown in Table 1.
The recommended treatment regimen for infants born to HBsAg positive mothers (irrespective of the mother's HBeAg status) is shown in Table 2.
The first dose of vaccine and immunoglobulin should preferably be given within 12 hours of birth at separate sites. The efficacy of HBIG decreases markedly if treatment is delayed beyond 48 hours. If this is not possible, vaccination should not be delayed beyond seven days after birth.
Testing for HBsAg and anti-HBs is suggested at 12 to 15 months of age. If HBsAg is not detectable and anti-HBs is present, the child has been protected.

Accelerated schedules.

In circumstances where more rapid protection is required (e.g. contacts of carriers, immunisation of travellers and newborns to carrier women) two accelerated vaccination schedules of 0, 1 and 2 months or 0, 7 and 21 days may be used. However, as higher seroprotective rates are observed following the 0, 1, 2 month schedule, it is recommended the 0, 7, 21 day schedule be administered only to adults, and only in exceptional circumstances (e.g. travellers commencing hepatitis B primary vaccination within one month of departure) (see Section 5.1 Pharmacodynamic Properties). Since the peak antibody levels reached after these shorter schedules of primary vaccination are lower compared to the 0, 1 and 6 month schedule, it is recommended that a fourth dose (booster) be given at 12 months after the first dose of vaccine, in order to ensure adequate seroprotection rates.

Dosage adjustment.

Renal impairment/dialysis.

Chronic adult haemodialysis patients/ patients with impaired renal function (creatinine clearance < 30 mL/minute) 16 years of age and above.

The primary vaccination schedule for chronic adult haemodialysis patients or patients with impaired renal function 16 years of age and above consists of four doses of 40 microgram. The 40 microgram (2 mL) dose may be administered as 2 x 20 microgram in one injection site or in each arm. (See Table 3.)
As vaccine induced protection in haemodialysis patients is less complete, boosting should be adapted in order to ensure the anti-HBs antibody titre remains above 10 IU/L (see Section 4.4 Special Warnings and Precautions for Use). The need for booster dosing should be assessed by antibody testing at 6 to 12 monthly intervals. Engerix-B booster doses of 40 microgram (2 x 20 microgram) are recommended for these patients.

Postexposure prophylaxis.

There are no adequately controlled studies on the effectiveness of hepatitis B immunoglobulin administration along with the vaccine in adults and older children exposed to hepatitis B virus through: needlestick, ocular or mucous membrane exposure to blood known or presumed to contain HBsAg; human bites by known or presumed HBsAg carriers that penetrate the skin; following intimate sexual contact with known or presumed HBsAg carriers.
Hepatitis B immunoglobulin (human) (400 IU) should be given intramuscularly as soon as possible (must be within 72 hours of exposure). Engerix-B should be given at a separate site within 7 days, and then at 1 month and 6 months. Passive immunisation will not interfere with active response to Engerix-B.

Booster dose.

The Australian Immunisation Handbook recommends that booster doses against hepatitis B are not required in immunocompetent individuals, since there is good evidence that a completed primary course of hepatitis B vaccination provides long lasting protection in these individuals. This applies to adults, children and all subgroups (such as healthcare workers). Booster doses are recommended for immunosuppressed individuals, for people living with HIV infection or with renal failure. The timing for boosting in these individuals should be decided by regular monitoring of hepatitis B antibody levels at 6 to 12 monthly intervals.

Method of administration.

The vaccine is a ready to use suspension. It must be shaken well before use since upon storage the vaccine settles down as a fine white deposit with a clear colourless supernatant. After shaking, the vaccine is a slightly opaque, white suspension.
The vaccine should be inspected visually for any foreign particulate matter and/or abnormal physical appearance prior to administration. In the event of either being observed, the vaccine should be discarded.
The monodose vial and prefilled syringe presentations are for use in a single patient only and any residue must be discarded.
Any unused product or waste material should be disposed of in accordance with local requirements.
Engerix-B should be injected intramuscularly. In adults, the injection should be given in the deltoid region but it may be preferable to inject Engerix-B in the anterolateral thigh in neonates and infants because of the small size of their deltoid muscle. Exceptionally, the vaccine may be administered subcutaneously in patients with thrombocytopenia or severe bleeding tendencies (e.g. haemophiliacs).
Engerix-B must not be given intravenously.
NB: Each vaccination should be carried out with a separate syringe.

4.7 Effects on Ability to Drive and Use Machines

The vaccine is considered unlikely to affect the ability to drive and operate machinery.

4.9 Overdose

Cases of overdose have been reported during postmarketing surveillance. Adverse events reported following overdosage were similar to those reported with normal vaccine administration.
For information on the management of overdose, contact the Poisons Information Centre on 131 126 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

The final vaccines also contain dibasic sodium phosphate, monobasic sodium phosphatedihydrate, sodium chloride, and water for injections and traces of polysorbate 20. Engerix-B contains no thiomersal.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

The shelf-life of Engerix-B is three years from the date of manufacture. When stored between +2°C to +8°C. Do not freeze, discard if the vaccine has been frozen.

6.4 Special Precautions for Storage

Engerix-B must be stored between +2°C to +8°C. Do not freeze, discard if the vaccine has been frozen.
The expiry date of the vaccine is indicated on the label and packaging.

6.5 Nature and Contents of Container

Engerix-B 20 microgram (adult dose).


Monodose vials (1 mL) in packs of 1, 10 and 25.
Pre-filled syringes in packs of 1, 10 and 25.

Engerix-B paediatric dose 10 microgram.


Monodose vials (0.5 mL) in packs of 1, 10 and 25.
Pre-filled syringe in packs of 1, 10 and 25.
Not all pack sizes and container types may be distributed in Australia.
The vials and syringes are made of neutral glass type 1, which conforms to European Pharmacopoeia requirements.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

Summary Table of Changes