Consumer medicine information

Twinrix (720/20) and Twinrix Junior (360/10) (preservative free)

Hepatitis A child/adolescent vaccine; Hepatitis B child vaccine

BRAND INFORMATION

Brand name

Twinrix Preservative Free

Active ingredient

Hepatitis A child/adolescent vaccine; Hepatitis B child vaccine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Twinrix (720/20) and Twinrix Junior (360/10) (preservative free).

SUMMARY CMI

TWINRIX (720/20) and TWINRIX JUNIOR (360/10)

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I being given TWINRIX?

TWINRIX is a combination vaccine used to prevent hepatitis A and hepatitis B infection. The vaccine works by causing the body to produce its own protection (antibodies) against these diseases.

For more information, see Section 1. Why am I being given TWINRIX? in the full CMI.

2. What should I know before I am given TWINRIX?

Do not use if you have ever had an allergic reaction to TWINRIX or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I am given TWINRIX? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with TWINRIX and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How is TWINRIX given?

  • TWINRIX will be injected into your upper arm muscle in adults and older children, and into the thigh muscle in infants. For some people with bleeding problems, the dose may need to be given under the skin (subcutaneously).
  • The dose using TWINRIX (720/20) is 1 mL.
  • The dose using TWINRIX JUNIOR (360/10) is 0.5 mL.

More instructions can be found in Section 4. How is TWINRIX given? in the full CMI.

5. What should I know while being given TWINRIX?

Things you should do
  • Remind any doctor, nurse or pharmacist you visit that you are using TWINRIX.
  • Check with your doctor if you have an allergy to yeast, you are or think you may be pregnant, or if you intend to become pregnant, you are breastfeeding, you have any medical conditions, such as a 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
Things you should not do
  • Do not have TWINRIX if you have/ your child has had an allergic reaction to TWINRIX, or any ingredient contained in this vaccine (e.g. neomycin sulphate), or you have a severe infection with a high temperature.
Driving or using machines
  • Be careful driving or operating machinery until you know how TWINRIX affects you. TWINRIX should not normally interfere with your ability to drive a car or operate machinery. In some people vaccination can cause dizziness or light-headedness.
Looking after your medicine
  • TWINRIX is usually stored at the doctor's clinic or surgery, or at the pharmacy. If you need to store TWINRIX always store in the refrigerator between +2°C and +8°C in the original pack until it is time for it to be given. The pack should never be frozen. Freezing destroys the vaccine.

For more information, see Section 5. What should I know while being given TWINRIX? in the full CMI.

6. Are there any side effects?

Side effects that have been most commonly reported include irritability, headache, pain and redness at injection site and fatigue. There is a rare risk of serious allergic reactions. 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. For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

TWINRIX (720/20) and TWINRIX JUNIOR (360/10)

Active ingredient(s): Hepatitis A virus and Hepatitis B surface protein (yeast)

Consumer Medicine Information (CMI)

This leaflet provides important information about using TWINRIX. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using TWINRIX.

Where to find information in this leaflet:

1. Why am I being given TWINRIX?
2. What should I know before I am given TWINRIX?
3. What if I am taking other medicines?
4. How is TWINRIX given?
5. What should I know while being given TWINRIX?
6. Are there any side effects?
7. Product details

1. Why am I being given TWINRIX?

TWINRIX is a combination vaccine used to prevent hepatitis A and hepatitis B infection. The vaccine works by causing the body to produce its own protection (antibodies) against these diseases. TWINRIX can be given to adults, adolescents, children and infants.

Hepatitis A and hepatitis B are infectious diseases, which cause the liver to become inflamed (swollen). These diseases are caused by viruses - hepatitis A and hepatitis B viruses.

Hepatitis A

Symptoms of hepatitis A usually begin 3 to 6 weeks after coming into contact with the virus. These consist of nausea (feeling sick), fever, aches and pains. After a few days the skin and/or the whites of the eyes may become yellowish (jaundice). The severity and type of symptoms can vary. Hepatitis A is often milder in young children. Most people recover completely but the illness is usually severe enough to keep adults off work for about a month.

The hepatitis A virus can be passed from person to person in food and drink, or by swimming in water contaminated by sewage. Hepatitis A is very common in many parts of the world and the risk of infection is greatest in those areas where hygiene and sanitation are poor. Hepatitis A occurs in Australia but is not common.

Vaccination is recommended for travellers to all developing countries, including people in the armed forces, or for those groups at a higher risk of exposure to the disease such as nursing staff, healthcare workers in contact with patients in childrens wards, infectious diseases wards, emergency rooms, intensive care units, day-care staff particularly where children have not been toilet trained, staff and residents of homes for the intellectually disabled, sewerage workers, food handlers, homosexual men, people in contact with an infected person, people with chronic liver disease, liver transplants or people that receive blood products.

Hepatitis B

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

Some groups of people are at a higher risk of exposure to hepatitis B. Vaccination is recommended for these people:

  • some healthcare workers
  • abusers of injectable drugs
  • people with many sexual partners
  • homosexual men
  • haemodialysis patients or people who receive certain blood products
  • people with chronic liver disease or hepatitis C
  • people in contact with a hepatitis B carrier or an infected person
  • staff and residents of institutions for the intellectually disabled
  • inmates and prison staff at some correctional institutions
  • some travellers to areas where the incidence of hepatitis B is high

There is no specific treatment for hepatitis A or hepatitis B. Vaccination is the best way to protect against infection.

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

2. What should I know before I am given TWINRIX?

Warnings

Do not use TWINRIX if:

  • you are allergic to TWINRIX, or any of the ingredients listed at the end of this leaflet (e.g. neomycin sulphate). Always check the ingredients to make sure you can use this medicine. Signs of an allergic reaction may include an itchy skin rash, shortness of breath and swelling of the face or tongue.

Tell your doctor, nurse or pharmacist before the vaccine is given:

  • if you have/ your child has had TWINRIX before and became unwell
  • you have/ your child has 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.

Check with your doctor if:

  • you have/ your child has an allergy to baker's yeast, medicines or substances, such as dyes, foods or preservatives.
  • you have/ your child has any medical conditions, such as:
    - a severe heart or lung disease
    - a liver or kidney problem
    - an immune deficiency condition (eg. HIV positive)
    - a nervous system illness
    - or a bleeding disorder
  • you / your child take any medicines for any condition
  • you have / your child has received another vaccine recently or are taking any prescription or OTC (over-the-counter) medicines.

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.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant. Your doctor will discuss with you the possible risks and benefits of receiving TWINRIX during pregnancy.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

It is not known if TWINRIX passes into breast milk, however the vaccine is not expected to cause problems for breast-fed babies.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines or vaccines may interfere with TWINRIX and affect how it works, in particular medicines which suppress the immune system, such as steroids or cyclosporin.

Your doctor, nurse or pharmacist will be able to tell you what to do if TWINRIX is to be given with another vaccine or medicine.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect TWINRIX.

4. How is TWINRIX given?

How much is given

  • The dose using TWINRIX (720/20) is 1 mL.
  • The dose using TWINRIX JUNIOR (360/10) is 0.5 mL.
  • The doctor or nurse will give TWINRIX as an injection. If you have any concerns about how this vaccine is to be given, talk to your doctor or pharmacist.

How is it given

TWINRIX will be injected into your upper arm muscle in adults and older children, and into the thigh muscle in infants. For some people with bleeding problems, the dose may need to be given under the skin (subcutaneously). Each dose of TWINRIX is for single use only. Any residual vaccine must be discarded.

The vaccine should never be given intravenously.

When is it given

Adults

TWINRIX (720/20) is generally given as a total of three doses over 6 months. Each dose is given on 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

For adults, TWINRIX (720/20) 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 schedule. Therefore, this rapid schedule should only be used under special circumstances (e.g. adult travellers wanting to be vaccinated within one month of departure). A booster dose is recommended at 12 months.

Children (1 to 15 years inclusive)

TWINRIX (720/20) is generally given as a total of two doses 6 to 12 months apart. Each dose is given on a separate visit. The first dose will be given on an elected date. The second dose will be given 6 to 12 months after the first dose.

First dose: at an elected date

Second dose: 6 to 12 months after the first dose.

In children who are travelling to areas where there is a risk of exposure to hepatitis B, TWINRIX Junior (360/10) should be given as a total of 3 doses over 6 months (a 0, 1, 6 month schedule).

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

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

If a dose is missed

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

If you use too much TWINRIX

If you think that you have used too much TWINRIX, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while being given TWINRIX?

Things you should do

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

Call your doctor straight away if:

  • you or your child do not feel well during or after having had a dose of TWINRIX.

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

Remind any doctor, nurse or pharmacist you visit that you have been given TWINRIX.

Things you should not do

  • Do not miss follow up doses.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how TWINRIX affects you.

TWINRIX 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 TWINRIX before you drive a car or operate machinery, or do anything that could be dangerous if you feel dizzy or lightheaded.

Looking after your medicine

TWINRIX is usually stored at the doctor's clinic or surgery, or at the pharmacy, but if you need to store TWINRIX always:

  • Keep TWINRIX 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 TWINRIX in the original pack until it is time for it to be given.

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep it where young children cannot reach it.

When to discard your medicine

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

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

Do not use this medicine if the packaging is torn or shows signs of tampering.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
General disorders and administration site conditions:
  • Soreness, redness, swelling, a hard lump, bruising or itching around the injection site
  • Immediate injection site pain, stinging and burning feeling
  • Fatigue, headache, unusual tiredness, drowsiness, dizziness or feeling generally unwell
  • Fever
  • Fainting or chills
  • Ringing in the ears
Gastrointestinal disorders:
  • Feeling sick or vomiting, stomach pains or diarrhoea,
  • Loss of appetite
Musculoskeletal disorders:
  • Muscle aches and pains, painful joints, neck stiffness
Psychiatric disorders:
  • Disturbed sleep
Respiratory and mouth disorders:
  • Cough, sore throat, respiratory infections
Skin disorders:
  • Sweating, flushing
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
General disorders and administration site conditions:
  • Feelings of numbness, weakness and/or fatigue in limbs, tingling in fingers or toes
  • Generalised stiffness, difficulty passing urine
  • Swollen glands, unusual bleeding, bleeding or bruising more easily than normal
  • Sudden headache, neck stiffness, dislike of bright lights, convulsions (fits)
Eye disorders:
  • Visual changes
  • Drooping eyelids or sagging facial muscles
As with all vaccines given by injection there is a very small risk of serious allergic reaction. This may occur days to weeks after vaccination:
  • 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.
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What TWINRIX contains

Active ingredientKilled hepatitis A virus and the surface protein of the hepatitis B virus (from genetically engineered yeast cells).
The vaccine is not infectious, and will not give you hepatitis A or hepatitis B.
Other ingredients
(inactive ingredients)		Aluminium hydroxide hydrate
Aluminium phosphate,
Sodium chloride
Amino acid supplement
Formaldehyde
Neomycin sulphate
Polysorbate 20
Dibasic sodium phosphate heptahydrate
Monobasic sodium phosphate
Trometamol
Water.
Potential allergensThe 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.

Do not take this medicine if you are allergic to any of these ingredients.

What TWINRIX looks like

TWINRIX comes in prefilled syringes. It is a white, slightly milky liquid. Two different vaccine dosages are available:

  • TWINRIX (720/20): 720 ELISA units of killed hepatitis A virus and 20 micrograms of the hepatitis B surface protein
    (AUST R 140575)
  • TWINRIX JUNIOR (360/10): 360 ELISA units of killed hepatitis A virus and 10 micrograms of the hepatitis B surface protein.
    (AUST R 140576).

Who distributes Twinrix

GlaxoSmithKline Australia Pty Ltd
Level 4, 436 Johnston Street,
Abbotsford, Victoria, 3067
Phone: 1800 033 109
www.gsk.com.au

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

©2025 GSK group of companies or its licensor.

This leaflet was prepared on 09 July 2025.

Version 7.0

Published by MIMS August 2025

BRAND INFORMATION

Brand name

Twinrix Preservative Free

Active ingredient

Hepatitis A child/adolescent vaccine; Hepatitis B child vaccine

Schedule

S4

 

1 Name of Medicine

Combined hepatitis A and hepatitis B vaccine.

2 Qualitative and Quantitative Composition

Twinrix is a non-infectious combination vaccine containing hepatitis A virus antigen and hepatitis B surface antigen (rys).
Each 1 mL dose of Twinrix contains 720 ELISA units of hepatitis A virus antigen and 20 micrograms of hepatitis B surface antigen (rys). The viral antigens are adsorbed on 0.45 mg aluminium in the form of aluminium phosphate and aluminium hydroxide hydrate and suspended in a solution containing 8.8 mg of sodium chloride.
Each 0.5 mL dose of Twinrix Junior contains 360 ELISA units of hepatitis A virus antigen and 10 micrograms of hepatitis B surface antigen (rys). The viral antigens are adsorbed on 0.225 mg aluminium in the form of aluminium phosphate and aluminium hydroxide hydrate and suspended in a solution containing 4.4 mg of sodium chloride.
Twinrix is formulated using the HM 175 strain of hepatitis A grown in human cell culture (MRC5), and inactivated with formaldehyde. The hepatitis B surface antigen (rys) component is produced by culturing genetically-engineered Saccharomyces cerevisiae yeast cells (Baker's yeast), which carry the relevant gene of an adw subtype, of the surface antigen of the hepatitis B virus. Both the hepatitis A virus antigen and hepatitis B surface antigen (rys) are purified by several physico-chemical steps, and formulated as separate antigen suspensions adsorbed onto aluminium salts. Twinrix is produced by pooling bulk preparations of the purified antigens. The bulk hepatitis A virus antigen and hepatitis B surface antigen (rys) preparations are identical to those used in the manufacture of the currently licensed monovalent hepatitis A (Havrix) and hepatitis B (Engerix-B) vaccines. Standardised fermentation and purification procedures ensure batch to batch consistency. The vaccines are free of association with human blood or blood products.
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.
Twinrix meets the World Health Organization requirements for the manufacture of biological substances.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Twinrix is a sterile suspension.

4 Clinical Particulars

4.1 Therapeutic Indications

Twinrix (720/20) is indicated for active immunisation against hepatitis A and hepatitis B virus infection in adults and children from 1 year of age. Twinrix Junior (360/10) is indicated for use in children aged 1 to 15 years.

Immunisation against hepatitis A is recommended in the following individuals.

Travellers.

Persons travelling to areas of intermediate or high endemicity for hepatitis A. This includes all developing countries.

Armed forces.

Armed forces personnel who travel to higher endemicity areas or to areas where hygiene is poor, have an increased risk of HAV infection.
Persons for whom hepatitis A is an occupational hazard or for whom there is an increased risk of transmission. These include:
employees in day care centres, particularly in situations where children have not been toilet trained;
teachers and other close contacts of the intellectually disabled;
staff and residents of residential facilities for the intellectually disabled;
healthcare workers and teachers in remote Aboriginal and Torres Strait Islander communities;
nursing staff and other healthcare workers in contact with patients in paediatric wards, infectious diseases wards, emergency rooms and intensive care units;
sewerage workers;
food handlers, since food hygiene procedures and food processing methods are not always adequate to protect from contamination from food handlers.

Homosexual men.

Increased incidence of hepatitis A infection among homosexual males suggests that the disease may be sexually transmitted in this group.

Contacts of infected persons.

Since virus shedding from infected persons may occur for a prolonged period, active immunisation of close contacts is recommended. The use of vaccine in outbreak control has been shown to be more effective than the use of immunoglobulin.
Specific population groups known to have a higher incidence of hepatitis A: e.g. Australian Aboriginals, those in settings with recognised community wide HAV epidemics.
Individuals with chronic liver disease and recipients of liver transplants, as hepatitis A infection is likely to be more severe in these groups. Many injecting drug users will have pre-existing liver disease from hepatitis B or hepatitis C infection.
Recipients of blood products, such as factor VIII concentrates.

Immunisation against hepatitis B is recommended in the following individuals.

Persons for whom hepatitis B is an occupational hazard or for whom there is an increased risk of transmission. These include:
healthcare workers directly involved in patient care, or in the handling of human blood or tissue;
embalmers;
staff and residents of residential facilities for the intellectually disabled;
inmates of long-term correctional facilities and staff of correctional facilities.
Individuals with chronic liver disease and/or hepatitis C.
Haemodialysis patients and recipients of certain blood products such as factor VIII concentrates.
Sexually active homosexual men and persons with multiple sexual partners: e.g. clients of STD (sexually transmitted disease) clinics. Sexual risk occurs in susceptible (anti-HBs negative) partners of HBV carriers and patients with acute hepatitis B.
Abusers of injectable drugs.
Close residential contacts of deinstitutionalised intellectually disabled individuals who are HBV carriers.
Household contacts of patients with acute hepatitis B and chronic hepatitis B carriers.

Others in whom vaccination against hepatitis B might be justified.

Police and members of the armed forces.
Travellers to areas of high endemicity for hepatitis B.
Participants in contact sports.

4.2 Dose and Method of Administration

The vaccine should be resuspended before use. When resuspended, the vaccine will have a uniform hazy white appearance.
Upon storage, a fine white deposit with a clear colourless layer above may be observed.

Resuspension of the vaccine to obtain a uniform hazy white suspension.

The vaccine can be resuspended following the steps below.
1. Hold the syringe upright in a closed hand.
2. Shake the syringe by tipping it upside down and back again.
3. Repeat this action vigorously for at least 15 seconds.
4. Inspect the vaccine again:
a. If the vaccine appears as a uniform hazy white suspension, it is ready to use - the appearance should not be clear.
b. If the vaccine still does not appear as a uniform hazy white suspension - tip upside down and back again for at least another 15 seconds - then inspect again.
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, do not administer the vaccine.

Instructions for the pre-filled syringe.

Hold the syringe by the barrel, not by the plunger.
Unscrew the syringe cap by twisting it anticlockwise.
To attach the needle, connect the hub to the Luer Lock Adaptor and rotate a quarter turn clockwise until you feel it lock.
Do not pull the syringe plunger out of the barrel. If it happens, do not administer the vaccine.
Each dose of Twinrix is for single use only. Any unused product or waste material should be disposed of in accordance with local requirements.
Twinrix should be injected intramuscularly into the deltoid region of the upper arm in adults and older children. The anterolateral aspect of the thigh may be used in infants.
Exceptionally, the vaccine may be administered subcutaneously in patients with thrombocytopenia or bleeding disorders (e.g. haemophiliacs) since bleeding may occur following an intramuscular administration to these subjects. (See Section 4.4 Special Warnings and Precautions for Use.)
Twinrix must not be given intravenously.

Immunisation schedule.

Twinrix (720/20). In children and adults not previously exposed to hepatitis A or hepatitis B viruses or vaccines the primary course of Twinrix is as follows in Table 1.

Rapid schedule.

The rapid schedule is used in exceptional circumstances in adults when more rapid protection is required, e.g. in travellers commencing vaccination within one month or more of departure. When this rapid schedule is used, a fourth dose is recommended 12 months after the first dose to ensure adequate protection, as lower seroprotection rates against hepatitis B were observed after the third dose as compared to the standard 0, 1, 6 month schedule (see Section 5.1 Pharmacodynamic Properties, Clinical trials).
Twinrix Junior (360/10). In circumstances where a child is at immediate risk of exposure to hepatitis B (e.g. travellers), and did not receive a primary course of hepatitis B vaccine as an infant, Twinrix Junior should be used as follows in Table 2.

Booster dose.

Long-term clinical studies have demonstrated persistence of anti-HAV and anti-HBs antibodies 20 years after immunisation with Twinrix (720/20) and 15 years after immunisation with Twinrix Junior (360/10). As persistence of antibodies were similar to those following the monovalent vaccines, general guidelines for booster vaccination can therefore be drawn from those for the monovalent vaccines.

Hepatitis B.

The need for a booster dose in healthy individuals who have received a full primary vaccination course has not been established. Thus a booster dose is not recommended in these circumstances. Booster doses are recommended for haemodialysis patients and other immunocompromised patients. Refer to the Australian Immunisation Handbook for further guidance.

Hepatitis A.

Data available from clinical studies using hepatitis A vaccine (Havrix) show persistence of antibodies after 8 years which is consistent with a projected 20 years persistence (based on mathematical calculations). Further long-term follow-up of immunised cohorts will be required to determine the duration of protection following hepatitis A immunisation and whether and when booster doses may be required.
In situations where a booster dose of both hepatitis A and hepatitis B are desired, the combined vaccine can be given. Alternatively, subjects primed with Twinrix may be administered a booster dose of either of the monovalent vaccines.

4.3 Contraindications

Twinrix should not be administered to subjects with known hypersensitivity to any component of the vaccine (e.g. neomycin sulphate), or to subjects having shown signs of hypersensitivity after previous administration of these combined vaccines or the monovalent hepatitis A or hepatitis B vaccines.
As for any vaccine, Twinrix should not be administered to subjects suffering from acute severe febrile illness. However, the presence of minor infection does not contraindicate vaccination.

4.4 Special Warnings and Precautions for Use

Twinrix should never be administered intravenously.
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.
As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of anaphylactic reactions following the administration of the vaccine.
Twinrix should not be administered in the gluteal region. It should not be routinely administered intradermally, or subcutaneously since these routes of administration may not result in an optimum immune response.
Twinrix should be administered with caution to subjects with thrombocytopenia or a bleeding disorder since bleeding may occur following an intramuscular administration to these subjects (see Section 4.2 Dose and Method of Administration).
In elderly subjects, haemodialysis patients and persons with an impaired immune system, adequate anti-HAV and anti-HBs antibody titres may not be obtained after a primary vaccination course. The monitoring of antibody titres and if appropriate the need for additional doses of the appropriate vaccine should be considered in such patients. The rapid schedule has not been studied and is not recommended in such patients.
Caution should be exercised in administering Twinrix 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.
It is possible that subjects may be in the incubation period of a hepatitis A or hepatitis B infection at the time of vaccination. It is not known whether Twinrix will prevent hepatitis A and hepatitis B in such cases. These vaccines will not induce the production of anti-HBs antibodies in hepatitis B carriers.
The vaccines will not protect against infection caused by hepatitis C or hepatitis E viruses, or other pathogens known to infect the liver.

Use in renal impairment.

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

Use in the elderly.

See Section 4.4 Special Warnings and Precautions for Use.

Paediatric use.

See Section 4.4 Special Warnings and Precautions for Use.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Clinical studies have demonstrated that Twinrix can be administered concomitantly with diphtheria, tetanus, acellular pertussis, inactivated poliomyelitis, Haemophilus influenzae type b and measles mumps rubella vaccines. In these trials, the injectable vaccines were given at a different injection site to Twinrix.

Guidance for coadministration of Twinrix Junior and Cervarix should be drawn from those individual vaccines.

Twinrix Junior (360/10) can be given concomitantly with human papillomavirus (HPV) vaccine (Cervarix). Administration of Twinrix Junior (360/10) at the same time as Cervarix (HPV vaccine) has shown no clinically relevant interference in the antibody response to the HPV and hepatitis A 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 subjects reaching anti-HBs ≥ 10 mIU/mL was 98.3% for concomitant vaccination and 100% for Twinrix Junior (360/10) alone. The Product Information documents for Twinrix Junior and Cervarix should be consulted for guidance with respect to appropriate usage, population and dosing guidelines for these vaccines.
The concomitant administration of Twinrix with other vaccines (e.g. pneumococcal, influenza) given at separate sites using separate syringes has not been specifically studied.
Twinrix must not be mixed with other vaccines in the same syringe.
As with other vaccines, it may be expected that patients receiving immunosuppressive therapy or patients with an immunodeficiency, may not achieve an adequate immune response. (See Section 4.4 Special Warnings and Precautions for Use.)
Concomitant administration of normal human immunoglobulin with the first dose of hepatitis A vaccine does not influence the seroconversion rate, but may result in a relatively lower anti-HAV antibody titre than when the primary course of vaccine is given alone. Twinrix and normal human immunoglobulin should be administered at separate injection sites.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

See Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy.
(Category B2)
Twinrix should be used during pregnancy only when clearly needed, and when the possible advantages outweigh the possible risks for the foetus.
The effect of Twinrix on embryofoetal, perinatal and postnatal survival and development has not been prospectively evaluated in clinical trials.
The effect of Twinrix on embryofoetal, perinatal and postnatal survival and development has been assessed in a study in rats. There were no direct or indirect harmful effects with respect to fertility, pregnancy, embryonal/foetal development, parturition or postnatal development, at 1/5 the adult human dose (9 times greater than the clinical adult exposure based on mg/m2).
 Adequate human data on use during lactation and adequate animal reproduction studies are not available.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Clinical trial data.

The safety profile presented below is based on data from more than 6,000 subjects who received either the standard 0, 1, 6 month schedule or the accelerated 0, 7, 21 days schedule of Twinrix (720/20).
Events are listed within body systems and categorised by frequency according to the following definitions: very common: ≥ 1/10; common: ≥ 1/100 and < 1/10; uncommon: ≥ 1/1000 and < 1/100; rare: ≥ 1/10,000 and < 1/1000; very rare: < 1/10,000.

Gastrointestinal disorders.

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

General disorders and administration site conditions.

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

Infections and infestations.

Common: viral infection.
Uncommon: upper respiratory tract infection.

Blood and lymphatic system disorders.

Rare: lymphadenopathy.

Metabolism and nutrition disorders.

Rare: decreased appetite.

Nervous system disorders.

Very common: headache.
Uncommon: dizziness.
Rare: hypoaesthesia, paraesthesia.

Vascular disorders.

Rare: hypotension.

Skin and subcutaneous tissue disorders.

Rare: rash, pruritus.
Very rare: urticaria.

Musculoskeletal and connective tissue disorders.

Uncommon: myalgia.
Rare: arthralgia.
In a clinical trial where Twinrix was administered at 0, 7, 21 days, solicited general symptoms were reported with the same categories of frequency as defined above. After a fourth dose given at month 12, the incidence of systemic adverse reactions was comparable to that seen after vaccination at 0, 7, 21 days.
During clinical studies with Twinrix Junior (360/10) (n = 538 doses of vaccines administered) the frequency of local reactions in children, although still considered common, were almost half that reported with Twinrix (720/20) in adults. Of the general reactions reported in these children, most were reported at a similar frequency to Twinrix (720/20) in adults except upper respiratory tract infection, fever and vomiting which were commonly reported at frequencies of 9.3%, 3.7% and 1.9%, respectively.
Other adverse events observed in clinical trials performed with Twinrix Junior include:

Blood and lymphatic system disorders.

Rare: lymphadenopathy.

Metabolism and nutrition disorders.

Common: appetite lost.

General disorders and administration site conditions.

Very common: pain and redness at the injection site.
Common: irritability, swelling at the injection site, injection site reaction, fatigue, malaise, fever (≥ 37.5°C).

Nervous system disorders.

Common: drowsiness, headache.
Rare: dizziness.

Gastrointestinal disorders.

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

Skin and subcutaneous tissue disorders.

Uncommon: rash.
Rare: urticaria.
In a comparative trial in children and adolescents, (n = 745 doses) the percentage of subjects reporting solicited adverse events after a primary course of Twinrix (720/20) used in a two dose schedule was similar to that seen with Twinrix Junior (360/10) given in a 3 dose schedule. Pain was reported in 50.7% of the Twinrix (720/20) group and in 39.1% of the Twinrix Junior (360/10) group. Incidence of redness was 16.1% and 11.9% and swelling was reported in 4.4% and 4.9% in the Twinrix and Twinrix Junior groups, respectively.
General reactions solicited in controlled clinical trials that may occur in temporal association with Twinrix used in a two dose schedule in children and adolescents include:

General disorders and administration site conditions.

Very rare: influenza-like illness, chills.

Nervous system disorders.

Very rare: hypoaesthesia, paraesthesia.

Gastrointestinal disorders.

Common: gastrointestinal symptoms (such as diarrhoea).

Musculoskeletal and connective tissue disorders.

Very rare: myalgia, arthralgia.

Skin and subcutaneous tissue disorders.

Very rare: pruritus.

Vascular disorders.

Very rare: hypotension.

Postmarketing data.

The following adverse reactions have been reported with either Twinrix or with monovalent hepatitis A or B vaccines.

Infections and infestations.

Meningitis.

Blood and lymphatic system disorders.

Thrombocytopenia, thrombocytopenic purpura.

Immune system disorders.

Anaphylaxis, allergic reactions including anaphylactoid reactions and mimicking serum sickness.

Nervous system disorders.

Encephalitis, encephalopathy, neuritis, neuropathy, paralysis, convulsions.

Vascular disorders.

Vasculitis.

Skin and subcutaneous tissue disorders.

Angioneurotic oedema, lichen planus, erythema multiforme.

Musculoskeletal and connective tissue disorders.

Arthritis, muscular weakness.

General disorders and administration site conditions.

Immediate injection site pain, stinging and burning sensation.

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.

4.9 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 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Twinrix induces the production of specific anti-HAV and anti-HBs antibodies, which confer immunity against HAV and HBV infection.

Clinical trials.

Adults - standard schedule. The immunogenicity of Twinrix (720/20) has been investigated using a 0, 1 and 6 month vaccination schedule in randomised clinical studies involving over 700 adult volunteers.
Specific humoral antibodies (seropositivity) against HAV were elicited in:
92-96% of vaccines one month after the first dose;
97-100% of vaccines one month after the second dose;
100% of vaccines one month after the third dose.
Seropositivity was defined as anti-HAV antibody titres ≥ 33 IU/L.
Seroprotective levels of anti-HBs antibodies (titers ≥ 10 IU/L) were elicited in:
33.7% of vaccines one month after the first dose;
83.9% of vaccines one month after the second dose;
99.3% of vaccines one month after the third dose.
An anti-HBs antibody titre above 10 IU/L correlates with protection against hepatitis B infection.
Adults - rapid schedule. The immunogenicity of Twinrix (720/20) has also been investigated using a 0, 7, 21 day primary schedule plus a fourth dose at month 12 in a randomised clinical study involving over 400 adult volunteers, of whom 239 received Twinrix (720/20).
Specific humoral antibodies (seropositivity) against HAV were elicited in:
100% of vaccines one week after the third dose;
99.5% of vaccines five weeks after the third dose;
100% of vaccines one month after the fourth dose.
Seroprotective levels of anti-HBs antibodies (titers ≥ 10 IU/L) were elicited in:
82% of vaccines one week after the third dose;
85% of vaccines five weeks after the third dose;
100% of vaccines one month after the fourth dose.
Children. The immunogenicity of Twinrix (720/20) has been investigated using a 0 and 6 month vaccination schedule in randomised clinical studies involving 451 subjects aged 1 to 15 years old.
Specific humoral antibodies (seropositivity) against HAV were elicited in:
99.1% of vaccines one month after the first dose;
100% of vaccines one month after the second dose.
Seroprotective levels of anti-HBs antibodies (titers ≥ 10 IU/L) were elicited in:
37.4% of vaccines one month after the first dose;
70.5% of vaccines 6 months after the first dose;
98.2% of vaccines one month after the second dose.
In a clinical study involving 117 subjects who received the second dose at month 12, specific humoral antibodies (seropositivity) against HAV were elicited in 99.0% of vaccines one month after the second dose, and seroprotective levels of anti-HBs were induced in 97.0% of subjects.
The immunogenicity of Twinrix Junior (360/10) has been investigated using a 0, 1 and 6 month vaccination schedule in randomised clinical studies involving 168 children: 54 subjects aged 1 to 6 years and 114 subjects aged 6 to 15 years.
Specific humoral antibodies (seropositivity) against HAV were elicited in:
100% of vaccines one month after the second dose;
100% of vaccines one month after the third dose.
Seroprotective levels of anti-HBs antibodies (titers ≥ 10 IU/L) were elicited in:
86.2% to 94.6% of vaccines one month after the second dose;
100% of vaccines one month after the third dose.
In a comparative study in children and adolescents, Twinrix (720/20) following a 0 and 6 month schedule was proven to be noninferior for both hepatitis A and B antibody responses to Twinrix Junior (360/10) following a 0, 1 and 6 month schedule. However, seroprotection rates for hepatitis B at month 2 after two doses of Twinrix Junior (given one month apart) were higher (85.6%) than after a single dose of Twinrix (38.0%).
Antibody persistence.

Twinrix Junior (360/10).

In two long-term clinical studies, persistence of anti-HAV and anti-HBs antibodies has been demonstrated up to 15 years in children aged 12-15 years and up to 5 years in children aged 1-11 years. For 1-11 years age cohort, after the primary vaccination with 0, 1, 6 month schedule of Twinrix Junior, all subjects followed up to 5 years (N = 102) retained ≥ 15 mIU/mL anti-HAV antibody and 97% retained anti-HBs antibody ≥ 10 mIU/mL. For 12-15 years age cohort, after the primary vaccination with 0, 1, 6 month schedule of Twinrix Junior, all subjects followed up to 15 years (N = 102) retained ≥ 15 mIU/mL anti-HAV antibody and 85% retained anti-HBs antibody ≥ 10 mIU/mL. A challenge dose of a HBV vaccine was given to a limited number of subjects (n = 11) whose anti-HBs antibody concentration decreased to < 10mIU/mL and 90.9% mounted an anamnestic response.

Twinrix (720/20).

In two long-term clinical studies conducted in 43 healthy adults aged 17-43 years, 20 years after the primary vaccination with Twinrix (720/20) the anti-HAV seropositivity rates were 100% and 96% respectively and the anti-HBs seroprotection rates were 94% and 92%, respectively.
In two clinical studies conducted in subjects over 40 years of age, the seropositivity rate for anti-HAV antibodies and seroprotection rate against hepatitis B following Twinrix (720/20) on a 0, 1, 6 month schedule were compared with the seropositivity and seroprotection rates of monovalent hepatitis A and B vaccines when administered separately.
The seroprotection rates against hepatitis B after the administration of Twinrix (720/20) were 92% and 57% at 7 and 48 months following the first dose, respectively, versus 80% and 40% after the GlaxoSmithKline Biologicals monovalent 20 microgram hepatitis B vaccine, and 71% and 27% after another licensed monovalent 10 microgram hepatitis B vaccine. In all groups, anti-HBs antibody concentrations decreased as age and body mass index increased; concentrations were also lower in males compared with females.
The seropositivity rates for anti-HAV antibodies after Twinrix (720/20) were 97% at both 7 and 48 months following the first dose versus 99% and 94% after the GlaxoSmithKline Biologicals monovalent hepatitis A vaccine and 99% and 96% after another licensed monovalent hepatitis A vaccine.
Subjects received an additional dose of Twinrix (720/20) to assess the immune memory 48 months after the first dose of the primary vaccination course with the same vaccine. One month after this dose, 95% of subjects elicited anti-HBV antibody concentration ≥ 10 mIU/mL and geometric mean concentrations (GMC) increased by 179-fold (GMC of 7233.7 mIU/mL) indicative of an immune memory response.
Anti-HAV and anti-HBs antibodies have been shown to persist for at least 24 months following the initiation of a 0, 6 month schedule of Twinrix (720/20) in children. Specific humoral antibodies (seropositivity) against HAV were elicited in 100% of vaccines at month 24, and anti-HBs seroprotective levels were present in 93.3% of subjects. In this study, the immune response for both antigen components was comparable to that seen after a 3 dose regimen of Twinrix Junior (360/10).
The persistence of anti-HAV and anti-HBs antibodies at month 24 was shown to be similar following a 0, 6 month or a 0, 12 month schedule of Twinrix (720/20) in children.
Hepatitis D. 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 Twinrix.

5.2 Pharmacokinetic Properties

Not relevant to vaccines.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

The vaccine preparation also contains ≤ 0.45 mg/mL aluminium in the form of aluminium phosphate and aluminium hydroxide hydrate suspended in a solution containing ≤ 8.8 mg/mL of sodium chloride, 1 mg/mL of amino acid supplement, < 20 nanogram/mL of neomycin sulphate, 50 microgram/mL of polysorbate 20, < 7 microgram/mL of dibasic sodium phosphate heptahydrate, < 5 microgram/mL of monobasic sodium phosphate, < 250 microgram/mL of trometamol and < 100 microgram/mL of formaldehyde.

6.2 Incompatibilities

See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Twinrix must be stored between +2°C to +8°C. Do not freeze; freezing destroys the potency of the product. Discard the vaccine if it has been frozen. Store in the original package in order to protect from light.

6.5 Nature and Contents of Container

Twinrix.

1 mL of suspension in a pre-filled syringe (type I glass) with a plunger stopper (butyl rubber) and with a rubber tip cap.

Twinrix Junior.

0.5 mL of suspension in a pre-filled syringe (type I glass) with a plunger stopper (butyl rubber) and with a rubber tip cap.
The tip cap and rubber plunger stopper of the pre-filled syringe are not made with natural rubber latex.
Twinrix and Twinrix Junior are available as a pre-filled syringe in packs of one or ten.
Not all presentations and pack sizes may be marketed in Australia.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Not relevant to vaccines.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes