AMBIRIX SUSPENSION FOR INJECTION IN PRE-FILLED SYRINGE

1. What is Ambirix and what is it used for

Ambirix is a vaccine used in infants, children, and young people from 1 year of age up to and including 15 years of age. It is used to prevent two diseases: hepatitis A and hepatitis B.

• Hepatitis A:Infection with the hepatitis A virus can cause liver inflammation. The virus is acquired from food or drinks that contain the virus. However, it can sometimes be acquired through other means, such as swimming in sewage or from another infected person. The virus is present in bodily fluids such as feces, serum, or saliva.

Symptoms start between 3 and 6 weeks after infection. Some people may experience nausea, fever, and pain. After several days, they may feel very tired, have dark urine, pale face, and yellowish skin or eyes (jaundice). The severity and type of symptoms can vary. Young children may not experience all the symptoms. Most children recover completely from the disease, although it is usually severe enough to make children ill for about a month.

• Hepatitis B:Infection with the hepatitis B virus can cause liver inflammation. The virus is usually acquired from another infected person. It is found in bodily fluids such as blood, semen, vaginal secretions, or saliva (sputum).

It is possible that no symptoms will be observed during the 6 weeks or 6 months after infection. Infected people do not always feel or appear ill. Some people may experience nausea, fever, and pain. However, others may become very ill. They may be very tired, have dark urine, pale face, and yellowish skin or eyes (jaundice). Some people may need to be hospitalized.

Most adults recover completely from the disease, although some people (particularly children) who do not have symptoms may remain infected. These people are known as "carriers" of hepatitis B and can continue to infect others throughout their lives. Additionally, carriers are at risk of developing serious liver problems, such as liver damage (cirrhosis) or liver cancer.

How Ambirix works

• Ambirix helps the body produce its own protection (antibodies) against these diseases. The vaccine does not contain live viruses (see section 6 for vaccine content) and therefore cannot cause infections with the hepatitis A or B virus.

• As with all vaccines, some people may not respond as well to a vaccine as others.

• Ambirix may not protect you from the disease if you have already acquired the hepatitis A or B virus.

• Ambirix can only help protect you against infections with the hepatitis A or B virus. It cannot protect against other infections that can affect the liver, even if those infections have similar symptoms to those caused by the hepatitis A or B virus.

2. What you need to know before you receive Ambirix

Ambirix must not be administered if:

• you are allergic to Ambirix or any of the other components of this vaccine (listed in section 6). The signs of an allergic reaction can include skin rash with itching, difficulty breathing, and swelling of your face or tongue.

• you have previously had an allergic reaction to any vaccine against hepatitis A or hepatitis B.

• you have a severe infection with high fever. The vaccine can be administered once you have recovered. A minor infection, such as a cold, should not be a problem for vaccination, but consult your doctor first.

Ambirix must not be administered if you are in any of the above situations. If you are unsure, consult your doctor, pharmacist, or nurse before receiving Ambirix.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before receiving Ambirix if:

• you need to be fully protected against hepatitis A and B infection within the next 6 months (your doctor may recommend a different vaccine).
• you have any bleeding problems or bruise easily (the injection can be given just under the skin instead of into a muscle to reduce bleeding or bruising).
• you have immune system problems (such as those due to disease, medication, or dialysis), the vaccine may not work completely. This means you may not be protected against one or both of the hepatitis A and B viruses. Your doctor will perform blood tests to check if additional injections are needed to help you be better protected.
• you have fainted previously or during a previous injection, to prevent it from happening again. Fainting (especially in adolescents) may occur before or after any injection.

If you are in any of the above situations (or are unsure), consult your doctor, pharmacist, or nurse before receiving Ambirix.

Other medicines and Ambirix

Tell your doctor if you are using, have recently used, or might use any other medicines or vaccines. This includes medicines obtained without a prescription and herbal medicines. Ask your doctor, pharmacist, or nurse if you have any questions.

Although you are taking medicines that affect your body's immune response, you can receive Ambirix if it is considered necessary. However, the vaccine may not work completely. This means you may not be protected against one or both of the hepatitis A and B viruses. Your doctor will perform blood tests to determine if additional injections are needed to help you be better protected.

Ambirix can be administered at the same time as other vaccines against measles, mumps, rubella, diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzaetype b, or some types of liver infection treatments called "immunoglobulins". Your doctor will ensure that the vaccines are injected into different parts of your body.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor, pharmacist, or nurse before receiving this vaccine. Ambirix is not usually administered to pregnant or breastfeeding women.

Driving and using machines

You may feel drowsy or dizzy after receiving Ambirix. If this happens, do not drive or ride a bicycle or use tools or machines.

Ambirix contains neomycin and sodium

This vaccine contains neomycin (an antibiotic). Ambirix must not be administered if you are allergic to neomycin.

This vaccine contains less than 1 mmol of sodium (23 mg) per dose; this is essentially "sodium-free".

3. How to administer Ambirix

How the injection is administered

• Your doctor or nurse will administer Ambirix as an injection into a muscle, usually in the upper arm.
• They will make sure that Ambirix is not administered into a vein.
• In very young children, the injection can be administered into the thigh muscle.

How much is administered

• You will usually receive a total of two injections. Each injection is given on a separate visit.
• The injections are administered within a period of 12 months:

• The first injection - on a date agreed with your doctor.
• The second injection - between 6 and 12 months after the first injection.

Your doctor will advise you on the need for additional doses and future booster doses.

If you miss a dose

• If you miss the second injection, talk to your doctor to schedule another visit as soon as possible.

• Make sure you complete the full series of two injections. Otherwise, you may not be protected against the diseases.

4. Possible side effects

Like all medicines, this vaccine can cause side effects, although not everybody gets them.

Serious side effects

• Tell your doctor immediately if you notice any of the following serious side effects (you may need urgent medical treatment):anaphylactic and allergic reactions: the signs can include skin rash with itching or blisters, swelling of the eyes and face, difficulty breathing or swallowing, sudden drop in blood pressure, and loss of consciousness.

Tell your doctor immediately if you notice any of the serious side effects listed above.

The side effects that occurred during clinical trials with Ambirix were:

Very common(may occur in more than 1 in 10 doses of the vaccine): headache, loss of appetite, feeling tired or irritable, pain and redness at the injection site.

Common(may occur in up to 1 in 10 doses of the vaccine): fever, feeling drowsy, stomach and digestive problems, swelling at the injection site.

Additional side effects reported during clinical trials with combined hepatitis A and hepatitis B vaccines very similar to this one include:

Common(may occur in up to 1 in 10 doses of the vaccine): general feeling of being unwell, diarrhea, nausea, reaction at the injection site.

Uncommon(may occur in up to 1 in 100 doses of the vaccine): feeling dizzy, stomach pain, vomiting, upper respiratory tract infections, muscle pain (myalgia).

Rare(may occur in up to 1 in 1,000 doses of the vaccine): low blood pressure, joint pain (arthralgia), itching (pruritus), skin rash, tingling (paresthesia), swelling of the lymph nodes in the neck, armpits, and groin (lymphadenopathy), flu-like symptoms such as high temperature, sore throat, runny nose, cough, and chills.

Very rare(may occur in up to 1 in 10,000 doses of the vaccine): hives (urticaria).

Consult your doctor if you experience any side effects similar to these.

The side effects that occurred during routine use of Ambirix were:fainting, loss of skin sensation to pain or touch (hypoesthesia).

Additional side effects reported during routine use of combined or individual hepatitis A and hepatitis B vaccines very similar to this one were:multiple sclerosis, spinal cord swelling (myelitis), abnormal liver test results, brain swelling or infection (encephalitis), inflammation of some blood vessels (vasculitis), a degenerative brain disease (encephalopathy), swelling of the face, mouth, and throat (angioneurotic edema), severe headache with stiff neck and sensitivity to light (meningitis), a temporary inflammation of the nerves that causes pain, weakness, and paralysis in the arms and legs and often progresses to the chest and face (Guillain-Barré syndrome), seizures or fits, nerve inflammation (neuritis), eye nerve disease (optic neuritis), numbness or weakness of the arms and legs (neuropathy), pain at the injection site, burning sensation, paralysis, drooping eyelid and muscle weakness on one side of the face (facial palsy), a disease that mainly affects the joints with pain and swelling (arthritis), muscle weakness, purple or reddish-purple spots on the skin (lichen planus), severe skin rashes (erythema multiforme), low platelet count, which increases the risk of bleeding or bruising (thrombocytopenia), purple or brownish-purple spots visible through the skin (thrombocytopenic purpura).

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if you think they are not serious. You can also report them directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Ambirix

Keep this vaccine out of the sight and reach of children.

Do not use this vaccine after the expiry date stated on the packaging. The expiry date is the last day of the month stated.

Store in a refrigerator (between 2°C and 8°C). Do not freeze. Freezing destroys the vaccine.

Store in the original packaging to protect from light.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container contents and additional information

Ambirix composition

• The active ingredients are:

• Hepatitis A virus (inactivated)1,2 720 ELISA Units
• Hepatitis B surface antigen3,4 20 micrograms

1Produced in human diploid cells (MRC-5)

2Adsorbed on hydrated aluminum hydroxide 0.05 milligrams Al3+

3Produced by recombinant DNA technology in yeast cells (Saccharomyces cerevisiae)

4Adsorbed on aluminum phosphate 0.4 milligrams Al3+

• The other components of Ambirix are: sodium chloride and water for injections.

Product appearanceand container contents

Ambirix is a white and slightly milky liquid.

Ambirix is available in a pre-filled syringe with or without separate needles, in pack sizes of 1, 10, and 50.

Only some pack sizes may be marketed.

Marketing authorization holder and manufacturer

GlaxoSmithKline Biologicals s.a.

Rue de l’Institut 89

B-1330 Rixensart

Belgium

For further information on this medicinal product, please contact the local representative of the marketing authorization holder:

Date of last revision of this leaflet:

Other sources of information

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu, and on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/).

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This information is intended for healthcare professionals only:

During storage, a fine white deposit with a clear and colorless layer on top may be observed.

The vaccine should be resuspended before use. Once resuspended, the vaccine will have a white, cloudy, and uniform appearance.

Resuspension of the vaccine to obtain a white, cloudy, and uniform suspension

The vaccine should be resuspended by following the steps below.

1. Hold the syringe upright with your hand closed.
2. Shake the syringe by turning it upside down and then back upright.
3. Repeat this action vigorously for at least 15 seconds.
4. Inspect the vaccine again:
   1. If the vaccine appears as a white, cloudy, and uniform suspension, it is ready to use (it should not have a clear appearance).
   2. If the vaccine still does not appear as a white, cloudy, and uniform suspension, turn it upside down and then back upright for at least another 15 seconds and then inspect again.

Before administration, the vaccine should be visually inspected for any foreign particles and/or abnormal physical appearance. If any of these circumstances are observed, do not administer the vaccine.

Instructions for the pre-filled syringe after resuspension

Disposal of waste

Disposal of unused medicinal products and all materials that have come into contact with them should be carried out in accordance with local regulations.