Ambirix, suspension for injectionHepatitis A (inactivated) and hepatitis B (rDNA) (HAB)vaccine (adsorbed)

Ambirix is a vaccine used in infants, children and adolescents from 1 year up to and including 15 years to prevent two infectious diseases: hepatitis A and hepatitis B. The vaccine works by causing the body to produce its own protection (antibodies) against these infectious diseases.

• Hepatitis A: Hepatitis A is an infectious disease that affects the liver, caused by the hepatitis A virus. The hepatitis A virus is usually caught from food or drink that contains the virus, but is sometimes spread by other means, such as swimming in water contaminated by sewage. Symptoms of hepatitis A begin 3 to 6 weeks after coming into contact with the virus. These consist of nausea (feeling sick), fever and aches and pains. After a few days the whites of eyes and skin may become yellowish (jaundice). The severity and type of symptoms can vary. Young children may not develop jaundice. Most people recover completely but the illness is usually severe enough to keep people ill for about a month.
• Hepatitis B: Infection with the hepatitis B virus may cause the liver to become swollen (inflamed). The virus is found in body fluids such as blood, semen, vaginal secretions, or saliva (spit) of infected people. Symptoms may not be seen for 6 weeks to 6 months after infection. Sometimes people who have been infected do not look or feel ill. Others have mild flu-like symptoms, but some people can become very ill. They may be extremely tired, and have dark urine, pale faces, 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. Hepatitis B carriers are at risk of serious liver disease, such as cirrhosis (liver scarring) and liver cancer.

The vaccine does not contain live virus and cannot cause hepatitis A or B infections.

As with all vaccines, Ambirix cannot completely prevent infections with hepatitis A or B viruses, even after you have/ your child has received both doses.

Also, if you have/ your child has already been infected with hepatitis A or B virus (although not yet feeling unwell) before having both doses of Ambirix, the vaccine may not be able to prevent you/ your child becoming ill.

Ambirix can only help to protect you/ your child against infections with hepatitis A or B viruses. It cannot protect you/ your child against other infections that can affect the liver that can cause symptoms similar to those of hepatitis A or B infections.

Ambirix should not be given:

• if you have/ your child has previously had any allergic reaction to Ambirix, or any ingredient contained in this vaccine including neomycin (antibiotic). The active substances and other ingredients in Ambirix are listed at the end of the leaflet. Signs of an allergic reaction may include itchy skin rash, shortness of breath and swelling of the face or tongue.
• if you have/ your child has previously had an allergic reaction to any vaccine against hepatitis A or hepatitis B diseases.
• if you have/ your child has a severe infection with a high temperature. In these cases, the vaccination will be postponed until you/ your child has recovered. A minor infection such as a cold should not be a problem, but talk to your doctor first.

Take special care with Ambirix:

• if you think that you need/your child needs to be protected rapidly against hepatitis B infection, that is, within six months and before the second dose will be due. If you are/ your child is likely to be at risk of hepatitis B infection between the timing of the first and second injections, your doctor will probably recommend that you do/ your child does not receive Ambirix. Instead, you/ your child will probably need to have three injections of a combined hepatitis A and hepatitis B vaccine that has a lower content in each dose of the active substances (360 ELISA Units of formalin inactivated hepatitis A virus and 10 micrograms of recombinant hepatitis B surface antigen). The second of the three doses of this lower dose vaccine is usually given at one month after the first dose, and it is more likely to protect you/ your child against hepatitis B before the course is completed. Your doctor will be able to advise you.
• if you have/your child has a bleeding problem or bruise/ bruises easily. Sometimes Ambirix is given as an injection just under the skin instead of into muscle in people who have severe bleeding problems.
• if you have/your child has a poor immune system due to illness or treatment or if you are/ your child is receiving haemodialysis. Ambirix can still be given but these people may not have a good response to the vaccine and it may be necessary to do a blood test to see how well they have responded.

Taking other medicines

Tell your doctor if you are/your child is taking any medicines (including any that you may have obtained without a prescription) or if you have/your child has recently had or expect to shortly have any other vaccinations or injections of immunoglobulins (antibodies). Ask your doctor if you are not sure.

People who are taking medicines that decrease the body?s immunity to infections can still have Ambirix if this is thought to be necessary but may not have a good immune response to the vaccine and so may not be protected against one or both of hepatitis A and B viruses.

Ambirix can be given at the same time as vaccine containing measles, mumps and rubella viruses and vaccines that are intended to protect you/your child against one or more of diphtheria, tetanus, pertussis (whooping cough), poliomyelitis or Haemophilus influenzae type b. Ambirix can be given at the same time as other vaccines if this is thought to be very necessary. If another vaccine is to be given at the same time as Ambirix, separate sites and preferably different limbs should be used.

If Ambirix has to be given at the same time as or shortly before or after an injection of immunoglobulins, it is likely that you/your child will still make a good immune response to the vaccine.

Pregnancy and breast-feeding

Tell your doctor if you are or think you may be pregnant or if you are breast-feeding. Ambirix is not usually given to women who are pregnant or breast-feeding unless it is urgent for them to be vaccinated against both hepatitis A and B.

Driving and using machines

Drowsiness and dizziness have sometimes occurred after having Ambirix or a similar vaccine.

Important information about some of the ingredients of Ambirix

Please tell your doctor if you have/your child has had an allergic reaction to neomycin (antibiotic).

You/ your child will receive a total of two injections. These will be given within 12 months. Each injection is given on a separate visit.
The first dose will be given on a date agreed with your doctor.
The second dose will be given between six and twelve months after the first dose.

It is not known exactly how long protection against infection with hepatits A and B viruses will last, although protection against hepatitis A virus probably lasts about 10 years.
Patients with poor immune systems may need more frequent additional doses. Your doctor will advise on the possible need for extra doses.

If you miss/ your child misses the visit scheduled for the second injection, talk to your doctor and arrange another visit as soon as possible.

Make sure you finish/ your child finishes the complete vaccination course of two injections. If not, you/ your child may not be fully protected against the diseases.

The doctor or nurse will give Ambirix as an injection into muscle, usually into the upper arm. In very small children, the injection may be given into the thigh muscle.
Your doctor or nurse will take care that Ambirix is not given into a vein.
The vaccine would not usually be given deep into the skin because protection may be less. This is usually done when there is a risk of severe bleeding after an injection into muscle.

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

The frequency of possible side effects listed below is defined using the following convention: Very common (these may occur with more than 1 in 10 doses of the vaccine)

Common (these may occur with up to 1 in 10 doses of the vaccine)
Uncommon (these may occur with up to 1 in 100 doses of the vaccine)
Rare (these may occur with up to 1 in 1,000 doses of the vaccine)

Side effects that occurred during clinical trials with Ambirix were as follows:

Very common Pain and redness where the injection was given Feeling tired Irritability Headache Loss of appetite

Common Swelling where the injection was given Fever Drowsiness Stomach and digestive complaints

Additional side effects that have been reported during clinical trials with very similar combined hepatitis A and hepatitis B vaccines, include:

Common Diarrheoa, nausea Generally feeling unwell Reaction where the injection was given

Uncommon Upper respiratory tract infection Feeling dizzy Vomiting Stomach pain Aching muscles myalgia

Rare Swollen glands in the neck, armpit or groin lymphadenopathy Pins and needles paraesthesia Low blood pressure Itching pruritus, rash Joint pain arthralgia Flu-like symptoms, such as high temperature, sore throat, runny nose, cough and chills

Side effects that occurred during routine use of Ambirix were as follows:

• Allergic reactions (anaphylaxis, anaphylactoid reactions including mimicking serum sickness): If you have an allergic reaction, see your doctor straight away. The signs may include:
• rashes that may be itchy or blistering where the injection was given. They may also cover other parts of your body.
• swelling of the eyes and face
• difficulty in breathing or swallowing
• a sudden drop in blood pressure and loss of consciousness

The signs usually start very soon after the injection has been given to you.

• Fainting
• Localised loss of skin sensitivity to pain or touch (hypoaesthesia)

Additional side effects that occurred during routine use of very similar combined or individual hepatitis A and hepatitis B vaccines were as follows:

• Severe headache with stiff neck and sensitivity to light (meningitis)
• Reduction in blood platelets, which increases risk of bleeding or bruising (thrombocytopenia), purple or red brown spots visible through the skin (thrombocytopenic purpura)
• Swelling of the face, mouth and throat (angioneurotic oedema)
• Multiple sclerosis, swelling or infection of the brain (encephalitis), a degenerative disease of the brain (encephalopathy), a temporary inflammation of the nerves, causing pain, weakness and paralysis in the extremities and often progressing to the chest and face (Guillain-Barré syndrome), swelling of the spinal cord (myelitis), fits or seizures, paralysis, drooping eyelid and sagging muscles on one side of the face (facial palsy), inflammation of nerves (neuritis), disease of the nerves of the eyes (optic neuritis), numbness or weakness of the arms and legs (neuropathy)
• Inflammation of some blood vessels (vasculitis)
• Abnormal laboratory liver test results
• Purple or reddish-purple bumps on the skin (lichen planus), serious skin rashes (erythema multiforme), hives (urticaria)
• Disease mainly affecting the joints with pain and swelling (arthritis), muscular weakness

Do not be alarmed by this list of possible side effects. It is possible that you have/your child has no side effects from vaccination.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Keep out of the reach and sight of children.

Do not use Ambirix after the expiry date which is stated on the carton. The expiry date refers to the last day of that month.

Store in a refrigerator (2°C - 8°C).
Do not freeze. Freezing destroys the vaccine.
Store in the original package in order 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. These measures will help to protect the environment.

What Ambirix contains

• The active substances are:

Hepatitis A virus inactivated1,2Hepatitis B surface antigen 3,4720 ELISA Units 20 micrograms

31Produced on human diploid MRC-5 cells 2Adsorbed on aluminium hydroxide, hydrated 0.05 milligrams Al3Produced in yeast cells Saccharomyces cerevisiae by recombinant DNA technology 4Adsorbed on aluminium phosphate 0.4 milligrams Al3

• The other ingredients in Ambirix are: sodium chloride and water for injections.

What Ambirix looks like and contents of the pack

Suspension for injection. (1 ml)

Ambirix is available in packs of 1 and 10 with or without needles and in a pack size of 50 without needles.

Ambirix is a white, slightly milky liquid presented in a prefilled syringe.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

GlaxoSmithKline Biologicals s.a.Rue de l?Institut 89
B-1330 Rixensart
Belgium

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

BelgiëBelgiqueBelgien GlaxoSmithKline s.a.n.v. TélTel 32 2 656 21 11 LuxembourgLuxemburg GlaxoSmithKline s.a.n.v. TélTel 32 2 656 21 11

Magyarország GlaxoSmithKline Kft. Tel. 36-1-2255300 . .10 1408 . 359 2 953 10 34

Malta GlaxoSmithKline Malta Ltd Tel 356 21 238131 eská republika GlaxoSmithKline s.r.o. Tel 420 2 22 00 11 11 czmailgsk.com

Danmark GlaxoSmithKline Pharma AS Tlf 45 36 35 91 00 dk-infogsk.com Nederland GlaxoSmithKline BV Tel 31 030 69 38 100 nlinfogsk.com

Deutschland GlaxoSmithKline GmbH Co. KG Tel 49 089 360448701 produkt.infogsk.com Norge GlaxoSmithKline AS Tlf 47 22 70 20 00 firmapostgsk.no

Eesti Österreich

GlaxoSmithKline Eesti OÜ Tel 372 667 6900 estoniagsk.com GlaxoSmithKline Pharma GmbH. Tel 43 1 970 75-0 at.infogsk.com

GlaxoSmithKline A.E.B.E. T 30 210 68 82 100 Polska GSK Commercial Sp. z o.o. Tel. 48 22 576 9000

España GlaxoSmithKline, S.A. Tel 34 902 202 700 es-cigsk.com Portugal Smith Kline French Portuguesa, Produtos Farmacêuticos, Lda. Tel 351 21 412 95 00 FI.PTgsk.com

România GlaxoSmithKline GSK SRL Tel 40 021 3028 208 France Laboratoire GlaxoSmithKline Tél 33 0 1 39 17 84 44 diamgsk.com

Ireland GlaxoSmithKline Ireland Ltd Tel 353 01 4955000 Slovenija GlaxoSmithKline d.o.o. Tel 386 0 1 280 25 00 medical.x.sigsk.com

Ísland GlaxoSmithKline ehf. Sími 354 530 3700 Slovenská republika GlaxoSmithKline Slovakia s.r.o. Tel 421 02 48 26 11 11 recepcia.skgsk.com

Italia GlaxoSmithKline S.p.A. Tel 39 04 59 21 81 11 SuomiFinland GlaxoSmithKline Oy PuhTel 358 10 30 30 30 Finland.tuoteinfogsk.com

GlaxoSmithKline Cyprus Ltd 357 22 39 70 00 Sverige GlaxoSmithKline AB Tel 46 08 638 93 00 info.produktgsk.com

Latvija GlaxoSmithKline Latvia SIA Tel 371 67312687 lv-epastsgsk.com United Kingdom GlaxoSmithKline UK Tel 44 0808 100 9997 customercontactukgsk.com

Lietuva
GlaxoSmithKline Lietuva UAB
Tel. +370 5 264 90 00
info.lt@gsk.com

This leaflet was last approved in

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The following information is intended for medical or healthcare professionals only:

Upon storage, a fine white deposit with a clear colourless supernatant can be observed.

Before administration, the vaccine should be well shaken to obtain a slightly opaque, white suspension.

The vaccine should be visually inspected before or after resuspension for any foreign particulate matter and/or change in physical appearance The vaccine must not be used if any change in the appearance of the vaccine has taken place.

Any unused vaccine or waste material should be disposed of in accordance with local requirements.