Ambirix

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Ambirix, suspension for injection in pre-filled syringe 
Hepatitis A (inactivated) and hepatitis B (rDNA) (HAB) vaccine (adsorbed). 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
1 dose (1 ml) contains: 
 
Hepatitis A virus (inactivated)1,2 720 ELISA Units 
Hepatitis B surface antigen3,4 20 micrograms 
 
1Produced on human diploid (MRC-5) cells 
2Adsorbed on aluminium hydroxide, hydrated 0.05 milligrams Al3+ 
3Produced in yeast cells (Saccharomyces cerevisiae) by recombinant DNA technology 
4Adsorbed on aluminium phosphate 0.4 milligrams Al3+ 
  
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension for injection. 
Ambirix is a turbid white suspension. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Ambirix is indicated in non-immune children and adolescents from 1 year up to and including 15 
years of age for protection against hepatitis A and hepatitis B infection. 
 
Protection against hepatitis B infections may not be obtained until after the second dose (see section 
5.1).  
Therefore: 
- Ambirix should be used only when there is a relatively low risk of hepatitis B infection during 

the vaccination course.  
- It is recommended that Ambirix should be administered in settings where completion of the 

two-dose vaccination course can be assured. 
 
4.2 Posology and method of administration 
 
Posology 
 
- Dosage 
 
A dose of 1.0 ml is recommended for subjects from 1 year up to and including 15 years of age. 
 
- Primary vaccination schedule 
 
The standard primary course of vaccination consists of two doses, the first administered at the elected 
date and the second between 6 and 12 months after the first dose.  
 



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The recommended schedule should be adhered to. Once initiated, the primary course of vaccination 
should be completed with the same vaccine. 
 
- Booster dose 
 
In situations where a booster dose of hepatitis A and/or hepatitis B is desired, a monovalent or 
combined vaccine can be given. The safety and immunogenicity of Ambirix administered as a booster 
dose following a two dose primary course have not been evaluated. 
 
Long-term antibody persistence data following vaccination with Ambirix are available up to 15 years 
after vaccination (see section 5.1). 
 
The anti-hepatitis B surface antigen (anti-HBs) and anti-hepatitis A virus (anti-HAV) antibody titres 
observed following a primary vaccination course with Ambirix are in the range of what is seen 
following vaccination with the monovalent hepatitis A and B vaccines. General guidelines for booster 
vaccination can therefore be drawn from experience with the monovalent vaccines, as follows.   

 
Hepatitis B 

 
The need for a booster dose of hepatitis B vaccine in healthy individuals who have received a full 
primary vaccination course has not been established. However some official vaccination programmes 
currently include a recommendation for a booster dose of hepatitis B vaccine and these should be 
respected. 
 
For some categories of subjects at risk of exposure to HBV (e.g. haemodialysis or 
immunocompromised patients) a precautionary attitude should be considered to ensure that a 
protective antibody level ≥ 10 mIU/ml is maintained. 

 
Hepatitis A 

 
It is not yet fully established whether immunocompetent individuals who have responded to hepatitis 
A vaccination will require booster doses as protection in the absence of detectable antibodies may be 
ensured by immunological memory. Guidelines for boosting are based on the assumption that 
antibodies are required for protection.  
 
Paediatric population 
 
The safety and efficacy of Ambirix in children aged less than 1 year have not been established. 
No data are available. 
 
Method of administration 
 
Ambirix is for intramuscular injection, usually into the deltoid muscle. However the anterolateral 
thigh may be used in very young subjects if preferred. 
 
Exceptionally, the vaccine may be administered subcutaneously in patients with thrombocytopenia or 
bleeding disorders. However, this route of administration may result in suboptimal immune response 
to the vaccine (see section 4.4). 
 
4.3 Contraindications 
 
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1, or neomycin. 
 
Hypersensitivity after previous administration of hepatitis A and/or hepatitis B vaccines. 
 



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As with other vaccines, the administration of Ambirix should be postponed in subjects suffering from 
acute severe febrile illness. 
 
4.4 Special warnings and precautions for use 
 
As with all injectable vaccines, appropriate medical treatment and supervision should always be 
readily available in case of a rare anaphylactic reactions following the administration of the vaccine. 
 
Syncope (fainting) can occur following, or even before, any vaccination especially in adolescents as a 
psychogenic response to the needle injection. This can be accompanied by several neurological signs 
such as transient visual disturbance, paraesthesia and tonic-clonic limb movements during recovery. It 
is important that procedures are in place to avoid injury from faints. 
 
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 Ambirix will prevent hepatitis A and hepatitis B in 
such cases. 
 
The vaccine will not prevent infection caused by other agents such as hepatitis C and hepatitis E and 
other pathogens known to infect the liver. 
 
Ambirix is not recommended for postexposure prophylaxis (e.g. needle stick injury). 
 
If rapid protection against hepatitis B is required, the standard three-dose regimen of the combined 
vaccine containing 360 ELISA Units of formalin inactivated hepatitis A virus and 10 micrograms of 
recombinant hepatitis B surface antigen is recommended. This is because, a higher proportion of 
subjects are protected in the interval between the second and third dose of the three-dose combined 
vaccine, than after a single dose of Ambirix. This difference is no longer present after the second dose 
of Ambirix (see section 5.1 for seroprotection rates). 
 
It is recommended that the two-dose regimen of Ambirix be completed prior to start of sexual activity. 
 
The vaccine has not been tested in patients with an impaired immune system. In haemodialysis 
patients and persons with an impaired immune system, adequate anti-HAV and anti-HBs antibody 
titers may not be obtained after the primary immunisation course. 
 
Since intradermal injection or intramuscular administration into the gluteal muscle could lead to a 
suboptimal response to the vaccine, these routes should be avoided. However, exceptionally Ambirix 
can be administered subcutaneously to subjects with thrombocytopenia or bleeding disorders since 
bleeding may occur following an intramuscular administration to these subjects. 
 
Ambirix should under no circumstances be administered intravascularly. 
 
Traceability 
In order to improve the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No data on concomitant administration of Ambirix with specific hepatitis A immunoglobulin or 
hepatitis B immunoglobulin have been generated. However, when the monovalent hepatitis A and 
hepatitis B vaccines were administered concomitantly with specific immunoglobulins there was no 
effect on seroconversion rates. Concomitant immunoglobulin administration may result in lower 
antibody titres. 
 
When Ambirix was administered concomitantly with, but as a separate injection to a combined 
diphtheria, tetanus, acellular pertussis, inactivated poliomyelitis and Haemophilus influenzae type b 



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vaccine (DTPa-IPV+Hib) or with a combined Measles-Mumps-Rubella vaccine in the second year of 
life, immune responses to all antigens were satisfactory (see section 5.1). 
 
Concomitant administration of Ambirix and other vaccines than those listed above has not been 
studied. It is advised that Ambirix should not be administered at the same time as other vaccines 
unless absolutely necessary.  
Concomitant vaccines should always be administered at separate injection sites and preferably into 
different limbs. 
 
It may be expected that in patients receiving immunosuppressive treatment or patients with 
immunodeficiency, an adequate response may not be achieved.  
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
Ambirix can be used during pregnancy only when clearly needed, and the possible advantages 
outweigh the potential risks for the foetus. 
 
Breast-feeding 
 
Ambirix should only be used during breast-feeding when the possible advantages outweigh the 
potential risks. 
 
Fertility 
 
No fertility data are available. 
 
4.7 Effects on ability to drive and use machines 
 
Ambirix has no or negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of safety profile 
 
Clinical trials involved the administration of 2029 doses of Ambirix to 1027 subjects from 1 year up 
to and including 15 years of age.  
In 2 comparative trials in subjects aged 1-15 years, the incidences of local and general solicited 
symptoms after a two-dose regimen of Ambirix was overall similar to that seen with the three-dose 
combined vaccine containing 360 ELISA Units of HAV and 10 µg of HBsAg. 

 
The most commonly reported adverse reactions following Ambirix administration are pain and fatigue 
occurring in an approximated per dose frequency of 50% and 30% respectively. 
  
List of adverse reactions 
 
Local and general adverse reactions reported following primary vaccination with Ambirix were 
categorised by frequency.   
 
Adverse reactions reported are listed according to the following frequency: 
Very common: ≥ 1/10 
Common: ≥ 1/100 to < 1/10 
Uncommon: ≥ 1/1,000 to < 1/100 
Rare:  ≥ 1/10,000 to < 1/1,000 



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Very rare: < 1/10,000 
 
The following adverse reactions were reported during clinical trials with Ambirix. 
 
• Clinical trial data 
 
Metabolism and nutrition disorders 
Very common: appetite lost 
 
Psychiatric disorders 
Very common: irritability 
 
Nervous system disorders 
Very common: headache 
Common: drowsiness 
 
Gastrointestinal disorders 
Common: gastrointestinal symptoms 
 
General disorders and administration site conditions 
Very common: fatigue, pain and redness at the injection site 
Common: fever, swelling at the injection site 
 
In addition, the following adverse reactions were reported during clinical trials with 
GlaxoSmithKline’s other combined hepatitis A and hepatitis B vaccines (given as a 3 or 4 dose 
schedule). 
 
Infections and infestations 
Uncommon: upper respiratory tract infection 
 
Blood and lymphatic system disorders 
Rare: lymphadenopathy 
 
Nervous system disorders 
Uncommon: dizziness 
Rare: paraesthesia 
 
Vascular disorders 
Rare: hypotension 
 
Gastrointestinal disorders 
Common: diarrhoea, nausea 
Uncommon: vomiting, abdominal pain* 
 
Skin and subcutaneous tissue disorders 
Rare: pruritus, rash 
Very rare: urticaria 
 
Musculoskeletal and connective tissue disorders 
Uncommon: myalgia 
Rare: arthralgia 
 
General disorders and administration site conditions 

 Common: malaise, injection site reaction 
Rare: chills, influenza like illness 
 



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* refers to adverse reactions observed in clinical trials performed with the paediatric formulation 
 
• Post-marketing data 
 
Because these events were reported spontaneously, it is not possible to reliably estimate their 
frequency. 
 
The following adverse reactions were reported during post-marketing surveillance following 
vaccination with Ambirix. 
 
Immune system disorders 
Allergic reactions including anaphylactic and anaphylactoid reactions 
 
Nervous system disorders 
Syncope or vasovagal responses to injection, localised hypoaesthesia 
 
Following widespread use of either GlaxoSmithKline’s combined hepatitis A and hepatitis B vaccines 
or the monovalent hepatitis A and/or hepatitis B vaccines, the following adverse reactions have 
additionally been reported. 
 
Infections and infestations 
Meningitis 
 
Blood and lymphatic system disorders 
Thrombocytopenic purpura, thrombocytopenia 
 
Immune system disorders 
Allergic reactions including mimicking serum sickness, angioneurotic oedema 
 
Nervous system disorders 
Multiple sclerosis, encephalitis, encephalopathy, polyneuritis such as Guillain-Barré syndrome (with 
ascending paralysis), myelitis, convulsions, paralysis, facial palsy, neuritis, optic neuritis, neuropathy 
 
Vascular disorders 
Vasculitis 
 
Hepatobiliary disorders 
Abnormal liver function tests 
 
Skin and subcutaneous tissue disorders 
Erythema multiforme, lichen planus 
 
Musculoskeletal and connective tissue disorders 
Arthritis, muscular weakness 
 
General disorders and administration site conditions 
Immediate injection site pain, stinging and burning sensation 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation 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 via the national reporting system 
listed in Appendix V. 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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4.9 Overdose  
 
Cases of overdose with GlaxoSmithKline’s combined hepatitis A and hepatitis B vaccine have been 
reported during post-marketing surveillance. Adverse reactions reported following overdosage were 
similar to those reported with normal vaccine administration. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmaco therapeutic group: Vaccines, Hepatitis vaccines, ATC code J07BC20. 
 
Mechanism of action 
Ambirix confers immunity against HAV and HBV infection by inducing specific anti-HAV and anti-
HBs antibodies. 
 
Clinical studies 

Immune responses post-primary vaccination 
In clinical studies involving subjects from 1 year up to and including 15 years old, seropositivity rates 
for anti-HAV antibodies were 99.1% one month after the first dose and 100% after the second dose 
given at month 6 (i.e month 7). Seropositivity rates for anti-HBs antibodies were 74.2% one month 
after the first dose and 100% after the second dose given at month 6 (i.e. month 7). The anti-HBs 
seroprotection rates (titers ≥ 10 mlU/ml) at these time points were 37.4% and 98.2% respectively. 

In a comparative clinical trial conducted among subjects aged from 12 years up to and including 15 
years of age, 142 received two doses of Ambirix and 147 received the standard three-dose (0, 1, 6 
months) of the combined HAB vaccine. The latter contained 360 ELISA Units of formalin inactivated 
hepatitis A virus and 10 micrograms of recombinant hepatitis B surface antigen. For the 289 subjects 
evaluable for immunogenicity, seroprotection rates (SP in the table below) against hepatitis B were 
significantly higher at months 2 and 6 with the three-dose vaccine than with Ambirix. The immune 
response elicited by Ambirix at month 7 (i.e. after completion of the vaccination course) was non-
inferior to that to the three-dose vaccine. 

Vaccine group Anti-HBs 
Month 2 
SP (%) 

Anti-HBs 
Month 6 
SP (%) 

Anti-HBs 
Month 7 
SP (%) 

Ambirix  38 68.3 97.9 
Combined HAB 
vaccine (360/10)* 

85.6 98.0 100 

* containing 360 ELISA Units of formalin inactivated hepatitis A virus and 10 micrograms of 
recombinant hepatitis B surface antigen 

 
Immune responses obtained one month after the full vaccination course (i.e at month 7) in a 
comparative clinical trial in children aged 1-11 years are presented in the following table. Also shown 
are the results reported in the comparative study performed in 12-15 year-olds. In both studies, 
subjects received either a two-dose schedule of Ambirix or a three-dose regimen of the combined 
HAB vaccine (360/10) containing 360 ELISA Units of formalin inactivated hepatitis A virus and 10 
micrograms of recombinant hepatitis B surface antigen. 

Age group Vaccine group Anti-HAV Anti-HBs 
N S+ (%) N SP (%) 

1-5 yrs old 
 

Ambirix 98 100 
 

98 98 
 

Combined HAB 
vaccine (360/10)* 

92 100 
 

92 100 
 



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6-11 yrs old 
 

Ambirix 103 100 
 

103 99 
 

Combined HAB 
vaccine (360/10)* 

96 100 
 

96 100 
 

12-15 yrs old 
 

Ambirix 142 100 
 

142 97.9 
 

Combined HAB 
vaccine (360/10)* 

147 100 
 

147 100 
 

* containing 360 ELISA Units of formalin inactivated hepatitis A virus and 10 micrograms of 
recombinant hepatitis B surface antigen 

 
Immune response post-primary vaccination using 0-12 month schedule  
In a clinical study, 102 subjects aged from 12 years up to and including 15 years received the second 
dose of Ambirix at month 12. Seropositivity rates for anti-HAV were 99.0% and seropositivity rates 
for anti-HBs were 99.0% at month 13 with seroprotection rates of 97.0%. 

Persistence of immune responses 
The persistence of immune responses was evaluated in children up to 15 years after primary 
vaccination with Ambirix and is presented in the Table below.  

Year after the 
first vaccine dose 

Age at primary 
vaccination 

Schedule (Month) Anti-HAV Anti-HBs 
S+ (%) SP (%) 

6 12-15 yrs old 
 

0, 6 100 
 

84.8 
 

0, 12 100 
 

92.9 
 

10 1-11 yrs old 
 

0, 6 100 
 

77.3 
 

15 12-15 yrs old 
 

0, 6 100 
 

81.1 
 

 

After 15 years in subjects aged 12-15 years at primary vaccination the anti-HAV and anti-HBs 
antibody concentrations were comparable between groups that had received Ambirix or a 3-dose 
regimen of the combined HAB vaccine (360/10). In the Ambirix group, a challenge dose of a HBV 
vaccine was given to a limited number of subjects (n=8) whose anti-HBs antibody concentrations 
decreased to < 10 mIU/ml and all mounted an anamnestic response. 

 
Concomitant vaccinations 
When the first dose of Ambirix was administered concomitantly with a booster dose of a combined 
diphtheria, tetanus, acellular pertussis, inactivated poliomyelitis and Haemophilus influenzae type b 
vaccine (DTPa-IPV+Hib) or with the first dose of a combined Measles-Mumps-Rubella vaccine in the 
second year of life, immune responses to all antigens were satisfactory. 

5.2 Pharmacokinetic properties 
 
Not applicable. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on general safety studies. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 



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6.1 List of excipients 
 
Sodium chloride 
Water for injections 
 
For adjuvants, see section 2. 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C - 8°C). 
 
Do not freeze. 
 
Store in the original package, in order to protect from light. 
 
6.5 Nature and contents of container 
 
1 ml of suspension in a pre-filled syringe (type I glass) with a plunger stopper (rubber butyl). 
 
Pack sizes of 1 and 10 pre-filled syringes with or without needles and pack size of 50 pre-filled 
syringes without needles. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Upon storage, a fine white deposit with a clear colourless layer above may be observed.  
 
The vaccine should be re-suspended before use. When re-suspended, the vaccine will have a uniform 
hazy white appearance. 
 
Re-suspension of the vaccine to obtain a uniform hazy white suspension 
 
The vaccine should be re-suspended 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. 
 



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Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
GlaxoSmithKline Biologicals s.a. 
rue de l'Institut 89 
B-1330 Rixensart, Belgium 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/02/224/001 
EU/1/02/224/002 
EU/1/02/224/003 
EU/1/02/224/004 
EU/1/02/224/005 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 30 August 2002 
Date of latest renewal: 20 July 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this product is available on the website of the European Medicines Agency  
http://www.ema.europa.eu 



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ANNEX II 
 
A. MANUFACTURER OF THE BIOLOGICAL ACTIVE 

SUBSTANCES AND MANUFACTURER RESPONSIBLE FOR 
BATCH RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION 
 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE 
SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 



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A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCES AND 

MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer of the biological active substances 
 
GlaxoSmithKline Biologicals s.a. 
Rue de l’Institut 89 
1330 Rixensart 
Belgium  
 
Name and address of the manufacturer responsible for batch release 
 
GlaxoSmithKline Biologicals s.a. 
Rue de l’Institut 89 
1330 Rixensart 
Belgium 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to medical prescription. 
 
• Official batch release  
 
In accordance with Article 114 of Directive 2001/83/EC as amended, the official batch release will be 
undertaken by a state laboratory or a laboratory designated for that purpose. 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic safety update reports (PSURs) 
 
The requirements for submission of PSURs for this medicinal product 
are set out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of 
Directive 2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk management plan (RMP) 
 
Not applicable.



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ANNEX III 
 

LABELLING AND PACKAGE LEAFLET  
 



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A. LABELLING 
 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
1 PRE-FILLED SYRINGE WITHOUT NEEDLE 
1 PRE-FILLED SYRINGE WITH 1 NEEDLE 
10 PRE-FILLED SYRINGES WITHOUT NEEDLES 
10 PRE-FILLED SYRINGES WITH 10 NEEDLES 
50 PRE-FILLED SYRINGES WITHOUT NEEDLES 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ambirix – Suspension for injection in pre-filled syringe 
Hepatitis A (inactivated) and hepatitis B (rDNA) (HAB) vaccine (adsorbed) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 dose (1 ml): 
Hepatitis A virus (inactivated)1,2 720 ELISA Units 
Hepatitis B surface antigen3,4 20 micrograms 
 
1Produced on human diploid (MRC-5) cells 
2Adsorbed on aluminium hydroxide, hydrated 0.05 milligrams Al3+ 
3Produced in yeast cells (Saccharomyces cerevisiae) by recombinant DNA technology 
4Adsorbed on aluminium phosphate 0.4 milligrams Al3+ 
 
 
3. LIST OF EXCIPIENTS 
 
Sodium chloride 
Water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection in pre-filled syringe 
 
1 pre-filled syringe 
1 dose (1 ml) 
 
1 pre-filled syringe + 1 needle 
1 dose (1 ml) 
 
10 pre-filled syringes 
10 x 1 dose (1 ml) 
 
10 pre-filled syringes + 10 needles 
10 x 1 dose (1 ml) 
 
50 pre-filled syringes 
50 x 1 dose (1 ml) 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 



17 

 
Read the package leaflet before use 
Intramuscular use 
Shake well before use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP: MM/YYYY 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator  
Do not freeze 
Store in the original package in order to protect from light 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
GlaxoSmithKline Biologicals s.a. 
Rue de l’Institut 89 
B-1330 Rixensart, Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/02/224/001 - pack of 1 without needle 
EU/1/02/224/002 - pack of 1 with 1 needle 
EU/1/02/224/003 - pack of 10 without needle 
EU/1/02/224/004 - pack of 10 with 10 needles 
EU/1/02/224/005 - pack of 50 without needle 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 



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14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
PRE-FILLED SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Ambirix, suspension for injection  
HAB vaccine 
IM 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP:  
 
 
4. BATCH NUMBER 
 
Lot: 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 dose (1 ml) 
 
 
6. OTHER 
 
 



20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 



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Package Leaflet: Information for the user 

 
Ambirix, suspension for injection in pre-filled syringe 

Hepatitis A (inactivated) and hepatitis B (rDNA) (HAB) vaccine (adsorbed) 
 
 
Read all of this leaflet carefully before you/your child starts receiving this vaccine because it 
contains important information for you. 
• Keep this leaflet. You may need to read it again. 
• If you have any further questions, ask your doctor, nurse or pharmacist. 
• This vaccine has been prescribed for you/your child only. Do not pass it on to others. 
• If you/your child gets any side effects, talk to your doctor, nurse or pharmacist. This includes 

any possible side effects not listed in this leaflet. See section 4. 
 
This leaflet has been written assuming the person receiving the vaccine is reading it, but it can be 
given to adolescents and children so you may be reading it for your child. 
 
What is in this leaflet 
1. What Ambirix is and what it is used for 
2. What you need to know before you receive Ambirix 
3. How Ambirix is given 
4. Possible side effects 
5. How to store Ambirix 
6. Contents of the pack and other information 
 
 
1.  What Ambirix is and what it is used for 
 

Ambirix is a vaccine used in infants, children and young people from 1 year up to and including 15 
years. It is used to prevent two diseases: hepatitis A and hepatitis B.  
 
• Hepatitis A: Infection with the hepatitis A virus may cause the liver to become swollen 

(inflamed).  The virus is usually caught from food or drink that contains the virus. However, it is 
sometimes caught in other ways, such as by swimming in water that has sewage in it or from 
another infected person. The virus is found in body fluids such as faeces, serum or saliva. 

 Symptoms begin 3 to 6 weeks after infection. Some people can feel sick, have a fever and aches 
and pains. After a few days they may be very tired, and have dark urine, pale faeces, yellowish 
skin or eyes (jaundice). The severity and type of symptoms can vary. Young children may not get 
all symptoms. Most children recover completely but the illness is usually severe enough to make 
children ill for about a month. 

 
• Hepatitis B: Infection with the hepatitis B virus may cause the liver to become swollen 

(inflamed). The virus is usually caught from another infected person. It is found in body fluids 
such as blood, semen, vaginal secretions, or saliva (spit).  
Symptoms may not be seen for 6 weeks to 6 months after infection. Not always people who have 
been infected look or feel ill. Some people can feel sick, have a fever and aches and pains. 
However, others can become very ill. They may be very tired, and have dark urine, pale faeces, 
yellowish skin or eyes (jaundice). Some people may need to go into hospital. 

 
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 “carriers” and can still infect 
other people throughout their lives. Carriers are also at risk of serious liver problems, such as 
scarring (cirrhosis) or liver cancer. 
 



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How Ambirix works 
 
• Ambirix helps the body to produce its own protection (antibodies) against these diseases. The  

vaccine does not contain live virus (see section 6 for the content of the vaccine) and therefore 
cannot cause hepatitis A or B infections. 

 
• As with all vaccines, some people respond less well to a vaccine than others. 
 
• Ambirix may not protect you from being ill if you have already caught the hepatitis A or B virus. 
 
• Ambirix can only help to protect you against infections with hepatitis A or B viruses. It cannot 

protect against other infections that can affect the liver – even though these infections might have 
signs similar to those caused by the hepatitis A or B virus. 

  
 
2.  What you need to know before you receive Ambirix 
 
Ambirix should not be given if: 
 
• you are allergic to Ambirix, or any of the other ingredients of this vaccine (listed in section 6). 

Signs of an allergic reaction may include itchy skin rash, shortness of breath and swelling of 
your face or tongue 

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

• you have a severe infection with a high temperature. The vaccine can be given after you have 
recovered. A minor infection such as a cold should not be a problem, but talk to your doctor 
first. 

 
Ambirix should not be given if any of the above apply. If you are not sure, talk to your doctor, nurse 
or pharmacist before having Ambirix. 
 
Warnings and precautions 
 
Talk to your doctor, nurse or pharmacist before having 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 a bleeding problem or bruise easily - the injection may be given just under the skin 

instead of into a muscle to reduce the amount of bleeding or bruising 
• you have immune system problems (such as due to an illness, treatment or dialysis) - the 

vaccine may not work fully. This means you may not be protected against one or both of the 
hepatitis A and B viruses. Your doctor will run blood tests to see whether more injections are 
needed to help you be better protected 

• you have fainted before or during a previous injection – in case this happens again. Fainting can 
occur (mostly in adolescents) following, or even before, any needle injection.  

 
If any of the above apply (or you are not sure), talk to your doctor, nurse or pharmacist before having 
Ambirix. 
 
Other medicines and Ambirix 
 
Tell your doctor if you are taking, have recently taken or might take any other medicines or vaccines. 
This includes medicines obtained without a prescription and herbal medicines. Ask your doctor, nurse 
or pharmasist if you are not sure. 
 



23 

If you are taking medicines that affect your body’s immune response, you can still have Ambirix if 
this is thought to be necessary. However, the vaccine may not work fully. This means that you may 
not be protected against one or both of the hepatitis A and B viruses. Your doctor will run blood tests 
to see whether more injections are needed to help you be better protected. 
 
Ambirix may need to be given at the same time as other vaccines for measles, mumps, rubella, 
diphtheria, tetanus, whooping cough (pertussis), poliomyelitis, Haemophilus influenzae type b or 
some types of treatments for hepatitis infections called “immunoglobulins”. Your doctor will make 
sure that the vaccines are injected into different parts of your body. 
 
Pregnancy, breast-feeding and fertility 
 
If you are pregnant or breast-feeding, think that you might be pregnant or are planning to have a baby, 
ask your doctor, nurse or pharmacist for advice before having this vaccine. Ambirix is not usually 
given to women who are pregnant or breast-feeding.  
 
Driving and using machines 
 
You may feel sleepy or dizzy after having Ambirix. If this happens, do not drive, cycle or use any 
tools or machines. 
 
Ambirix contains neomycin and sodium 
 
This vaccine contains neomycin (an antibiotic). Ambirix should not be given if you are allergic to 
neomycin.  
 
This medicinal product contains less than 1 mmol sodium (9 mg) per dose, i.e. essentially ‘sodium-
free’. 
 
 
3. How Ambirix is given 
 
How the injection is given 
 
• The doctor or nurse will give Ambirix as an injection into a muscle. This is usually into the 

upper arm. 
• They will take care that Ambirix is not given into a vein.  
• In very small children, the injection may be given into the thigh muscle. 
 
How much is given  
 
• You will normally have a total of two injections. Each is given on a separate visit. 
• The injections will be given within 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 on the possible need for extra doses, and future booster dosing. 
 
Missing a dose 
 
• If you miss the second injection, talk to your doctor and arrange another visit as soon as 

possible. 
 
• Make sure you finish the complete course of two injections. If not, you may not be protected 

against the diseases. 



24 

 
 
4.  Possible side effects 
 
Like all medicines, this vaccine can cause side effects, although not everybody gets them. 
 
Serious side effects 
Tell your doctor straight away if you notice any of the following serious side effects – you may 
need urgent medical treatment: 
 
• allergic and anaphylactic reactions - the signs can include a rash that may be itchy or blistering, 

swelling of the eyes and face, difficulty in breathing or swallowing, a sudden drop in blood 
pressure and loss of consciousness. 

Tell your doctor straight away if you notice any of the serious side effects listed above. 
 
Side effects that occurred during clinical trials with Ambirix were as follows: 
 
Very common (These may occur with more than 1 in 10 doses of the vaccine) : 
• headache 
• loss of appetite 
• feeling tired or irritable 
• pain and redness where the injection was given 
 
Common (These may occur with up to 1 in 10 doses of the vaccine) : 
• fever 
• feeling drowsy 
• stomach and digestive problems 
• swelling where the injection was given 
 
Additional side effects that have been reported  during clinical trials with very similar 
combined hepatitis A and hepatitis B vaccines, include: 
 
Common (These may occur with up to 1 in 10 doses of the vaccine) : 
• generally feeling unwell 
• diarrhoea, feeling sick (nausea) 
• reaction where the injection was given 
 
Uncommon (These may occur with up to 1 in 100 doses of the vaccine) : 
• feeling dizzy 
• stomach pain 
• being sick (vomiting) 
• upper airway infections 
• aching muscles (myalgia) 
 
Rare (These may occur with up to 1 in 1,000 doses of the vaccine) : 
• low blood pressure 
• joint pain (arthralgia) 
• itching (pruritus), rash 
• pins and needles (paraesthesia) 
• swollen glands in the neck, armpit or groin (lymphadenopathy) 
• flu-like symptoms, such as high temperature, sore throat, runny nose, cough and chills 

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



25 

 
Please contact your doctor if you have similar side effects. 

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

 
• fainting 
• 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: 
 
• multiple sclerosis 
• swelling of the spinal cord (myelitis) 
• abnormal test results relating to the liver 
• swelling or infection of the brain (encephalitis) 
• inflammation of some blood vessels (vasculitis) 
• a degenerative disease of the brain (encephalopathy) 
• swelling of the face, mouth and throat (angioneurotic oedema) 
• severe headache with stiff neck and sensitivity to light (meningitis) 
• a temporary inflammation of the nerves, causing pain, weakness and paralysis in the arms and legs 

and often progressing to the chest and face (Guillain-Barré syndrome)   
• fits or seizures  
• inflammation of the nerves (neuritis) 
• disease of the nerves of the eyes (optic neuritis) 
• numbness or weakness of the arms and legs (neuropathy) 
• immediate injection site pain, stinging and burning feeling 
• paralysis, drooping eyelid and sagging muscles on one side of the face (facial palsy)   
• disease mainly affecting the joints with pain and swelling (arthritis), muscular weakness 
• purple or reddish-purple bumps on the skin (lichen planus), serious skin rashes (erythema 

multiforme) 
• reduction in blood platelets, which increases risk of bleeding or bruising (thrombocytopenia), 

purple or red brown spots visible through the skin (thrombocytopenic purpura) 
   

Reporting of side effects  
 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet.You can also report side effects directly via 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.  How to store Ambirix 
 
Keep this vaccine out of the sight and reach of children. 
Do not use this vaccine 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 to 8°C). Do not freeze. Freezing destroys the vaccine. 
Store in the original package in order to protect from light. 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Ambirix contains 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


26 

 
• The active substances are:  
 

- Hepatitis A virus (inactivated) 1,2        720 ELISA Units 
- Hepatitis B surface antigen 3,4          20 micrograms 

 
1Produced on human diploid (MRC-5) cells 
2Adsorbed on aluminium hydroxide, hydrated  0.05 milligrams Al3+ 
3Produced 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 in a pre-filled syringe.  
Ambirix is a white, slightly milky liquid presented in a glass 1 ml pre-filled syringe. 
Ambirix is available in packs of 1 and 10 pre-filled syringes (with or without needles) and in pack 
sizes of 50 pre-filled syringes without needles. 
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: 
 
België/Belgique/Belgien 
GlaxoSmithKline Pharmaceuticals s.a./n.v. 
Tél/Tel: + 32 10 85 52 00 
 

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

България 
ГлаксоСмитКлайн ЕООД 
Тел.: + 359 2 953 10 34 

Luxembourg/Luxemburg 
GlaxoSmithKline Pharmaceuticals s.a./n.v. 
Tél/Tel: + 32 10 85 52 00 
 

Česká republika 
GlaxoSmithKline s.r.o. 
Tel: + 420 2 22 00 11 11 
cz.info@gsk.com 
 

Magyarország 
GlaxoSmithKline Kft. 
Tel.: + 36-1-2255300 
 

Danmark 
GlaxoSmithKline Pharma A/S 
Tlf: + 45 36 35 91 00 
dk-info@gsk.com 
 

Malta 
GlaxoSmithKline (Malta) Ltd 
Tel: + 356 21 238131 
 

Deutschland 
GlaxoSmithKline GmbH & Co. KG 
Tel: + 49 (0)89 360448701 
produkt.info@gsk.com 
 

Nederland 
GlaxoSmithKline BV 
Tel: + 31 (0)30 69 38 100 
 

Eesti Norge 



27 

GlaxoSmithKline Eesti OÜ  
Tel: +372 667 6900 
estonia@gsk.com 
 

GlaxoSmithKline AS 
Tlf: + 47 22 70 20 00 
 
 

Ελλάδα 
GlaxoSmithKline Μονοπρόσωπη A.E.B.E. 
Tηλ: + 30 210 68 82 100 
 

Österreich 
GlaxoSmithKline Pharma GmbH. 
Tel: + 43 1 970 75-0 
at.info@gsk.com  
 

España 
GlaxoSmithKline, S.A. 
Tel: + 34 900 202 700 
es-ci@gsk.com  
 

Polska 
GSK Services Sp. z o.o. 
Tel.: + 48 (22) 576 9000 
 

France 
Laboratoire GlaxoSmithKline 
Tél: + 33 (0) 1 39 17 84 44 
diam@gsk.com 
 
 
Hrvatska 
GlaxoSmithKline d.o.o. 
Tel.: + 385 (0)1 6051999 
 

Portugal 
Smith Kline & French Portuguesa - Produtos 
Farmacêuticos, Lda. 
Tel: + 351 21 412 95 00 
FI.PT@gsk.com 
 
România 
GlaxoSmithKline (GSK) SRL  
Tel: + 40 (0)21 3028 208 
 

Ireland 
GlaxoSmithKline (Ireland) Ltd 
Tel: + 353 (0)1 495 5000 
 

Slovenija 
GlaxoSmithKline d.o.o. 
Tel: + 386 (0) 1 280 25 00 
medical.x.si@gsk.com 
 

Ísland 
Vistor hf.  
Sími: +354 535 7000  

Slovenská republika 
GlaxoSmithKline Slovakia s.r.o. 
Tel: + 421 (0)2 48 26 11 11 
recepcia.sk@gsk.com 
 

Italia 
GlaxoSmithKline S.p.A. 
Tel: + 39 04 59 21 81 11 
 

Suomi/Finland 
GlaxoSmithKline Oy 
Puh/Tel: + 358 10 30 30 30 
  

Κύπρος 
GlaxoSmithKline (Cyprus) Ltd 
Τηλ: + 357 22 39 70 00 
gskcyprus@gsk.com 

Sverige 
GlaxoSmithKline AB 
Tel: + 46 (0)8 638 93 00 
info.produkt@gsk.com 
 

Latvija 
GlaxoSmithKline Latvia SIA 
Tel: + 371 67312687 
lv-epasts@gsk.com 
 

United Kingdom 
GlaxoSmithKline UK 
Tel: +44 (0)800 221 441 
customercontactuk@gsk.com 
 

  
This leaflet was last revised in  
  
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/. 
 



28 

--------------------------------------------------------------------------------------------------------------------- 
 
The following information is intended for healthcare professionals only: 
 
Upon storage, a fine white deposit with a clear colourless layer above may be observed.  
 
The vaccine should be re-suspended before use. When re-suspended, the vaccine will have a uniform 
hazy white appearance. 
 
Re-suspension of the vaccine to obtain a uniform hazy white suspension 
 
The vaccine should be re-suspended 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. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCES AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET