Twinrix Paediatric

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 

 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Twinrix Paediatric, suspension for injection in pre-filled syringe 
Hepatitis A (inactivated) and hepatitis B (rDNA) (HAB) vaccine (adsorbed). 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
1 dose (0.5 ml) contains: 
 
Hepatitis A virus (inactivated)1,2 360 ELISA Units 
Hepatitis B surface antigen3,4 10 micrograms 
 
1Produced on human diploid (MRC-5) cells 
2Adsorbed on aluminium hydroxide, hydrated 0.025 milligrams Al3+ 
3Produced in yeast cells (Saccharomyces cerevisiae) by recombinant DNA technology 
4Adsorbed on aluminium phosphate 0.2 milligrams Al3+ 
 
The vaccine may contain traces of neomycin which is used during the manufacturing process (see 
section 4.3). 
  
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension for injection. 
Turbid white suspension. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Twinrix Paediatric is indicated for use in non immune infants, children and adolescents from 1 year up 
to and including 15 years who are at risk of both hepatitis A and hepatitis B infection. 
 
4.2 Posology and method of administration 
 
Posology 
 
- Dosage 
 
The dose of 0.5 ml (360 ELISA Units HA/10 µg HBsAg) is recommended for infants, children and 
adolescents from 1 year up to and including 15 years of age. 
 
- Primary vaccination schedule 
 
The standard primary course of vaccination with Twinrix Paediatric consists of three doses, the first 
administered at the elected date, the second one month later and the third six months after the first 
dose. 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 



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combined vaccine can be given. The safety and immunogenicity of Twinrix Paediatric administered as 
a booster dose following a three-dose primary course have not been evaluated. 
 
Long-term antibody persistence data following vaccination with Twinrix Paediatric are available up to 
15 years after vaccination (see section 5.1).  
The anti-HBs and anti-HAV antibody titres observed following a primary vaccination course with the 
combined vaccine are in the range of what is seen following vaccination with the monovalent 
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 or patients exposed to HBV (e.g. haemodialysis or 
immunocompromised patients) a precautionary attitude should be considered to ensure a protective 
antibody level ≥ 10IU/l. 
 
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. 
 
In situations where a booster dose of both hepatitis A and hepatitis B are desired, Twinrix Paediatric 
can be given. Alternatively, subjects primed with Twinrix Paediatric may be administered a booster 
dose of either of the monovalent vaccines. 
 
Method of administration 
 
Twinrix Paediatric is for intramuscular injection, preferably in the deltoid region in adolescents and 
children or in the anterolateral thigh in infants. 
 
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. 
 
The administration of Twinrix Paediatric should be postponed in subjects suffering from acute severe 
febrile illness. 
 
4.4 Special warnings and precautions for use 
 
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. 
 



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It is possible that subjects may be in the incubation period of a HA or HB infection at the time of 
vaccination. It is not known whether Twinrix Paediatric will prevent HA and HB 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. 
 
Twinrix Paediatric is not recommended for postexposure prophylaxis (e.g. needle stick injury). 
 
The vaccine has not been tested in patients with impaired immunity.  In haemodialysis patients, 
patients receiving immunosuppressive treatment or patients with an impaired immune system, the 
anticipated immune response may not be achieved after the primary immunisation course. Such 
patients may require additional doses of vaccine; nevertheless immunocompromised patients may fail 
to demonstrate an adequate response. 
 
As with all injectable vaccines, appropriate medical treatment and supervision should always be 
readily available in case of a rare anaphylactic event following the administration of the vaccine. 
 
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 Twinrix 
Paediatric can be administered subcutaneously to subjects with thrombocytopenia or bleeding 
disorders since bleeding may occur following an intramuscular administration to these subjects (see 
section 4.2). 
 
Twinrix Paediatric 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 Twinrix Paediatric 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, 
no influence on seroconversion was observed although it may result in lower antibody titres. 
 
Twinrix Paediatric can be given concomitantly with Human Papillomavirus (HPV) vaccine. 
Administration of Twinrix Paediatric 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 co-administration, 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 alone. 
 
Only the concomitant administration of Twinrix Paediatric with Cervarix has been specifically 
studied. It is advised that vaccines other than Cervarix should not be administered at the same time as 
Twinrix Paediatric. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
The effect of Twinrix Paediatrict on embryo-fetal, peri-natal and post-natal survival and development 
has been assessed in rats. This study did not indicate direct or indirect harmful effects with respect to 
fertility, pregnancy, embryonal/fetal development, parturition or post-natal development. 
 
The effect of Twinrix Paediatric on embryo-fetal, peri-natal and post-natal survival and development 



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has not been prospectively evaluated in clinical trials. 
 
Data on outcomes of a limited number of pregnancies in vaccinated women do not indicate any 
adverse effects of Twinrix Paediatric on pregnancy or on the health of the fetus/newborn child. While 
it is not expected that recombinant hepatitis B virus surface antigen would have adverse effects on 
pregnancies or the fetus it is recommended that vaccination should be delayed until after delivery 
unless there is an urgent need to protect the mother against hepatitis B infection. 
 
Breast-feeding 
 
It is unknown whether Twinrix Paediatric is excreted in human breast milk. The excretion of Twinrix 
Paediatric in milk has not been studied in animals. A decision on whether to continue/discontinue 
breast-feeding or to continue/discontinue therapy with Twinrix Paediatric should be made taking into 
account the benefit of breast-feeding to the child and the benefit of Twinrix Paediatric therapy to the 
woman. 
 
4.7 Effects on ability to drive and use machines 
 
Twinrix Paediatric has no or negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects  
 
Summary of the safety profile 
 
The safety profile presented below is based on data from approximately 800 subjects. The most 
commonly reported adverse reactions following Twinrix Paediatric administration are pain and 
redness occurring in a per dose frequency of 28.5% and 11.5% respectively. 
 
Tabulated list of adverse reactions 
 
Frequencies are reported as: 
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 
Very rare: < 1/10,000 
 
System Organ Class Frequency Adverse reactions 
Clinical trials 
Infections and infestations Uncommon Upper respiratory tract infection* 
Blood and lymphatic system disorders Rare Lymphadenopathy 
Metabolism and nutrition disorders Common Appetite lost 
Psychiatric disorders Common Irritability 
Nervous system disorders Common Drowsiness, headache 

Rare Hypoaesthesia*, paraesthesia*, 
dizziness 

Vascular disorders Rare Hypotension* 
Gastrointestinal disorders Common Gastrointestinal symptoms, nausea 

Uncommon Diarrhoea, vomiting, abdominal pain 
Skin and subcutaneous tissue disorders Uncommon Rash 

Rare Urticaria, pruritus* 
Musculoskeletal and connective tissue 
disorders 

Uncommon Myalgia* 
Rare Arthralgia* 

General disorders and administration site 
conditions 

Very common Pain and redness at the injection site 
Common Swelling at the injection site, injection 

site reaction (such as bruising), fatigue, 



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malaise, fever (≥ 37.5°C) 
Rare Influenza like illness*, chills* 

Post-marketing surveillance 
The following adverse reactions have been reported with either Twinrix or with GlaxoSmithKline 
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 

Following widespread use of the monovalent hepatitis A and/or hepatitis B vaccines, the following  
undesirable events have additionally been reported in temporal association with vaccination: 
Nervous system disorders Multiple sclerosis, myelitis, facial palsy, polyneuritis such 

as Guillain-Barré syndrome (with ascending paralysis), 
optic neuritis 

General disorders and administration site 
conditions 

Stinging and burning sensation 

Investigations Abnormal liver function tests 
* refers to adverse reactions observed in clinical trials performed with the adult formulation 
 
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. 
 
4.9 Overdose 
 
Cases of overdose have been reported during post-marketing surveillance. Adverse events reported 
following overdosage were similar to those reported with normal vaccine administration. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmaco-therapeutic group: Hepatitis vaccines, ATC code: J07BC20. 
 
Twinrix Paediatric is a combined vaccine formulated by pooling bulk preparations of the purified, 
inactivated hepatitis A (HA) virus and purified hepatitis B surface antigen (HBsAg), separately 
adsorbed onto aluminium hydroxide and aluminium phosphate. 
The HA virus is propagated in MRC5 human diploid cells. HBsAg is produced by culture, in a 
selective medium, of genetically engineered yeast cells. 
Twinrix Paediatric confers immunity against HAV and HBV infection by inducing specific anti-HA 
and anti-HBs antibodies. 
 
Protection against hepatitis A and hepatitis B develops within 2-4 weeks.  In the clinical studies, 
specific humoral antibodies against hepatitis A were observed in approximately 89% of the subjects 

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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one month after the first dose and in 100% one month after the third dose (i.e. month 7).  Specific 
humoral antibodies against hepatitis B were observed in approximately 67% of the subjects after the 
first dose and 100% after the third dose. 
 
In two long-term clinical trials, persistence of anti-HAV and anti-HBs antibodies has been 
demonstrated up to 5 years in children aged 1-11 years and up to 15 years in children aged 12-15 
years.  
At 5 years following initiation of a 0, 1, 6 month schedule of Twinrix Paediatric in children aged 1-11 
years all subjects followed up retained ≥15 mIU/ml anti-HAV antibody and 97% had anti-HBs 
antibody ≥10 mIU/ml. 
 
At 15 years following the initiation of a 0, 1, 6 month schedule of Twinrix Paediatric in children aged 
12-15 years, all subjects followed up retained ≥15 mIU/ml anti-HAV antibody and 81.8% had 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 concentrations had decreased to <10 mIU/ml and 10 of the 
11 subjects (90.9%) mounted an anamnestic response. 
 
5.2 Pharmacokinetic properties 
 
Evaluation of pharmacokinetic properties is not required for vaccines. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on general safety studies. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sodium chloride 
Water for injections 
 
For adjuvants, see section 2. 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
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 
 
0.5 ml of suspension in a pre-filled syringe (type I glass) with a plunger stopper (rubber butyl).  
Pack sizes of 1, 10 and 50 with or without needles. 
 



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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. 
 
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/1/97/029/001 
EU/1/97/029/002 
EU/1/97/029/006 
EU/1/97/029/007 
EU/1/97/029/008 
EU/1/97/029/009 
EU/1/97/029/010 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 10 February 1997 
Date of latest renewal: 28 August 2006 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal 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 MANUFATURER 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, 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 
10 PRE-FILLED SYRINGES WITHOUT NEEDLE 
50 PRE-FILLED SYRINGES WITHOUT NEEDLE 
1 PRE-FILLED SYRINGE WITH 1 NEEDLE 
10 PRE-FILLED SYRINGES WITH 10 NEEDLES 
1 PRE-FILLED SYRINGE WITH 2 NEEDLES 
10 PRE-FILLED SYRINGES WITH 20 NEEDLES 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Twinrix Paediatric – 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 (0.5 ml): 
Hepatitis A virus (inactivated)1,2 360 ELISA Units 
Hepatitis B surface antigen3,4 10 micrograms 
 
1Produced on human diploid (MRC-5) cells 
2Adsorbed on aluminium hydroxide, hydrated 0.025 milligrams Al3+ 
3Produced in yeast cells (Saccharomyces cerevisiae) by recombinant DNA technology 
4Adsorbed on aluminium phosphate 0.2 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 (0.5 ml) 
 
10 pre-filled syringes 
10 x 1 dose (0.5 ml) 
 
50 pre-filled syringes 
50 x 1 dose (0.5 ml) 
 
1 pre-filled syringe + 1 needle 
1 dose (0.5 ml) 
 
10 pre-filled syringes + 10 needles 
10 x 1 dose (0.5 ml) 
 



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1 pre-filled syringe + 2 needles 
1 dose (0.5 ml) 
 
10 pre-filled syringes + 20 needles 
10 x 1 dose (0.5 ml) 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Intramuscular use 
Shake 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/1/97/029/001 – pack of 1 without needle  
EU/1/97/029/002 – pack of 10 without needle 
EU/1/97/029/008 – pack of 50 without needle 
EU/1/97/029/006 – pack of 1 with 1 needle 
EU/1/97/029/007 – pack of 10 with 10 needles 



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EU/1/97/029/009 – pack of 1 with 2 needles 
EU/1/97/029/010 – pack of 10 with 20 needles 
 
 
13. BATCH NUMBER 
 
LOT: 
 
 
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 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Twinrix Paediatric, suspension for injection 
HAB vaccine 
I.M. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP:  
 
 
4. BATCH NUMBER 
 
LOT:  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 dose (0.5 ml) 
 
 
6. OTHER 
 



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B. PACKAGE LEAFLET 



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Package leaflet: Information for the user 

 
Twinrix Paediatric, 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 start/ 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 or your pharmacist. 
- This vaccine has been prescribed for you/ your child only. Do not pass it on to others. 
- If you get / your child gets any side effects, talk to your doctor 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 Twinrix Paediatric is and what it is used for 
2. What you need to know before you receive Twinrix Paediatric 
3. How Twinrix Paediatric is given 
4. Possible side effects 
5. How to store Twinrix Paediatric 
6. Contents of the pack and other information 
 
 
1. What Twinrix Paediatric is and what it is used for 
 
Twinrix Paediatric is a vaccine used in infants, children and adolescents from 1 year up to and 
including 15 years to prevent two diseases: hepatitis A and hepatitis B. The vaccine works by causing 
the body to produce its own protection (antibodies) against these diseases. 
 
• Hepatitis A: Hepatitis A is an infectious disease, which can affect the liver. This disease is 

caused by the hepatitis A virus. The hepatitis A virus can be passed from person to person in 
food and drink, or by 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 off work for about a month. 

 
• Hepatitis B: Hepatitis B is caused by the hepatitis B virus.  It causes 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. 

 
Vaccination is the best way to protect against these diseases. None of the components in the vaccine 
are infectious.  
 
 
2. What you need to know before you receive Twinrix Paediatric  
 
Twinrix Paediatric should not be given if 
• you are allergic to: 

- the active substances, or any of the ingredients of this medicine (listed in section 6). 
- neomycin.   
Signs of an allergic reaction may include itchy skin rash, shortness of breath and swelling of the 
face or tongue. 



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

• you have a severe infection with a high temperature (over 38°C).  A minor infection such as a 
cold should not be a problem, but talk to your doctor first. 

 
Warnings and precautions 
Talk to you doctor or pharmacist before you receive Twinrix Paediatric if:  
• you have experienced any health problems after previous administration of a vaccine. 
• you have a poor immune system due to illness or drug treatment. 
• you have a bleeding problem or bruise/ bruises easily. 
 
Fainting can occur (mostly in adolescents) following, or even before, any needle injection. Therefore 
tell the doctor or nurse if you fainted with a previous injection. 
 
Other medicines and Twinrix Paediatric  
Twinrix Paediatric can be given with a Human Papillomavirus (HPV) vaccine at a separate injection 
site (another part of your body, e.g. the other arm) during the same visit. 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think that you may be pregnant or are planning to have a baby,  
ask your doctor or pharmacist for advice before you are given this vaccine. 
It is not known if Twinrix Paediatric passes into breast milk, however the vaccine is not expected to 
cause problems in breast-fed babies. 
 
Twinrix Paediatric contains neomycin 
Please tell your doctor if you have had an allergic reaction to neomycin (antibiotic). 
 
 
3. How Twinrix Paediatric is given  
 
You will receive a total of three injections over 6 months. Each injection 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 
 
Your doctor will advise on the possible need for extra doses, and future booster dosing. 
 
If you miss a scheduled injection, talk to your doctor and arrange another visit. 
 
Make sure you finish the complete vaccination course of three injections. If not, you may not be fully 
protected against the diseases. 
 
The doctor will give Twinrix Paediatric as an injection into your upper arm muscle or into the thigh 
muscle of your child.   
 
The vaccine should never be given into a vein. 
 
If you have any further questions on the use of this vaccine, ask your doctor or pharmacist. 
 
 



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4.  Possible side effects  
 
Like all medicines, this vaccine can cause side effects, although not everybody gets them. 
 
Side effects that may occur are the following: 
 
Side effects occured during clinical studies or routine use of the vaccine or with individual hepatitis A 
and hepatitis B vaccines or with the adult formulation of Twinrix. 
 
Very common (these may occur with more than 1 in 10 doses of the vaccine) 
• Pain and redness at the injection site 
 
Common (these may occur with up to 1 in 10 doses of the vaccine) 
• Drowsiness, headache 
• Nausea 
• Loss of appetite 
• Swelling or bruising at the injection site 
• Generally feeling unwell, tiredness 
• Fever equal to or greater than 37.5°C 
• Irritability 
 
Uncommon (these may occur with up to 1 in 100 doses of the vaccine) 
• Diarrhoea, vomiting, stomach pain 
• Rash 
• Aching muscles 
• Upper respiratory tract infection 
 
Rare (these may occur with up to 1 in 1,000 doses of the vaccine) 
• Swollen glands in the neck armpit or groin (lymphadenopathy) 
• Dizziness 
• Loss of skin sensitivity to pain or touch (hypoaesthesia) 
• Feeling of pins and needles (paraesthesia) 
• Hives, itching 
• Joint pain 
• Low blood pressure 
• 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) 
• Reduction in blood platelets, which increases risk of bleeding or bruising (thrombocytopenia) 
• Purple or red brown spots visible through the skin (thrombocytopenic purpura) 
• Swelling or infection of the brain (encephalitis) 
• Degenerative disease of the brain (encephalopathy) 
• Inflammation of nerves (neuritis) 
• Numbness or weakness of the arms and legs (neuropathy), paralysis 
• Fits or seizures 
• Swelling of the face, mouth or throat (angioneurotic oedema) 
• Purple or reddish-purple bumps on the skin (lichen planus), serious skin rashes (erythema 

multiforme) 
• Joint swelling, muscular weakness 
• Infection around the brain which may give severe headache with stiff neck and sensitivity to light 

(meningitis) 
• Inflammation of some blood vessels (vasculitis) 
• Serious allergic reactions (anaphylaxis, anaphylactoid reactions and mimicking serum sickness). 

Signs of serious allergic reactions may be rashes 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 



21 

consciousness. Such reactions may occur before leaving the doctor’s surgery. However, if you get 
any of these symptoms you should contact a doctor urgently. 

• Abnormal laboratory liver test results 
• Multiple sclerosis, swelling of the spinal cord (myelitis) 
• Drooping eyelid and sagging muscles on one side of the face (facial palsy) 
• 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) 
• A disease of the nerves of the eye (optic neuritis) 
• Immediate injection site pain, stinging and burning feeling 
 
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 Twinrix Paediatric  
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine 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).  
Store in the original package in order to protect from light.   
Do not freeze.  Freezing destroys the vaccine. 
 
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 Twinrix Paediatric contains 
 
- The active substances are:  

Hepatitis A virus (inactivated)1,2 360 ELISA Units 
Hepatitis B surface antigen3,4 10 micrograms 
 
1Produced on human diploid (MRC-5) cells 
2Adsorbed on aluminium hydroxide, hydrated 0.025 milligrams Al3+ 
3Produced in yeast cells (Saccharomyces cerevisiae) by recombinant DNA technology 
4Adsorbed on aluminium phosphate 0.2 milligrams Al3+ 

 
- The other ingredients in Twinrix Paediatric are: sodium chloride, water for injections. 
 
What Twinrix Paediatric looks like and contents of the pack 
 
Suspension for injection in pre-filled syringe. 
 
Twinrix Paediatric is a white, slightly milky liquid presented in a glass pre-filled syringe (0.5 ml). 
 
Twinrix Paediatric is available in packs of 1, 10 and 50 with or without needles. 
 
Not all pack sizes may be marketed. 
 

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


22 

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: 
 
Belgique/België/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 
nlinfo@gsk.com 

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

Norge 
GlaxoSmithKline AS 
Tlf: + 47 22 70 20 00 
 

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

Österreich 
GlaxoSmithKline Pharma GmbH 
Tel: + 43 (0)1 970750 
at.info@gsk.com  
 

España 
GlaxoSmithKline, S.A. 
Tel: + 34 902 202 700 
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. 

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



23 

Tel.: + 385 (0)1 6051999 
 

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 (0)45 9218 111 
 

Suomi/Finland 
GlaxoSmithKline Oy 
Puh/Tel: + 358 10 30 30 30 
Finland.tuoteinfo@gsk.com  
 

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 
 
--------------------------------------------------------------------------------------------------------------------- 
 
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 



24 

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