Twinrix Adult

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ANNEX I 

 
SUMMARY OF PRODUCT CHARACTERISTICS 

 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Twinrix Adult, 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+ 
 
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 Adult is indicated for use in non immune adults and adolescents 16 years of age and above 
who are at risk of both hepatitis A and hepatitis B infection. 
 
4.2 Posology and method of administration 
 
Posology 
 
- Dosage 
 
A dose of 1.0 ml is recommended for adults and adolescents 16 years of age and above. 
 
- Primary vaccination schedule 
 
The standard primary course of vaccination with Twinrix Adult 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. 
 
In exceptional circumstances in adults, when travel is anticipated within one month or more after 
initiating the vaccination course, but where insufficient time is available to allow the standard 0, 1, 6 
month schedule to be completed, a schedule of three intramuscular injections given at 0, 7 and 21 days 
may be used. When this schedule is applied, a fourth dose is recommended 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 
 
Long-term antibody persistence data following vaccination with Twinrix Adult are available up to 20 
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.  
 
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 Adult can 
be given. Alternatively, subjects primed with Twinrix Adult may be administered a booster dose of 
either of the monovalent vaccines. 
 
Method of administration 
 
Twinrix Adult is for intramuscular injection, preferably in the deltoid region. 
 
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 Adult 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 hepatitis A or hepatitis B infection at 
the time of vaccination. It is not known whether Twinrix Adult 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. 
 
Twinrix Adult 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 and 
persons with an impaired immune system, adequate anti-HAV and anti-HBs antibody titres may not be 
obtained after the primary immunisation course and such patients may therefore require administration 
of additional doses of vaccine. 
 
Obesity (defined as BMI ≥ 30 kg/m2) has been observed to reduce the immune response to hepatitis A 
vaccines. A number of factors have been observed to reduce the immune response to hepatitis B 
vaccines. These factors include older age, male gender, obesity, smoking, route of administration, and 
some chronic underlying diseases. Consideration should be given to serological testing of those 
subjects who may be at risk of not achieving seroprotection following a complete course of Twinrix 
Adult. Additional doses may need to be considered for persons who do not respond or have a sub-
optimal response to a course of vaccinations. 
 
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 
Adult 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 Adult should under no circumstances be administered intravascularly. 
 
As with any vaccine, a protective immune response may not be elicited in all vaccinees. 
 
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 Adult 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. 
 
Although the concomitant administration of Twinrix Adult and other vaccines has not specifically 
been studied, it is anticipated that, if different syringes and other injection sites are used, no interaction 
will be observed. 
 
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 
 



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The effect of Twinrix Adult 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 Adult on embryo-fetal, peri-natal and post-natal survival and development 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 Adult 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 Adult is excreted in human breast milk. The excretion of Twinrix 
Adult in milk has not been studied in animals. A decision on whether to continue/discontinue breast-
feeding or to continue/discontinue therapy with Twinrix Adult should be made taking into account the 
benefit of breast-feeding to the child and the benefit of Twinrix Adult therapy to the woman. 
 
4.7 Effects on ability to drive and use machines 
 
Twinrix Adult 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 a pooled analysis of events per dose from more than 
6,000 subjects who received either the standard 0, 1, 6 month schedule (n=5,683) or the accelerated 0, 
7, 21 days schedule (n=320). The most commonly reported adverse reactions following Twinrix Adult 
administration with the standard 0, 1, 6 month schedule are pain and redness occurring in a per dose 
frequency of 37.6% and 17.0% respectively. 
 
In the two clinical trials in which Twinrix Adult was administered at 0, 7, 21 days, overall solicited 
general and local symptoms were reported with the same categories of frequency as defined below. 
After a fourth dose given at month 12, the incidence of systemic and local adverse reactions was 
comparable to that seen after vaccination at 0, 7, 21 days. 
 
In comparative studies, it was noted that the frequency of solicited adverse events following the 
administration of Twinrix Adult is not different from the frequency of solicited adverse events 
following the administration of the monovalent vaccines. 
 
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 
 
 
 
 
 
 



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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 Rare Decreased appetite 
Nervous system disorders Very common Headache 

Uncommon Dizziness 
Rare Hypoaesthesia, paraesthesia 

Vascular disorders Rare Hypotension 
Gastrointestinal disorders Common Gastrointestinal symptoms, diarrhoea, 

nausea 
Uncommon Vomiting, abdominal pain* 

Skin and subcutaneous tissue disorders Rare Rash, pruritus 
Very rare Urticaria 

Musculoskeletal and connective tissue 
disorders 

Uncommon Myalgia 
Rare Arthralgia 

General disorders and administration site 
conditions 

Very common Pain and redness at the injection site, 
fatigue 

Common Swelling at the injection site, injection 
site reactions (such as haematoma, 
pruritus and bruising), malaise 

Uncommon 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 paediatric 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. 
 

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 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 Adult 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 Adult confers immunity against HAV and HBV infection by inducing specific anti-HAV 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 94% of the adults 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 70% of the adults after the first dose and 
approximately 99% after the third dose. 
 
The 0, 7 and 21 day primary schedule plus a fourth dose at month 12 is for use in exceptional 
circumstances in adults. In a clinical trial where Twinrix Adult was administered according to this 
schedule, 82% and 85% of vaccinees had seroprotective levels of anti-HBV antibodies at 1 and 5 
weeks respectively following the third dose (i.e. at months 1 and 2 after the initial dose). The 
seroprotection rate against hepatitis B increased to 95.1% by three months after the first dose. 
 
Seropositivity rates for anti-HAV antibodies were 100%, 99.5% and 100% at months 1, 2 and 3 after 
the initial dose. One month after the fourth dose, all vaccinees demonstrated seroprotective levels of 
anti-HBs antibodies and were seropositive for anti-HAV antibodies. 
 
In a clinical study conducted in subjects over 40 years of age, the seropositivity rate for anti-HAV 
antibodies and seroprotection rate against hepatitis B of Twinrix Adult following a 0, 1, 6 months 
schedule were compared with the seropositivity and seroprotection rates of monovalent hepatitis A 
and B vaccines when administered in opposite arms. 
The seroprotection rate against hepatitis B after the administration of Twinrix Adult was 92% and 
56% at 7 and 48 months respectively, versus 80% and 43% after the GlaxoSmithKline Biologicals 
monovalent 20µg hepatitis B vaccine, and 71% and 31% after another licensed monovalent 10µg 
hepatitis B vaccine. Anti-HBs antibody concentrations decreased as age and body mass index 
increased; they were also lower in male than in female subjects. 
The seropositivity rate for anti-HAV antibodies after Twinrix Adult was 97% at both 7 and 48 months 
versus 99% and 93% after the GlaxoSmithKline Biologicals monovalent hepatitis A vaccine and 99% 
and 97% after another licensed monovalent hepatitis A vaccine. 
Subjects received an additional dose of the same vaccine(s) 48 months after the first dose of the 
primary vaccination course. One month after this dose, 95% of the subjects vaccinated with Twinrix 
Adult achieved seroprotective levels of anti-HBV antibodies (≥ 10 mIU/ml). 
 
In two long-term clinical studies conducted in adults aged 17 years to 43 years, respectively 18 and 25 
subjects had evaluable tests 20 years after the primary vaccination with Twinrix Adult; the anti-HAV 
seropositivity rates were 100% and 96% respectively and the anti-HBs seroprotection rates were 94% 
and 92%, respectively.  



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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 
 
1 ml of suspension in a pre-filled syringe (type I glass) with a plunger stopper (rubber butyl).  
Pack sizes of 1, 10 and 25 with or 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: 



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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/1/96/020/001 
EU/1/96/020/002 
EU/1/96/020/003 
EU/1/96/020/007 
EU/1/96/020/008 
EU/1/96/020/009 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 20 September 1996 
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. 
 



10 

 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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, 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. 
 
 
 



12 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 

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 
25 PRE-FILLED SYRINGES WITHOUT NEEDLE 
1 PRE-FILLED SYRINGE WITH 1 NEEDLE 
10 PRE-FILLED SYRINGES WITH 10 NEEDLES 
25 PRE-FILLED SYRINGES WITH 25 NEEDLES 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Twinrix Adult – 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) 
 
10 pre-filled syringes 
10 x 1 dose (1 ml) 
 
25 pre-filled syringes 
25 x 1 dose (1 ml) 
 
1 pre-filled syringe + 1 needle 
1 dose (1 ml) 
 
10 pre-filled syringes + 10 needles 
10 x 1 dose (1 ml) 
 
25 pre-filled syringes + 25 needles 
25 x 1 dose (1 ml) 



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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/1/96/020/001 - pack of 1 without needle 
EU/1/96/020/002 - pack of 10 without needle 
EU/1/96/020/003 - pack of 25 without needle 
EU/1/96/020/007 - pack of 1 with 1 needle 
EU/1/96/020/008 - pack of 10 with 10 needles 
EU/1/96/020/009 - pack of 25 with 25 needles 
 
 
13. BATCH NUMBER 
 



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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 Adult, 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 (1 ml) 
 
 
6. OTHER 
 



18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 



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Package leaflet: Information for the user 

 
Twinrix Adult, 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 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 only. Do not pass it on to others. 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
1. What Twinrix Adult is and what it is used for 
2. What you need to know before you receive Twinrix Adult 
3. How Twinrix Adult is given 
4. Possible side effects 
5. How to store Twinrix Adult 
6. Contents of the pack and other information 
 
 
1.   What Twinrix Adult is and what it is used for   
 
Twinrix Adult is a vaccine used in adults and adolescents 16 years of age and above 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 ill 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 Adult  
 
Twinrix Adult should not be given if 
• you are allergic to: 

- the active substances or any of the other 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. 

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



20 

• 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 your doctor or pharmacist before receiving Twinrix Adult 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 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. 
 
A poor response to the vaccine, possibly without achieving protection against hepatitis A, has been 
observed in obese people. A poor response to the vaccine, possibly without achieving protection 
against hepatitis B, has also been observed in older people, men rather than women, smokers, obese 
people, and people with long standing illnesses, or people on some type of drug treatments. Your 
doctor may advise you to have a blood test after you have completed the course of vaccinations to 
check if you have made a satisfactory response. If not, your doctor will advise you on the possible 
need to have extra doses. 
 
Other medicines and Twinrix Adult  
Tell your doctor or pharmacist if you are taking or 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 
Adult passes into breast milk, however the vaccine is not expected to cause problems in breast-fed 
babies. 
 
Twinrix Adult contains neomycin 
Please tell your doctor if you have had an allergic reaction to neomycin (antibiotic). 
 
 
3. How Twinrix Adult 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 
 
Twinrix Adult can also be given as a total of three doses over 1 month.  This schedule may be given to 
adults only needing a rapid protection (e.g. overseas travellers).  The first dose will be given on an 
elected date.  The remaining 2 doses will be given 7 days and 21 days after the first dose.  A fourth 
dose is recommended at 12 months. 
 
• First dose: at an elected date 
• Second dose: 7 days later 
• Third dose: 21 days after the first dose 
• Fourth dose: 12 months after the first dose 
 
Your doctor will advise on the possible need for extra doses, and future booster dosing. 
 



21 

As indicated in section 2, a poor response to the vaccine, possibly without achieving protection against 
hepatitis B, is more common in older people, men rather than women, smokers, obese people, and 
people with long standing illnesses, or people on some type of drug treatments. Your doctor may 
advise you to have a blood test after you have completed the course of vaccinations to check if you 
have made a satisfactory response. If not, your doctor will advise you on the possible need to have 
extra doses. 
 
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 Adult as an injection into your upper arm muscle.   
 
The vaccine should not be given (deep) into the skin or intramuscularly into the buttock because 
protection may be less. 
 
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.  
 
 
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: 
 
Very common (These may occur in 1 in 10 doses or more of the vaccine): 

• Headache 
• Pain and redness at the injection site 
• Tiredness 

 
Common (These may occur in up to 1 in 10 doses of the vaccine): 

• Diarrhoea, nausea 
• Swelling, bruising or itching at the injection site 
• Generally feeling unwell 

 
Uncommon (These may occur in up to 1 in 100 doses of the vaccine): 

• Dizziness 
• Vomiting, stomach pain 
• Aching muscles 
• Upper respiratory tract infection 
• Fever equal to or greater than 37.5°C 

 
Rare (These may occur in up to 1 in 1,000 doses of the vaccine): 

• Swollen glands in the neck armpit or groin (lymphadenopathy) 
• Loss of skin sensitivity to pain or touch (hypoaesthesia) 
• Feeling of pins and needles (paraesthesia) 
• Rash, itching 
• Joint pain 
• Loss of appetite 
• Low blood pressure 
• Flu-like symptoms such as high temperature, sore throat, runny nose, cough and chills 

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



22 

Side effects occurred very rarely during clinical studies or routine use of the vaccine or with 
individual hepatitis A and hepatitis B vaccines include: 
• 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), hives 
• 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 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 Adult  
 
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 Adult 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


23 

- The active substances are:  
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+ 

 
- The other ingredients in Twinrix Adult are: sodium chloride, water for injections. 
 
What Twinrix Adult looks like and contents of the pack 
 
Suspension for injection in pre-filled syringe. 
 
Twinrix Adult is a white, slightly milky liquid presented in a glass pre-filled syringe (1 ml). 
 
Twinrix Adult is available in packs of 1, 10, and 25 with or 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: 
 
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  

Norge 
GlaxoSmithKline AS 



24 

Tel: +372 667 6900 
estonia@gsk.com 
 

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. 
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 (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. 
 
--------------------------------------------------------------------------------------------------------------------- 



25 

 
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