Arepanrix

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  1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Arepanrix suspension and emulsion for emulsion for injection 
Pandemic influenza vaccine (H1N1)v (split virion, inactivated, adjuvanted) 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
After mixing, 1 dose (0.5 ml) contains: 
 
Split influenza virus, inactivated, containing antigen* equivalent to: 
 
A/California/7/2009 (H1N1)v-like strain (X-179A) 3.75 micrograms** 
 
* propagated in eggs 
** haemagglutinin 
 
This vaccine complies with the WHO recommendation and EU decision for the pandemic. 
 
AS03 adjuvant composed of squalene (10.69 milligrams), DL-α-tocopherol (11.86 milligrams) and 
polysorbate 80 (4.86 milligrams) 
 
The suspension and emulsion, once mixed, form a multidose vaccine in a vial. See section 6.5 for the 
number of doses per vial. 
 
Excipients: the vaccine contains 5 micrograms thiomersal 
 
For a full list of excipients see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension and emulsion for emulsion for injection. 
The suspension is a translucent to off white opalescent suspension, which may sediment slightly. 
The emulsion is a whitish homogeneous liquid. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Prophylaxis of influenza in an officially declared pandemic situation (see sections 4.2 and 5.1).  
 
Pandemic influenza vaccine should be used in accordance with Official Guidance. 
 
4.2 Posology and method of administration 
 
Posology 
 
The dose recommendations take into account available data from: 
 
• Ongoing clinical studies in healthy subjects who received a single dose of Arepanrix (H1N1) 
• Clinical studies in healthy subjects (including elderly subjects) who received two doses of a 

version of Arepanrix containing 3.75 µg HA derived from A/Indonesia/05/2005 (H5N1) 



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And also from: 
 
• On-going clinical studies in healthy subjects who received a single dose or two doses of an 

AS03-containing vaccine containing HA from H1N1v manufactured using a different process 
• Clinical studies in healthy subjects who received two doses of an AS03-containing vaccine 

containing HA from H5N1 manufactured using a different process. 
 
In some age groups there are limited clinical study data (adults aged 60-79 years and children aged 10 
to 17 years), very limited clinical study data (adults aged 80 years and older, children aged 6 months to 
9 years) or no data (children aged less than 6 months) with an AS03-containing vaccine containing HA 
from H5N1 or from H1N1v manufactured using a different process as detailed in sections 4.4, 4.8 and 
5.1. 
 
Adults aged 18-60 years: 
One dose of 0.5 ml at an elected date. 
Immunogenicity data obtained at three weeks after administration of Arepanrix (H1N1) in clinical 
studies suggest that a single dose may be sufficient.  
If a second dose is administered there should be an interval of at least three weeks between the first 
and the second dose. 
 
Elderly (>60 years) 
One dose of 0.5 ml at an elected date. 
Immunogenicity data obtained at three weeks after administration of an AS03-containing vaccine 
containing HA from H1N1v manufactured using a different process in clinical studies suggest that a 
single dose may be sufficient.  
If a second dose is administered there should be an interval of at least three weeks between the first 
and the second dose. 
 
Children and adolescents aged 10-17 years 
Immunogenicity data obtained at three weeks after administration of an AS03-containing vaccine 
containing HA from H1N1v manufactured using a different process in clinical studies suggest that 
dosing may be in accordance with the recommendations for adults.   
 
Children aged from 6 months to 9 years 
One dose of 0.25 ml at an elected date.  
Preliminary immunogenicity data obtained with an AS03-containing vaccine containing HA from 
H1N1v manufactured using a different process in a limited number of children aged 6-35 months 
show that there is a further immune response to a second dose of 0.25 ml administered after an interval 
of three weeks. 
 
The use of a second dose should take into consideration the information provided in sections 4.4, 4.8 
and 5.1. 
 
Children aged less than 6 months 
Vaccination is not currently recommended in this age group. 
 
It is recommended that subjects who receive a first dose of Arepanrix should complete the vaccination 
course with Arepanrix (see section 4.4). 
 
Method of administration 
 
Immunisation should be carried out by intramuscular injection preferably into the deltoid muscle or 
anterolateral thigh (depending on the muscle mass). 
 



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4.3 Contraindications 
 
History of an anaphylactic (i.e. life-threatening) reaction to any of the constituents or trace residues 
(egg and chicken protein, ovalbumin, formaldehyde and sodium deoxycholate) of this vaccine. If 
vaccination is considered to be necessary, facilities for resuscitation should be immediately available 
in case of need. 
 
See section 4.4 for Special warnings and special precautions for use. 
 
4.4 Special warnings and precautions for use 
 
Caution is needed when administering this vaccine to persons with a known hypersensitivity (other 
than anaphylactic reaction) to the active substance, to any of the excipients, to thiomersal and to 
residues (egg and chicken protein, ovalbumin, formaldehyde and sodium deoxycholate). 
 
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. 
 
If the pandemic situation allows, immunisation shall be postponed in patients with severe febrile 
illness or acute infection. 
 
Arepanrix should under no circumstances be administered intravascularly. 
There are no data with Arepanrix using the subcutaneous route.  Therefore, healthcare providers need 
to assess the benefits and potential risks of administering the vaccine in individuals with 
thrombocytopenia or any bleeding disorder that would contraindicate intramuscular injection unless 
the potential benefit outweighs the risk of bleedings. 
 
There are no data on administration of AS03-adjuvanted vaccines before or following other types of 
influenza vaccines intended for pre-pandemic or pandemic use. 
 
Antibody response in patients with endogenous or iatrogenic immunosuppression may be insufficient. 
 
A protective immune response may not be elicited in all vaccinees (see section 5.1). 
 
There are no safety and immunogenicity data available from clinical studies with Arepanrix or with an 
AS03-containing vaccine containing HA from H1N1v manufactured using a different process in 
children aged less than 6 months. There are limited data available from a clinical study with an AS03-
containing vaccine containing HA from H1N1v manufactured using a different process in healthy 
children aged from 10 to 17 years, very limited data with the AS03-containing vaccine containing HA 
from H1N1v manufactured using a different process in healthy children aged from 6 to 35 months and 
limited data from a study with a version of an AS03-containing vaccine containing HA from H5N1 
manufactured using a different process in children aged from 3 to 9 years. 
 
Very limited data with an AS03-containing vaccine containing HA from H1N1v manufactured using a 
different process in children aged 6 to 35 months (N=51) who received two doses of 0.25 ml (half of 
the adult dose) with an interval of 3 weeks between doses indicate an increase in the rates of injection 
site reactions and general symptoms (see section 4.8).  In particular rates of fever (axillary temperature 
≥38°C) may increase considerably after the second dose. Therefore, monitoring of temperature and 
measures to lower the fever (such as antipyretic medication as seems clinically necessary) are 
recommended in young children (e.g. up to approximately 6 years of age) after each vaccination. 
 
There are limited data available from clinical studies with an AS03-containing vaccine containing HA 
from H1N1v manufactured using a different process in adults aged over 60 years and very limited data 
in adults aged over 80 years.  
 



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There are no safety, immunogenicity or efficacy data to support interchangeability of Arepanrix with 
other H1N1 pandemic vaccines. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Data obtained on co-administration of an AS03-containing vaccine containing HA from H1N1v 
manufactured using a different process with non-adjuvanted seasonal influenza vaccine (Fluarix, a 
split virion vaccine) in healthy adults aged over 60 years did not suggest any significant interference in 
the immune response to the AS03-containing vaccine containing HA from H1N1v. The immune 
response to Fluarix was satisfactory.   Co-administration was not associated with higher rates of local 
or systemic reactions compared to administration of the AS03-containing vaccine containing HA from 
H1N1v alone.  
Therefore the data indicate that Arepanrix may be co-administered with non-adjuvanted seasonal 
influenza vaccines (with injections made into opposite limbs). 
 
Data obtained on the administration of a non-adjuvanted seasonal influenza vaccine (Fluarix, a split 
virion vaccine) three weeks before a dose of an AS03-containing vaccine containing HA from H1N1v 
manufactured using a different process in healthy adults over 60 years of age, did not suggest any 
significant interference in the immune response to the AS03-containing vaccine containing HA from 
H1N1v. Therefore the data indicate that Arepanrix may be administered three weeks after the 
administration of non-adjuvanted seasonal influenza vaccines. 
 
There are no data on co-administration of Arepanrix with other vaccines. If co-administration with 
another vaccine is considered, immunisation should be carried out on separate limbs. It should be 
noted that the adverse reactions may be intensified. 
 
The immunological response may be diminished if the patient is undergoing immunosuppressant 
treatment. 
 
Following influenza vaccination, false-positive serology test results may be obtained by the ELISA 
method for antibody to human immunodeficiency virus-1 (HIV-1), hepatitis C virus and, especially, 
HTLV-1. In such cases, the Western blot method is negative.  These transitory false-positive results 
may be due to IgM production in response to the vaccine. 
 
4.6  Pregnancy and lactation 
 
There are currently no data available on the use of Arepanrix in pregnancy. Data from pregnant 
women vaccinated with different inactivated non-adjuvanted seasonal vaccines do not suggest 
malformations or fetal or neonatal toxicity. 
 
Animal studies with Arepanrix do not indicate reproductive toxicity (see section 5.3). 
 
The use of Arepanrix may be considered during pregnancy if this is thought to be necessary, taking 
into account official recommendations. 
 
Arepanrix may be used in lactating women. 
 
4.7 Effects on ability to drive and use machines 
 
Some of the effects mentioned under section 4.8 “Undesirable Effects” may affect the ability to drive 
or operate machinery. 
 
4.8 Undesirable effects 
 
• Clinical trials 



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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) 
Very rare (<1/10,000) 
 
Clinical studies have evaluated the incidence of adverse reactions in approximately 4,500 subjects 18 
years old and above who received a version of Arepanrix containing 3.75 microgram HA derived from 
A/Indonesia/5/2005 (H5N1). 
 
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 
Blood and lymphatic system disorders 
Uncommon: lymphadenopathy 
 
Psychiatric disorders 
Uncommon: insomnia 
 
Nervous system disorders 
Very common: headache 
Uncommon: dizziness, paraesthesia 
 
Ear and labyrinth disorders 
Uncommon: vertigo 
 
Respiratory, thoracic and mediastinal disorders 
Uncommon: dyspnoea 
 
Gastrointestinal disorders 
Common: nausea, diarrhoea 
Uncommon: abdominal pain, vomiting, dyspepsia, stomach discomfort 
 
Skin and subcutaneous tissue disorders 
Common: sweating 
Uncommon: pruritus, rash 
 
Musculoskeletal and connective tissue disorders 
Very common: joint pain, muscle aches 
Uncommon: back pain, musculoskeletal stiffness, neck pain, muscle spasms, pain in extremity 
 
General disorders and administration site conditions 
Very common: pain at the injection site, fatigue 
Common: redness at the injection site, swelling at the injection site, fever, shivering  
Uncommon: injection site reactions (such as bruising, induration, pruritus, warmth), asthenia, chest 
pain, malaise 
 
Additional data on reactogenicity are available from clinical studies in healthy subjects of various age 
groups from 6 months of age upwards who received an AS03-containing vaccine containing HA from 
H1N1v manufactured using a different process. The available data are as follows: 
 
Adults 
 



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In a clinical study that evaluated the reactogenicity of the first 0.5 ml dose of an AS03-containing 
vaccine containing HA from H1N1v manufactured using a different process in healthy adults aged 18-
60 (N=120) and above 60 years (N=120) the frequency of adverse reactions was similar between age 
groups, except for redness (more common in subjects aged >60 years) and shivering and sweating 
(more common in subjects aged 18-60 years).  
 
In a clinical study that evaluated reactogenicity in healthy adults aged 18-60 years who received two 
0.5 ml doses (21 days apart) of an AS03-containing vaccine containing HA from H1N1v 
manufactured using a different process, there were higher rates of most general solicited symptoms 
(such as fatigue, headache, arthralgia, shivering, sweating and fever) after the second dose compared 
to the first dose. 
 
Children aged 10-17 years 
 
In a clinical study that evaluated the reactogenicity in children 10 to 17 years of age who received two 
0.5 ml doses (21 days apart) of an AS03-containing vaccine containing HA from H1N1v 
manufactured using a different process, there was no increase in reactogenicity after the second dose 
compared to the first dose. Gastro-intestinal symptoms and shivering were reported at higher rates 
compared to the rates reported from studies with AS03-containing vaccine containing HA from H5N1 
manufactured using a different process. 
 
Children aged 3-9 years 
 
In a clinical study that evaluated reactogenicity in children 3 to 5 and 6 to 9 years of age who received 
a single half adult (i.e. 0.25 ml) dose of an AS03-containing vaccine containing HA from H1N1 
manufactured using a different process, the frequency of the following adverse reactions was as shown 
in the table: 
 
Adverse reactions 3-5 years 6-9 years 
Pain 60.0% 63.1% 
Redness 26.7% 23.1% 
Swelling 21.7% 23.1% 
Shivering 13.3% 10.8% 
Sweating 10.0% 6.2% 
Fever >38°C 10.0% 4.6% 
Fever >39°C 1.7% 0.0% 
Diarrhoea 5.0% NA 
Drowsiness 23.3% NA 
Irritability 20.0% NA 
Loss of appetite 20.0% NA 
Arthralgia NA 15.4% 
Myalgia NA 16.9% 
Fatigue NA 27.7% 
Gastrointestinal NA 13.8% 
Headache NA 21.5% 
NA= not available 
 
No data are available at present on reactogenicity after a second half adult (i.e. 0.25 ml) dose of an 
AS03-containing vaccine containing HA from H1N1 manufactured using a different process in 
children aged 3 to 9 years. However, in another clinical study which evaluated reactogenicity in 
children 3 to 9 years who received two adult (i.e. 0.5 ml) doses (21 days apart) of an AS03-containing 
vaccine containing HA from H1N1 manufactured using a different process there was an increase in 
injection site reactions and general symptoms after the second dose compared to the first dose. 
 



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Children aged 6-35 months 
 
In a clinical study that evaluated reactogenicity in children aged 6 to 35 months who received two half 
adult (i.e. 0.25 ml) doses (21 days apart) of an AS03-containing vaccine containing HA from H1N1v 
manufactured using a different process there was an increase in injection site reactions and general 
symptoms after the second dose compared to the first dose particularly in rates of axillary fever 
(≥38°C).  The per-dose frequency of the following adverse reactions was as shown in the table: 
 
Adverse reactions Post dose 1 Post dose 2 
Pain 31.4% 41.2% 
Redness 19.6% 29.4% 
Swelling 15.7% 23.5% 
Fever (≥38°C) axillary 5.9% 43.1% 
Fever (≥39°C) axillary 0.0% 3.9% 
Drowsiness  7.8% 35.3% 
Irritability 21.6% 37.3% 
Loss of appetite 9.8% 39.2% 
 
Reactogenicity was also evaluated in healthy adults aged 18-60 years who received a first 0.5 ml dose 
of either Arepanrix (H1N1) (N=167) or an AS03-containing vaccine containing HA from H1N1v 
manufactured using a different process (N=167). The frequency of adverse reactions was similar 
between the two groups. 
 
• Post-marketing surveillance 
 
AS03-containing vaccine containing HA from H1N1v manufactured using a different process 
 
In addition to the adverse reactions reported in the clinical trials, the following have been reported 
during post-marketing experience with an AS03-containing vaccine containing HA from H1N1v 
manufactured using a different process: 
 
Immune system disorders 
Anaphylaxis, allergic reactions 
 
Nervous system disorders 
Febrile convulsions 
 
Skin and subcutaneous tissue disorders 
Angioedema, generalised skin reactions, urticaria 
 
Interpandemic trivalent vaccines 
 
From Post-marketing surveillance with interpandemic trivalent vaccines, the following adverse 
reactions have also been reported: 
 
Rare:  
Neuralgia, transient thrombocytopenia. 
 
Very rare: 
Vasculitis with transient renal involvement. 
Neurological disorders, such as encephalomyelitis, neuritis and Guillain Barré syndrome. 
 
This medicinal product contains thiomersal (an organomercuric compound) as a preservative and 
therefore, it is possible that sensitisation reactions may occur (see section 4.4). 
 



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4.9 Overdose 
 
No case of overdose has been reported. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Influenza vaccines, ATC Code J07BB02. 
 
This medicinal product has been authorised under a so-called “conditional approval” scheme.  This 
means that further evidence on this medicinal product is awaited. The European Medicines Agency 
(EMEA) will review any new information on this medicine and this SPC will be updated as necessary. 
 
A clinical study with Arepanrix (H1N1) provides limited safety and immunogenicity data obtained up 
to three weeks after administration of a single 0.5 ml dose to healthy adults aged 18-60 years. 
 
Clinical studies with an AS03-containing vaccine containing HA from H1N1v manufactured using a 
different process currently provide: 
 
• Limited safety and immunogenicity data obtained three weeks after administration of a single 

dose to healthy adults aged 18-79 years. 
• Limited safety and immunogenicity data obtained after administration of two doses to healthy 

adults aged 18-60 years. 
• Very limited safety and immunogenicity data obtained three weeks after administration of a 

single dose to healthy adults aged over 80 years. 
• Limited immunogenicity data obtained three weeks after administration of a single dose of 0.25 

ml or 0.5 ml to healthy children aged 10-17 years. 
• Limited safety data obtained after administration of 0.25 ml or two doses of 0.5 ml to healthy 

children aged 10-17 years. 
• Very limited safety and immunogenicity data obtained three weeks after a single administration 

of half the adult dose (i.e. 0.25 ml) to healthy children aged 3-9 years. 
• Very limited safety and immunogenicity data obtained three weeks after a single administration 

of half the adult dose (i.e. 0.25 ml) to healthy children aged 6-35 months. 
 
Clinical studies with a version of Arepanrix containing 3.75 µg HA derived from A/Indonesia/05/2005 
(H5N1) provide additional safety and immunogenicity data in healthy adults, including the elderly. 
 
Immune response to Arepanrix (H1N1) in adults aged 18-60 years: 
 
In a clinical study that evaluated immunogenicity in healthy subjects aged 18-60 years who received 
either Arepanrix (H1N1) (N=167) or an AS03-containing vaccine containing HA from H1N1v 
manufactured using a different process (N=167), the anti-HA antibody responses 21 days after a first 
dose were as follows: 
 
anti-HA antibody Immune response to A/California/7/2009 (H1N1)v-like 
 Arepanrix (H1N1) 

N=164) 
AS03-containing vaccine containing 

HA from H1N1v manufactured using a 
different process 

N=164 
Seroprotection rate1 100% 97.6% 
Seroconversion rate2 97.6% 93.9% 
Seroconversion 41.5 32.0 



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factor3 
1 seroprotection rate: proportion of subjects with haemagglutination inhibition (HI) titre ≥1:40; 
2seroconversion rate: proportion of subjects who were either seronegative at pre-vaccination and have 
a protective post-vaccination titre of ≥1:40, or who were seropositive at pre-vaccination and have a 4-
fold increase in titre;  
3seroconversion factor: ratio of the post-vaccination geometric mean titre (GMT) and the pre-
vaccination GMT. 
 
Immune response to an AS03-containing vaccine containing HA from H1N1v manufactured using a 
different process: 
 
Adults aged 18-60 years 
 
In two clinical studies (D-Pan H1N1-007 and D-Pan H1N1-008) that evaluated immunogenicity in 
healthy subjects aged 18-60 years the anti-HA antibody responses were as follows: 
 
anti-HA 
antibody 

Immune response to A/California/7/2009 (H1N1)v-like 

 D-Pan H1N1-007 D-Pan H1N1-008 
 21 days after 1st dose 21 days after 2nd dose 21 days after 1st dose 
 Total 

enrolled 
subjects 
N=60 

[95% CI] 

Seronegative 
subjects 
prior to 

vaccination 
N=40 

[95% CI] 

Total 
enrolled 
subjects 
N=59 

[95% CI] 

Seronegative 
subjects prior 

to 
vaccination 

N=37 
[95% CI] 

Total 
enrolled 
subjects 
N=120 

[95% CI] 

Seronegative 
subjects prior 
to vaccination 

N=76 
[95% CI] 

Seroprotection 
rate1 

100% 
[94.0;100] 

100% 
[90.5;100] 

100% 
[93.9;100] 

100% 
[90.5;100] 

97.5% 
[92.9;99.5] 

96.1% 
[88.9;99.2] 

Seroconversion 
rate2 

98.3% 
[91.1;100] 

100% 
[90.5;100] 

98.3% 
[90.9;100] 

100% 
[90.5;100] 

95.0% 
[89.4;98.1] 

96.1% 
[88.9;99.2] 

Seroconversion 
factor3 

38.1 47.0 72.9 113.3 42.15 
[33.43.53.16] 

50.73 
[37.84;68.02] 

1 seroprotection rate: proportion of subjects with haemagglutination inhibition (HI) titre ≥1:40; 
2seroconversion rate: proportion of subjects who were either seronegative at pre-vaccination and have 
a protective post-vaccination titre of ≥1:40, or who were seropositive at pre-vaccination and have a 4-
fold increase in titre;  
3seroconversion factor: ratio of the post-vaccination geometric mean titre (GMT) and the pre-
vaccination GMT. 
 
Elderly (>60 years) 
 
Study D-Pan H1N1-008 evaluated immunogenicity in healthy subjects (N=120) aged >60 years 
(stratified in ranges from 61 to 70, 71 to 80 and > 80 years of age).  The anti-HA antibody responses 
21 days after a first dose were as follows: 
 
anti-HA 
antibody 

Immune response to A/California/7/2009 (H1N1)v-like 

 61-70 years 71-80 years >80 years 
 Total 

enrolled 
subjects 
N=75 

[95% CI] 

Seronegative 
subjects prior 

to 
vaccination 

N=43 
[95% CI] 

Total 
enrolled 
subjects 
N=40 

[95% CI] 

Seronegative 
subjects prior 

to 
vaccination 

N=23 
[95% CI] 

Total 
enrolled 
subjects 

N=5 
[95% CI] 

Seronegative 
subjects prior 

to 
vaccination 

N=3 
[95% CI] 



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Seroprotection 
rate1 

88.0% 
[78.4;94.4] 

81.4% 
[66.6;91.6] 

87.5% 
[73.2;95.8]

82.6% 
[61.2;95.0] 

80.0% 
[28.4;99.5] 

66.7% 
[9.4;99.2] 

Seroconversion 
rate2 

80.0% 
[69.2;88.4] 

81.4% 
[66.6;91.6] 

77.5% 
[61.5;89.2]

82.6% 
[61.2;95.0] 

80.0% 
[28.4;99.5] 

66.7% 
[9.4;99.2] 

Seroconversion 
factor3 

13.5 
[10.3;17.7] 

20.3 
[13.94;28.78]

13.5 
[8.6;21.1] 

20.67 
[11.58;36.88]

18.4 
[4.3;78.1] 

17.95 
[0.55;582.25]

1 seroprotection rate: proportion of subjects with haemagglutination inhibition (HI) titre ≥1:40; 
2seroconversion rate: proportion of subjects who were either seronegative at pre-vaccination and have 
a protective post-vaccination titre of ≥1:40, or who were seropositive at pre-vaccination and have a 4-
fold increase in titre;  
3seroconversion factor: ratio of the post-vaccination geometric mean titre (GMT) and the pre-
vaccination GMT. 
 
Children aged 10-17 years 
 
Two clinical studies evaluated the immunogenicity of a half (0.25 ml) dose and a full (0.5 ml) adult 
dose in healthy children 10 to 17 years of age.  The anti-HA antibody responses 21 days after a first 
dose were as follows: 
 
anti-HA antibody Immune response to A/California/7/2009 (H1N1)v-like 
 Half dose Full dose 
 Total enrolled 

subjects 
N=58 

[95% CI] 

Seronegative 
subjects prior to 

vaccination 
N=38 

[95% CI] 

Total enrolled 
subjects 
N=97 

[95% CI] 

Seronegative 
subjects prior to 

vaccination 
N=61 

[95% CI] 
Seroprotection 
rate1 

98.3% 
[90.8;100] 

97.4% 
[86.2;99.9] 

100% 
[96.3;100] 

100% 
[94.1;100] 

Seroconversion 
rate2 

96.6% 
[88.1;99.6] 

97.4% 
[86.2;99.9] 

96.9% 
[91.2;99.4] 

100% 
[94.1;100] 

Seroconversion 
factor3 

46.7 
[34.8;62.5] 

67.0 
[49.1;91.3] 

69.0 
[52.9;68.4] 

95.8 
[78.0;117.7] 

1 seroprotection rate: proportion of subjects with haemagglutination inhibition (HI) titre ≥1:40; 
2seroconversion rate: proportion of subjects who were either seronegative at pre-vaccination and have 
a protective post-vaccination titre of ≥1:40, or who were seropositive at pre-vaccination and have a 4-
fold increase in titre;  
3seroconversion factor: ratio of the post-vaccination geometric mean titre (GMT) and the pre-
vaccination GMT. 
 
Children aged 3 to 9 years 
 
In a clinical study in which children aged 3 to 9 years old received a half adult dose (0.25 ml) of 
AS03-adjuvanted vaccine containing 3.75 µg HA derived from A/California/7/2009 (H1N1)v-like the 
anti-HA antibody responses 21 days after a first dose were as follows: 
 
anti-HA antibody Immune response to A/California/7/2009 (H1N1)v-like 
 3-5 years 6-9 years 

 Total enrolled 
subjects 
N=30 

[95% CI] 

Seronegative 
subjects prior to 

vaccination 
N=27 

[95% CI] 

Total enrolled 
subjects 
N=30 

[95% CI] 

Seronegative 
subjects prior to 

vaccination 
N=29 

[95% CI] 
Seroprotection 
rate1 

100% 
[88.4;100] 

100% 
[87.2;100] 

100% 
[88.4;100] 

100% 
[88.1;100] 



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Seroconversion 
rate2 

100% 
[88.4;100] 

100% 
[87.2;100] 

100% 
[88.4;100] 

100% 
[88.1;100] 

Seroconversion 
factor3 

32.4 
[25.4;41.2] 

36.4 
[29.1;45.4] 

36.3 
[28.0;47.2] 

37.4 
[28.7;48.7] 

1 seroprotection rate: proportion of subjects with haemagglutination inhibition (HI) titre ≥1:40; 
2seroconversion rate: proportion of subjects who were either seronegative at pre-vaccination and have 
a protective post-vaccination titre of ≥1:40, or who were seropositive at pre-vaccination and have a 4-
fold increase in titre;  
3seroconversion factor: ratio of the post-vaccination geometric mean titre (GMT) and the pre-
vaccination GMT. 
 
Children aged 6-35 months 
 
In a clinical study in healthy children 6 months to 35 months of age (stratified in ranges from 6 to 11, 
12 to 23 and 24-35 months of age) the anti-HA antibody responses 21 days after a first and a second 
half adult dose (i.e. 0.25 ml) were as follows: 
 
anti-HA antibody Immune response to A/California/7/2009 (H1N1)v-like 
 6-11 months 12-23 months4 24-35 months4 
 Post dose 

1 
Post dose 

2 
Post dose 1 Post dose 

1 
Post 

dose 2 
Post 

dose 1 
Post 

dose 2 
 Total enrolled subjects 

 [95% CI] 
Seronegative 
subjects prior 

to 
vaccination 
 [95% CI] 

Total enrolled 
subjects 

 [95% CI] 

Total enrolled 
subjects 

 [95% CI] 

 N=17 
 

N = 17 N=14 
 

N=17 
 

N= 16 N=16 
 

N= 17 

Seroprotection 
rate1 

100% 
[80.5; 
100] 

100% 
[80.5; 
100] 

 

100% 
[76.8;100] 

100% 
[80.5; 
100] 

100% 
[79.4; 
100] 

100% 
[79.4; 
100] 

100% 
[80.5; 
100] 

Seroconversion 
rate2 

94.1% 
[71.3; 
99.9] 

100% 
[80.5; 
100] 

 

100% 
[76.8;100] 

100% 
[80.5; 
100] 

100% 
[79.4; 
100] 

 

100% 
[79.4; 
100] 

100% 
[80.5; 
100] 

Seroconversion 
factor3 

44.4 
[24.1; 
81.5] 

221.9 
[102.6; 
480.2] 

70.67 
[51.91; 
96.20] 

76.9 
[55.7; 
106.1] 

378.0 
[282.0; 
506.7] 

53.8 
[40.7; 
71.1] 

409.1 
[320.7; 
521.9] 

1 seroprotection rate: proportion of subjects with haemagglutination inhibition (HI) titre ≥1:40; 
2seroconversion rate: proportion of subjects who were either seronegative at pre-vaccination and have 
a protective post-vaccination titre of ≥1:40, or who were seropositive at pre-vaccination and have a 4-
fold increase in titre;  
3seroconversion factor: ratio of the post-vaccination geometric mean titre (GMT) and the pre-
vaccination GMT. 
4all subjects seronegative prior to vaccination 
 
The clinical relevance of the haemagglutination inhibition (HI) titre ≥1:40 in children is unknown. 
 
Analysis of a subset of 36 subjects aged 6 months to 35 months old showed that 80.6 % had a 4 fold 
increase in serum neutralising antibodies 21 days after the first dose (66.7 % in 12 subjects aged 6 to 
11 months old, 91.7 % in 12 subjects aged 12 to 23 months old and 83.3 % in 12 subjects aged 24 to 
35 months old). 
 



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Immune response to a version of Arepanrix containing 3.75 µg HA derived from A/Indonesia/05/2005 
(H5N1): 
 
Three clinical studies have evaluated the immunogenicity of a version of Arepanrix containing 3.75 µg 
HA derived from A/Indonesia/05/2005 (H5N1) in subjects from the age of 18 years onwards following 
a 0, 21 days schedule. 
 
In a consistency study, the anti-haemagglutinin (anti-HA) antibody responses twenty-one days and six 
months after the second dose were as follows: 
 
anti-HA antibody Immune response to A/Indonesia/5/2005 
 18-60 years >60 years 
 Day 42 

N=1,488 
Day 180 
N=353 

Day 42 
N=479 

Day 180 
N=104 

Seroprotection rate1 91% 62% 76.8% 63.5% 
Seroconversion rate2 91% 62% 76.4% 62.5% 
Seroconversion factor3 51.4 7.4 17.2 7.8 
1seroprotection rate (i.e. proportion of subjects with HI titre ≥ 1:40); 
2seroconversion rate (i.e. proportion of subjects who were either seronegative at pre-vaccination and 
have a protective post-vaccination titre of ≥ 1:40, or who were seropositive at pre-vaccination and 
have a 4-fold increase in titre); 
3seroconversion factor (i.e. ratio of the post-vaccination GMT and the pre-vaccination GMT) 
 
Twenty-one days after the second dose, a 4-fold increase in serum neutralising antibody against 
A/Indonesia/5/2005 was achieved in 94.4% of subjects aged 18-60 years and in 80.4% of subjects over 
60 years of age. 
 
In another clinical study, the anti-haemagglutinin (anti-HA) antibody responses in subjects aged 18-64 
years were as follows: 
 

anti-HA antibody Immune response to A/Indonesia/5/2005 
 Day 21 

N=145 
Day 42 
N=145 

Day 180 
N=141 

Seroprotection rate1 42.1% 97.2% 54.6% 
Seroconversion rate2 42.1% 97.2% 54.6% 
Seroconversion factor3 4.5 92.9 5.6 
1seroprotection rate (i.e. proportion of subjects with HI titre ≥ 1:40); 
2seroconversion rate (i.e. proportion of subjects who were either seronegative at pre-vaccination and 
have a protective post-vaccination titre of ≥ 1:40, or who were seropositive at pre-vaccination and 
have a 4-fold increase in titre); 
3seroconversion factor (i.e. ratio of the post-vaccination GMT and the pre-vaccination GMT) 
 
A 4-fold increase in serum neutralising antibody titres against A/Indonesia/5/2005 was achieved in 
76.6% of subjects at day 21, 97.9% at day 42 and 91.5% at day 180. 
 
Cross-reactive immune responses elicited by a version of Arepanrix containing 3.75 µg HA derived 
from A/Indonesia/05/2005 (H5N1): 
 
In the consistency study, a 4-fold increase in serum neutralising antibody against 
A/Vietnam/1194/2004 was at day 42 achieved in 65.5% of subjects aged 18-60 years and in 24.1% of 
subjects over 60 years of age. 
 



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In another clinical study, anti-HA responses against A/Vietnam/1194/2004 following administration of 
a version of Arepanrix containing 3.75 µg HA derived from A/Indonesia/05/2005 (H5N1) were as 
follows: 
 
anti-HA antibody Immune response to A/Vietnam/1194/2004 
 Day 21 

N=145 
Day 42 
N=145 

Day 180 
N=141 

Seroprotection rate1 15.2% 64.1% 10.6% 
Seroconversion rate2 13.1% 62.1% 9.2% 
Seroconversion factor3 1.9 7.6 1.7 
1seroprotection rate (i.e. proportion of subjects with HI titre ≥ 1:40); 
2seroconversion rate (i.e. proportion of subjects who were either seronegative at pre-vaccination and 
have a protective post-vaccination titre of ≥ 1:40, or who were seropositive at pre-vaccination and 
have a 4-fold increase in titre); 
3seroconversion factor (i.e; ratio of the post-vaccination GMT and the pre-vaccination GMT) 
 
A 4-fold increase in serum neutralising antibody against A/Vietnam/1194/2004 was achieved in 44.7% 
of subjects at day 21, 53.2% at day 42 and 38.3% at day 180. 
 
Information from non-clinical studies: 
 
The ability to induce protection against homologous and heterologous vaccine strains was assessed 
non-clinically with A/Indonesia/05/05 (H5N1) using ferret challenge models. 
 
- Challenge with a homologous pandemic H5N1 strain (A/Indonesia/5/05) 

In this protection experiment, the ferrets (six ferrets/group) were immunized intramuscularly with 
vaccine candidate containing three different doses of H5N1 antigen (7.5, 3.8 and 1.9 µg of HA 
antigen) adjuvanted with the standard dose or half dose of AS03. Control groups included ferrets 
immunized with adjuvant alone and non-adjuvanted vaccine (7.5 micrograms HA). Ferrets immunized 
with the non adjuvanted H5N1 influenza vaccine were not protected from death and showed similar 
lung viral loads and degree of viral shedding in the upper respiratory tract as those exhibited by ferrets 
immunized with the adjuvant alone. Conversely the combination of a range of doses of H5N1 antigen 
with AS03 adjuvant was able to protect against mortality and to reduce lung virus loads and viral 
shedding after intra-tracheal challenge with a homologous wild type H5N1 virus.  Serological testing 
indicated a direct correlation between vaccines induced HI and neutralising antibody titres in protected 
animals compared to antigen and adjuvant controls. 
 
- Challenge with a heterologous pandemic H5N1 strain (A/Hong Kong/156/97) 

In this protection experiment, the ferrets (six ferrets/group) were immunized intramuscularly with 
vaccine candidate containing four different doses of H5N1 antigen (3.75, 1.5, 0.6 and 0.24 µg of HA 
antigen) adjuvanted with half dose of AS03. In addition, one group of six ferrets were immunized with 
vaccine candidate containing 3.75 µg H5N1 + full dose of AS03 and one control group included 
ferrets immunized with non-adjuvanted vaccine (3.75 micrograms HA). The results of this 
heterologous challenge study indicate 80.7%-100% protection in all adjuvanted candidate vaccines 
compared to 43% protection with the non adjuvanted vaccine, showing the benefit of AS03 
adjuvantation. 
 
5.2 Pharmacokinetic properties 
 
Not applicable. 
 
5.3  Preclinical safety data 
 



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Non-clinical data obtained with a version of Arepanrix containing 3.75 µg HA derived from 
A/Indonesia/05/2005 (H5N1) reveal no special hazard for humans based on conventional studies of 
safety pharmacology, acute and repeated dose toxicity, local tolerance, female fertility, embryo-fetal 
and postnatal toxicity (up to the end of the lactation period). 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Suspension vial: 
Thiomersal 
Sodium chloride (NaCl) 
Disodium hydrogen phosphate (Na2HPO4) 
Potassium dihydrogen phosphate (KH2PO4) 
Potassium chloride (KCl) 
Water for injections 
 
Emulsion vial: 
Sodium chloride (NaCl) 
Disodium hydrogen phosphate (Na2HPO4) 
Potassium dihydrogen phosphate (KH2PO4) 
Potassium chloride (KCl) 
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 
 
12 months. 
After mixing, the vaccine should be used within 24 hours. Chemical and physical in-use stability has 
been demonstrated for 24 hours at 25°C. 
 
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 
 
One pack containing: 
- one pack of 50 vials (type I glass) of 2.5 ml suspension with a stopper (butyl rubber). 
- two packs of 25 vials (type I glass) of 2.5 ml emulsion with a stopper (butyl rubber). 
 
The volume after mixing 1 vial of suspension (2.5 ml) with 1 vial of emulsion (2.5 ml) corresponds to 
10 doses of vaccine (5 ml). 
 
6.6 Special precautions for disposal and other handling 
 



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Arepanrix consists of two containers:  
Suspension: multidose vial containing the antigen,  
Emulsion: multidose vial containing the adjuvant.  
 
Prior to administration, the two components should be mixed. 
 
Instructions for mixing and administration of the vaccine: 
 
1. Before mixing the two components, the emulsion (adjuvant) and suspension (antigen) should be 

allowed to reach room temperature.  Whitish sediments may be observed in the suspension vial; 
these sediments are part of the normal physical appearance of the suspension.  The emulsion 
presents as a whitish appearance. 

2. Each vial should be shaken and inspected visually for any foreign particulate matter (other than 
the white sediments described above) and/or abnormal physical appearance. In the event of 
either being observed (including rubber particles from the stopper), discard the vaccine. 

3. The vaccine is mixed by withdrawing the entire contents of the vial containing the adjuvant by 
means of a syringe and by adding it to the vial containing the antigen.  

4. After the addition of the adjuvant to the antigen, the mixture should be well shaken. The mixed 
vaccine is a whitish emulsion.  In the event of other variation being observed, discard the 
vaccine. 

5. The volume of the Arepanrix vial after mixing is at least 5 ml. The vaccine should be 
administered in accordance with the recommended posology (see section 4.2). 

6. The vial should be shaken prior to each administration and inspected visually for any foreign 
particulate matter and/or abnormal physical appearance.  In the event of either being observed 
(including rubber particles from the stopper), discard the vaccine. 

7. Each vaccine dose of 0.5 ml (full dose) or 0.25 ml (half dose) is withdrawn into a syringe for 
injection and administered intramuscularly.  

8. After mixing, use the vaccine within 24 hours. The mixed vaccine can either be stored in a 
refrigerator (2°C – 8°C) or at room temperature not exceeding 25°C. If the mixed vaccine is 
stored in a refrigerator, it should be allowed to reach room temperature before each withdrawal. 

 
Any unused 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/1/10/624/001 
 
 
9.  DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 23/03/2010 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency (EMEA) http://www.emea.europa.eu/. 

http://www.emea.europa.eu/


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  17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 ANNEX II 
 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE 
SUBSTANCE AND MANUFACTURING AUTHORISATION 
HOLDER RESPONSIBLE FOR BATCH RELEASE 

 
B. CONDITIONS OF THE MARKETING AUTHORISATION 
 
C. SPECIFIC OBLIGATIONS TO BE FULFILLED BY THE 

MARKETING AUTHORISATION HOLDER 
 

 



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  18 

 
A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 

MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH 
RELEASE 

 
Name and address of the manufacturer of the biological active substance 
 
IB Biomedical Corporation of Quebec doing business as 
GlaxoSmithKline Biologicals North America 
2323 du parc Technologique Blvd. 
Saint-Foy, Quebec, 
Canada G1P 4R8 
 
Name and address of the manufacturer responsible for batch release 
 
GlaxoSmithKline Biologicals S.A. 
89, rue de l'Institut 
B-1330 Rixensart 
Belgium 
 
 
B. CONDITIONS OF THE MARKETING AUTHORISATION 
 
• CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON 

THE MARKETING AUTHORISATION HOLDER 
 
Medicinal product subject to medical prescription. 
 
Arepanrix can only be marketed when there is an official WHO/EU declaration of an influenza 
pandemic, on the condition that the Marketing Authorisation Holder for Arepanrix takes due account 
of the officially declared pandemic strain. 
 
• CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• The Applicant/MAH shall agree with Member States to measures facilitating the identification 

and traceability of the A/H1N1 pandemic vaccine administered to each patient, in order to 
minimise medication errors and aid patients and health care professionals to report adverse 
reactions. The MAH should check regarding the possible confounding layouts with other 
pandemic vaccine supplied in EU. 

 
• The Applicant/MAH shall agree with Member States on mechanisms allowing patients and 

health care professionals to have continuous access to updated information regarding Arepanrix.   
 
• The Applicant/MAH shall agree with Member Sates on the provision of a targeted 

communication to healthcare professionals which should address the following: 
 

• The correct way to prepare the vaccine prior to administration. 
 
• Adverse events to be prioritised for reporting, i.e. fatal and life-threatening adverse 

reactions, unexpected severe adverse reactions, adverse events of special interest (AESI). 
 
• The minimal data elements to be transmitted in individual case safety reports in order to 

facilitate the evaluation and the identification of the vaccine administered to each subject, 
including the invented name, the vaccine manufacturer and the batch number. 



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  19 

 
• If a specific notification system has been put in place, how to report adverse reactions. 

 
 
• OTHER CONDITIONS 
 
Official batch release: in accordance with Article 114 Directive 2001/83/EC as amended, the official 
batch release will be undertaken by a state laboratory or a laboratory designated for that purpose. 
 
Pharmacovigilance system 
The MAH must ensure that the system of pharmacovigilance, as described in version 3.05 (dated 
September 2009) presented in Module 1.8.1 of the marketing authorisation application, is in place and 
functioning before the product is placed on the market and for as long as the marketed product remains 
in use. 
 
PSUR submission during the influenza pandemic:  
 
During a pandemic situation, the frequency of submission of periodic safety update reports specified 
in Article 24 of Regulation (EC) No 726/2004 will not be adequate for the safety monitoring of a 
pandemic vaccine for which high levels of exposure are expected within a short period of time.  Such 
situation requires rapid notification of safety information that may have the greatest implications for 
benefit-risk balance in a pandemic. Prompt analysis of cumulative safety information, in light of the 
extent of exposure, will be crucial for regulatory decisions and protection of the population to be 
vaccinated.  The MAH shall submit on a monthly basis a simplified periodic safety update report with 
the timelines, format and content as defined in the CHMP Recommendations for the 
Pharmacovigilance Plan as part of the Risk Management Plan to be submitted with the Marketing 
Authorisation Application for a Pandemic Influenza Vaccine (EMEA/359381/2009) and any 
subsequent update. 
 
Risk Management Plan 
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in 
the Pharmacovigilance Plan, as agreed in version 4 (dated January 2010) of the Risk Management Plan 
(RMP) presented in Module 1.8.2. of the Marketing Authorisation Application and any subsequent 
updates of the RMP agreed by the CHMP. 
 
 
C. SPECIFIC OBLIGATIONS TO BE FULFILLED BY THE MARKETING 

AUTHORISATION HOLDER 
 
The Applicant/Marketing Authorisation Holder shall complete the following programme of studies 
within the specified time frame, the results of which shall form the basis of the continuous 
reassessment of the benefit/risk profile. 
 

Area Description 
 

Due Date 

Quality The Applicant/MAH commits not to release lots prepared 
using the extended formulation/fill process until the 
relevant validation data have been submitted and 
approved (RR#7Q5) 

31-January-2010 
 

Quality The Applicant/MAH commits to set a maximum decrease 
of 20% of HA content for the Drug Substance and to 
review when data for H1N1 become available. 
(Arise from Q1 RR#13) 

26-February-2010 

Clinical The Applicant/MAH commits to provide abridged report 
for the following study performed in children 

 
 

http://www.emea.europa.eu/pdfs/human/pandemicinfluenza/35938109en.pdf
http://www.emea.europa.eu/pdfs/human/pandemicinfluenza/35938109en.pdf
http://www.emea.europa.eu/pdfs/human/pandemicinfluenza/35938109en.pdf


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  20 

Study Q-Pan H1N1-003 (6 months-8 yrs, Dose finding,) 
 

- abridged report for post dose 1 Wave 1 
immuno data, solicited and unsolicited 
symptoms, SAEs ) 

 
-  abridged report for post dose 2 Waves 1 and 

2 (immuno data, solicited and unsolicited 
symptoms, SAEs ) 

 
 
05 March 2010 
 
 
 
04 June 2010  

Clinical The Applicant/MAH commits to provide abridged report 
for the following study performed in adults: 
Study Q-Pan H1N1-001 abridged report for post dose 1 
and post dose 2 (≥ 18 yrs, Dose finding, adjuvanted 
vaccine vs plain) 
 

 
30 April 2010 

Clinical The Applicant/MAH commits to provide abridged report 
for the following study performed in adults 
Study Q-Pan H1N1-019 (18-60 yrs, TIV effect and co-
administration) 
 
-   abridged report for post dose 3 (immuno & solicited 
and unsolicited symptoms, SAEs) 

 
 
 
 
 
04 June 2010  

Clinical The Applicant/MAH commits to provide abridged report 
for the following study performed in children 
Study Q-Pan H1N1-031 (9-17 yrs, Safety/ 
Immunogenicity) 
-   abridged report for post dose 1 & post dose 2 (immuno 
& solicited and unsolicited symptoms, SAEs ) 

 
 
 
 
04 June 2010  

Clinical The Applicant/MAH commits to provide abridged report 
for the following study performed in children 
Study Q-Pan H1N1-032 (2-5 months, Safety/ 
Immunogenicity) 
-   abridged report for post dose 1 & post dose 2 (immuno 
& solicited and unsolicited symptoms, SAEs ) 

 
 
 
 
08 July 2010 
(pending on 
enrolment of 
subjects and data 
availability) 

Pharmacovigilance The Applicant/MAH will support one prospective and 
one retrospective cohort safety study with Arepanrix, in at 
least 9,000 patients, in accordance with the protocols 
submitted with the Risk Management Plan. Interim and 
final results will be submitted one week after being 
available.  
 

Timelines described 
in the RMP 
 
Prospective cohort: 
initiated 23 Oct 
2009; First endpoints 
available in Feb 
2010 
Retrospective 
cohort: to be 
initiated in Feb 
2010; Preliminary 
analysis in April 

Pharmacovigilance The Applicant/MAH commits to provide the results of a 
study in a pregnancy registry conducted with Arepanrix.  

 
 
 
Results, including all 
preliminary analysis, 



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  21 

have to be provided 
in the (simplified) 
PSUR 

Pharmacovigilance The Applicant/MAH commits to support an effectiveness 
study with Arepanrix ongoing and submit the results one 
week after being available. 

Results submitted 1 
week after being 
available. 
 
Study initiated in 
October 2009; Final 
report foreseen in 
April 2010 
 

Pharmacovigilance The Applicant/MAH commits to support a Post-
authorisation study in immunocompromised subjects 
(adults with HIV) being conducted by PCIRN (Public 
Health Agency of Canada - Canadian Institutes of Health 
Research Influenza Research Network) and provide the 
final result 

Updated status and 
available results, 
including all 
preliminary analysis, 
have to be provided 
in the (simplified) 
PSUR 
  

Pharmacovigilance The Applicant/MAH commits to establish the 
mechanisms to promptly investigate issues affecting the 
benefit-risk balance of the vaccine.  
 
The MAH should provide an inventory of all valuable 
database ready to be use to promptly investigate issues 
affecting the benefit-risk balance of the vaccine.  
Details regarding databases (e.g., data sources, 
characteristics of the data, potential analysis) need to be 
reported. 

The characteristics 
and the validity of 
these sources is to be 
agreed with EMEA 
within 1 month of 
the Commission 
Decision granting 
the Marketing 
Authorisation in 
order to conduct 
additional studies for 
emerging benefit-
risk evaluation. 

 



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  22 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



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  23 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



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  24 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
PACK CONTAINING 1 PACK OF 50 VIALS OF SUSPENSION AND 2 PACKS OF 25 VIALS 
OF EMULSION 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Arepanrix suspension and emulsion for emulsion for injection. 
Pandemic influenza vaccine (H1N1) (split virion, inactivated, adjuvanted) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
After mixing, 1 dose (0.5 ml) contains: 
 
Split influenza virus inactivated, containing antigen equivalent to: 
 
A/California/7/2009 (H1N1)v-like strain (X-179A) 3.75 micrograms* 
 
AS03 adjuvant composed of squalene, DL-α-tocopherol and polysorbate 80 
 
* haemagglutinin 
 
 
3. LIST OF EXCIPIENTS 
 
Thiomersal 
Sodium chloride (NaCl) 
Disodium hydrogen phosphate (Na2HPO4) 
Potassium dihydrogen phosphate (KH2PO4) 
Potassium chloride (KCl) 
Water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension and emulsion for emulsion for injection  
 
50 vials: suspension (antigen) 
50 vials: emulsion (adjuvant) 
 
The volume after mixing 1 vial of suspension (2.5 ml) with 1 vial of emulsion (2.5 ml) corresponds to 
10 doses of vaccine (5 ml) 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intramuscular use 
Shake before use 
Read the package leaflet before use 
 
 



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6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE REACH AND SIGHT OF CHILDREN 

 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Suspension and emulsion to be mixed before administration 
 
 
8. EXPIRY DATE 
 
EXP: 
 
 
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 

 
Dispose of in accordance with local regulations 
 
 
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/1/10/624/001 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 



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16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
PACK OF 50 VIALS OF SUSPENSION (ANTIGEN) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Suspension for emulsion for injection for Arepanrix 
Pandemic influenza vaccine (H1N1) (split virion, inactivated, adjuvanted) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Split influenza virus, inactivated, containing antigen* equivalent to: 
 3.75 micrograms haemagglutinin/dose 
*Antigen: A/California/7/2009 (H1N1)v-like strain (X-179A) 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: Thiomersal, sodium chloride, disodium hydrogen phosphate, potassium dihydrogen 
phosphate, potassium chloride, water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Antigen suspension for injection 
50 vials: suspension 
2.5 ml per vial.  
After mixing with adjuvant emulsion: 10 doses of 0.5 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intramuscular use 
Shake before use 
Read the package leaflet before use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Suspension to be exclusively mixed with adjuvant emulsion before administration 
 
 
8. EXPIRY DATE 
 



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EXP 
 
 
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 
 
GSK Biologicals, Rixensart - Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/10/624/001 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
PACK OF 25 VIALS OF EMULSION (ADJUVANT) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Emulsion for emulsion for injection for Arepanrix 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Content: AS03 adjuvant composed of squalene (10.69 milligrams), DL-α-tocopherol (11.86 
milligrams) and polysorbate 80 (4.86 milligrams) 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: Sodium chloride, disodium hydrogen phosphate, potassium dihydrogen phosphate, 
potassium chloride, water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Adjuvant emulsion for injection 
25 vials: emulsion 
2.5 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intramuscular use 
Shake before use 
Read the package leaflet before use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Emulsion to be exclusively mixed with antigen suspension before administration 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



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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 
 
GSK Biologicals, Rixensart - Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/10/624/001 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
SUSPENSION VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Antigen suspension for Arepanrix 
Pandemic influenza vaccine 
A/California/7/2009 (H1N1)v-like strain (X-179A)  
I.M. 
 
 
2. METHOD OF ADMINISTRATION 
 
Mix with adjuvant emulsion before use 
 
 
3. EXPIRY DATE 
 
EXP 
After mixing: Use within 24 hours and do not store above 25°C. 
Date and time of mixing: 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
2.5 ml 
After mixing with adjuvant emulsion: 10 doses of 0.5 ml 
 
 
6. OTHER 
 
Storage (2ºC-8ºC), do not freeze, protect from light 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
EMULSION VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Adjuvant emulsion for Arepanrix 
I.M. 
 
 
2. METHOD OF ADMINISTRATION 
 
Mix into Antigen suspension before use 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
2.5 ml 
 
 
6. OTHER 
 
Storage (2ºC-8ºC), do not freeze, protect from light 



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  33 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 



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PACKAGE LEAFLET: INFORMATION FOR THE USER 

 
Arepanrix suspension and emulsion for emulsion for injection 

Pandemic influenza vaccine (H1N1) (split virion, inactivated, adjuvanted) 
 

For the most up-to-date information please consult the website of the European Medicines 
Agency (EMEA): http://www.emea.europa.eu/. 

 
Read all of this leaflet carefully before you receive this vaccine. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or nurse. 
- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor. 
 
In this leaflet:  
1. What Arepanrix is and what it is used for 
2. Before you receive Arepanrix 
3. How Arepanrix is given 
4. Possible side effects 
5. How to store Arepanrix 
6. Further information 
 
 
1. What Arepanrix is and what it is used for 
 
Arepanrix is a vaccine against a pandemic influenza (flu).  
 
Pandemic flu is a type of influenza that occurs every few decades and which spreads rapidly around 
the world. The symptoms of pandemic flu are similar to those of ordinary flu but may be more severe. 
 
When a person is given the vaccine, the immune system (the body’s natural defence system) will 
produce its own protection (antibodies) against the disease. None of the ingredients in the vaccine can 
cause flu. 
 
As with all vaccines, Arepanrix may not fully protect all persons who are vaccinated. 
 
 
2. Before you are given Arepanrix 
 
You should not receive Arepanrix: 
 
• if you have previously had a sudden life-threatening allergic reaction to any ingredient of 

Arepanrix (these are listed at the end of the leaflet) or to any of the substances that may be 
present in trace amounts as follows: egg and chicken protein, ovalbumin, formaldehyde or 
sodium deoxycholate. Signs of an allergic reaction may include itchy skin rash, shortness of 
breath and swelling of the face or tongue. However, in a pandemic situation, it may be 
appropriate for you to have the vaccine provided that appropriate medical treatment is 
immediately available in case of an allergic reaction. 

 
If you are not sure, talk to your doctor or nurse before having this vaccine. 
 
Take special care with Arepanrix: 
 
• if you have had any allergic reaction other than a sudden life-threatening allergic reaction to any  

http://www.emea.europa.eu/


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  35 

ingredient contained in the vaccine, to thiomersal, to egg and chicken protein, ovalbumin, 
formaldehyde  or to sodium deoxycholate. (see section 6. Further information). 

• if you have a severe infection with a high temperature (over 38°C). If this applies to you then 
your vaccination will usually be postponed until you are feeling better. A minor infection such 
as a cold should not be a problem, but your doctor will advise whether you could still be 
vaccinated with Arepanrix. 

• if you have a poor immune response (as for example because of immunosuppressive therapy, 
e.g. corticosteroid treatments or chemotherapy for cancer), 

• if you are having a blood test to look for evidence of infection with certain viruses. In the first 
few weeks after vaccination with Arepanrix the results of these tests may not be correct. Tell the 
doctor requesting these tests that you have recently been given Arepanrix. 

In any of these cases, TELL YOUR DOCTOR OR NURSE, as vaccination may not be recommended, 
or may need to be delayed. 
 
If your child receives the vaccine, you should be aware that the side effects may be more intense after 
the second dose, especially temperature over 38°C. Therefore monitoring of temperature and measures 
to lower the temperature (such as giving paracetamol or other medicines that lower fever) after each 
dose are recommended.  
 
Please inform your doctor or nurse if you have a bleeding problem or bruise easily. 
 
Taking other medicines 
Please tell your doctor or nurse if you are taking or have recently taken any other medicines, including 
medicines obtained without a prescription or have recently been given any other vaccine. 
 
Areapanrix can be given at the same time as seasonal influenza vaccines that do not contain an 
adjuvant. 
 
Persons who have received a seasonal influenza vaccine that does not contain an adjuvant may receive 
Arepanrix after an interval of at least three weeks. 
 
There is no information on administration of Arepanrix with other vaccines and no information on 
administration of the AS03-containing vaccine containing HA from H1N1v manufactured using a 
different process with any other vaccines than non-adjuvanted seasonal influenza vaccine. However, if 
this cannot be avoided, the vaccines should be injected into separate limbs.  In such cases, you should 
be aware that the side effects may be more intense.  
 
Pregnancy and breast-feeding 
Tell your doctor if you are pregnant, think you may be pregnant, plan to become pregnant. You should 
discuss with your doctor whether you should receive Arepanrix. 
The vaccine may be used during breast-feeding. 
 
Driving and using machines 
Some effects mentioned under section 4. “Possible side effects” may affect the ability to drive or use 
machines. 
 
Important information about some of the ingredients of Arepanrix 
This vaccine contains thiomersal as a preservative and it is possible that you may experience an 
allergic reaction. Tell your doctor if you have any known allergies. 
 
This medicinal product contains less than 1 mmol sodium (23 mg) and less than 1 mmol of potassium 
(39 mg) per dose, i.e. essentially sodium- and potassium-free. 
 
 



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3. How Arepanrix is given 
 
Your doctor or nurse will administer the vaccine in accordance with official recommendations. 
 
The vaccine will be injected into a muscle (usually in the upper arm).  
 
Adults including the elderly and children from the age of 10 years onwards: 
A dose (0.5 ml) of the vaccine will be given 
Clinical data with an AS03-containing vaccine containing HA from H1N1v manufactured using a 
different process suggest that a single dose may be sufficient. 
If a second dose is administered there should be an interval of at least three weeks between the first 
and second dose. 
 
Children from 6 months to 9 years of age 
A dose (0.25 ml) of the vaccine will be given.  
If a second dose of 0.25 ml is given this will be administered at least three weeks after the first dose.  
 
Children aged less than 6 months of age 
Vaccination is currently not recommended in this age group. 
 
When Arepanrix is given for the first dose, it is recommended that Arepanrix (and not another vaccine 
against H1N1) be given for the complete vaccination course. 
 
 
4. Possible side effects 
 
Like all medicines, Arepanrix can cause side effects, although not everybody gets them. 
 
Allergic reactions may occur following vaccination, in rare cases leading to shock. Doctors are aware 
of this possibility and have emergency treatment available for use in such cases. 
 
The frequency of possible side effects listed below is defined using the following convention: 
 
Very common (affects more than 1 user in 10) 
Common (affects 1 to 10 users in 100) 
Uncommon (affects 1 to 10 users in 1,000) 
Rare (affects 1 to 10 users in 10,000) 
Very rare (affects less than 1 user in 10,000) 
 
The side effects listed below have occurred with Arepanrix (H5N1) in clinical studies in adults, 
including the elderly. In these clinical studies most side effects were mild in nature and short term. 
The side-effects are generally similar to those related to seasonal flu vaccines.  
 
These side effects have also been observed with similar frequencies in clinical studies in adults 
including the elderly and in children aged 10 to 17 years with a similar vaccine (H1N1), except for 
redness (uncommon in the adults and common in the elderly) and fever (uncommon in the adults and 
elderly). Gastro-intestinal symptoms and shivering were at a higher rate in the children 10-17 years of 
age. In children aged 3-9 years who received a first half adult dose of a similar vaccine (H1N1), the 
side effects were similar compared to the side effects reported in adults, with the exception of 
shivering, sweating and gastro-intestinal symptoms which were reported at a higher rate in children 
aged 3 to 9 years. Additionally, in children aged 3 to 5 years of age, drowsiness, irritability and loss of 
appetite were reported very commonly. 
 
Very common: 
• Pain at the injection site 



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• Headache 
• Tiredness 
• Aching muscles, joint pain 
 
Common: 
• Redness and swelling at the injection site 
• Fever 
• Sweating 
• Shivering 
• Diarrhoea, feeling sick 
 
Uncommon: 
• Reactions at the injection site such as bruising, hard lump, itching, warmth 
• Swollen glands in the axilla 
• Dizziness 
• Generally feeling unwell 
• Unusual weakness  
• Being sick, stomach pain, acid indigestion 
• Inability to sleep 
• Tingling or numbness of the hands or feet 
• Shortness of breath 
• Pain in the chest 
• Itching, rash 
• Pain in the back or neck, stiffness in the muscles, muscle spasms, pain in extremity such as leg 

or hand 
 
In children aged 6-35 months who received a half of the adult dose (0.25 ml) of a similar vaccine 
(H1N1), fever and irritability occurred more often compared to the children 3-9 years who received a 
half of the adult dose (0.25 ml) of a similar vaccine (H5N1). 
 
In children aged 6-35 months who received two doses of 0.25 ml (half of the adult dose) the side 
effects after the second dose were more intense, especially fever (≥38°C), which occurred very 
commonly.  
 
These side effects usually disappear within 1 to 2 days without treatment. If they persist, CONSULT 
YOUR DOCTOR. 
 
The side effects listed below have occurred during post-marketing surveillance with a similar vaccine 
(H1N1).  These side effects may occur with Arepanrix. 
 
• Allergic reactions leading to a dangerous decrease of blood pressure, which, if untreated, may 

lead to shock. Doctors are aware of this possibility and have emergency treatment available for 
use in such cases. 

• Generalised skin reactions including facial swelling and urticaria (hives) 
• Fits due to fever 
 
The side effects listed below have occurred in the days or weeks after vaccination with vaccines given 
routinely every year to prevent flu.  These side effects may occur with Arepanrix. 
 
Rare 
• Severe stabbing or throbbing pain along one or more nerves 
• Low blood platelet count which can result in bleeding or bruising  
 
Very rare 



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  38 

• Vasculitis (inflammation of the blood vessels which can cause skin rashes, joint pain and kidney 
problems) 

• Neurological disorders such as encephalomyelitis (inflammation of the central nervous system), 
neuritis (inflammation of nerves) and a type of paralysis known a Guillain-Barré Syndrome 

 
If any of these side effects occur, please tell your doctor or nurse immediately. 
 
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please 
tell your doctor. 
 
 
5. How to store Arepanrix 
 
Keep out of the reach and sight of children. 
 
Before the vaccine is mixed: 
Do not use the suspension and the emulsion 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).  
Store in the original package in order to protect from light. 
Do not freeze.   
 
After the vaccine is mixed: 
After mixing, use the vaccine within 24 hours and do not store above 25°C. 
 
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to 
dispose of medicines no longer required.  These measures will help to protect the environment. 
 
 
6. Further information 
 
What Arepanrix contains 
 
• Active substance: 

Split influenza virus, inactivated, containing antigen* equivalent to: 
 

A/California/7/2009 (H1N1)v-like strain (X-179A)  3.75 micrograms** per 0.5 ml dose 
 

*propagated in eggs 
** expressed in microgram haemagglutinin 
 
This vaccine complies with the WHO recommendation and EU decision for the pandemic. 

 
• Adjuvant: 

 The vaccine contains an ‘adjuvant’ AS03 to stimulate a better response. This adjuvant contains 
squalene (10.69 milligrams), DL-α-tocopherol (11.86 milligrams) and polysorbate 80 (4.86 
milligrams) 

 
• Other ingredients:  

The other ingredients are: thiomersal, sodium chloride, disodium hydrogen phosphate, 
potassium dihydrogen phosphate, potassium chloride, water for injections 

 
What Arepanrix looks like and contents of the pack 
 



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Suspension and emulsion for emulsion for injection. 
The suspension is a translucent to off white opalescent suspension, which may sediment slightly. 
The emulsion is a whitish homogeneous liquid. 
 
Prior to administration, the two components should be mixed. The mixed vaccine is a whitish 
emulsion. 
 
One pack of Arepanrix consists of:  
• one pack containing 50 vials of 2.5 ml suspension (antigen) 
• two packs containing 25 vials of 2.5 ml emulsion (adjuvant) 
 
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 s.a./n.v. 
Tél/Tel: + 32 2 656 21 11 
 

Luxembourg/Luxemburg 
GlaxoSmithKline s.a./n.v. 
Tél/Tel: + 32 2 656 21 11 

България 
ГлаксоСмитКлайн ЕООД 
ул. Димитър Манов бл.10 
София 1408 
Тел. + 359 2 953 10 34 
 

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

Česká republika 
GlaxoSmithKline s.r.o. 
Tel: + 420 222 001 111 
gsk.czmail@gsk.com 
 

Malta 
GlaxoSmithKline Malta 
Tel: + 356 21 238131 
 

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

Nederland 
GlaxoSmithKline BV 
Tel: + 31 (0)30 69 38 100 
nlinfo@gsk.com 

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

Norge 
GlaxoSmithKline AS 
Tlf: + 47 22 70 20 00 
firmapost@gsk.no 
 

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

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

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

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



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  40 

España 
GlaxoSmithKline, S.A. 
Tel: + 34 902 202 700 
es-ci@gsk.com  
 

Portugal 
GlaxoSmithKline - Produtos Farmacêuticos, Lda. 
Tel: + 351 21 412 95 00 
FI.PT@gsk.com 
 

France 
Laboratoire GlaxoSmithKline 
Tél: + 33 (0) 800 00 12 12 
grippeA@gsk.com 
 

România 
GlaxoSmithKline (GSK) SRL 
Tel: +40 (0)21 3028 208 
 
 

Ireland 
GlaxoSmithKline (Ireland) Ltd 
Tel: + 353 (0)1 4955000 
 

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

Ísland 
GlaxoSmithKline ehf. 
Sími: +354 530 3700 
 

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 
Finland.tuoteinfo@gsk.com  
 

Κύπρος 
GlaxoSmithKline (Cyprus) Ltd 
Τηλ: + 357 22 39 70 00 
 

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)808 100 9997 
customercontactuk@gsk.com 
 

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

 

 
This leaflet was last approved in {MM/YYYY}. 
 
Arepanrix has been authorised under “Conditional Approval”. 
This means that there is more evidence to come about this medicine. 
The European Medicines Agency (EMEA) will regularly review any new information on the medicine 
and this package leaflet will be updated as necessary. 
 
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web 
site: http://www.emea.europa.eu/ 
 
--------------------------------------------------------------------------------------------------------------------- 
 
The following information is intended for medical or healthcare professionals only: 
 
Arepanrix consists of two containers:  

mailto:grippeA@gsk.com
mailto:info.produkt@gsk.com
http://www.emea.europa.eu/


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Suspension: multidose vial containing the antigen,  
Emulsion: multidose vial containing the adjuvant.  
 
Prior to administration, the two components should be mixed. 
 
Instructions for mixing and administration of the vaccine: 
 
1. Before mixing the two components, the emulsion (adjuvant) and suspension (antigen) should be 

allowed to reach room temperature. Whitish sediments may be observed in the suspension vial; 
these sediments are part of the normal physical appearance of the suspension.  The emulsion 
presents as a whitish appearance 

2. Each vial should be shaken and inspected visually for any foreign particulate matter (other than 
the white sediments described above) and/or abnormal physical appearance. In the event of 
either being observed (including rubber particles from the stopper), discard the vaccine. 

3. The vaccine is mixed by withdrawing the entire contents of the vial containing the adjuvant by 
means of a syringe and by adding it to the vial containing the antigen.  

4. After the addition of the adjuvant to the antigen, the mixture should be well shaken. The mixed 
vaccine is a whitish emulsion.  In the event of other variation being observed, discard the 
vaccine. 

5. The volume of the Arepanrix vial after mixing is at least 5 ml. The vaccine should be 
administered in accordance with the recommended posology (see section 3 “How Arepanrix is 
given”). 

6. The vial should be shaken prior to each administration and inspected visually for any foreign 
particulate matter and/or abnormal physical appearance.  In the event of either being observed 
(including rubber particles from the stopper), discard the vaccine. 

7. Each vaccine dose of 0.5 ml (full dose) or 0.25 ml (half dose) is withdrawn into a syringe for 
injection and administered intramuscularly. 

8. After mixing, use the vaccine within 24 hours. The mixed vaccine can either be stored in a 
refrigerator (2°C - 8°C) or at room temperature not exceeding 25°C. If the mixed vaccine is 
stored in a refrigerator, it should be allowed to reach room temperature before each withdrawal. 

 
The vaccine should not be administered intravascularly. 
 
Any unused product or waste material should be disposed of in accordance with local requirements. 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OF THE MARKETING AUTHORISATION
	C. SPECIFIC OBLIGATIONS TO BE FULFILLED BY THE MARKETING AUTHORISATION HOLDER
	A. LABELLING
	B. PACKAGE LEAFLET