Pumarix

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Pumarix suspension and emulsion for emulsion for injection 
Pandemic influenza vaccine (H5N1) (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/Indonesia/05/2005 (H5N1) like strain used (PR8-IBCDC-RG2) 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. 
 
Excipient with known effect: the vaccine contains 5 micrograms thiomersal 
 
For the 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 
 
Adults from the age of 18 years onwards: 
 
One dose of 0.5 ml at an elected date. 
A second dose of 0.5 ml should be given after an interval of at least three weeks. 
 

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Persons previously vaccinated with one or two doses of AS03-containing vaccine containing HA 
derived from a different clade of the same subtype 
 
Adults from the age of 18 years onwards: one dose of 0.5 ml at an elected date. 
 
Paediatric population 
 
There are very limited safety and immunogenicity data available on the administration of an AS03-
adjuvanted vaccine containing 3.75 µg HA derived from A/Vietnam/1194/2004 (H5N1) manufactured 
using a different process and on administration of half a dose of the same vaccine (i.e. 1.875 µg HA 
and half the amount of AS03 adjuvant) at 0 and 21 days in children aged 3 to 9 years.  See sections 4.8 
and 5.1. 
 
The safety and efficacy of Pumarix in children aged less than 3 years and in children and adolescents 
aged 10 to 17 years have not been established. No data are available. 
 
For further information, see section 5.1. 
 
It is recommended that subjects who receive a first dose of Pumarix, complete the vaccination course 
with Pumarix. 
 
Method of administration 
 
Immunisation should be carried out by intramuscular injection preferably into the deltoid muscle or 
anterolateral thigh (depending on the muscle mass). 
 
For instructions on mixing of the medicinal product before administration, see section 6.6. 
 
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.  
However, in a pandemic situation, it may be appropriate to give the vaccine provided that facilities for 
resuscitation should be immediately available in case of need. 
 
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 listed in section 6.1, 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. 
 
Pumarix should under no circumstances be administered intravascularly. There are no data with 
Pumarix 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. 
 

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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). 
 
Syncope (fainting) can occur following, or even before, any vaccination 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. 
 
Paediatric population 
 
Clinical data in children less than 6 years of age who received two doses of another Pandemic 
influenza vaccine (H5N1 manufactured in Dresden, Germany) indicate an increase in frequency of 
fever (axillary≥38°C) after the administration of 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) post-
vaccination. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
There are no data on co-administration of Pumarix 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  Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are currently no data available on the use of Pumarix in pregnancy.  
 
An AS03-containing vaccine containing HA from H1N1v has been administered to women in each 
trimester of pregnancy.  Information on outcomes from estimated more than 200,000 women who 
have been vaccinated during pregnancy is currently limited. There was no evidence of an increased 
risk of adverse outcomes in over 100 pregnancies that were followed in a prospective clinical study. 
 
Animal studies with Pumarix do not indicate reproductive toxicity (see section 5.3). 
 
Data from pregnant women vaccinated with different inactivated non-adjuvanted seasonal vaccines do 
not suggest malformations or fetal or neonatal toxicity. 
 
The use of Pumarix may be considered during pregnancy if this is thought to be necessary, taking into 
account official recommendations. 
 
Breast-feeding 

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Pumarix may be used in lactating women. 
 
Fertility 
 
No fertility data are available. 
 
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 use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
Clinical studies have evaluated the incidence of adverse reactions in approximately 4,500 subjects 18 
years old and above who received Pumarix or placebo. 
 
In adults 18 to 64 years of age, the most frequently reported adverse reactions after vaccination were 
injection site pain (80.5%), muscle aches (37.2%), fatigue (25.2%), headache (25.1%), joint pain 
(17.7%) and shivering (11.1%). 
 
In subjects > 64 years of age, the most frequently reported adverse reactions after vaccination were 
injection site pain (58.0%), muscle aches (19.7%), fatigue (13.5%), headache (12.4%) and joint pain 
(10.3%). 
 
List of adverse reactions 
 
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) 
 
Adverse reactions from clinical trials with the mock-up vaccine are listed here below (see section 5.1 
for more information on mock-up vaccines). 
 
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 
 

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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 
 
No post-marketing surveillance data are available following Pumarix administration. 
 
From post-marketing experience with AS03-containing vaccines containing 3.75 µg HA derived from 
A/California/7/2009 (H1N1), the following adverse reactions have been reported: 
 
Immune system disorders 
Anaphylaxis, allergic reactions 
 
Nervous system disorders 
Febrile convulsions 
 
Skin and subcutaneous tissue disorders 
Angioedema, generalised skin reactions, urticaria 
 
In addition, from post-marketing surveillance with interpandemic trivalent vaccines, the following 
adverse reactions have been reported: 
 
Rare:  
Neuralgia, transient thrombocytopenia. 
 
Very rare: 
Vasculitis with transient renal involvement. 
Neurological disorders, such as encephalomyelitis, neuritis and Guillain Barré syndrome. 
 
Paediatric population 
 
A clinical study (D-H5N1-009), evaluated the reactogenicity in children 3 to 5 and 6 to 9 years of age 
who received either two adult (i.e. 0.5 ml) doses or two half adult (i.e. 0.25 ml) doses (21 days apart) 
of another Pandemic influenza vaccine (H5N1 A/Vietnam/1194/2004 manufactured in Dresden, 
Germany).  
 
The per-dose frequency of local and general solicited adverse reactions observed in the groups of 
children who received two adult (0.5 ml) doses was higher than that observed in the groups of children 
who received two half adult (i.e. 0.25 ml) doses, except for redness in the 6-9 years of age group. The 

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administration of a second half adult or an adult dose did not enhance the reactogenicity, except for 
rates of general symptoms which were higher after the second dose, particularly for rates of fever in 
<6 year olds. The per-dose frequency of adverse reactions was as follows: 
 
Adverse reactions 3-5 years 6-9 years 
 Half dose Full dose Half dose Full dose 
Induration 9.9% 18.6% 12.0% 12.2% 
Pain 48.5% 62.9% 68.0% 73.5% 
Redness 10.9% 19.6% 13.0% 6.1% 
Swelling 11.9% 24.7% 14.0% 20.4% 
Fever (>38°C) 4.0% 11.3% 2.0% 17.3% 
Fever (>39°C) 
- per-dose 

frequency 
- per-subject 

frequency 

 
2.0% 

 
3.9% 

 
5.2% 

 
10.2% 

 
0% 

 
0% 

 
7.1% 

 
14.3% 

Drowsiness 7.9% 13.4% NA NA 
Irritability 7.9% 18.6% NA NA 
Loss of appetite 6.9% 16.5% NA NA 
Shivering 1.0% 12.4% 4.0% 14.3% 
NA=not available 
 
In other clinical studies where children 6 months to 17 years received another pandemic influenza 
vaccine (H5N1 A/Indonesia/05/2005 manufactured in Dresden, Germany), increases in the frequency 
of some side effects (including injection site pain, redness and fever) were seen after the second dose 
in children aged less than 6 years. 

 
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). 
 
4.9 Overdose 
 
No case of overdose has been reported. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Influenza vaccines, ATC Code J07BB02. 
 
Pharmacodynamic effects 
 
This section describes the clinical experience with the mock-up vaccines following a two-dose 
administration.  
 
Mock-up vaccines contain influenza antigens that are different from those in the currently circulating 
influenza viruses. These antigens can be considered as “novel” antigens and simulate a situation where 
the target population for vaccination is immunologically naïve. Data obtained with the mock-up 
vaccine will support a vaccination strategy that is likely to be used for the pandemic vaccine: clinical 
immunogenicity, safety and reactogenicity data obtained with mock-up vaccines are relevant for the 
pandemic vaccines. 
 
Immune response against A/Indonesia/5/2005 (H5N1) 

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Adults 
 
Clinical studies have evaluated the immunogenicity of AS03-adjuvanted vaccine containing 3.75 µg 
HA derived from A/Indonesia/5/2005 in subjects from the age of 18 years onwards following a 0, 21 
days schedule. 
 
In a consistency study (Q-Pan-H5N1-002), 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. At day 42, 100% of subjects aged 18-60 years and 96.4% of subjects aged >60 years 
had a titre of at least 1:80. 
 
In another clinical study (Q-Pan-H5N1-001), 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 and 100% of subjects had a titre of 
at least 1:80 at day 42 and 180. 
 
Administration of an AS03-adjuvanted vaccine containing 3.75 µg HA derived from 
A/Vietnam/1194/2004 (H5N1) manufactured using a different process 
 
Paediatric population  
 
In a clinical study (D-Pan-H5N1-009, -023), children aged 3 to 5 and 6 to 9 years old received two 
doses of either a full (0.5 ml) or a half dose (0.25 ml) of an AS03-adjuvanted vaccine containing 3.75 

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µg HA derived from A/Vietnam/1194/2004 (H5N1) at 0 and 21 days. At day 42 and six months after 
the second dose, the anti-HA antibody responses were as follows: 
 
anti-HA 
antibody 

Immune response to A/Vietnam/1194/2004 

 3 to 5 years 6 to 9 years 
 Day 42 Day 180 Day 42 Day 180 
 Half 

dose 
N=49 

Full 
dose 
N=44 

Half 
dose 
N=50 

Full 
dose 
N=29 

Half 
dose 
N=43 

Full 
dose 
N=43 

Half 
dose 
N=44 

Full 
dose 
N=41 

Seroprotection 
rate1 

95.9% 100% 56.0% 82.8% 100% 100% 63.6% 78% 

Seroconversion 
rate2 

95.9% 100% 56.0% 82.8% 100% 100% 61.0% 78% 

Seroconversion 
factor3 

78.5 191.3 5.9 16 108.1 176.7 6.1 12.3 

1seroprotection 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. 
 
The clinical relevance of the haemagglutination inhibition (HI) titre ≥1:40 in children is unknown. 
 
At day 42, the neutralising antibody responses were as follows: 
 
Serum neutralising 
antibody 

Immune response to A/Vietnam/1194/2004 

 21 days after 2nd dose 
 3 to 5 years 6 to 9 years 
 Half dose 

N=47 
Full dose 

N=42 
Half dose 

N=42 
Full dose 

N=42 
GMT1 1044.4 4578.3 1155.1 3032.5 
Seroconversion rate2 95.6% 97.4% 100% 100% 
≥1:803 100% 100% 100% 100% 
1 Geometric Mean Titre 
2 4-fold increase in serum neutralising antibody titre 
3 % of subjects reaching a serum neutralising antibody titre of at least 1:80 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Pumarix in one or more subsets of the paediatric population in influenza infection caused by an 
influenza strain contained in the vaccine or related to a strain contained in the vaccine. (see section 4.2 
for information on paediatric use). 
 
Cross-reactive immune responses elicited by AS03-adjuvanted vaccine containing 3.75 µg HA derived 
from A/Indonesia/5/2005 (H5N1): 
 
In the consistency study (Q-Pan-H5N1-002), 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. A titre of 1:80 was achieved in 84.2% of subjects aged 18-60 years and 
in 92.6% of subjects aged >60 years. 
 

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In another clinical study (Q-Pan-H5N1-001), anti-HA responses against A/Vietnam/1194/2004 
following administration of AS03-adjuvanted vaccine containing 3.75 µg derived from 
A/Indonesia/5/2005 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. A titre of 1:80 was achieved in 95.7% of 
subjects at days 21 and 42 and in 85.1% at day 180. 
 
One dose of AS03-adjuvanted vaccine containing 3.75 µg HA derived from A/Indonesia/05/2005 
manufactured using a different process administered after one or two doses of AS03-adjuvanted 
vaccine containing 3.75 µg HA derived from A/Vietnam/1194/2004 manufactured using a different 
process 
 
In a clinical study (D-Pan-H5N1-012), subjects aged 18-60 years received a dose of AS03-adjuvanted 
vaccine containing 3.75 µg HA derived from either A/Vietnam/1194/2004 or Indonesia/5/2005 six 
months after they had received one or two priming doses of AS03-adjuvanted vaccine containing 3.75 
µg HA derived from A/Vietnam/1194/2004 on day 0 or on days 0 and 21 respectively.  The anti-HA 
responses were as follows: 
 
anti-HA antibody Against A/Vietnam 21 days after 

boosting with A/Vietnam 
N=46 

Against A/Indonesia 21 days after 
boosting with A/Indonesia 

N=49 
 After one 

priming dose 
After two  

priming doses 
After one  

priming dose 
After two  

priming doses 
Seroprotection rate1 89.6% 91.3% 98.1% 93.9% 
Booster 
seroconversion rate2 

87.5% 82.6% 98.1% 91.8% 

Booster factor3 29.2 11.5 55.3 45.6 
1 seroprotection rate: proportion of subjects with haemagglutination inhibition (HI) titre ≥1:40; 
2booster seroconversion rate: proportion of subjects who were either seronegative at pre-booster and 
have a protective post-vaccination titre of ≥1:40, or who were seropositive at pre-booster and have a 4-
fold increase in titre;  
3booster factor: ratio of the post-booster geometric mean titre (GMT) and the pre-booster GMT. 
 
Regardless of whether one or two doses of priming vaccine had been given 6 months earlier, the 
seroprotection rates against A/Indonesia were >80% after a dose of AS03-adjuvanted vaccine 
containing 3.75 µg HA derived from A/Vietnam/1194/2004 and the seroprotection rates against 
A/Vietnam were >90% after a dose of AS03-adjuvanted vaccine containing 3.75 µg HA derived from 
A/Indonesia/05/2005. All subjects achieved a neutralising antibody titre of at least 1:80 against each of 
the two strains regardless of the HA type in the vaccine and the previous number of doses. 
 

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In another clinical study, 39 subjects aged 18-60 years received a dose of AS03-adjuvanted vaccine 
containing 3.75 µg HA derived from A/Indonesia/5/2005 fourteen months after they had received two 
doses of AS03-adjuvanted vaccine containing 3.75 µg HA derived from A/Vietnam/1194/2004 
administered on day 0 and day 21.  The seroprotection rate against A/Indonesia 21 days after booster 
vaccination was 92% and 69.2% at day 180. 
 
One dose of AS03-adjuvanted vaccine containing 3.75 µg HA derived from A/Turkey/Turkey/1/2005 
administered after two doses of AS03-adjuvanted vaccine containing 3.75 µg HA derived from 
Indonesia/5/2005 
 
In a clinical study (Q-Pan-H5N1-010), a booster dose of AS03-adjuvanted vaccine containing 3.75 µg 
HA derived from A/Turkey/Turkey/1/2005 was given 15 months after primary vaccination.  Ten days 
after the booster dose, the seroprotection rate against A/Turkey/Turkey/1/2005 and 
A/Indonesia/5/2005 was 99.2%. Forty-two days after the booster dose, the seroprotection rate against 
both strains was 98.4%. 
 
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. 
 
This medicinal product has been authorised under ’exceptional circumstances’. 
This means that for scientific reasons it has not been possible to obtain complete information on this 
medicinal product.  
The European Medicines Agency will review any new information which may become available every 
year and this SmPC will be updated as necessary. 
 
5.2 Pharmacokinetic properties 
 
Not applicable. 

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5.3  Preclinical safety data 
 
Non-clinical data obtained with Pumarix 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 
 
18 months. 
After mixing, the vaccine should be used within 24 hours. Chemical and physical in-use stability has 
been demonstrated for 24 hours at 30°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. 
 
For storage conditions after mixing of the medicinal product, see section 6.3. 
 
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). 
 

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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 
 
Pumarix 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 

brought to room temperature (allow a minimum of 15 minutes).  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 5 ml syringe and by adding it to the vial containing the antigen. It is recommended 
to equip the syringe with a 23-G needle.  However, in the case this needle size would not be 
available, a 21-G needle might be used.  The vial containing the adjuvant should be maintained 
in upside down position to facilitate the withdrawal of the full content. 

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 Pumarix 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 is withdrawn into a 1 ml syringe for injection and administered 
intramuscularly. It is recommended to equip the syringe with a needle gauge not larger than 23-
G. 

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 (25°C – 30°C).  If the mixed vaccine is stored 
in a refrigerator, it should be brought to room temperature (allow a minimum of 15 minutes) 
before each withdrawal. 

 
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/1/10/664/001 

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9.  DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 04 March 2011 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu/.

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ANNEX II 
 

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

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION  
 

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A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 

MANUFACTURER 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 OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to medical prescription. 
 
Pumarix 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 Pumarix takes due account of 
the officially declared pandemic strain. 
 
 
• 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 
 
Pharmacovigilance system 
The MAH must ensure that the system of pharmacovigilance, presented in Module 1.8.1 of the 
Marketing Authorisation, is in place and functioning before and whilst the medicinal product is on the 
market. 
 
The MAH shall perform the studies and pharmacovigilance activities detailed in the 
Pharmacovigilance Plan and requested as specific obligations. 
 
Risk Management plan (RMP) 
The MAH shall perform the pharmacovigilance activities detailed in the Pharmacovigilance Plan, as 
agreed in the RMP presented in Module 1.8.2 of the Marketing Authorisation and any subsequent 
updates of the RMP agreed by the Committee for Medicinal Products for Human Use (CHMP). 
 
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the 
updated RMP should be submitted at the same time as the next Periodic Safety Update Report 
(PSUR). 
 

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In addition, an updated RMP should be submitted: 
 

• When new information is received that may impact on the current Safety Specification, 
Pharmacovigilance Plan or risk minimisation activities 

• Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being 
reached  

• At the request of the European Medicines Agency 
 

PSURs  
Outside of the pandemic period, the normal PSUR periodicity and format will be maintained, with a 
specific review of AESI and possible adverse events related to adjuvants. This should include data 
from ongoing studies, or actual use if applicable, of the ‘mock-up’ strains and any safety data relevant 
to the adjuvant system. 
 
During a pandemic situation (Phase 6 of the WHO global Influenza preparedness plan), bi-weekly 
"simplified PSUR" accompanied by a summary of vaccine distribution will be provided according to 
the cRMP guidance (Doc. Ref. EMEA/32706/2007 for 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 risk-benefit balance in a pandemic.  Prompt analysis of 
cumulative safety information, in light of extent of exposure, will be crucial for regulatory 
decisions and protection of the population to be vaccinated.  In addition, duration a pandemic, 
resources needed for an in-depth evaluation of Periodic Safety Update Reports in the format as 
defined in Volume 9a of the Rules Governing Medicinal Product in the European Union may 
not be adequate for a rapid identification of a new safety issue.  
In consequence, as soon as the pandemic is declared (Phase 6 of the WHO global Influenza 
preparedness plan) and the pandemic vaccine is used, the MAH shall submit periodic safety 
update reports with periodicity and format defined as follows:  

 
Frequency of submission 
-   The clock will start from the first Monday after shipment of the first batch of vaccine. 
-   First data-lock point is 14 days later. 
-   Report submission is no later than day 22 (i.e. the following Monday). 
-   Reporting to be fortnightly for the first 3 months of the pandemic. 
-   Periodicity will be reviewed by the MAH and the (Co)Rapporteur at 3 monthly intervals.   
 
When it has been agreed by the CHMP that the S-PSUR is no longer necessary, a full PSUR covering 
the period since the data lock point of the last routine PSUR will be submitted within a time frame to 
be agreed with the Rapporteur. 
 
Format  
The report shall include the following tables of aggregate data using the agreed templates: 
 

1. Fatal and/or life-threatening reactions – for each Preferred Term (PT), including the 
proportion of fatal reports  

2. Adverse Events of Special Interest (PTs)  
3. Serious unexpected reactions (PTs)  
4. All events occurring in the following age groups: 6-23 months, 2-8 years, 8-17 years, 18-60 

years, >60 years  
5. All events occurring in pregnant women  
6. All events reported by patients that have been entered into the database by data-lock point 

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7. A cumulative overview of all events reported during the period, stratified according to type of 
reporter (patient or health care professional), seriousness, expectedness, and whether 
spontaneous or solicited. 

 
Presentation of data will take into consideration the following recommendations: 
 
- Serious expected reactions will be reviewed by the MAH as part of their signal detection 

procedures and will only form part of the report if an issue of concern arises.   
- All tables will be based on number of events (presented on PT level, sorted by System Organ Class 

(SOC)) and not number of cases. 
- Tables 1 to 4 will be based on events reported from healthcare professionals only. 
- In Tables 1 to 5, numbers will be provided for events received during the reporting period and 

cumulatively. 
- All tables will be based on generic and not product-specific data.  Product-specific data can be 

evaluated during signal work-up. 
-   A measure of relative reporting rate of signals for each reported PT should be provided if possible   
    (e.g. Proportional reporting ratio (PRR), Information Component (IC) or the Empirical Bayesian     
     Geometric Mean (EBMG)); this is not mandatory as all MAHs do not yet have this capability. 
-   No line listings are required – these can be provided in signal evaluation reports as necessary. 
 

A short summary shall also be provided with the periodic safety update reports, in which any 
area of concern should be highlighted, signal work-up prioritised (if the event of multiple 
signals) and appropriate timelines for submission of a full signal evaluation report provided.  
All signal evaluation reports should be provided, including those that were subsequently not 
identified as being signals. 

 
A summary of vaccine distribution shall be included and provide details of the number of 
doses of vaccine distributed in: 

i) EU member states for the reporting period by batch number,  
ii) EU member states cumulatively and  
iii) the rest of the world 

 
 
• CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
Not applicable. 

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• SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION 
MEASURES FOR THE MARKETING AUTHORISATION UNDER 
EXCEPTIONAL CIRCUMSTANCES 

 
This being an approval under exceptional circumstances and pursuant to Article 14(8) of Regulation 
(EC) No 726/2004, the MAH shall conduct, within the stated timeframe, the following measures: 
 
Description Due date 
During the pandemic, the applicant will conduct a 
surveillance on the safety of the vaccine during 
pregnancy using dedicated registry.  
 

Protocol of the registry will be 
submitted as part of RMP, during the 
pandemic 
 

During the pandemic, the applicant will conduct a 
prospective cohort study as identified in the 
Pharmacovigilance plan. 
 

Depending on and after 
implementation of vaccine strain, 
when first pandemic will take place. 

 

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  20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 

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A. LABELLING 

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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 
 
Pumarix suspension and emulsion for emulsion for injection. 
Pandemic influenza vaccine (H5N1) (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/Indonesia/05/2005 (H5N1) like strain used (PR8-IBCDC-RG2) 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 SIGHT AND REACH OF CHILDREN 

 
Keep out of the sight and reach 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/1/10/664/001 
 
 
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 Pumarix 
Pandemic influenza vaccine (H5N1) (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/Indonesia/5/2005 (H5N1) like strain used (PR8-IBCDC-RG2) 
 
 
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/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 SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach 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 
 
Storage 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/1/10/664/001 
 
 
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 Pumarix 
 
 
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 SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach 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 
 
Storage 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/1/10/664/001 
 
 
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 Pumarix 
Pandemic influenza vaccine 
A/Indonesia/5/2005 (H5N1) like strain used (PR8-IBCDC-RG2) 
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 30°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 Pumarix 
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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B. PACKAGE LEAFLET 
 

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Package Leaflet: Information for the user 

 
Pumarix suspension and emulsion for emulsion for injection 

Pandemic influenza vaccine (H5N1) (split virion, inactivated, adjuvanted) 
 

Read all of this leaflet carefully before you receive 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 nurse. 
- 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. This includes any possible side effects not listed 

in this leaflet. 
 
What is in this leaflet:  
1. What Pumarix is and what it is used for 
2. What you need to know before you are given Pumarix 
3. How Pumarix is given 
4. Possible side effects 
5. How to store Pumarix 
6. Contents of the pack and other information 
 
 
1. What Pumarix is and what it is used for 
 
What Pumarix is and what it is used for 
Pumarix is a vaccine for use in adults from 18 years old to prevent pandemic flu (influenza).  
 
Pandemic flu is a type of influenza that happens at intervals that vary from less than 10 years to many 
decades. It spreads rapidly around the world. The signs of pandemic flu are similar to those of 
ordinary flu but may be more serious. 
 
How Pumarix works 
When a person is given the vaccine, the body’s natural defence system (immune system) produces its 
own protection (antibodies) against the disease. None of the ingredients in the vaccine can cause flu. 
 
As with all vaccines, Pumarix may not fully protect all persons who are vaccinated. 
 
 
2. What you need to know before you are given Pumarix 
 
Pumarix should not be given: 
 
• if you have previously had a sudden life-threatening allergic reaction to any ingredient of this 

vaccine (listed in section 6) or to anything else that may be present in very small amounts, such 
as: 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, you may still be given the vaccine. This is as long as 

medical treatment is available straight away, in case you have an allergic reaction. 
 
Do not have Pumarix if any of the above apply to you.   
If you are not sure, talk to your doctor or nurse before having this vaccine. 
 
Warnings and precautions 

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Talk to your doctor or nurse before you are given Pumarix: 
• if you have had any allergic reaction other than a sudden life-threatening allergic reaction to any  

ingredient contained in this vaccine (listed in section 6) or to thiomersal, to egg and chicken 
protein, ovalbumin, formaldehyde or to sodium deoxycholate. 

• if you have a serious 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 Pumarix. 

• if you have problems with your immune system, since your response to the vaccine may then be 
poor. 

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

• if you have a bleeding problem or you bruise easily. 
 
If any of the above apply to you (or you are not sure), talk to your doctor or nurse before having 
Pumarix.  This is because the vaccination may not be recommended, or may need to be delayed. 
 
Fainting can occur following, or even before, any needle injection. Therefore tell the doctor or nurse if 
you fainted with a previous injection. 
 
Children: 
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. 
 
Other medicines and Pumarix 
Tell your doctor or nurse if you are taking, have recently taken or might take any other medicines or 
have recently received any other vaccine. 
 
In particular, please tell your doctor or nurse if you are having any treatments (such as corticosteroid 
treatments or chemotherapy for cancer) that affect the immune system.  Pumarix can still be given but 
your response to the vaccine may be poor. 
 
Pumarix is not intended to be given at the same time as some other vaccines. However, if this needs to 
happen, the other vaccine will be injected into the other arm.  Any side effects that happen may be 
more serious.  
 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before you receive this vaccine. 
 
Driving and using machines 
Some effects listed in Section 4 “Possible side effects” may affect your ability to drive or use tools or 
machines. It is best to see how Pumarix affects you before you try these activities. 
 
Pumarix contains thiomersal  
Pumarix 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. 
 
Pumarix contains sodium and potassium  
Pumarix contains less than 1 mmol sodium (23 mg) and less than 1 mmol of potassium (39 mg) per 
dose. It is essentially sodium- and potassium-free. 

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3. How Pumarix is given 
 
• Adults from 18 years onwards: you will receive two doses of Pumarix. The second dose should 

be given after an interval of at least three weeks after the first dose. 
 
If you have previously received one or two doses of a similar H5N1 AS03-containing vaccine 
 
• Adults from 18 years onwards: you will receive one dose of Pumarix.  
 
Use in children 
There is limited information available on the use of vaccine very similar to Pumarix (but manufactured 
in a different facility) to children aged from 3-9 years who received either two adult doses or two half 
adult doses given three weeks apart. There is no information available on use in children aged less 
than 3 years or aged from 10-17 years. 
 
Your doctor or nurse will give you Pumarix. 
• They will give Pumarix as an injection into a muscle 
• This will usually be in the upper arm. 
 
If you have any further questions on the use of this vaccine, ask your doctor or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this vaccine can cause side effects, although not everybody gets them. 
 
Allergic reactions 
Allergic reactions which may cause you to have dangerously low blood pressure.  If this is not treated 
it may lead to shock. Your doctors know that this might happen and will have emergency treatment 
ready to use. 
 
Other side effects: 
 
Very common: may affect more than 1 in 10 people 
• Pain where the injection was given 
• Headache 
• Feeling tired 
• Aching muscles, joint pain 
 
Common: may affect up to 1 in 10 people 
• Redness and swelling where the injection was given 
• Fever 
• Sweating 
• Shivering 
• Diarrhoea, feeling sick 
 
Uncommon: may affect up to 1 in 100 people 
• Reactions where the injection was given such as bruising, a hard lump, itching, warmth 
• Swollen glands in your neck 
• Feeling dizzy 
• Generally feeling unwell 
• Unusual weakness  

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• Being sick, stomach pain, acid indigestion 
• Not being able 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, stiff muscles, muscle spasms, pain in your leg or hand 
 
Additional side effects in children 
 
When a dose of 0.5 ml of a similar vaccine was given to children aged 3-9 years, fever occurred more 
often than when half of this dose (0.25 ml of vaccine) was given. Also fever occurred more often in 
children aged 6-9 years compared to the children aged 3-5 years. There was no increase after the 
second dose whether the children received half of the adult or the adult dose, except for some side 
effects which were higher after the second dose, particularly for rates of fever in < 6 years old 
children. 
 
In other clinical studies where children 6 months to 17 years received a similar vaccine containing 
A/Indonesia/05/2005, increases in the frequency of some side effects (including injection site pain, 
redness and fever) were seen after the second dose in children aged less than 6 years. 

 
The side effects listed below have happened with H1N1 AS03-containing vaccines. They may also 
happen with Pumarix. If any of the side effects below occur, please tell your doctor or nurse 
immediately: 
 
• Allergic reactions leading to a dangerously low blood pressure. If this is not treated, it may lead 

to shock.  Your doctors will know that this might happen and will have emergency treatment 
ready to use 

• Fits 
• Generalised skin reactions including urticaria (hives) 
 
The side effects listed below have happened in the days or weeks after vaccination with vaccines given 
routinely every year to prevent flu.  They may also happen with Pumarix. If any of the side effects 
below occur, please tell your doctor or nurse immediately: 
 
Rare: may affect up to 1 in 1,000 people 
• Serious stabbing or throbbing pain along one or more of your nerves 
• Low blood platelet count. This can cause bleeding or bruising.  
 
Very rare: may affect up to 1 in 10,000 people 
• Inflammation of your blood vessels (vasculitis). This can cause skin rashes, joint pain and 

kidney problems 
• Problems with your brain and nerves such as inflammation of the central nervous system 

(encephalomyelitis), inflammation of nerves (neuritis) or a type of paralysis known as ‘Guillain-
Barré Syndrome’. 

 
If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this 
leaflet. 
 
 
5. How to store Pumarix 
 
Keep this vaccine out of the sight and reach of children. 

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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 30°C. 
 
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 Pumarix contains 
 
• Active substance: 

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

A/H5N1/Indonesia/5/2005 like strain used (PR8-IBCDC-RG2)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. This adjuvant contains squalene (10.69 milligrams), 
DL-α-tocopherol (11.86 milligrams) and polysorbate 80 (4.86 milligrams). Adjuvants are used 
to improve the body’s response to the vaccine. 

 
• Other ingredients:  

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

 
What Pumarix looks like and contents of the pack 
 
The suspension is a translucent to off white opalescent suspension, which may sediment slightly.  
The emulsion is a whitish homogeneous liquid. 
 
Before the vaccine is given, the two parts will be mixed together. The mixed vaccine is a whitish 
emulsion. 
 
One pack of Pumarix 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. 

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  37 

Rue de l’Institut 89 
B-1330 Rixensart 
Belgium 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
GlaxoSmithKline Pharmaceuticals s.a./n.v. 
Tél/Tel: + 32 10 85 52 00 
 

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

България 
ГлаксоСмитКлайн ЕООД 
Тел. + 359 2 953 10 34 
 

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

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

Malta 
GlaxoSmithKline (Malta) Ltd 
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 
 

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) 1 39 17 84 44 
diam@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 
 

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  38 

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 revised in {MM/YYYY}. 
 
This medicine has been authorised under ’exceptional circumstances’. 
This means that for scientific reasons it has been impossible to get complete information on this 
medicine.  
The European Medicines Agency will review any new information on this medicine every year and 
this leaflet will be updated as necessary. 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
--------------------------------------------------------------------------------------------------------------------- 
 
The following information is intended for healthcare professionals only: 
 
Pumarix 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 

brought to room temperature (allow a minimum of 15 minutes).  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. 

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  39 

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 5 ml syringe and by adding it to the vial containing the antigen. It is recommended 
to equip the syringe with a 23-G needle.  However, in the case this needle size would not be 
available, a 21-G needle might be used.  The vial containing the adjuvant should be maintained 
in upside down position to facilitate the withdrawal of the full content. 

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 Pumarix vial after mixing is at least 5 ml.  The vaccine should be 
administered in accordance with the recommended posology (see section 3. “How Pumarix 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 is withdrawn into a 1 ml syringe for injection and administered 
intramuscularly. It is recommended to equip the syringe with a needle not larger than 23-G. 

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 (25°C – 30°C).  If the mixed vaccine is stored 
in a refrigerator, it should be brought to room temperature (allow a minimum of 15 minutes) 
before each withdrawal. 

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

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  40 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX IV 
 
SCIENTIFIC CONCLUSIONS AND GROUNDS RECOMMENDING THE VARIATION TO 

THE TERMS OF THE MARKETING AUTHORISATION 

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Scientific conclusions  
 
Taking into account the PRAC Assessment Report on the PSUR for Pumarix, the scientific 
conclusions of the PRAC are as follows:  
 
In relation to the identified risk of fever in children (<6 years), the PRAC does not agree with the 
MAH that the EU SmPC contains appropriate information on this safety concern. As an identified 
risk, an appropriate warning should be included in section 4.4. Moreover section 4.8 should be 
revised to reflect reactogenicity data from the three paediatric studies D-Pan H5N1-009, -013 and 
032.  
 
Therefore, in view of the available data regarding fever in children, the PRAC considered that 
changes to the product information were warranted.  
The CHMP agrees with the scientific conclusions made by the PRAC. 
 
Grounds recommending the variation to the terms of the Marketing Authorisation  
 
On the basis of the scientific conclusions for Pumarix, the CHMP is of the opinion that the benefit-
risk balance of the medicinal product containing the active substance purified antigen fractions of 
inactivated split virion A/Indonesia/05/2005 (H5N1)/PR8-IBCDC-RG2 is favourable subject to the 
proposed changes to the product information. 
 
The CHMP recommends that the terms of the Marketing Authorisation should be varied. 
 
 

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	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	A. LABELLING
	B. PACKAGE LEAFLET
	SCIENTIFIC CONCLUSIONS AND GROUNDS RECOMMENDING THE VARIATION TO THE TERMS OF THE MARKETING AUTHORISATION