Prepandrix

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 
 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Prepandrix suspension and emulsion for emulsion for injection. 
Prepandemic 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 
 
AS03 adjuvant composed of squalene (10.69 milligrams), DL-α-tocopherol (11.86 milligrams) and 
polysorbate 80 (4.86 milligrams) 
 
The suspension and emulsion vials once mixed form a multidose container. See section 6.5 for the 
number of doses per vial. 
 
Excipient with known effect  
The vaccines contains 5 micrograms thiomersal (see section 4.4). 
 
For the full list of excipients see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension and emulsion for emulsion for injection. 
The suspension is a colourless light opalescent liquid. 
The emulsion is a whitish to yellowish homogeneous milky liquid. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Active immunisation against H5N1 subtype of Influenza A virus. 
This indication is based on immunogenicity data from healthy subjects from the age of 18 years 
onwards following administration of two doses of vaccine prepared with H5N1 subtype strains (see 
section 5.1). 
 
Prepandrix should be used in accordance with official guidance.  
 
4.2 Posology and method of administration 
 
Posology 
 
Adults from the age of 18 years: 
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 and up to twelve 
months after the first dose for maximum efficacy. 
 



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Special population: 
 
Based on very limited data, adults aged >80 years may require a double dose of Prepandrix on an 
elected date and again after an interval of at least three weeks in order to achieve an immune response 
(see section 5.1). 
 
A complete vaccination course with Prepandrix consists of two doses.  However, in the event of an 
officially declared influenza pandemic, persons previously vaccinated with one or two doses of 
Prepandrix that contained HA antigen derived from a different clade of the same influenza subtype as 
the pandemic influenza strain may receive a single dose of Adjupanrix instead of two doses that are 
required in previously unvaccinated individuals. 
 
Paediatric population 
 
The safety and efficacy of Prepandrix 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. 
 
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) and on 
administration of half a dose of the 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 4.4, 4.8 and 5.1. 
 
Method of administration 
 
Immunisation should be carried out by intramuscular injection preferably into the deltoid muscle or 
anterolateral thigh (depending on the muscle mass). 
 
If a double dose is given, the injections should be given into opposite limbs. 
 
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, gentamicin sulphate and sodium deoxycholate) of 
this vaccine. See sections 4.4, 4.8 and 6.1. 
 
Immunisation should be postponed in subjects with a severe febrile illness or acute infection. 
 
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, gentamicin sulphate 
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. 
 
Prepandrix should under no circumstances be administered intravascularly.  
There are no data with Prepandrix 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. 



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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. 
 
Epidemiological studies relating to another AS03-adjuvanted vaccine (Pandemrix H1N1, also 
manufactured in the same facility as Prepandrix), in several European countries have indicated an 
increased risk of narcolepsy with or without cataplexy in vaccinated as compared with unvaccinated 
individuals. In children/adolescents (aged up to 20 years), these studies have indicated an additional 
1.4 to 8 cases in 100,000 vaccinated subjects. Available epidemiological data in adults aged over 20 
years have indicated approximately 1 additional case per 100,000 vaccinated subjects. These data 
suggest that the excess risk tends to decline with increasing age at vaccination. There is currently no 
evidence to indicate that Prepandrix may be associated with a risk of narcolepsy. 
 
Paediatric population 
 
Clinical data in children less than 6 years of age who received two doses of pandemic preparedness or 
zoonotic influenza vaccine (H5N1) 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 Prepandrix 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 Prepandrix 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 Prepandrix containing A/Vietnam/1194/2004 do not indicate reproductive toxicity 
(see section 5.3). 
 



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Data from pregnant women vaccinated with different inactivated non-adjuvanted seasonal vaccines do 
not suggest malformations or foetal or neonatal toxicity. 
 
The use of Prepandrix may be considered during pregnancy if this is thought to be necessary taking 
into account official recommendations. 
 
Breast-feeding 
 
Prepandrix 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 operate machinery. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
Clinical studies have evaluated the incidence of adverse reactions in approximately 5,000 subjects 18 
years old and above who received Prepandrix containing A/Vietnam/1194/2004 (H5N1) strain with at 
least 3.75 µg HA. 
 
In adults 18 to 60 years of age, the most frequently reported adverse reactions after vaccination were 
injection site pain (76.6%), muscle aches (46.8%), fatigue (43.6%), headache (25.3%) and joint pain 
(13.5%). 
 
In subjects > 60 years of age, the most frequently reported adverse reaction after vaccination was 
injection site pain (32.6%). 
 
In clinical trials in which subjects (N=201) received Prepandrix containing 3.75 microgram HA/AS03 
of A/Indonesia/05/2005 (H5N1) strain, the types and frequencies of adverse reactions were 
comparable with those reported below. 
 
List of adverse reactions 
Adverse reactions reported are listed according to the following frequency: 
 
Frequencies are reported as: 
Very common (≥1/10) 
Common (≥1/100 to <1/10) 
Uncommon (≥1/1,000 to <1/100) 
Rare (≥1/10,000 to <1/1,000) 
Very rare (<1/10,000) 
 
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 
Blood and lymphatic system disorders 
Common: lymphadenopathy 
 
Psychiatric disorders 
Uncommon: insomnia 
 
Nervous system disorders 



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Very common: headache 
Uncommon: paraesthesia, somnolence, dizziness  
 
Gastrointestinal disorders 
Uncommon: gastro-intestinal symptoms (such as diarrhoea, vomiting, abdominal pain, nausea) 
 
Skin and subcutaneous tissue disorders 
Common: ecchymosis at the injection site, sweating increased 
Uncommon: pruritus, rash 
 
Musculoskeletal and connective tissue disorders 
Very common: arthralgia, myalgia 
 
General disorders and administration site conditions 
Very common: induration, swelling, pain and redness at the injection site, fever, fatigue,  
Common: shivering, influenza like illness, injection site reactions (such as warmth, pruritus)  
Uncommon: malaise 
 
No post-marketing surveillance data are available following Prepandrix 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 pandemic preparedness vaccine (H5N1 A/Vietnam/1194/2004 manufactured in Dresden, Germany).  
 
A difference in the frequency of local and general solicited adverse reactions between half adult and 
adult doses was observed after each dose.  The 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% 



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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 Prepandrix, 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). 
 
Reporting of suspected adverse reactions  
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
No case of overdose has been reported. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Influenza vaccines, ATC Code J07BB02 
 
Pharmacodynamic effects 
 
Immune response against A/Indonesia/05/2005 (H5N1) 
 
In a clinical study (Q-Pan-H5N1-001) in which two doses of AS03-adjuvanted vaccine containing 
3.75 µg HA derived from A/Indonesia/05/2005 were administered on days 0 and 21 to 140 subjects 
aged 18-60 years, the anti-HA antibody responses were as follows: 
 
anti-HA antibody Immune response to A/Indonesia/05/2005 
 Day 21 

N=140 
Day 42 
N=140 

Day 180 
N=138 

Seroprotection rate1 45.7% 96.4% 49.3% 
Seroconversion rate2 45.7% 96.4% 48.6% 
Seroconversion factor3 4.7 95.3 5.2 
1seroprotection rate: proportion of subjects with haemagglutination inhibition (HI) titre ≥1:40;  



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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. 
 
A 4-fold increase in serum neutralising antibody titres was observed in 79.2% of subjects twenty-one 
days after the first dose, 95.8% twenty-one days after the second dose and 87.5% six months after the 
second dose. 
 
In a second study, 49 subjects aged 18-60 years received two doses of AS03-adjuvanted vaccine 
containing 3.75 µg HA derived from A/Indonesia/05/2005 on days 0 and 21.  At day 42, the anti-HA 
antibody seroconversion rate was 98%, all subjects were seroprotected and the seroconversion factor 
was 88.6.  In addition, all subjects had neutralising antibody titres of at least 1:80. 
 
Administration of an AS03-adjuvanted vaccine containing 3.75 µg HA derived from 
A/Vietnam/1194/2004 (H5N1) 
 
Paediatric population  
 
In a clinical study (D-Pan-H5N1-009), 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 µg HA 
derived from A/Vietnam/1194/2004 (H5N1) at 0 and 21 days. At day 42, 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 
 Half dose 

N=49 
Full dose 

N=44 
Half dose 

N=43 
Full dose 

N=43 
Seroprotection rate1 95.9% 100% 100% 100% 
Seroconversion rate2 95.9% 100% 100% 100% 
Seroconversion factor3 78.5 191.3 108.1 176.7 
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. 
 
Subjects of D-Pan-H5N1-009 were followed up for persistence of the immune response.  The 
seroprotection rates 6, 12 and 24 months after vaccination were as follows: 
 
anti-HA antibody Immune response to A/Vietnam/1194/2004 

3-5 years 
 6 months after 

vaccination 
12 months after 

vaccination 
24 months after 

vaccination 
 Half dose 

(N=50) 
Full dose 
(N=29) 

Half dose 
(N=47) 

Full dose 
(N=27) 

Half dose 
(N=27) 

Full dose 
(N=26) 

Seroprotection rate1 56.0% 82.8% 38.3% 48.1% 38.3% 73.1% 
1seroprotection rate: proportion of subjects with haemagglutination inhibition (HI) titre ≥1:40 
 
anti-HA antibody Immune response to A/Vietnam/1194/2004 

6-9 years 
 6 months after 12 months after 24 months after 



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vaccination vaccination vaccination 
 Half dose 

(N=44) 
Full dose 
(N=41) 

Half dose 
(N=37) 

Full dose 
(N=35) 

Half dose 
(N=37) 

Full dose 
(N=34) 

Seroprotection rate1 63.6% 78.0% 24.3% 62.9% 24.3% 67.6% 
1seroprotection rate: proportion of subjects with haemagglutination inhibition (HI) titre ≥1:40 
 
At day 42, and after 6, 12 and 24 months the neutralising antibody responses were as follows: 
 
Serum neutralising 
antibody 

Immune response to A/Vietnam/1194/2004 
 

 3-5 years 
 21 days after 2nd dose 6 months after 

vaccination 
12 months after 

vaccination 
24 months after 

vaccination 
 Half dose 

N=47 
Full dose 

N=42 
Half dose 

N=49 
Half dose 

N=47 
Half dose 

N=47 
GMT1 1044.4 4578.3 781.2 238.9 302.5 
Seroconversion rate2 95.6% 97.4% 87.2%  82.2% 80.0% 
≥1:803 100% 100% 100%  93.6% 95.7% 
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 
 
Serum neutralising 
antibody 

Immune response to A/Vietnam/1194/2004 
 

 6-9 years 
 21 days after 2nd dose 6 months after 

vaccination 
12 months after 

vaccination 
24 months after 

vaccination 
 Half dose 

N=42 
Full dose 

N=42 
Half dose 

N=40 
Half dose 

N=36 
Half dose 

N=38 
 

GMT1 1155.1 3032.5 756.1  179.4 234.5 
Seroconversion 
rate2 

100% 100% 95.0% 67.6%  63.9% 

≥1:803 100% 100% 100% 86.1% 97.4% 
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 
Prepandrix 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 response elicited by AS03-adjuvanted vaccine containing 3.75 µg HA 
derived from A/Indonesia/05/2005 (H5N1) 
 
After two doses of AS03-adjuvanted vaccine containing 3.75 µg HA derived from 
A/Indonesia/05/2005 administered on days 0 and 21 to 140 subjects aged 18-60 years, the anti-HA 
antibody responses to A/Vietnam/1194/2004 were as follows: 
 
anti-HA antibody Immune response to A/Vietnam/1194/2004 
 Day 21 

N=140 
Day 42 
N=140 

Seroprotection rate1 15% 59.3% 
Seroconversion rate2 12.1% 56.4% 
Seroconversion factor3 1.7 6.1 



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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. 
 
At day 180, the seroprotection rate was 13%. 
 
A 4-fold increase in serum neutralising antibody titres against A/Vietnam was obtained in 49% of 
subjects twenty-one days after the first dose, 67.3% twenty-one days after the second dose and 44.9% 
six months after the second dose. 
 
Cross-reactive immune responses elicited by AS03-adjuvanted vaccine containing 3.75 µg HA 
derived from A/Vietnam/1194/2004 (H5N1): 
 
In the subjects aged 3 to 5 and 6 to 9 years old who received two doses of either a full or a half dose of 
AS03-adjuvanted vaccine containing 3.75 µg HA derived from A/Vietnam/1194/2004 (H5N1), the 
anti-HA antibody responses against A/Indonesia/5/2005 at day 42 were as follows: 
 
anti-HA antibody Immune response to A/Indonesia/5/2005 
 3 to 5 years 6 to 9 years 
 Half dose 

N=49 
Full dose 

N=44 
Half dose 

N=43 
Full dose 

N=43 
Seroprotection rate1 71.4% 95.5% 74.4% 79.1% 
Seroconversion rate2 71.4% 95.5% 74.4% 79.1% 
Seroconversion factor3 10.7 33.6 12.2 18.5 
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. 
 
Subjects of D-Pan-H5N1-009 were followed up for persistence of the immune response.  The 
seroprotection at month 6, 12 and 24 were as follows: 
 
anti-HA 
antibody 

Immune response to A/Indonesia/5/2005 

 3 to 5 years 
 Month 6 Month 12 Month 24 
 Half dose 

N=49 
Full dose 

N=27 
Half dose 

N=47 
Full dose 

N=27 
Half dose 

N=47 
Full dose 

N=26 
Seroprotection 
rate1 

6.1% 70.4% 36.2% 44.4% 10.6% 53.8% 

1seroprotection rate: proportion of subjects with haemagglutination inhibition (HI) titre ≥1:40 
 
anti-HA 
antibody 

Immune response to A/Indonesia/5/2005 

 6 to 9 years 
 Month 6 Month 12 Month 24 
 Half dose 

N=42 
Full dose 

N=34 
Half dose 

N=36 
Full dose 

N=35 
Half dose 

N=37 
Full dose 

N=34 
Seroprotection 
rate1 

4.8% 64.7% 19.4% 42.9% 10.8% 29.4% 

1seroprotection rate: proportion of subjects with haemagglutination inhibition (HI) titre ≥1:40 



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Furthermore, in the group of children that received a half dose of vaccine, the rate of subjects with a 
titre of neutralising antibodies above 1:80 remained high up to 24 months after the first dose. The 
neutralising antibody responses were as follows: 
 
Serum 
neutralising 
antibody 

Immune response to A/Indonesia/5/2005 

 3 to 5 years 6 to 9 years 
 Day 42 

N=46 
Month 6 

N=48 
Month 

12 
N=47 

Month 
24 

N=47 

Day 42 
N=42 

Month 6 
N=40 

Month 
12 

N=35 

Month 
24 

N=38 
GMT1 331.4 242.1 177.7 188.5 412.1 208.4 128.1 146.0 
Seropositivity 
rate2 

95.6% 93.0% 97.9% 97.9% 97.2% 97.3% 94.4% 97.4% 

≥1:803 75.6% 72.1% 85.1% 80.9% 88.9% 70.3% 86.1% 81.6% 
1 Geometric Mean Titre 
2 % of subjects with titres ≥1:28 
3 % of subjects reaching a serum neutralising antibody titre of at least 1:80 
 
Alternative schedules 

An extended dosing interval was investigated in study D-H5N1-012 in which a group of subjects 18-
60 years of age received two doses of Prepandrix containing the A/Vietnam/1194/2004 strain 6 
months or 12 months apart. Twenty-one days after the second dose, the seroprotection rate and the 
vaccine response rate against A/Vietnam/1194/2004 in subjects who received the vaccine 6 months 
apart were 89.6% and 95.7%, respectively. Twenty-one days after the second dose, the seroprotection 
rate and the vaccine response rate in subjects who received the vaccine 12 months apart were 92.0% 
and 100%, respectively. 

In this study, cross-reactive immune responses against A/Indonesia/5/2005 were also observed. 
Twenty-one days after the second dose, the seroprotection rate and the vaccine response rate in 
subjects who received the vaccine 6 months apart were 83.3% and 100%, respectively. Twenty-one 
days after the second dose, the seroprotection rate and the vaccine response rate in subjects who 
received the vaccine 12 months apart were 84.0% and 100%, respectively. 
 
One dose of AS03-adjuvanted vaccine containing 3.75 µg HA derived from A/Indonesia/05/2005 
administered after one or two doses of AS03-adjuvanted vaccine containing 3.75 µg HA derived 
from A/Vietnam/1194/2004. 
 
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.  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 



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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. 
 
In another clinical study (D-Pan-H5N1-015), 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. 
 
In another clinical study (D-Pan-H5N1-038), 387 subjects aged 18-60 years received 1 dose of AS03-
adjuvanted vaccine containing 3.75 µg HA derived from A/Indonesia/5/2005 36 months after they had 
received two doses of A/Vietnam/1194/2004. The seroprotection rate, booster seroconversion rate and 
booster factor against A/Indonesia/5/2005 21 days after booster vaccination was 100%, 99.7% and 
123.8, respectively. 
 
Other information 
 
The anti-HA and neutralising antibody responses to A/Indonesia/05/2005 elicited by AS03-adjuvanted 
vaccine containing 3.75 µg HA derived from this same strain have been shown to be comparable with 
the immune responses to A/Vietnam/1194/2004 elicited by AS03-adjuvanted vaccine containing 3.75 
µg HA derived from this same strain.  Therefore, the data that have been generated with AS03-
adjuvanted vaccine containing 3.75 µg HA derived from A/Vietnam/1194/2004 are considered to be 
relevant to the use of AS03-adjuvanted vaccine containing 3.75 µg HA derived from 
A/Indonesia/05/2005. 
 
In clinical studies that evaluated the immunogenicity of AS03-adjuvanted vaccine containing 3.75 µg 
HA derived from A/Vietnam/1194/2004 (H5N1) in subjects 18-60 years old, the anti-haemagglutinin 
(anti-HA) antibody responses were as follows: 
 
anti-HA antibody Immune response to A/Vietnam/1194/2004 
 0, 21 days schedule 

(D-Pan-H5N1-002) 
0, 6 months schedule 
(D-Pan-H5N1-012) 

 21 days after 
1st dose 
N=925 

21 days after 
2nd dose 
N=924 

21 days 
after 1st 

dose 
N=55 

7 days after 
2nd dose 
N=47 

21 days 
after 2nd 

dose 
N=48 

Seroprotection rate1 44.5% 94.3% 38.2% 89.4% 89.6% 
Seroconversion rate2 42.5% 93.7% 38.2% 89.4% 89.6% 
Seroconversion factor3 4.1 39.8 3.1 38.2 54.2 
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. 
 



13 

After two doses given 21 days or 6 months apart, 96.0% of subjects had a 4-fold increase in serum 
neutralising antibody titre and 98-100% had a titre of at least 1:80. 
 
Subjects of D-Pan-H5N1-002 were followed up for persistence of the immune response.  The 
seroprotection rates 6, 12, 24 and 36 months after the first dose were as follows: 
 
anti-HA antibody Immune response to A/Vietnam/1194/2004 
 6 months after the 

1st dose 
N=256 

12 months after 
the 1st dose 

N=559 

24 months after 
the 1st dose 

N=411 

36 months after 
the 1st dose 

N=387 
Seroprotection rate1 40.2% 23.4% 16.3% 16.3% 
1 seroprotection rate: proportion of subjects with haemagglutination inhibition (HI) titre ≥1:40 
 
In another clinical study (D-Pan-H5N1-010), 297 subjects aged > 60 years (stratified in ranges from 
61 to 70, 71 to 80 and > 80 years of age) received either a single or a double dose of AS03-adjuvanted 
vaccine containing 3.75 µg HA derived from A/Vietnam/1194/2004 (H5N1) at 0 and 21 days. At day 
42, the anti-HA antibody responses were as follows: 
 
anti-HA 
antibody 

Immune response to A/Vietnam/1194/2004 (D42) 

 61 to 70 years 71 to 80 years  >80 years 
Single 
dose 
N=91 

Double 
dose 
N=92 

Single 
dose 
N=48 

Double 
dose 
N=43 

Single 
dose 
N=13 

Double 
dose 
N=10 

Seroprotection 
rate1 

84.6% 97.8% 87.5% 93.0% 61.5% 90.0% 

Seroconversion 
rate2 

74.7% 90.2% 77.1% 93.0% 38.5% 50.0% 

Seroconversion 
factor3 

11.8 26.5 13.7 22.4 3.8 7.7 

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. 
 
Although an adequate immune response was achieved at day 42 following two administrations of a 
single dose of AS03-adjuvanted vaccine containing 3.75 µg HA derived from A/Vietnam/1194/2004 
(H5N1), a higher response was observed following two administrations of a double dose of vaccine. 
 
Very limited data in seronegative subjects >80 years of age (N=5) showed that no subject achieved 
seroprotection following two administrations of a single dose of AS03-adjuvanted vaccine containing 
3.75 µg HA derived from A/Vietnam/1194/2004 (H5N1). However, following two administrations of 
a double dose of vaccine, the seroprotection rate at day 42 was 75%. 
 
Subjects of D-Pan-H5N1-010 were followed up for persistence of the immune response.  The 
seroprotection rates 6, 12 and 24 months after vaccination were as follows: 
 
anti-HA antibody Immune response to A/Vietnam/1194/2004 
 6 months after 

vaccination 
12 months after 

vaccination 
24 months after 

vaccination 
 Single 

dose 
(N=140) 

Double 
dose 

(N=131) 

Single 
dose 

(N=86) 

Double 
dose 

(N=81) 

Single 
dose 

(N=86) 

Double 
dose 

(N=81) 
Seroprotection rate1 52.9% 69.5% 45.3% 44.4% 37.2% 30.9% 



14 

1seroprotection rate: proportion of subjects with haemagglutination inhibition (HI) titre ≥1:40 
 
In addition, 44.8% and 56.1% of subjects in respective dose groups had a 4-fold increase in serum 
neutralising antibody titres from day 0 to day 42 and 96.6% and 100% of subjects had a titre of at least 
1:80 at day 42. 
 
Twelve and twenty-four months after vaccination, the neutralising antibody titres were as follows: 
 
Serum neutralising 
antibody 

Immune response to A/Vietnam/1194/2004 

 12 months after vaccination 24 months after vaccination 
 Single dose 

N=51 
Double dose 

N=54 
Single dose 

N=49 
Double dose 

N=54 
GMT1 274.8 272.0 391.0 382.8 
Seroconversion 
rate2 

27.5% 27.8% 36.7% 40.7% 

≥1:803 82.4% 90.7% 91.8% 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 
 
Information from non-clinical studies: 
 
The ability to induce protection against homologous and heterologous vaccine strains was assessed 
non-clinically using ferret challenge models. 
 
In each experiment, four groups of six ferrets were immunized intramuscularly with an AS03 
adjuvanted vaccine containing HA derived from H5N1/A/Vietnam/1194/04 (NIBRG-14). Doses of 15, 
5, 1.7 or 0.6 micrograms of HA were tested in the homologous challenge experiment, and doses of 15, 
7.5, 3.8 or 1.75 micrograms of HA were tested in the heterologous challenge experiment. Control 
groups included ferrets immunized with adjuvant alone, non-adjuvanted vaccine (15 micrograms HA) 
or phosphate buffered saline solution. Ferrets were vaccinated on days 0 and 21 and challenged by the 
intra-tracheal route on day 49 with a lethal dose of either H5N1/A/Vietnam/1194/04 or heterologous 
H5N1/A/Indonesia/5/05. Of the animals receiving adjuvanted vaccine, 87% and 96% were protected 
against the lethal homologous or heterologous challenge, respectively. Viral shedding into the upper 
respiratory tract was also reduced in vaccinated animals relative to controls, suggesting a reduced risk 
of viral transmission. In the unadjuvanted control group, as well as in the adjuvant control group, all 
animals died or had to be euthanized as they were moribund, three to four days after the start of 
challenge. 
 
5.2 Pharmacokinetic properties 
 
Not applicable. 
 
5.3  Preclinical safety data 
 
Non-clinical data 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). The reproductive toxicity studies have been 
conducted using Prepandrix containing A/Vietnam/1194/2004.   
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 



15 

Suspension vial: 
Polysorbate 80 
Octoxynol 10 
Thiomersal 
Sodium chloride (NaCl) 
Disodium hydrogen phosphate (Na2HPO4) 
Potassium dihydrogen phosphate (KH2PO4) 
Potassium chloride (KCl) 
Magnesium chloride (MgCl2) 
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 
 
5 years 
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. 
 
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).   
 
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 
 
Prepandrix 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: 



16 

 
1. Before mixing the two components, the emulsion (adjuvant) and suspension (antigen) should be 

allowed to reach room temperature (for a minimum of 15 minutes); each vial should be shaken 
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. 

2. 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.  

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

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

5. 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. 

6. 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.  

7. 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 (for 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/1/08/453/002 
 
 
9.  DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 14 May 2008 
Date of latest renewal: 28 November 2017 
 
 
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/ 



17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND USE OF THE MEDICINAL PRODUCT 
 



18 

 
A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 

MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer of the biological active substance 
 
GlaxoSmithKline Biologicals 
Branch of SmithKline Beecham Pharma GmbH & Co. KG 
Zirkusstraße 40, D-01069 Dresden 
Germany 
 
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. 
 
• Official batch release 
 
In accordance with Article 114 of Directive 2001/83/EC, the official batch release will be undertaken 
by a state laboratory or a laboratory designated for that purpose. 
 
 
C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

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

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan (RMP) 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the  
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP. 
 
An updated RMP should be submitted: 

• At the request of the European Medicines Agency 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 
 

 



19 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



21 

 
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 
 
Prepandrix suspension and emulsion for emulsion for injection  
Prepandemic 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 
 
Polysorbate 80 
Octoxynol 10 
Thiomersal 
Sodium chloride (NaCl) 
Disodium hydrogen phosphate (Na2HPO4) 
Potassium dihydrogen phosphate (KH2PO4) 
Potassium chloride (KCl) 
Magnesium chloride (MgCl2) 
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 0.5 ml vaccine 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intramuscular use 
Shake before use 
Read the package leaflet before use 



22 

 
 
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: MM/YYYY 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator 
Do not freeze 
Store in the original package in order to protect from light 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
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/1/08/453/002 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 



23 

 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN: 



24 

 
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
PACK OF 50 VIALS OF SUSPENSION 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Suspension for emulsion for injection for Prepandrix 
Prepandemic 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/05/2005 (H5N1) like strain used (PR8-IBCDC-RG2)  
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: 
Polysorbate 80 
Octoxynol 10 
Thiomersal 
Sodium chloride 
Disodium hydrogen phosphate 
Potassium dihydrogen phosphate 
Potassium chloride 
Magnesium 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 SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 



25 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Suspension to be exclusively mixed with adjuvant emulsion before administration 
 
 
8. EXPIRY DATE 
 
EXP: MM/YYYY 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator 
Do not freeze 
Store in the original package in order to protect from light 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
GSK Biologicals, Rixensart - Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/08/453/002 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 



26 

 
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
PACK OF 25 VIALS OF EMULSION 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Emulsion for emulsion for injection for Prepandrix 
 
 
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: MM/YYYY 



27 

 
 
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/1/08/453/002 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 



28 

 
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 Prepandrix  
A/Indonesia/05/2005 (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 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 



29 

 
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 Prepandrix 
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 



30 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



31 

 
Package Leaflet: Information for the user 

 
Prepandrix suspension and emulsion for emulsion for injection 

Prepandemic 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. See section 4. 
 
What is in this leaflet  
1. What Prepandrix is and what it is used for 
2. What you need to know before you receive Prepandrix 
3. How Prepandrix is given 
4. Possible side effects 
5. How to store Prepandrix 
6. Contents of the pack and other information 
 
 
1. What Prepandrix is and what it is used for 
 
What Prepandrix is and what it is used for 
Prepandrix is a vaccine for use in adults from 18 years old. It is intended to be given before or during 
the next influenza (flu) pandemic to prevent flu caused by the H5N1 type of the virus. 
 
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 Prepandrix 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, Prepandrix may not fully protect all persons who are vaccinated. 
 
 
2. What you need to know before you receive Prepandrix 
 
Prepandrix 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, gentamicin sulphate (antibiotic) or 
sodium deoxycholate. Signs of an allergic reaction may include itchy skin rash, shortness of 
breath and swelling of the face or tongue. 

 
• if you have a serious infection with a high temperature (over 38°C). If this applies to you then 

your vaccination will 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 
Prepandrix. 

 
Do not have Prepandrix if any of the above apply to you.   
 



32 

If you are not sure, talk to your doctor or nurse before having this vaccine. 
 
Warnings and precautions 
 
Talk to your doctor or nurse before you are given Prepandrix: 
 
• 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, gentamicin sulphate (antibiotic) or to sodium deoxycholate. 

• 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 Prepandrix the results of these tests may not be correct. Tell 
the doctor requesting these tests that you have recently received Prepandrix. 

• if you have a bleeding problem or you bruise easily. 
 
Fainting can occur following, or even before, any needle injection. Therefore tell the doctor or nurse if 
you fainted with a previous injection. 
 
If any of the above apply to you (or you are not sure), talk to your doctor or nurse before having 
Prepandrix.  This is because the vaccination may not be recommended, or may need to be delayed. 
 
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 Prepandrix 
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, tell your doctor or nurse if you are having any treatments (such as corticosteroid 
treatments or chemotherapy for cancer) that affect the immune system.  Prepandrix can still be given 
but your response to the vaccine may be poor. 
 
Prepandrix 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 side 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 Prepandrix affects you before you try these activities. 
 
Prepandrix contains thiomersal  
Prepandrix 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. 
 
Prepandrix contains sodium and potassium  
Prepandrix 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. 
 
 



33 

3. How Prepandrix is given 
 
• From 18 years onwards: you will receive two doses of Prepandrix. The second dose should be 

given after an interval of at least three weeks and up to twelve months after the first dose. 
 
• From 80 years onwards:  you may receive two double injections of Prepandrix. The first two 

injections should be given at the elected date and the two other injections should preferably be 
given 3 weeks after. 

 
Use in children 
 
In a clinical study, children 3 to 9 years of age have received either two adult (0.5 ml) or two half adult 
(0.25 ml) doses of a similar vaccine containing A/Vietnam/1194/2004.  Your doctor will decide the 
appropriate dose for your child. 
 
Your doctor or nurse will give you Prepandrix. 
 
• They will give Prepandrix as an injection into a muscle. 
• This will usually be in the upper arm. 
• The double injections will be given in opposite arms. 
 
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 
• Feeling tired 
• Headache 
• Pain, redness, swelling or a hard lump where the injection was given 
• Fever 
• Aching muscles, joint pain 

 
Common: may affect up to 1 in 10 people 
• Warmth, itching or bruising where the injection was given 
• Increased sweating, shivering, flu-like symptoms 
• Swollen glands in your neck, armpit or groin 
 
Uncommon: may affect upt o 1 in 100 people 
• Tingling or numbness of the hands or feet 
• Feeling dizzy 
• Sleepiness 
• Sleeplessness 
• Diarrhoea, vomiting, stomach pain, feeling sick 
• Itching, rash 
• Generally feeling unwell 
 



34 

 
Additional side effects in children 
 
In a clinical study, children 3 to 9 years of age have received either two adult (0.5 ml) or two half adult 
(0.25 ml) doses of a similar vaccine containing A/Vietnam/1194/2004.  The frequency of side effects 
was lower in the group of children who received half of the adult dose.  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 Prepandrix, 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 Prepandrix. 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 other vaccines 
given routinely every year to prevent flu.  These side effects may also happen with Prepandrix. If any 
of the side effects below occur, please tell your doctor or nurse immediately: 
 
Very rare: may affect up to 1 in 10,000 people 
• 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’. 

• Inflammation of your blood vessels (vasculitis).  This can cause skin rashes, joint pain and 
kidney problems 

 
Rare: may affect up to 1 in 1,000 people 
• Serious stabbing or throbbing pain along one or more nerves 
• Low blood platelet count. This can cause bleeding or bruising  
 
Reporting of side effects  
If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this 
leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. 
By reporting side effects you can help provide more information on the safety of this medicine. 
 
 
5. How to store Prepandrix 
 
Keep this vaccine out of the sight and reach 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 - 8°C).  
Store in the original package in order to protect from light. 
Do not freeze. 



35 

 
After the vaccine is mixed: 
After mixing, use the vaccine within 24 hours and do not store above 25°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 Prepandrix contains 
 
• Active substance: 

Split influenza virus, inactivated, containing antigen* equivalent to: 
 
A/Indonesia/05/2005 (H5N1) like strain used (PR8-IBCDC-RG2) 3.75 micrograms** per 0.5 
ml 
 
*propagated in eggs 
**expressed in microgram haemagglutinin 
 

• 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: polysorbate 80, octoxynol 10, thiomersal, sodium chloride, disodium 
hydrogen phosphate, potassium dihydrogen phosphate, potassium chloride, magnesium 
chloride, water for injections 

 
What Prepandrix looks like and contents of the pack 
 
The suspension is a colourless light opalescent liquid.  
The emulsion is a whitish to yellowish homogeneous milky liquid. 
 
Before the vaccine is given, the two parts will be mixed together. The mixed vaccine is a whitish to 
yellowish homogeneous milky liquid emulsion. 
 
One pack of Prepandrix 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 vaccine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
 
Belgique/België/Belgien Lietuva 



36 

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

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

 
България 
ГлаксоСмитКлайн ЕООД 
Тел. + 359 2 953 10 34 
 

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

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

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

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

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

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

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

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

Norge 
GlaxoSmithKline AS 
Tlf: + 47 22 70 20 00 
 
 

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

Österreich 
GlaxoSmithKline Pharma GmbH 
Tel: + 43 (0)1 97075 0 
at.info@gsk.com  
 

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

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

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

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

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

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

Ísland 
Vistor hf.  
Sími: +354 535 7000 
 

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

  



37 

Italia 
GlaxoSmithKline S.p.A. 
Tel: + 39 (0)45 9218 111 
 

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

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

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

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

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

This leaflet was last revised in 
 
Other sources of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
--------------------------------------------------------------------------------------------------------------------- 
 
The following information is intended for healthcare professionals only: 
 
Prepandrix 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 (for a minimum of 15 minutes); each vial should be shaken 
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. 

2.  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. 

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

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

5.  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. 

6.  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.  

7. 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 



38 

stored in a refrigerator, it should be allowed to reach room temperature (for 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. 
 
 


	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
	D CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET