ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
1.
Focetria suspension for injection in pre-filled syringe
Influenza vaccine H1N1v (surface antigen, inactivated, adjuvanted)
2.
Influenza virus surface antigens (haemagglutinin and neuraminidase)* of strain:
A/California/07/2009 (H1N1)-derived strain used NYMC X-181
7.5 micrograms** per 0.5 ml
* propagated in eggs
** expressed in microgram haemagglutinin.
Adjuvant MF59C.1 containing:
squalene 9.75 milligrams
polysorbate 80 1.175 milligrams
sorbitan trioleate 1.175 milligrams
For a full list of excipients, see section 6.1.
3.
Suspension for injection in pre-filled syringe.
Milky-white liquid.
4.
Prophylaxis of influenza caused by AH1N1v 2009 virus (see section 4.4).
Influenza vaccine should be used in accordance with Official Guidance.
The dose recommendations take into account the safety and immunogenicity data from clinical studies
in healthy subjects.
No data are available in children aged less than 6 months (see sections 4.8 and 5.1).
Posology:
Adults (18-60 years):
One dose of 0.5 ml at an elected date.
Immunogenicity data obtained at three weeks after one dose of Focetria H1N1v suggest that a single
dose may be sufficient.
If a second dose is administered there should be an interval of at least three weeks between the first
and second dose.
Elderly (>60 years):
One dose of 0.5 ml at an elected date.
A second dose of vaccine should be given after an interval of at least three weeks.
2
dose
Children and adolescents aged 3-17 years:
One dose of 0.5 ml at an elected date.
Immunogenicity data obtained at three weeks after one dose of Focetria H1N1v suggest that a single
dose may be sufficient. If a second dose is administered there should be an interval of at least three
weeks between the first and second dose.
Children aged 6 months to 35 months
:
One dose of 0.5 ml at an elected date.
There is a further immune response to a second dose of 0.5 ml administered after an interval of three
weeks.
Children aged less than 6 months:
Vaccination is not currently recommended in this age group.
It is recommended that subjects who receive a first dose of Focetria, should complete the vaccination
course with Focetria H1N1v (see section 4.4).
The use of a second dose should take into consideration the information provided in 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).
History of an anaphylactic (i.e. life-threatening) reaction to any of the constituents or trace residues
(egg and chicken proteins, ovalbumin, kanamycin and neomycin sulphate, formaldehyde and
cetyltrimethylammonium bromide (CTAB)) of this vaccine.
See section 4.4 for Special warnings and special precautions for use.
The vaccine can only be expected to protect against influenza caused by A/California/07/2009
(H1N1)v-like strains.
Caution is needed when administrating this vaccine to persons with a known hypersensitivity (other
than anaphylactic reaction) to the active substance, to any of the excipients and to residues (eggs and
chicken protein, ovalbumin, kanamycin and neomycin sulphate, formaldehyde and
cetyltrimethylammonium bromide (CTAB)).
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.
Immunisation should be postponed in patients with severe febrile illness or acute infection.
Focetria should under no circumstances be administered intravascularly.
There are no data with Focetria 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.
Antibody response in patients with endogenous or iatrogenic immunosuppression may be insufficient.
A protective response may not be elicited in all vaccinees (see section 5.1).
3
In the event that a second dose is to be administered it should be noted that there are no safety,
immunogenicity or efficacy data to support interchangeability of Focetria with other H1N1v vaccines.
Focetria H1N1v may be co-administered with a non adjuvanted seasonal influenza vaccine.
Data on
co-administration of Focetria H1N1v with a non-adjuvanted seasonal influenza subunit vaccine in
healthy adults aged 18-60 years of age did not suggest any interference in the immune response to
Focetria. The immune response to the seasonal antigens was satisfactory.
Co-administration was not associated with higher rates of local or systemic reactions compared to
administration of Focetria alone.
The same study demonstrated that previous administration of adjuvanted or unadjuvanted seasonal
influenza vaccines to adults and elderly does not interfere with the immune response to Focetria.
Therefore the data indicate that Focetria may be co-administered with non adjuvanted seasonal
influenza vaccines (with injections made into opposite limbs).
There are no data on co-administration of Focetria 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.
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.
It is estimated that more than 90,000 women have been vaccinated during pregnancy with Focetria
H1N1v.
However information on outcomes is currently limited. Preliminary data from spontaneously reported
events and ongoing post-marketing studies (pregnancy registry and prospective interventional study)
do not suggest direct or indirect harmful effects with respect to pregnancy.
Data from pregnant women vaccinated with different inactivated non-adjuvanted seasonal vaccines do
not suggest malformations or fetal or neonatal toxicity.
An animal study with H5N1 mock-up vaccine did not indicate reproductive toxicity (see section 5.3).
The use of Focetria during pregnancy has to take into account official recommendations.
Focetria may be administered to lactating women.
Some of the effects mentioned under section 4.8 “Undesirable Effects” may affect the ability to drive
or use machines.
•
Clinical trials
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).
4
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness:
Adult and Elderly
In a clinical trial 131 adults and 123 elderly were exposed to two doses of the 7.5 µg Focetria. The
safety profile of Focetria was similar to that of the H5N1 mock up vaccines. Most of the reactions
were mild in nature and of short duration. The incidence of symptoms observed in subjects over 60
years of age was generally lower as compared to the 18-60 years old population.
Very common: pain, induration and erythema, myalgia, headache, sweating, malaise and fatigue
In clinical trials with different formulations (H5N3, H9N2 and H5N1) approximately 3400 subjects
were exposed to the mock-up vaccines.
Most of the reactions were mild in nature, of short duration and qualitatively similar to those induced
by conventional seasonal influenza vaccines. It is widely accepted that the adjuvant effect leading to
increased immunogenicity is associated with a slightly higher frequency of local reactions (mostly
mild pain) compared with conventional, nonadjuvanted influenza vaccines. There were fewer reactions
after the second vaccination compared with the first.
Adverse reactions from clinical trials with the mock-up vaccine are listed below.
The incidence of symptoms observed in subjects over 60 years of age was lower as compared to the
18-60 years old population.
Nervous system disorders
Very common: headache
Rare: convulsions
Skin and subcutaneous tissue disorders
Common: sweating
Uncommon: urticaria
Rare: eye swelling
Muscoskeletal, connective tissue and bone disorders
Very common: myalgia
Common: arthralgia
Gastrointestinal disorders
Common: nausea
General disorders and administration site conditions
Very common: injection site swelling, injection site pain, injection site induration, injection site
redness, fatigue, malaise and shivering
Common: injection site ecchymosis and fever
Uncommon: influenza like illness
Rare: anaphylaxis
The common reactions usually disappear within 1-2 days without treatment.
Children and adolescents 6 months to 17 years of age
Clinical trials with Focetria H1N1v
Safety data after the first and second dose in children and adolescents suggest a comparable safety
profile with that reported for the H5N1 mock-up vaccine formulation.
Adverse reactions in the week following vaccination from 87 children 3-8 years old and 95 children
and adolescents 9-17 years old receiving the 7.5 µg formulation were reported as follows:
Injection 1
Injection 2
5
Children (3 to 8 years of age)
N=87
N=85
Any adverse reaction
67%
61%
Local
56%
49%
Systemic
32%
31%
Fever ≥ 38°C to 38.9°C
3%
1%
Fever 39°C to 39.9°C
0%
1%
Fever ≥ 40° C
0%
0%
Any other AE
13%
15%
Adolescents (9 to 17 years of age)
N=95
N=94
Any adverse reaction
67%
55%
Local
60%
49%
Systemic
38%
26%
Fever ≥38°C to 38.9°C
2%
1%
Fever 39°C to 39.9°C
0%
0%
Fever ≥ 40° C
0%
0%
Any other AE
11%
9%
Data in children and adolescents 3-17 years suggest a slight decrease in reactogenicity after the second
dose, with no increase in rates of fever.
Very common reactions reported in children and adolescents 3 to 17 years of age:
Pain, induration and erythema, malaise, myalgia, headache and fatigue.
Adverse reactions in the week following vaccination from 80 infants 6-11 months old and 82 toddlers
12-35 months old, receiving the 7.5 µg formulation were reported as follows:
Injection 1
Injection 2
Infants (6 to 11 months of age)
N=80
N=75
Any adverse reaction
79%
65%
Local
44%
29%
Systemic
69%
55%
Fever ≥38°C to 38.9°C
9%
6%
Fever 39°C to 39.9°C
2%
4%
Fever ≥ 40° C
0%
0%
Any other AE
29%
28%
Toddlers (12 to 35 months of age)
N=82
N=81
Any adverse reaction
70%
70%
Local
50%
48%
Systemic
55%
44%
Fever ≥38°C to 38.9°C
10%
11%
Fever 39°C to 39.9°C
4%
1%
Fever ≥ 40° C
1%
0%
Any other AE
21%
22%
Data in infants and toddlers 6-35 months of age suggest a slight decrease in reactogenicity after the
second dose, with no increase in rates of fever.
Very common reactions reported in 233 infants and toddlers 6 to 35 months of age:
Tenderness, erythema, irritability, unusual crying, sleepiness, diarrhoea and change in eating habits.
Induration was a common reaction in toddlers but was less common in infants.
•
Post-marketing surveillance
Focetria H1N1v
6
In addition to the adverse reactions reported in the clinical trials, the following have been reported
during post-marketing experience with Focetria H1N1v:
Blood and lymphatic system disorders
Lymphadenopathy.
Cardiac disorders
Palpitation, tachycardia.
General disorders and administration site conditions
Asthenia.
Muscoskeletal, connective tissue and bone disorders
Muscular weakness, pain in extremities.
Respiratory disorders
Cough.
Skin and subcutaneous tissue disorders
Generalised skin reactions including pruritus, urticaria or non-specific rash; angioedema.
Gastrointestinal disorders
Gastrointestinal disorders such as nausea, vomiting, abdominal pain and diarrhoea.
Nervous system disorders
Headache, dizziness, somnolence, syncope.
N
eurological disorders, such as neuralgia, paraesthesia,
convulsions and neuritis.
Immune system disorders
Allergic reactions, anaphylaxis including dyspnoea, bronchospasm, laryngeal oedema, in rare cases
leading to shock.
In addition, from Post-marketing surveillance with seasonal trivalent vaccines in all age groups and
with the MF59 adjuvanted seasonal trivalent vaccine with the similar composition of Focetria (surface
antigen, inactivated, adjuvanted with MF59C.1), licensed for use in elderly subjects above 65 years of
age, the following adverse events have been reported:
Rare
:
Transient thrombocytopenia.
Very rare
:
Vasculitis with transient renal involvement and exudative erythema multiforme.
Neurological disorders, such as encephalomyelitis and Guillain Barré syndrome.
No case of overdose has been reported.
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Influenza vaccine, ATC Code: J07BB02
Clinical studies with Focetria H1N1v currently provide:
7
•
Safety and immunogenicity data obtained after administration of one or two doses of Focetria
H1N1v to healthy children and adolescents aged 6 months-17 years and to healthy adults,
including the elderly.
Clinical studies in which a version of Focetria containing HA derived from A/Vietnam/1194/2004
(H5N1) was administered at day 1 and at day 22 provide:
•
Safety and immunogenicity data in healthy children and adolescents aged from 6 months to 17
years and in adults, including the elderly
Immune response to Focetria H1N1v
•
Studies in adults and elderly:
Immunogencity results with two doses of 7.5 µg Focetria H1N1v vaccine from the ongoing clinical
trial in adults and elderly are shown below.
The seroprotection rate*, seroconversion rate* and the seroconversion factor ** for anti-HA antibody
to A/H1N1v in adult and elderly subjects by HI assay after administration of 7.5 µg of Focetria were
as follows:
Adults (18-60 years)
Anti-HA antibody
21 days after 1
st
dose(day 22)
21 days after 2
nd
dose (day 43)
Total
N=120
Seronegative at
baseline
N=46
Total
N=120
Seronegative at
baseline
N=46
Seroprotection rate
(95% CI)
96% (91-99)
98% (88-100)
100% (97-100)
100% (92-100)
GMR (95% CI)
17 (13-23)
44 (24-80)
23 (17-30)
75 (45-124)
Seroconversion or
Significant Increase
(95% CI)
88% (81-93)
98% (88-100)
95% (89-98)
100% (92-100)
* measured by HI assay
** geometric mean ratios of HI
Elderly (>60 years)
Anti-HA antibody
21 days after 1
st
dose(day 22)
21 days after 2
nd
dose (day 43)
Total
N=117
Seronegative at
baseline
N=25
Total
N=117
Seronegative at
baseline
N=25
Seroprotection rate
(95% CI)
73% (64-80)
60% (39-79)
88% (81-93)
84% (64-95)
GMR (95% CI)
4.02 (3.1-5.2)
5.48 (2.82-11)
6.85 (5.36-8.75)
18 (8.9-35)
Seroconversion or
Significant Increase
(95% CI)
43% (34-52)
60% (39-79)
62% (53-71)
84% (64-95)
•
Studies in children
The seroprotection rate*, seroconversion rate* and the seroconversion factor** for anti-HA antibody
to H1N1v in children and adolescents aged 9-17 years by HI assay after administration of 7.5 µg of
Focetria were as follows:
Children and Adolescents (9-17 years)
Anti-HA antibody
21 days after 1
st
dose(day 22)
21 days after 2
nd
dose (day 43)
Total
Seronegative at
Total
Seronegative at
8
N=88
baseline
N=51
N=88
baseline
N=51
Seroprotection rate
(95% CI)
97% (90-99)
94% (84-99)
99% (94-100)
98% (90-100)
GMR (95% CI)
62 (38-100)
102 (60-170)
83 (54-127)
169 (122-235)
Seroconversion or
Significant Increase
(95% CI)
94% (87-98)
94% (84-99)
94% (87-98)
98% (90-100)
* measured by HI assay
** geometric mean ratios of HI
Data on responses to a second dose administered after an interval of three weeks showed an increase in
overall GMT from 793 to 1065 (N=88) and an increase in GMT from 522 to 870 in children who were
seronegative at baseline (N=51).
The seroprotection rate*, seroconversion rate* and the seroconversion factor** for anti-HA antibody
to H1N1v in children aged 3-8 years by HI assay after administration of 7.5 µg of Focetria were as
follows:
Children (3-8 years)
Anti-HA antibody
21 days after 1
st
dose(day 22)
21 days after 2
nd
dose (day 43)
Total
N=70
Seronegative at
baseline
N=48
Total
N=70
Seronegative at
baseline
N=48
Seroprotection rate
(95% CI)
100% (95-100)
100% (93-100)
100% (95-100)
100% (93-100)
GMR (95% CI)
37 (25-55)
50 (32-76)
81 (52-125)
146 (100-212)
Seroconversion or
Significant Increase
(95% CI)
99% (92-100)
100% (93-100)
99% (92-100)
100% (93-100)
* measured by HI assay
** geometric mean ratios of HI
Data on responses to a second dose administered after an interval of three weeks showed an increase in
overall GMT from 319 to 702 (N=70) and an increase in GMT from 247 to 726 in children who were
seronegative at baseline (N=48).
The seroprotection rate*, seroconversion rate* and the seroconversion factor** for anti-HA antibody
to H1N1v in children aged 12-35 months by HI assay after administration of 7.5 µg of Focetria were
as follows:
Children 12-35 months
Anti-HA antibody
21 days after 1
st
dose(day 22)
21 days after 2
nd
dose (day 43)
Total
N=66
Seronegative at
baseline
N=45
Total
N=66
Seronegative at
baseline
N=45
Seroprotection rate
(95% CI)
100% (95-100) 100% (92-100)
100%
(95-100)
100% (92-100)
GMR (95% CI)
33 (21-51)
48 (29-79)
93
(54-159)
145 (88-238)
Seroconversion or
Significant Increase
(95% CI)
100% (95-100) 100% (92-100) 100% (95-100) 100% (92-100)
* measured by HI assay
** geometric mean ratios of HI
9
Data on responses to a second dose administered after an interval of three weeks showed an increase in
overall GMT from 307 to 873 (N=66) and an increase in GMT from 243 to 733 in children who were
seronegative at baseline (N=45).
The seroprotection rate*, seroconversion rate* and the seroconversion factor** for anti-HA antibody
to H1N1v in infants aged 6-11 months by HI assay after administration of 7.5 µg of Focetria were as
follows:
Infants 6-11 months
Anti-HA antibody
21 days after 1
st
dose(day 22)
21 days after 2
nd
dose (day 43)
Total
N=57
Seronegative at
baseline
N=37
Total
N=57
Seronegative at
baseline
N=37
Seroprotection rate
(95% CI)
100% (94-100) 100% (91-100) 100% (94-100) 100% (91-100)
GMR (95% CI)
21 (14-30)
32 (18-55)
128 (74-221)
274 (196-383)
Seroconversion or
Significant Increase
(95% CI)
96% (88-100) 100% (91-100) 98% (91-100)
100% (91-100)
* measured by HI assay
** geometric mean ratios of HI
Data on responses to a second dose administered after an interval of three weeks showed an increase in
overall GMT from 274 to 1700 (N=57) and an increase in GMT from 162 to 1399 in children who
were seronegative at baseline (N=37).
Additional information is available from the studies conducted with a vaccine similar in composition
to Focetria but containing antigen derived from H5N1 viruses. Please consult the Product Information
of
Pandemic influenza vaccine (H5N1) (surface antigen, inactivated, adjuvanted).
5.2 Pharmacokinetic properties
Not applicable.
5.3 Preclinical safety data
Non-clinical data obtained with the mock-up vaccine (MF59C.1-adjuvanted H5N1 vaccine) and with
seasonal vaccine containing MF59C.1 adjuvant reveal no special hazard for humans based on
conventional studies of efficacy, repeated dose toxicity, and reproductive and developmental toxicity.
6.
6.1 List of excipients
Sodium chloride,
Potassium chloride,
Potassium dihydrogen phosphate,
Disodium phosphate dihydrate,
Magnesium chloride hexahydrate,
Calcium chloride dihydrate,
Sodium citrate,
Citric acid,
Water for injections.
10
For the adjuvant, 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
1 year.
6.4 Special precautions for storage
Store in a refrigerator (2°C - 8°C). Do not freeze. Store in the original package in order to protect from
light.
6.5 Nature and contents of container
0.5 ml in pre-filled syringe (type I glass) with plunger-stopper (bromo-butyl rubber). Packs of 1 and
10.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
The vaccine should be allowed to reach room temperature before use. Gently shake before use.
Any unused vaccine or waste material should be disposed of in accordance with local requirements.
7.
Novartis Vaccines and Diagnostics S.r.l. - Via Fiorentina, 1 – Siena, Italy.
8.
EU/1/07/385/001
EU/1/07/385/002
9.
02 May 2007
Detailed information on this product is available on the website of the European Medicines Agency
(EMA): http://www.ema.europa.eu/.
11
1.
Focetria suspension for injection in multidose container
Influenza vaccine H1N1v (surface antigen, inactivated, adjuvanted)
2.
Influenza virus surface antigens (haemagglutinin and neuraminidase)* of strain:
A/California/07/2009 (H1N1)-derived strain used NYMC X-181
7.5 micrograms ** per 0.5
* propagated in eggs
** expressed in microgram haemagglutinin.
Adjuvant MF59C.1 containing:
squalene 9.75 milligrams
polysorbate 80 1.175 milligrams
sorbitan trioleate 1.175 milligrams
Excipients:
thiomersal 0.05 milligrams
This is a multidose container.
See section 6.5 for the number of doses per vial.
For a full list of excipients, see section 6.1.
3.
Suspension for injection.
Milky-white liquid.
4.
Prophylaxis of influenza caused by AH1N1v 2009 virus (see section 4.4).
Influenza vaccine should be used in accordance with Official Guidance.
The dose recommendations take into account the safety and immunogenicity data from clinical studies
in healthy subjects.
No data are available in children aged less than 6 months(see sections 4.8 and 5.1).
Posology:
Adults (18-60 years):
One dose of 0.5 ml at an elected date.
Immunogenicity data obtained at three weeks after one dose of Focetria H1N1v suggest that a single
dose may be sufficient.
If a second dose is administered there should be an interval of at least three weeks between the first
and second dose.
12
ml dose
Elderly (>60 years):
One dose of 0.5 ml at an elected date.
A second dose of vaccine should be given after an interval of at least three weeks.
Children and adolescents aged 3-17 years:
One dose of 0.5 ml at an elected date.
Immunogenicity data obtained at three weeks after one dose of Focetria H1N1v suggest that a single
dose may be sufficient.
If a second dose is administered there should be an interval of at least three weeks between the first
and second dose.
Children aged 6 months to 35 months
:
One dose of 0.5 ml at an elected date.
There is a further immune response to a second dose of 0.5 ml administered after an interval of three
weeks.
Children aged less than 6 months:
Vaccination is not currently recommended in this age group.
It is recommended that subjects who receive a first dose of Focetria, should complete the vaccination
course with Focetria H1N1v (see section 4.4).
The use of a second dose should take into consideration the information provided in 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).
History of an anaphylactic (i.e. life-threatening) reaction to any of the constituents or trace residues
(egg and chicken proteins, ovalbumin, kanamycin and neomycin sulphate, formaldehyde and
cetyltrimethylammonium bromide (CTAB)) of this vaccine.
See section 4.4. for Special warnings and special precautions for use.
The vaccine can only be expected to protect against influenza caused by A/California/07/2009
(H1N1)v-like strains.
Caution is needed when administrating this vaccine to persons with a known hypersensitivity (other
than anaphylactic reaction) to the active substance, to any of the excipients, to thiomersal and to
residues (eggs and chicken protein, ovalbumin, kanamycin and neomycin sulphate, formaldehyde and
cetyltrimethylammonium bromide (CTAB)).
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.
Immunisation should be postponed in patients with severe febrile illness or acute infection.
Focetria should under no circumstances be administered intravascularly.
There are no data with Focetria 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.
13
Antibody response in patients with endogenous or iatrogenic immunosuppression may be insufficient.
A protective response may not be elicited in all vaccinees (see section 5.1).
In the event that a second dose is to be administered it should be noted that there are no safety,
immunogenicity or efficacy data to support interchangeability of Focetria with other H1N1v vaccines.
Focetria H1N1v may be co-administered with a non adjuvanted seasonal influenza vaccine.
Data on
co-administration of Focetria H1N1v with a non-adjuvanted seasonal influenza subunit vaccine in
healthy adults aged 18-60 years of age did not suggest any interference in the immune response to
Focetria. The immune response to the seasonal antigens was satisfactory.
Co-administration was not associated with higher rates of local or systemic reactions compared to
administration of Focetria alone.
The same study demonstrated that previous administration of adjuvanted or unadjuvanted seasonal
influenza vaccines to adults and elderly does not interfere with the immune response to Focetria.
Therefore the data indicate that Focetria may be co-administered with non adjuvanted seasonal
influenza vaccines (with injections made into opposite limbs).
There are no data on co-administration of Focetria with other vaccines.
If co-administration with another vaccine is indicated, immunisation should be carried out on separate
limbs. It should be noted that the adverse reactions may be intensified.
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 have been observed. In such cases, the Western Blot method is negative. These transitory
false-positive results may due to IgM production in response to the vaccine.
It is estimated that more than 90,000 women have been vaccinated during pregnancy with Focetria
H1N1v.
However information on the number of outcomes is currently limited. Preliminary data on outcomes
from spontaneously reported events and ongoing post-marketing studies (pregnancy registry and
prospective interventional study) do not suggest direct or indirect harmful effects with respect to
pregnancy.
Data from pregnant women vaccinated with different inactivated non-adjuvanted seasonal vaccines do
not suggest malformations or fetal or neonatal toxicity.
An animal study with H5N1 mock-up vaccine did not indicate reproductive toxicity (see section 5.3).
The use of Focetria during pregnancy has to take into account official recommendations.
Focetria may be administered to lactacting women.
Some of the effects mentioned under section 4.8 “Undesirable Effects” may affect the ability to drive
or use machines.
14
•
Clinical trials
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).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness:
Adults and elderly
In clinical trial 131 adults and 123 elderly were exposed to two doses of the 7.5 µg Focetria. The
safety profile of Focetria was similar to that of the H5N1 mock up vaccines. Most of the reactions
were mild in nature and of short duration. The incidence of symptoms observed in subjects over 60
years of age was generally lower as compared to the 18-60 years old population.
Very common: pain, induration and erythema, myalgia, headache, sweating, malaise and fatigue
In clinical trials with different formulations (H5N3, H9N2 and H5N1) approximately 3400 subjects
were exposed to the candidate vaccine.
Most of the reactions were mild in nature, of short duration and qualitatively similar to those induced
by conventional seasonal influenza vaccines. It is widely accepted that the adjuvant effect leading to
increased immunogenicity is associated with a slightly higher frequency of local reactions (mostly
mild pain) compared with conventional, nonadjuvanted influenza vaccines. There were fewer reactions
after the second vaccination compared with the first.
Adverse reactions from clinical trials with the mock-up vaccine are listed below.
The incidence of symptoms observed in subjects over 60 years of age was lower as compared to the
18-60 years old population.
Nervous system disorders
Very common: headache
Rare: convulsions
Skin and subcutaneous tissue disorders
Common: sweating
Uncommon: urticaria
Rare: eye swelling
Muscoskeletal, connective tissue and bone disorders
Very common: myalgia
Common: arthralgia
Gastrointestinal disorders
Common: nausea
General disorders and administration site conditions
Very common: injection site swelling, injection site pain, injection site induration, injection site
redness, fatigue, malaise and shivering
Common: injection site ecchymosis and fever
Uncommon: influenza like illness
Rare: anaphylaxis
15
The common reactions usually disappear within 1-2 days without treatment.
Children and adolescents 6 months to 17 years of age
Clinical trials with Focetria H1N1v
Safety data after the first and second dose in children and adolescents suggest a comparable safety
profile with that reported for the H5N1 mock-up vaccine formulation.
Adverse reactions in the week following vaccination from 87 children 3-8 years old and 95 children
and adolescents 9-17 years old, receiving the 7.5 µg formulation were reported as follows:
Injection 1
Injection 2
Children (3 to 8 years of age)
N=87
N=85
Any adverse reaction
67%
61%
Local
56%
49%
Systemic
32%
31%
Fever ≥38°C to 38.9°C
3%
1%
Fever 39°C to 39.9°C
0%
1%
Fever ≥ 40° C
0%
0%
Any other AE
13%
15%
Adolescents (9 to 17 years of age)
N=95
N=94
Any adverse reaction
67%
55%
Local
60%
49%
Systemic
38%
26%
Fever ≥38°C to 38.9°C
2%
1%
Fever 39°C to 39.9°C
0%
0%
Fever ≥ 40° C
0%
0%
Any other AE
11%
9%
Data in children and adolescents 3-17 years suggest a slight decrease in reactogenicity after the second
dose, with no increase in rates of fever.
Very common reactions reported in children and adolescents 3 to 17 years of age:
Pain, induration and erythema, malaise, myalgia, headache and fatigue.
Adverse reactions in the week following vaccination from 80 infants 6-11 months old and 82 toddlers
12-35 months old, receiving the 7.5 µg formulation were reported as follows:
Injection 1
Injection 2
Infants (6 to 11 months of age)
N=80
N=75
Any adverse reaction
79%
65%
Local
44%
29%
Systemic
69%
55%
Fever ≥38°C to 38.9°C
9%
6%
Fever 39°C to 39.9°C
2%
4%
Fever ≥ 40° C
0%
0%
Any other AE
29%
28%
Toddlers (12 to 35 months of age)
N=82
N=81
Any adverse reaction
70%
70%
Local
50%
48%
Systemic
55%
44%
Fever ≥38°C to 38.9°C
10%
11%
Fever 39°C to 39.9°C
4%
1%
Fever ≥ 40° C
1%
0%
Any other AE
21%
22%
16
Data in infants and toddlers 6-35 months of age suggest a slight decrease in reactogenicity after the
second dose, with no increase in rates of fever.
Very common reactions reported in 233 infants and toddlers 6 to 35 months of age:
Tenderness, erythema, irritability, unusual crying, sleepiness, diarrhoea and change in eating habits.
Induration was a common reaction in toddlers but was less common in infants.
•
Post-marketing surveillance
Focetria H1N1v
In addition to the adverse reactions reported in the clinical trials, the following have been reported
during post-marketing experience with Focetria H1N1v:
Blood and lymphatic system disorders
Lymphadenopathy.
Cardiac disorders
Palpitation, tachycardia.
General disorders and administration site conditions
Asthenia.
Muscoskeletal, connective tissue and bone disorders
Muscular weakness, pain in extremities.
Respiratory disorders
Cough.
Skin and subcutaneous tissue disorders
Generalised skin reactions including pruritus, urticaria or non-specific rash; angioedema.
Gastrointestinal disorders
Gastrointestinal disorders such as nausea, vomiting, abdominal pain and diarrhoea.
Nervous system disorders
Headache, dizziness, somnolence, syncope. Neurological disorders, such as neuralgia, paraesthesia,
convulsions and neuritis.
Immune system disorders
Allergic reactions, anaphylaxis including dyspnoea, bronchospasm, laryngeal oedema, in rare cases
leading to shock.
In addition, from Post-marketing surveillance with seasonal trivalent vaccines in all age groups and
with the MF59 adjuvanted seasonal trivalent vaccine with the similar composition of Focetria (surface
antigen, inactivated, adjuvanted with MF59C.1), licensed for use in elderly subjects above 65 years of
age, the following adverse events have been reported:
Rare
:
Transient thrombocytopenia.
Very rare
:
Vasculitis with transient renal involvement and exudative erythema multiforme.
Neurological disorders, such as encephalomyelitis and Guillain Barré syndrome.
Thiomersal
:
17
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).
No case of overdose has been reported.
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Influenza vaccine, ATC Code: J07BB02
Clinical studies with Focetria H1N1v currently provide:
•
Safety and immunogenicity data obtained after administration of a one or two doses of Focetria
H1N1v to healthy children and adolescents aged 6 months-17 years and to healthy adults,
including the elderly.
Clinical studies in which a version of Focetria containing HA derived from A/Vietnam/1194/2004
(H5N1) was administered at day 1 and at day 22 provide:
•
Safety and immunogenicity data in healthy children and adolescents aged from 6 months to 17
years and in adults, including the elderly
Immune response to Focetria H1N1v
•
Studies in adults and elderly
Immunogencity results with two doses of 7.5 µg Focetria H1N1v vaccine from the ongoing clinical
trial in adults and elderly are shown below.
The seroprotection rate*, seroconversion rate* and the seroconversion factor ** for anti-HA antibody
to A/H1N1v in adult and elderly subjects by HI assay after administration of 7.5 µg of Focetria were
as follows:
Adults (18-60 years)
Anti-HA antibody
21 days after 1
st
dose(day 22)
21 days after 2
nd
dose (day 43)
Total
N=120
Seronegative at
baseline
N=46
Total
N=120
Seronegative at
baseline
N=46
Seroprotection rate
(95% CI)
96% (91-99)
98% (88-100)
100% (97-100)
100% (92-100)
GMR (95% CI)
17 (13-23)
44 (24-80)
23 (17-30)
75 (45-124)
Seroconversion or
Significant Increase
(95% CI)
88% (81-93)
98% (88-100)
95% (89-98)
100% (92-100)
* measured by HI assay
** geometric mean ratios of HI
Elderly (>60 years)
Anti-HA antibody
21 days after 1
st
dose(day 22)
21 days after 2
nd
dose (day 43)
Total
N=117
Seronegative at
baseline
N=25
Total
N=117
Seronegative at
baseline
N=25
Seroprotection rate
(95% CI)
73% (64-80)
60% (39-79)
88% (81-93)
84% (64-95)
18
GMR (95% CI)
4.02 (3.1-5.2)
5.48 (2.82-11)
6.85 (5.36-8.75)
18 (8.9-35)
Seroconversion or
Significant Increase
(95% CI)
43% (34-52)
60% (39-79)
62% (53-71)
84% (64-95)
•
Studies in children
The seroprotection rate*, seroconversion rate* and the seroconversion factor** for anti-HA antibody
to H1N1v in children and adolescents aged 9-17 years by HI assay administration of 7.5 µg of Focetria
were as follows:
Children and Adolescents (9-17 years)
Anti-HA antibody
21 days after 1
st
dose(day 22)
21 days after 2
nd
dose (day 43)
Total
N=88
Seronegative at
baseline
N=51
Total
N=88
Seronegative at
baseline
N=51
Seroprotection rate
(95% CI)
97% (90-99)
94% (84-99)
99% (94-100)
98% (90-100)
GMR (95% CI)
62 (38-100)
102 (60-170)
83 (54-127)
169 (122-235)
Seroconversion or
Significant Increase
(95% CI)
94% (87-98)
94% (84-99)
94% (87-98)
98% (90-100)
* measured by HI assay
** geometric mean ratios of HI
Data on responses to a second dose administered after an interval of three weeks showed an increase in
overall GMT from 793 to 1065 (N=88) and an increase in GMT from 522 to 870 in children who were
seronegative at baseline (N=51).
The seroprotection rate*, seroconversion rate* and the seroconversion factor** for anti-HA antibody
to H1N1v in children aged 3-8 years by HI assay after administration of 7.5 µg of Focetria were as
follows:
Children (3-8 years)
Anti-HA antibody
21 days after 1
st
dose(day 22)
21 days after 2
nd
dose (day 43)
Total
N=70
Seronegative at
baseline
N=48
Total
N=70
Seronegative at
baseline
N=48
Seroprotection rate
(95% CI)
100% (95-100)
100% (93-100)
100% (95-100)
100% (93-100)
GMR (95% CI)
37 (25-55)
50 (32-76)
81 (52-125)
146 (100-212)
Seroconversion or
Significant Increase
(95% CI)
99% (92-100)
100% (93-100)
99% (92-100)
100% (93-100)
* measured by HI assay
** geometric mean ratios of HI
Data on responses to a second dose administered after an interval of three weeks showed an increase in
overall GMT from 319 to 702 (N=70) and an increase in GMT from 247 to 726 in children who were
seronegative at baseline (N=48).
The seroprotection rate*, seroconversion rate* and the seroconversion factor** for anti-HA antibody
to H1N1v in children aged 12-35 months by HI assay after administration of 7.5 µg of Focetria were
as follows:
Children 12-35 months
19
Anti-HA antibody
21 days after 1
st
dose(day 22)
21 days after 2
nd
dose (day 43)
Total
N=66
Seronegative at
baseline
N=45
Total
N=66
Seronegative at
baseline
N=45
Seroprotection rate
(95% CI)
100% (95-100) 100% (92-100)
100%
(95-100)
100% (92-100)
GMR (95% CI)
33 (21-51)
48 (29-79)
93
(54-159)
145 (88-238)
Seroconversion or
Significant Increase
(95% CI)
100% (95-100) 100% (92-100) 100% (95-100) 100% (92-100)
* measured by HI assay
** geometric mean ratios of HI
Data on responses to a second dose administered after an interval of three weeks showed an increase in
overall GMT from 307 to 873 (N=66) and an increase in GMT from 243 to 773 in children who were
seronegative at baseline (N=45).
The seroprotection rate*, seroconversion rate* and the seroconversion factor** for anti-HA antibody
to H1N1v in infants aged 6-11 months by HI assay after administration of 7.5 µg of Focetria were as
follows:
Infants 6-11 months
Anti-HA antibody
21 days after 1
st
dose(day 22)
21 days after 2
nd
dose (day 43)
Total
N=57
Seronegative at
baseline
N=37
Total
N=57
Seronegative at
baseline
N=37
Seroprotection rate
(95% CI)
100% (94-100) 100% (91-100) 100% (94-100) 100% (91-100)
GMR (95% CI)
21 (14-30)
32 (18-55)
128 (74-221)
274 (196-383)
Seroconversion or
Significant Increase
(95% CI)
96% (88-100) 100% (91-100) 98% (91-100)
100% (91-100)
* measured by HI assay
** geometric mean ratios of HI
Data on responses to a second dose administered after an interval of three weeks showed an increase in
overall GMT from 274 to 1700 (N=57) and an increase in GMT from 162 to 1399 in children who
were seronegative at baseline (N=37).
Additional information is available from the studies conducted with a vaccine similar in composition
to Focetria but containing antigen derived from H5N1 viruses. Please consult the Product Information
of
Pandemic influenza vaccine (H5N1) (surface antigen, inactivated, adjuvanted).
5.2 Pharmacokinetic properties
Not applicable.
5.3 Preclinical safety data
Non-clinical data obtained with the mock-up vaccine (MF59C.1-adjuvanted H5N1 vaccine) and with
seasonal vaccine containing MF59C.1 adjuvant reveal no special hazard for humans based on
conventional studies of efficacy, repeated dose toxicity, and reproductive and developmental toxicity.
20
6.
6.1 List of excipients
Sodium chloride,
Potassium chloride,
Potassium dihydrogen phosphate,
Disodium phosphate dihydrate,
Magnesium chloride hexahydrate,
Calcium chloride dihydrate,
Sodium citrate,
Citric acid,
Thiomersal,
Water for injections.
For the adjuvant, 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
1 year.
6.4 Special precautions for storage
Store in a refrigerator (2°C - 8°C). Do not freeze. Store in the original package in order to protect from
light.
6.5 Nature and contents of container
5.0 ml in 10-dose vial (type I glass) with stopper (halo-butyl rubber). Packs of 10.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
Gently shake the multidose vial each time before withdrawing a dose (0.5 ml) of the vaccine into a
syringe. Prior to administration, the withdrawn vaccine should be allowed reach room temperature.
Although Focetria in multidose vials contains a preservative that inhibits microbial growth,
minimisation of the risk of contamination of the multidose vial during withdrawal of each dose is the
responsibility of the user.
Record date and time of the first dose withdrawal on the vial label.
Between uses, return the multidose vial to the recommended storage conditions between 2° and 8° C
(36° and 46° F). The multidose vial should preferably be used within 24 hours after first withdrawal.
Data are available that suggest that multidose vials could be used up to a maximum of 72 hours after
first withdrawal, although such pro-longed storage periods should not be the preferred option.
Any unused vaccine or waste material should be disposed of in accordance with local requirements.
7.
21
Novartis Vaccines and Diagnostics S.r.l. - Via Fiorentina, 1 – Siena, Italy.
8.
EU/1/07/385/004
9.
02 May 2007
Detailed information on this product is available on the website of the European Medicines Agency
(EMA): http://www.ema.europa.eu/
H
.
22
ANNEX II
A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE
SUBSTANCE AND MANUFACTURING AUTHORISATION
HOLDER RESPONSIBLE FOR BATCH RELEASE
B. CONDITIONS OF THE MARKETING AUTHORISATION
23
A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND
MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH
RELEASE
Name and address of the manufacturers of the biological active substance
(Manufacturer responsible for monovalent pooled harvests, before final filtration):
Novartis Vaccines and Diagnostics S.r.l.
Via Fiorentina, 1 – 53100 Siena
Italy
(Manufacturer responsible for final filtration of monovalent pooled harvest):
Novartis Vaccines and Diagnostics S.r.l.
Loc. Bellaria – 53018 Rosia – Sovicille (SI)
Italy
Name and address of the manufacturer(s) responsible for batch release
Novartis Vaccines and Diagnostics S.r.l.
Loc. Bellaria – 53018 Rosia – Sovicille (SI)
Italy
B. CONDITIONS OF THE MARKETING AUTHORISATION
•
Medicinal product subject to medical prescription.
•
CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND
EFFECTIVE USE OF THE MEDICINAL PRODUCT
•
The MAH shall agree with Member States to measures facilitating the identification and
traceability of the A/H1N1 vaccine administered to each patient, in order to minimise
medication errors and aid patients and health care professionals to report adverse reactions. This
may include the provision by the MAH of stickers with invented name and batch number with
each pack of the vaccine.
•
The MAH shall agree with Member States on mechanisms allowing patients and health care
professionals to have continuous access to updated information regarding Focetria.
•
The MAH shall agree with Member States on the provision of a targeted communication to
healthcare professionals which should address the following:
•
The correct way to prepare the vaccine prior to administration.
•
Adverse events to be prioritised for reporting, i.e. fatal and life-threatening adverse
reactions, unexpected severe adverse reactions, adverse events of special interest (AESI).
•
The minimal data elements to be transmitted in individual case safety reports in order to
facilitate the evaluation and the identification of the vaccine administered to each subject,
including the invented name, the vaccine manufacturer and the batch number.
•
If a specific notification system has been put in place, how to report adverse reactions.
•
OTHER CONDITIONS
24
Official batch release
:
In accordance with Article 114 Directive 2001/83/EC as amended, the official batch release will be
undertaken by a state laboratory or a laboratory designated for that purpose.
Pharmacovigilance system
The MAH must ensure that the system of pharmacovigilance, as described in version 12.4 (dated 23
March 2010) presented in Module 1.8.1 of the marketing authorisation application, is in place and
functioning before the product is placed on the market and for as long as the marketed product remains
in use.
PSUR submission
The marketing Authorisation holder will submit periodic safety update reports on a 6-month cycle,
unless the CHMP decides otherwise.
Risk Management plan
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in
the Pharmacovigilance Plan, as agreed in version RMP 1.6 (dated 29 January 2010) of the Risk
Management Plan (RMP) presented in Module 1.8.2. of the Marketing Authorisation Application and
any subsequent updates of the RMP agreed by the CHMP.
Follow-up Measures (FUMs)
The Marketing Authorisation Holder shall complete the following programme of studies within the
specified time frame, the results of which shall form the basis of the continuous reassessment of the
benefit/risk profile.
Area
Description
Due Date
Clinical FUM 28
Study V111_03: The MAH commits to provide the final
report
End August 2011
Results of study to be provided within
two weeks of availability.
Interim report on effectiveness by
August 2010
Final report on effectiveness: nine
months after the end of the pandemic
declared by WHO.
Clinical FUM 29
The MAH commits to provide the results of the clinical
effectiveness study
Pharmacovigilance
FUM 30
The MAH will submit the results of a prospective cohort
safety study in at least 9,000 patients in different age
groups, including immunocompromised subjects, in
accordance with the protocol submitted with the Risk
Management Plan. Observed-to-Expected analyses will
be performed.
Final study report
by end August 2010:
Pharmacovigilance
FUM 31
The MAH commits to report the results of a study in a
pregnancy registry.
Upon issuance of Commission Decision
25
Pharmacovigilance
FUM 37
The next updated RMP
By 21 November 2010
Clinical FUM 36.1
Clinical trials timelines – The MAH commits to report
the results
V111_02
and V111_03: Interim and
final results will be submitted in
accordance with the protocol. Final study
report for V111_02 by end July 2011 and
final study report for V111_03 by
August 2011
Clinical FUM 40.1
The MAH commits to provide additional data as listed in
the AR for FUM 40 at the time of the submission of the
clinical data for the annual update variation of seasonal
influenza vaccines 2010-11.
By September 2010
Quality FUM 43
The applicant should provide all stability data
By end July 2010
The MAH commit to submit on a monthly basis safety
report including:
- a frequency table of all spontaneous cases per country,
stratified according to type of report (medically
confirmed or non-medically confirmed) and seriousness,
for the period covered by the report and cumulatively
- a frequency table of all spontaneous adverse reactions
by SOC, High Level Term (HLT) and Preferred Term
(PT), stratified according to type of report (medically
confirmed or non-medically confirmed) and including
the number of fatal reports, for the period covered by the
report and cumulatively.
- a line listing of Adverse events of special interest (as
defined in the CHMP Recommendations
[EMEA/359381/2009]) reported from countries of the
European Economic Area.
Submission to continue on a monthly
basis until otherwise informed by the
CHMP.
Pharmacovigilance
Furthermore, the MAH commits to submit 6-monthly
PSURs for the medicinal product authorised by this
decision until further review by CHMP.
Next PSUR submission date: 21
November 2010
26
ANNEX III
LABELLING AND PACKAGE LEAFLET
27
A. LABELLING
28
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
CARDBOARD BOX FOR SYRINGE
1.
Focetria suspension for injection in pre-filled syringe
Influenza vaccine H1N1v (surface antigen, inactivated, adjuvanted)
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
One dose of 0.5 ml contains: Active Ingredients: Influenza virus surface antigens (haemagglutinin and
neuraminidase), propagated in eggs, and adjuvanted with MF59C.1, of strain:
A/California/07/2009 (H1N1)-derived strain used NYMC X-181
7.5 micrograms haemagglutinin
Adjuvant
: MF59C.1 oil in water emulsion containing squalene, as the oil phase, stabilised with
polysorbate 80 and sorbitan trioleate in a citrate buffer.
3.
LIST OF EXCIPIENTS
Sodium chloride, potassium chloride, potassium dihydrogen phosphate, disodium phosphate dihydrate,
magnesium chloride hexahydrate, calcium chloride dihydrate, sodium citrate, citric acid, water for
injections.
4.
Suspension for injection.
1 x single dose of 0.5 ml pre-filled syringe
10 x single dose of 0.5 ml pre-filled syringes
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
To be administered intramuscularly into the deltoid muscle.
Warning
: Do not inject intravascularly.
Read the package leaflet before use.
The vaccine should be allowed to reach room temperature before use. Gently shake before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
29
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
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.
Novartis Vaccines and Diagnostics S.r.l. - Via Fiorentina, 1 – Siena, Italy.
EU/1/07/385/001
EU/1/07/385/002
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
30
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
CARDBOARD BOX FOR 10-DOSE VIAL
1.
Focetria suspension for injection in multidose container
Influenza vaccine H1N1v (surface antigen, inactivated, adjuvanted)
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
One dose of 0.5 ml contains: Active Ingredients: Influenza virus surface antigens (haemagglutinin and
neuraminidase), propagated in eggs, and adjuvanted with MF59C.1, of strain:
A/California/07/2009 (H1N1)-derived strain used NYMC X-181
7.5 micrograms haemagglutinin
Adjuvant
: MF59C.1 oil in water emulsion containing squalene, as the oil phase, stabilised with
polysorbate 80 and sorbitan trioleate in a citrate buffer.
3.
LIST OF EXCIPIENTS
Sodium chloride, potassium chloride, potassium dihydrogen phosphate, disodium phosphate dihydrate,
magnesium chloride hexahydrate, calcium chloride dihydrate, sodium citrate, citric acid, thiomersal,
water for injections.
4.
Suspension for injection.
Vials
10 x 10 doses of 0.5 ml vaccine (5 ml)
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
To be administered intramuscularly into the deltoid muscle.
Warning
: Do not inject intravascularly.
Read the package leaflet before use.
The vaccine should be allowed to reach room temperature before use. Gently shake before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
31
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 requirements
Novartis Vaccines and Diagnostics S.r.l. - Via Fiorentina, 1 – Siena, Italy.
EU/1/07/385/004
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
32
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
LABEL FOR SYRINGE
1.
Focetria injection
Influenza vaccine H1N1v
Intramuscular use
2.
METHOD OF ADMINISTRATION
Shake before use.
3.
EXPIRY DATE
EXP.:
4.
BATCH NUMBER
Lot:
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
0.5 ml
6.
OTHER
Store in a refrigerator.
Novartis V&D S.r.l.
33
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
LABEL FOR 10-DOSE VIAL
1.
Focetria injection
Influenza vaccine H1N1v
Intramuscular use.
2.
METHOD OF ADMINISTRATION
Gently shake before use.
3.
EXPIRY DATE
EXP.:
4.
BATCH NUMBER
Lot:
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
Multidose vial (5 ml)
6.
OTHER
Store in a refrigerator.
Novartis V&D S.r.l.
34
B. PACKAGE LEAFLET
35
PACKAGE LEAFLET: INFORMATION FOR THE USER
Focetria suspension for injection
Influenza vaccine H1N1v (surface antigen, inactivated, adjuvanted)
Read all of this leaflet carefully before you receive this vaccine.
-
If you have any further questions, ask your doctor or nurse.
-
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor.
In this leaflet
:
1. What Focetria is and what it is used for
2. Before you receive Focetria
3. How Focetria is given
4. Possible side effects
5.
How to store Focetria
6.
Further information
1.
WHAT FOCETRIA IS AND WHAT IT IS USED FOR
Focetria is a vaccine to prevent influenza (flu) caused by A(H1N1v) 2009 virus.
When a person is given the vaccine, the immune system (the body’s natural defence system) will
produce its own protection (antibodies) against the disease. None of the ingredient in the vaccine can
cause flu.
2.
BEFORE YOU RECEIVE FOCETRIA
You should not receive Focetria:
•
if you have previously had a sudden life-threatening allergic reaction to any ingredient of
Focetria (these are listed at the end of the leaflet) or to any of the substances that may be present
in trace amounts as follows: egg and chicken protein, ovalbumin, formaldehyde, kanamycin and
neomycin sulphate (antibiotics) or cetyltrimethylammonium bromide (CTAB). Signs of an
allergic reaction may include itchy skin rash, shortness of breath and swelling of the face or
tongue.
If you are not sure, talk to your doctor or nurse before having this vaccine.
Take special care with Focetria:
•
if you have had any allergic reaction other than a sudden life-threatening allergic reaction to any
ingredient contained in the vaccine, to thiomersal (only for the multidose vial presentation), to
egg and, chicken protein, ovalbumin, formaldehyde, kanamycin and neomycin sulphate
(antibiotics) or cetyltrimethylammonium bromide (CTAB). (see section 6. Further information).
•
if you have a severe infection with a high temperature (over 38°C). If this applies to you then
your vaccination will usually be postponed until you are feeling better. A minor infection such
as a cold should not be a problem, but your doctor or nurse should advise whether you could
still be vaccinated with Focetria,
•
if you are having a blood test to look for evidence of infection with certain viruses. In the first
few weeks after vaccination with Focetria the results of these tests may not be correct. Tell the
36
-
Keep this leaflet. You may need to read it again.
doctor requesting these tests that you have recently been given Focetria.
In any of these cases, TELL YOUR DOCTOR OR NURSE, as vaccination may not be recommended,
or may need to be delayed.
Please inform your doctor or nurse if you have a bleeding problem or bruise easily.
Taking other medicines
Please tell your doctor or nurse if you are taking or have recently taken any other medicines, including
medicines obtained without a prescriptionor have recently been given any other vaccine.
Focetria can be given at the same time as non-adjuvanted seasonal influenza vaccines, with injections
made into separate limbs.
There is no information on administration of the vaccine Focetria with any other vaccines. However, if
this cannot be avoided, the vaccines should be injected into separate limbs. In such cases, you should
be aware that the side effects may be more intense.
Pregnancy and breast-feeding
Tell your doctor if you are pregnant, think you may be pregnant, plan to become pregnant. You should
discuss with your doctor whether you should receive Focetria.
The vaccine may be used during breast-feeding.
Driving and using machines
Some effects mentioned under section 4. “Possible side effects” may affect the ability to drive or use
machines.
Important information about some of the ingredients of Focetria
This vaccine in a multi-dose vial contains thiomersal as a preservative and it is possible that you may
experience an allergic reaction. Tell your doctor if you have any known allergies.
This medicinal contains less than 1 mmol sodium (23 mg) and less than 1 mmol of potassium (39 mg)
per 0.5 ml dose, i.e. essentially sodium- and potassium free.
3.
HOW FOCETRIA IS GIVEN
Your doctor or nurse will administer the vaccine in accordance with official recommendations.
The vaccine will be injected into a muscle (usually in the upper arm).
Adults
A dose (0.5 ml) of the vaccine will be given.
Clinical data suggest that a single dose may be sufficient.
If a second dose is administered there should be an interval of at least three weeks between the first
and second dose.
Elderly:
A dose (0.5 ml) of the vaccine and a second dose of 0.5 ml at least three weeks later.
Children and adolescents 3-17 years of age:
You or your child will receive one dose of 0.5 ml vaccine.
Available clinical data suggest that a single dose may be sufficient.
If a second dose is administered there should be an interval of at least three weeks between the first
and second dose.
37
Children 6 months to 35 months:
You or your child will receive one dose of 0.5 ml vaccine.
If a second dose is administered there should be an interval of at least three weeks between the first
and second dose.
Children aged less than 6 months of age:
Vaccination is currently not recommended in this age group.
When Focetria is given for the first dose, it is recommended that Focetria (and not another vaccine
against H1N1v) be given for the complete vaccination course.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Focetria can cause side effects, although not everybody gets them.
Allergic reactions may occur following vaccination, in rare cases leading to shock. Doctors are aware
of this possibility and have emergency treatment available for use in such cases.
In the clinical studies with the vaccine, most side effects were mild in nature and short term. The side-
effects are generally similar to those related to the seasonal flu vaccine.
The frequency of possible side effects listed below is defined using the following convention:
very common (affects more than 1 user in 10)
common (affects 1 to 10 users in 100)
uncommon (affects 1 to 10 users in 1,000)
rare (affects 1 to 10 users in 10,000)
very rare (affects less than 1 user in 10,000)
The side effects listed below have occurred with Focetria in clinical studies in adults, including the
elderly:
Very common:
Pain, hardening of the skin at the injection site, injection site redness, injection site swelling, pain at
the site of injection, aching muscles, headache, sweating, fatigue, generally feeling unwell and
shivering
Common
:
Bruising of the skin at the injection site, fever and nausea
Uncommon:
Flu like symptoms
Rare:
Convulsion, eye swelling and anaphylaxis
These side effects usually disappear within 1-2 days without treatment. If they persist, CONSULT
YOUR DOCTOR.
Side effects from clinical studies in children
A clinical study was conducted with the same vaccine in children. General side effects reported very
commonly in the 6 months-35 months of age group per dose were irritability, unusual crying,
sleepiness, diarrhoea and change in eating habits. Among the adolescents the very common events
were: sweating, nausea and chills. Very commonly reported reactions in both children and adolescents
were pain, hardening of the skin at the injection site, injection site redness, generally feeling unwell,
muscle ache, headache and fatigue.
38
Other side effects
The side effects listed below have occurred in the days or weeks after vaccination with Focetria.
Generalised skin reactions including itching, urticaria (hives), rash or swelling of the skin and mucous
membranes.
Disorders of the gut such as nausea, vomiting, abdominal pain and diarrhoea.
Headache, dizziness, drowsiness, fainting.
Neurological disorders such as severe stabbing or throbbing pain along one or more nerves, tingling,
fits, and neuritis (inflammation of nerves).
Swollen lymph nodes, palpitations, weakness, pain in the extremities and cough.
Allergic reactions possibly with shortness of breath, wheezing, swelling of the throat, or leading to a
dangerous decrease of blood pressure, which, if untreated, may lead to shock. Doctors are aware of
this possibility and have emergency treatment available for use in such cases.
Data in children and adolescents suggest a slight decrease in reactogenicity after the second dose of
the vaccine, with no increase in rates of fever.
In addition, the side effects listed below have occurred in the days or weeks after vaccination with
adjuvanted and non-adjuvanted vaccines given routinely every year to prevent flu. These side effects
may occur with Focetria.
Rare
:
Low blood platelet count which can result in bleeding or bruising.
Very rare
:
Vasculitis (inflammation of the blood vessels which can cause skin rashes, joint pain and kidney
problems), exudative erythema multiforme.
Neurological disorders such as encephalomyelitis (inflammation of the central nervous system), and a
type of paralysis known as Guillain-Barré Syndrome.
If any of these side effects occur, please tell your doctor or nurse immediately.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor.
5.
HOW TO STORE FOCETRIA
Keep out of the reach and sight of children.
Do not use Focetria after the expiry date which is stated on the carton and the label. 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.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help to protect the environment.
6.
FURTHER INFORMATION
What Focetria contains
-
Active Substance:
39
Influenza virus surface antigens (haemagglutinin and neuraminidase)* of strain:
A/California/07/2009 (H1N1)-derived strain used NYMC X-181
7.5 micrograms**
* propagated in eggs
** expressed in microgram haemagglutinin.
-
Adjuvant
:
The vaccine contains an ‘adjuvant’ (MF59C.1) to stimulate a better response. MF59C.1 is an
oil/water emulsion containing 9.75 mg squalene, 1.175 mg polysorbate 80 and 1.175 mg
sorbitan trioleate in a citrate buffer. Quantities are expressed per 0.5 ml vaccine dose.
-
Other Ingredients
:
The other ingredients are: thiomersal (multidose vial only), sodium chloride, potassium
chloride, potassium dihydrogen phosphate, disodium phosphate dihydrate, magnesium chloride
hexahydrate, calcium chloride dihydrate, sodium citrate, citric acid and water for injections.
What Focetria looks like and contents of the pack
Focetria is a milky-white liquid.
It is provided in:
- a ready-to-use syringe, containing a single dose of 0.5 ml for injection;
- vial containing ten doses of 0.5 ml each for injection.
Not all pack sizes may be marketed.
Marketing Authorisation Holder
Novartis Vaccines and Diagnostics S.r.l.
Via Fiorentina, 1 – Siena,
Italy.
Manufacturer
Novartis Vaccines and Diagnostics S.r.l.
Loc. Bellaria
53018 Rosia
Sovicille (SI)
Italy.
The following information is intended for medical or healthcare professionals only:
Instructions for administration of the vaccine
:
Ready-to-use syringe, containing a single dose of 0.5 ml for injection:
The vaccine should be allowed to reach room temperature before use.
Gently shake before use.
Vial containing ten doses (0.5 ml each) for injection:
Gently shake the multidose vial each time before withdrawing a dose (0.5 ml) of the vaccine into a
syringe. Prior to administration, the withdrawn vaccine should be allowed to reach room temperature.
Although Focetria in multidose vials contains a preservative that inhibits microbial growth,
minimisation of the risk of contamination of the multidose vial during withdrawal of each dose is the
responsibility of the user.
Record date and time of the first dose withdrawal on the vial label.
40
per 0.5 ml dose
Between uses, return the multidose vial to the recommended storage conditions between 2° and 8° C
(36° and 46° F). The multidose vial should preferably be used within 24 hours after first withdrawal.
Data are available that suggest that multidose vials could be used up to a maximum of 72 hours after
first withdrawal, although such pro-longed storage periods should not be the preferred option.
The vaccine should not be administered intravascularly.
Any unused vaccine or waste material should be disposed of in accordance with local requirements.
This leaflet was last approved in {MM/YYYY}.
Detailed information on this medicine is available on the European Medicines Agency (EMA) web
site: http://www.ema.europa.eu/
41
Source: European Medicines Agency
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