ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
1.
Foclivia suspension for injection in pre-filled syringe
Pandemic influenza vaccine (surface antigen, inactivated, adjuvanted)
2.
Influenza virus surface antigens (haemagglutinin and neuraminidase)* of strain:
A/Vietnam/1194/2004 (H5N1)
7.5 micrograms** per 0.5 ml dose
* 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
This vaccine complies with the WHO recommendations and EU decision for the pandemic.
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 in an officially declared pandemic situation.
Pandemic influenza vaccine should be used in accordance with Official Guidance (see sections 4.2 and
5.1).
Foclivia has been evaluated in adults aged 18-60 years and elderly over 60 years following a 0, 21 day
schedule.
Adults and elderly: 0.5 ml.
A second dose of vaccine should be given after an interval of at least 3 weeks.
Immunisation should be carried out by intramuscular injection into the deltoid muscle.
No data are available in subjects below 18 years or in children. Therefore health care providers need to
assess the benefits and potential risks of administering the vaccine in that population.
For pregnant women, see section 4.6.
For further information, see section 5.1.
2
History of an anaphylactic (i.e. life-threatening) reaction to any of the constituents or trace residues of
eggs, chicken proteins, kanamycin and neomycin sulphate, formaldehyde and
cetyltrimethylammonium bromide (CTAB) of this vaccine. However, in a pandemic situation, it may
be appropriate to give the vaccine, provided that facilities for resuscitation are immediately available
in case of need.
See section 4.4. for Special warnings and special precautions for use.
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 eggs, chicken
proteins, 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.
If the pandemic situation allows, immunisation shall be postponed in patients with severe febrile
illness or acute infection.
The vaccine should under no circumstances be administered intravascularly or subcutaneously.
Antibody response in patients with endogenous or iatrogenic immunosuppression may be insufficient.
A protective response may not be induced in all vaccines (see section 5.1).
Foclivia should not be given at the same time as other vaccines. However, 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.
The immunological response may be diminished if the patient is undergoing immunosuppressant
treatment.
Following influenza vaccination, false positive results in serology tests using the ELISA method to
detect antibodies against HIV1, Hepatitis C and especially HTLV1 have been observed. The Western
Blot technique disproves the results. The transient false positive reactions could be due to the IgM
response by the vaccine.
No data have been generated with Foclivia in pregnant women. Therefore health care providers need
to assess the benefits and potential risks of administering the vaccine to pregnant women taking into
consideration official recommendations.
Data from vaccinations with seasonal interpandemic inactivated trivalent vaccines in pregnant women
do not indicate that adverse foetal and maternal outcomes were attributable to the vaccine.
The vaccine may be used during lactation.
Foclivia is unlikely to produce any effect on the ability to drive and use machines.
•
Clinical trials
In clinical trials with different formulations (H5N3, H9N2 and H5N1) 542 subjects were exposed to
the candidate vaccine. Of theses subjects, 464 subjects received the mock-up vaccine (A/H5N1).
From the clinical trials with the pandemic 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,
3
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 (see section 5.1 for
more information on mock-up vaccines).
The incidence of symptoms observed in subjects over 60 years of age was lower as compared to the
18-60 years old population.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness:
Nervous system disorders
U
Common (>1/100, <1/10): headache
Skin and subcutaneous tissue disorders
U
Common (>1/100, <1/10): sweating
U
Muscoskeletal, connective tissue and bone disorders
U
Common (>1/100, <1/10): arthralgia and myalgia
U
General disorders and administration site conditions
U
Common (>1/100, <1/10): injection site redness, injection site swelling, injection site induration,
injection site ecchymosis and injection site pain, fever, malaise, fatigue and shivering
These reactions usually disappear within 1-2 days without treatment.
•
U
Post-marketing surveillance
From Post-marketing surveillance with adjuvanted interpandemic trivalent vaccines with the similar
composition of Foclivia (surface antigen, inactivated, adjuvanted with MF59C.1), the following
adverse events have been reported:
Uncommon
U
(>1/1,000, <1/100):
Generalised skin reactions including pruritus, urticaria or non-specific rash.
Rare
U
(>1/10,000, <1/1,000):
Neuralgia, paraesthesia, convulsions, transient thrombocytopenia.
Allergic reactions, in rare cases leading to shock, have been reported.
Very rare
U
(<1/10,000):
Vasculitis with transient renal involvement and exudative erythema multiforme.
Neurological disorders, such as encephalomyelitis, neuritis and Guillain Barré syndrome.
Adverse event(s) from post-marketing surveillance with the pandemic vaccine: not applicable.
No case of overdose has been reported.
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Influenza vaccine, ATC Code: J07BB02
4
This section describes the clinical experience with the mock-up vaccines following a two-dose
administration.
Mock-up vaccines contain influenza antigens that are different from those in the currently circulating
influenza viruses. These antigens can be considered as ‘novel’ antigens and simulate a situation where
the target population for vaccination is immunologically naïve. Data obtained with a mock-up vaccine
will support a vaccination strategy that is likely to be used for the pandemic vaccine: clinical efficacy
and safety data obtained with mock-up vaccines are relevant for the pandemic vaccines.
A clinical trial was conducted with a H5N1 vaccine combined with MF59C.1 adjuvant in 486 healthy
adult volunteers. Two doses of vaccine containing H5N1 (A/Vietnam/1194/2004) at 2 different
dosages (7.5 and 15 µg hemagglutinin [HA]/dose) with MF59C.1 adjuvant were administered three
weeks apart.
The seroprotection rate*, seroconversion rate* and the seroconversion factor** for anti-HA antibody
in the adults measured by SRH were as follows:
anti-HA antibody
22 days after 1
P
st
P
dose
21 days after 2
P
nd
P
dose
Seroprotection rate
41% (95% CI: 33-49)
86% (95% CI: 79-91)
Seroconversion rate
39% (95% CI: 31-47)
85% (95% CI: 79-91)
Seroconversion factor
2.42 (2.02-2.89)
7.85 (6.7-9.2)
* measured by SRH assay ≥ 25 mm
** geometric mean ratios of SRH
The seroprotection rate*, seroconversion rate* and the seroconversion factor ** for anti-HA antibody
in subjects aged over 60 measured by SRH were as follows:
anti-HA antibody
22 days after 1
P
st
P
dose
21 days after 2
P
nd
P
dose
Seroprotection rate
53% (95% CI: 42-64)
81% (95% CI: 71-89)
Seroconversion rate
45% (95% CI: 34-56)
71% (95% CI: 60-81)
Seroconversion factor
2.85 (2.22-3.66)
5.02 (3.91-6.45)
* measured by SRH assay ≥ 25 mm
** geometric mean ratios of SRH
The persistence of antibodies for the mock-up vaccines varies. With the interpandemic trivalent
vaccines it is usually 6-12 months, but for this vaccine no data are available yet with the H5N1 strain.
•
Supportive Studies
In two dose finding studies 78 adults received an adjuvanted mock-up vaccine (H5N3 or H9N2).
Two doses of vaccine with H5N3 (A/Duck/Singapore/97) strain at 3 different dosages (7.5, 15 and 30
µg HA/dose) were administered three weeks apart.
Serum samples were tested against the original H5N3 and also a number of H5N1 isolates.
Serologic responses obtained with the SRH assay showed that 100% of subjects achieved
seroprotection and 100% seroconverted after two 7.5 µg injections. The adjuvanted vaccine was also
found to induce antibodies that cross-protected against the H5N1 strains isolated in 2003 and 2004,
which exhibit some antigenic drift compared to the original strains.
Two doses of vaccine containing H9N2 (A/chicken/Hong Kong/G9/97) strain at 4 different dosages
(3.75, 7.5, 15 and 30 µg HA/dose), were administered four weeks apart. Serologic responses obtained
with the Hemagglutination Inhibition (HI) assay showed that 92% of subjects achieved seroprotection
and 75% seroconverted after two 7.5 µg injections.
Foclivia has been authorised under “Exceptional Circumstances”.
This means that for scientific reasons, it has not been possible to obtain complete information on this
5
medicinal product. The European Medicines Agency (EMEA) will review any new information which
may become available every year and this SPC will be updated as necessary.
5.2 Pharmacokinetic properties
Not applicable.
5.3 Preclinical safety data
Not applicable.
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.
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.
6
8.
9.
7
1.
Foclivia suspension for injection
Pandemic influenza vaccine (surface antigen, inactivated, adjuvanted)
2.
Influenza virus surface antigens (haemagglutinin and neuraminidase)* of strain:
A/Vietnam/1194/2004 (H5N1)
7.5 micrograms** per 0.5 ml dose
* 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
This vaccine complies with the WHO recommendations and EU decision for the pandemic.
For a full list of excipients, see section 6.1.
3.
Suspension for injection.
Milky-white liquid.
4.
Prophylaxis of influenza in an officially declared pandemic situation.
Pandemic influenza vaccine should be used in accordance with Official Guidance (see sections 4.2 and
5.1).
Foclivia has been evaluated in adults aged 18-60 years and elderly over 60 years following a 0, 21 day
schedule.
Adults and elderly: 0.5 ml.
A second dose of vaccine should be given after an interval of at least 3 weeks.
Immunisation should be carried out by intramuscular injection into the deltoid muscle.
No data are available in subjects below 18 years or in children. Therefore health care providers need to
assess the benefits and potential risks of administering the vaccine in that population.
For pregnant women, see section 4.6.
For further information, see section 5.1.
8
History of an anaphylactic (i.e. life-threatening) reaction to any of the constituents or trace residues of
eggs, chicken proteins, kanamycin and neomycin sulphate, formaldehyde and
cetyltrimethylammonium bromide (CTAB) of this vaccine. However, in a pandemic situation, it may
be appropriate to give the vaccine, provided that facilities for resuscitation are immediately available
in case of need.
See section 4.4. for Special warnings and special precautions for use.
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 eggs, chicken
proteins, 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.
If the pandemic situation allows, immunisation shall be postponed in patients with severe febrile
illness or acute infection.
The vaccine should under no circumstances be administered intravascularly or subcutaneously.
Antibody response in patients with endogenous or iatrogenic immunosuppression may be insufficient.
A protective response may not be induced in all vaccines (see section 5.1).
Foclivia should not be given at the same time as other vaccines. However, 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.
The immunological response may be diminished if the patient is undergoing immunosuppressant
treatment.
Following influenza vaccination, false positive results in serology tests using the ELISA method to
detect antibodies against HIV1, Hepatitis C and especially HTLV1 have been observed. The Western
Blot technique disproves the results. The transient false positive reactions could be due to the IgM
response by the vaccine.
No data have been generated with Foclivia in pregnant women. Therefore health care providers need
to assess the benefits and potential risks of administering the vaccine to pregnant women taking into
consideration official recommendations.
Data from vaccinations with seasonal interpandemic inactivated trivalent vaccines in pregnant women
do not indicate that adverse foetal and maternal outcomes were attributable to the vaccine.
The vaccine may be used during lactation.
Foclivia is unlikely to produce any effect on the ability to drive and use machines.
•
Clinical trials
In clinical trials with different formulations (H5N3, H9N2 and H5N1) 542 subjects were exposed to
the candidate vaccine. Of theses subjects, 464 subjects received the mock-up vaccine (A/H5N1).
From the clinical trials with the pandemic 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,
9
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 (see section 5.1 for
more information on mock-up vaccines).
The incidence of symptoms observed in subjects over 60 years of age was lower as compared to the
18-60 years old population.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness:
Nervous system disorders
U
Common (>1/100, <1/10): headache
Skin and subcutaneous tissue disorders
U
Common (>1/100, <1/10): sweating
U
Muscoskeletal, connective tissue and bone disorders
U
Common (>1/100, <1/10): arthralgia and myalgia
U
General disorders and administration site conditions
U
Common (>1/100, <1/10): injection site redness, injection site swelling, injection site induration,
injection site ecchymosis and injection site pain, fever, malaise, fatigue and shivering
These reactions usually disappear within 1-2 days without treatment.
•
U
Post-marketing surveillance
From Post-marketing surveillance with adjuvanted interpandemic trivalent vaccines with the similar
composition of Foclivia (surface antigen, inactivated, adjuvanted with MF59C.1), the following
adverse events have been reported:
Uncommon
U
(>1/1,000, <1/100):
Generalised skin reactions including pruritus, urticaria or non-specific rash.
Rare
U
(>1/10,000, <1/1,000):
Neuralgia, paraesthesia, convulsions, transient thrombocytopenia.
Allergic reactions, in rare cases leading to shock, have been reported.
Very rare
U
(<1/10,000):
Vasculitis with transient renal involvement and exudative erythema multiforme.
Neurological disorders, such as encephalomyelitis, neuritis and Guillain Barré syndrome.
Adverse event(s) from post-marketing surveillance with the pandemic vaccine: not applicable.
No case of overdose has been reported.
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Influenza vaccine, ATC Code: J07BB02
10
This section describes the clinical experience with the mock-up vaccines following a two-dose
administration.
Mock-up vaccines contain influenza antigens that are different from those in the currently circulating
influenza viruses. These antigens can be considered as ‘novel’ antigens and simulate a situation where
the target population for vaccination is immunologically naïve. Data obtained with a mock-up vaccine
will support a vaccination strategy that is likely to be used for the pandemic vaccine: clinical efficacy
and safety data obtained with mock-up vaccines are relevant for the pandemic vaccines.
A clinical trial was conducted with a H5N1 vaccine combined with MF59C.1 adjuvant in 486 healthy
adult volunteers. Two doses of vaccine containing H5N1 (A/Vietnam/1194/2004) at 2 different
dosages (7.5 and 15 µg hemagglutinin [HA]/dose) with MF59C.1 adjuvant were administered three
weeks apart.
The seroprotection rate*, seroconversion rate* and the seroconversion factor** for anti-HA antibody
in the adults measured by SRH were as follows:
anti-HA antibody
22 days after 1
P
st
P
dose
21 days after 2
P
nd
P
dose
Seroprotection rate
41% (95% CI: 33-49)
86% (95% CI: 79-91)
Seroconversion rate
39% (95% CI: 31-47)
85% (95% CI: 79-91)
Seroconversion factor
2.42 (2.02-2.89)
7.85 (6.7-9.2)
* measured by SRH assay ≥ 25 mm
** geometric mean ratios of SRH
The seroprotection rate*, seroconversion rate* and the seroconversion factor** for anti-HA antibody
in subjects aged over 60 measured by SRH were as follows:
anti-HA antibody
22 days after 1
P
st
P
dose
21 days after 2
P
nd
P
dose
Seroprotection rate
53% (95% CI: 42-64)
81% (95% CI: 71-89)
Seroconversion rate
45% (95% CI: 34-56)
71% (95% CI: 60-81)
Seroconversion factor
2.85 (2.22-3.66)
5.02 (3.91-6.45)
* measured by SRH assay ≥ 25 mm
** geometric mean ratios of SRH
The persistence of antibodies for the mock-up vaccines varies. With the interpandemic trivalent
vaccines it is usually 6-12 months, but for this vaccine no data are available yet with the H5N1 strain.
•
Supportive Studies
In two dose finding studies 78 adults received an adjuvanted mock-up vaccine (H5N3 or H9N2).
Two doses of vaccine with H5N3 (A/Duck/Singapore/97) strain at 3 different dosages (7.5, 15 and 30
µg HA/dose) were administered three weeks apart.
Serum samples were tested against the original H5N3 and also a number of H5N1 isolates.
Serologic responses obtained with the SRH assay showed that 100% of subjects achieved
seroprotection and 100% seroconverted after two 7.5 µg injections. The adjuvanted vaccine was also
found to induce antibodies that cross-protected against the H5N1 strains isolated in 2003 and 2004,
which exhibit some antigenic drift compared to the original strains.
Two doses of vaccine containing H9N2 (A/chicken/Hong Kong/G9/97) strain at 4 different dosages
(3.75, 7.5, 15 and 30 µg HA/dose), were administered four weeks apart. Serologic responses obtained
with the Hemagglutination Inhibition (HI) assay showed that 92% of subjects achieved seroprotection
and 75% seroconverted after two 7.5 µg injections.
Foclivia has been authorised under “Exceptional Circumstances”.
This means that for scientific reasons, it has not been possible to obtain complete information on this
11
medicinal product. The European Medicines Agency (EMEA) will review any new information which
may become available every year and this SPC will be updated as necessary.
5.2 Pharmacokinetic properties
Not applicable.
5.3 Preclinical safety data
Not applicable.
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.
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 single-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
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.
12
8.
9.
13
1.
Foclivia suspension for injection in multidose container
Pandemic influenza vaccine (surface antigen, inactivated, adjuvanted)
2.
Influenza virus surface antigens (haemagglutinin and neuraminidase)* of strain:
A/Vietnam/1194/2004 (H5N1)
7.5 micrograms ** per 0.5 ml dose
* 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.
This vaccine complies with the WHO recommendations and EU decision for the pandemic.
For a full list of excipients, see section 6.1.
3.
Suspension for injection.
Milky-white liquid.
4.
Prophylaxis of influenza in an officially declared pandemic situation.
Pandemic influenza vaccine should be used in accordance with Official Guidance (see sections 4.2 and
5.1).
Foclivia has been evaluated in adults aged 18-60 years and elderly over 60 years following a 0, 21 day
schedule.
Adults and elderly: 0.5 ml.
A second dose of vaccine should be given after an interval of at least 3 weeks.
Immunisation should be carried out by intramuscular injection into the deltoid muscle.
No data are available in subjects below 18 years or in children. Therefore health care providers need to
assess the benefits and potential risks of administering the vaccine in that population.
14
For pregnant women, see section 4.6.
For further information, see section 5.1.
History of an anaphylactic (i.e. life-threatening) reaction to any of the constituents or trace residues of
eggs, chicken proteins, kanamycin and neomycin sulphate, formaldehyde and
cetyltrimethylammonium bromide (CTAB) of this vaccine. However, in a pandemic situation, it may
be appropriate to give the vaccine, provided that facilities for resuscitation are immediately available
in case of need.
See section 4.4. for Special warnings and special precautions for use.
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 eggs,
chicken proteins, 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.
If the pandemic situation allows, immunisation shall be postponed in patients with severe febrile
illness or acute infection.
The vaccine should under no circumstances be administered intravascularly or subcutaneously.
Antibody response in patients with endogenous or iatrogenic immunosuppression may be insufficient.
A protective response may not be induced in all vaccines (see section 5.1).
Foclivia should not be given at the same time as other vaccines. However, 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.
The immunological response may be diminished if the patient is undergoing immunosuppressant
treatment.
Following influenza vaccination, false positive results in serology tests using the ELISA method to
detect antibodies against HIV1, Hepatitis C and especially HTLV1 have been observed. The Western
Blot technique disproves the results. The transient false positive reactions could be due to the IgM
response by the vaccine.
No data have been generated with Foclivia in pregnant women. Therefore health care providers need
to assess the benefits and potential risks of administering the vaccine to pregnant women taking into
consideration official recommendations.
Data from vaccinations with seasonal interpandemic inactivated trivalent vaccines in pregnant women
do not indicate that adverse foetal and maternal outcomes were attributable to the vaccine.
The vaccine may be used during lactation.
Foclivia is unlikely to produce any effect on the ability to drive and use machines.
Clinical trials
In clinical trials with different formulations (H5N3, H9N2 and H5N1) 542 subjects were exposed to
the candidate vaccine. Of theses subjects, 464 subjects received the mock-up vaccine (A/H5N1).
15
•
From the clinical trials with the pandemic 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 (see section 5.1 for
more information on mock-up vaccines).
The incidence of symptoms observed in subjects over 60 years of age was lower as compared to the
18-60 years old population.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness:
Nervous system disorders
U
Common (>1/100, <1/10): headache
Skin and subcutaneous tissue disorders
U
Common (>1/100, <1/10): sweating
Muscoskeletal, connective tissue and bone disorders
U
Common (>1/100, <1/10): arthralgia and myalgia
U
General disorders and administration site conditions
U
Common (>1/100, <1/10): injection site redness, injection site swelling, injection site induration,
injection site ecchymosis and injection site pain, fever, malaise, fatigue and shivering
These reactions usually disappear within 1-2 days without treatment.
•
U
Post-marketing surveillance
From Post-marketing surveillance with adjuvanted interpandemic trivalent vaccines with the similar
composition of Foclivia (surface antigen, inactivated, adjuvanted with MF59C.1), the following
adverse events have been reported:
Uncommon
U
(>1/1,000, <1/100):
Generalised skin reactions including pruritus, urticaria or non-specific rash.
Rare
U
(>1/10,000, <1/1,000):
Neuralgia, paraesthesia, convulsions, transient thrombocytopenia.
Allergic reactions, in rare cases leading to shock, have been reported.
Very rare
U
(<1/10,000):
Vasculitis with transient renal involvement and exudative erythema multiforme.
Neurological disorders, such as encephalomyelitis, neuritis and Guillain Barré syndrome.
Adverse event(s) from post-marketing surveillance with the pandemic vaccine: not applicable.
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.
16
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Influenza vaccine, ATC Code: J07BB02
This section describes the clinical experience with the mock-up vaccines following a two-dose
administration.
Mock-up vaccines contain influenza antigens that are different from those in the currently circulating
influenza viruses. These antigens can be considered as ‘novel’ antigens and simulate a situation where
the target population for vaccination is immunologically naïve. Data obtained with a mock-up vaccine
will support a vaccination strategy that is likely to be used for the pandemic vaccine: clinical efficacy
and safety data obtained with mock-up vaccines are relevant for the pandemic vaccines.
A clinical trial was conducted with a H5N1 vaccine combined with MF59C.1 adjuvant in 486 healthy
adult volunteers. Two doses of vaccine containing H5N1 (A/Vietnam/1194/2004) at 2 different
dosages (7.5 and 15 µg hemagglutinin [HA]/dose) with MF59C.1 adjuvant were administered three
weeks apart.
The seroprotection rate* seroconversion rate* and the seroconversion factor ** for anti-HA antibody
in the adults measured by SRH were as follows:
anti-HA antibody
22 days after 1
P
st
P
dose
21 days after 2
P
nd
P
dose
Seroprotection rate
41% (95% CI: 33-49)
86% (95% CI: 79-91)
Seroconversion rate
39% (95% CI: 31-47)
85% (95% CI: 79-91)
Seroconversion factor
2.42 (2.02-2.89)
7.85 (6.7-9.2)
* measured by SRH assay ≥ 25 mm
** geometric mean ratios of SRH
The seroprotection rate* seroconversion rate* and the seroconversion factor ** for anti-HA antibody
in subjects aged over 60 measured by SRH were as follows:
anti-HA antibody
22 days after 1
P
st
P
dose
21 days after 2
P
nd
P
dose
Seroprotection rate
53% (95% CI: 42-64)
81% (95% CI: 71-89)
Seroconversion rate
45% (95% CI: 34-56)
71% (95% CI: 60-81)
Seroconversion factor
2.85 (2.22-3.66)
5.02 (3.91-6.45)
* measured by SRH assay ≥ 25 mm
** geometric mean ratios of SRH
The persistence of antibodies for the mock-up vaccines varies. With the interpandemic trivalent
vaccines it is usually 6-12 months, but for this vaccine no data are available yet with the H5N1 strain.
•
U
Supportive Studies
In two dose finding studies 78 adults received an adjuvanted mock-up vaccine (H5N3 or H9N2).
Two doses of vaccine with H5N3 (A/Duck/Singapore/97) strain at 3 different dosages (7.5, 15 and 30
µg HA/dose) were administered three weeks apart.
Serum samples were tested against the original H5N3 and also a number of H5N1 isolates.
Serologic responses obtained with the SRH assay showed that 100% of subjects achieved
seroprotection and 100% seroconverted after two 7.5 µg injections. The adjuvanted vaccine was also
found to induce antibodies that cross-protected against the H5N1 strains isolated in 2003 and 2004,
which exhibit some antigenic drift compared to the original strains.
17
Two doses of vaccine containing H9N2 (A/chicken/Hong Kong/G9/97) strain at 4 different dosages
(3.75, 7.5, 15 and 30 µg HA/dose), were administered four weeks apart. Serologic responses obtained
with the Hemagglutination Inhibition (HI) assay showed that 92% of subjects achieved seroprotection
and 75% seroconverted after two 7.5 µg injections.
Foclivia has been authorised under “Exceptional Circumstances”.
This means that for scientific reasons, it has not been possible to obtain complete information on this
medicinal product. The European Medicines Agency (EMEA) will review any new information which
may become available every year and this SPC will be updated as necessary.
5.2 Pharmacokinetic properties
Not applicable.
5.3 Preclinical safety data
Not applicable.
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
18
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.
9.
19
ANNEX II
A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE
SUBSTANCE AND MANUFACTURING AUTHORISATION
HOLDER RESPONSIBLE FOR BATCH RELEASE
B. CONDITIONS OF THE MARKETING AUTHORISATION
20
A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND
MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH
RELEASE
U
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 – Sociville (SI)
Italy
Name and address of the manufacturer responsible for batch release
U
Novartis Vaccines and Diagnostics S.r.l.
Loc. Bellaria – 53018 Rosia – Sociville (SI)
Italy
B. CONDITIONS OF THE MARKETING AUTHORISATION
•
Medicinal product subject to medical prescription.
Foclivia can only be marketed when there is an official WHO/EU declaration of an influenza
pandemic, on the condition that the Marketing Authorisation Holder for Foclivia takes due account of
the officially declared pandemic strain.
•
CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND
EFFECTIVE USE OF THE MEDICINAL PRODUCT
Not applicable
•
OTHER CONDITIONS
a.
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.
b. Pharmacovigilance system
The MAH must ensure that the system of pharmacovigilance, as described in the version dated July
2009 presented in Module 1.8.1 of the Marketing Authorisation Application, is in place and
functioning before the product is placed on the market and for as long as the marketed product remains
in use.
c. Risk Management plan
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in
the Pharmacovigilance Plan, as agreed in the version of the Risk Management Plan (RMP) dated 29
21
March 2009 presented in Module 1.8.2. of the Marketing Authorisation Application and any
subsequent updates of the RMP agreed by the CHMP.
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the
updated RMP should be submitted at the same time as the next Periodic Safety Update Report (PSUR)
(i.e. in the pre-pandemic period).
In addition, an updated RMP should be submitted
•
When new information is received that may impact on the current Safety Specification,
Pharmacovigilance Plan or risk minimisation activities
•
Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being
reached
•
At the request of the EMEA
d- Periodic Safety Update Reports
Outside of the pandemic period, the normal PSUR periodicity and format will be maintained, with a
specific review of AESI and possible adverse events related to adjuvants. This should include data
from ongoing studies, or actual use if applicable, of the ‘mock-up’ strains and any safety data relevant
to the adjuvant system.
During a pandemic situation, the resources must be concentrated on a timely and effective monitoring
of the safety profile of the influenza vaccines used during the pandemic. Moreover, a 6-monthly cycle
may be too long to allow assessment of the safety of a vaccine for which high levels of exposure are
expected within a short period of time. Therefore, 6-monthly or annual PSURs falling within the
pandemic period will be replaced by monthly “simplified PSURs” (S-PSUR) accompanied by a
summary of vaccine distribution.
·
Frequency of submission:
-
The clock should start from the first Monday after shipment of the first batch of vaccine.
-
First data-lock point is 30 days later.
- S-PSUR submission to the Rapporteur and CHMP members on Day 45.
-
Rapporteur’s assessment report is circulated to CHMP members on Day 50.
-
CHMP report is circulated to the vaccine manufacturer on Day 55.
- Reporting to be monthly for the first 6 months.
- Periodicity should be reviewed by the MAH and the (Co-)Rapporteur at 6 monthly intervals.
When it has been agreed by the CHMP that the S-PSUR is no longer necessary, a full PSUR covering
the period since the data lock point of the last routine PSUR will be submitted within a time frame to
be agreed with the Rapporteur.
·
Format of the simplified PSUR:
Only spontaneously reported data should be included in the PSUR. The report should include the
following Tables of aggregate data (using the pre-defined templates attached in Annex 2).
1.
An overview for 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.
2.
An overview for 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.
22
3.
Adverse Events of Special Interest stratified according to type of report (medically confirmed
or non-medically confirmed). AESIs will be defined as follows:
-
Neuritis: PT “Neuritis”
-
Convulsion: narrow SMQ “Convulsions”
-
Anaphylaxis: narrow SMQ “Anaphylactic reaction” and narrow SMQ
“Angioedema”
-
Encephalitis: narrow SMQ “Non-infectious encephalitis”
-
Vasculitis: narrow SMQ “Vasculitis”
-
Guillain-Barré syndrome: narrow SMQ “Guillain-Barré syndrome”
-
Demyelination:
narrow SMQ “Demyelination” (as GBS is also included in
this SMQ, there will be an overlap in the number of cases for
these two categories).
-
Bell’s palsy:
PT “Bell’s palsy”
-
Vaccination failure:
PT “Vaccination failure”.
4.
Serious unlisted adverse reactions (SOC, HLT, PTs) stratified according to type of report
(medically confirmed or non-medically confirmed), for the period covered by the report and
cumulatively.
5.
All spontaneous adverse reactions by age group, per SOC, HLT and PT, stratified according to
type of report (medically confirmed or non-medically confirmed), for the period covered by
the report and cumulatively. The following age groups will be used: < 2 years, 2-8 years,
>
9
years.
6.
All spontaneous adverse reactions (SOC, HLT, PT) occurring in pregnant women, stratified
according to type of report (medically confirmed or non-medically confirmed), for the period
covered by the report and cumulatively.
The following principles should be followed when compiling the data:
- Except for Table 1, all tables will be based on number of reactions (presented on PT level, sorted
by System Organ Class [SOC] and High Level Term [HLT]) and not number of cases.
- All tables will be based on generic and not product-specific data
1
.
Product-specific data can be
evaluated during signal work-up.
- “Cumulatively” means since the use of the vaccine; events not reported during the period of
interest should not be presented in the tables.
-
All non-medically confirmed events are those that have been entered into the database by the data-
lock point. Those which have not yet been entered should be reported in the following S-PSUR.
- A line listing of fatal cases will be provided in an Annex.
A short summary should be provided in which validated signals and areas of concern are highlighted,
taking into account information arising from the prospective cohort study described in 4.5. In the
event of multiple signals, signal work-up may be prioritised and appropriate timelines for submission
of a full signal evaluation report should be provided.
Vaccine distribution report
To put the safety report into context, a summary of vaccine distribution should be included and should
provide details of the number of doses of vaccine distributed in
i)
EU member states for the reporting period by batch number,
ii)
EU member states cumulatively and
1
Based on the assumption that product name will not be provided in a significant proportion of cases.
23
iii)
the rest of the world.
C. SPECIFIC OBLIGATIONS TO BE FULFILLED BY THE MARKETING
AUTHORISATION HOLDER
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 annual reassessment of the
benefit/risk profile.
Quality
During the pandemic, the applicant will collect clinical safety
and effectiveness data of the pandemic vaccine and submit
this information to the CHMP for evaluation.
Depending on
and after
implementation
of vaccine when
first pandemic
will take place.
Pharmacovigilance
During the pandemic, the applicant will conduct a
prospective cohort study as identified in the
Pharmacovigilance plan
Depending on
and after
implementation
of vaccine when
first pandemic
will take place.
24
ANNEX III
LABELLING AND PACKAGE LEAFLET
25
A. LABELLING
26
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
CARDBOARD BOX FOR SYRINGE
1.
Foclivia suspension for injection in pre-filled syringe
Pandemic Influenza Vaccine (surface antigen, inactivated, adjuvanted)
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
One dose (0.5 ml) contains: Active Ingredients: Influenza virus surface antigens (haemagglutinin and
neuraminidase), propagated in eggs, and adjuvanted with MF59C.1, of strain:
A/Vietnam/1194/2004 (H5N1)
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 (0.5 ml) pre-filled syringe
10 x single dose (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 or subcutaneously.
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.
27
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.
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
28
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
CARDBOARD BOX FOR 1-DOSE VIAL
1.
Foclivia suspension for injection
Pandemic Influenza Vaccine (surface antigen, inactivated, adjuvanted)
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
One dose (0.5 ml) contains: Active Ingredients: Influenza virus surface antigens (haemagglutinin and
neuraminidase), propagated in eggs, and adjuvanted with MF59C.1, of strain:
A/Vietnam/1194/2004 (H5N1)
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.
Vial
10 x 1 dose
1 dose (0.5 ml)
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
To be administered intramuscularly into the deltoid muscle.
Warning
: Do not inject intravascularly or subcutaneously.
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 requirements.
Novartis Vaccines and Diagnostics S.r.l. - Via Fiorentina, 1 – Siena, Italy.
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.
Foclivia suspension for injection in multidose container
Pandemic Influenza Vaccine (surface antigen, inactivated, adjuvanted)
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
One dose (0.5 ml) contains: Active Ingredients: Influenza virus surface antigens (haemagglutinin and
neuraminidase), propagated in eggs, and adjuvanted with MF59C.1, of strain:
A/Vietnam/1194/2004 (H5N1)
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.
Vial
10 x 10 doses
1 dose (0.5 ml)
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
To be administered intramuscularly into the deltoid muscle.
Warning
: Do not inject intravascularly or subcutaneously.
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.
31
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 requirements
Novartis Vaccines and Diagnostics S.r.l. - Via Fiorentina, 1 – Siena, Italy.
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 AND 1-DOSE VIAL
1.
Foclivia injection
Pandemic influenza vaccine (surface antigen, inactivated, adjuvanted)
I.M. injection into the deltoid muscle
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
1 dose (0.5 ml)
6.
OTHER
Novartis V&D S.r.l. - Italy
Store in a refrigerator.
33
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
LABEL FOR 10-DOSE VIAL
1.
ADMINISTRATION
Foclivia injection
Pandemic Influenza Vaccine (surface antigen, inactivated, adjuvanted)
I.M. injection into the deltoid muscle
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
5 ml vial containing 10 doses (0.5 ml/dose)
6.
OTHER
Novartis V&D S.r.l. - Italy
Store in a refrigerator.
34
B. PACKAGE LEAFLET
35
PACKAGE LEAFLET: INFORMATION FOR THE USER
Foclivia suspension for injection in pre-filled syringe
Pandemic Influenza Vaccine (surface antigen, inactivated, adjuvanted)
Read all of this leaflet carefully before you start receiving this medicine.
-
Keep this leaflet. You may need to read it again.
-
If you have any further questions, ask your doctor.
-
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 Foclivia is and what it is used for
2. Before you receive Foclivia
3. How to receive Foclivia
4. Possible side effects
5.
How to store Foclivia
6.
Further information
1.
WHAT FOCLIVIA IS AND WHAT IT IS USED FOR
Foclivia is a vaccine against a pandemic influenza (flu).
It has to be used for the prophylaxis of influenza in an officially declared pandemic situation.
The vaccine works by causing the body to produce its own protection (antibodies) against the disease
2.
BEFORE YOU RECEIVE FOCLIVIA
Do not take Foclivia if you:
- have experienced serious allergic reaction (i.e. life-threatening) to any of the constituents of
Foclivia,
- are allergic (hypersensitive) to influenza vaccines or any of the ingredients of Foclivia,
- are allergic to eggs, chicken protein,
- are allergic to any antibiotic, formaldehyde, cetyltrimethylammonium bromide (CTAB) and
polysorbate 80.
Take special care with Foclivia if you:
- feel feverish,
- have any illness or infection,
- are having immunosuppressive therapy, e.g. corticosteroid treatment or chemotherapy for
cancer, or if you have any condition which makes you prone to infections (immunodeficiency
conditions),
In any of these cases, TELL YOUR DOCTOR, as vaccination may not be recommended, or may need
to be delayed.
Taking other medicines
Please tell your doctor if you are taking or have recently taken any other medicines, including
medicines obtained without a prescription. Foclivia should not be given at the same time as other
vaccines (if another vaccine is required at the same time, then the injection should be carried out on a
different limb. In such cases, the side effects may be more intense).
Pregnancy and breast-feeding
In a severe pandemic situation, the administration of the vaccine is recommended in pregnant women,
irrespective of their stage of pregnancy. The vaccine may be used during lactation.
36
Driving and using machines
The vaccine is unlikely to produce any effect on the ability to drive and use machines.
3.
HOW TO RECEIVE FOCLIVIA
Your doctor or nurse administers the vaccine.
A dose (0.5 ml) of the vaccine will be injected into the upper arm (deltoid muscle).
A second dose of vaccine should be given after an interval of at least 3 weeks.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Foclivia can cause side effects, although not everybody gets them.
Common
(in more than 1 out of 100 people, but less than 1 in 10).
Common side effects include: redness, swelling, pain at the site of injection, bruising, hardening of the
skin injection site. In some cases the effects may also include raised temperature, malaise (generally
feeling unwell), shivering, tiredness, headache, sweating, pain in muscles and joints. These reactions
usually disappear within 1-2 days without treatment. If they persist, CONSULT YOUR DOCTOR.
Uncommon
: (in more than 1 out of 1,000 people, but less than 1 in 100).
Uncommon side effects may include: generalised skin reactions including itching, bumps on the skin
or a non-specific rash.
Rare
(in more than 1 out of 10,000 people, but less than 1 in 1,000). Rare side effects include:
numbness or tingling sensations, involuntary muscle contractions or transient thrombocytopenia (a low
platelet count in the blood which can result in bleeding or bruising).
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.
Very rare
(in less than 1 in 10,000). Very rare side effects include: vasculitis (inflammation of the
blood vessels which can cause skin rashes, joint pain and kidney problems) and exudative Stevens-
Johnson syndrome (erythema multiforme). Neurological disorders such as encephalomyelitis
(inflammation of the central nervous system), neuritis (inflammation of nerves) and a type of paralysis
known as Guillain-Barré Syndrome.
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 FOCLIVIA
Keep out of the reach and sight of children.
Do not use Foclivia after the expiry date which is stated on the carton and the label after EXP. The
expiry date refers to the last day of that month.
Store in a refrigerator (2°C - 8°C). Do not freeze. Store in the original package in order to protect from
light.
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
37
What Foclivia contains
-
Active Substance:
Foclivia
does not
contain live virus particles and so it cannot cause Pandemic influenza. The active
ingredients of the vaccine are purified viral proteins (called haemagglutinin and neuraminidase). They
are isolated from the surface of influenza virus particles, which are grown in hen’s eggs and
inactivated with formaldehyde. These viral proteins are prepared from the strain of influenza virus that
complies with the WHO recommendations and EU decision in an officially declared Pandemic
situation.
One dose (0.5 ml) of the vaccine contains at least 7.5 micrograms of haemagglutinin from the
following recommended influenza virus strain:
A/Vietnam/1194/2004 (H5N1)
-
Adjuvant
:
The vaccine contains an ‘adjuvant’ (a compound containing squalene) to stimulate a better response.
The adjuvant includes also polysorbate 80 and sorbitan trioleate in a citrate buffer.
-
Other Ingredients
:
The other ingredients are: 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 Foclivia looks like and contents of the pack
Foclivia is a milky-white liquid.
It is provided in a ready-to-use syringe, containing a single dose (0.5 ml) 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
This leaflet was last approved in
{MM/YYYY}.
Foclivia has been authorised under “Exceptional Circumstances”.
This means that for scientific reasons, it has not been possible to obtain complete information on this
medicinal product. The European Medicines Agency (EMEA) will review any new information on the
medicine every year and this leaflet will be updated as necessary.
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web
38
PACKAGE LEAFLET: INFORMATION FOR THE USER
Foclivia suspension for injection
Pandemic Influenza Vaccine (surface antigen, inactivated, adjuvanted)
Read all of this leaflet carefully before you start receiving this medicine.
-
Keep this leaflet. You may need to read it again.
-
If you have any further questions, ask your doctor.
-
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 Foclivia is and what it is used for
2. Before you receive Foclivia
3. How to receive Foclivia
4. Possible side effects
6.
How to store Foclivia
6.
Further information
1.
WHAT FOCLIVIA IS AND WHAT IT IS USED FOR
Foclivia is a vaccine against a pandemic influenza (flu).
It has to be used for the prophylaxis of influenza in an officially declared pandemic situation.
The vaccine works by causing the body to produce its own protection (antibodies) against the disease
2.
BEFORE YOU RECEIVE FOCLIVIA
Do not take Foclivia if you:
- have experienced serious allergic reaction (i.e. life-threatening) to any of the constituents of
Foclivia,
-
are allergic (hypersensitive) to influenza vaccines or any of the ingredients of Foclivia,
-
are allergic to eggs, chicken protein,
-
are allergic to any antibiotic, formaldehyde, cetyltrimethylammonium bromide (CTAB) and
Take special care with FOCLIVIA if you:
- feel feverish,
- have any illness or infection,
- are having immunosuppressive therapy, e.g. corticosteroid treatment or chemotherapy for
cancer, or if you have any condition which makes you prone to infections (immunodeficiency
conditions),
In any of these cases, TELL YOUR DOCTOR, as vaccination may not be recommended, or may need
to be delayed.
Taking other medicines
Please tell your doctor if you are taking or have recently taken any other medicines, including
medicines obtained without a prescription. Foclivia should not be given at the same time as other
vaccines (if another vaccine is required at the same time, then the injection should be carried out on a
different limb. In such cases, the side effects may be more intense).
Pregnancy and breast-feeding
In a severe pandemic situation, the administration of the vaccine is recommended in pregnant women,
irrespective of their stage of pregnancy. The vaccine may be used during lactation.
39
polysorbate 80.
Driving and using machines
The vaccine is unlikely to produce any effect on the ability to drive and use machines.
3.
HOW TO RECEIVE FOCLIVIA
Your doctor or nurse administers the vaccine.
A dose (0.5 ml) of the vaccine will be injected into the upper arm (deltoid muscle).
A second dose of vaccine should be given after an interval of at least 3 weeks.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Foclivia can cause side effects, although not everybody gets them.
Common
(in more than 1 out of 100 people, but less than 1 in 10).
Common side effects include: redness, swelling, pain at the site of injection, bruising, hardening of the
skin injection site. In some cases the effects may also include raised temperature, malaise (generally
feeling unwell), shivering, tiredness, headache, sweating, pain in muscles and joints. These reactions
usually disappear within 1-2 days without treatment. If they persist, CONSULT YOUR DOCTOR.
Uncommon
: (in more than 1 out of 1,000 people, but less than 1 in 100).
Uncommon side effects may include: generalised skin reactions including itching, bumps on the skin
or a non-specific rash.
Rare
(in more than 1 out of 10,000 people, but less than 1 in 1,000). Rare side effects include:
numbness or tingling sensations, involuntary muscle contractions or transient thrombocytopenia (a low
platelet count in the blood which can result in bleeding or bruising).
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.
Very rare
(in less than 1 in 10,000). Very rare side effects include: vasculitis (inflammation of the
blood vessels which can cause skin rashes, joint pain and kidney problems) and exudative Stevens-
Johnson syndrome (erythema multiforme). Neurological disorders such as encephalomyelitis
(inflammation of the central nervous system), neuritis (inflammation of nerves) and a type of paralysis
known as Guillain-Barré Syndrome.
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 FOCLIVIA
Keep out of the reach and sight of children.
Do not use Foclivia after the expiry date which is stated on the carton and the label after EXP. The
expiry date refers to the last day of that month.
Store in a refrigerator (2°C - 8°C). Do not freeze. Store in the original package in order to protect from
light.
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
40
What Foclivia contains
-
Active Substance:
Foclivia
does not
contain live virus particles and so it cannot cause Pandemic influenza. The active
ingredients of the vaccine are purified viral proteins (called haemagglutinin and neuraminidase). They
are isolated from the surface of influenza virus particles, which are grown in hen’s eggs and
inactivated with formaldehyde. These viral proteins are prepared from the strain of influenza virus that
complies with the WHO recommendations and EU decision in an officially declared Pandemic
situation.
One dose (0.5 ml) of the vaccine contains at least 7.5 micrograms of haemagglutinin from the
following recommended influenza virus strain:
A/Vietnam/1194/2004 (H5N1)
-
Adjuvant
:
The vaccine contains an ‘adjuvant’ (a compound containing squalene) to stimulate a better response.
The adjuvant includes also polysorbate 80 and sorbitan trioleate in a citrate buffer.
-
Other Ingredients
:
The other ingredients are: 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 Foclivia looks like and contents of the pack
Foclivia is a milky-white liquid.
It is provided in a vial containing a single dose (0.5 ml) 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
This leaflet was last approved in
{MM/YYYY}.
Foclivia has been authorised under “Exceptional Circumstances”.
This means that for scientific reasons, it has not been possible to obtain complete information on this
medicinal product. The European Medicines Agency (EMEA) will review any new information on the
medicine every year and this leaflet will be updated as necessary.
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web
41
PACKAGE LEAFLET: INFORMATION FOR THE USER
Foclivia suspension for injection in multidose container
Pandemic Influenza Vaccine (surface antigen, inactivated, adjuvanted)
Read all of this leaflet carefully before you start receiving this medicine.
-
Keep this leaflet. You may need to read it again.
-
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 Foclivia is and what it is used for
2. Before you receive Foclivia
3. How to receive Foclivia
4. Possible side effects
7.
How to store Foclivia
6.
Further information
1.
WHAT FOCLIVIA IS AND WHAT IT IS USED FOR
Foclivia is a vaccine against a pandemic influenza (flu).
It has to be used for the prophylaxis of influenza in an officially declared pandemic situation.
The vaccine works by causing the body to produce its own protection (antibodies) against the disease
2.
BEFORE YOU RECEIVE FOCLIVIA
Do not take Foclivia if you:
-
have experienced serious allergic reaction (i.e. life-threatening) to any of the constituents of
Foclivia,
-
are allergic (hypersensitive) to influenza vaccines or any of the ingredients of Foclivia,
-
are allergic to eggs, chicken protein,
-
are allergic to any antibiotic, formaldehyde, cetyltrimethylammonium bromide (CTAB) and
polysorbate 80.
Take special care with Foclivia if you:
- feel feverish,
- have any illness or infection,
- are having immunosuppressive therapy, e.g. corticosteroid treatment or chemotherapy for
cancer, or if you have any condition which makes you prone to infections (immunodeficiency
conditions),
In any of these cases, TELL YOUR DOCTOR, as vaccination may not be recommended, or may need
to be delayed.
Taking other medicines
Please tell your doctor if you are taking or have recently taken any other medicines, including
medicines obtained without a prescription. Foclivia should not be given at the same time as other
vaccines (if another vaccine is required at the same time, then the injection should be carried out on a
different limb. In such cases, the side effects may be more intense).
Pregnancy and breast-feeding
In a severe pandemic situation, the administration of the vaccine is recommended in pregnant women,
irrespective of their stage of pregnancy. The vaccine may be used during lactation.
Driving and using machines
42
-
If you have any further questions, ask your doctor.
The vaccine is unlikely to produce any effect on the ability to drive and use machines.
Important information about some of the ingredients of Foclivia
This medicinal product in 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.
3.
HOW TO RECEIVE FOCLIVIA
Your doctor or nurse administers the vaccine.
A dose (0.5 ml) of the vaccine will be injected into the upper arm (deltoid muscle).
A second dose of vaccine should be given after an interval of at least 3 weeks.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Foclivia can cause side effects, although not everybody gets them.
Common
(in more than 1 out of 100 people, but less than 1 in 10).
Common side effects include: redness, swelling, pain at the site of injection, bruising, hardening of the
skin injection site. In some cases the effects may also include raised temperature, malaise (generally
feeling unwell), shivering, tiredness, headache, sweating, pain in muscles and joints. These reactions
usually disappear within 1-2 days without treatment. If they persist, CONSULT YOUR DOCTOR.
Uncommon
: (in more than 1 out of 1,000 people, but less than 1 in 100).
Uncommon side effects may include: generalised skin reactions including itching, bumps on the skin
or a non-specific rash.
Rare
(in more than 1 out of 10,000 people, but less than 1 in 1,000). Rare side effects include:
numbness or tingling sensations, involuntary muscle contractions or transient thrombocytopenia (a low
platelet count in the blood which can result in bleeding or bruising).
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.
Very rare
(in less than 1 in 10,000). Very rare side effects include: vasculitis (inflammation of the
blood vessels which can cause skin rashes, joint pain and kidney problems) and exudative Stevens-
Johnson syndrome (erythema multiforme). Neurological disorders such as encephalomyelitis
(inflammation of the central nervous system), neuritis (inflammation of nerves) and a type of paralysis
known as Guillain-Barré Syndrome.
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 FOCLIVIA
Keep out of the reach and sight of children.
Do not use Foclivia after the expiry date which is stated on the carton and the label after EXP. The
expiry date refers to the last day of that month.
Store in a refrigerator (2°C - 8°C). Do not freeze. Store in the original package in order to protect from
light.
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.
43
6.
FURTHER INFORMATION
What Foclivia contains
-
Active Substance:
Foclivia
does not
contain live virus particles and so it cannot cause Pandemic influenza. The active
ingredients of the vaccine are purified viral proteins (called haemagglutinin and neuraminidase). They
are isolated from the surface of influenza virus particles, which are grown in hen’s eggs and
inactivated with formaldehyde. These viral proteins are prepared from the strain of influenza virus that
complies with the WHO recommendations and EU decision in an officially declared Pandemic
situation.
One dose (0.5 ml) of the vaccine contains at least 7.5 micrograms of haemagglutinin from the
following recommended influenza virus strain:
A/Vietnam/1194/2004 (H5N1)
-
Adjuvant
:
The vaccine contains an ‘adjuvant’ (a compound containing squalene) to stimulate a better response.
The adjuvant includes also polysorbate 80 and sorbitan trioleate in a citrate buffer.
-
Other Ingredients
:
The other ingredients are: thiomersal, 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 Foclivia looks like and contents of the pack
Foclivia is a milky-white liquid.
It is provided in a vial containing ten doses (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
This leaflet was last approved in
{MM/YYYY}.
Foclivia has been authorised under “Exceptional Circumstances”.
This means that for scientific reasons, it has not been possible to obtain complete information on this
medicinal product. The European Medicines Agency (EMEA) will review any new information on the
medicine every year and this leaflet will be updated as necessary.
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web
44
Source: European Medicines Agency
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