ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
1.
IXIARO suspension for injection
Japanese encephalitis vaccine (inactivated, adsorbed)
2.
1 dose (0.5 ml) of IXIARO contains:
Japanese encephalitis virus strain SA
14
-14-2 (inactivated)
1,2
6 micrograms
3
corresponding to a potency of
≤ 460 ng ED
50
1
produced in Vero cells
2
adsorbed on aluminium hydroxide, hydrated
3
total protein content
0.25 milligrams Al
3+
For a full list of excipients, see section 6.1.
3.
Suspension for injection.
Clear liquid with a white precipitate.
4.
IXIARO is indicated for active immunization against Japanese encephalitis in adults.
IXIARO should be considered for use in individuals at risk of exposure through travel or in the course of
their occupation.
Posology
Adults
The primary vaccination series consists of two separate doses of 0.5 ml each according to the following
schedule:
First dose at Day 0.
Second dose: 28 days after first dose.
It is recommended that vacinees who received the first dose of IXIARO complete the primary 2-dose
vaccination course with IXIARO.
If the primary immunization of two injections is not completed, full protection against the disease might not
be achieved. There is data that a second injection given up to 11 months after the first dose results in high
seroconversion rates (see section 5.1).
Booster Dose
A booster dose (third dose) should be given within the second year (i.e. 12 - 24 months) after the
recommended primary immunization, prior to potential re-exposure to JEV. Persons at continuous risk for
acquiring Japanese encephalitis (laboratory personnel or persons residing in endemic areas) should receive a
booster dose at month 12 after primary immunization (see section 5.1). Data on the need for further booster
doses are not available.
2
Paediatric
IXIARO is not recommended for use in children and adolescents due to lack of data on safety and efficacy.
Method of administration
The vaccine should be administered by intramuscular injection into the deltoid muscle. It should never be
injected intravascularly.
Exceptionally, IXIARO can also be administered subcutaneously to patients with thrombocytopenia or
bleeding disorders since bleeding may occur following an intramuscular administration. Subcutaneous
administration could lead to a suboptimal response to the vaccine (see section 4.4). However, it should be
noted that there are no clinical efficacy data to support administration by the subcutaneous route.
Hypersensitivity to the active substance or to any of the excipients or to any residuals (e.g. protamin
sulphate).
Individuals who show hypersensitivity reactions after receiving the first dose of the vaccine should not be
given the second dose.
Administration must be postponed in persons with acute severe febrile conditions.
As with all injectable vaccines, appropriate medical treatment and supervision should always be available to
treat rare cases of anaphylactic reactions following the administration of the vaccine.
Under no circumstances should IXIARO be administered intravascularly.
As with any other vaccine, vaccination with IXIARO may not result in protection in all cases.
IXIARO will not protect against encephalitis caused by other micro-organisms.
Like other intramuscular injections, this vaccine should not be administered intramuscularly to persons with
thrombocytopenia, haemophilia or other bleeding disorders (see section 4.2).
A seroconversion rate of 29.4 % has been observed 10 days after the first vaccination, and 97.3 % one week
after the second vaccination. Hence, primary immunization should be completed at least one week prior to
potential exposure to Japanese encephalitis virus (JEV).
Protection against Japanese Encephalitis is not ensured until the second dose has been received.
Concomitant administration of IXIARO with inactivated hepatitis A vaccine has been evaluated in one
clinical study. There was no interference with the immune response to Japanese encephalitis virus (JEV) and
hepatitis A virus (HAV) vaccines, respectively. Concomitant administration of IXIARO and hepatitis A
vaccine was shown to be non inferior to single vaccinations with regard to geometric mean titres (GMT) of
anti JEV neutralizing antibody and HAV antibody, and for seroconversion rates (see section 5.1).
There were no statistically significant higher rates in systemic or injection site adverse reactions among
subjects who received concomitant vaccination with IXIARO and hepatitis A vaccine compared with those
who received IXIARO or hepatitis A vaccine alone.
In patients receiving immunosuppressive therapy or patients with immunodeficiency an adequate immune
response may not be obtained.
Pregnancy
There are limited amount of data from the use of IXIARO in pregnant or breast-feeding women.
In animal studies findings of unclear clinical relevance have been identified (see section 5.3).
As a precautionary measure, the use of IXIARO during pregnancy or lactation should be avoided.
3
Lactation
It is unknown whether IXIARO is excreted in human milk.
No effects on the breastfed newborn/infant are anticipated since the systemic exposure of the breast-feeding
woman to IXIARO is negligible.
No studies on the effects of IXIARO on the ability to drive and use machines have been performed.
The safety of the vaccine was assessed in different controlled and uncontrolled clinical studies in which
4,043 healthy adults received IXIARO.
Approximately 40% of treated subjects can be expected to experience adverse reactions. They usually occur
within the first three days after vaccination, are usually mild and disappear within a few days. No increase in
the number of adverse reactions was noted between first and second doses or following a booster dose.
Most commonly reported adverse reactions included headache and myalgia occurring in approximately 20%
and 13% of subjects, respectively.
Adverse reactions are listed according to the following frequencies:
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, not known (cannot be estimated from the available data)
Infections and infestations
Uncommon: nasopharyngitis, rhinitis
Blood and lymphatic system disorders
Uncommon: lymphadenopathy
Rare: thrombocytopenia
Nervous system disorders
Very common: headache
Uncommon: migraine, dizziness
Rare: paraesthesia, neuritis
Ear and labyrinth disorders
Uncommon: vertigo
Cardiac disorders
Rare: palpitations, tachycardia
Respiratory, thoracic and mediastinal disorders
Rare: dyspnoea
Gastrointestinal disorders
Common: nausea
Uncommon: vomiting, diarrhoea, abdominal pain
Skin and subcutaneous tissue disorders
Uncommon: rash, pruritus
Rare: urticaria, erythema
4
Musculoskeletal and connective tissue disorders
Very common: myalgia
Uncommon: musculoskeletal stiffness
Rare: pain in extremity, arthralgia
General disorders and administration site conditions
Very common: injection site: pain, tenderness
Common: fatigue , influenza like illness, pyrexia, injection site: redness, hardening, swelling, itching
Uncommon: chills, malaise. injection site: haematoma
Rare: oedema peripheral
Investigations
Uncommon: hepatic enzymes increased
No case of overdose has been reported.
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Encephalitis vaccines. ATC code: J07BA02
Mechanism of action
The mechanism of action of Japanese encephalitis (JE) vaccines is not well understood. Studies in animals
have shown that the vaccine triggers the immune system to produce antibodies against Japanese encephalitis
virus that are most often protective. Challenge studies were performed in mice that were treated with human
IXIARO antisera. These studies showed that almost all mice that had a Plaque Reduction Neutralization Test
titre of at least 1:10 were protected from a lethal Japanese encephalitis virus challenge.
Clinical studies
No prospective efficacy trials have been performed. Immunogenicity of IXIARO was studied in
approximately 2,228 healthy adult subjects included in seven randomized, controlled clinical studies and
three uncontrolled trials.
Immunogenicity of the vaccine was evaluated in a randomized, active controlled, observer blinded,
multicenter Phase 3 clinical trial including 867 healthy male and female subjects given IXIARO or the US
licensed JEV vaccine JE VAX (on a 0, 7 and 28 day schedule by subcutaneous injection). The co primary
endpoint was seroconversion rate (anti JEV antibody titer ≥1:10) and geometric mean titers (GMT) at Day 56
as assessed by a Plaque Reduction Neutralization Test (PRNT) for the entire study population.
By Day 56, the proportion of subjects who had seroconverted was similar for both treatment groups (96.4%
vs. 93.8% for IXIARO and JE VAX, respectively). GMT increased by Day 56 to 243.6 for IXIARO and to
102.0 for JE VAX, respectively. The immune responses elicited by IXIARO were non inferior to those
induced by JE VAX (Table 1).
Table 1:
Seroconversion rates and geometric mean titers of IXIARO and JE VAX in the Per Protocol
Population. Neutralising antibody titers against JEV were measured against the JEV strain
SA14-14-2.
Seroconversion rate
Time point
IXIARO
N=365
% (n)
JE-VAX
N=370
% (n)
5
Visit 0 (Screening)
0
0
Visit 3 (Day 28)
54 (197)
86.8 (321)
Visit 4 (Day 56)
96.4 (352)
93.8 (347)
Geometric mean titer (by plaque reduction neutralization test)
Time point
IXIARO
N=365
GMT (n)
JE-VAX
N=370
GMT (n)
Visit 0 (Screening)
5.0 (365)
5.0 (370)
Visit 3 (Day 28)
17.4 (363)
76.9 (367)
Visit 4 (Day 56)
243.6 (361)
102.0 (364)
The effect of age on the immune response to IXIARO and JE VAX was assessed as a secondary endpoint in
this active controlled study, comparing subjects over 50 years of age (N=262, mean age 59.8) with those
below 50 years of age (N=605, mean age 33.9).
There was no significant difference between seroconversion rates of IXIARO and JE VAX in subjects aged
<50 years compared to those aged ≥50 years at Day 28 or Day 56 following vaccination. Geometric mean
titers were significantly higher at Day 28 in subjects aged <50 years than those aged ≥50 years in the JE
VAX group (80.9 vs. 45.9, p=0.0236) but there was no significant difference at Day 56 for this treatment
group. There were no significant effects of age on geometric mean titer in the group receiving IXIARO.
There was no significant difference between seroconversion rates in subjects aged <50 years compared to
those aged ≥50 years at Day 28 or Day 56 for either treatment group.
Antibody persistence
Antibody persistence was evaluated in an uncontrolled Phase 3 follow up clinical trial, enrolling
subjects who had completed two pivotal studies, and who received at least one dose of IXIARO.
Long term immunogenicity of IXIARO was assessed in a subset of 181 subjects up to month 24
(Intent-to-treat (ITT) population
) and in 152 subjects up to month 36 after the first IXIARO vaccination.
Rates of subjects with PRNT
50
≥1:10 and GMTs at Months 2, 6, 12, 24 and 36 are summarized in Table 2 for
the ITT population.
Table 2
Rates of subjects with PRNT
50
≥1:10 and geometric mean titers (GMT) at Month 2, 6, 12 , 24
and 36 after vaccination with IXIARO (ITT population)
Time point
Rate of subjects with PRNT
50
≥1:10
GMT
GMT (N) 95% Confidence
Interval
Month 2 98.9 (179/181) [96.1, 99.7] 310.8 (181) [268.8, 359.4]
Month 6 95.0 (172/181) [90.8, 97.4] 83.5 (181) [70.9, 98.4]
Month 12 83.4 (151/181) [77.3, 88.1] 41.2 (181) [34.4, 49.3]
Month 24 81.8 (148/181) [75.5, 86.7] 44.3 (181) [36.7, 53.4]
Month 36 84.9 (129/152) [78.32, 89.70] 43.8 (152) [36.5, 52.6]
The observed decline in GMT is as expected and compares well with data from other inactivated JE
vaccines.
% (n/N)
95% Confidence
Interval
In another open-label, follow-up Phase 3 study, the persistence of antibodies up to 24 months after primary
vaccination was assessed. A total of 116 subjects who had received the recommended primary schedule of
IXIARO were included in this follow-up study. Rates of subjects with PRNT
50
≥1:10 were 82.8% (95% CI:
74.9, 88.6, N=116) at Month 6 and 58.3% at Month 12 (95% CI: 49.1, 66.9, N=115). At Month 24, 48.3%
(95% CI: 39.4, 57.3, N=116) of subjects who completed the recommended primary immunization still had
PRNT
50
titers of
≥
1:10. GMT in these subjects was 16.2 (95% CI: 13.8, 19.0) at Month 24.
Booster immunisation
6
In an uncontrolled, open-label phase 3 study a single 6 mcg booster dose of IXIARO was given at month 15
after primary immunization. All of the 198 subjects treated were included in the ITT and Safety Populations.
Rates of subjects with PRNT
50
≥1:10 and GMT over time are summarised below in table 3:
Table 3: Rates of subjects with PRNT
50
≥1:10 and GMT before and at months 1, 6 and 12 after a single 6 mcg
booster dose administered to subjects at 15 months after recommended primary immunization with IXIARO
(ITT population)
Rate of subjects with PRNT
50
≥1:10
GMT
95% CI
95% CI
Pre-booster, Day 0
(n=198)
69.2%
[62.4%, 75.2%]
22.5
[19.0, 26.7]
Day 28 (n=198)
100.0%
[98.1%, 100.0%]
900.1
[742.4, 1091.3]
Month 6 (n=197)
98.5%
[95.6%, 99.5%]
487.4
[390.7, 608.1]
Month 12 (n=194)
98.5%
[95.6%, 99.5%]
361.4
[294.5, 443.5]
Incomplete primary immunization
The immunogenicity of booster doses was also assessed in the study investigating persistence of immunity
following different primary immunization regimens (2x6 mcg: N=116, 1x12mcg: N=116 or 1x6 mcg:
N=117). A single 6 mcg booster dose was administered at 11 or 23 months after the first dose to subjects,
which were determined to be seronegative (PRNT
50
titers < 1:10) at month 6 and/or month 12 after the
primary immunization. Results indicate that the second injection of the primary immunization series can be
given up to 11 months after the first dose. The immune responses to further doses at different time points
after complete or incomplete primary immunization are shown in table 4.
Table 4: SCR and GMT at four weeks after a single 6 mcg booster dose administered to subjects with a
PRNT
50
<1:10 (PRNT
50
<1:10 means a subject is no longer seroprotected) at month 11 or month 23 after
recommended primary immunization (2x 6 mcg) or incomplete (1x6 mcg) primary immunization with
IXIARO (ITT population)
(n / N)
SCR
GMT
[
95% CI
]
Booster following recommended
primary immunization (2x6 mcg)
Booster at Month 11
(17 / 17)
100 %
673.6
[378.7, 1198.2]
Booster at Month 23
Second dose following incomplete
primary immunization (1x6 mcg)
(27 / 27)
100 %
2536.7 [1467.7, 4384.]
Second dose at Month 11
Second dose at Month 23
(99 / 100)
99 %
504.3
[367.3, 692.3]
(5 / 5)
100 %
571.4
[88.2, 3702.9]
Concommitant use
The concomitant use of IXIARO with inactivated hepatitis A virus (HAV) vaccine (HAVRIX 1440) has been
explored in one clinical trial. There was no interference with the immune response to the JE virus and HAV,
respectively. Concomitant administration of IXIARO and inactivated hepatitis A vaccine was shown to be
non-inferior to single vaccinations with regard to GMT of anti-JE virus neutralizing antibody and HAV
antibody, and for seroconversion rates of both antibody types (Table 5).
Table 5:
Seroconversion rates and geometric mean titer of anti JEV neutralizing antibody at Day 56 and
seroconversion rates and geometric mean titer for HAV antibody at Day 28 in the Per Protocol
Population
7
Seroconversion rates and geometric mean titer for anti-JEV neutralizing antibody at Day 56
% with SCR
GMT
95% CI
Group C: IXIARO + HAVRIX1440
100.0
202.7
[153.7, 261.2]
Group A: IXIARO + Placebo
98.2
192.2
[147.9, 249.8]
Seroconversion rates and geometric mean titer for HAV antibody at Day 28
% with SCR
GMT
95% CI
Group C: IXIARO + HAVRIX 1440
100.0
150.0
[111.7, 202.3]
Group B: HAVRIX + Placebo
96.2
124.0
[91.4, 168.2]
5.2 Pharmacokinetic properties
Evaluation of pharmacokinetic properties is not required for vaccines.
5.3 Preclinical safety data
Non-clinical toxicity data are limited.
In a reproductive and pre-/post-natal toxicity study, no vaccine-related effects were detected on reproduction,
foetal weight, survival and development of the off-spring. However, incomplete ossification of parts of the
skeleton was observed in the group receiving 2 doses, but not in the group receiving 3 doses. It is currently
difficult to explain if this phenomenon is treatment related or not.
6.
6.1 List of excipients
Phosphate buffered saline consisting of:
Sodium chloride
Potassium dihydrogen phosphate
Disodium hydrogen phosphate
Water for injections
For adjuvant, see section 2.
6.2 Incompatibilities
In the absence of compatibility studies, this vaccine must not be mixed with other medicinal products.
6.3 Shelf life
18 months
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
8
0.5 ml of suspension in a pre-filled syringe (Type I glass) with a plunger stopper (chlorobutyl elastomer).
Pack size of 1 syringe with or without a separate needle.
6.6 Special precautions for disposal
Do not use if the blister foil is not intact or packaging is damaged.
Upon storage, a fine white deposit with a clear colourless supernatant can be observed.
The pre-filled syringe is ready to use. If a needle is not provided, use a sterile needle. To attach Luer needle,
remove the syringe tip cap by gently twisting it.
Do not attempt to snap or pull the tip off as this may
damage the syringe.
Shake before use. Thorough agitation immediately before administration is necessary to maintain suspension
of the vaccine. The full recommended dose of the vaccine should be used.
Prior to agitation, IXIARO may appear as a clear liquid with a white precipitate. After thorough agitation, it
forms a white, cloudy liquid/suspension. The vaccine should be visually inspected for particulate matter and
discoloration prior to administration. Discard the product if particulates are present or if it appears
discoloured or if the syringe appears to be physically damaged.
Any unused product or waste material should be disposed of in accordance with local requirements.
7.
Intercell AG
Campus Vienna Biocenter 3
A-1030 Vienna
Austria
8.
EU/1/08/501/001
EU/1/08/501/002
9.
31/03/ 2009
Detailed information on this medicinal product is available on the website of the European Medicines
Agency
http://www.ema.europa.eu
9
ANNEX II
A.
MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE
SUBSTANCE(S) AND MANUFACTURING AUTHORISATION
HOLDER(S) RESPONSIBLE FOR BATCH RELEASE
B.
CONDITIONS OF THE MARKETING AUTHORISATION
10
A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND
MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCH
RELEASE
Name and address of the manufacturer(s) of the biological active substance(s)
Intercell Biomedical Ltd.
Oakbank Park Road
Livingston EH53 0TG
United Kingdom
Name and address of the manufacturer(s) responsible for batch release
Intercell Biomedical Ltd.
Oakbank Park Road
Livingston EH53 0TG
United Kingdom
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.
The printed package leaflet of the medicinal product must state the name and address of the manufacturer
responsible for the release of the concerned batch.
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
Not applicable
•
OTHER CONDITIONS
Pharmacovigilance system
The MAH must ensure that the system of pharmacovigilance, as described in version 7.0 (14 May 2009)
presented in Module 1.8.1. of the Marketing Authorisation Application, is in place and functioning before
and whilst the product is on the market.
Risk Management Plan
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in the
Pharmacovigilance Plan, as agreed in version 1.4 (18 May 2009) 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.
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).
In addition, an updated RMP should be submitted
11
•
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
12
ANNEX III
LABELLING AND PACKAGE LEAFLET
13
A. LABELLING
14
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
Outer carton
1.
IXIARO suspension for injection
Japanese encephalitis vaccine (inactivated, adsorbed)
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
1 dose (0.5 ml) of IXIARO contains:
6 micrograms (total protein content, corresponding to a potency of ≤ 460 ng ED
50
) of inactivated Japanese
encephalitis virus strain SA
14
-14-2 (produced in Vero cells) adsorbed on aluminium hydroxide, hydrated
(approximately 0.25 mg Al
3+
).
3.
LIST OF EXCIPIENTS
Phosphate buffered solution consisting of sodium chloride, potassium dihydrogen phosphate, disodium
hydrogen phosphate and water for injections.
4.
Suspension for injection.
0.5 ml single dose in a pre-filled syringe.
0.5 ml single dose in a pre-filled syringe + 1 needle
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Intramuscular (IM) use.
Shake to form a uniform suspension.
Read the package leaflet before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF
THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
Do not inject intravascularly.
8.
EXPIRY DATE
EXP:
15
9.
SPECIAL STORAGE CONDITIONS
Store in a refrigerator (2°C-8°C).
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
Intercell AG
Campus Vienna Biocenter 3
A-1030 Vienna
Austria
EU/1/08/501/001
EU/1/08/501/002
13. BATCH NUMBER
Lot:
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
16
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
Blister foil
Blank white foil without any printed information.
17
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
Pre-filled syringe label
1.
IXIARO suspension for injection
Japanese encephalitis vaccine
Intramuscular (IM) use
2.
METHOD OF ADMINISTRATION
3.
EXPIRY DATE
EXP:
4.
BATCH NUMBER
Lot:
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
1 dose, 0.5ml
6.
OTHER
Store in a refrigerator
Do not freeze
18
B. PACKAGE LEAFLET
19
PACKAGE LEAFLET: INFORMATION FOR THE USER
IXIARO suspension for injection
Japanese encephalitis vaccine (inactivated, adsorbed)
Read all of this leaflet carefully before you start receiving this vaccine.
-
Keep this leaflet. You may need to read it again.
-
If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor.
In this leaflet
:
1. What IXIARO is and what it is used for
2. Before you receive IXIARO
3. How IXIARO is given
4. Possible side effects
5.
How to store IXIARO
6.
Further information
1.
WHAT IXIARO IS AND WHAT IT IS USED FOR
What IXIARO is
IXIARO is a vaccine against the Japanese encephalitis virus.
The vaccine causes the body to produce its own protection (antibodies) against this disease.
What IXIARO is used for
IXIARO is used to prevent infection with the Japanese encephalitis virus (JEV). This virus is mainly found
in Asia and is transmitted to humans by mosquitoes that have bitten an infected animal (like pigs). Many
infected people develop mild symptoms or no symptoms at all. In people who develop severe disease, JE
usually starts as a flu-like illness, with fever, chills, tiredness, headache, nausea, and vomiting. Confusion
and agitation also occur in the early stage.
IXIARO should be given to adults (18 years and older).
2.
BEFORE YOU RECEIVE IXIARO
You must NOT receive IXIARO
•
if you are allergic (hypersensitive) to the active substance or any of the other ingredients of IXIARO.
The active substance and other ingredients are listed at the end of the leaflet (see Section 6 “Further
Information
”
).
•
if you have developed an allergic reaction after receiving a former dose of IXIARO. Signs of an
allergic reaction may include an itchy rash, shortness of breath and swelling of the face and tongue.
•
if you are ill with a high fever. In this case, your doctor will postpone the vaccination.
Take special care with IXIARO
IXIARO must not be injected into a blood vessel.
Primary immunization should be completed at least one week prior to potential exposure to JEV.
Tell your doctor:
•
if you have experienced any health problems after previous administration of any vaccine.
•
if you have any other known allergies.
20
-
If you have any further questions, ask your doctor.
•
if you have a bleeding disorder (a disease that makes you bleed more than normal) or a reduction in
blood platelets, which increases risk of bleeding or bruising (thrombocytopenia).
•
if you are
under 18
. Since IXIARO has not been tested in people under 18 it is not recommended to
be used in this group.
•
if your immune system does not work properly (immunodeficiency) or you are taking medicines
affecting your immune system
(such as a medicine called cortisone or cancer medicine).
Your doctor will discuss with you the possible risks and benefits of receiving IXIARO.
Please note that:
•
IXIARO cannot cause the disease it protects against.
•
You should take appropriate precautions to reduce mosquito bites (adequate clothing, use of repellents,
mosquito nets) even after receiving IXIARO.
Using other medicines or vaccines
A study in humans to evaluate the effectiveness and safety of medicines (clinical trial) has shown that
IXIARO can be given at the same time with hepatitis A vaccine.
Please tell your doctor if you are taking or have recently taken any other medicines, including medicines
obtained without a prescription or have recently received any other vaccine.
Pregnancy and breast-feeding
There are limited amount of data from the use of IXIARO in pregnant or breast-feeding women.
As a precautionary measure, the use of IXIARO during pregnancy or breast-feeding should be avoided.
Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines
No studies on the effect of IXIARO on the ability to drive or use machines have been preformed.
3.
HOW IXIARO IS GIVEN
Dosage for adults
You will receive a total of 2 injections:
•
the first injection on Day 0
•
the second injection 28 days after the first injection (Day 28).
Make sure you finish the complete vaccination course of 2 injections. The second injection should be given
at least 1 week before you will be at risk of exposure to JE virus. If not, you may not be fully protected
against the disease.
A booster dose can be given within the second year (i.e. 12 - 24 months) after the first dose of the
recommended primary immunization. Your doctor will decide on requirement of booster.
Administration
IXIARO is injected into your upper arm muscle (deltoid muscle) by your doctor or a nurse. It must not be
injected into a blood vessel. In case you suffer from a bleeding disorder, your doctor may decide to
administer the vaccine under the skin (subcutaneously).
If you have any further questions on the use of this product, ask your doctor or pharmacist.
If you forget to take IXIARO
If you miss a scheduled injection, talk to your doctor and arrange another visit for the second injection.
Without the second injection you will not be fully protected against the disease. There is data that the second
injection can be given up to 11 months after the first one.
21
•
IXIARO will not prevent infections caused by other viruses than the Japanese encephalitis virus.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, IXIARO can cause side effects, although not everybody gets them.
The frequency of the side effects are defined as follows:
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
Not known
Frequency cannot be estimated from the available data
The majority of the side effects listed below have been observed during clinical trials. They usually occur
within the first 3 days after vaccination, are usually mild and disappear within a few days.
Very common:
•
headache
•
muscle pain
•
tiredness
•
injection site reactions (pain, tenderness)
Common:
•
fatigue
•
nausea
•
influenza like illness
•
fever
•
injection site reactions (redness, hardening, swelling, itching)
Uncommon:
•
vomiting
•
skin rash
•
changes in the lymph-nodes
•
migraine (throbbing headache, often accompanied by nausea and vomiting and sensitivity to light)
•
dizziness
•
vertigo (spinning sensation)
•
diarrhoea
•
belly pain
•
itching
•
chills
•
runny or blocked nose
•
inflammation of nose and throat
•
general condition of feeling unwell
•
musculoskeletal stiffness
•
injection site reactions (bleeding, bruising)
•
abnormal laboratory liver test results
Rare:
•
palpitations
•
rapid heart beat
•
difficulty to breathe
•
abnormal sensation of skin
•
hives
•
skin redness
•
pain in leg or arm
22
•
joint pain
•
platelet deficiency
•
nerve inflammation
•
foot, leg and ankle swelling
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell
your doctor or pharmacist.
5.
HOW TO STORE IXIARO
•
Keep out of the reach and sight of children.
•
Do not use IXIARO after the expiry date which is stated on the carton and 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. If the vaccine has been frozen it should not be used.
•
Store in the original package in order to protect from light.
•
Any unused product or waste material should be disposed of in accordance with local requirements.
6.
FURTHER INFORMATION
What IXIARO contains
1 dose (0.5 ml) of IXIARO contains:
Japanese encephalitis virus strain SA
14
-14-2 (inactivated)
1,2
6 micrograms
3
corresponding to a potency of ≤ 460 ng ED
50
1
produced in Vero cells
2
adsorbed on aluminium hydroxide, hydrated 0.25 milligrams Al
3+
3
total protein content
Aluminium hydroxide is included in this vaccine as an adjuvant.
The other ingredients are: Sodium chloride, potassium dihydrogen phosphate, disodium hydrogen phosphate,
water for injections
What IXIARO looks like and contents of the pack
IXIARO is a suspension for injection (0.5 ml in a glass syringe with or without a separate needle, pack size
of 1).
IXIARO is a white and slightly milky sterile suspension which becomes homogenous on shaking.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Intercell AG
Campus Vienna Biocenter 3
A-1030 Vienna
Austria
Manufacturer:
Intercell Biomedical Ltd.
Oakbank Park Road,
Livingston EH53 0TG, Scotland,
United Kingdom
23
For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder:
België/Belgique/Belgien
Novartis Vaccines and Diagnostics Ltd
Tél/Tel: +44 (0) 845 745 1500
Luxembourg/Luxemburg
Novartis Vaccines and Diagnostics Ltd
Tél/Tel: +44 (0) 845 745 1500
България/Bulgaria
Novartis Vaccines and Diagnostics Ltd
Te
л.
:
+44 (0) 845 745 1500
Magyarország/Hungary
Novartis Vaccines and Diagnostics Ltd
Tél/Tel: +44 (0) 845 745 1500
Česká republika/Czech Republic
Novartis Vaccines and Diagnostics Ltd
Tel: +44 (0) 845 745 1500
Malta
Novartis Vaccines and Diagnostics Ltd
Tel.: +44 (0) 845 745 1500
Danmark
SBL Vaccin AB
Tlf: + 46 (0)8 735 10 00
Nederland
Novartis Vaccines and Diagnostics Ltd
Tel: +44 (0) 845 745 1500
Deutschland
Novartis Vaccines and Diagnostics GmbH & Co.
KG
Emil -von-Behring-Str. 76
D-35041 Marburg
Tel: +49 (0) 6421 39-15
Norge/Norway
SBL Vaccin AB
Tlf: + 46 (0)8 735 10 00
Eesti/Estonia
Novartis Vaccines and Diagnostics Ltd
Tel: +44 (0) 845 745 1500
Österreich/Austria
Novartis Pharma GmbH
Brunner Strasse 59
A-1235 Wien
Tel: +43 186 6570
Ελλάδα/Greece
Novartis Vaccines and Diagnostics Ltd
Τηλ: +44 (0) 845 745 1500
Polska/Poland
Novartis Vaccines and Diagnostics Ltd
Tel: +44 (0) 845 745 1500
España/Spain
Novartis Vaccines and Diagnostics, S.L.
B-58564808
Gran Vía de les Corts Catalanes 764
08013 Barcelona
Tel: +34 93 306 42 00
Portugal
Novartis Vaccines and Diagnostics Ltd
Tel: +44 (0) 845 745 1500
France
Novartis Vaccines and Diagnostics SAS
10, rue Chevreul
F-92150 Suresnes
Tél: +33 1 4138 7400
România
Novartis Vaccines and Diagnostics Ltd
Tel: +44 (0) 845 745 1500
Ireland
Novartis Vaccines and Diagnostics Ltd
Tel: +44 (0) 845 745 1500
Slovenija/Slovenia
Novartis Vaccines and Diagnostics Ltd
Tel: +44 (0) 845 745 1500
Ísland/Iceland
Novartis Vaccines and Diagnostics Ltd
Sími: +44 (0) 845 745 1500
Slovenská republika/Slovakia
Novartis Vaccines and Diagnostics Ltd
Tel: +44 (0) 845 745 1500
24
Italia
Novartis Vaccines and Diagnostics Srl
Via Florentina 1
I-53100 Siena
Tel: 8000 16888 (+39 0577 243111)
Suomi/Finland
SBL Vaccin AB
Puh/Tel: + 46 (0) 8 735 10 00
Κύπρος/Cyprus
Novartis Vaccines and Diagnostics Ltd
Τηλ: +44 (0) 845 745 1500
Sverige/Sweden
SBL Vaccin AB
SE-105 21 Stockholm
Tel: + 46 (0)8 735 10 00
Latvija/Latvia
Novartis Vaccines and Diagnostics Ltd
Tel: +44 (0) 845 745 1500
United Kingdom
Novartis Vaccines and Diagnostics Ltd
Gaskill Road Speke
Liverpool L24 9GR
Tel: +44 (0) 845 745 1500
Lietuva/Lithuania
Novartis Vaccines and Diagnostics Ltd
Tel: +44 (0) 845 745 1500
This leaflet was last approved in
03/2010.
Detailed information on this medicine is available on the European Medicines Agency web site:
<-----------------------------------------------------------------------------------------------------------------------------
The following information is intended for medical or healthcare professionals only:
The vaccine should be well shaken before administration to obtain a homogenous suspension. The pre-filled
syringe is for single use only and should not be used for more than 1 person. The entire content of a syringe
has to be injected.
25
Source: European Medicines Agency
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