ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
1.
Ambirix, suspension for injection
Hepatitis A (inactivated) and hepatitis B (rDNA) (HAB) vaccine (adsorbed).
2.
1 dose (1 ml) contains:
Hepatitis A virus (inactivated)
1,2
720 ELISA Units
Hepatitis B surface antigen
3,4
20 micrograms
1
Produced on human diploid (MRC-5) cells
2
Adsorbed on aluminium hydroxide, hydrated 0.05 milligrams Al
3+
3
Produced in yeast cells (
Saccharomyces
cerevisiae
) by recombinant DNA technology
4
Adsorbed on aluminium phosphate
0.4 milligrams Al
3+
For a full list of excipients, see section 6.1.
3.
Suspension for
injection .
Ambirix is a turbid white suspension.
4.
Ambirix is indicated in non-immune children and adolescents from 1 year up to and including 15
years for protection against hepatitis A and hepatitis B infection.
Protection against hepatitis B infections may not be obtained until after the second dose (see section
5.1).
Therefore:
-
Ambirix should be used only when there is a relatively low risk of hepatitis B infection during
the vaccination course.
-
It is recommended that Ambirix should be administered in settings where completion of the
two-dose vaccination course can be assured.
Posology
-
Dosage
A dose of 1.0 ml is recommended for subjects from 1 year up to and including 15 years of age.
The safety and efficacy of Ambirix in children aged less than 1 year have not been established.
No data are available.
-
Primary vaccination schedule
2
The standard primary course of vaccination with Ambirix consists of two doses, the first administered
at the elected date and the second between six and twelve months after the first dose.
The recommended schedule should be adhered to. Once initiated, the primary course of vaccination
should be completed with the same vaccine.
-
Booster dose
In situations where a booster dose of hepatitis A and/or hepatitis B is desired, a monovalent or
combined vaccine can be given. The safety and immunogenicity of Ambirix administered as a booster
dose following a two dose primary course have not been evaluated.
The anti-hepatitis B surface antigen (anti-HBs) and anti-hepatitis A virus (anti-HAV) antibody titres
observed following a primary vaccination course with Ambirix are in the range of what is seen
following vaccination with the monovalent hepatitis A and B vaccines. General guidelines for booster
vaccination can therefore be drawn from experience with the monovalent vaccines, as follows.
Hepatitis B
The need for a booster dose of hepatitis B vaccine in healthy individuals who have received a full
primary vaccination course has not been established. However some official vaccination programmes
currently include a recommendation for a booster dose of hepatitis B vaccine and these should be
respected.
For some categories of subjects at risk of exposure to HBV (e.g. haemodialysis or
immunocompromised patients) a precautionary attitude should be considered to ensure that a
protective antibody level ≥ 10 mIU/ml is maintained.
Hepatitis A
It is not yet fully established whether immunocompetent individuals who have responded to hepatitis
A vaccination will require booster doses as protection in the absence of detectable antibodies may be
ensured by immunological memory. Guidelines for boosting are based on the assumption that
antibodies are required for protection.
Method of administration
Ambirix is for intramuscular injection, usually into the deltoid muscle. However the anterolateral
thigh may be used in very young subjects if preferred.
Exceptionally, the vaccine may be administered subcutaneously in patients with thrombocytopenia or
bleeding disorders. However, this route of administration may result in suboptimal immune response
to the vaccine. (see section 4.4)
Hypersensitivity to the active substances or to any of the excipients or neomycin.
Hypersensitivity after previous administration of hepatitis A and/or hepatitis B vaccines.
As with other vaccines, the administration of Ambirix should be postponed in subjects suffering from
acute severe febrile illness.
3
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.
It is possible that subjects may be in the incubation period of a hepatitis A or hepatitis B infection at
the time of vaccination. It is not known whether Ambirix will prevent hepatitis A and hepatitis B in
such cases.
The vaccine will not prevent infection caused by other agents such as hepatitis C and hepatitis E and
other pathogens known to infect the liver.
Ambirix is not recommended for postexposure prophylaxis (e.g. needle stick injury).
If rapid protection against hepatitis B is required, the standard three dose regimen of the combined
vaccine containing 360 ELISA Units of formalin inactivated hepatitis A virus and 10 micrograms of
recombinant hepatitis B surface antigen is recommended. This is because, a higher proportion of
subjects are protected in the interval between the second and third dose of the three dose combined
vaccine, than after a single dose of Ambirix. This difference is no longer present after the second dose
of Ambirix (see section 5.1 for seroprotection rates).
It is recommended that the two-dose regimen of Ambirix be completed prior to start of sexual
activity.
The vaccine has not been tested in patients with an impaired immune system. In haemodialysis
patients and persons with an impaired immune system, adequate anti-HAV and anti-HBs antibody
titers may not be obtained after the primary immunisation course.
Since intradermal injection or intramuscular administration into the gluteal muscle could lead to a
suboptimal response to the vaccine, these routes should be avoided. However, exceptionally Ambirix
can be administered subcutaneously to subjects with thrombocytopenia or bleeding disorders since
bleeding may occur following an intramuscular administration to these subjects.
AMBIRIX SHOULD UNDER NO CIRCUMSTANCES BE ADMINISTERED
INTRAVASCULARLY.
No data on concomitant administration of Ambirix with specific hepatitis A immunoglobulin or
hepatitis B immunoglobulin have been generated. However, when the monovalent hepatitis A and
hepatitis B vaccines were administered concomitantly with specific immunoglobulins there was no
effect on seroconversion rates. Concomitant immunoglobulin administration may result in lower
antibody titres.
When Ambirix was administered concomitantly with, but as a separate injection to a combined
diphtheria, tetanus, acellular pertussis, inactivated poliomyelitis and
Haemophilus influenzae
type b
vaccine (DTPa-IPV/Hib) or with a combined Measles-Mumps-Rubella vaccine in the second year of
life, immune responses to all antigens were satisfactory (see section 5.1)
Concomitant administration of Ambirix and other vaccines than those listed above has not been
studied. It is advised that Ambirix should not be administered at the same time as other vaccines
unless absolutely necessary.
Concomitant vaccines should always be administered at separate injection sites and preferably into
different limbs.
It may be expected that in patients receiving immunosuppressive treatment or patients with
immunodeficiency, an adequate response may not be achieved.
4
Pregnancy
The effect of Ambirix on foetal development has not been assessed. Ambirix should not be used
during pregnancy unless it is clearly necessary.
Breastfeeding
The effect on breastfed infants of Ambirix administered to the mothers has not been evaluated in
clinical studies. Ambirix should not be used during lactation unless it is clearly necessary.
Fertility
No fertility data are available.
Ambirix has no or negligible influence on the ability to drive and use machines.
Clinical trials involved the administration of 2029 doses of Ambirix to 1027 subjects from 1 year up
to and including 15 years of age.
In 2 comparative trials in subjects aged 1-15 years, the incidences of local and general solicited
symptoms after a two dose regimen of Ambirix was overall similar to that seen with the three dose
combined vaccine containing 360 ELISA Units of HAV and 10 µg of HBsAg.
The most commonly reported adverse reactions following Ambirix administration are pain and fatigue
occurring in an approximated per dose frequency of 50% and 30% respectively.
•
Clinical trials
Local and general adverse reactions reported following primary vaccination with Ambirix were
categorised by frequency.
Adverse reactions reported are listed according to the following frequency:
Very common: ≥ 1/10
Common: ≥ 1/100 to < 1/10
Uncommon: ≥ 1/1,000 to < 1/100
Rare: ≥ 1/10,000 to < 1/1,000
Very rare:
< 1/10,000
The following adverse reactions were reported during clinical trials with Ambirix.
Metabolism and nutrition disorders
Very common: appetite lost
Psychiatric disorders
Very common: irritability
Nervous system disorders
Very common: headache
Common: drowsiness
5
Gastrointestinal disorders
Common: gastrointestinal symptoms
General disorders and administration site conditions
Very common: fatigue, pain and redness at the injection site
Common: fever, swelling at the injection site
In addition, the following adverse reactions were reported during clinical trials with
GlaxoSmithKline’s other combined hepatitis A and hepatitis B vaccines (given as a 3 or 4 dose
schedule)
Infections and infestations
Uncommon: upper respiratory tract infection
Blood and lymphatic system disorders
Nervous system disorders
Uncommon: dizziness
Rare: paraesthesia
Vascular disorders
Rare: hypotension
Gastrointestinal disorders
Common: diarrhoea, nausea
Uncommon: vomiting, abdominal pain*
Skin and subcutaneous tissue disorders
Rare: pruritus, rash
Very rare: urticaria
Musculoskeletal and connective tissue disorders
Uncommon: myalgia
Rare: arthralgia
General disorders and administration site conditions
Common: malaise, injection site reaction
Rare: chills, influenza like illness
* refers to adverse reactions observed in clinical trials performed with the paediatric formulation
•
Because these events were reported spontaneously, it is not possible to reliably estimate their
frequency.
The following adverse reactions were reported during post-marketing surveillance following
vaccination with Ambirix.
Immune system disorders
Allergic reactions including anaphylactic and anaphylactoid reactions
Nervous system disorders
Syncope or vasovagal responses to injection, localised hypoaesthesia
6
Rare: lymphadenopathy
Post-marketing surveillance
Following widespread use of either GlaxoSmithKline’s combined hepatitis A and hepatitis B
vaccines or the monovalent hepatitis A and/or hepatitis B vaccines, the following adverse reactions
have additionally been reported.
Infections and infestations
Meningitis
Blood and lymphatic system disorders
Thrombocytopenic purpura, thrombocytopenia
Immune system disorders
Allergic reactions including mimicking serum sickness, angioneurotic oedema
Nervous system disorders
Multiple sclerosis, encephalitis, encephalopathy,polyneuritis such as Guillain-Barré syndrome (with
ascending paralysis), myelitis, convulsions, paralysis, facial palsy, neuritis, optic neuritis, neuropathy
Vascular disorders
Vasculitis
Hepatobiliary disorders
Abnormal liver function tests
Skin and subcutaneous tissue disorders
Erythema multiforme, lichen planus
Musculoskeletal and connective tissue disorders
Arthritis, muscular weakness
Cases of overdose with GlaxoSmithKline’s combined hepatitis A and hepatitis B vaccine have been
reported during post-marketing surveillance. Adverse reactions reported following overdosage were
similar to those reported with normal vaccine administration.
5.
5.1 Pharmacodynamic properties
Pharmaco-therapeutic group: Hepatitis vaccines, ATC code J07BC20.
Ambirix confers immunity against HAV and HBV infection by inducing specific anti-HAV and anti-
HBs antibodies.
In clinical studies involving subjects from 1 year up to and including 15 years old, seropositivity rates
for anti-HAV antibodies were 99.1% one month after the first dose and 100% after the second dose
given at month 6 (i.e month 7). Seropositivity rates for anti-HBs antibodies were 74.2% one month
after the first dose and 100% after the second dose given at month 6 (i.e. month 7). The anti-HBs
seroprotection rates (titers ≥ 10 mlU/ml) at these time points were 37.4% and 98.2% respectively.
In a comparative clinical trial conducted among subjects aged from 12 years up to and including 15
years of age, 142 received two doses of Ambirix and 147 received the standard three-dose combined
vaccine. The latter contained 360 ELISA Units of formalin inactivated hepatitis A virus and 10
micrograms of recombinant hepatitis B surface antigen. For the 289 subjects evaluable for
7
immunogenicity, seroprotection rates (SP in the table below) against hepatitis B were significantly
higher at months 2 and 6 with the three-dose vaccine than with Ambirix.
Vaccine group
Anti-HBs
Month 2
SP (%)
Anti-HBs
Month 6
SP (%)
Anti-HBs
Month 7
SP (%)
Ambirix
38
68.3
97.9
Combined HAB
vaccine (360/10)
85.6
98.0
100
Immune responses obtained one month after the full vaccination course (i.e at month 7) in a
comparative clinical trial in children aged 1-11 years are presented in the following table. Also
shown are the results reported in the comparative study performed in 12-15 year-olds. In both
studies, subjects received either a two dose schedule of Ambirix or a three dose regimen of the
combined vaccine containing 360 ELISA Units of formalin inactivated hepatitis A virus and 10
micrograms of recombinant hepatitis B surface antigen.
Age group
Vaccine group
Anti-HAV
Anti-HBs
N
S+ (%)
N
SP (%)
1-5 yrs old
Ambirix
98
100
98
98
Combined HAB
vaccine (360/10)
92
100
92
100
6-11 yrs old
Ambirix
103
100
103
99
Combined HAB
vaccine (360/10)
96
100
96
100
12-15 yrs old
Ambirix
142
100
142
97.9
Combined HAB
vaccine (360/10)
147
100
147
100
In a clinical study, 102 subjects aged from 12 years up to and including 15 years received the second
dose of Ambirix at month 12. Seropositivity rates for anti-HAV were 99.0% and seropositivity rates
for anti-HBs were 99.0% at month 13 with seroprotection rates of 97.0%.
At 10 years following the initiation of a 0, 6 month schedule of Ambirix in children aged 1-15 years,
all subjects followed up retained ≥15 mIU/ml anti-HAV antibody. The percentages with anti-HBs
antibody ≥10 mIU/ml at this time point for subjects aged 1-11 years or 12-15 years at the time of the
first dose were 81.7% and 85.9%, respectively. In subjects aged 12-15 years at primary vaccination
the anti-HAV and anti-HBs antibody concentrations were comparable between groups that had
received Ambirix or a 3-dose regimen of the combined vaccine (content as described above).
At 6 years following the initiation of a 0, 6 month or a 0, 12 month schedule of Ambirix in children
aged 12-15 years all subjects followed up retained ≥15 mIU/ml anti-HAV antibody. The percentages
with anti-HBs antibody ≥10 mIU/ml at this time point for subjects vaccinated at the 0, 6 and 0, 12
month schedules were 84.8% and 92.9%, respectively.
When the first dose of Ambirix was administered concomitantly with a booster dose of a combined
diphtheria, tetanus, acellular pertussis, inactivated poliomyelitis and
Haemophilus influenzae
type b
vaccine (DTPa-IPV/Hib) or with the first dose of a combined Measles-Mumps-Rubella vaccine in the
second year of life, immune responses to all antigens were satisfactory.
5.2 Pharmacokinetic properties
8
Evaluation of pharmacokinetic properties is not required for vaccines.
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on general safety studies.
6.
6.1 List of excipients
Sodium chloride
Water for injections
For adjuvants, see section 2.
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years.
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
1 ml of suspension in a prefilled syringe (type I glass) with a plunger stopper (rubber butyl).
Pack sizes of 1 and 10 with or without needles and pack size of 50 without needles.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
Upon storage, a fine white deposit with a clear colourless supernatant can be observed.
Before administration, the vaccine should be well shaken to obtain a slightly opaque, white
suspension.
The vaccine should be visually inspected both before and after resuspension for any foreign
particulate matter and/or change in physical appearance. The vaccine must not be used if any change
in the appearance of the vaccine has taken place.
Any unused product or waste material should be disposed of in accordance with local requirements.
9
7.
GlaxoSmithKline Biologicals s.a.
rue de l'Institut 89
B-1330 Rixensart, Belgium
8.
EU/1/02/224/001
EU/1/02/224/002
EU/1/02/224/003
EU/1/02/224/004
EU/1/02/224/005
9.
Date of first authorisation: 30 August 2002
Date of latest renewal: 30 August 2007
Detailed information on this product is available on the website of the European Medicines Agency
10
ANNEX II
A.
MANUFACTURER OF THE BIOLOGICAL ACTIVE
SUBSTANCES AND MANUFACTURING
AUTHORISATION HOLDER RESPONSIBLE FOR BATCH
RELEASE
B.
CONDITIONS OF THE MARKETING AUTHORISATION
11
A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCES AND
MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR
BATCH RELEASE
Name and address of the manufacturer of the biological active substances
GlaxoSmithKline Biologicals s.a.
Rue de l’Institut 89
1330 Rixensart
Belgium
Name and address of the manufacturer responsible for batch release
GlaxoSmithKline Biologicals s.a.
Rue de l’Institut 89
1330 Rixensart
Belgium
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
Official batch release: in accordance with Article 114 of 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 holder of marketing authorisation will continue to submit annual PSURs.
12
ANNEX III
LABELLING AND PACKAGE LEAFLET
13
A. LABELLING
14
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
1 PRE-FILLED SYRINGE WITHOUT NEEDLE
1 PRE-FILLED SYRINGE WITH NEEDLE
10 PRE-FILLED SYRINGES WITHOUT NEEDLES
10 PRE-FILLED SYRINGES WITH NEEDLES
50 PRE-FILLED SYRINGES WITHOUT NEEDLES
1.
Ambirix– Suspension for injection
Hepatitis A (inactivated) and hepatitis B(rDNA) (HAB) vaccine (adsorbed).
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
1 dose (1 ml):
Hepatitis A virus (inactivated)
1,2
720 ELISA Units
Hepatitis B surface antigen
3,4
20 micrograms
1
Produced on human diploid (MRC-5) cells
2
Adsorbed on aluminium hydroxide, hydrated 0.05 milligrams Al
3+
3
Produced in yeast cells (
Saccharomyces
cerevisiae
) by recombinant DNA technology
4
Adsorbed on aluminium phosphate
0.4 milligrams Al
3+
3.
LIST OF EXCIPIENTS
Sodium chloride
Water for injections
4.
Suspension for injection
1 pre-filled syringe without needle
1 pre-filled syringe with needle
10 pre-filled syringes without needles
10 pre-filled syringes with needles
50 pre-filled syringes without needles
1 dose (1 ml)
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Read the package leaflet before use.
Intramuscular use
Shake before use
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
15
Keep out of the reach and sight of children
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP: MM/YYYY
9.
SPECIAL STORAGE CONDITIONS
Store in a refrigerator
Do not freeze
Store in the original package in order to protect from light
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Dispose of in accordance with local regulations.
GlaxoSmithKline Biologicals s.a.
Rue de l’Institut 89
B-1330 Rixensart, Belgium
EU/1/02/224/001 1 pre-filled syringe without needle
EU/1/02/224/002 1 pre-filled syringe with needle
EU/1/02/224/003 10 pre-filled syringes without needles
EU/1/02/224/004 10 pre-filled syringes with needles
EU/1/02/224/005 50 pre-filled syringes without needles
13. BATCH NUMBER
Lot:
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription
15. INSTRUCTIONS ON USE
16
16. INFORMATION IN BRAILLE
Justification for not including Braille accepted
17
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
PRE-FILLED SYRINGE
1.
Ambirix, suspension for injection
HAB vaccine
IM
2.
METHOD OF ADMINISTRATION
3.
EXPIRY DATE
EXP:
4.
BATCH NUMBER
Lot:
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
1 dose (1 ml)
6.
OTHER
18
B. PACKAGE LEAFLET
19
PACKAGE LEAFLET: INFORMATION FOR THE USER
Ambirix suspension for injection
Hepatitis A (inactivated) and hepatitis B (rDNA) (HAB) vaccine (adsorbed)
Read all of this leaflet carefully before you start/ your child starts receiving this vaccine.
-
Keep this leaflet. You may need to read it again.
-
If you have any further questions, ask your doctor or pharmacist.
-
This vaccine has been prescribed for you/ your child. Do not pass it on to others.
-
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.
In this leaflet:
1.
What Ambirix is and what it is used for
2.
Before you receive/ your child receives Ambirix
3.
How Ambirix is given
4.
Possible side effects
5.
How to store Ambirix
6.
1. WHAT AMBIRIX IS AND WHAT IT IS USED FOR
Ambirix is a vaccine used in infants, children and adolescents from 1 year up to and including 15
years to prevent two infectious diseases: hepatitis A and hepatitis B. The vaccine works by causing
the body to produce its own protection (antibodies) against these infectious diseases.
•
Hepatitis A:
Hepatitis A is an infectious disease that affects the liver, caused by the hepatitis A
virus. The hepatitis A virus is usually caught from food or drink that contains the virus, but is
sometimes spread by other means, such as swimming in water contaminated by sewage. Symptoms
of hepatitis A begin 3 to 6 weeks after coming into contact with the virus. These consist of nausea
(feeling sick), fever and aches and pains. After a few days the whites of eyes and skin may become
yellowish (jaundice). The severity and type of symptoms can vary. Young children may not
develop jaundice. Most people recover completely but the illness is usually severe enough to keep
people ill for about a month.
•
Hepatitis B:
Infection with the hepatitis B virus may cause the liver to become swollen
(inflamed). The virus is found in body fluids such as blood, semen, vaginal secretions, or saliva
(spit) of infected people. Symptoms may not be seen for 6 weeks to 6 months after infection.
Sometimes people who have been infected do not look or feel ill. Others have mild flu-like
symptoms, but some people can become very ill. They may be extremely tired, and have dark
urine, pale faces, yellowish skin and/or eyes (jaundice), and other symptoms possibly requiring
hospitalisation.
Most adults fully recover from the disease. But some people, particularly children, who may not
have had symptoms can remain infected. They are called hepatitis B virus carriers. Hepatitis B
carriers can infect others throughout their lives. Hepatitis B carriers are at risk of serious liver
disease, such as cirrhosis (liver scarring) and liver cancer.
The vaccine does not contain live virus and cannot cause hepatitis A or B infections.
As with all vaccines, Ambirix cannot completely prevent infections with hepatitis A or B viruses,
even after you have/ your child has received both doses.
20
Further information
Also, if you have/ your child has already been infected with hepatitis A or B virus (although not yet
feeling unwell) before having both doses of Ambirix, the vaccine may not be able to prevent you/
your child becoming ill.
Ambirix can only help to protect you/ your child against infections with hepatitis A or B viruses. It
cannot protect you/ your child against other infections that can affect the liver that can cause
symptoms similar to those of hepatitis A or B infections.
2. BEFORE YOU RECEIVE/ YOUR CHILD RECEIVES AMBIRIX
Ambirix should not be given:
•
if you have/ your child has previously had any allergic reaction to Ambirix, or any ingredient
contained in this vaccine including neomycin (antibiotic). The active substances and other
ingredients in Ambirix are listed at the end of the leaflet. Signs of an allergic reaction may
include itchy skin rash, shortness of breath and swelling of the face or tongue.
•
if you have/ your child has previously had an allergic reaction to any vaccine against hepatitis
A or hepatitis B diseases.
•
if you have/ your child has a severe infection with a high temperature. In these cases, the
vaccination will be postponed until you/ your child has recovered. A minor infection such as a
cold should not be a problem, but talk to your doctor first.
Take special care with Ambirix:
•
if you think that you need/your child needs to be protected rapidly against hepatitis B
infection, that is, within six months and before the second dose will be due. If you are/ your
child is likely to be at risk of hepatitis B infection between the timing of the first and second
injections, your doctor will probably recommend that you do/ your child does not receive
Ambirix. Instead, you/ your child will probably need to have three injections of a combined
hepatitis A and hepatitis B vaccine that has a lower content in each dose of the active
substances (360 ELISA Units of formalin inactivated hepatitis A virus and 10 micrograms of
recombinant hepatitis B surface antigen). The second of the three doses of this lower dose
vaccine is usually given at one month after the first dose, and it is more likely to protect you/
your child against hepatitis B before the course is completed. Your doctor will be able to
advise you.
•
if you have/your child has a bleeding problem or bruise/ bruises easily. Sometimes Ambirix is
given as an injection just under the skin instead of into muscle in people who have severe
bleeding problems.
•
if you have/your child has a poor immune system due to illness or treatment or if you are/ your
child is receiving haemodialysis. Ambirix can still be given but these people may not have a
good response to the vaccine and it may be necessary to do a blood test to see how well they
have responded.
Taking other medicines
Tell your doctor if you are/your child is taking any medicines (including any that you may have
obtained without a prescription) or if you have/your child has recently had or expect to shortly have
any other vaccinations or injections of immunoglobulins (antibodies). Ask your doctor if you are not
sure.
People who are taking medicines that decrease the body’s immunity to infections can still have
Ambirix if this is thought to be necessary but may not have a good immune response to the vaccine
and so may not be protected against one or both of hepatitis A and B viruses.
21
Ambirix can be given at the same time as vaccine containing measles, mumps and rubella viruses and
vaccines that are intended to protect you/your child against one or more of diphtheria, tetanus,
pertussis (whooping cough), poliomyelitis or
Haemophilus influenzae
type b. Ambirix can be given at
the same time as other vaccines if this is thought to be very necessary. If another vaccine is to be
given at the same time as Ambirix, separate sites and preferably different limbs should be used.
If Ambirix has to be given at the same time as or shortly before or after an injection of
immunoglobulins, it is likely that you/your child will still make a good immune response to the
vaccine.
Pregnancy and breast-feeding
Tell your doctor if you are or think you may be pregnant or if you are breast-feeding. Ambirix is not
usually given to women who are pregnant or breast-feeding unless it is urgent for them to be
vaccinated against both hepatitis A and B.
Driving and using machines
Drowsiness and dizziness have sometimes occurred after having Ambirix or a similar vaccine.
Important information about some of the ingredients of Ambirix
Please tell your doctor if you have/your child has had an allergic reaction to neomycin (antibiotic).
3.
HOW AMBIRIX IS GIVEN
You/ your child will receive a total of two injections. These will be given within 12 months.
Each injection is given on a separate visit.
The first dose will be given on a date agreed with your doctor.
The second dose will be given between six and twelve months after the first dose.
It is not known exactly how long protection against infection with hepatits A and B viruses will last,
although protection against hepatitis A virus probably lasts about 10 years.
Patients with poor immune systems may need more frequent additional doses. Your doctor will advise
on the possible need for extra doses.
If you miss/ your child misses the visit scheduled for the second injection, talk to your doctor and
arrange another visit as soon as possible.
Make sure you finish/ your child finishes the complete vaccination course of two injections.
If not,
you/ your child may not be fully protected against the diseases.
The doctor or nurse will give Ambirix as an injection into muscle, usually into the upper arm. In very
small children, the injection may be given into the thigh muscle.
Your doctor or nurse will take care that Ambirix is not given into a vein.
The vaccine would not usually be given deep into the skin because protection may be less. This is
usually done when there is a risk of severe bleeding after an injection into muscle.
4. POSSIBLE SIDE EFFECTS
Like all medicines, Ambirix can cause side effects, although not everybody gets them.
The frequency of possible side effects listed below is defined using the following convention:
Very common (these may occur with more than 1 in 10 doses of the vaccine)
22
Common (these may occur with up to 1 in 10 doses of the vaccine)
Uncommon (these may occur with up to 1 in 100 doses of the vaccine)
Rare (these may occur with up to 1 in 1,000 doses of the vaccine)
Side effects that occurred during clinical trials with Ambirix were as follows:
♦
Very common
:
•
Pain and redness where the injection was given
•
Feeling tired
•
Irritability
•
Headache
•
Loss of appetite
♦
Common
:
•
Swelling where the injection was given
•
Fever
•
Drowsiness
•
Stomach and digestive complaints
Additional side effects that have been reported during clinical trials with very similar combined
hepatitis A and hepatitis B vaccines, include:
♦
Common:
•
Diarrheoa, nausea
•
Generally feeling unwell
•
Reaction where the injection was given
♦
Uncommon:
•
Upper respiratory tract infection
•
Feeling dizzy
•
Vomiting
•
Stomach pain
•
Aching muscles (myalgia)
♦
Rare:
•
Swollen glands in the neck, armpit or groin (lymphadenopathy)
•
Pins and needles (paraesthesia)
•
Low blood pressure
•
Itching (pruritus), rash
•
Joint pain (arthralgia)
•
Flu-like symptoms, such as high temperature, sore throat, runny nose, cough and chills
Side effects that occurred during routine use of Ambirix were as follows:
•
Allergic reactions (anaphylaxis, anaphylactoid reactions including mimicking serum
sickness):
If you have an allergic reaction, see your doctor straight away.
The signs may include:
-
rashes that may be itchy or blistering where the injection was given. They may also
cover other parts of your body.
-
swelling of the eyes and face
-
difficulty in breathing or swallowing
-
a sudden drop in blood pressure and loss of consciousness
23
The signs usually start very soon after the injection has been given to you.
•
Fainting
•
Localised loss of skin sensitivity to pain or touch (hypoaesthesia)
Additional side effects that occurred during routine use of very similar combined or individual
hepatitis A and hepatitis B vaccines were as follows:
•
Severe headache with stiff neck and sensitivity to light (meningitis)
•
Reduction in blood platelets, which increases risk of bleeding or bruising
(thrombocytopenia), purple or red brown spots visible through the skin (thrombocytopenic
purpura)
•
Swelling of the face, mouth and throat (angioneurotic oedema)
•
Multiple sclerosis, swelling or infection of the brain (encephalitis), a degenerative disease
of the brain (encephalopathy), a temporary inflammation of the nerves, causing pain,
weakness and paralysis in the extremities and often progressing to the chest and face
(Guillain-Barré syndrome), swelling of the spinal cord (myelitis), fits or seizures,
paralysis, drooping eyelid and sagging muscles on one side of the face (facial palsy),
inflammation of nerves (neuritis), disease of the nerves of the eyes (optic neuritis),
numbness or weakness of the arms and legs (neuropathy)
•
Inflammation of some blood vessels (vasculitis)
•
Abnormal laboratory liver test results
•
Purple or reddish-purple bumps on the skin (lichen planus), serious skin rashes (erythema
multiforme), hives (urticaria)
•
Disease mainly affecting the joints with pain and swelling (arthritis), muscular weakness
Do not be alarmed by this list of possible side effects. It is possible that you have/your child has no
side effects from vaccination.
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 AMBIRIX
Keep out of the reach and sight of children.
Do not use Ambirix after the expiry date which is stated on the carton. The expiry date refers to the
last day of that month.
Store in a refrigerator (2°C - 8°C).
Do not freeze. Freezing destroys the vaccine.
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
What Ambirix contains
-
The active substances are:
Hepatitis A virus (inactivated)
1,2
720 ELISA Units
Hepatitis B surface antigen
3,4
20 micrograms
24
1
Produced on human diploid (MRC-5) cells
2
Adsorbed on aluminium hydroxide, hydrated 0.05 milligrams Al
3+
3
Produced in yeast cells (
Saccharomyces
cerevisiae
) by recombinant DNA technology
4
Adsorbed on aluminium phosphate
0.4 milligrams Al
3+
-
The other ingredients in Ambirix are: sodium chloride and water for injections.
What Ambirix looks like and contents of the pack
Suspension for injection. (1 ml)
Ambirix is available in packs of 1 and 10 with or without needles and in a pack size of 50 without
needles.
Ambirix is a white, slightly milky liquid presented in a prefilled syringe.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
GlaxoSmithKline Biologicals s.a.
Rue de l’Institut 89
B-1330 Rixensart
Belgium
For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder:
België/Belgique/Belgien
GlaxoSmithKline s.a./n.v.
Tél/Tel: + 32 2 656 21 11
Luxembourg/Luxemburg
GlaxoSmithKline s.a./n.v.
Tél/Tel: + 32 2 656 21 11
България
ГлаксоСмитКлайн ЕООД
ул. Димитър Манов бл.10
София 1408
Тел.: + 359 2 953 10 34
Magyarország
GlaxoSmithKline Kft.
Tel.: + 36-1-2255300
Česká republika
GlaxoSmithKline s.r.o.
Tel: + 420 2 22 00 11 11
czmail@gsk.com
Malta
GlaxoSmithKline (Malta) Ltd
Tel: + 356 21 238131
Danmark
GlaxoSmithKline Pharma A/S
Tlf: + 45 36 35 91 00
dk-info@gsk.com
Nederland
GlaxoSmithKline BV
Tel: + 31 (0)30 69 38 100
nlinfo@gsk.com
Deutschland
GlaxoSmithKline GmbH & Co. KG
Tel: + 49 (0)89 360448701
produkt.info@gsk.com
Norge
GlaxoSmithKline AS
Tlf: + 47 22 70 20 00
firmapost@gsk.no
Eesti
Österreich
25
GlaxoSmithKline Eesti OÜ
Tel: +372 667 6900
estonia@gsk.com
GlaxoSmithKline Pharma GmbH.
Tel: + 43 1 970 75-0
at.info@gsk.com
Ελλάδα
GlaxoSmithKline A.E.B.E.
Tηλ: + 30 210 68 82 100
Polska
GSK Commercial Sp. z o.o.
Tel.: + 48 (22) 576 9000
España
GlaxoSmithKline, S.A.
Tel: + 34 902 202 700
es-ci@gsk.com
Portugal
Smith Kline & French Portuguesa, Produtos
Farmacêuticos, Lda.
Tel: + 351 21 412 95 00
FI.PT@gsk.com
France
Laboratoire GlaxoSmithKline
Tél: + 33 (0) 1 39 17 84 44
diam@gsk.com
România
GlaxoSmithKline (GSK) SRL
Tel: + 40 (0)21 3028 208
Ireland
GlaxoSmithKline (Ireland) Ltd
Tel: + 353 (0)1 4955000
Slovenija
GlaxoSmithKline d.o.o.
Tel: + 386 (0) 1 280 25 00
medical.x.si@gsk.com
Ísland
GlaxoSmithKline ehf.
Sími: +354 530 3700
Slovenská republika
GlaxoSmithKline Slovakia s.r.o.
Tel: + 421 (0)2 48 26 11 11
recepcia.sk@gsk.com
Italia
GlaxoSmithKline S.p.A.
Tel:+ 39 04 59 21 81 11
Suomi/Finland
GlaxoSmithKline Oy
Puh/Tel: + 358 10 30 30 30
Finland.tuoteinfo@gsk.com
Κύπρος
GlaxoSmithKline (Cyprus) Ltd
Τηλ: + 357 22 39 70 00
Sverige
GlaxoSmithKline AB
Tel: + 46 (0)8 638 93 00
info.produkt@gsk.com
Latvija
GlaxoSmithKline Latvia SIA
Tel: + 371 67312687
lv-epasts@gsk.com
United Kingdom
GlaxoSmithKline UK
Tel: + 44 (0)808 100 9997
customercontactuk@gsk.com
Lietuva
GlaxoSmithKline Lietuva UAB
Tel. +370 5 264 90 00
info.lt@gsk.com
This leaflet was last approved in
Detailed information on this medicine is available on the European Medicines Agency web site:
---------------------------------------------------------------------------------------------------------------------
26
The following information is intended for medical or healthcare professionals only:
Upon storage, a fine white deposit with a clear colourless supernatant can be observed.
Before administration, the vaccine should be well shaken to obtain a slightly opaque, white
suspension.
The vaccine should be visually inspected before or after resuspension for any foreign particulate
matter and/or change in physical appearance The vaccine must not be used if any change in the
appearance of the vaccine has taken place.
Any unused vaccine or waste material should be disposed of in accordance with local requirements.
27
Source: European Medicines Agency
- Please bookmark this page (add it to your favorites).
- If you wish to link to this page, you can do so by referring to the URL address below this line.
https://theodora.com/drugs/eu/ambirix.html
Copyright © 1995-2021 ITA all rights reserved.