ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
1.
HBVAXPRO 5 micrograms/0.5 ml
Suspension for injection
Hepatitis B vaccine (rDNA)
2.
One dose (0.5 ml) contains:
Hepatitis B virus surface antigen, recombinant (HBsAg) * ................... 5.00 micrograms
Adsorbed on amorphous aluminium hydroxyphosphate sulfate (0.25 milligram Al
+
)
* produced from recombinant strain of the yeast
Saccharomyces cerevisiae
(strain 2150-2-3)
For a full list of excipients, see section 6.1
3.
Suspension for injection
Slightly opaque white suspension.
4.
This vaccine is indicated for active immunisation against hepatitis B virus infection caused by all known
subtypes in children and adolescents (from birth through 15 years of age) considered at risk of exposure to
hepatitis B virus.
The specific at risk categories to be immunised are to be determined on the basis of the official
recommendations.
It can be expected that hepatitis D will also be prevented by immunisation with HBVAXPRO as hepatitis
D (caused by the delta agent) does not occur in the absence of hepatitis B infection.
Posology
Children and adolescents (birth through 15 years of age): 1 dose (5 µg) of 0.5 ml at each injection is
intended for use.
Primary vaccination:
A course of vaccination should include at least three injections.
Two primary immunisation schedules can be recommended:
0, 1, 6 month
s: two injections with an interval of one month; a third injection 6 months after the first
administration.
2
0, 1, 2, 12 month
s: three injections with an interval of one month; a fourth dose should be administered at
12 months.
It is recommended that the vaccine be administered in the schedules indicated. Infants receiving the
compressed regimen (0, 1, 2 months dosing schedule) must receive the 12 month booster to induce higher
antibody titres.
Booster:
Immunocompetent vaccinees
The need for a booster dose in healthy individuals who have received a full primary vaccination course
has not been established. However, some local vaccination schedules currently include a recommendation
for a booster dose and these should be respected.
Immunocompromised vaccinees (e.g. dialysis patients, transplant patients)
In vaccinees with an impaired immune system, administration of additional doses of vaccine should be
considered if the antibody level against hepatitis B virus surface antigen (anti-HBsAg) is less than 10 IU/l.
Revaccination of nonresponders
When persons who do not respond to the primary vaccine series are revaccinated, 15-25 % produce an
adequate antibody response after one additional dose and 30-50 % after three additional doses. However,
because data are insufficient concerning the safety of hepatitis B vaccine when additional doses in excess
of the recommended series are administered, revaccination following completion of the primary series is
not routinely recommended. Revaccination should be considered for high-risk individuals, after weighing
the benefits of vaccination against the potential risk of experiencing increased local or systemic adverse
reactions.
Special dosage recommendations:
Dosage recommendation for neonates of mothers who are hepatitis B virus carriers
-
At birth, one dose of hepatitis B immunoglobulin (within 24 hours).
-
The first dose of the vaccine should be given within 7 days of birth and can be administered
simultaneously with hepatitis B immunoglobulin but at a separate injection site.
-
Subsequent doses of vaccine should be given according to the locally recommended vaccination
schedule.
Dosage recommendation for known or presumed exposure to hepatitis B virus (e.g needlestick with
contaminated needle)
-
Hepatitis B immunoglobulin should be given as soon as possible after exposure (within 24 hours).
-
The first dose of the vaccine should be given within 7 days of exposure and can be administered
simultaneously with hepatitis B immunoglobulin but at a separate injection site.
-
Serologic testing is also recommended, with the administration of subsequent doses of vaccine, if
necessary, (i.e according to the serologic status of the patient) for short and long term protection.
-
In the case of unvaccinated or incompletely vaccinated individuals, additional doses should be
given as in the recommended immunisation schedule. The accelerated schedule including the 12
month booster dose can be proposed.
3
Method of administration
This vaccine should be administered intramuscularly.
The anterolateral thigh is the preferred site for injection in neonates and infants. The deltoid muscle is the
preferred site for injection in children and adolescents.
Do not inject intravascularly.
Exceptionally, the vaccine may be administered subcutaneously in patients with thrombocytopoenia or
bleeding disorders.
See section 6.6 for the instructions for preparation
-
Hypersensitivity to the active substance or to any of the excipients
-
Severe febrile illness
Because of the long incubation period of hepatitis B, it is possible for unrecognised hepatitis B infection to
be present at the time of vaccination. The vaccine may not prevent hepatitis B infection in such cases.
The vaccine will not prevent infection caused by other agents such as hepatitis A, hepatitis C and hepatitis
E and other pathogens known to infect the liver.
As with all injectable vaccines, appropriate medical treatment should always be readily available in case
of rare anaphylactic reactions following the administration of the vaccine.
This vaccine may contain traces of formaldehyde and potassium thiocyanate, which are used during the
manufacturing process. Therefore, sensitisation reactions may occur.
The potential risk of apnoea and the need for respiratory monitoring for 48-72 h should be considered
when administering the primary immunisation series to very premature infants (born ≤ 28 weeks of
gestation) and particularly for those with a previous history of respiratory immaturity. As the benefit of
vaccination is high in this group of infants, vaccination should not be withheld or delayed.
This vaccine can be administered:
- with hepatitis B immunoglobulin, at a separate injection site.
- to complete a primary immunisation course or as a booster dose in subjects who have previously
received another hepatitis B vaccine.
- concomitantly with other vaccines, using separate sites and syringes.
The concomitant administration of pneumococcal conjugate vaccine (PREVENAR) given with hepatitis B
vaccine using the 0, 1 and 6 and 0, 1, 2 and 12 month schedules has not been sufficiently studied.
Not applicable.
4
Not relevant.
The following undesirable effects have been reported following the widespread use of the vaccine.
As with other hepatitis B vaccines, in many instances, the causal relationship to the vaccine has not been
established.
Blood and the lymphatic system disorders
Very rare (<1/10,000)
Thrombocytopenia, lymphadenopathy
Immune system disorders
Very rare (<1/10,000)
Serum sickness, anaphylaxis, polyarteritis nodosa
Nervous system disorders
Very rare (<1/10,000)
Paresthesia, paralysis (Bell's palsy), peripheral neuropathies (polyradiculoneuritis, facial paralysis),
neuritis (including Guillain Barre Syndrome, optical neuritis, myelitis including transverse
myelitis), encephalitis, demyelinating disease of the central nervous system, exacerbation of
multiple sclerosis, multiple sclerosis, seizure, headache, dizziness, syncope
Vascular disorders
Very rare (<1/10,000)
Hypotension, vasculitis
Respiratory, thoracic and mediastinal disorders
Very rare (<1/10,000)
Bronchospasm-like symptoms, apnoea in very premature infants (≤ 28 weeks of gestation) (see
section 4.4)
Gastrointestinal disorders
Very rare (<1/10,000)
Vomiting, nausea, diarrhoea, abdominal pain
Skin and subcutaneous tissue disorders
Very rare (<1/10,000)
Rash, alopecia, pruritus, urticaria, erythema multiforme, angioedema, eczema
Musculoskeletal, connective tissue and bone disorders
Very rare (<1/10,000)
Arthralgia, arthritis, myalgia, pain in extremity
General disorders and administration site conditions
Common (>1/100, <1/10)
Local reactions (injection site): transient soreness, erythema, induration
Very rare (<1/10,000)
Fatigue, fever, malaise, influenza-like symptoms
5
Investigations
Very rare (<1/10,000)
Elevation of liver enzymes
No case of overdose has been reported.
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: anti-infectious, ATC code: J07BC01
The vaccine induces specific humoral antibodies against hepatitis B virus surface antigen (anti-HBsAg).
Development of an antibody titre against hepatitis B virus surface antigen (anti-HBsAg) equal to or
greater than 10 IU/l measured 1 to 2 months after the last injection correlates with protection to hepatitis B
virus infection.
In clinical trials, 96 % of 1,497 healthy infants, children, adolescents and adults given a 3 dose course of a
previous formulation of Merck’s recombinant hepatitis B vaccine developed a protective level of
antibodies against hepatitis B virus surface antigen (≥ 10 IU/l). In two infant trials using different dosing
schedules and concomitant vaccines, the proportion of infants with protective levels of antibodies were
97.5 % and 97.2 % with geometric mean titres of 214 and 297 IU/l, respectively.
The protective efficacy of a dose of hepatitis B immunoglobulin at birth followed by 3 doses of a previous
formulation of Merck’s recombinant hepatitis B vaccine has been demonstrated for neonates born to
mothers positive for both hepatitis B virus surface antigen (HBsAg) and hepatitis B virus e antigen
(HBeAg). Among 130 vaccinated infants, the estimated efficacy in prevention of chronic hepatitis B
infection was 95 % as compared to the infection rate in untreated historical controls.
Although the duration of the protective effect of a previous formulation of Merck’s recombinant hepatitis
B vaccine in healthy vaccinees is unknown, follow-up over 5-9 years of approximately 3,000 high-risk
subjects given a similar plasma-derived vaccine has revealed no cases of clinically apparent hepatitis B
infection.
In addition, persistence of vaccine-induced immunologic memory for hepatitis B virus surface antigen
(HBsAg) has been demonstrated through an anamnestic antibody response to a booster dose of a previous
formulation of Merck’s recombinant hepatitis B vaccine.
As with other hepatitis B vaccines, the duration
of the protective effect in healthy vaccinees is unknown at present. The need for a
booster dose of
HBVAXPRO is not yet defined beyond the 12 month booster dose required for the 0, 1, 2 compressed
schedule.
Reduced risk of Hepatocellular Carcinoma
Hepatocellular carcinoma is a serious complication of hepatitis B virus infection. Studies have
demonstrated the link between chronic hepatitis B infection and hepatocellular carcinoma and 80 % of
hepatocellular carcinomas are caused by hepatitis B virus infection. Hepatitis B vaccine has been
recognized as the first anti-cancer vaccine because it can prevent primary liver cancer.
5.2 Pharmacokinetic properties
6
Not applicable.
5.3 Preclinical safety data
Animal reproduction studies have not been conducted.
6.
6.1 List of excipients
Sodium chloride
Borax
Water for injections
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal
products.
6.3 Shelf life
3 years.
6.4 Special precautions for storage
Store in a refrigerator (2 °C – 8 °C).
Do not freeze.
6.5 Nature and contents of container
0.5 ml of suspension in vial (Type I glass). Pack size of 1, 10
0.5 ml of suspension in vial (Type I glass) and an empty sterile injection syringe with needle. Pack size of
1.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
Before use, the vaccine should be well shaken.
Once the vial has been penetrated, the withdrawn vaccine should be used promptly, and the vial must be
discarded.
Any unused product or waste material should be disposed of in accordance with local requirements.
7.
SANOFI PASTEUR MSD SNC
8, rue Jonas Salk
F-69007 Lyon
France
7
8.
EU/1/01/183/001
EU/1/01/183/018
EU/1/01/183/019
9.
Date of first authorisation: 27/04/2001
Date of latest renewal: 04/08/2006
8
1.
HBVAXPRO 5 micrograms/0.5 ml
Suspension for injection in pre-filled syringe
Hepatitis B vaccine (rDNA)
2.
One dose (0.5 ml) contains:
Hepatitis B virus surface antigen, recombinant (HBsAg) * ................... 5.00 micrograms
Adsorbed on amorphous aluminium hydroxyphosphate sulfate (0.25 milligram Al
+
)
* produced from recombinant strain of the yeast
Saccharomyces cerevisiae
(strain 2150-2-3)
For a full list of excipients, see section 6.1
3.
Suspension for injection in pre-filled syringe
Slightly opaque white suspension.
4.
This vaccine is indicated for active immunisation against hepatitis B virus infection caused by all known
subtypes in children and adolescents (from birth through 15 years of age) considered at risk of exposure to
hepatitis B virus.
The specific at risk categories to be immunised are to be determined on the basis of the official
recommendations.
It can be expected that hepatitis D will also be prevented by immunisation with HBVAXPRO as hepatitis
D (caused by the delta agent) does not occur in the absence of hepatitis B infection.
Posology
Children and adolescents (birth through 15 years of age): 1 dose (5 µg) of 0.5 ml at each injection is
intended for use.
Primary vaccination:
A course of vaccination should include at least three injections.
Two primary immunisation schedules can be recommended:
0, 1, 6 month
s: two injections with an interval of one month; a third injection 6 months after the first
administration.
9
0, 1, 2, 12 months
: three injections with an interval of one month; a fourth dose should be administered at
12 months.
It is recommended that the vaccine be administered in the schedules indicated. Infants receiving the
compressed regimen (0, 1, 2 months dosing schedule) must receive the 12 month booster to induce higher
antibody titres.
Booster:
Immunocompetent vaccinees
The need for a booster dose in healthy individuals who have received a full primary vaccination course
has not been established. However, some local vaccination schedules currently include a recommendation
for a booster dose and these should be respected.
Immunocompromised vaccinees (e.g. dialysis patients, transplant patients)
In vaccinees with an impaired immune system, administration of additional doses of vaccine should be
considered if the antibody level against hepatitis B virus surface antigen (anti-HBsAg) is less than 10 IU/l.
Revaccination of nonresponders
When persons who do not respond to the primary vaccine series are revaccinated, 15-25 % produce an
adequate antibody response after one additional dose and 30-50 % after three additional doses. However,
because data are insufficient concerning the safety of hepatitis B vaccine when additional doses in excess
of the recommended series are administered, revaccination following completion of the primary series is
not routinely recommended. Revaccination should be considered for high-risk individuals, after weighing
the benefits of vaccination against the potential risk of experiencing increased local or systemic adverse
reactions.
Special dosage recommendations:
Dosage recommendations for neonates born to mothers who are hepatitis B virus carriers
-
At birth, one dose of hepatitis B immunoglobulin (within 24 hours).
-
The first dose of the vaccine should be given within 7 days of birth and can be administered
simultaneously with hepatitis B immunoglobulin at birth, but at a separate injection site.
-
Subsequent doses of vaccine should be given according to the locally recommended vaccination
schedule.
Dosage recommendation for known or presumed exposure to hepatitis B virus (e.g needlestick with
contaminated needle)
-
Hepatitis B immunoglobulin should be given as soon as possible after exposure (within 24 hours).
-
The first dose of the vaccine should be given within 7 days of exposure and can be administered
simultaneously with hepatitis B immunoglobulin but at a separate injection site.
-
Serologic testing is also recommended, with the administration of subsequent doses of vaccine, if
necessary, (i.e according to the serologic status of the patient) for short and long term protection.
-
In the case of unvaccinated or incompletely vaccinated individuals, additional doses should be given
as in the recommended immunisation schedule. The accelerated schedule including the 12 month
booster dose can be proposed.
10
Method of administration
This vaccine should be administered intramuscularly.
The anterolateral thigh is the preferred site for injection in neonates and infants. The deltoid muscle is the
preferred site for injection in children and adolescents.
Do not inject intravascularly.
Exceptionally, the vaccine may be administered subcutaneously in patients with thrombocytopoenia or
bleeding disorders.
See section 6.6 for the instructions for preparation
-
Hypersensitivity to the active substance or to any of the excipients
-
Because of the long incubation period of hepatitis B, it is possible for unrecognised hepatitis B infection to
be present at the time of vaccination. The vaccine may not prevent hepatitis B infection in such cases.
The vaccine will not prevent infection caused by other agents such as hepatitis A, hepatitis C and hepatitis
E and other pathogens known to infect the liver.
As with all injectable vaccines, appropriate medical treatment should always be readily available in case
of rare anaphylactic reactions following the administration of the vaccine.
This vaccine may contain traces of formaldehyde and potassium thiocyanate which are used during the
manufacturing process. Therefore, sensitisation reactions may occur.
The potential risk of apnoea and the need for respiratory monitoring for 48-72 h should be considered
when administering the primary immunisation series to very premature infants (born ≤ 28 weeks of
gestation) and particularly for those with a previous history of respiratory immaturity. As the benefit of
vaccination is high in this group of infants, vaccination should not be withheld or delayed.
This vaccine can be administered:
- with hepatitis B immunoglobulin, at a separate injection site.
-
to complete a primary immunisation course or as a booster dose in subjects who have
previously received another hepatitis B vaccine.
- concomitantly with other vaccines, using separate sites and syringes.
The concomitant administration of pneumococcal conjugate vaccine (PREVENAR) given with hepatitis B
vaccine using the 0, 1 and 6 and 0, 1, 2 and 12 month schedules has not been sufficiently studied.
Not applicable.
11
Severe febrile illness
Not relevant.
The following undesirable effects have been reported following the widespread use of the vaccine.
As with other hepatitis B vaccines, in many instances, the causal relationship to the vaccine has not been
established.
Blood and the lymphatic system disorders
Very rare (<1/10,000)
Thrombocytopenia, lymphadenopathy
Immune system disorders
Very rare (<1/10,000)
Serum sickness, anaphylaxis, polyarteritis nodosa
Nervous system disorders
Very rare (<1/10,000)
Paresthesia, paralysis (Bell's palsy), peripheral neuropathies (polyradiculoneuritis, facial paralysis),
neuritis (including Guillain Barre Syndrome, optical neuritis, myelitis including transverse
myelitis), encephalitis, demyelinating disease of the central nervous system, exacerbation of
multiple sclerosis, multiple sclerosis, seizure, headache, dizziness, syncope
Vascular disorders
Very rare (<1/10,000)
Hypotension, vasculitis
Respiratory, thoracic and mediastinal disorders
Very rare (<1/10,000)
Bronchospasm-like symptoms, apnoea in very premature infants (≤ 28 weeks of gestation) (see
section 4.4)
Gastrointestinal disorders
Very rare (<1/10,000)
Vomiting, nausea, diarrhoea
,
abdominal pain
Skin and subcutaneous tissue disorders
Very rare (<1/10,000)
Rash, alopecia, pruritus, urticaria, erythema multiforme, angioedema, eczema
Musculoskeletal, connective tissue and bone disorders
Very rare (<1/10,000)
Arthralgia, arthritis, myalgia , pain in extremity
General disorders and administration site conditions
Common (>1/100, <1/10)
Local reactions (injection site): transient soreness, erythema, induration
Very rare (<1/10,000)
Fatigue, fever, malaise, influenza-like symptoms
12
Investigations
Very rare (<1/10,000)
Elevation of liver enzymes
No case of overdose has been reported.
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: anti-infectious, ATC code: J07BC01
The vaccine induces specific humoral antibodies against hepatitis B virus surface antigen (anti-HBsAg).
Development of an antibody titre against hepatitis B virus surface antigen (anti-HBsAg) equal to or
greater than 10 IU/l measured 1 to 2 months after the last injection correlates with protection to hepatitis B
virus infection.
In clinical trials, 96 % of 1,497 healthy infants, children, adolescents and adults given a 3 dose course of a
previous formulation of Merck’s recombinant hepatitis B vaccine developed a protective level of
antibodies against hepatitis B virus surface antigen (≥ 10 IU/l).
In two infant trials using different dosing
schedules and concomitant vaccines, the proportion of infants with protective levels of antibodies were
97.5 % and 97.2 % with geometric mean titres of 214 and 297 IU/l, respectively
.
The protective efficacy of a dose of hepatitis B immunoglobulin at birth followed by 3 doses of a previous
formulation of Merck’s recombinant hepatitis B vaccine has been demonstrated for neonates born to
mothers positive for both hepatitis B virus surface antigen (HBsAg) and hepatitis B virus e antigen
(HBeAg). Among 130 vaccinated infants, the estimated efficacy in prevention of chronic hepatitis B
infection was 95 % as compared to the infection rate in untreated historical controls.
Although the duration of the protective effect of a previous formulation of Merck’s recombinant hepatitis
B vaccine in healthy vaccinees is unknown, follow-up over 5-9 years of approximately 3,000 high-risk
subjects given a similar plasma-derived vaccine has revealed no cases of clinically apparent hepatitis B
infection.
In addition, persistence of vaccine-induced immunologic memory for hepatitis B virus surface antigen
(HBsAg) has been demonstrated through an anamnestic antibody response to a booster dose of a previous
formulation of Merck’s recombinant hepatitis B vaccine.
As with other hepatitis B vaccines, the duration
of the protective effect in healthy vaccinees is unknown at present. The need for a
booster dose of
HBVAXPRO is not yet defined beyond the 12 month booster dose required for the 0, 1, 2 compressed
schedule.
Reduced risk of Hepatocellular Carcinoma
Hepatocellular carcinoma is a serious complication of hepatitis B virus infection. Studies have
demonstrated the link between chronic hepatitis B infection and hepatocellular carcinoma and 80 % of
hepatocellular carcinomas are caused by hepatitis B virus infection. Hepatitis B vaccine has been
recognized as the first anti-cancer vaccine because it can prevent primary liver cancer.
5.2 Pharmacokinetic properties
13
Not applicable.
5.3 Preclinical safety data
Animal reproduction studies have not been conducted.
6.
6.1 List of excipients
Sodium chloride
Borax
Water for injections
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal
products.
6.3 Shelf life
3 years.
6.4 Special precautions for storage
Store in a refrigerator (2 °C – 8 °C).
Do not freeze.
6.5 Nature and contents of container
0.5 ml of suspension in pre-filled syringe (Type I glass) without needle with a plunger stopper
(chlorobutyl). Pack size of 1, 10, 20, 50.
0.5 ml of suspension in pre-filled syringe (Type I glass) with 1 separate needle with a plunger stopper
(chlorobutyl). Pack size of 1, 10
0.5 ml of suspension in pre-filled syringe (Type I glass) with 2 separate needles with a plunger stopper
(chlorobutyl). Pack size of 1, 10, 20, 50
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
Before use, the vaccine should be well shaken.
Hold the syringe barrel and attach the needle by twisting in clockwise direction, until the needle fits
securely on the syringe.
Any unused product or waste material should be disposed of in accordance with local requirements.
7.
SANOFI PASTEUR MSD SNC
8, rue Jonas Salk
14
F-69007 Lyon
France
8.
EU/1/01/183/004
EU/1/01/183/005
EU/1/01/183/020
EU/1/01/183/021
EU/1/01/183/022
EU/1/01/183/023
EU/1/01/183/024
EU/1/01/183/025
EU/1/01/183/030
EU/1/01/183/031
9.
Date of first authorisation: 27/04/2001
Date of latest renewal: 04/08/2006
15
1.
HBVAXPRO 10 micrograms/ml
Suspension for injection
Hepatitis B vaccine (rDNA)
2.
One dose (1 ml) contains:
Hepatitis B virus surface antigen, recombinant (HBsAg) * ................... 10.00 micrograms
Adsorbed on amorphous aluminium hydroxyphosphate sulfate (0.50 milligram Al
+
)
* produced from recombinant strain of the yeast
Saccharomyces cerevisiae
(strain 2150-2-3)
For a full list of excipients, see section 6.1
3.
Suspension for injection
Slightly opaque white suspension.
4.
This vaccine is indicated for active immunisation against hepatitis B virus infection caused by all known
subtypes in adults and adolescents (16 years of age and older) considered at risk of exposure to hepatitis B
virus.
The specific at risk categories to be immunised are to be determined on the basis of the official
recommendations.
It can be expected that hepatitis D will also be prevented by immunisation with HBVAXPRO as hepatitis
D (caused by the delta agent) does not occur in the absence of hepatitis B infection.
Posology
Adults and adolescents (16 years of age and older): 1 dose (10 µg) of 1 ml at each injection is intended for
use.
Primary vaccination:
A course of vaccination should include at least three injections.
Two primary immunisation schedules can be recommended:
0, 1, 6 month
s: two injections with an interval of one month; a third injection 6 months after the first
administration.
16
0, 1, 2, 12 month
s: three injections with an interval of one month; a fourth dose should be administered at
12 months.
It is recommended that the vaccine be administered in the schedules indicated. Those receiving the
compressed regimen (0, 1, 2 months dosing schedule) must receive the 12 month booster to induce higher
antibody titres.
Booster:
Immunocompetent vaccinees
The need for a booster dose in healthy individuals who have received a full primary vaccination course
has not been established. However, some local vaccination schedules currently include a recommendation
for a booster dose and these should be respected.
Immunocompromised vaccinees (e.g. dialysis patients, transplant patients)
In vaccinees with an impaired immune system, administration of additional doses of vaccine should be
considered if the antibody level against hepatitis B virus surface antigen (anti-HBsAg) is less than 10 IU/l.
Revaccination of nonresponders
When persons who do not respond to the primary vaccine series are revaccinated, 15-25 % produce an
adequate antibody response after one additional dose and 30-50 % after three additional doses. However,
because data are insufficient concerning the safety of hepatitis B vaccine when additional doses in excess
of the recommended series are administered, revaccination following completion of the primary series is
not routinely recommended. Revaccination should be considered for high-risk individuals, after weighing
the benefits of vaccination against the potential risk of experiencing increased local or systemic adverse
reactions.
Special dosage recommendations for known or presumed exposure to hepatitis B virus (e.g needlestick
with contaminated needle):
-
Hepatitis B immunoglobulin should be given as soon as possible after exposure (within 24
hours).
-
The first dose of the vaccine should be given within 7 days of exposure and can be administered
simultaneously with hepatitis B immunoglobulin, but at a separate injection site.
-
Serologic testing is also recommended, with the administration of subsequent doses of vaccine, if
necessary, (i.e according to the serologic status of the patient) for short and long term protection.
-
In the case of unvaccinated or incompletely vaccinated individuals, additional doses should be
given as in the recommended immunisation schedule. The accelerated schedule including the 12
month booster dose can be proposed.
Method of administration
This vaccine should be administered intramuscularly.
The deltoid muscle is the preferred site for injection in adults and adolescents.
Do not inject intravascularly.
17
Exceptionally, the vaccine may be administered subcutaneously in patients with thrombocytopoenia or
bleeding disorders.
See section 6.6 for the instructions for preparation
-
Hypersensitivity to the active substance or to any of the excipients
-
Severe febrile illness
Because of the long incubation period of hepatitis B, it is possible for unrecognised hepatitis B infection to
be present at the time of vaccination. The vaccine may not prevent hepatitis B infection in such cases.
A number of factors have been observed to reduce the immune response to hepatitis B vaccines. These
factors include older age, male gender, obesity, smoking, route of administration and some chronic
underlying diseases. Consideration should be given to serological testing of those subjects who may be at
risk of not achieving seroprotection following a complete course of HBVAXPRO. Additional doses may
need to be considered for persons who do not respond or have a sub-optimal response to a course of
vaccinations.
The vaccine will not prevent infection caused by other agents such as hepatitis A, hepatitis C and hepatitis
E and other pathogens known to infect the liver.
As with all injectable vaccines, appropriate medical treatment should always be readily available in case
of rare anaphylactic reactions following the administration of the vaccine.
This vaccine may contain traces of formaldehyde and potassium thiocyanate which are used during the
manufacturing process. Therefore, sensitisation reactions may occur.
This vaccine can be administered:
-
with hepatitis B immunoglobulin, at a separate injection site.
-
to complete a primary immunisation course or as a booster dose in subjects who have previously
received another hepatitis B vaccine.
-
concomitantly with other vaccines, using separate sites and syringes.
For the hepatitis B virus surface antigen (HBsAg) no clinical data on exposed pregnancies are available.
However, as with all inactivated viral vaccines, one does not expect harm for the foetus. Utilisation during
pregnancy requires that the potential benefit justifies the potential risk to the foetus. Caution should be
exercised when prescribing to pregnant women.
The effect on breastfed infants of the administration of this vaccine has not been assessed ; no
contraindication has been established.
18
No studies on the effects on the ability to drive and use machines have been performed. However, some of
machinery.
The following undesirable effects have been reported following the widespread use of the vaccine.
As with other hepatitis B vaccines, in many instances, the causal relationship to the vaccine has not been
established.
Blood and lymphatic system disorders
Very rare (<1/10,000)
Thrombocytopenia, lymphadenopathy
Immune system disorders
Very rare (<1/10,000)
Serum sickness, anaphylaxis, polyarteritis nodosa
Nervous system disorders
Very rare (<1/10,000)
Paresthesia, paralysis (Bell's palsy), peripheral neuropathies (polyradiculoneuritis, facial paralysis),
neuritis (including Guillain Barre Syndrome, optical neuritis, myelitis including transverse
myelitis), encephalitis, demyelinating disease of the central nervous system, exacerbation of
multiple sclerosis, multiple sclerosis, seizure, headache, dizziness, syncope
Vascular disorders
Very rare (<1/10,000)
Hypotension, vasculitis
Respiratory, thoracic and mediastinal diosrders
Very rare (<1/10,000)
Bronchospasm-like symptoms
Gastrointestinal disorders
Very rare (<1/10,000)
Vomiting, nausea, diarrhoea, abdominal pain
Skin and subcutaneous tissue disorders
Very rare (<1/10,000)
Rash, alopecia, pruritus, urticaria, erythema multiforme, angioedema, eczema
Musculoskeleta, connective tissue and bone disorders
Very rare (<1/10,000)
Arthralgia, arthritis, myalgia, pain in extremity
General disorders and administration site conditions
Common (>1/100, <1/10)
Local reactions (injection site): transient soreness, erythema, induration
Very rare (<1/10,000)
Fatigue, fever, malaise, influenza-like symptoms
19
Investigations
Very rare (<1/10,000)
Elevation of liver enzymes
No case of overdose has been reported.
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: anti-infectious, ATC code: J07BC01
The vaccine induces specific humoral antibodies against hepatitis B virus surface antigen (anti-HBsAg).
Development of an antibody titre against hepatitis B (anti-HBsAg) equal to or greater than 10 IU/l
measured 1 to 2 months after the last injection correlates with protection to hepatitis B virus infection.
In clinical trials, 96 % of 1,497 healthy infants, children, adolescents and adults given a 3 dose course of a
previous formulation of Merck’s recombinant hepatitis B vaccine developed a protective level of
antibodies against hepatitis B virus surface antigen (≥ 10 IU/l). In two trials conducted in older
adolescents and adults, 95.6-97.5 % of vaccinees developed a protective level of antibodies, with
geometric mean titres in these trials ranging from 535 – 793 IU/l.
Although the duration of the protective effect of a previous formulation of Merck’s recombinant hepatitis
B vaccine in healthy vaccinees is unknown, follow-up over 5-9 years of approximately 3,000 high-risk
subjects given a similar plasma-derived vaccine has revealed no cases of clinically apparent hepatitis B
infection.
In addition, persistence of vaccine-induced immunologic memory for hepatitis B virus surface antigen
(HBsAg) has been demonstrated through an anamnestic antibody response to a booster dose of a previous
formulation of Merck’s recombinant hepatitis B vaccine in healthy adults. As with other hepatitis B
vaccines, the duration of the protective effect in healthy vaccinees is unknown at present. The need for a
booster dose of HBVAXPRO is not yet defined beyond the 12 month booster dose required for the 0, 1, 2
compressed schedule.
Reduced risk of Hepatocellular Carcinoma
Hepatocellular carcinoma is a serious complication of hepatitis B virus infection. Studies have
demonstrated the link between chronic hepatitis B infection and hepatocellular carcinoma and 80 % of
hepatocellular carcinomas are caused by hepatitis B virus infection. Hepatitis B vaccine has been
recognized as the first anti-cancer vaccine because it can prevent primary liver cancer.
5.2 Pharmacokinetic properties
Not applicable.
5.3 Preclinical safety data
Animal reproduction studies have not been conducted.
20
6.
6.1 List of excipients
Sodium chloride
Borax
Water for injections
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal
products.
6.3 Shelf life
3 years.
6.4 Special precautions for storage
Store in a refrigerator (2 °C – 8 °C).
Do not freeze.
6.5 Nature and contents of container
1 ml of suspension in vial (Type I glass). Pack size of 1, 10
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
Before use, the vaccine should be well shaken.
Any unused product or waste material should be disposed of in accordance with local requirements.
7.
SANOFI PASTEUR MSD SNC
8, rue Jonas Salk
F-69007 Lyon
France
8.
EU/1/01/183/007
EU/1/01/183/008
9.
Date of first authorisation: 27/04/2001
Date of latest renewal: 04/08/2006
21
1.
HBVAXPRO 10 micrograms/ml
Suspension for injection in pre-filled syringe
Hepatitis B vaccine (rDNA)
2.
One dose (1 ml) contains:
Hepatitis B virus surface antigen, recombinant (HBsAg) * ................... 10.00 micrograms
Adsorbed on amorphous aluminium hydroxyphosphate sulfate (0.50 milligram Al
+
)
* produced from recombinant strain of the yeast
Saccharomyces cerevisiae
(strain 2150-2-3)
For a full list of excipients, see section 6.1
3.
Suspension for injection in pre-filled syringe
Slightly opaque white suspension.
4.
This vaccine is indicated for active immunisation against hepatitis B virus infection caused by all known
subtypes in adults and adolescents (16 years of age and older) considered at risk of exposure to hepatitis B
virus.
The specific at risk categories to be immunised are to be determined on the basis of the official
recommendations.
It can be expected that hepatitis D will also be prevented by immunisation with HBVAXPRO as hepatitis
D (caused by the delta agent) does not occur in the absence of hepatitis B infection.
Posology
Adults and adolescents (16 years of age and older): 1 dose (10 µg) of 1 ml at each injection is intended for
use.
Primary vaccination:
A course of vaccination should include at least three injections.
Two primary immunisation schedules can be recommended:
0, 1, 6 month
s: two injections with an interval of one month; a third injection 6 months after the first
administration.
23
0, 1, 2, 12 month
s: three injections with an interval of one month; a fourth dose should be administered at
12 months.
It is recommended that the vaccine be administered in the schedules indicated. Those receiving the
compressed regimen (0, 1, 2 months dosing schedule) must receive the 12 month booster to induce higher
antibody titres.
Booster:
Immunocompetent vaccinees
The need for a booster dose in healthy individuals who have received a full primary vaccination course
has not been established. However, some local vaccination schedules currently include a recommendation
for a booster dose and these should be respected.
Immunocompromised vaccinees (e.g. dialysis patients, transplant patients)
In vaccinees with an impaired immune system, administration of additional doses of vaccine should be
considered if the antibody level against hepatitis B virus surface antigen (anti-HBsAg) is less than 10 IU/l.
Revaccination of nonresponders
When persons who do not respond to the primary vaccine series are revaccinated, 15-25 % produce an
adequate antibody response after one additional dose and 30-50 % after three additional doses. However,
because data are insufficient concerning the safety of hepatitis B vaccine when additional doses in excess
of the recommended series are administered, revaccination following completion of the primary series is
not routinely recommended. Revaccination should be considered for high-risk individuals, after weighing
the benefits of vaccination against the potential risk of experiencing increased local or systemic adverse
reactions.
Special dosage recommendations for known or presumed exposure to hepatitis B virus (e.g needlestick
with contaminated needle):
-
Hepatitis B immunoglobulin should be given as soon as possible after exposure (within 24
hours).
-
The first dose of the vaccine should be given within 7 days of exposure and can be administered
simultaneously with hepatitis B immunoglobulin but at a separate injection site.
-
Serologic testing is also recommended, with the administration of subsequent doses of vaccine, if
necessary, (i.e according to the serologic status of the patient) for short and long term protection.
-
In the case of unvaccinated or incompletely vaccinates individuals, additional doses should be given
as in the recommended immunisation schedules. The accelerated schedule including the 12 month
booster dose can be proposed.
Method of administration
This vaccine should be administered intramuscularly.
The deltoid muscle is the preferred site for injection in adults and adolescents.
Do not inject intravascularly.
24
Exceptionally, the vaccine may be administered subcutaneously in patients with thrombocytopoenia or
bleeding disorders.
See section 6.6 for the instructions for preparation
-
Hypersensitivity to the active substance or to any of the excipients
-
Severe febrile illness
Because of the long incubation period of hepatitis B, it is possible for unrecognised hepatitis B infection to
be present at the time of vaccination. The vaccine may not prevent hepatitis B infection in such cases.
A number of factors have been observed to reduce the immune response to hepatitis B vaccines. These
factors include older age, male gender, obesity, smoking, route of administration and some chronic
underlying diseases. Consideration should be given to serological testing of those subjects who may be at
risk of not achieving seroprotection following a complete course of HBVAXPRO. Additional doses may
need to be considered for persons who do not respond or have a sub-optimal response to a course of
vaccinations.
The vaccine will not prevent infection caused by other agents such as hepatitis A, hepatitis C and hepatitis
E and other pathogens known to infect the liver.
As with all injectable vaccines, appropriate medical treatment should always be readily available in case
of rare anaphylactic reactions following the administration of the vaccine.
This vaccine may contain traces of formaldehyde and potassium thiocyanate which are used during the
manufacturing process. Therefore, sensitisation reactions may occur.
This vaccine can be administered:
- with hepatitis B immunoglobulin, at a separate injection site.
- to complete a primary immunisation course or as a booster dose in subjects who have previously
received another hepatitis B vaccine.
- concomitantly with other vaccines, using separate sites and syringes.
4.6
For the hepatitis B virus surface antigen (HBsAg) no clinical data on exposed pregnancies are available.
However, as with all inactivated viral vaccines, one does not expect harm for the foetus. Utilisation during
pregnancy requires that the potential benefit justifies the potential risk to the foetus. Caution should be
exercised when prescribing to pregnant women.
The effect on breast-fed infants of the administration of this vaccine has not been assessed ; no
contraindication has been established.
4.7
25
No studies on the effects on the ability to drive and use machines have been performed. However, some of
machinery.
4.8
The following undesirable effects have been reported following the widespread use of the vaccine.
As with other hepatitis B vaccines, in many instances, the causal relationship to the vaccine has not been
established.
Blood and the lymphatic system disorders
Very rare (<1/10,000)
Thrombocytopenia, lymphadenopathy
Immune system disorders
Very rare (<1/10,000)
Serum sickness, anaphylaxis, polyarteritis nodosa
Nervous system disorders
Very rare (<1/10,000)
Paresthesia, paralysis (Bell's palsy), peripheral neuropathies (polyradiculoneuritis, facial paralysis),
neuritis (including Guillain Barre Syndrome, optical neuritis, myelitis including transverse
myelitis), encephalitis, demyelinating disease of the central nervous system, exacerbation of
multiple sclerosis, multiple sclerosis, seizure, headache , dizziness, syncope
Vascular disorders
Very rare (<1/10,000)
Hypotension, vasculitis
Respiratory, thoracic and mediastinal disorders
Very rare (<1/10,000)
Bronchospasm-like symptoms
Gastrointestinal disorders
Very rare (<1/10,000)
Vomiting, nausea, diarrhoea, abdominal pain
Skin and subcutaneous tissue disorders
Very rare (<1/10,000)
Rash, alopecia, pruritus, urticaria, erythema multiforme, angioedema, eczema
Musculoskeletal, connective tissue and bone disorders
Very rare (<1/10,000)
Arthralgia, arthritis, myalgia , pain in extremity
General disorders and administration site conditions
Common (>1/100, <1/10)
Local reactions (injection site): transient soreness, erythema, induration
Very rare (<1/10,000)
Fatigue, fever, malaise, influenza-like symptoms
26
Investigations
Very rare (<1/10,000)
Elevation of liver enzymes
No case of overdose has been reported.
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: anti-infectious, ATC code: J07BC01
The vaccine induces specific humoral antibodies against hepatitis B virus surface antigen (anti-HBsAg).
Development of an antibody titre against hepatitis B virus surface antigen (anti-HBsAg) equal to or
greater than 10 IU/l measured 1 to 2 months after the last injection correlates with protection to hepatitis B
virus infection.
In clinical trials, 96 % of 1,497 healthy infants, children, adolescents and adults given a 3 dose course of a
previous formulation of Merck’s recombinant hepatitis B vaccine developed a protective level of
antibodies against hepatitis B virus surface antigen (≥ 10 IU/l). In two trials conducted in older
adolescents and adults, 95.6-97.5 % of vaccinees developed a protective level of antibodies, with
geometric mean titres in these trials ranging from 535 – 793 IU/l.
Although the duration of the protective effect of a previous formulation of Merck’s recombinant hepatitis
B vaccine in healthy vaccinees is unknown, follow-up over 5-9 years of approximately 3,000 high-risk
subjects given a similar plasma-derived vaccine has revealed no cases of clinically apparent hepatitis B
infection.
In addition, persistence of vaccine-induced immunologic memory for hepatitis B virus surface antigen
(HBsAg) has been demonstrated through an anamnestic antibody response to a booster dose of a previous
formulation of Merck’s recombinant hepatitis B vaccine in healthy adults. As with other hepatitis B
vaccines, the duration of the protective effect in healthy vaccinees is unknown at present. The need for a
booster dose of HBVAXPRO is not yet defined beyond the 12 month booster dose required for the 0, 1, 2
compressed schedule.
Reduced risk of Hepatocellular Carcinoma
Hepatocellular carcinoma is a serious complication of hepatitis B virus infection. Studies have
demonstrated the link between chronic hepatitis B infection and hepatocellular carcinoma and 80 % of
hepatocellular carcinomas are caused by hepatitis B virus infection. Hepatitis B vaccine has been
recognized as the first anti-cancer vaccine because it can prevent primary liver cancer.
5.2 Pharmacokinetic properties
Not applicable.
5.3 Preclinical safety data
Animal reproduction studies have not been conducted.
27
6.
6.1 List of excipients
Sodium chloride
Borax
Water for injections
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal
products.
6.3 Shelf life
3 years.
6.4 Special precautions for storage
Store in a refrigerator (2 °C – 8 °C).
Do not freeze.
6.5 Nature and contents of container
1 ml of suspension in pre-filled syringe (Type I glass) without needle with a plunger stopper (chlorobutyl).
Pack size of 1, 10
1 ml of suspension in pre-filled syringe (Type I glass) with 1 separate needle with a plunger stopper
(chlorobutyl). Pack size of 1, 10
1 ml of suspension in pre-filled syringe (Type I glass) with 2 separate needles with a plunger stopper
(chlorobutyl). Pack size of 1, 10, 20
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
Before use, the vaccine should be well shaken.
Hold the syringe barrel and attach the needle by twisting in clockwise direction, until the needle fits
securely on the syringe.
Any unused product or waste material should be disposed of in accordance with local requirements.
7.
SANOFI PASTEUR MSD SNC
8, rue Jonas Salk
F-69007 Lyon
France
28
8.
EU/1/01/183/011
EU/1/01/183/013
EU/1/01/183/026
EU/1/01/183/027
EU/1/01/183/028
EU/1/01/183/029
EU/1/01/183/032
9.
Date of first authorisation: 27/04/2001
Date of latest renewal: 04/08/2006
29
1.
HBVAXPRO 40 micrograms/ml
Suspension for injection
Hepatitis B vaccine (rDNA)
2.
One dose (1 ml) contains:
Hepatitis B virus surface antigen, recombinant (HBsAg) * ................... 40.00 micrograms
Adsorbed on amorphous aluminium hydroxyphosphate sulfate (0.50 milligram Al
+
)
* produced from recombinant strain of the yeast
Saccharomyces cerevisiae
(strain 2150-2-3)
For a full list of excipients, see section 6.1
3.
Suspension for injection
Slightly opaque white suspension.
4.
This vaccine is indicated for the active immunisation against hepatitis B virus infection caused by all
known subtypes in predialysis and dialysis adult patients.
It can be expected that hepatitis D will also be prevented by immunisation with HBVAXPRO as hepatitis
D (caused by the delta agent) does not occur in the absence of hepatitis B infection.
Posology
Predialysis and dialysis adult patients: 1 dose (40 µg) of 1 ml at each injection is intended for use.
Primary vaccination:
A course of vaccination should include three injections:
Schedule 0, 1, 6 months: two injections with an interval of one month; a third injection 6 months after the
first administration.
Booster:
A booster dose must be considered in these vaccinees if the antibody level against hepatitis B virus surface
antigen (anti-HBsAg) after primary series is less than 10 IU/l.
30
In accordance with standard medical practice for hepatitis B vaccine administration, regular antibody
testing should be done in hemodialysis patients. A booster dose should be given when antibody levels
decline below 10 IU/l.
Special dosage recommendations for known or presumed exposure to hepatitis B virus (e.g needlestick
with contaminated needle):
-
Hepatitis B immunoglobulin should be given as soon as possible after exposure (within 24
hours).
-
The first dose of the vaccine should be given within 7 days of exposure and can be administered
simultaneously with hepatitis B immunoglobulin but at a separate injection site.
-
Serologic testing is also recommended, with the administration of subsequent doses of vaccine, if
necessary, (i.e according to the serologic status of the patient) for short and long term protection.
-
In the case of unvaccinated or incompletely vaccinated individuals, additional doses should be given
as in the recommended immunisation schedule.
Method of administration
This vaccine should be administered intramuscularly.
The deltoid muscle is the preferred site for injection in adults.
Do not inject intravascularly.
Exceptionally, the vaccine may be administered subcutaneously in patients with thrombocytopoenia or
bleeding disorders.
See section 6.6 for the instructions for preparation
-
Hypersensitivity to the active substance or to any of the excipients
-
Severe febrile illness
Because of the long incubation period of hepatitis B, it is possible for unrecognised hepatitis B infection to
be present at the time of vaccination. The vaccine may not prevent hepatitis B infection in such cases.
The vaccine will not prevent infection caused by other agents such as hepatitis A, hepatitis C and hepatitis
E and other pathogens known to infect the liver.
As with all injectable vaccines, appropriate medical treatment should always be readily available in case
of rare anaphylactic reactions following the administration of the vaccine.
This vaccine may contain traces of formaldehyde and potassium thiocyanate which are used during the
manufacturing process. Therefore, sensitisation reactions may occur.
This vaccine can be administered:
-
with hepatitis B immunoglobulin, at a separate injection site.
-
to complete a primary immunisation course or as a booster dose in subjects who have
previously received another hepatitis B vaccine.
31
-
concomitantly with other vaccines, using separate sites and syringes.
For the hepatitis B virus surface antigen (HBsAg) no clinical data on exposed pregnancies are available.
However, as with all inactivated viral vaccines, one does not expect harm for the foetus. Utilisation during
pregnancy requires that the potential benefit justifies the potential risk to the foetus. Caution should be
exercised when prescribing to pregnant women.
The effect on breast-fed infants of the administration of this vaccine has not been assessed; no
contraindication has been established.
No studies on the effects on the ability to drive and use machines have been performed. However, some of
machinery.
The following undesirable effects have been reported following the widespread use of the vaccine.
As with other hepatitis B vaccines, in many instances, the causal relationship to the vaccine has not been
established.
Blood and the lymphatic system disorders
Very rare (<1/10,000)
Thrombocytopenia, lymphadenopathy
Immune system disorders
Very rare (<1/10,000)
Serum sickness, anaphylaxis, polyarteritis nodosa
Nervous system disorders
Very rare (<1/10,000)
Paresthesia, paralysis (Bell's palsy), peripheral neuropathies (polyradiculoneuritis, facial paralysis),
neuritis (including Guillain Barre Syndrome, optical neuritis, myelitis including transverse
myelitis), encephalitis, demyelinating disease of the central nervous system, exacerbation of
multiple sclerosis, multiple sclerosis, seizure, headache, dizziness, syncope
Vascular disorders
Very rare (<1/10,000)
Hypotension, vasculitis
Respiratory, thoracic and mediastinal disorders
Very rare (<1/10,000)
Bronchospasm-like symptoms
Gastrointestinal disorders
Very rare (<1/10,000)
Vomiting, nausea, diarrhoea, abdominal pain
32
Skin and subcutaneous tissue disorders
Very rare (<1/10,000)
Rash, alopecia, pruritus, urticaria, erythema multiforme, angioedema, eczema
Musculoskeletal, connective tissue and bone disorders
Very rare (<1/10,000)
Arthralgia, arthritis, myalgia , pain in extremity
General disorders and administration site conditions
Common (>1/100, <1/10)
Local reactions (injection site): transient soreness, erythema, induration
Very rare (<1/10,000)
Fatigue, fever, malaise, influenza-like symptoms
Investigations
Very rare (<1/10,000)
Elevation of liver enzymes
No case of overdose has been reported.
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: anti-infectious, ATC code: J07BC01
The vaccine induces specific humoral antibodies against hepatitis B virus surface antigen (anti-HBsAg).
Development of an antibody titre against hepatitis B virus surface antigen (anti-HBsAg) equal to or
greater than 10 IU/l measured 1 to 2 months after the last injection correlates with protection to hepatitis B
virus infection.
In clinical trials, 96 % of 1,497 healthy infants, children, adolescents and adults given a 3 dose course of a
previous formulation of Merck’s recombinant hepatitis B vaccine developed a protective level of
antibodies against hepatitis B virus surface antigen (≥ 10 IU/l).
Although the duration of the protective effect of a previous formulation of Merck’s recombinant hepatitis
B vaccine in healthy vaccinees is unknown, follow-up over 5-9 years of approximately 3,000 high-risk
subjects given a similar plasma-derived vaccine has revealed no cases of clinically apparent hepatitis B
infection.
In addition, persistence of vaccine-induced immunologic memory for hepatitis B virus surface antigen
(HBsAg) has been demonstrated through an anamnestic antibody response to a booster dose of a previous
formulation of Merck’s recombinant hepatitis B vaccine in healthy adults.
In accordance with standard medical practice for hepatitis B vaccine administration, regular antibody
testing should be done in hemodialysis patients. A booster dose should be given when antibody levels
decline below 10 IU/l. In subjects in whom insufficient antibody titres are achieved after boosting, the use
of alternative hepatitis B vaccines should be considered.
33
Reduced risk of Hepatocellular Carcinoma
Hepatocellular carcinoma is a serious complication of hepatitis B virus infection. Studies have
demonstrated the link between chronic hepatitis B infection and hepatocellular carcinoma and 80 % of
hepatocellular carcinomas are caused by hepatitis B virus infection. Hepatitis B vaccine has been
recognized as the first anti-cancer vaccine because it can prevent primary liver cancer.
5.2 Pharmacokinetic properties
Not applicable.
5.3 Preclinical safety data
Animal reproduction studies have not been conducted.
6.
6.1 List of excipients
Sodium chloride
Borax
Water for injections.
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal
products.
6.3 Shelf life
3 years.
6.4 Special precautions for storage
Store in a refrigerator (2 °C – 8 °C).
Do not freeze.
6.5
Nature and contents of container
1 ml of suspension in vial (Type I glass) - Pack size of 1
6.6 Special precautions for disposal
Before use, the vaccine should be well shaken.
Any unused product or waste material should be disposed of in accordance with local requirements.
7.
SANOFI PASTEUR MSD SNC
8, rue Jonas Salk
F-69007 Lyon
34
France
8.
EU/1/01/183/015
Date of first authorisation: 27/04/2001
Date of latest renewal: 04/08/2006
35
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
36
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
Merck Sharp & Dohme Corp.Sumneytown Pike
West POINT, Pennsylvania 19486
USA
Name and address of the manufacturer(s) responsible for batch release
MERCK Manufacturing Division Haarlem
Waaderweg 39, P.O. Box 581
2031 BN, 20030 PC Haarlem
The Netherlands
B
CONDITIONS OF THE MARKETING AUTHORISATION
•
Medicinal product subject to medical prescription
•
OTHER CONDITIONS
Pharmacovigilance system
The MAH must ensure that the system of pharmacovigilance, as described in version 2.0 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.
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
PSUR: The marketing authorisation holder will continue to submit periodic safety update reports on a 1-
year cycle.
37
ANNEX III
LABELLING AND PACKAGE LEAFLET
38
A. LABELLING
39
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
HBVAXPRO
5 micrograms/0.5 ml
- single dose vial - Pack of 1, 10
1.
HBVAXPRO 5 micrograms/0.5 ml
Suspension for injection
Hepatitis B vaccine (rDNA)
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
1 dose (0.5 ml) contains:
Hepatitis B virus surface antigen, recombinant (HBsAg) * ................... 5.00 micrograms
Adsorbed on amorphous aluminium hydroxyphosphate sulfate (0.25 milligram Al
+
)
* produced from recombinant strain of the yeast
Saccharomyces cerevisiae
(strain 2150-2-3)
3.
LIST OF EXCIPIENTS
Sodium chloride, borax and water for injections.
4.
Suspension for injection
1 single dose 0.5 ml vial
10 single doses 0.5 ml vials
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Shake well before use.
Read the package leaflet before use.
Intramuscular 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
40
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Store in a refrigerator
Do not freeze
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
SANOFI PASTEUR MSD SNC
8, rue Jonas Salk
F-69007 Lyon
France
EU/1/01/183/001 1 vial
EU/1/01/183/018 10 vials
13. MANUFACTURER’S BATCH NUMBER
Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
41
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
HBVAXPRO 5 micrograms/0.5 ml - single dose vial + syringe with needle - Pack of 1
1.
HBVAXPRO 5 micrograms/0.5 ml
Suspension for injection
Hepatitis B vaccine (rDNA)
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
1 dose (0.5 ml) contains:
Hepatitis B virus surface antigen, recombinant (HBsAg) * ................... 5.00 micrograms
Adsorbed on amorphous aluminium hydroxyphosphate sulfate (0.25 milligram Al
+
)
* produced from recombinant strain of the yeast
Saccharomyces cerevisiae
(strain 2150-2-3)
3.
LIST OF EXCIPIENTS
Sodium chloride, borax and water for injections.
4.
Suspension for injection
1 single dose 0.5 ml vial
1 sterile injection syringe with needle.
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Shake well before use.
Read the package leaflet before use.
Intramuscular 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
42
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Store in a refrigerator
Do not freeze
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
SANOFI PASTEUR MSD SNC
8, rue Jonas Salk
F-69007 Lyon
France
EU/1/01/183/019
13. MANUFACTURER’S BATCH NUMBER
Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
43
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
HBVAXPRO 5 micrograms/0.5 ml
1.
HBVAXPRO 5 µg/0.5 ml
Suspension for injection
Hepatitis B vaccine (rDNA)
IM use
2.
METHOD OF ADMINISTRATION
Shake well before use
3.
EXPIRY DATE
EXP
4.
BATCH NUMBER
Lot
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
0.5 ml
6.
OTHER
SANOFI PASTEUR MSD SNC
44
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
HBVAXPRO 5 micrograms/0.5 ml - single dose pre-filled syringe without needle - Pack of 1, 10, 20,
50
1.
HBVAXPRO 5 micrograms/0.5 ml
Suspension for injection in pre-filled syringe
Hepatitis B vaccine (rDNA)
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
1 dose (0.5 ml) contains:
Hepatitis B virus surface antigen, recombinant (HBsAg) * ................... 5.00 micrograms
Adsorbed on amorphous aluminium hydroxyphosphate sulfate (0.25 milligram Al
+
)
* produced from recombinant strain of the yeast
Saccharomyces cerevisiae
(strain 2150-2-3)
3.
LIST OF EXCIPIENTS
Sodium chloride, borax and water for injections.
4.
Suspension for injection
1 single dose 0.5 ml pre-filled syringe without needle
10 single dose 0.5 ml pre-filled syringes without needle
20 single dose 0.5 ml pre-filled syringes without needle
50 single dose 0.5 ml pre-filled syringes without needle
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Shake well before use.
Read the package leaflet before use.
Intramuscular 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
45
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Store in a refrigerator
Do not freeze
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
SANOFI PASTEUR MSD SNC
8, rue Jonas Salk
F-69007 Lyon
France
EU/1/01/183/004 1 pre-filled syringe
EU/1/01/183/005 10 pre-filled syringes
EU/1/01/183/020 20 pre-filled syringes
EU/1/01/183/021 50 pre-filled syringes
13. MANUFACTURER’S BATCH NUMBER
Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
46
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
HBVAXPRO 5 micrograms/0.5 ml - single dose pre-filled syringe with 1 separate needle - Pack of 1,
10
1.
HBVAXPRO 5 micrograms/0.5 ml
Suspension for injection in pre-filled syringe
Hepatitis B vaccine (rDNA)
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
1 dose (0.5 ml) contains:
Hepatitis B virus surface antigen, recombinant (HBsAg) * ................... 5.00 micrograms
Adsorbed on amorphous aluminium hydroxyphosphate sulfate (0.25 milligram Al
+
)
* produced from recombinant strain of the yeast
Saccharomyces cerevisiae
(strain 2150-2-3)
3.
LIST OF EXCIPIENTS
Sodium chloride, borax and water for injections.
4.
Suspension for injection
1 single dose 0.5 ml pre-filled syringe with 1 separate needle
10 single dose 0.5 ml pre-filled syringes with 1 separate needle (for each syringe)
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Shake well before use.
Read the package leaflet before use.
Intramuscular 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
47
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Store in a refrigerator
Do not freeze
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
SANOFI PASTEUR MSD SNC
8, rue Jonas Salk
F-69007 Lyon
France
EU/1/01/183/022 1 pre-filled syringe
EU/1/01/183/023 10 pre-filled syringes
13. MANUFACTURER’S BATCH NUMBER
Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
48
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
HBVAXPRO 5 micrograms/0.5 ml - single dose pre-filled syringe with 2 separate needles - Pack of
1, 10, 20, 50
1.
HBVAXPRO 5 micrograms/0.5 ml
Suspension for injection in pre-filled syringe
Hepatitis B vaccine (rDNA)
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
1 dose (0.5 ml) contains:
Hepatitis B virus surface antigen, recombinant (HBsAg) * ................... 5.00 micrograms
Adsorbed on amorphous aluminium hydroxyphosphate sulfate (0.25 milligram Al
+
)
* produced from recombinant strain of the yeast
Saccharomyces cerevisiae
(strain 2150-2-3)
3.
LIST OF EXCIPIENTS
Sodium chloride, borax and water for injections.
4.
Suspension for injection
1 single dose 0.5 ml pre-filled syringe with 2 separate needles
10 single dose 0.5 ml pre-filled syringes with 2 separate needles (for each syringe)
20 single dose 0.5 ml pre-filled syringes with 2 separate needles (for each syringe)
50 single dose 0.5 ml pre-filled syringes with 2 separate needles (for each syringe)
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Shake well before use.
Read the package leaflet before use.
Intramuscular 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
49
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Store in a refrigerator
Do not freeze
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
SANOFI PASTEUR MSD SNC
8, rue Jonas Salk
F-69007 Lyon
France
EU/1/01/183/024 1 pre-filled syringe
EU/1/01/183/025 10 pre-filled syringes
EU/1/01/183/030 20 pre-filled syringes
EU/1/01/183/031 50 pre-filled syringes
13. MANUFACTURER’S BATCH NUMBER
Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
50
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
HBVAXPRO 5 micrograms/0.5 ml
1.
HBVAXPRO 5 µg/0.5 ml
Suspension for injection
Hepatitis B vaccine (rDNA)
IM use
2.
METHOD OF ADMINISTRATION
Shake well before use
3.
EXPIRY DATE
EXP
4.
BATCH NUMBER
Lot
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
0.5 ml
6.
OTHER
SANOFI PASTEUR MSD SNC
51
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
HBVAXPRO 10 micrograms/ml - single dose vial - Pack of 1, 10
1.
HBVAXPRO 10 micrograms/ml
Suspension for injection
Hepatitis B vaccine (rDNA)
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
1 dose (1 ml) contains:
Hepatitis B virus surface antigen, recombinant (HBsAg) * ................... 10.00 micrograms
Adsorbed on amorphous aluminium hydroxyphosphate sulfate (0.50 milligram Al
+
)
* produced from recombinant strain of the yeast
Saccharomyces cerevisiae
(strain 2150-2-3)
3.
LIST OF EXCIPIENTS
Sodium chloride, borax and water for injections.
4.
Suspension for injection
1 single dose 1 ml vial.
10 single dose 1 ml vials.
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Shake well before use.
Read the package leaflet before use.
Intramuscular 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
52
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Store in a refrigerator
Do not freeze
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
SANOFI PASTEUR MSD SNC
8, rue Jonas Salk
F-69007 Lyon
France
EU/1/01/183/007 1 vial
EU/1/01/183/008 10 vials
13. MANUFACTURER’S BATCH NUMBER
Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
53
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
HBVAXPRO 10 micrograms/ml
1.
HBVAXPRO 10 µg/ml
Suspension for injection
Hepatitis B vaccine (rDNA)
IM use
2.
METHOD OF ADMINISTRATION
Shake well before use
3.
EXPIRY DATE
EXP
4.
BATCH NUMBER
Lot
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
1 ml
6.
OTHER
SANOFI PASTEUR MSD SNC
54
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
HBVAXPRO 10 micrograms/ml - single dose pre-filled syringe without needle - Pack of 1, 10
1.
HBVAXPRO 10 micrograms/ml
Suspension for injection in pre-filled syringe
Hepatitis B vaccine (rDNA)
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
1 dose (1 ml) contains:
Hepatitis B virus surface antigen, recombinant (HBsAg) * .................... 10.00 micrograms
Adsorbed on amorphous aluminium hydroxyphosphate sulfate (0.50 milligram Al
+
)
* produced from recombinant strain of the yeast
Saccharomyces cerevisiae
(strain 2150-2-3)
3.
LIST OF EXCIPIENTS
Sodium chloride, borax and water for injections.
4.
Suspension for injection
1 single dose 1 ml pre-filled syringe without needle
10 single dose 1 ml pre-filled syringes without needle
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Shake well before use.
Read the package leaflet before use.
Intramuscular 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
55
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Store in a refrigerator
Do not freeze
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
SANOFI PASTEUR MSD SNC
8, rue Jonas Salk
F-69007 Lyon
France
EU/1/01/183/011 1 pre-filled syringe
EU/1/01/183/013 10 pre-filled syringes
13. MANUFACTURER’S BATCH NUMBER
Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
56
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
HBVAXPRO 10 micrograms/ml - single dose pre-filled syringe with 1 separate needle - Pack of 1, 10
1.
HBVAXPRO 10 micrograms/ml
Suspension for injection in pre-filled syringe
Hepatitis B vaccine (rDNA)
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
1 dose (1 ml) contains:
Hepatitis B virus surface antigen, recombinant (HBsAg) * .................... 10.00 micrograms
Adsorbed on amorphous aluminium hydroxyphosphate sulfate (0.50 milligram Al
+
)
* produced from recombinant strain of the yeast
Saccharomyces cerevisiae
(strain 2150-2-3)
3.
LIST OF EXCIPIENTS
Sodium chloride, borax and water for injections.
4.
Suspension for injection
1 single dose 1 ml pre-filled syringe with 1 separate needle
10 single dose 1 ml pre-filled syringes with 1 separate needle (for each syringe)
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Shake well before use.
Read the package leaflet before use.
Intramuscular 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
57
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Store in a refrigerator
Do not freeze
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
SANOFI PASTEUR MSD SNC
8, rue Jonas Salk
F-69007 Lyon
France
EU/1/01/183/026 1 pre-filled syringe
EU/1/01/183/027 10 pre-filled syringe
13. MANUFACTURER’S BATCH NUMBER
Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
58
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
HBVAXPRO 10 micrograms/ml - single dose pre-filled syringe with 2 separate needles - Pack of 1,
10, 20
1.
HBVAXPRO 10 micrograms/ml
Suspension for injection in pre-filled syringe
Hepatitis B vaccine (rDNA)
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
1 dose (1 ml) contains:
Hepatitis B virus surface antigen, recombinant (HBsAg) * .................... 10.00 micrograms
Adsorbed on amorphous aluminium hydroxyphosphate sulfate (0.50 milligram Al
+
)
* produced from recombinant strain of the yeast
Saccharomyces cerevisiae
(strain 2150-2-3)
3.
LIST OF EXCIPIENTS
Sodium chloride, borax and water for injections.
4.
Suspension for injection
1 single dose 1 ml pre-filled syringe with 2 separate needles
10 single dose 1 ml pre-filled syringes with 2 separate needles (for each syringe)
20 single dose 1 ml pre-filled syringes with 2 separate needles (for each syringe)
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Shake well before use.
Read the package leaflet before use.
Intramuscular 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
59
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Store in a refrigerator
Do not freeze
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
SANOFI PASTEUR MSD SNC
8, rue Jonas Salk
F-69007 Lyon
France
EU/1/01/183/028 1 pre-filled syringe
EU/1/01/183/029 10 pre-filled syringes
EU/1/01/183/032 20 pre-filled syringes
13. MANUFACTURER’S BATCH NUMBER
Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
60
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
HBVAXPRO 10 micrograms/ml
1.
HBVAXPRO 10 µg/ml
Suspension for injection
Hepatitis B vaccine (rDNA)
IM use
2.
METHOD OF ADMINISTRATION
Shake well before use
3.
EXPIRY DATE
EXP
4.
BATCH NUMBER
Lot
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
1 ml
6.
OTHER
SANOFI PASTEUR MSD SNC
61
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
HBVAXPRO 40 micrograms/ml - single dose vial - Pack of 1
1.
HBVAXPRO 40 micrograms/ml
Suspension for injection
Hepatitis B vaccine (rDNA)
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
1 dose (1 ml) contains:
Hepatitis B virus surface antigen, recombinant (HBsAg) * ................... 40.00 micrograms
Adsorbed on amorphous aluminium hydroxyphosphate sulfate (0.50 milligram Al
+
)
* produced from recombinant strain of the yeast
Saccharomyces cerevisiae
(strain 2150-2-3)
3.
LIST OF EXCIPIENTS
Sodium chloride, borax and water for injections.
4.
Suspension for injection
1 single dose 1 ml vial.
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Shake well before use.
Read the package leaflet before use.
Intramuscular 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
62
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Store in a refrigerator
Do not freeze
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
SANOFI PASTEUR MSD SNC
8, rue Jonas Salk
F-69007 Lyon
France
EU/1/01/183/015
13. MANUFACTURER’S BATCH NUMBER
Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
63
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
HBVAXPRO 40 micrograms/ml
1.
HBVAXPRO 40 µg/ml
Suspension for injection
Hepatitis B vaccine (rDNA)
IM use
2.
METHOD OF ADMINISTRATION
Shake well before use
3.
EXPIRY DATE
EXP
4.
BATCH NUMBER
Lot
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
1 ml
6.
OTHER
SANOFI PASTEUR MSD SNC
64
B. PACKAGE LEAFLET
65
PACKAGE LEAFLET: INFORMATION FOR THE USER
HBVAXPRO 5 micrograms/0.5 ml, suspension for injection
Hepatitis B vaccine (rDNA)
Read all of this leaflet carefully before your child is vaccinated.
-
Keep this leaflet. You may need to read it again.
-
If you have any further questions, ask your doctor or pharmacist.
-
If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.
In this leaflet
:
1.
What HBVAXPRO 5 micrograms/0.5 ml is and what it is used for
2.
Before you use HBVAXPRO 5 micrograms/0.5 ml
3.
How to use HBVAXPRO 5 micrograms/0.5 ml
4.
Possible side effects
5.
How to store HBVAXPRO 5 micrograms/0.5 ml
6.
Further information
1.
WHAT HBVAXPRO 5 micrograms/0.5 ml IS AND WHAT IT IS USED FOR
This vaccine is indicated for active immunisation against hepatitis B virus infection caused by all known
subtypes in children and adolescents (from birth trough 15 years of age) considered at risk of exposure to
hepatitis B virus.
It can be expected that hepatitis D will also be prevented by immunisation with HBVAXPRO as hepatitis
D does not occur in the absence of hepatitis B infection.
The vaccine will not prevent infection caused by other agents such as hepatitis A, hepatitis C and hepatitis
E and other pathogens known to infect the liver.
2.
BEFORE YOU USE HBVAXPRO 5 micrograms/0.5 ml
Do not use HBVAXPRO 5 micrograms/0.5 ml:
-
if your child is allergic (hypersensitive) to hepatitis B surface antigen or to any of the other
ingredients of HBVAXPRO (see section 6.)
-
if your child has a severe febrile illness
Using other vaccines:
This vaccine can be administered simultaneously with hepatitis B immunoglobulin, at a separate injection
site.
This vaccine can be used to complete a primary immunisation course or as a booster dose in subjects who
have previously received another hepatitis B vaccine.
This vaccine may be administered concomitantly with some other vaccines, using separate sites and
syringes.
Please tell your doctor or pharmacist if your child is taking or has recently taken any other medicines,
including medicines obtained without a prescription
.
66
3.
HOW TO USE HBVAXPRO 5 micrograms/0.5 ml:
Posology:
The recommended dose for each injection (0.5 ml) is 5 micrograms for children and adolescents (birth
through 15 years of age).
A course of vaccination should include at least three injections.
Two immunisation schedules can be recommended:
-
two injections with an interval of one month followed by a third injection 6 months after the first
administration (0,1,6 months).
-
three injections with an interval of one month and a fourth dose 1 year later, if a rapid immunity is
requested (0,1,2,12 months).
In case of a recent exposure to the hepatitis B virus, a first dose of HBVAXPRO together with the
appropriate dose of immunoglobulin can be given.
Some local vaccination schedules currently include recommendations for a booster dose. Your doctor or
pharmacist will inform you if a booster dose should be given.
Method of administration:
It should be well shaken until a slightly opaque white suspension is obtained.
Once the vial has been penetrated, the withdrawn vaccine should be used promptly, and the vial must be
discarded.
The doctor will give the vaccine as an injection into muscle. The upper side of the thigh is the preferred
site for injection in neonates and infants. The upper arm muscle is the preferred site for injection in
children and adolescents.
This vaccine should never be given into a vein.
Exceptionally, the vaccine may be administered subcutaneously in patients with thrombocytopoenia
(diminution of blood platelets) or to persons at risk of haemorrhage.
If you forget one dose of HBVAXPRO 5 micrograms/0.5 ml:
If you miss a scheduled injection, your doctor will decide when to give the missed dose.
If you have any further questions on the use of this product, ask your doctor or pharmacist.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, HBVAXPRO can cause side effects, although not everybody gets them.
As with other hepatitis B vaccines, in many instances, the causal relationship of side effects to the vaccine
has not been established.
HBVAXPRO is generally well tolerated.
The most common side effects seen are injection-site reactions: soreness, redness and hardening.
67
Other side effects are reported very rarely: low platelet count, lymph node disease, allergic reactions,
nervous system disorders such as pins and needles, facial paralysis, nerve inflammations including
Guillain-Barre Syndrome, inflammation of the nerve of the eye that leads to impaired vision, brain
inflammation, exacerbation of multiple sclerosis,
multiple sclerosis, convulsions, headache, dizziness and
fainting, low blood pressure, blood vessel inflammation, asthma-like symptoms, vomiting, nausea,
diarrhoea, abdominal pain, skin reactions such as eczema, rash, hair loss, itching, hives and skin blistering,
joint pain, arthritis, muscle pain, pain in extremity, fatigue, fever, vague illness, flu-like symptoms and
elevations of liver enzymes.
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 HBVAXPRO 5 micrograms/0.5 ml
Keep out of the reach and sight of children.
Do not use HBVAXPRO after the expiry date which is stated on the label.
Store in a refrigerator (2 °C – 8 °C)
Do not freeze
6.
FURTHER INFORMATION
What HBVAXPRO 5 micrograms/0.5 ml contains
The active substance is, for one dose of 0.5 ml:
Hepatitis B virus surface antigen, recombinant (HBsAg) * ................... 5.00 micrograms
Adsorbed on amorphous aluminium hydroxyphosphate sulfate (0.25 milligram Al
+
)
* produced from recombinant strain of the yeast
Saccharomyces cerevisiae
(strain 2150-2-3)
The other ingredients are sodium chloride, borax and water for injections.
What HBVAXPRO 5 micrograms/0.5 ml looks like and contents of the pack
Each dose contains 0.5 ml of suspension for injection in a vial.
Pack sizes of 1 and 10 vials without syringe/needle.
Pack size of 1 vial with syringe and needle.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder: Sanofi Pasteur MSD SNC, 8 rue Jonas Salk, F-69007 Lyon, France
Manufacturer Responsible for Batch Release: Merck Sharp and Dohme, B.V., Waarderweg, 39, 2031 BN
Haarlem, The Netherlands
For any information about this medicinal product, please contact the local representative of the Marketing
Authorisation Holder.
68
België/Belgique/Belgien:
Sanofi Pasteur MSD, Tél/Tel: +32.2.726.95.84
България:
Мерк Шарп и Доум България ЕООД, Тел. + 359 2 8193740
Česká republika:
Merck Sharp & Dohme, IDEA,
Inc., org. sl., Tel.: +420.233.010.111
Danmark:
Sanofi Pasteur MSD, Tlf: +45 23 32 69 29
Deutschland:
Sanofi Pasteur MSD GmbH, Tel: +49.6224.5940
Eesti:
Merck Sharp & Dohme OÜ, Tel: +372.613.9750
Ελλάδα:
ΒΙΑΝΕΞ Α.Ε., Τηλ: +30.210.8009111
España:
Sanofi Pasteur MSD S.A., Tel: +34.91.371.78.00
France:
Sanofi Pasteur MSD SNC, Tél: +33.4.37.28.40.00
Ireland:
Sanofi Pasteur MSD Ltd, Tel: +3531.468.5600
Ísland:
Sanofi Pasteur MSD, Tel: +32.2.726.95.84
Italia:
Sanofi Pasteur MSD Spa, Tel: +39.06.664.092.11
Kύπρος:
Merck Sharp & Dohme (Middle East) Limited., Τηλ: +357 22866700
Latvija:
SIA Merck Sharp & Dohme Latvija, Tel: +371.67364.224
Lietuva:
UAB Merck Sharp & Dohme, Tel.: +370.5.2780.247
Luxembourg/Luxemburg:
Sanofi Pasteur MSD, Tél: +32.2.726.95.84
Magyarország:
MSD Magyarország Kft, Tel.: + 36.1.888.5300
Malta:
Merck Sharp & Dohme (Middle East) Limited, Tel: +357 22866700
Nederland:
Sanofi Pasteur MSD, Tel: +31.23.567.96.00
Norge:
Sanofi Pasteur MSD, Tlf: +47.67.50.50.20
Österreich:
Sanofi Pasteur MSD GmbH, Tel: +43.1.866.70.22.202
Polska:
MSD Polska Sp. z o.o., Tel.: +48.22.549.51.00
Portugal
: Sanofi Pasteur MSD, SA, Tel: +351 21 470 45 50
România
: Merck Sharp & Dohme Romania S.R.L., Tel: + 4021 529 29 00
Slovenija:
Merck Sharp & Dohme,
inovativna zdravila d.o.o., Tel: +386.1.520.4201
Slovenská republika:
Merck Sharp & Dohme IDEA, Inc., Tel: +421.2.58282010
Suomi/Finland:
Sanofi Pasteur MSD, Puh/Tel: +358.9.565.88.30
Sverige:
Sanofi Pasteur MSD, Tel: +46.8.564.888.60
United Kingdom:
Sanofi Pasteur MSD Ltd, Tel: +44 1 628 785 291
This leaflet was last approved in ………….
69
PACKAGE LEAFLET: INFORMATION FOR THE USER
HBVAXPRO 5 micrograms/0.5 ml, suspension for injection in pre-filled syringe
Hepatitis B vaccine (rDNA)
Read all of this leaflet carefully before your child is vaccinated.
-
Keep this leaflet. You may need to read it again.
-
If you have any further questions, ask your doctor or pharmacist.
-
If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.
In this leaflet
:
1.
What HBVAXPRO 5 micrograms/0.5 ml is and what it is used for
2.
Before you use HBVAXPRO 5 micrograms/0.5 ml
3.
How to use HBVAXPRO 5 micrograms/0.5 ml
4.
Possible side effects
5.
How to store HBVAXPRO 5 micrograms/0.5 ml
6.
Further information
1.
WHAT IS HBVAXPRO 5 micrograms/0.5 ml AND WHAT IT IS USED FOR
This vaccine is indicated for active immunisation against hepatitis B virus infection caused by all known
subtypes in children and adolescents (from birth through 15 years of age) considered at risk of exposure to
hepatitis B virus.
It can be expected that hepatitis D will also be prevented by immunisation with HBVAXPRO as hepatitis
D does not occur in the absence of hepatitis B infection.
The vaccine will not prevent infection caused by other agents such as hepatitis A, hepatitis C and hepatitis
E and other pathogens known to infect the liver.
2.
BEFORE YOU USE HBVAXPRO 5 micrograms/0.5 ml
Do not use HBVAXPRO 5 micrograms/0.5 ml:
-
if your child is allergic (hypersensitive) to hepatitis B surface antigen or to any of the other
ingredients of HBVAXPRO (see section 6.)
-
if your child has a severe febrile illness
Using other vaccines:
This vaccine can be administered simultaneously with hepatitis B immunoglobulin, at a separate injection
site.
This vaccine can be used to complete a primary immunisation course or as a booster dose in subjects who
have previously received another hepatitis B vaccine.
This vaccine may be administered concomitantly with some other vaccines, using separate sites and
syringes.
Please tell your doctor or pharmacist if your child is taking or has recently taken any other medicines,
including medicines obtained without a prescription.
70
3.
HOW TO USE HBVAXPRO 5 micrograms/0.5 ml
Posology:
The recommended dose for each injection (0.5 ml) is 5 micrograms for children and adolescents (birth
through 15 years of age).
A course of vaccination should include at least three injections.
Two immunisation schedules can be recommended:
-
two injections with an interval of one month followed by a third injection 6 months after the first
administration (0,1,6 months).
-
three injections with an interval of one month and a fourth dose 1 year later, if a rapid immunity is
requested (0,1,2,12 months).
In case of a recent exposure to the hepatitis B virus, a first dose of HBVAXPRO together with the
appropriate dose of immunoglobulin can be given.
Some local vaccination schedules currently include recommendations for a booster dose. Your doctor or
pharmacist will inform you if a booster dose should be given.
Method of administration:
It should be well shaken until a slightly opaque white suspension is obtained.
The needle is attached by twisting in clockwise direction, until the needle fits securely on the syringe.
The doctor will give the vaccine as an injection into muscle. The upper side of the thigh is the preferred
site for injection in neonates and infants. The upper arm muscle is the preferred site for injection in
children and adolescents.
This vaccine should never be given into a vein.
Exceptionally, the vaccine may be administered subcutaneously in patients with thrombocytopoenia
(diminution of blood platelets) or to persons at risk of haemorrhage.
If you forget one dose of HBVAXPRO 5 micrograms/0.5 ml:
If you miss a scheduled injection, your doctor will decide when to give the missed dose.
If you have any further questions on the use of this product, ask your doctor or pharmacist.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, HBVAXPRO can cause side effects, although not everybody gets them.
As with other hepatitis B vaccines, in many instances, the causal relationship of side effects to the vaccine
has not been established.
HBVAXPRO is generally well tolerated.
The most common side effects seen are injection-site reactions: soreness, redness and hardening.
71
Other side effects are reported very rarely: low platelet count, lymph node disease, allergic reactions,
nervous system disorders such as pins and needles, facial paralysis, nerve inflammations including
Guillain-Barre Syndrome, inflammation of the nerve of the eye that leads to impaired vision, brain
inflammation, exacerbation of multiple sclerosis,
multiple sclerosis, convulsions, headache, dizziness and
fainting, low blood pressure, blood vessel inflammation, asthma-like symptoms, vomiting, nausea,
diarrhoea, abdominal pain, skin reactions such as eczema, rash, hair loss, itching, hives and skin blistering,
joint pain, arthritis, muscle pain, pain in extremity, fatigue, fever, vague illness, flu-like symptoms and
elevations of liver enzymes.
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 HBVAXPRO 5 micrograms/0.5 ml
Keep out of the reach and sight of children.
Do not use HBVAXPRO after the expiry date which is stated on the label.
Store in a refrigerator (2 °C – 8 °C)
Do not freeze
6.
FURTHER INFORMATION
What HBVAXPRO 5 micrograms/0.5 ml contains
The active substance is, for one dose of 0.5 ml:
Hepatitis B virus surface antigen, recombinant (HBsAg) * ................... 5.00 micrograms
Adsorbed on amorphous aluminium hydroxyphosphate sulfate (0.25 milligram Al
+
)
* produced from recombinant strain of the yeast
Saccharomyces cerevisiae
(strain 2150-2-3)
The other ingredients are sodium chloride, borax and water for injections.
What HBVAXPRO 5 micrograms/0.5 ml looks like and contents of the pack
Each dose contains 0.5 ml of suspension for injection in a syringe.
Pack sizes of 1, 10, 20 and 50 pre-filled syringes without needle or with 2 separate needles,
Pack sizes of 1 and 10 pre-filled syringes with 1 separate needle.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder: Sanofi Pasteur MSD SNC, 8 rue Jonas Salk, F-69007 Lyon, France
Manufacturer Responsible for Batch Release: Merck Sharp and Dohme, B.V., Waarderweg, 39, 2031 BN
Haarlem, The Netherlands
For any information about this medicinal product, please contact the local representative of the Marketing
Authorisation Holder.
72
België/Belgique/Belgien:
Sanofi Pasteur MSD, Tél/Tel: +32.2.726.95.84
България:
Мерк Шарп и Доум България ЕООД, Тел. + 359 2 8193740
Česká republika:
Merck Sharp & Dohme, IDEA, Inc., org. sl., Tel.: +420.233.010.111
Danmark:
Sanofi Pasteur MSD, Tlf: +45 23 32 69 29
Deutschland:
Sanofi Pasteur MSD GmbH, Tel: +49.6224.5940
Eesti:
Merck Sharp & Dohme OÜ, Tel: +372.613.9750
Ελλάδα:
ΒΙΑΝΕΞ Α.Ε., Τηλ: +30.210.8009111
España:
Sanofi Pasteur MSD S.A., Tel: +34.91.371.78.00
France:
Sanofi Pasteur MSD SNC, Tél: +33.4.37.28.40.00
Ireland:
Sanofi Pasteur MSD Ltd, Tel: +3531.468.5600
Ísland:
Sanofi Pasteur MSD, Tel: +32.2.726.95.84
Italia:
Sanofi Pasteur MSD Spa, Tel: +39.06.664.092.11
Kύπρος:
Merck Sharp & Dohme (Middle East) Limited., Τηλ: +357 22866700
Latvija:
SIA Merck Sharp & Dohme Latvija, Tel: +371.67364.224
Lietuva:
UAB Merck Sharp & Dohme, Tel.: +370.5.2780.247
Luxembourg/Luxemburg:
Sanofi Pasteur MSD, Tél: +32.2.726.95.84
Magyarország:
MSD Magyarország Kft, Tel.: + 36.1.888.5300
Malta:
Merck Sharp & Dohme (Middle East) Limited, Tel: +357 22866700
Nederland:
Sanofi Pasteur MSD, Tel: +31.23.567.96.00
Norge:
Sanofi Pasteur MSD, Tlf: +47.67.50.50.20
Österreich:
Sanofi Pasteur MSD GmbH, Tel: +43.1.866.70.22.202
Polska:
MSD Polska Sp. z o.o., Tel.: +48.22.549.51.00
Portugal
: Sanofi Pasteur MSD, SA, Tel: +351 21 470 45 50
România
: Merck Sharp & Dohme Romania S.RL., Tel: + 4021 529 29 00
Slovenija:
Merck Sharp & Dohme,
inovativna zdravila d.o.o., Tel: +386.1.520.4201
Slovenská republika:
Merck Sharp & Dohme IDEA, Inc., Tel: +421.2.58282010
Suomi/Finland:
Sanofi Pasteur MSD, Puh/Tel: +358.9.565.88.30
Sverige:
Sanofi Pasteur MSD, Tel: +46.8.564.888.60
United Kingdom:
Sanofi Pasteur MSD Ltd, Tel: +44 1 628 785 291
This leaflet was last approved in ………….
73
PACKAGE LEAFLET: INFORMATION FOR THE USER
HBVAXPRO 10 micrograms/ml, suspension for injection
Hepatitis B vaccine (rDNA)
Read all of this leaflet carefully before you are vaccinated.
-
Keep this leaflet. You may need to read it again.
-
If you have any further questions, ask your doctor or pharmacist.
-
If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.
In this leaflet
:
1.
What HBVAXPRO 10 micrograms/ml is and what it is used for
2.
Before you use HBVAXPRO 10 micrograms/ml
3.
How to use HBVAXPRO 10 micrograms/ml
4.
Possible side effects
5.
How to store HBVAXPRO 10 micrograms/ml
6.
Further information
1.
WHAT HBVAXPRO 10 micrograms/ml IS AND WHAT IT IS USED FOR
This vaccine is indicated for active immunisation against hepatitis B virus infection caused by all known
subtypes in adults and adolescents (16 years of age and older) considered at risk of exposure to hepatitis B
virus.
It can be expected that hepatitis D will also be prevented by immunisation with HBVAXPRO as hepatitis
D does not occur in the absence of hepatitis B infection.
The vaccine will not prevent infection caused by other agents such as hepatitis A, hepatitis C and hepatitis
E and other pathogens known to infect the liver.
2.
BEFORE YOU USE HBVAXPRO 10 micrograms/ml
Do not use HBVAXPRO 10 micrograms/ml:
-
if you are allergic (hypersensitive) to hepatitis B surface antigen or to any of the other ingredients of
HBVAXPRO (see section 6.)
-
if you have a severe febrile illness
Take special care with
HBVAXPRO 10 micrograms/ml:
Pregnancy and Breast-feeding:
Caution should be exercised when prescribing to pregnant women.
Breast-feeding is not a contraindication.
Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines:
Some of the rare effects may affect the ability to drive or operate machinery.
Using other vaccines:
74
This vaccine can be administered simultaneously with hepatitis B immunoglobulin, at a separate injection
site.
This vaccine can be used to complete a primary immunisation course or as a booster dose in subjects who
have previously received another hepatitis B vaccine.
This vaccine can be administered concomitantly with other vaccines, using separate sites and syringes.
Please inform your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription
.
3.
HOW TO USE HBVAXPRO 10 micrograms/ml
Posology:
The recommended dose for each injection (1 ml) is 10 micrograms for adults and adolescents (16 years of
age and older).
A course of vaccination should include three injections.
Two immunisation schedules can be recommended:
-
two injections with an interval of one month followed by a third injection 6 months after the
first administration (0,1,6 months)
-
three injections with an interval of one month and a fourth dose 1 year later, if a rapid immunity is
requested (0,1,2,12 months).
In case of a recent exposure to the hepatitis B virus, a first dose of HBVAXPRO together with the
appropriate dose of immunoglobulin can be given.
Some local vaccination schedules currently include recommendations for a booster dose. Your doctor or
pharmacist will inform you if a booster dose should be given.
Method of administration:
It should be well shaken until a slightly opaque white suspension is obtained.
The doctor will give the vaccine as an injection into muscle. The upper arm muscle is the preferred site for
injection in adults and adolescents.
This vaccine should never be given into a vein.
Exceptionally, the vaccine may be administered subcutaneously in patients with thrombocytopoenia
(diminution of blood platelets) or to persons at risk of haemorrhage.
If you forget one dose of HBVAXPRO 10 micrograms/ml:
If you missed a scheduled injection, your doctor will decide when to give the missed dose.
If you have any further questions on the use of this product, ask your doctor or pharmacist.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, HBVAXPRO can cause side effects, although not everybody gets them.
75
As with other hepatitis B vaccines, in many instances, the causal relationship of side effects to the vaccine
has not been established.
HBVAXPRO is generally well tolerated.
The most common side effects seen are injection-site reactions: soreness, redness and hardening.
Other side effects are reported very rarely: low platelet count, lymph node disease, allergic reactions,
nervous system disorders such as pins and needles, facial paralysis, nerve inflammations including
Guillain-Barre Syndrome, inflammation of the nerve of the eye that leads to impaired vision, brain
inflammation, exacerbation of multiple sclerosis,
multiple sclerosis, convulsions, headache, dizziness and
fainting, low blood pressure, blood vessel inflammation, asthma-like symptoms, vomiting, nausea,
diarrhoea, abdominal pain, skin reactions such as eczema, rash, hair loss, itching, hives and skin blistering,
joint pain, arthritis, muscle pain, pain in extremity, fatigue, fever, vague illness, flu-like symptoms and
elevations of liver enzymes.
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 HBVAXPRO 10 micrograms/ml
Keep out of the reach and sight of children.
Do not use HBVAXPRO after the expiry date which is stated on the label.
Store in a refrigerator (2 °C – 8 °C)
Do not freeze
6.
FURTHER INFORMATION
What HBVAXPRO 10 micrograms/ml contains
The active substance is, for one dose of 1 ml:
Hepatitis B virus surface antigen, recombinant (HBsAg) * ................... 10.00 micrograms
Adsorbed on amorphous aluminium hydroxyphosphate sulfate (0.50 milligram Al
+
)
* produced from recombinant strain of the yeast
Saccharomyces cerevisiae
(strain 2150-2-3)
The other ingredients are sodium chloride, borax and water for injections.
What HBVAXPRO 10 micrograms/ml looks like and contents of the pack
Each dose contains 1 ml of suspension for injection in a vial.
Pack sizes of 1 and 10 vials.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder: Sanofi Pasteur MSD SNC, 8 rue Jonas Salk, F-69007 Lyon, France
Manufacturer Responsible for Batch Release: Merck Sharp and Dohme, B.V., Waarderweg, 39, 2031 BN
Haarlem, The Netherlands
76
For any information about this medicinal product, please contact the local representative of the Marketing
Authorisation Holder.
België/Belgique/Belgien:
Sanofi Pasteur MSD, Tél/Tel: +32.2.726.95.84
България:
Мерк Шарп и Доум България ЕООД, Тел. + 359 2 8193740
Česká republika:
Merck Sharp & Dohme, IDEA, Inc., org. sl., Tel.: +420.233.010.111
Danmark:
Sanofi Pasteur MSD, Tlf: +45 23 32 69 29
Deutschland:
Sanofi Pasteur MSD GmbH, Tel: +49.6224.5940
Eesti:
Merck Sharp & Dohme OÜ, Tel: +372.613.9750
Ελλάδα:
ΒΙΑΝΕΞ Α.Ε., Τηλ: +30.210.8009111
España:
Sanofi Pasteur MSD S.A., Tel: +34.91.371.78.00
France:
Sanofi Pasteur MSD SNC, Tél: +33.4.37.28.40.00
Ireland:
Sanofi Pasteur MSD Ltd, Tel: +3531.468.5600
Ísland:
Sanofi Pasteur MSD, Tel: +32.2.726.95.84
Italia:
Sanofi Pasteur MSD Spa, Tel: +39.06.664.092.11
Kύπρος:
Merck Sharp & Dohme (Middle East) Limited., Τηλ: +357 22866700
Latvija:
SIA Merck Sharp & Dohme Latvija, Tel: +371.67364.224
Lietuva:
UAB Merck Sharp & Dohme, Tel.: +370.5.2780.247
Luxembourg/Luxemburg:
Sanofi Pasteur MSD, Tél: +32.2.726.95.84
Magyarország:
MSD Magyarország Kft, Tel.: + 36.1.888.5300
Malta:
Merck Sharp & Dohme (Middle East) Limited, Tel: +357 22866700
Nederland:
Sanofi Pasteur MSD, Tel: +31.23.567.96.00
Norge:
Sanofi Pasteur MSD, Tlf: +47.67.50.50.20
Österreich:
Sanofi Pasteur MSD GmbH, Tel: +43.1.866.70.22.202
Polska:
MSD Polska Sp. z o.o., Tel.: +48.22.549.51.00
Portugal
: Sanofi Pasteur MSD, SA, Tel: +351 21 470 45 50
România
: Merck Sharp & Dohme Romania S.R.L., Tel: + 4021 529 29 00
Slovenija:
Merck Sharp & Dohme,
inovativna zdravila d.o.o., Tel: +386.1.520.4201
Slovenská republika:
Merck Sharp & Dohme IDEA, Inc., Tel: +421.2.58282010
Suomi/Finland:
Sanofi Pasteur MSD, Puh/Tel: +358.9.565.88.30
Sverige:
Sanofi Pasteur MSD, Tel: +46.8.564.888.60
United Kingdom:
Sanofi Pasteur MSD Ltd, Tel: +44 1 628 785 291
This leaflet was last approved in ………….
77
PACKAGE LEAFLET: INFORMATION FOR THE USER
HBVAXPRO 10 micrograms/ml, suspension for injection in pre-filled syringe
Hepatitis B vaccine (rDNA)
Read all of this leaflet carefully before you are vaccinated.
-
Keep this leaflet. You may need to read it again.
-
If you have any further questions, ask your doctor or pharmacist.
-
If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.
In this leaflet
:
1.
What HBVAXPRO 10 micrograms/ml is and what it is used for
2.
Before you use HBVAXPRO 10 micrograms/ml
3.
How to use HBVAXPRO 10 micrograms/ml
4.
Possible side effects
5.
How to store HBVAXPRO 10 micrograms/ml
6.
Further information
1.
WHAT HBVAXPRO 10 micrograms/ml IS AND WHAT IT IS USED FOR
This vaccine is indicated for active immunisation against hepatitis B virus infection caused by all known
subtypes in adults and adolescents (16 years of age and older) considered at risk of exposure to hepatitis B
virus.
It can be expected that hepatitis D will also be prevented by immunisation with HBVAXPRO as hepatitis
D does not occur in the absence of hepatitis B infection.
The vaccine will not prevent infection caused by other agents such as hepatitis A, hepatitis C and hepatitis
E and other pathogens known to infect the liver.
2.
BEFORE YOU USE HBVAXPRO 10 micrograms/ml
Do not use HBVAXPRO 10 micrograms/ml:
-
if you are allergic (hypersensitive) to hepatitis B surface antigen or to any of the other ingredients
of HBVAXPRO (see section 6.)
-
if you have a severe febrile illness
Take special care with
HBVAXPRO 10 micrograms/ml:
Pregnancy and Breast-feeding:
Caution should be exercised when prescribing to pregnant women.
Breast-feeding is not a contraindication.
Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines:
Some of the rare effects may affect the ability to drive or operate machinery.
Using other vaccines:
78
This vaccine can be administered simultaneously with hepatitis B immunoglobulin, at a separate injection
site.
This vaccine can be used to complete a primary immunisation course or as a booster dose in subjects who
have previously received another hepatitis B vaccine.
This vaccine can be administered concomitantly with other vaccines, using separate sites and syringes.
Please inform your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription
.
3.
HOW TO USE HBVAXPRO 10 micrograms/ml
Posology:
The recommended dose for each injection (1 ml) is 10 micrograms for adults and adolescents (16 years of
age and older).
A course of vaccination should include at least three injections.
Two immunisation schedules can be recommended:
-
two injections with an interval of one month followed by a third injection 6 months after the first
administration (0,1,6 months)
-
three injections with an interval of one month and a fourth dose 1 year later, if a rapid immunity is
requested (0,1,2,12 months).
In case of a recent exposure to the hepatitis B virus, a first dose of HBVAXPRO together with the
appropriate dose of immunoglobulin can be given.
Some local vaccination schedules currently include recommendations for a booster dose. Your doctor or
pharmacist will inform you if a booster dose should be given.
Method of administration:
It should be well shaken until a slightly opaque white suspension is obtained.
The needle is attached by twisting in clockwise direction, until the needle fits securely on the syringe.
The doctor will give the vaccine as an injection into muscle. The upper arm muscle is the preferred site for
injection in adults and adolescents.
This vaccine should never be given into a vein.
Exceptionally, the vaccine may be administered subcutaneously in patients with thrombocytopoenia
(diminution of blood platelets) or to persons at risk of haemorrhage.
If you forget one dose of HBVAXPRO 10 micrograms/ml:
If you miss a scheduled injection, your doctor will decide when to give the missed dose.
If you have any further questions on the use of this product, ask your doctor or pharmacist.
4.
POSSIBLE SIDE EFFECTS
79
Like all medicines, HBVAXPRO can cause side effects, although not everybody gets them.
As with other hepatitis B vaccines, in many instances, the causal relationship of side effects to the vaccine
has not been established.
HBVAXPRO is generally well tolerated.
The most common side effects seen are injection-site reactions: soreness, redness and hardening.
Other side effects are reported very rarely: low platelet count, lymph node disease, allergic reactions,
nervous system disorders such as pins and needles, facial paralysis, nerve inflammations including
Guillain-Barre Syndrome, inflammation of the nerve of the eye that leads to impaired vision, brain
inflammation, exacerbation of multiple sclerosis,
multiple sclerosis, convulsions, headache, dizziness and
fainting, low blood pressure, blood vessel inflammation, asthma-like symptoms, vomiting, nausea,
diarrhoea, abdominal pain, skin reactions such as eczema, rash, hair loss, itching, hives and skin blistering,
joint pain, arthritis, muscle pain, pain in extremity, fatigue, fever, vague illness, flu-like symptoms and
elevations of liver enzymes.
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 HBVAXPRO 10 micrograms/ml
Keep out of the reach and sight of children.
Do not use HBVAXPRO after the expiry date which is stated on the label.
Store in a refrigerator (2 °C – 8 °C)
Do not freeze
6.
FURTHER INFORMATION
What HBVAXPRO 10 micrograms/ml contains
The active substance is, for one dose of 1 ml:
Hepatitis B virus surface antigen, recombinant (HBsAg) * ................... 10.00 micrograms
Adsorbed on amorphous aluminium hydroxyphosphate sulfate (0.50 milligram Al
+
)
* produced from recombinant strain of the yeast
Saccharomyces cerevisiae
(strain 2150-2-3)
The other ingredients are sodium chloride, borax and water for injections.
What HBVAXPRO 10 micrograms/ml looks like and contents of the pack
Each dose contains 1 ml of suspension for injection in a syringe.
Pack sizes of 1, 10 and 20 pre-filled syringes with 2 separate needles.
Pack sizes of 1 and 10 pre-filled syringes without needle, or with 1 separate needle.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder: Sanofi Pasteur MSD SNC, 8 rue Jonas Salk, F-69007 Lyon, France
80
Manufacturer Responsible for Batch Release: Merck Sharp and Dohme, B.V., Waarderweg, 39, 2031 BN
Haarlem, The Netherlands
For any information about this medicinal product, please contact the local representative of the Marketing
Authorisation Holder.
België/Belgique/Belgien:
Sanofi Pasteur MSD, Tél/Tel: +32.2.726.95.84
България:
Мерк Шарп и Доум България ЕООД, Тел. + 359 2 8193740
Česká republika:
Merck Sharp & Dohme, IDEA, Inc., org. sl., Tel.: +420.233.010.111
Danmark:
Sanofi Pasteur MSD, Tlf: +45 23 32 69 29
Deutschland:
Sanofi Pasteur MSD GmbH, Tel: +49.6224.5940
Eesti:
Merck Sharp & Dohme OÜ, Tel: +372.613.9750
Ελλάδα:
ΒΙΑΝΕΞ Α.Ε., Τηλ: +30.210.8009111
España:
Sanofi Pasteur MSD S.A., Tel: +34.91.371.78.00
France:
Sanofi Pasteur MSD SNC, Tél: +33.4.37.28.40.00
Ireland:
Sanofi Pasteur MSD Ltd, Tel: +3531.468.5600
Ísland:
Sanofi Pasteur MSD, Tel: +32.2.726.95.84
Italia:
Sanofi Pasteur MSD Spa, Tel: +39.06.664.092.11
Kύπρος:
Merck Sharp & Dohme (Middle East) Limited., Τηλ: +357 22866700
Latvija:
SIA Merck Sharp & Dohme Latvija, Tel: +371.67364.224
Lietuva:
UAB Merck Sharp & Dohme, Tel.: +370.5.2780.247
Luxembourg/Luxemburg:
Sanofi Pasteur MSD, Tél: +32.2.726.95.84
Magyarország:
MSD Magyarország Kft, Tel.: + 36.1.888.5300
Malta:
Merck Sharp & Dohme (Middle East) Limited, Tel: +357 22866700
Nederland:
Sanofi Pasteur MSD, Tel: +31.23.567.96.00
Norge:
Sanofi Pasteur MSD, Tlf: +47.67.50.50.20
Österreich:
Sanofi Pasteur MSD GmbH, Tel: +43.1.866.70.22.202
Polska:
MSD Polska Sp. z o.o., Tel.: +48.22.549.51.00
Portugal
: Sanofi Pasteur MSD, SA, Tel: +351 21 470 45 50
România
: Merck Sharp & Dohme Romania S.R.L., Tel: + 4021 529 29 00
Slovenija:
Merck Sharp & Dohme,
inovativna zdravila d.o.o., Tel: +386.1.520.4201
Slovenská republika:
Merck Sharp & Dohme IDEA, Inc., Tel: +421.2.58282010
Suomi/Finland:
Sanofi Pasteur MSD, Puh/Tel: +358.9.565.88.30
Sverige:
Sanofi Pasteur MSD, Tel: +46.8.564.888.60
United Kingdom:
Sanofi Pasteur MSD Ltd, Tel: +44 1 628 785 291
This leaflet was last approved in …………..
81
PACKAGE LEAFLET: INFORMATION FOR THE USER
HBVAXPRO 40 micrograms/ml, suspension for injection
Hepatitis B vaccine (rDNA)
Read all of this leaflet carefully before you are vaccinated.
-
Keep this leaflet. You may need to read it again.
-
If you have any further questions, ask your doctor or pharmacist.
-
If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.
In this leaflet
:
1.
What HBVAXPRO 40 micrograms/ml is and what it is used for
2.
Before you use HBVAXPRO 40 micrograms/ml
3.
How to use HBVAXPRO 40 micrograms/ml
4.
Possible side effects
5.
How to store HBVAXPRO 40 micrograms/ml
6.
Further information
1.
WHAT HBVAXPRO 40 micrograms/ml IS AND WHAT IT IS USED FOR
This vaccine is indicated for active immunisation against hepatitis B virus infection caused by all known
subtypes in predialysis and dialysis adult patients.
It can be expected that hepatitis D will also be prevented by immunisation with HBVAXPRO as hepatitis
D (caused by the delta agent) does not occur in the absence of hepatitis B infection.
The vaccine will not prevent infection caused by other agents such as hepatitis A, hepatitis C and hepatitis
E and other pathogens known to infect the liver.
2.
BEFORE YOU USE HBVAXPRO 40 micrograms / ml
Do not use HBVAXPRO 40 micrograms/ml:
-
if you are allergic (hypersensitive) to hepatitis B surface antigen or to any of the other ingredients of
HBVAXPRO (see section 6.)
-
if you have a severe febrile illness
Take special care with
HBVAXPRO 40 micrograms/ml:
Pregnancy and Breast-feeding:
Caution should be exercised when prescribing to pregnant women.
Breast-feeding is not a contraindication.
Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines:
Some of the rare effects may affect the ability to drive or operate machinery.
Using other vaccines:
82
This vaccine can be administered simultaneously with hepatitis B immunoglobulin, at a separate injection
site.
This vaccine can be used to complete a primary immunisation course or as a booster dose in subjects who
have previously received another hepatitis B vaccine.
This vaccine can be administered concomitantly with other vaccines, using separate sites and syringes.
Please inform your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription.
3.
HOW TO USE HBVAXPRO 40 micrograms/ml
Posology:
The recommended dose for each injection (1 ml) is 40 micrograms for predialysis and dialysis adult
patients
A course of vaccination should include three injections.
The schedule is two injections with an interval of one month followed by a third injection 6 months after
the first administration (0,1,6 months).
A booster dose must be considered in these vaccinees if the antibody level against hepatitis B virus surface
antigen is less than 10 IU/l.
Method of administration:
It should be well shaken until a slightly opaque white suspension is obtained.
The doctor will give the vaccine as an injection into muscle. The upper arm muscle is the preferred site for
injection in adults.
This vaccine should never be given into a vein.
Exceptionally, the vaccine may be administered subcutaneously in patients with thrombocytopoenia
(diminution of blood platelets) or to persons at risk of haemorrhage.
If you forget one dose of HBVAXPRO 40 micrograms/ml:
If you miss a scheduled injection, your doctor will decide when to give the missed dose.
If you have any further questions on the use of this product, ask your doctor or pharmacist.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, HBVAXPRO can cause side effects, although not everybody gets them.
As with other hepatitis B vaccines, in many instances, the causal relationship of side effects to the vaccine
has not been established.
HBVAXPRO is generally well tolerated.
The most common side effects seen are injection-site reactions: soreness, redness and hardening.
83
Other side effects are reported very rarely: low platelet count, lymph node disease, allergic reactions,
nervous system disorders such as pins and needles, facial paralysis, nerve inflammations including
Guillain-Barre Syndrome, inflammation of the nerve of the eye that leads to impaired vision, brain
inflammation, exacerbation of multiple sclerosis,
multiple sclerosis, convulsions, headache, dizziness and
fainting, low blood pressure, blood vessel inflammation, asthma-like symptoms, vomiting, nausea,
diarrhoea, abdominal pain, skin reactions such as eczema, rash, hair loss, itching, hives and skin blistering,
joint pain, arthritis, muscle pain, pain in extremity, fatigue, fever, vague illness, flu-like symptoms and
elevations of liver enzymes.
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 HBVAXPRO 40 micrograms/ml
Keep out of the reach and sight of children.
Do not use HBVAXPRO after the expiry date which is stated on the label.
Store in a refrigerator (2 °C – 8 °C)
Do not freeze
6.
FURTHER INFORMATION
What HBVAXPRO 40 micrograms/ml contains
The active substance is, for one dose of 1 ml:
Hepatitis B virus surface antigen, recombinant (HBsAg) * ................... 40.00 micrograms
Adsorbed on amorphous aluminium hydroxyphosphate sulfate (0.50 milligram Al
+
)
* produced from recombinant strain of the yeast
Saccharomyces cerevisiae
(strain 2150-2-3)
The other ingredients are sodium chloride, borax and water for injections.
What HBVAXPRO 40 micrograms/ml looks like and contents of the pack
Each dose contains 1 ml of suspension for injection in a vial.
Pack size of 1 vial.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder: Sanofi Pasteur MSD SNC, 8 rue Jonas Salk, F-69007 Lyon, France
Manufacturer Responsible for Batch Release: Merck Sharp and Dohme, B.V., Waarderweg, 39, 2031 BN
Haarlem, The Netherlands
For any information about this medicinal product, please contact the local representative of the Marketing
Authorisation Holder.
84
België/Belgique/Belgien:
Sanofi Pasteur MSD, Tél/Tel: +32.2.726.95.84
България:
Мерк Шарп и Доум България ЕООД, Тел. + 359 2 8193740
Česká republika:
Merck Sharp & Dohme, IDEA, Inc., org. sl., Tel.: +420.233.010.111
Danmark:
Sanofi Pasteur MSD, Tlf: +45 23 32 69 29
Deutschland:
Sanofi Pasteur MSD GmbH, Tel: +49.6224.5940
Eesti:
Merck Sharp & Dohme OÜ, Tel: +372.613.9750
Ελλάδα:
ΒΙΑΝΕΞ Α.Ε., Τηλ: +30.210.8009111
España:
Sanofi Pasteur MSD S.A., Tel: +34.91.371.78.00
France:
Sanofi Pasteur MSD SNC, Tél: +33.4.37.28.40.00
Ireland:
Sanofi Pasteur MSD Ltd, Tel: +3531.468.5600
Ísland:
Sanofi Pasteur MSD, Tel: +32.2.726.95.84
Italia:
Sanofi Pasteur MSD Spa, Tel: +39.06.664.092.11
Kύπρος:
Merck Sharp & Dohme (Middle East) Limited., Τηλ: +357 22866700
Latvija:
SIA Merck Sharp & Dohme Latvija, Tel: +371.67364.224
Lietuva:
UAB Merck Sharp & Dohme, Tel.: +370.5.2780.247
Luxembourg/Luxemburg:
Sanofi Pasteur MSD, Tél: +32.2.726.95.84
Magyarország:
MSD Magyarország Kft, Tel.: + 36.1.888.5300
Malta:
Merck Sharp & Dohme (Middle East) Limited, Tel: +357 22866700
Nederland:
Sanofi Pasteur MSD, Tel: +31.23.567.96.00
Norge:
Sanofi Pasteur MSD, Tlf: +47.67.50.50.20
Österreich:
Sanofi Pasteur MSD GmbH, Tel: +43.1.866.70.22.202
Polska:
MSD Polska Sp. z o.o., Tel.: +48.22.549.51.00
Portugal
: Sanofi Pasteur MSD, SA, Tel: +351 21 470 45 50
România
: Merck Sharp & Dohme Romania S.R.L., Tel: + 4021 529 29 00
Slovenija:
Merck Sharp & Dohme,
inovativna zdravila d.o.o., Tel: +386.1.520.4201
Slovenská republika:
Merck Sharp & Dohme IDEA, Inc., Tel: +421.2.58282010
Suomi/Finland:
Sanofi Pasteur MSD, Puh/Tel: +358.9.565.88.30
Sverige:
Sanofi Pasteur MSD, Tel: +46.8.564.888.60
United Kingdom:
Sanofi Pasteur MSD Ltd, Tel: +44 1 628 785 291
This leaflet was last approved in ………….
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Source: European Medicines Agency
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