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VIATIM SUSPENSION AND SOLUTION FOR SUSPENSION FOR INJECTION IN PRE-FILLED SYRINGE

Active substance(s): HEPATITIS A VIRUS INACTIVATED / SALMONELLA TYPHI TY2 VI CAPSULAR POLYSACCHARIDE PURIFIED

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SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT
ViATIM, Suspension and solution for suspension for injection in pre-filled syringe.

Hepatitis A (inactivated, adsorbed) and Typhoid polysaccharide vaccine

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
The dual-chamber syringe contains 0.5 millilitre of inactivated hepatitis A
vaccine and 0.5 millilitre of typhoid polysaccharide vaccine which are mixed
prior to administration.
After reconstitution, 1 dose (1ml) contains:
Originally contained in the suspension:
Hepatitis A virus, GBM strain (inactivated)1,2………….160 U3
1
produced in human diploid (MRC-5) cells
2
adsorbed on aluminium hydroxide, hydrated (0.3 milligrams Al)
3
In the absence of an international standardised reference, the antigen content
is expressed using an in-house reference
Originally contained in the solution:
Salmonella typhi (Ty 2 strain) capsular Vi polysaccharide………25
micrograms
For the full list of excipients, see section 6.1.
ViATIM may contain traces of neomycin, which is used during the
manufacturing process (see section 4.3).

3

PHARMACEUTICAL FORM
Suspension and solution for suspension for injection in pre-filled syringe.
The inactivated hepatitis A vaccine is a cloudy and white suspension and the
typhoid polysaccharide vaccine is a clear and colourless solution.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
ViATIM is indicated for simultaneous active immunisation against typhoid
fever and hepatitis A virus infection in subjects from 16 years of age.
ViATIM should be given in accordance with official recommendations.

4.2

Posology and method of administration
Posology
The recommended dosage for subjects of at least 16 years of age is 1 millilitre
of the mixed vaccine.
Initial protection is achieved with one single dose of ViATIM. Protective
levels of antibody may not be reached until 14 days after administration of the
vaccine.
In order to provide long-term protection against infection caused by the
hepatitis A virus, a second dose (booster) of an inactivated hepatitis A vaccine
should be given. ViATIM may be used to provide one or both doses of
hepatitis A vaccine as follows:


In subjects who have received one dose of ViATIM:
- either a dose of monovalent hepatitis A vaccine should be given within
36 months and preferably within 6 to 12 months (see section 5.1)
- or, if continued protection against typhoid is also required, a second
dose of ViATIM may be given provided that approximately 36 months
have elapsed since the first dose.



In subjects who have received one dose of monovalent hepatitis A vaccine:
- ViATIM may be used to provide the second dose (booster) of hepatitis
A vaccine if protection against typhoid fever is also desirable. It should
be given within 36 months of the hepatitis A vaccine and preferably
within 6 to 12 months.

It is predicted that HAV antibodies persist for many years (beyond 10 years)
after the second dose (booster).
In subjects who remain at risk of typhoid fever, revaccination against typhoid
fever should be carried out with a single dose of a typhoid Vi polysaccharide
vaccine every 3 years (see section 5.1).
Paediatric population
The safety and efficacy of ViATIM in children and adolescents below 16
years have not yet been established. No data are available.
Method of administration
ViATIM should be administered by slow intramuscular injection in the deltoid
region.
ViATIM must not be administered intravascularly.

ViATIM should not be administered into the buttocks due to the varying
amount of fatty tissue in this region, nor by the intradermal route, since these
methods of administration may induce a weaker immune response. ViATIM
may be administered by the subcutaneous route in patients with
thrombocytopenia or in those at risk of haemorrhage.
For instructions for preparation of the medicinal product before
administration, see section 6.6.

4.3

Contraindications
Hypersensitivity to the active substance(s) or to any of the excipients listed in
section 6.1 or to neomycin (present in trace amounts as a residual of the
manufacturing process).
Vaccination should be delayed in subjects with an acute severe febrile illness.

4.4

Special warnings and precautions for use
As with all vaccines, appropriate facilities and medication such as epinephrine
(adrenaline) should be readily available for immediate use in case of
anaphylaxis or hypersensitivity following injection.
Syncope (fainting) can occur following, or even before, any vaccination
especially in adolescents as a psychogenic response to the needle injection.
This can be accompanied by several neurological signs such as transient visual
disturbance, paraesthesia and tonic-clonic limb movements during recovery. It
is important that procedures are in place to avoid injury from faints.
Immunogenicity of ViATIM could be impaired by immunosuppressive
treatment or in immunodeficient subjects. It is recommended to delay
vaccination until the completion of any immunosuppressive treatment.
Subjects with chronic immunodeficiency such as HIV infection may be
vaccinated if the underlying immunodeficiency allows the induction of an
antibody response, even if limited.
Because of the incubation period of hepatitis A disease, infection may be
present but not clinically apparent at the time of vaccination. It is not known
whether ViATIM will prevent hepatitis A in this case.
ViATIM does not protect against infection caused by other known liver
pathogens including hepatitis B, hepatitis C and hepatitis E viruses.
ViATIM does not protect against infection by Salmonella enterica other than
serotype typhi.

As with any vaccine, a protective immune response may not be elicited in all
vaccinees.

4.5

Interaction with other medicinal products and other forms of interaction
ViATIM must not be mixed with any other vaccine in the same syringe.
Concomitant administration of ViATIM with the combined, adsorbed, tetanus,
low dose diphtheria and inactivated poliomyelitis vaccine (Td-IPV) at two
separate sites demonstrated non-inferiority compared to the separate
administration of the two vaccines at different time points for all valences,
except for the Vi valence, in terms of immune response obtained one month
after vaccination. Nevertheless, anti-Vi seroconversion rate (≥ 4-fold rise) for
concomitant administration was non-inferior to the separate administration in
subjects who were not seroprotected before vaccination (see section 5.1).
Since the seroprotection rate (the percentage of subjects reaching the threshold
of protection for anti-Vi antibodies ≥1 μg/mL) was consistent with the
expected range of responses when ViATIM is given alone, it is unlikely that
concomitant administration of ViATIM and the Td-IPV at different sites will
have clinical consequences. Therefore, concomitant administration of ViATIM
with the Td-IPV at two separate sites can be performed.
No interaction studies have been performed with ViATIM and other
inactivated vaccines. However, based on data obtained from the concomitant
administration of the monovalent typhoid Vi polysaccharide vaccine with
diphtheria-tetanus (DT), tetanus-inactivated poliomyelitis (T-IPV), rabies,
meningococcal polysaccharide A/C and hepatitis B vaccines and from the
concomitant administration of the monovalent inactivated hepatitis A vaccine
with hepatitis B vaccines, no interference with the immune responses to any of
these antigens would be expected.
Concomitant administration of yellow fever vaccine with ViATIM has not
been specifically assessed. However, based on data obtained from the
concomitant administration of the monovalent vaccines (typhoid Vi
polysaccharide vaccine and inactivated hepatitis A vaccine) with yellow fever
vaccine, no interference with the immune responses to any of these antigens
would be expected.
The effect of concomitant administration of immunoglobulins on the
immunogenicity of ViATIM has not been assessed. Therefore, interference
with the immune response of ViATIM cannot be ruled out. Data obtained from
concomitant administration of immunoglobulins with the monovalent
inactivated hepatitis A vaccine showed that anti-HAV seroconversion rates
were not modified whereas anti-HAV antibody titres could be lower than after
vaccination with the monovalent vaccine alone.

4.6

Pregnancy and lactation

Pregnancy
Data on a limited number (more than 150 cases with monovalent typhoid Vi
polysaccharide vaccine, more than 40 cases with monovalent inactivated
hepatitis A vaccine and more than 10 cases with ViATIM or the two
components given simultaneously) of exposed pregnancies indicate no adverse
effects of ViATIM on pregnancy or on the health of the foetus/new born child.
To date no other relevant epidemiological data are available. Animal studies
do not indicate direct or indirect harmful effects with respect to pregnancy,
embryonal/foetal development, parturition or post-natal development (see
section 5.3).
Caution should be exercised when prescribing to pregnant women.
When the patient is considered to be at risk of only one of hepatitis A or
typhoid fever, the monovalent vaccine should be used.
Breast-feeding
It is unknown whether ViATIM is excreted in human breast milk. The
excretion of ViATIM in milk has not been studied in animals. A decision on
whether to continue/discontinue breast-feeding or to administer or not
administer ViATIM should be made taking into account the benefit of breastfeeding to the child and the benefit of ViATIM to the woman.
Fertility
No fertility data are available.

4.7

Effects on ability to drive and use machines
ViATIM has a minor influence on the ability to drive and use machines.
Dizziness has been observed as an uncommon reaction (≥1/1000, <1/100)
following administration of this vaccine (see section 4.8).

4.8

Undesirable effects
a. Summary of the safety profile
During clinical studies, the most commonly reported reactions were those
occurring at the injection site.
Pain at the ViATIM injection site was reported in 89.9% of subjects (severe in
4.5%). For subjects who received the two monovalent vaccines concomitantly
at separate injection sites, pain was reported in 83.2% of subjects (severe in
5.0%) for both vaccine sites combined. Pain was reported by 79.3% of
subjects (severe in 5.0%) at the Vi vaccine site and by 50.3% of subjects
(severe in 0.6%) at the hepatitis A vaccine site.

Pain at the injection site lasting more than 3 days was reported by 17.4% of
subjects after ViATIM, by 2.8% of subjects for the monovalent Vi vaccine site
and by 0.6% of subjects for the monovalent hepatitis A vaccine site.
Severe oedema/induration (> 5 cm) was reported in 7.9% of subjects at the
ViATIM site. For subjects who received the two monovalent vaccines
concomitantly at separate injection sites, severe oedema/induration was
reported in 1.7% of subjects for both vaccine sites combined (in 1.1% of
subjects at the Vi vaccine site and in 0.6% of subjects at the hepatitis A
vaccine site).
The overall incidence of systemic reactions was similar between subjects who
were vaccinated with ViATIM and subjects who received the two monovalent
vaccines concomitantly at separate injection sites.
All reactions resolved without any sequelae.
b. Tabulated list of adverse reactions
Adverse reaction data are derived from clinical trials and worldwide post
marketing experience.
Within each system organ class the adverse reactions are ranked under
headings of frequency, most frequent reactions first, using the following
convention:
Very common (≥1/10),
Common (≥1/100, <1/10),
Uncommon (≥1/1000, <1/100),
Rare (≥1/10,000, <1/1000),
Very rare (<1/10,000),
Not known: cannot be estimated from the available data. Based on
spontaneous reporting, these adverse events have been very rarely reported
following commercial use of ViATIM. Because events are reported
voluntarily from a population of uncertain size, it is not always possible to
reliably estimate their frequency or establish a causal relationship to vaccine
exposure.
Within each frequency grouping, adverse reactions are ranked in order of
decreasing seriousness.
Immune system disorders
Not known: anaphylactic/anaphylactoid reactions, including shock; serum
sickness.
Nervous system disorders
Very common: headache.
Uncommon: dizziness.
Not known: vasovagal syncope in response to injection, paraesthesia.
Gastrointestinal disorders
Common: nausea, diarrhoea.
Not known: vomiting, abdominal pain.
Skin and subcutaneous tissue disorders
Uncommon: pruritus, rash.

Not known: urticaria.
Musculoskeletal and connective tissue disorders
Very common: myalgia.
Common: arthralgia.
General disorders and administration site conditions
Very common: malaise, asthenia, injection site disorders (pain, induration,
oedema, erythema).
Common: fever.
Investigations
Not known: transaminases increased (mild and reversible).
The following adverse reactions were not reported during the commercial use
of ViATIM but were reported respectively following the use of the
monovalent typhoid Vi polysaccharide vaccine and the monovalent inactivated
hepatitis A vaccine:
Respiratory, thoracic and mediastinal disorders
Not known: aggravation of asthma.
General disorders and administration site conditions
Very rare: injection site nodule.
c. Paediatric Population
No data on the safety of ViATIM in children and adolescents below 16 years
are available.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal
product is important. It allows continued monitoring of the benefit/risk balance
of the medicinal product. Healthcare professionals are asked to report any
suspected adverse reactions via the Yellow Card Scheme at:
https://yellowcard.mhra.gov.uk/.

4.9

Overdose
Cases of overdose have been reported with ViATIM where it was
administered concomitantly with typhoid polysaccharide and/or hepatitis A
vaccines. When adverse reactions were reported, they did not differ in nature
from those described in section 4.8.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: Bacterial and viral vaccines combined
ATC code: J07CA10 typhoid-hepatitis A

Four clinical studies provided useful data on immune responses to ViATIM. A
total of 1090 subjects were included, with 179, 610, 243 and 58 subjects
vaccinated in each study.
After the primary vaccination the seroprotection rate for HAV (% ≥
20mIU/mL) ranged between 95.6% and 99.4% after 14 days and
between 98.7% and 100% after 28 days.
The seroprotection rate for Vi (%≥1µg/mL) ranged between 83% and 89%
after 14 days and between 69.8% and 91% after 28 days.
In one study that evaluated anti-Vi antigen seroprotection rates at years 1, 2
and 3 after the first dose of ViATIM and after re-vaccination with ViATIM at
year 3, results were as follows:

Year 1

Number of
vaccinees
% of vaccinees
seroprotected
(95% CI)

Year 2

ViATIM
Year 3

28 days after
Revaccination at
Year 3

139

124

112

46

44.6

40.3

32.1

69.6

(36.2-53.3) (31.6-49.5) (23.6-41.6)

(54.2-82.3)

Serological data show continuing protection against hepatitis A for up to 36
months in subjects who responded to the first dose of ViATIM. Anti-HAV antigen
seroprotection rates at years 1, 2 and 3 after the first dose of ViATIM and after revaccination with ViATIM at year 3 were as follows:

Year 1

Number of
vaccinees
% ≥ 20 mIU/ml
(95% CI)

140
99.3
(96.1-100)

Year 2

124
98.4

ViATIM
Year 3

112
99.1

(94.3-99.8) (95.1-100)

28 days after
Revaccination at
Year 3
46
100
(92.3-100)

Similar results were seen at all timepoints in the control group who received
concomitant monovalent typhoid Vi polysaccharide and inactivated hepatitis A
vaccines.

In an open randomised study, the immunogenicity of the concomitant
administration of ViATIM with the combined, adsorbed, tetanus, low dose
diphtheria and inactivated poliomyelitis vaccine (Td-IPV) at two separate sites was
compared to the separate administration at different time points in healthy adults.
Seroconversion/seroprotection rates observed 28 days after vaccination in Per
Protocol subjects were as follows:
Group A
(Concomitant administration)
N=161

Anti-HAV seroconversion rate (≥ 20 mIU/mL)
n (%)
139 (100%)*
[95% CI]
[97.3; 100.0]
Anti-Vi seroconversion rate (≥ 4-fold rise)
n (%)
134 (83.2%)
[95% CI]
[76.7; 88.2]
Anti-D seroprotection rate (≥ 0.1 IU/mL)
n (%)
158 (98.1%)
[95% CI]
[94.7; 99.4]
Anti-T seroprotection rate (≥ 0.1 IU/mL)
n (%)
161 (100%)
[95% CI]
[97.7; 100.0]
Anti-Polio 1 {1/dil} seroprotection rate (≥ 5)
n (%)
161 (100%)
[95% CI]
[97.7; 100.0]
Anti-Polio 2 {1/dil} seroprotection rate (≥ 5)
n (%)
161 (100%)
[95% CI]
[97.7; 100.0]
Anti-Polio 3 {1/dil} seroprotection rate (≥ 5)
n (%)
161 (100%)
[95% CI]
[97.7; 100.0]
* N=139 (initially HAV seronegative subjects)
** N=127 (initially HAV seronegative subjects)

Group B
(Separate administration)
N=154
127 (100%)**
[97.1; 100.0]
135 (87.7%)
[81.5; 92.0]
149 (96.8%)
[92.6; 98.6]
154 (100%)
[97.6; 100.0]
154 (100%)
[97.6; 100.0]
154 (100%)
[97.6; 100.0]
154 (100%)
[97.6; 100.0]

Non-inferiority of the concomitant administration of ViATIM and Td-IPV
vaccines compared to the separate administration was demonstrated for all the
valences, except for the Vi valence.
For the Vi valence, the seroprotection rates (anti-Vi titres ≥ 1 μg/mL) increased
from 7.5% in Group A and 7.1% in Group B at Day 0 to 86.3% and 94.8%
respectively, 28 days after vaccination. In initially non-protected individuals (antiVi titres < 1 μg/mL), seroconversion rates observed 28 days after vaccination were
as follows:

Anti-Vi seroconversion rate (≥ 4-fold rise)
n (%)
[95% CI]

Group A
(Concomitant administration)
N=149

Group B
(Separate administration)
N=143

132 (88.6%)
[82.5 , 92.8]

128 (89.5%)
[83.4 , 93.5]

In initially non-protected individuals, the anti-Vi seroconversion rate (≥ 4-fold rise)
for concomitant vaccines administration was non-inferior to the separate
administration.
Paediatric Population

No data on the efficacy of ViATIM in children and adolescents below 16 years are
available.

5.2

Pharmacokinetic properties
Not applicable.

5.3

Preclinical safety data
Non-clinical data obtained with this vaccine, or with the monovalent vaccines
contained within this combined vaccine, reveal no special hazard for humans
based on single, repeated dose and local tolerance toxicity studies.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Inactivated hepatitis A vaccine component:
2-Phenoxyethanol solution
Formaldehyde
Medium 199 Hanks (without phenol red)* supplemented with polysorbate 80
*Medium 199 Hanks (without phenol red) is a complex mixture of amino
acids (including phenylalanine), mineral salts, vitamins and other components
(including glucose), diluted in water for injections and pH adjusted with
hydrochloric acid or sodium hydroxide
Typhoid Vi polysaccharide vaccine component:
Phosphate buffer solution:
Sodium chloride
Disodium phosphate dihydrate
Sodium dihydrogen phosphate dihydrate
Water for Injections

6.2

Incompatibilities
In the absence of compatibility studies, this vaccine must not be mixed with
other vaccines or 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.
Keep the vaccine in the outer carton in order to protect from light.

6.5

Nature and contents of container
Dual-chamber pre-filled syringe (type I glass): 0.5 ml of suspension in the
chamber closest to the plunger and 0.5 ml of solution in the chamber closest to
the needle, with a plunger-stopper (chlorobutyl and bromobutyl rubber
elastomer blend), a tip cap (elastomer) and a by-pass stopper (elastomer).
Pack size of 1 or 10 pre-filled syringes supplied with or without needle.
Not all pack sizes may be marketed

6.6

Special precautions for disposal
The two vaccine components should only be mixed immediately prior to
injection.
Shake before mixing and again prior to injection to obtain a homogeneous
suspension. The contents of the two chambers are mixed by slowly advancing
the plunger. The final volume to be injected is 1 millilitre.
The vaccine should be visually inspected before administration for any foreign
particulate matter. The mixed vaccine is a cloudy, whitish suspension. The
vaccine should not be used in case of unexpected particles in it.
Any unused medicinal product or waste material should be disposed of in
accordance with local requirements.

7

MARKETING AUTHORISATION HOLDER

Sanofi Pasteur Europe

2 Avenue Pont Pasteur
69007 Lyon
FRANCE
Distributed in the UK by:
Sanofi
One Onslow Street
Guildford
Surrey
GU1 4YS

8

MARKETING AUTHORISATION NUMBER(S)
PL 46602/0009

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
02/09/2006

10

DATE OF REVISION OF THE TEXT
10/02/2017

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