VIVAXIM

COMBINED TYPHOID (PURIFIED Vi POLYSACCHARIDE) AND HEPATITIS A

(INACTIVATED) VACCINE
Suspension for injection in a prefilled dual chamber syringe

Read all of this leaflet carefully before you are vaccinated.

- Keep this leaflet until you have completed the vaccination schedule. You may need to
read it again.
- Follow carefully the advice of your doctor or nurse. If you have further questions, please
ask your doctor or nurse.
- Make sure you complete the full vaccination schedule. Otherwise you may not be fully
vaccinated. This vaccine has been prescribed for you personally and you should not pass
it on to others.
For a 1 ml dose of the mixed vaccine: The active substances are:
- Salmonella typhi (strain Ty 2) capsular polysaccharide (purified Vi) …. 25 micrograms
- Inactivated hepatitis A virus* …………………………………… 160 antigenic units**
Adjuvant for inactivated hepatitis A vaccine:
- Aluminium hydroxide …. 0.3 milligrams of Al3+
*GBM strain grown on MRC-5 human diploid cells.
**As there is no standardized international reference, the antigen content is expressed
using an in-house reference
The other ingredients are:
Phosphate buffer solution (sodium chloride, disodium phosphate dihydrate, sodium dihydrogen
phosphate dihydrate and water for injections), 2-phenoxyetanol solution, formaldehyde and
Hanks medium 199 (without phenol red) supplemented with polysorbate 80.

Pada proses pembuatannya bersinggungan dengan bahan bersumber babi

MARKETING AUTHORIZATION HOLDER & MANUFACTURER BY

Sanofi Pasteur SA
2, avenue du Pont Pasteur – 69007 Lyon – France
PHARMACODYNAMIC PROPERTIES
The immunogenicity profile of VIVAXIM was assessed on approximately 800 subjects (aged
from 16 to 65 years) included in 3 clinical trials.
Fourteen day after vaccination with VIVAXIM 86.4% of subjects (153/177) seroconverted for
typhoid fever, with a fourfold increase in pre-vaccination antibody titers (measured in µg/ml)
and 95.6% (153/160) of initially HAV seronegative subjects seroconverted (anti-HAV antibody
titers above 20 mlU/ml) for hepatitis A. When vaccine against typhoid fever and hepatitis A were
administered simultaneously at different injection sites, the percentage of subjects who
seroconverted was 88.2% (157/178) for typhoid fever and 94.2% (146/155) for hepatitis A.
One month after vaccination with VIVAXIM, 90.4% (703/778) of subject seroconverted for Vi
antigen and 99.7% (736/738) for hepatitis A. After simultaneous administration of a vaccine
against typhoid fever an inactivated hepatitis A vaccine at two separate sites, the percentage of
seroconversion was 84.9% (146/172) for typhoid fever and 100% (149/149) for hepatitis A.
Follow-up data showed that the persistence of anti-HAV and anti-Vi antigens was identical two
years after for subjects vaccinated with VIVAXIM and subjects given the two monovalent
vaccines simultaneously at separate injection sites.

Preclinical safety data

Pre-clinical safety data obtained with the monovalent vaccines contained in this vaccine
combination reveal no special hazard for humans.

1. WHAT IS VIVAXIM AND WHAT IS IT USED FOR?

VIVAXIM is indicated for combined active immunization against typhoid fever and infection
with Hepatitis A virus in subjects aged 16 years or more.
VIVAXIM must be administered according to official recommendations.

2. INFORMATION REQUIRED BEFORE YOU USE VIVAXIM?

Special warnings and special precautions for use
As for all injectable vaccine, suitable medical treatment and in particular adrenaline must be
available for immediate management of any anaphylactic or hypersensitivity reactions occurring
after vaccine administration.
The immunogenicity of the vaccine may be reduced in patients receiving immunosuppressant
drugs or suffering from immune deficiency disorders. In this case treatment should be delayed
until all immunosuppressant treatment has been discontinued. Subjects with chronic immune
deficiency still allows induction of an antibody response, even if the response might be limited.
As hepatitis A has a long incubation period, infection may have occurred but clinical symptoms
may not have appeared at the time of vaccination. In this case, VIVAXIM may not protect
against hepatitis A. VIVAXIM does not protect against infections caused by other hepatitis-
inducing agents such as hepatitis B, C or E viruses.
VIVAXIM does not protect against infections caused by Salmonella enterica other than the typhi
serotype. As for all vaccine, a protective immune response is not acquired by all vaccinated
subjects.

Do not use VIVAXIM:

- If you are allergic to one of the ingredients of the vaccine.
- If you are allergic to neomycin as substance is used during the manufacture of the
vaccine.
- Delay vaccination if you are feverish, shivering or suffering pain.

Take special care with VIVAXIM:

- To make sure that the vaccine is not administered by the intravascular route (the needle
must not penetrate a blood vessel).
- Not to inject VIVAXIM in the buttock as this may induce a smaller immune response
(because of the variable amount of fat tissue in this region of the body).
- If you are receiving a treatment that lowers immune deficiency or if you present deficient
immune defenses, the immune response to the vaccine may be reduced.
- If you suffer from blood clotting disorders, VIVAXIM must be injected subcutaneously.
- If you may soon be exposed to hepatitis A or typhoid fever, take care as protection
conferred by VIVAXIM only appears 14-day vaccination.

Pregnancy and lactation

This vaccine should not be used during pregnancy or lactation except where otherwise indicated
by your doctor.
If you discover that you are pregnant, inform your doctor who will adjust the vaccination
schedule to your situation.
Data on use during pregnancy are available for more than 150 cases for monovalent Vi
polysaccharide typhoid vaccine, more than 40 cases for inactivated monovalent hepatitis A
vaccine and more than 10 cases for VIVAXIM when the two components are administered
simultaneously.
The data showed no adverse effects on pregnancy or the health of the fetus or infant. Studies in
experimental animals carried out with monovalent Vi polysaccharide typhoid vaccine failed to
show any direct or indirect harmful effects on pregnancy, embryonic or fetal development,
delivery, or postnatal development. However, VIVAXIM may only be used in pregnancy after
careful assessment of the risk-benefit ratio. When the patient is considered to be a high risk
subject for hepatitis A alone or typhoid fever alone, a monovalent vaccine must be used.
There is no data on the administration of VIVAXIM during lactation.
VIVAXIM must only be used during lactation after careful evaluation of the risk-benefit ratio.

Driving and using machines

If a few rare cases vertigo has been observed following the administration of this vaccine.

Contraindication
Known hypersensitivity to one of the ingredients of VIVAXIM.
Known hypersensitivity to neomycin (presence of residual of traces of neomycin due to its use
during manufacture).
Vaccination must not delayed in the case of severe acute infection with fever.

Use of other vaccines

VIVAXIM must not be mixed with other vaccines in same syringe.
VIVAXIM is a combination of a purified Vi polysaccharide typhoid vaccine and an inactivated
hepatitis A vaccine. Although the simultaneous administration of VIVAXIM with other
inactivated vaccines using different syringe and injection sites, has not been specifically studied,
no interactions are expected. Concomitant administration of yellow fever vaccine and VIVAXIM
has not been specifically studied. However, data obtained during simultaneous administration of
monovalent vaccines (purified Vi polysaccharide typhoid vaccine and inactivated hepatitis A
vaccine) with yellow fever vaccine show that no interference between the immune response to
these three antigens is expected. The effect of the concomitant administration of
immunoglobulins on the immunogenicity of VIVAXIM has not been evaluated. However,
interference with the immune response to VIVAXIM cannot be excluded. Data obtained during
concomitant administration of immunoglobulins and inactivated monovalent hepatitis A vaccine
showed that rates of seroconversion were unchanged even though the anti-HAV antibody titers
were sometimes lower than after vaccination with a monovalent vaccine alone.

3. HOW USE VIVAXIM?

Posology:
The recommended dose is 1 ml of mixed vaccine.
Initial protection is obtained after a single injection of VIVAXIM. Protective antibody levels are
only obtained 14 days after administration of the vaccine.
In order to obtain long term protection against hepatitis A virus, a booster dose of inactivated
hepatitis A virus must be given 6 to 12 month later. Anti HAV antibodies persist for several
years (at least 10 years) after the booster.
Limited data available suggest that a booster dose of VIVAXIM may be administered to subjects
who have received a first injection with another anti-hepatitis A vaccine 6 to 12 months earlier
and who also require protection against typhoid fever.
In subject who remain exposed to the risk of typhoid, vaccination with a single dose of purified
Vi polysaccharide typhoid vaccine must be repeated every three years, but if it is also necessary
to administer a booster hepatitis A vaccine VIVAXIM may be used.
As this vaccine has not been evaluated in subjects aged under 16 years, it is not recommended to
use in this age group.

Method of administration
VIVAXIM is a vaccine in a prefilled dual chamber syringe containing 0.5 ml of purified Vi
polysaccharide typhoid vaccine and 0.5 ml of inactivated hepatitis A vaccine, which are mixed
before administration. The two monovalent vaccines must be mixed immediately before
injection.
Shake and mix the contents of the two compartments by gently pushing the plunger.
Shake to obtain a homogeneous suspension before injection.
Make a visual check of the absence of any foreign particles in the vaccine before administration.
The mixed vaccine is a whitish opalescent suspension.
The final volume to be injected is 1 ml.
Administer by intramuscular route.
VIVAXIM must be given by slow intramuscular injection in the deltoid muscle.
VIVAXIM must not be given by the intravascular route.
VIVAXIM must not be injected in the buttock, because of the variable of adipose tissue in this
region of the body, or by the intradermal route, as these methods of administration may cause a
reduced immune response. VIVAXIM may be administered subcutaneously in patients suffering
from thrombocytopenia or a risk of hemorrhage.

4. WHAT ARE THE POSSIBLE UNDESIRABLE EFFECTS?

The safety profile of VIVAXIM was evaluated in approximately 800 subjects included in three
clinical trials. The most frequently observed reactions were those observed at the injection site.
Pain at the VIVAXIM injection site was reported by 89.9% of subjects (severe in 4.5% of cases).
Pain was reported by 83.2% of subjects given the two monovalent vaccines simultaneously at
two separate injection sites (severe in 5.0% of cases) for the two sites combined. Injection site
pain was reported by 79.3% of subjects vaccinated with the typhoid vaccine (severe in 5.0% of
cases) and by 50.3% of subjects vaccinated with hepatitis A vaccine (severe in 0.6% of cases).
Injection site pain persisting for more than 3 days was reported by 17.4% of subjects after
vaccination with VIVAXIM 2.8% of subjects after vaccination with monovalent Vi vaccine and
0.6% of subjects with monovalent hepatitis A vaccine.
Severe injection site edema/induration (>5cm) was reported by 7.9% of subjects vaccinated with
VIVAXIM. For subjects vaccinated simultaneously with two monovalent vaccines at different
injection sites, severe edema/induration was reported in 1.7% of subjects for two injection sites
combined (1.1% of subject at the typhoid injection site and 0.8% at the hepatitis A injection site).
The overall incidence of systemic reactions was similar in subjects vaccinated with VIVAXIM
and in subjects vaccinated simultaneously with the 2 monovalent vaccines at two separate
injection sites. All reactions disappeared spontaneously without sequelae.
The following adverse reactions were observed with VIVAXIM.
Nervous system disorders, rare (0.1-1%): Dizziness.
Gastrointestinal disorders, frequent (1-10%): nausea, diarrhea.
Cutaneous or subcutaneous tissue disorders, rare (0.1-1%): pruritic, rash.
Musculoskeletal, connective tissue and bone disorders, frequent (1-105): myalgia, arthralgia.
Systemic disorder very frequent (>10%): asthenia, headache and frequent (1-10%): malaise,
fever
Disorder at injection site, very frequent (>10%): pain, induration/edema and erythema.
Adverse effects reported after the use of a purified monovalent Vi polysaccharide vaccine (and
not listed above for VIVAXIM) comprise:
Rare cases of vomiting and abdominal pain have been reported. Allergic reactions such as serum
sickness, urticaria and anaphylactic reactions, worsening of asthma and paresthesia have been
reported very rarely. Adverse effects reported after the use of a monovalent hepatitis A vaccine
(and not listed above for VIVAXIM) comprise:
A nodule at the injection site was observed in a few, very rare, cases. Transient, moderate
elevation of transaminase levels occurred rarely. Skin reaction such as urticaria were reported in
a few rare cases after marketing.

5. HOW TO STORE VIVAXIM

Keep out of the reach and sight of children.
Store in refrigerator at between +2°C and +8°C. Do not freeze.
Do not use after the expiry date stated on the label and the box.
Do not use VIVAXIM if you notice the presence of foreign particles.

Harus dengan resep dokter

IMPORTED BY:
PT Aventis Pharma
Jakarta, Indonesia
Reg. No. DKI1159702843A1