Vaxigrip 20 Professional 20 Insert 2021

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PROFESSIONAL INFORMATION FOR VAXIGRIP TETRA
SCHEDULING STATUS S2
1. NAME OF THE MEDICINE
VAXIGRIP TETRA 2024 strains suspension for injection
Quadrivalent influenza vaccine (split virion, inactivated).
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Composition per 0,5 mL dose:
Active substance:
Split influenza virus, inactivated strains for 2024 Southern Hemisphere
A/Victoria/4897/2022 (H1N1)pdm09-like strain (A/Victoria/4897/2022, IVR-238) 15 micrograms*
A/Thailand/8/2022 (H3N2)-like strain (A/California/122/2022, SAN-022) 15 micrograms*
B/Austria/1359417/2021-like strain (B/Michigan/01/2021, wild type) 15 micrograms*
B/Phuket/3073/2013-like strain (B/Phuket/3073/2013, wild type) 15 micrograms*
* Haemagglutinin
This vaccine complies with WHO Southern Hemisphere recommendations for the 2024 season.
Sugar free.
For the full list of excipients, see section 6.1.
VAXIGRIP TETRA may contain traces of eggs, such as ovalbumin, and of neomycin,
formaldehyde and octoxinol-9, which are used during the manufacturing process (see section 4.3).
3. PHARMACEUTICAL FORM
Suspension for injection.
Colourless opalescent liquid and free from visible particulate matter, presented in a pre-filled
syringe that contains one dose of 0,5 mL.

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4. CLINICAL PARTICULARS
4.1 Therapeutic indications
VAXIGRIP TETRA is indicated for the prevention of influenza disease caused by the two influenza
A virus subtypes and the two influenza B virus types contained in the vaccine for:
• active immunisation of adults, including pregnant women, and children from 6 months of age
and older,
• passive protection of infant(s) from birth to less than 6 months of age following vaccination of
pregnant women (see sections 4.4, 4.6 and 5.1).
4.2 Posology and method of administration
Posology
Due to the variation of the influenza virus and the duration of immunity provided by the vaccine, it
is recommended to perform vaccination against influenza every year at the beginning of the risk
period.
Adults: one dose of 0,5 mL.
Paediatric population:
• Children from 6 months to 17 years of age: one dose of 0,5 mL.
For children less than 9 years of age who have not previously been vaccinated, a second dose
of 0,5 mL should be given after an interval of at least 4 weeks.
• Infants less than 6 months of age: the safety and efficacy of VAXIGRIP TETRA administration
(active immunisation) have not been established. No data are available.
Regarding passive protection: one 0,5 mL dose given to pregnant women may protect infants
from birth to less than 6 months of age; however, not all these infants will be protected (see
section 5.1).
Method of administration
The vaccine should be given by intramuscular or deep subcutaneous injection.

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The preferred sites for intramuscular injection are the anterolateral aspect of the thigh (or the
deltoid muscle, if muscle mass is adequate) in children 6 months through 35 months of age, or the
deltoid muscle in children from 36 months of age and adults.
Precautions to be taken before handling or administering VAXIGRIP TETRA:
For instructions on preparation of VAXIGRIP TETRA before administration, see section 6.6.
4.3 Contraindications
VAXIGRIP TETRA should not be administered to subjects with a history of severe allergic reaction
to egg proteins (eggs or egg products), to chicken proteins, to any component of the vaccine (i.e.
as defined under sections 2 and 6.1 including manufacturing residuals) or a history of severe
allergic reaction after previous administration of VAXIGRIP TETRA or a vaccine containing the
same components.
Administration of VAXIGRIP TETRA should be postponed in subjects suffering from moderate or
severe febrile disease or acute disease.
4.4 Special warnings and precautions for use
As each dose may contain undetectable traces of neomycin, which is used during vaccine
production, caution should be exercised when VAXIGRIP TETRA is administered to subjects with
hypersensitivity to this antibiotic (and other antibiotics of the same class).
Vaccination with VAXIGRIP TETRA may not protect all vaccinees.
Regarding passive protection, not all infants less than 6 months of age born to women vaccinated
during pregnancy will be protected (see section 5.1).
Influenza virus is remarkably unpredictable in that significant antigenic changes may occur from
time to time.
It is known that VAXIGRIP TETRA as constituted per annual seasonal composition, is not effective
against all possible strains of influenza virus.
VAXIGRIP TETRA is intended to provide protection against those strains of virus from which the
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vaccine is prepared.
If VAXIGRIP TETRA is used in immunocompromised persons whether due to genetic,
immunodeficiency disease, or immunosuppressive therapy, they may have a reduced immune
response to vaccination.
Interference with serological testing
See section 4.5.
Do not administer VAXIGRIP TETRA by intravascular injection.
• The vaccine must be administered with caution to subjects with thrombocytopenia or a bleeding
disorder, since bleeding may occur following an intramuscular administration to these subjects.
• Appropriate medical treatment and supervision should be readily available for immediate use in
case of an anaphylactic reaction following the administration of the vaccine.
• As a precautionary measure, adrenaline (epinephrine) injection (1:1 000) must be immediately
available in case of unexpected anaphylactic or serious allergic reactions.
• Syncope (fainting) can occur following, or even before, any vaccination as a psychogenic
response to the needle injection. Procedures should be in place to prevent falling injury and
manage syncopal reactions.
4.5 Interaction with other medicines and other forms of interaction
No studies regarding the simultaneous administration of VAXIGRIP TETRA and other vaccines
have been conducted.
Nevertheless, clinical data showing that VAXIGRIP can be administered concomitantly with other
vaccines are available for the following vaccines: Pneumococcal polysaccharide vaccine in elderly
subjects, Tdap-IPV (Adacel QUADRA®) in adults aged ≥ 60 years and zoster vaccine (Zostavax®)
in adults aged 50 years and older.
In addition, according to ACIP, there is no evidence that inactivated vaccines interfere with the
immune response to other inactivated vaccines or to live vaccines. Any inactivated vaccine can be
administered either simultaneously or at any time before or after a different inactivated vaccine or
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live vaccine.
VAXIGRIP TETRA should not be mixed with any other vaccines or medicines in the same syringe.
Separate injection sites and separate syringes should be used in case of concomitant
administration. Persons deficient in producing antibodies due to immunosuppressive therapy may
have a reduced immune response to vaccination.
Following influenza vaccination, false positive results in serology tests using the ELISA method to
detect antibodies against HIV-1, hepatitis C and especially HTLV-1 have been observed. The
western blot technique disproves the false-positive ELISA test results. The transient false positive
reactions could be due to the IgM response by the vaccine.
4.6 Fertility, pregnancy and lactation
Pregnancy
One developmental and reproductive toxicity study conducted in rabbits with VAXIGRIP TETRA
did not show any effects on mating performance, embryo-fetal development and early postnatal
development.
Pregnant women are at high risk of influenza complications, including premature labour and
delivery, hospitalisation, and death; therefore, pregnant women should receive an influenza
vaccine, whatever their stage of pregnancy during the influenza season.
VAXIGRIP TETRA can be administered in all stages of pregnancy based on the safety data from
clinical studies and post-marketing experience with VAXIGRIP TETRA and with the Sanofi Pasteur
trivalent influenza vaccine, VAXIGRIP thiomersal free.
Data from worldwide use of inactivated influenza vaccines, including experience with use of
VAXIGRIP TETRA and VAXIGRIP in countries where inactivated influenza vaccines are
recommended in all stages of pregnancy, and data from a clinical study conducted in Finland with
VAXIGRIP TETRA administered in pregnant women during the second or third trimester (230
exposed pregnancies and 231 live births) did not indicate any adverse fetal or maternal outcomes
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attributable to the vaccine.
Data from four clinical studies conducted with VAXIGRIP thiomersal free administered to pregnant
women during the second and third trimesters (more than 5 000 exposed pregnancies and more
than 5 000 live births, followed up to approximately 6 months post-partum), did not indicate any
adverse fetal, newborn, infant or maternal outcomes attributable to the vaccine.
In clinical studies conducted in South Africa and Nepal, there were no significant differences
between the VAXIGRIP and placebo groups with regards to fetal, newborn, infant and maternal
outcomes (including miscarriage, stillbirth, premature birth, low birth weight).
In a study conducted in Mali, there were no significant differences between the VAXIGRIP and
control vaccine (quadrivalent meningococcal conjugate vaccine) groups with regards to prematurity
rate, stillbirth rate and low birth weight/small for gestational age rate.
In these clinical studies, none of the serious adverse events reported in women, fetuses or infants
were considered related to VAXIGRIP TETRA or VAXIGRIP.
Breastfeeding
There are no data on the effect of the vaccine in breastfed newborns/infants of women vaccinated
with VAXIGRIP TETRA during the breastfeeding period.
Based on inactivated influenza vaccines experience, VAXIGRIP TETRA may be used during
breastfeeding.
Fertility
There are no fertility data available in humans.
One animal study with VAXIGRIP TETRA did not indicate harmful effects on female fertility.
4.7 Effects on ability to drive and use machines

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VAXIGRIP TETRA has no or negligible influence on the ability to drive a vehicle and use
machines.
4.8 Undesirable effects
Within each system organ class, the adverse events are ranked under headings of frequency,
using the following convention:
Very common: ≥ 1/10 (≥ 10 %)
Common (frequent): ≥ 1/100 and < 1/10 (≥ 1 % and < 10 %)
Uncommon (infrequent): ≥ 1/1 000 and < 1/100 (≥ 0,1 % and < 1 %)
Rare: ≥ 1/10 000 and < 1/1 000 (≥ 0,01 % and < 0,1 %)
Very rare: < 1/10 000 (< 0,01 %)
Not known: cannot be estimated from available data.
Adverse event information is derived from clinical trials with VAXIGRIP TETRA and from worldwide
post-marketing experience with VAXIGRIP TETRA and VAXIGRIP (trivalent).
Data from clinical studies
The safety of VAXIGRIP TETRA was assessed in six randomised, controlled clinical trials in which
3 040 adults from 18 to 60 years of age, 1 392 elderly patients over 60 years of age and 429
children and adolescents from 9 to 17 years of age received one dose (0,5 mL) of VAXIGRIP
TETRA, and 884 children from 3 to 8 years of age received one or two doses (0,5 mL) of
VAXIGRIP TETRA and 1 614 children from 6 to 35 months of age received two doses (0,5 mL) of
VAXIGRIP TETRA. In all of these trials, the comparator vaccine was VAXIGRIP (trivalent).
In addition, a placebo was also used as comparator in the 6 to 35 months population.
The overall safety profile of VAXIGRIP TETRA was comparable to VAXIGRIP (trivalent). For all
subjects, safety evaluations were performed during the first 21 days following vaccination, except
for children 6 months to 8 years of age, where safety evaluations were performed during the first
28 days after any vaccination. Serious adverse reactions were collected during six months of
follow-up. Most of the reactions usually occurred within the first 3 days following vaccination, and
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resolved spontaneously within 1 to 3 days after onset. The intensity of these reactions was mild.
(Grade I: Fever: ≥ 38,0 °C to ≤ 38,4 °C except for < 24 months of age: ≥ 38,0 °C to ≤ 38,5 °C /
Injection site reactions: ≥ 25 to ≤ 50 mm except for children under 12 years old: < 25 mm / Other
reactions: no interference with activity).
The most frequently reported adverse reaction after vaccination, in all populations, including the
whole group of children from 6 months to 35 months of age, was injection site pain.
In the subpopulation of children less than 24 months of age, the most frequently reported adverse
reaction was irritability and in the subpopulation of children from 24 to 35 months of age it was
malaise.
Overall, adverse reactions were generally less frequent in the elderly than in adults and in children.
Adults
In 3 randomised active-controlled studies, 3 040 adults from 18 to 60 years of age received one
dose (0,5 mL) of VAXIGRIP TETRA, and 557 received one dose (0,5 mL) of VAXIGRIP.
The most frequently reported reactions following VAXIGRIP TETRA administration were injection
site pain, headache, myalgia and malaise.
Side effects reported within 7 days after vaccination with VAXIGRIP TETRA in adults from
18 to 60 years of age
Nervous system disorders
Very common: headache
Musculoskeletal and connective tissue disorders
Very common: myalgia
General disorders and administration site conditions
Very common: injection site pain, malaise
Common: injection site erythema, injection site swelling, injection site induration,
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shivering, fever
Uncommon: injection site ecchymosis.
Side effects reported within 21 days after vaccination with VAXIGRIP TETRA in adults from
18 to 60 years of age
Blood and lymphatic system disorders
Uncommon: lymphadenopathy
Immune system disorders
Rare: hypersensitivity
Rare: dizziness, paraesthesia, somnolence
Respiratory, thoracic and mediastinal disorders
Rare: dyspnoea
Gastrointestinal disorders
Uncommon: diarrhoea, nausea
Skin and subcutaneous tissue disorders
Rare: urticaria, angioedema, allergic dermatitis, erythema, hyperhidrosis, pruritus,
generalised pruritus
Rare: arthralgia
Uncommon: injection site pruritus, injection site warmth, fatigue

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Rare: injection site discomfort, influenza-like illness, asthenia.
Elderly patients
In 2 randomised, active-controlled studies, 1 392 elderly patients over 60 years of age received
one dose (0,5 mL) of VAXIGRIP TETRA, and 502 received one dose (0,5 mL) of VAXIGRIP
(trivalent).
site pain, headache and myalgia.
Side effects reported within 7 days after vaccination with VAXIGRIP TETRA in elderly
patients over 60 years of age
Very common: injection site pain
Common: injection site erythema, injection site swelling, injection site induration,
shivering, malaise
Uncommon: injection site ecchymosis, fever.
Side effects reported within 21 days after vaccination with VAXIGRIP TETRA in elderly
patients over 60 years of age
Uncommon: dizziness
Rare: paraesthesia, somnolence

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Vascular disorders
Uncommon: hot flushes
Uncommon: diarrhoea
Rare: nausea
Uncommon: pruritus
Rare: erythema, hyperhidrosis
Uncommon: injection site pruritus, injection site warmth, fatigue
Rare: asthenia, influenza-like illness.
Children and adolescents 9 to17 years of age
In a randomised, active-controlled study and an uncontrolled study, 429 children and adolescents
from 9 to 17 years of age received one dose (0,5 mL) of VAXIGRIP TETRA and 55 received one
dose (0,5 mL) of VAXIGRIP (trivalent).
site pain (54,5 %), myalgia (29,1 %), headache (24,7 %) malaise (20,3 %) and injection site
swelling (10,7 %).
Side effects reported within 7 days after vaccination with VAXIGRIP TETRA in children and
adolescents from 9 to 17 years of age

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Very common: injection site pain, injection site swelling, malaise
Common: injection site erythema, injection site induration, injection site ecchymosis,
shivering, fever.
Side effects reported within 21 days after vaccination with VAXIGRIP TETRA in children and
adolescents 9 to 17 years of age
Uncommon: diarrhoea
Uncommon: injection site pruritus.
Children from 3 to 8 years of age
In a randomised, active-controlled study, 884 children from 3 to 8 years of age received one or two
doses (0,5 mL) of VAXIGRIP TETRA and 354 received one or two doses (0,5 mL) of VAXIGRIP
(trivalent). The safety profile of VAXIGRIP TETRA was similar after the first and the second
injections.
site pain (56,5 %), malaise (30,7 %), myalgia (28,5 %), headache (25,7 %), injection site swelling
(20,5 %), injection site erythema (20,4 %), injection site induration (16,4 %), shivering (11,2 %).
Side effects reported within 7 days after any vaccination with VAXIGRIP TETRA in children
from 3 to 8 years of age

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Very common: injection site pain, injection site swelling, injection site erythema, injection site
induration, malaise, shivering
Common: injection site ecchymosis, fever.
Side effects reported within 28 days after any vaccination with VAXIGRIP TETRA in children
from 3 to 8 years of age
Uncommon: thrombocytopenia
Psychiatric disorders
Uncommon: restlessness, moaning
Uncommon: dizziness
Uncommon: diarrhoea, vomiting, upper abdominal pain
Uncommon: arthralgia
Uncommon: fatigue, injection site warmth.
Children from 6 to 35 months of age

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In one study, 1 614 children from 6 to 35 months of age received 2 doses (0,5 mL) of VAXIGRIP
TETRA, 1 612 received 2 doses (0,5 mL) of placebo and 367 received 2 doses (0,5 mL) of
VAXIGRIP.
The safety profile of VAXIGRIP TETRA was similar after the first and the second injections, with a
trend of lower incidence of adverse reactions after the second injection compared to the first one.
The most frequently reported reactions following VAXIGRIP TETRA administration were:
• For all children from 6 to 35 months of age: injection site pain/tenderness (26,8 %), fever
(20,4 %) and injection site erythema (17,2 %).
• In subpopulation of children less than 24 months of age: irritability (32,3 %), appetite loss
(28,9 %), abnormal crying (27,1 %), vomiting (16,1 %) and drowsiness (13,9 %).
• In a subpopulation of children from 24 to 35 months of age: malaise (26,8 %), headache
(11,9 %) and myalgia (11,6 %).
Side effects reported within 7 days after any vaccination with VAXIGRIP TETRA compared
to VAXIGRIP in children from 6 months to 35 months of age
Very common: headache*
Very common: vomiting†
Very common: myalgia*
Very common: injection site pain/tenderness, injection site erythema, fever, malaise*,
abnormal crying†, drowsiness†, irritability†, appetite loss†
Common: injection site swelling, injection site induration, ecchymosis, shivering*.
* Solicited, recorded for subjects ≥ 24 months.

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† Solicited, recorded for subjects < 24 months.
Side effects within 28 days after any vaccination with VAXIGRIP TETRA compared to
VAXIGRIP in children from 6 months to 35 months of age
Uncommon: hypersensitivity
Metabolism and nutrition disorders
Rare: decreased appetite(a)
Uncommon: diarrhoea, vomiting(a)
Rare: generalised pruritus, papular rash
Rare: myalgia(b)
Rare: influenza-like illness, injection site pruritus, injection site rash, irritability(a),
malaise(b).
(a) In children ≥ 24 months of age.
(b) In children < 24 months of age.
Other special populations
The safety profile of VAXIGRIP TETRA observed in a limited number of subjects with co-
morbidities enrolled in the clinical studies does not differ from the one observed in the overall
population. In addition, studies conducted with VAXIGRIP in renal transplant patients and
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asthmatic patients showed no major differences in terms of safety profile of VAXIGRIP in these
populations.
Pregnant women:
In clinical studies conducted in pregnant women in South Africa and Mali with VAXIGRIP (see
sections 4.6 and 5.1), frequencies of local and systemic solicited reactions reported within 7 days
following administration of VAXIGRIP were consistent with those reported for the adult population
during clinical studies conducted with VAXIGRIP. In the South Africa study, local reactions were
more frequent in the VAXIGRIP group than in the placebo group in both HIV-negative and HIV-
positive cohorts. There were no other significant differences in solicited reactions between
VAXIGRIP and placebo groups in both cohorts.
In one clinical study conducted in pregnant women in Finland with VAXIGRIP TETRA (see sections
4.6 and 5.1), frequencies of local and systemic solicited reactions reported within 7 days following
administration of VAXIGRIP TETRA were consistent with those reported for the nonpregnant adult
population during clinical studies conducted with VAXIGRIP TETRA, even though higher for some
adverse reactions (injection site pain, malaise, shivering, headache, myalgia).
When higher frequencies were observed, this increase was also seen with VAXIGRIP, used as
comparator, suggesting a clinical study effect in this pregnant women population.
Data from post-marketing experience
Not known: allergic reactions, including anaphylactic reactions.
Adverse events
The following adverse events were reported following commercial use of VAXIGRIP (trivalent). A
causal relationship with VAXIGRIP TETRA has not been established.

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Transient thrombocytopenia*, lymphadenopathy*
Severe allergic reactions: shock
Allergic reactions: rash, generalised erythema
Paraesthesia*, Guillain-Barré syndrome (GBS), neuritis, neuralgia, convulsions, encephalomyelitis
Vascular disorders
Vasculitis, such as Henoch-Schönlein purpura, with transient renal involvement in certain cases.
* These adverse events were reported during clinical trials with VAXIGRIP TETRA only in some
age groups (see “Data from clinical studies” above).
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows
continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked
to report any suspected adverse reactions to:
• The Pharmacovigilance Unit at Sanofi: [email protected] (email) or 011 256 3700
(tel), or
• SAHPRA via the “Adverse Drug Reactions Reporting Form” found online under SAHPRA’s
publications: https://www.sahpra.org.za/Publications/Index/8.
4.9 Overdose
Cases of administration of more than the recommended dose (overdose) have been reported with
VAXIGRIP TETRA. When adverse reactions were reported, the information was consistent with the
known safety profile of VAXIGRIP TETRA described in section 4.8.

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5. PHARMACOLOGICAL PROPERTIES
Category and class: A 30.2 Antigens
Pharmacotherapeutic group: Influenza vaccine, ATC code: J07BB02.
5.1 Pharmacodynamic properties
VAXIGRIP TETRA provides active immunisation against four influenza virus strains (two A
subtypes and two B types) contained in the vaccine.
VAXIGRIP TETRA induces humoral antibodies against the haemagglutinins within 2 to 3 weeks.
These antibodies neutralise influenza viruses.
Specific levels of haemagglutination inhibition (HAI) antibody titre postvaccination with inactivated
influenza virus vaccines have not been correlated with protection from influenza illness but the HAI
antibody titres have been used as a measure of vaccine activity. In some human challenge studies,
HAI antibody titres of ≥ 1:40 have been associated with protection from influenza illness in up to
50 % of subjects.
Since influenza viruses constantly evolve, the virus strains selected in the vaccine are reviewed
annually by the WHO.
Annual revaccination with VAXIGRIP TETRA has not been studied. However, based on clinical
experience with the trivalent vaccine, annual influenza vaccination is recommended given the
duration of immunity provided by the vaccine and because circulating strains of influenza virus
changes from year to year.
Efficacy of VAXIGRIP TETRA
Paediatric population
Children from 6 to 35 months of age (active immunisation)
A randomised placebo-controlled study was conducted in 4 regions (Africa, Asia, Latin America
and Europe) over 4 influenza seasons (Southern Hemisphere 2014, Northern Hemisphere 2014 –
2015, Southern Hemisphere 2015, Northern Hemisphere 2015 – 2016), in more than 5 400
children from 6 to 35 months of age who received two doses (0,5 mL) of VAXIGRIP TETRA (N =
2 722), or placebo (N = 2 717) 28 days apart to assess VAXIGRIP TETRA efficacy for the
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prevention of laboratory-confirmed influenza illness caused by any strain A and/or B and caused by
vaccine-similar strains (as determined by sequencing).
Laboratory-confirmed influenza illness was defined as influenza-like illness (ILI) [occurrence of
fever ≥ 38 °C (that lasts at least 24 hours) concurrently with at least one of the following symptoms:
cough, nasal congestion, rhinorrhoea, pharyngitis, otitis, vomiting, or diarrhoea], laboratory-
confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) and/or viral culture.
Table 1: Influenza attack rates and VAXIGRIP TETRA efficacy against laboratory-confirmed
influenza illness in children from 6 to 35 months of age
VAXIGRIP Placebo Efficacy
TETRA (N = 2 591)
(N = 2 584)
n Influenza n Influenza %
attack rate (%) attack rate (%) (2-sided 95 % CI)
Laboratory-confirmed influenza illness caused by:
Any influenza A or B type 122 4,72 255 9,84 52,03
(40,24; 61,66)
Viral strains similar to 26 1,01 85 3,28 69,33
those contained in the (51,93; 81,03)
vaccine
N: Number of children (full set).
n: Number of subjects fulfilling the item listed.
CI: Confidence interval.
In addition, a predefined complementary analysis showed VAXIGRIP TETRA prevented 56,6 %
(95 % CI: 37,0; 70,5) of severe laboratory-confirmed influenza illnesses due to any strain, and
71,7 % (95 % CI: 43,7; 86,9) of severe laboratory-confirmed influenza illnesses due to vaccine-
similar strains. Furthermore, subjects receiving VAXIGRIP TETRA were 59,2 % (95 % CI: 44,4;
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70,4) less likely to experience a medically attended influenza illness than subjects receiving
placebo.
Severe laboratory-confirmed influenza illnesses were defined as ILI laboratory-confirmed by RT-
PCR and/or viral culture with at least one of the following items:
• fever > 39,5 °C for subjects aged < 24 months or ≥ 39,0 °C for subjects aged ≥ 24 months,
• and/or at least one significant ILI symptom which prevents daily activity (cough, nasal
congestion, rhinorrhoea, pharyngitis, otitis, vomiting, diarrhoea),
• and/or one of the following events: acute otitis media, acute lower respiratory infection
(pneumonia, bronchiolitis, bronchitis, croup), inpatient hospitalisation.
Children from 3 to 8 years of age (active immunisation)
Based on immune responses observed in children 3 to 8 years of age, the efficacy of VAXIGRIP
TETRA in this population is expected to be at least similar to the efficacy observed in children from
6 to 35 months (see above “Children from 6 to 35 months of age” and below “Immunogenicity”).
Pregnant women
There are no clinical efficacy data describing use of VAXIGRIP TETRA in pregnant women.
In randomised, controlled phase IV clinical studies conducted in Mali, Nepal and South Africa,
approximately 5 000 pregnant women received VAXIGRIP (trivalent influenza thiomersal-free
vaccine) and approximately 5 000 pregnant women received placebo or control vaccine
(quadrivalent meningococcal conjugate vaccine) during the second or third trimester of pregnancy.
Vaccine efficacy against laboratory-confirmed influenza in pregnant women was evaluated as a
secondary endpoint in all three studies.
The studies conducted in Mali and South Africa demonstrated the efficacy of VAXIGRIP for the
prevention of influenza in pregnant women following vaccination during these trimesters of
pregnancy (see Table 2 below). In the study conducted in Nepal, the efficacy of VAXIGRIP for the
prevention of influenza in pregnant women following vaccination during these trimesters of
pregnancy was not demonstrated.

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Table 2: Influenza attack rates and VAXIGRIP efficacy against laboratory-confirmed
influenza in pregnant women
Influenza attack rate VAXIGRIP efficacy
(any influenza A or B type) % (n/N) % (95 % CI)

VAXIGRIP Control*
Mali 0,5 (11/2 108) 1,9 (40/2 085) 70,3 (42,2 to 85,8)
VAXIGRIP Placebo
South Africa 1,8 (19/1 062) 3,6 (38/1 054) 50,4 (14,5 to 71,2)
* Meningococcal vaccine.
N: Number of pregnant women included in analysis.
n: Number of subjects with laboratory-confirmed influenza.
Infants less than 6 months of age born to vaccinated pregnant women (passive protection) Infants
less than 6 months of age are at high risk of influenza, resulting in high rates of hospitalisation;
however, influenza vaccines are not indicated for active immunisation in this age group.
There are no clinical efficacy data in infants born to women vaccinated with VAXIGRIP TETRA
during pregnancy.
Efficacy in infants of women who received a single 0,5 mL dose of VAXIGRIP TETRA during the
second or third trimester of pregnancy has not been studied; however, efficacy in infants of women
who received a single 0,5 mL dose of VAXIGRIP during the second or third trimester has been
demonstrated in clinical trials and can be extrapolated to VAXIGRIP TETRA.
Efficacy of the trivalent inactivated influenza vaccine VAXIGRIP in infants following vaccination of
pregnant women during the first trimester has not been studied in these trials. Necessary influenza
vaccination during the first trimester should not be postponed (see section 4.6).
In the randomised, controlled, phase IV clinical studies conducted in Mali, Nepal and South Africa,
the efficacy of VAXIGRIP thiomersal free, for the prevention of influenza in infants younger than 6
months of age following vaccination of women during the second or third trimester of pregnancy,
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was confirmed (see Table 3 below).

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Table 3: Influenza attack rates and VAXIGRIP efficacy against laboratory-confirmed
influenza in infants following vaccination in pregnant women
Influenza attack rate VAXIGRIP efficacy
(any influenza A or B type) % (95% CI)
% (n/N)
VAXIGRIP Control*
Mali 2,4 (45/1 866) 3,8 (71/1 869) 37,3 (7,6 to 57,8)
VAXIGRIP Placebo
Nepal 4,1 (74/1 820) 5,8 (105/1 826) 30,0 (5 to 48)
South Africa 1,9 (19/1 026) 3,6 (37/1 023) 48,8 (11,6 to 70,4)
* Meningococcal vaccine.
N: Number of infants included in the analysis.
n: Number of subjects with laboratory-confirmed influenza.
The efficacy data indicate a waning protection of the infants born to vaccinated mothers by time
after birth.
In the trial conducted in South Africa, vaccine efficacy was highest among infants 8 weeks of age
or younger (85,8 % [95 % CI: 38,3 to 98,4]) and decreased over time; vaccine efficacy was 25,5 %
(95 % CI: -67,9 to 67,8) for infants > 8 to 16 weeks of age and 30,4 % (95 % CI: -154,9 to 82,6) for
infants > 16 to 24 weeks of age.
In the trial conducted in Mali, there is also a trend of higher efficacy of the trivalent inactivated
influenza vaccine in infants during the first 4 months after birth (70,2 % [95 % CI: 35,7 to 87,6]),
with lower efficacy within the fifth month of surveillance (60,7 % [95 % CI: 33,8 to 77,5]) and a
marked fall within the sixth month (37,3 % [95 % CI: 7,6 to 57,8]).
The prevention of influenza disease can only be expected if the infant(s) are exposed to strains
included in the vaccine administered to the mother.
Immunogenicity
Internal
Clinical studies performed in adults from 18 to 60 years of age, in elderly patients over 60 years of
age and in children 3 to 8 years of age and from 6 to 35 months of age assessed the non-inferiority
of VAXIGRIP TETRA versus VAXIGRIP (trivalent) for HAI geometric mean antibody titre (GMT) at
Day 21 (for adults) and at Day 28 (for children), HAI seroconversion rate (4-fold rise in reciprocal
titre or change from undetectable [< 10] to a reciprocal titre of ≥ 40), and HAI GMT ratio (post-/pre-
vaccination titres).
One clinical study performed in adults from 18 to 60 years of age and in children from 9 to 17 years
of age described the immune response of VAXIGRIP TETRA versus VAXIGRIP (trivalent) for HAI
geometric mean antibody titre (GMT) at Day 21.
Another clinical study performed in children from 9 to 17 years of age described only the immune
response of VAXIGRIP TETRA.
One clinical study performed in pregnant women described the immune response of VAXIGRIP
TETRA versus VAXIGRIP for HAI GMT at Day 21, HAI seroconversion rate and HAI GMTR after
one dose administered during the second or third trimester of pregnancy. In this study, the
transplacental transfer was evaluated using HAI GMTs of mother blood, of cord blood and of ratio
cord blood/mother blood, at delivery.
VAXIGRIP TETRA induced a significant immune response to the 4 influenza strains contained in
the vaccine.
VAXIGRIP TETRA elicited a superior immune response against the additional B strain included in
VAXIGRIP TETRA compared to VAXIGRIP (trivalent).
Adults and elderly patients
A total of 1 114 adults from 18 to 60 years of age and 1 111 elderly patients over 60 years of age
were randomised to receive either one dose of VAXIGRIP TETRA or one dose of VAXIGRIP
(trivalent). The immunogenicity of VAXIGRIP TETRA was assessed 21 days after injection by the
haemagglutination inhibition (HAI) method in all subjects.

Internal
Table 4: Immunogenicity results by HAI method in adults from 18 to 60 years, 21 days
postvaccination with VAXIGRIP TETRA or VAXIGRIP (trivalent)
VAXIGRIP TETRA Alternative VAXIGRIP (a) Licensed VAXIGRIP (b)
Antigen strain N = 832 (B Victoria) N = 140 (B Yamagata) N = 138
GMT (95 % CI)
A (H1N1) (c)(d) 608 (563; 657) 685 (587; 800)
A (H3N2) (c) 498 (459; 541) 629 (543; 728)
B (Victoria) 708 (661; 760) 735 (615; 879) 204 (170; 243)
B (Yamagata) 1 715 (1 607; 1 830) 689 (556; 854) 1 735 (1 490; 2 019)
SC % (95 % CI) (e)
A (H1N1) (c)(d) 64,1 (60,7; 67,4) 65,1 (59,2; 70,7)
A (H3N2) (c) 66,2 (62,9; 69,4) 73,4 (67,8; 78,5)
B (Victoria) 70,9 (67,7; 74,0) 70,0 (61,7; 77,4) 38,4 (30,3; 47,1)
B (Yamagata) 63,7 (60,3; 67,0) 42,1 (33,9; 50,8) 60,9 (52,2; 69,1)
GMTR (95 % CI) (f)
A (H1N1) (c)(d) 9,77 (8,69; 11,0) 10,3 (8,35; 12,7)
A (H3N2) (c) 10,3 (9,15; 11,5) 14,9 (12,1; 18,4)
B (Victoria) 11,6 (10,4; 12,9) 11,4 (8,66; 15,0) 3,03 (2,49; 3,70)
B (Yamagata) 7,35 (6,66; 8,12) 3,22 (2,67; 3,90) 6,08 (4,79; 7,72)
N: Number of subjects with available data for the considered endpoint.
GMT: Geometric mean titre.
GMTR: Geometric mean titre ratio.
SC: Seroconversion.
SI: Significant increase.
(a) Alternative VAXIGRIP containing A/California/7/2009 (H1N1), A/Texas/50/2012 (H3N2), and
B/Brisbane/60/2008 (Victoria lineage).
(b) 2014-2015 licensed VAXIGRIP containing A/California/7/2009 (H1N1), A/Texas/50/2012 (H3N2),
and B/Massachusetts/2/2012 (Yamagata lineage).
(c) Pooled TIV group includes participants vaccinated with either Alternative VAXIGRIP or licensed
Internal
VAXIGRIP, N = 278.
(d) N = 833 for VAXIGRIP TETRA group.
(e) For subjects with a pre-vaccination titre < 10 (1/dil), proportion of subjects with a post-vaccination
titre ≥ 40 (1/dil) and for subjects with a pre-vaccination titre ≥10 (1/dil), proportion of subjects with
a ≥ four-fold increase from pre- to post-vaccination titre.
(f) Geometric mean of individual ratios (post-/pre-vaccination titres).
Table 5: Immunogenicity results by HAI method in elderly patients over 60 years of age, 21
days postvaccination with VAXIGRIP TETRA or VAXIGRIP (trivalent)
Antigen strain VAXIGRIP TETRA Alternative Licensed
N = 831 VAXIGRIP (a) VAXIGRIP (b)
(B Victoria) N = 138 (B Yamagata) N = 137

GMT (95 % CI)
A (H1N1) (c)(d) 219 (199; 241) 268 (228; 314)
A (H3N2) (c) 359 (329; 391) 410 (352; 476)
B (Victoria) 287 (265; 311) 301 (244; 372) 121 (101; 147)
B (Yamagata) 55 (611; 701) 351 (294; 420) 697 (593; 820)
SC % (95% CI) (e)
A (H1N1) (c)(d) 45,6 (42,1; 49,0) 50,2 (44,1; 56,2)
A (H3N2) (c) 47,5 (44,1; 51,0) 48,5 (42,5; 54,6)
B (Victoria) 45,2 (41,8; 48,7) 43,5 (35,1; 52,2) 21,2 (14,7; 29,0)
B (Yamagata) 42,7 (39,3; 46,2) 28,3 (20,9; 36,5) 38,7 (30,5; 47,4)
GMTR (95 % CI) (f)
A (H1N1) (c)(d) 4,94 (4,46; 5,47) 6,03 (4,93; 7,37)
A (H3N2) (c) 5,60 (5,02; 6,24) 5,79 (4,74; 7,06)
B (Victoria) 4,61 (4,18; 5,09) 4,60 (3,50; 6,05) 1,99 (1,70; 2,34)
B (Yamagata) 4,11 (3,73; 4,52) 2,04 (1,71; 2,43) 4,11 (3,19; 5,30)
(a) Alternative TIV containing A/California/7/2009 (H1N1), A/Texas/50/2012 (H3N2), and

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(b) 2014-2015 licensed TIV containing A/California/7/2009 (H1N1), A/Texas/50/2012 (H3N2), and
B/Massachusetts/2/2012 (Yamagata lineage).
(c) Pooled TIV group includes participants vaccinated with either alternative TIV or licensed TIV, N =
275.
(d) N = 832 for QIV group.
(e) SC: Seroconversion or significant increase: for subjects with a pre- vaccination titre < 10 (1/dil),
proportion of subjects with a post-vaccination titre ≥ 40 (1/dil) and for subjects with a pre-
vaccination titre ≥ 10 (1/dil), proportion of subjects with a ≥ four-fold increase from pre- to post-
vaccination titre.
(f) GMTR: Geometric mean of individual titre ratios (post-/pre-vaccination titres).
Pregnant women and transplacental transfer
A randomised, controlled clinical study was conducted in Finland in pregnant women to describe
the immune response of VAXIGRIP TETRA compared to VAXIGRIP, 21 days after vaccination and
to evaluate the transplacental transfer of antibody from mother to newborn from the cord blood
after 1 dose of VAXIGRIP TETRA or of VAXIGRIP.
A total of 230 pregnant women received VAXIGRIP TETRA and 116 pregnant women received
VAXIGRIP during the second or third trimester of pregnancy (from 20 to 32 weeks of pregnancy).
Immunogenicity results by HAI method, in pregnant women 21 days after vaccination with
VAXIGRIP TETRA or VAXIGRIP TETRA, are presented in table 6 below.
Table 6: Immunogenicity results by HAI method in pregnant women, 21 days
postvaccination with VAXIGRIP TETRA or VAXIGRIP
Antigen strain VAXIGRIP TETRA VAXIGRIP
N = 216 (B Victoria) N = 109
GMT (95 % CI)
A (H1N1)* 525 (466; 592) 638 (529; 769)
A (H3N2)* 341 (286; 407) 369 (283; 483)
B1 (Victoria)* 568 (496; 651) 697 (569; 855)

Internal
B2 (Yamagata)* 993 (870; 1 134) 529 (415; 674)
≥ 4-fold rise n (%) (a)
A (H1N1)* 38,0 (31,5; 44,8) 41,3 (31,9; 51,1)
A (H3N2)* 59,3 (52,4; 65,9) 62,4 (52,6; 71,5)
B1 (Victoria)* 61,1 (54,3; 67,7) 60,6 (50,7; 69,8)
B2 (Yamagata)* 59,7 (52,9; 66,3) 38,5 (29,4; 48,3)
GMTR (95 % CI) (b)
A (H1N1)* 3,81 (3,11; 4,66) 5,26 (3,66; 7,55)
A (H3N2)* 8,63 (6,85; 10,9) 9,23 (6,56; 13,0)
B1 (Victoria)* 8,48 (6,81; 10,6) 9,62 (6,89; 13,4)
B2 (Yamagata)* 6,26 (5,12; 7,65) 3,40 (2,68; 4,32)
* A/H1N1: A/Michigan/45/2015 (H1N1) pdm09 - like virus; A/H3N2: A/Hong Kong/4801/2014 (H3N2) -
like virus;
B1: B/Brisbane/60/2008-like virus (B/Victoria lineage): this strain was included in the VAXIGRIP
composition;
B2: B/Phuket/3073/2013 - like virus (B/Yamagata lineage): this strain was not included in the
VAXIGRIP composition.
(a) SC: Seroconversion or significant increase: for subjects with a pre-vaccination titre < 10 (1/dil),
proportion of subjects with a post-vaccination titre ≥ 40 (1/dil) and for subjects with a pre-vaccination
titre ≥ 10 (1/dil), proportion of subjects with a ≥ four-fold increase from pre- to post-vaccination titre.
(b) GMTR: Geometric mean of individual titre ratios (post-/pre-vaccination titres).

Internal
Immunogenicity descriptive assessment by HAI method, at delivery, in blood sample of mother
(BL03M), in cord blood sample (BL03B) and of the transplacental transfer (BL03B/BL03M) are
presented in Table 7 below.
Table 7: Immunogenicity descriptive assessment by HAI method of VAXIGRIP TETRA or
VAXIGRIP (trivalent) at delivery
Antigen strain VAXIGRIP TETRA VAXIGRIP (B Victoria)
N = 178 N = 89
BL03M†
GMT (95 % CI)

A (H1N1)* 304 (265; 349) 411 (332; 507)
A (H3N2)* 178 (146; 218) 186 (137; 250)
B1 (Victoria)* 290 (247; 341) 371 (299; 461)
B2 (Yamagata)* 547 (463; 646) 367 (281; 479)
BL03B**
GMT (95 % CI)
A (H1N1)* 576 (492; 675) 751 (605; 932)
A (H3N2)* 305 (246; 379) 324 (232; 452)
B1 (Victoria)* 444 (372; 530) 608 (479; 772)
B2 (Yamagata)* 921 (772; 1 099) 539 (389; 748)
Transplacental transfer: BL03B/BL03M§
GMT (95 % CI)

A (H1N1)* 1,89 (1,72; 2,08) 1,83 (1,64; 2,04)
A (H3N2)* 1,71 (1,56; 1,87) 1,75 (1,55; 1,97)
B1 (Victoria)* 1,53 (1,37; 1,71) 1,64 (1,46; 1,85)
B2 (Yamagata)* 1,69 (1,54; 1,85) 1,47 (1,28; 1,69)

N: Number of subjects with available data for the considered endpoint: women who received
VAXIGRIP TETRA or VAXIGRIP, delivered at least 2 weeks after injection and with available cord
blood and mother blood at the time of delivery.
GMT: Geometric mean titre;

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* A/H1N1: A/Michigan/45/2015 (H1N1)pdm09 - like virus; A/H3N2: A/Hong Kong/4801/2014 (H3N2) -
like virus;
B1: B/Brisbane/60/2008 - like virus (B/Victoria lineage): this strain was included in the VAXIGRIP
composition;
B2: B/Phuket/3073/2013 - like virus (B/Yamagata lineage): this strain was not included in the
VAXIGRIP composition.
† BL03M: Blood sample of mother at delivery.
** BL03B: Cord blood sample at delivery.
§ If a mother has X babies, her titre value is counted X times.
At delivery, the level of antibodies in the cord sample compared to the mother sample was almost
doubled for the A/H1N1 strain and increased between 1,5 and 1,7 times for the A/H3N2,
B/Brisbane and B/Phuket strains, supporting that there is transplacental antibody transfer from
mother to the newborn, following vaccination of women with VAXIGRIP TETRA or VAXIGRIP
(trivalent) during the second or third trimester of pregnancy.
These data are consistent with the passive protection demonstrated in infants from birth to
approximately 6 months of age following vaccination of women during the second or third trimester
of pregnancy with VAXIGRIP (trivalent) in studies conducted in Mali, Nepal and South Africa (see
section 5.1).
Paediatric population
• Children from 9 to 17 years of age
In a total of 429 children from 9 to 17 years of age who received one dose of VAXIGRIP TETRA
the immune response against the 4 strains contained in the vaccine was similar to the immune
response induced in adults 18 to 60 years of age.
• Children from 6 months to 8 years of age
A total of 1 242 children 3 to 8 years of age were randomised to receive either one or two doses of
VAXIGRIP TETRA or of VAXIGRIP (trivalent) (control vaccine) depending on their previous

Internal
influenza vaccination history.
Children who received a one- or two-dose schedule of VAXIGRIP TETRA presented a similar
immune response following the last dose of the respective schedule.
Table 8: Immunogenicity results by HAI method in children from 3 to 8 years of age, 28
days after the last injection of VAXIGRIP TETRA or VAXIGRIP
Antigen strain QIV Alternative Licensed

(B Victoria) (B Yamagata)
N = 176 N = 168
GMT (95 % CI)
A (H1N1) (c) 971 (896; 1 052) 1 141 (1 006; 1 295)
A (H3N2) (c) 1 568 (1 451; 1 695) 1 746 (1 551; 1 964)
B (Victoria) (d) 1 050 (956; 1 154) 1 120 (921; 1 361) 170 (125; 232)
B (Yamagata) (e) (f) 1 173 (1 078; 1 276) 217 (171; 276) 1 211 (1 003; 1 462)
SC % (95 % CI) (g)
A (H1N1) (c) 65,7 (62,4; 68,9) 65,7 (60,4; 70,7)
A (H3N2) (c) 64,8 (61,5; 68,0) 67,7 (62,5; 72,6)
B (Victoria) (d) 84,8 (82,3; 87,2) 90,3 (85,0; 94,3) 38,5 (31,1; 46,2)
(Yamagata) (e) (f) 88,5 (86,2; 90,6) 46,0 (38,4; 53,7) 89,9 (84,3; 94,0)
GMTR (95 % CI) (h)
A (H1N1) (c) 6,86 (6,24; 7,53) 7,65 (6,54; 8,95)
A (H3N2) (c) 7,49 (6,72; 8,35) 7,61 (6,69; 9,05)
B (Victoria) (d) 17,1 (15,5; 18,8) 17,8 (14,5; 22,0) 3,52 (2,93; 4,22)
B (Yamagata) (e) (f) 25,3 (22,8; 28,2) 4,60 (3,94; 5,37) 30,4 (23,8; 38,4)
(c) Pooled VAXIGRIP group includes participants vaccinated with either alternative VAXIGRIP or
Internal
licensed VAXIGRIP, N = 344.
(d) N = 169 for VAXIGRIP (B Yamagata) group.
(e) N = 862 for VAXIGRIP TETRA group.
(f) N = 175 for VAXIGRIP (B Victoria) group.
(g) SC: Seroconversion or significant increase: for subjects with a pre-vaccination titre < 10 (1/dil),
vaccination titre.
(h) GMTR: Geometric mean of individual titre ratios (post-/pre-vaccination titres).
Table 9: Immunogenicity results by SN method in children from 3 to 8 years of age, 28 days
after the last injection of VAXIGRIP TETRA or VAXIGRIP

N = 86 N = 83
GMT (95 % CI)
A (H1N1) (c) (d) 3 499 (3 138; 3 902) 4 462 (3 778; 5 268)
A (H3N2) (c) 475 (430; 525) 542 (467; 629)
B (Victoria) 905 (788; 1 039) 980 (722; 1 329) 203 (139; 298)
B (Yamagata) 731 (638; 838) 131 (94,4; 181) 952 (709; 1 279)
≥ 4-fold rise n (%) (e)
A (H1N1) (c) (d) 60,3(55,5; 65,0) 60,9 (53,2; 68,3)
A (H3N2) (c) 52,0 (47,1; 56,8) 52,1 (44,3; 59,8)
B (Victoria) 80,3 (76,2; 83,9) 89,5 (81,1; 95,1) 41,0 (30,3; 52,3)
B (Yamagata) 84,7 (80,9; 88,0) 39,5 (29,2; 50,7) 86,7 (77,5; 93,2)
GMTR (95 % CI) (f)
A (H1N1) (c) (d) 8,45 (7,20; 9,92) 8,21 (6,37; 10,6)
A (H3N2) (c) 5,03 (4,46; 5,68) 5,45 (4,50; 6,61)
B (Victoria) 13,6 (11,9; 15,5) 15,6 (12,1; 20,1) 3,51 (2,78; 4,44)
B (Yamagata) 19,3 (16,8; 22,1) 3,87 (3,12; 4,81) 25,2 (18,1; 35,1)
*: 28 days for primed subjects and 56 days for unprimed subjects.
N: number of subjects with available data for the considered endpoint.

Internal
(c) Pooled VAXIGRIP group includes participants vaccinated with either alternative VAXIGRIP or
licensed VAXIGRIP, N = 169.
(d) N = 431 for VAXIGRIP TETRA group.
(e) For subjects with a pre-vaccination titre < 10 (1/dil), proportion of subjects with a post-vaccination
titre ≥ 40 (1/dil) and for subjects with a pre-vaccination titre ≥ 10 (1/dil), proportion of subjects with a
≥ four-fold increase from pre- to post-vaccination titre.
Children from 6 to 35 months of age
In addition to the VAXIGRIP TETRA efficacy, the immunogenicity of two 0,5 mL doses of
VAXIGRIP TETRA (N = 341) compared to two 0,5 mL doses of VAXIGRIP (N = 369) was
assessed 28 days after receipt of the last injection of VAXIGRIP TETRA by haemagglutination
inhibition (HAI) method in children 6 to 35 months of age and by seroneutralisation (SN) method in
subsets of subjects.
Table 10: Immunogenicity results by HAI method in children from 6 to 35 months of age, 28

N = 341 VAXIGRIP (a) VAXIGRIP (b) (c)
N = 172 N = 178
GMT (95 % CI)
A (H1N1) 641 (547; 752) 637 (500; 812) 628 (504; 781)
A (H3N2) 1 071 (925; 1 241) 1 021 (824; 1 266) 994 (807; 1 224)
B (Victoria) 623 (550; 706) 835 (691; 1 008) 10,0 (8,27; 12,1)
B (Yamagata) (d) 1 010 (885; 1 153) 39,9 (31,2; 51,0) 1 009 (850; 1 198)
SC % (95 % CI) (e)

Internal
A (H1N1) 90,3 (86,7; 93,2) 87,2 (81,3; 91,8) 90,4 (85,1; 94,3)
A (H3N2) 90,3 (86,7; 93,2) 88,4(82,6; 92,8) 87,6 (81,9; 92,1)
B (Victoria) 98,8 (97,0; 99,7) 99,4 (96,8; 100,0) 2,2 (0,6; 5,7)
B (Yamagata) 96,8 (94,3; 98,4) 33,9 (26,9; 41,5) 99,4 (96,9; 100,0)
GMTR (95 % CI) (f)
A (H1N1) 36,6 (30,8; 43,6) 35,3 (27,4; 45,5) 40,6 (32,6; 50,5)
A (H3N2) 42,6 (35,1; 51,7) 44,1 (33,1; 58,7) 37,1 (28,3; 48,6)
B (Victoria) 100 (88,9; 114) 114 (94,4; 138) 1,52 (1,40; 1,64)
B (Yamagata) 93,9 (79,5; 111) 4,34 (3,62; 5,20) 111 (91,3; 135)
(b) 2014-2015 licensed VAXIGRIP containing A/California/7/2009 (H1N1), A/Texas/50/2012 (H3N2)
(c) Dose of 0,5 mL.
(d) N = 171 for Alternate VAXIGRIP (B Victoria) group.
(e) SC: Seroconversion or significant increase: for subjects with a pre-vaccination titre < 10 (1/dil),
vaccination titre.
These immunogenicity data provide supportive information in addition to vaccine efficacy data
available in this population (see “Efficacy of VAXIGRIP TETRA”).
Table 11: Immunogenicity results by SN method in children from 6 to 35 months of age, 28

Internal
N = 86 N = 88
GMT (95 % CI)
A (H1N1) (c) 2 207 (1 767; 2 756) 2 824 (2 142; 3 723) 2 280 (1 725; 3 013)
A (H3N2) 516 (432; 617) 574 (441; 748) 643 (491; 841)
B (Victoria) 494 (415; 587) 907 (690; 1 191) 18,9 (14,5; 24,7)
B (Yamagata) 371 (308; 447) 20,6 (16,0; 26,5) 440 (334; 579)
≥ 4-fold rise n (%) (d)
A (H1N1) (c) 77,5 (70,5; 83,6) 72,6 (61,8; 81,8) 84,1 (74,8; 91,0)
A (H3N2) 84,6 (78,3; 89,7) 78,8 (68,6; 86,9) 84,1 (74,8; 91,0)
B (Victoria) 98,2 (94,9; 99,6) 98,8 (93,6; 100,0) 31,8 (22,3; 42,6)
B (Yamagata) 97,0 (93,2; 99,0) 27,1 (18,0; 37,8) 95,5 (88,8; 98,7)
GMTR (95 % CI) (e)
A (H1N1) (c) 73,3 (50,0; 108) 70,7 (40,1; 125) 96,6 (59,3; 157)
A (H3N2) 16,1 (12,9; 20,1) 12,8 (9,36; 17,4) 16,5 (11,9; 22,7)
B (Victoria) 66,8 (55,7; 80,1) 98,3 (73,4; 132) 2,96 (2,46; 3,56)
B (Yamagata) 44,4 (36,5; 53,9) 2,57 (2,16; 3,06) 54,1 (41,4; 70,7)
*: 28 days for primed subjects and 56 days for unprimed subjects.
(b) 2014-2015 licensed TIV containing A/California/7/2009 (H1N1), A/Texas/50/2012 (H3N2), and
B/Massachusetts/2/2012 (Yamagata lineage).
(c) N = 85 for alternate VAXIGRIP.
(d) For subjects with a pre-vaccination titre < 10 (1/dil), proportion of subjects with a post-vaccination
titre ≥ 40 (1/dil) and for subjects with a pre-vaccination titre ≥ 10 (1/dil), proportion of subjects with a
≥ four-fold increase from pre- to post-vaccination titre.
(e) GMTR: Geometric mean of individual titre ratios (post-/pre- vaccination titres).
5.2 Pharmacokinetic properties
No pharmacokinetic studies have been performed.

Internal
5.3 Preclinical safety data
Non-clinical data revealed no special hazard for humans based on conventional studies of repeat
dose and local toxicity, reproductive and developmental toxicity and safety pharmacology studies.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Buffer saline solution containing:
• sodium chloride
• potassium chloride
• disodium phosphate dihydrate
• potassium dihydrogen phosphate
• water for injections.
6.2 Incompatibilities
In the absence of compatibility studies, VAXIGRIP TETRA must not be mixed with other medicines
in the same syringe (see section 4.5).
6.3 Shelf life
1 year.
6.4 Special precautions for storage
Store in a refrigerator between 2 °C and 8 °C. Shake before use.
Do not freeze.
Do not use after the expiry date indicated on the label or the package.
Keep the syringe in the outer carton in order to protect from light.
6.5 Nature and contents of container
Type I clear, colourless glass single-dose pre-filled syringe with a black bromobutyl or chlorobutyl
plunger-stopper without or with a (25 G 5/8) needle.

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Pack sizes: 1, 10 or 20.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
The vaccine should be allowed to reach room temperature before use.
Shake before use to distribute the suspension uniformly before administration.
Inspect the vaccine visually for particulate matter and/or discolouration prior to administration. If
either of these conditions exists, the vaccine should not be administered.
Any unused medicine or waste material should be disposed of in accordance with local
requirements.
7. HOLDER OF CERTIFICATE OF REGISTRATION
sanofi-aventis south africa (pty) ltd
Hertford Office Park
Building 1, 5th Floor
90 Bekker Road
Vorna Valley, Midrand 2196
Tel: 011 256 3700
8. REGISTRATION NUMBER
51/30.1/0838
9. DATE OF FIRST AUTHORISATION
Registration date: 20 March 2019
10. DATE OF REVISION OF THE TEXT
February 2024

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PROFESSIONAL INFORMATION FOR VAXIGRIP TETRA

1. NAME OF THE MEDICINE

VAXIGRIP TETRA 2024 strains suspension for injection

Quadrivalent influenza vaccine (split virion, inactivated).

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Composition per 0,5 mL dose:

Split influenza virus, inactivated strains for 2024 Southern Hemisphere

A/Victoria/4897/2022 (H1N1)pdm09-like strain (A/Victoria/4897/2022, IVR-238) 15 micrograms*

A/Thailand/8/2022 (H3N2)-like strain (A/California/122/2022, SAN-022) 15 micrograms*

B/Austria/1359417/2021-like strain (B/Michigan/01/2021, wild type) 15 micrograms*

B/Phuket/3073/2013-like strain (B/Phuket/3073/2013, wild type) 15 micrograms*

For the full list of excipients, see section 6.1.

Suspension for injection.

syringe that contains one dose of 0,5 mL.

4.1 Therapeutic indications

pregnant women (see sections 4.4, 4.6 and 5.1).

4.2 Posology and method of administration

Adults: one dose of 0,5 mL.

• Children from 6 months to 17 years of age: one dose of 0,5 mL.

of 0,5 mL should be given after an interval of at least 4 weeks.

(active immunisation) have not been established. No data are available.

The vaccine should be given by intramuscular or deep subcutaneous injection.

deltoid muscle in children from 36 months of age and adults.

Precautions to be taken before handling or administering VAXIGRIP TETRA:

Administration of VAXIGRIP TETRA should be postponed in subjects suffering from moderate or

severe febrile disease or acute disease.

4.4 Special warnings and precautions for use

hypersensitivity to this antibiotic (and other antibiotics of the same class).

Vaccination with VAXIGRIP TETRA may not protect all vaccinees.

during pregnancy will be protected (see section 5.1).

against all possible strains of influenza virus.

If VAXIGRIP TETRA is used in immunocompromised persons whether due to genetic,

immunodeficiency disease, or immunosuppressive therapy, they may have a reduced immune

Interference with serological testing

See section 4.5.

Do not administer VAXIGRIP TETRA by intravascular injection.

case of an anaphylactic reaction following the administration of the vaccine.

• As a precautionary measure, adrenaline (epinephrine) injection (1:1 000) must be immediately

available in case of unexpected anaphylactic or serious allergic reactions.

manage syncopal reactions.

4.5 Interaction with other medicines and other forms of interaction

have been conducted.

in adults aged 50 years and older.

administration. Persons deficient in producing antibodies due to immunosuppressive therapy may

have a reduced immune response to vaccination.

reactions could be due to the IgM response by the vaccine.

4.6 Fertility, pregnancy and lactation

vaccine, whatever their stage of pregnancy during the influenza season.

trivalent influenza vaccine, VAXIGRIP thiomersal free.

attributable to the vaccine.

adverse fetal, newborn, infant or maternal outcomes attributable to the vaccine.

outcomes (including miscarriage, stillbirth, premature birth, low birth weight).

were considered related to VAXIGRIP TETRA or VAXIGRIP.

with VAXIGRIP TETRA during the breastfeeding period.

There are no fertility data available in humans.

4.7 Effects on ability to drive and use machines

4.8 Undesirable effects

using the following convention:

Very common: ≥ 1/10 (≥ 10 %)