Fluarix Tetra is a quadrivalent vaccine indicated for active immunisation of adults and
children from 6 months of age for the prevention of influenza disease caused by influenza
virus types A and B contained in the vaccine (see Pharmacodynamics).

Fluarix Tetra should be administered as a single 0.5 ml injection.
Children 6 months to less than 9 years of age who have not previously been vaccinated
against influenza should receive a second dose of 0.5 ml after an interval of at least 4 weeks.
Children aged <6 months
The safety and efficacy of Fluarix Tetra in children aged less than 6 months have not been
established.
Vaccination should be carried out by intramuscular injection preferably into the deltoid
muscle or anterolateral thigh (depending on the muscle mass).

It is good clinical practice to precede vaccination by a review of the medical history (especially
with regard to previous vaccination and possible occurrence of undesirable events) and a
clinical examination.
As with all injectable vaccines, appropriate medical treatment and supervision should always
be readily available in case of an anaphylactic event following the administration of the
vaccine.
As with other vaccines, vaccination with Fluarix Tetra should be postponed in subjects
suffering from an acute severe febrile illness. The presence of a minor infection, such as a cold,
should not result in the deferral of vaccination.
It may be expected that in patients receiving immunosuppressive treatment or patients with
immunodeficiency, an adequate immune response may not be elicited.
Fluarix Tetra is not effective against all possible strains of influenza virus. Fluarix Tetra is
intended to provide protection against those strains of virus from which the vaccine is prepared
and to closely related strains.
As with any vaccine, a protective immune response may not be elicited in all vaccinees.
FLUARIX TETRA SHOULD UNDER NO CIRCUMSTANCES BE ADMINISTERED
INTRAVASCULARLY.
As with other vaccines administered intramuscularly, Fluarix Tetra should be given with
caution to individuals with thrombocytopenia or any coagulation disorder since bleeding may
occur following an intramuscular administration to these subjects.
Syncope (fainting) can occur following, or even before, any vaccination as a psychogenic
response to the needle injection. It is important that procedures are in place to avoid injury from
faints.

Fluarix Tetra can be concomitantly administered with pneumococcal vaccines (see
Pharmacodynamics).
If Fluarix Tetra is to be given at the same time as another injectable vaccine, the vaccines
should always be administered at different injection sites.
False positive ELISA serologic tests for HIV-1, Hepatitis C, and especially HTLV-1 may occur
following influenza vaccination. These transient false-positive results may be due to crossreactive
IgM elicited by the vaccine. For this reason, a definitive diagnosis of HIV-1, Hepatitis
C, or HTLV-1 infection requires a positive result from a virus-specific confirmatory test (e.g.,Western Blot or immunoblot).

The safety of Fluarix Tetra when administered to pregnant women has not been evaluated.
Animal studies with Fluarix Tetra do not indicate direct or indirect harmful effects with respect
to reproductive and developmental toxicity (see Pre-clinical Safety Data).
Fluarix Tetra should be used during pregnancy only when clearly needed, and the possible
advantages outweigh the potential risks for the foetus.
The safety of Fluarix Tetra when administered to breast-feeding women has not been evaluated.
It is unknown whether Fluarix Tetra is excreted in human breast milk.
Fluarix Tetra should only be used during breast-feeding when the possible advantages
outweigh the potential risks.

NA

Adverse reactions reported for Fluarix Tetra in the different age groups are listed according to
the following frequency categories: Very common (≥1/10); Common (≥1/100 to <1/10);
Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000); Very rare (<1/10,000)
Clinical trial data
Adults
A clinical study with Fluarix Tetra in adults has evaluated the incidence of adverse reactions
in subjects ≥18 years who received one dose of Fluarix Tetra (N = 3,036) or Fluarix (N =
1,010).
The following adverse reactions per dose have been reported:

Children aged 6 months to <18 years
Two clinical studies evaluated the reactogenicity and safety of Fluarix Tetra in children who
received at least one dose of Fluarix Tetra or a control vaccine.

One study enrolled children 3 to <18 years of age who received Fluarix Tetra (N = 915) or
Fluarix (N = 912). The second study enrolled children 6 to <36 months of age who received
Fluarix Tetra (N = 6,006) or a non-influenza vaccine control (N = 6,012) (see
Pharmacodynamics).
The following adverse reactions per dose have been reported:

Post-marketing data
The following adverse reactions have been observed for Fluarix and/or Fluarix Tetra during
post-marketing surveillance.1

Kingdom of Saudi Arabia
-National Pharmacovigilance centre (NPC)

• Fax: +966-11-205-7662
• Call NPC at +966-11-2038222, Ext: 2317-2356-2353-2354-2334-2340
• Toll-free: 8002490000
• E-mail: npc.drug@sfda.gov.sa
• Website: www.sfda.gov.sa/npc
-GlaxoSmithKline - Head Office, Jeddah
• Tel: +966-12-6536666
• Mobile: +966-56-904-9882
• Email: gcc.medinfo@gsk.com
• website: https://healthksa.gsk.com/
• P.O. Box 55850, Jeddah 21544, Saudi Arabia

NA

Mechanism of Action
Fluarix Tetra induces haemagglutination-inhibition (HI) antibodies against the four influenza
virus strains contained in the vaccine. While specific levels of HI antibody in response to
inactivated influenza virus vaccines have not been correlated with protection from influenza
illness the HI antibody titres have been used as a measure of vaccine activity. In some human
challenge studies, HI antibody titres of ≥1:40 have been associated with protection from
influenza illness in up to 50% of subjects.
Annual revaccination with the current vaccine is recommended because immunity declines
during the year after vaccination, and because circulating strains of influenza virus might
change from year to year.
Pharmacodynamic Effects
Efficacy in children 6-35 months of age:

The efficacy of Fluarix Tetra was evaluated in clinical study D-QIV-004, a randomised,
observer-blind, non-influenza vaccine-controlled trial conducted during influenza seasons
2011 to 2014. Healthy subjects aged 6 through 35 months were randomised (1:1) to receive
Fluarix Tetra (N = 6,006) or an age appropriate non-influenza control vaccine (N = 6,012).
Subjects were administered 1 dose (in case of history of influenza vaccination) or 2 doses,
approximately 28 days apart.
Efficacy of Fluarix Tetra was assessed for the prevention of influenza A and/or B disease
(moderate to severe and of any severity) due to any seasonal influenza strain, starting 2 weeks
post-vaccination until the end of the influenza season (approximately 6 months later). Fluarix
Tetra met the predefined criteria for primary and secondary vaccine efficacy objectives (Table
1).

Table 1: Attack rates and vaccine efficacy in children 6-35 months of age (ATP (according to
protocol) cohort for efficacy – time to event)

Exploratory analyses were conducted on the Total Vaccinated Cohort (TVC) including 12,018
subjects. Fluarix Tetra was efficacious in the prevention of moderate to severe influenza caused
by each of the 4 strains (Table 2), even when there was significant antigenic mismatch with 2
of the vaccine strains (A/H3N2 and B/Victoria).
Table 2: Attack rates and vaccine efficacy for RT-PCR confirmed moderate to severe disease
by Influenza A subtype and Influenza B lineage in children 6-35 months of age (TVC)

Additionally, for RT-PCR confirmed cases of any severity, Fluarix Tetra reduced the risk of
visits to the general practitioner by 47% (Relative Risk (RR): 0.53 [95% CI: 0.46; 0.61], i.e.,

310 versus 583 visits) and to the emergency room by 79% (RR: 0.21 [95% CI: 0.09; 0.47], i.e.,
7 versus 33 visits). The use of antibiotics was reduced by 50% (RR: 0.50 [95% CI: 0.42; 0.60],
i.e., 172 versus 341 subjects).
Immunogenicity in children and adults:
Immunogenicity of Fluarix Tetra was evaluated in terms of HI Geometric mean antibody titre
(GMT) at 28 days after the last dose (children) or Day 21 (adults) and HI seroconversion rate
(4-fold rise in reciprocal titre or change from undetectable [< 10] to a reciprocal titre of ≥ 40).
In study D-QIV-004, the evaluation was performed in a sub-cohort of 1,332 children. The
results are presented in Table 3.
The effect of a 2-dose priming schedule in D-QIV-004 was evaluated by assessing the immune
response after revaccination one year later with 1 dose of Fluarix Tetra in study D-QIV-009.
This study demonstrated that 7 days post-vaccination, immune memory in children 6 to 35
months of age had been elicited for all four vaccine strains.
Immunogenic non-inferiority of Fluarix Tetra was assessed versus Fluarix in children (study
D-QIV-003) and in adults (study D-QIV-008). Children received 1 or 2 doses and adults
received 1 dose of either vaccine. In both studies, Fluarix Tetra elicited an immune response
against the three strains in common that was non-inferior to Fluarix and a superior immune
response against the additional B strain included in Fluarix Tetra. The results are presented in
Table 3.
Table 3: Post-vaccination GMT and seroconversion rates (SCR) in children (6-35 months; 3 to
< 18 years) and adults 18 years or older (ATP (95% CI))

Concomitant administration with pneumococcal vaccines:
In clinical study D-QIV-010 involving 356 adults ≥50 years of age at risk for complications of
influenza and pneumococcal diseases, subjects received Fluarix Tetra and 23-valent
pneumococcal polysaccharide vaccine (PPV23) either concomitantly or separately. For all four
Fluarix Tetra vaccine strains and the six pneumococcal serotypes (1, 3, 4, 7F, 14, and 19A) in
PPV23 evaluated in the pre-specified primary analysis, the immune response was non-inferior
between the two treatment groups. Based on a descriptive analysis for six additional
pneumococcal vaccine serotypes (5, 6B, 9V, 18C, 19F, and 23F), the immune response was
comparable between groups, with 91.7% to 100% and 90.7% to 100% of subjects attaining
seroprotective antibody levels against these serotypes in the separate and concomitant
administration group respectively.
Immunological non-inferiority has been demonstrated based on published data for all 3
Fluarix trivalent strains (D-TIV) and all 13-valent pneumococcal conjugate vaccine (PCV13)
serotypes in adults 50-59 years of age, as well as for 2 of 3 D-TIV strains and 12 of 13
PCV13 serotypes in adults >65 years of age. A lower immune response to some
pneumococcal serotypes was observed when PCV13 was given concomitantly with D-TIV as
compared to separate administration, however the clinical relevance of this observation is
unknown.

NA

Non-clinical data reveal no special hazards for humans based on conventional studies of
acute toxicity, local tolerance, repeated dose toxicity and reproductive/developmental
toxicity.

Sodium chloride, disodium phosphate dodecahydrate, potassium dihydrogen phosphate,
potassium chloride, magnesium chloride hexahydrate, α-tocopheryl hydrogen succinate,
polysorbate 80, octoxinol 10 and water for injections.
Hydrocortisone, gentamicin sulphate, ovalbumin, formaldehyde and sodium deoxycholate are
present as residues from the manufacturing process.

In the absence of compatibility studies, this medicinal product must not be mixed with other
medicinal products.

Store at 2°C - 8°C (in a refrigerator) ─ Do not freeze ─ Store in the original package in order
to protect from light.

0.5 ml in pre-filled syringe (type I glass) – pack size of 1 or 10.
Not all presentations are available in every country.

The vaccine presents as a colourless to slightly opalescent suspension.
The syringe should be shaken and inspected visually for any foreign particulate matter and/or
variation of physical aspect prior to administration. In the event of either being observed,
discard the vaccine.

1. Holding the syringe barrel in one hand (avoid holding the syringe plunger), unscrew
the syringe cap by twisting it anticlockwise.
2. To attach the needle to the syringe, twist the needle clockwise into the syringe until you
feel it lock (see picture).
3. Remove the needle protector, which on occasion can be a little stiff.
4. Administer the vaccine.

Any unused product or waste material should be disposed of in accordance with local
requirements.
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