a N = number of subjects with safety data.
b Moderate: pain, tenderness, myalgia, fatigue, headache, arthralgia, chills,
nausea, vomiting defined as “some limitation in normal daily activity”,
diarrhea defined as “4 to 5 stools a day”.
c Severe: pain, tenderness, myalgia, fatigue, headache, arthralgia, chills,
nausea, vomiting defined as “unable to perform normal daily activity”,
diarrhea defined as “6 or more watery stools a day”.
d Potentially life threatening (PLT) reaction defined as requiring emergency
room visit or hospitalization.
Unsolicited Adverse Events (AEs): The clinical safety of FLUAD
was assessed in fifteen (15) randomized, controlled studies. The
total safety population in these trials included 10,952 adults 65
years of age and older, comprising 5,754 who received FLUAD
and 5,198 who received other US licensed influenza vaccines.
The percentage of subjects with an unsolicited AE within 30 days
following vaccination was similar between vaccine groups (16.9%
FLUAD vs. 18.0% active comparator).
Serious Adverse Events (SAEs) and Deaths: In Study 1, in which
subjects were followed for SAEs and deaths for one year following
vaccination (N=3,545 FLUAD, N=3,537 AGRIFLU), the percentages
of subjects with an SAE were similar between vaccine groups (7%
FLUAD vs. 7% AGRIFLU). Four SAEs (1 FLUAD and 3 AGRIFLU)
were assessed as related to study vaccination over one year of
observation and 2 of these occurred (1 FLUAD and 1 AGRIFLU)
within 21 days following study vaccination. There were 98 deaths
(n=52 FLUAD, n=46 AGRIFLU) over one year of which none occurred
within the first 21 days following vaccination.
In 14 additional randomized, controlled studies, SAEs were collected
over a 3 to 4-week period in 4 studies, over a 8-week period in 1
study, and over a 6-month period in 9 studies (N= 2,209 FLUAD,
N=1,661 US licensed influenza vaccines). The percentages of subjects
with an SAE within 30 days (1.1% FLUAD vs. 1.8% AGRIFLU) or within
6 months (4.3% FLUAD vs. 5.9% AGRIFLU) were similar between
vaccine groups. The percentages of deaths within 30 days (0.3%
FLUAD vs. 0.6% active comparator) or within 6 months (1.0% FLUAD
vs. 1.5% active comparator) were also similar.
Adverse Events of Special Interest (AESIs): Rates of new onset
neuroinflammatory and immune mediated diseases were assessed
in a post hoc analysis of the 15 randomized controlled studies
over the time periods specified above for SAEs. The percentage
of subjects with an AESI at any time after vaccination was similar
between vaccine groups (0.9% FLUAD vs. 0.9% active comparator).
There were no notable imbalances for specific AESIs.
Safety of Annual Revaccination: In 5 of the randomized,
controlled trials, subjects were followed for SAEs and deaths
for 6 months following revaccination (N=492 FLUAD, N=330 US
licensed and non-US licensed influenza vaccines). After the
second annual vaccination, the percentages of subjects with
an SAE were similar between vaccine groups (6.1% FLUAD vs.
5.5% comparator influenza vaccines); 23 deaths (n=17 FLUAD,
n=6 comparator influenza vaccines) were reported. Causes of
death included cardiovascular events, malignancy, trauma,
gastrointestinal disorders, and respiratory failure. Clinical
characteristics of the deaths, including the variable causes,
timing since vaccination, and underlying medical conditions, do
not provide evidence for a causal relationship with FLUAD.
6.2 Postmarketing Experience
The following adverse events have been spontaneously reported
during post-approval use of FLUAD in Europe and other regions
Because these 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 the vaccine.
Blood and lymphatic system disorders:
Thrombocytopenia (some cases were severe with platelet
counts less than 5,000 per mm3), lymphadenopathy
General disorders and administration site conditions:
Extensive swelling of injected limb lasting more than one
week, injection site cellulitis-like reactions (some cases of
swelling, pain, and redness extending more than 10 cm and
lasting more than 1 week)
Immune system disorders:
Allergic reactions including anaphylactic shock, anaphylaxis
Musculoskeletal and connective tissue disorders:
Nervous system disorders:
Encephalomyelitis, Guillain-Barré Syndrome, convulsions,
neuritis, neuralgia, paraesthesia, syncope, presyncope
Skin and subcutaneous tissue disorders:
Generalized skin reactions including erythema multiforme,
urticaria pruritus or non-specific rash
Vasculitis with transient renal involvement
7 DRUG INTERACTIONS
7.1 Concomitant Use With Other Vaccines
There are no data to assess the concomitant administration of
FLUAD with other vaccines. If FLUAD is to be given at the same
time as other injectable vaccine(s), the vaccine(s) should be
administered at different injection sites.
Do not mix FLUAD with any other vaccine in the same syringe.
7.2 Concurrent Use With Immunosuppressive Therapies
Immunosuppressive or corticosteroid therapies may reduce the
immune response to FLUAD.
8 USE IN SPECIFIC POPULATIONS
Pregnancy Category B: A reproductive and developmental
toxicity study has been performed in rabbits with a dose level
that was approximately 15 times the human dose based on
body weight. The study revealed no evidence of impaired female
fertility or harm to the fetus due to FLUAD. There are, however,
no adequate and well-controlled studies in pregnant women.
Because animal reproduction studies are not always predictive of
human response, this vaccine should be used during pregnancy
only if clearly needed.
In a reproductive and developmental toxicity study, the effect
of FLUAD on embryo-fetal and post-natal development was
evaluated in pregnant rabbits. Animals were administered FLUAD
by intramuscular injection twice prior to gestation, during the
period of organogenesis (gestation day 7) and later in pregnancy
(gestation day 20), 0.5 mL (45 mcg)/rabbit/occasion (approximately
15-fold excess relative to the adult human dose based on body
weight). No adverse effects on mating, female fertility, pregnancy,
embryo-fetal development, or post-natal development were
observed. There were no vaccine-related fetal malformations or
other evidence of teratogenesis.
8.4 Pediatric Use
The safety and effectiveness of FLUAD in the pediatric population
has not been established.
8.5 Geriatric Use
Safety and immunogenicity of FLUAD have been evaluated in
adults 65 years of age and older. See Adverse Reactions (6.1) and
Clinical Studies (14)
FLUAD is a registered trademark of Seqirus Inc.
Manufactured by: Seqirus Vaccines Limited,
An affiliate of: Seqirus Inc., Holly Springs, NC 27540, USA
Systemic (cont from previous page)
Any 2.9 2.8
Moderate 0.4 0.6
Severe 0.1 0.1
PLT <0.1 0.0
Any 1.4 1.7
Moderate 0.4 0.5
Severe <0.1 0.1
PLT <0.1 0.0