Systemic (cont from previous page) Any


Moderate Severe PLT Any


Moderate Severe PLT

a N = number of subjects with safety data. b

2.9 0.4 0.1

<0.1 1.4 0.4

<0.1 <0.1

2.8 0.6 0.1 0.0 1.7 0.5 0.1 0.0

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.

Important Safety Information: INDICATIONS AND USAGE

FLUAD is an inactivated influenza vaccine indicated for active immunization against influenza disease caused by influenza virus subtypes A and type B contained in the vaccine. FLUAD is approved for use in persons 65 years of age and older.


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.

Severe allergic reaction to any component of the vaccine, including egg protein, or after a previous dose of any influenza vaccine.


• If Guillain-Barré Syndrome (GBS) has occurred within six weeks of previous influenza vaccination, the decision to give FLUAD should be based on careful consideration of the potential benefits and risks.

• The tip caps of the prefilled syringes contain natural rubber latex which may cause allergic reactions in latex sensitive individuals.

6.2 Postmarketing Experience The following adverse events have been spontaneously reported during post-approval use of FLUAD in Europe and other regions since 1997.

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.

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 and angioedema

Musculoskeletal and connective tissue disorders: Muscular weakness

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

Vascular disorders: Vasculitis with transient renal involvement


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.


• The most common (≥10%) local (injection-site) adverse reactions observed in clinical studies were injection site pain (25%) and tenderness (21%).

• The most common (≥10%) systemic adverse reactions observed in clinical studies were myalgia (15%), headache (13%), and fatigue (13%).

Please see accompanying US Full Prescribing Information for FLUAD

8.1 Pregnancy 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 UK Limited or its affiliates.

Manufactured by: Seqirus Vaccines Limited Speke, Liverpool, L249GR, UK

Distributed by: Seqirus USA Inc. 25 Deforest Avenue, Summit, NJ 07901, USA


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