Systemic Myalgia
Any
Moderate Severe Any
Fatigue
Moderate Severe PLTd Any
Headache
Moderate Severe PLT Any
Arthralgia
Moderate Severe Any
Chills
Moderate Severe PLT Any
Diarrhea
Moderate Severe PLT Any
≥ 38.0°C to ≤ 38.4°C
Fever
≥ 38.5°C to ≤ 38.9°C
39.0°C to ≤ 40.0°C
≥ 40.0°C Any
Nausea
Moderate Severe PLT Any
Vomiting
Moderate Severe PLT
14.7 2.6 0.3
13.3 3.1 0.4 0.0
13.2 3.0 0.4 0.0 8.5 1.6 0.2 6.7 1.5 0.3
<0.1 4.8 1.3 0.3
<0.1 3.6 1.8
1.3 0.4
0.1 2.9 0.4 0.1
<0.1 1.4 0.4
<0.1 <0.1
a N = number of subjects with safety data. b
9.7 1.8 0.7
10.4 2.4 0.6
<0.1 11.2 2.6 0.6
<0.1 7.8 1.6 0.6 4.7 1.2 0.3 0.0 4.5 0.9 0.2
<0.1 3.4 1.7
1.3 0.4
0.0 2.8 0.6 0.1 0.0 1.7 0.5 0.1 0.0
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
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
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.
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
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 since 1997.
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