What is Afluria Quadrivalent (Influenza Vaccine), and how does it work?
Generic drug: Influenza Vaccine
Brand name: Afluria Quadrivalent
Afluria Quadrivalent (Influenza Vaccine) is an inactivated influenza vaccine indicated for active immunization against influenza disease caused by influenza A subtype viruses and type B viruses contained in the vaccine.
Afluria Quadrivalent is approved for use in persons 18 years of age and older.
What are the side effects of Afluria Quadrivalent?
In adults 18 through 64 years of age, the most commonly reported injection-site adverse reaction observed in clinical studies with
Afluria Quadrivalent administered by needle and syringe was pain (≥40%).
The most common systemic adverse events observed were
In adults 65 years of age and older, the most commonly reported injection-site adverse reaction observed in clinical studies with
Afluria Quadrivalent administered by needle and syringe was pain (≥20%).
The most common systemic adverse event observed was
- myalgia (≥10%).
The safety experience with Afluria (trivalent formulation) is relevant to
Afluria Quadrivalent because both vaccines
are manufactured using the same process and have overlapping compositions.
In adults 18 through 64 years of age, the most commonly reported injection-site adverse reactions observed in a clinical study with
Afluria (trivalent formulation) using the PharmaJet Stratis Needle-Free Injection System were
The most common systemic adverse events were
Clinical Trials Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a vaccine cannot be directly compared to rates in the clinical studies of another vaccine and may not reflect the rates observed in clinical practice.
- Clinical safety data for Afluria Quadrivalent have been collected in one clinical trial, Study 1, a randomized, double-blind, active-controlled trial conducted in the US in 3449 subjects ages 18 years and older.
- Subjects in the safety population received one dose of either
Afluria Quadrivalent (N=1721) or one of two formulations of comparator trivalent influenza vaccine (Afluria, TIV-1 N=864 or TIV-2 N=864) each containing an influenza type
B virus
that corresponded to one of the two B viruses in Afluria Quadrivalent (a type B
virus of the Yamagata lineage or a type B virus of the Victoria lineage),
respectively. - The mean age of the population was 58 years, 57% were female, and
racial groups consisted of 82% White, 16% Black, and 2% other; 5% of subjects
were Hispanic/Latino. - The age sub-groups were 18 through 64 years and 65 years
and older with mean ages of 43 years and 73 years, respectively. In this study,
Afluria Quadrivalent and comparator trivalent influenza vaccines were
administered by needle and syringe. - Local (injection-site) adverse reactions and systemic adverse events were solicited for 7 days post-vaccination (Table 1).
- Injection site
cellulitis, cellulitis-like reactions (defined as concurrent Grade 3 pain, redness, and swelling/lump), and Grade 3 swelling/lump were monitored for 28 days post-vaccination. - Unsolicited adverse events were collected for 28 days post-vaccination. Serious adverse events (SAEs), including deaths, were collected for 180 days post-vaccination.
Table 1: Proportion of Subjects Per Age Cohort with Any Solicited Local Adverse Reactions or Systemic Adverse Events within 7 Days after Administration of
Afluria Quadrivalent or Trivalent Influenza Vaccine (Study 1)a
Percentage (%) b of Subjects in each Age Cohort Reporting an Event
Subjects 18 through 64 years
Subjects ≥ 65 years
Afluria Quadrivalent
N= 854 c
TIV-1
N= 428 c
TIV-2
N= 430 c
Afluria Quadrivalent
N= 867 c
TIV-1
N= 436 c
TIV-2
N= 434 c
Any
Gr 3
Any
Gr 3
Any
Gr 3
Any
Gr 3
Any
Gr 3
Any
Gr 3
Local dverse Reactions d
Pain
47.9
0.7
43.7
1.4
50.7
1.2
24.6
0.1
22.7
0
21.0
0.2
Swelling/Lump
3.7
0.1
2.3
0
3.5
0.2
3.2
0.5
1.8
0
1.6
0
Redness
2.9
0
2.8
0
2.8
0
4.2
0.3
2.1
0
2.5
0.2
Systemic Adverse Events e
Myalgia (muscle ache)
25.5
1.9
23.4
1.4
24.2
1.2
12.7
0.3
14.0
0.7
12.2
0.5
Headache
21.7
1.7
15.2
0.9
19.1
1.2
8.4
0
7.1
0.2
7.8
0.7
Malaise
8.9
0.7
9.1
0
9.3
0.7
4.4
0.5
5.0
0.2
5.1
0.2
Nausea
6.9
0.6
7.7
0.5
6.3
1.2
1.6
0
1.8
0
2.1
0.2
Chills
4.8
0.6
4.4
0.2
4.7
0.5
2.0
0
2.1
0.5
1.4
0.2
Vomiting
1.5
0.4
0.9
0
2.3
0.7
0.5
0.1
0
0
0.7
0.2
Fever
1.1
0.4
0.9
0
0.5
0
0.2
0
0.9
0
0.5
0.2
Abbreviations: Gr 3, Grade 3.
a NCT02214225
b Proportion of subjects reporting each solicited local adverse reaction or systemic adverse event by study vaccine group based on the number of subjects contributing any follow up safety information for at least one data value of an individual sign/symptom.
c N = number of subjects in the Safety Population for each study vaccine group.
d Local adverse reactions: Grade 3 pain is that which prevents daily activity; Swelling/Lump and redness: any = ≥ 20mm diameter, Grade 3 = ≥ 100mm diameter.
e Systemic adverse events: Fever: any = ≥ 100.4°F, Grade 3 = ≥ 102.2°F; Grade 3 for all other adverse events is that which prevents daily activity.
- In the 28 days following vaccination, no subject experienced cellulitis or a cellulitis-like reaction. All Grade 3 swelling/lump reactions began within 7 days of vaccination and are included in Table 1.
- In the 28 days following vaccination, 20.5%, 20.1%, and 20.7% of adults 18 through 64 years and 20.3%, 24.1%, and 20.0% of adults ≥65 years who received
Afluria Quadrivalent , TIV-1, and TIV-2, respectively, reported unsolicited adverse events. Rates of individual events were similar between treatment groups, and most events were mild to moderate in severity. - In the 180 days following vaccination, 2.3%, 1.6%, and 1.5% of all subjects who received
Afluria Quadrivalent , TIV-1, and TIV-2, respectively, experienced SAEs, including six deaths, five in the
Afluria Quadrivalent group and one in the TIV-2 group. The majority of SAEs occurred after Study Day 28 and in subjects ≥65 years of age who had
co-morbid illnesses. No SAEs or deaths appeared related to the study vaccines. - Safety information has also been collected in a clinical study of
Afluria (trivalent formulation) administered using the PharmaJet Stratis Needle-Free Injection System (Study 2). - Study 2 included 1,247 subjects for safety analysis, ages 18 through 64 years, randomized to receive
Afluria by either the PharmaJet Stratis Needle-Free Injection System (624 subjects) or needle and syringe (623 subjects). - No deaths or vaccine-related serious adverse events were reported in Study 2. Local (injection-site) adverse reactions and systemic adverse events were solicited for 7 days post-vaccination (Table 2).
Table 2: Proportion of Subjects 18 through 64 Years of Age with Solicited Local Adverse Reactions or Systemic Adverse Events within 7 Days after Administration of
Afluria (trivalent formulation) by PharmaJet Stratis Needle-Free Injection System or Needle and Syringe (Study 2)a
Percentage b of Subjects Reporting Event
Study 2
Subjects 18 through 64 years
Afluria (trivalent formulation)
PharmaJet Stratis Needle-Free Injection System
N=540-616 c
Needle and Syringe
N=599-606 c
Any
Grade 3
Any
Grade 3
Local Adverse Reactions d
Tenderness
89.4
2.1
77.9
1.0
Swelling
64.8
1.7
19.7
0.2
Pain
64.4
0.8
49.3
0.7
Redness
60.1
1.3
19.2
0.3
Itching f
28.0
0.0
9.5
0.2
Bruising
17.6
0.2
5.3
0.0
Systemic Adverse Events e
Myalgia
36.4
0.8
35.5
1.0
Malaise
31.2
0.7
28.4
0.5
Headache
24.7
1.3
22.1
1.3
Chills
7.0
0.2
7.2
0.2
Nausea
6.6
0.2
6.5
0.0
Vomiting
1.3
0.0
1.8
0.2
Fever
0.3
0.0
0.3
0.0
a NCT01688921
b Proportion of subjects reporting each local adverse reaction or systemic adverse event by treatment group based on the number of subjects contributing at least one data value for an individual sign/symptom (individual event denominators).
c N = number of subjects in the Safety Population for each treatment group. Denominators for the PharmaJet Stratis Needle-Free Injection System group were: N=540 for itching and N=605-616 for all other parameters. Denominators for the needle and syringe group were: N=527 for itching and N=599-606 for all other parameters.
d Local adverse reactions: Grade 3 is pain, tenderness or itching that prevents daily activity; Swelling, redness or bruising: any = ≥ 25mm diameter, Grade 3 = > 100mm diameter.
e Systemic adverse events: Fever: any = ≥ 100.4°F, Grade 3 = ≥ 102.2°F; Grade 3 for all other adverse events is that which prevents daily activity.
f A total of 155 subjects (approximately randomly distributed between PharmaJet Stratis Needle-Free Injection System and needle and syringe groups) received Diary Cards without itching listed as a solicited symptom.
In adults 18 through 64 years who received Afluria (trivalent formulation) administered via PharmaJet Stratis Needle-Free Injection System, commonly reported unsolicited adverse events were
- headache (4.2%),
- injection site
hematoma (1.8%), - injection site
erythema (1.1%), - myalgia (1.0%) and
- nausea (1.0%).
Postmarketing Experience
Because postmarketing reporting of adverse events is voluntary and from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure. The adverse events described have been included in this section because they:
- 1) represent reactions that are known to occur following immunizations generally or influenza immunizations specifically;
- 2) are potentially serious; or
- 3) have been reported frequently.
There are no postmarketing data available for Afluria Quadrivalent . The adverse events listed below reflect experience in both children and adults and include those identified during post-approval use of
Afluria (trivalent formulation) outside the US since 1985.
The post-marketing experience with Afluria (trivalent formulation) included the following:
Blood And Lymphatic System Disorders
Immune System Disorders
- Allergic or immediate hypersensitivity reactions including
anaphylactic shock and serum sickness
Nervous System Disorders
-
Neuralgia,
paresthesia, convulsions (including febrile seizures),
encephalomyelitis,
encephalopathy, neuritis or
neuropathy,
transverse myelitis, and
GBS
Vascular Disorders
- Vasculitis which may be associated with transient renal involvement
Skin And Subcutaneous Tissue Disorders
General Disorders And Administration Site Conditions
- Cellulitis and large injection site swelling
- Influenza-like illness
What is the dosage for Afluria Quadrivalent?
For Intramuscular (IM) Use Only.
- By needle and syringe (18 years of age and older)
- By PharmaJet Stratis Needle-Free Injection System (18 through 64 years of age)
Administer as a single 0.5 mL dose.
Immediately before use, shake thoroughly and inspect visually. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever suspension and container permit. If either of these conditions exists, the vaccine should not be administered.
The preferred site for intramuscular injection is the deltoid muscle of the upper arm.
When using the multi-dose vial, shake the vial thoroughly before withdrawing each dose.
It is recommended that small syringes (0.5 mL or 1 mL) be used to minimize any product loss.
To use the PharmaJet Stratis Needle-Free Injection System, refer to the Instructions for Use for the PharmaJet Stratis Needle-Free Injection System.
What drugs interact with Afluria Quadrivalent?
No interaction studies have been performed on interaction between influenza vaccines in general and other vaccines or medications.
Is Afluria Quadrivalent safe to use while pregnant or breastfeeding?
- All pregnancies have a risk of birth defect, loss, or other adverse outcomes.
- In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
- There are no data for Afluria Quadrivalent administered to pregnant women to inform vaccine-associated risks in pregnancy.
- Available data on Afluria (trivalent formulation) administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy.
- It is not known whether Afluria Quadrivalent is excreted in human milk.
- Data are not available to assess the effects of Afluria Quadrivalent on the breastfed infant or on milk production/excretion.