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.

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

•  myalgia and
• headache (≥20%).

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

• tenderness (≥80%),
• swelling,
• pain,
• redness (≥60%),
• itching (≥20%) and
• bruising (≥10%).

The most common systemic adverse events were

• myalgia,
• malaise (≥30%) and
• headache (≥20%).

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

• 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

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

• Thrombocytopenia

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

• Pruritus, urticaria, and rash

General Disorders and Administration Site Conditions

• Cellulitis and large injection site swelling
• Influenza-like illness

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.

No interaction studies have been performed on interaction between influenza vaccines in general and other vaccines or medications.

• 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.