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AFLURIA® QUADRIVALENT, for Intramuscular Injection DESCRIPTION AFLURIA QUADRIVALENT, Influenza Vaccine for intramuscular injection, is a sterile, clear, colorless to slightly opalescent suspension with some sediment that resuspends upon shaking to form a homogeneous suspension. AFLURIA QUADRIVALENT is prepared from influenza virus propagated in the allantoic fluid of embryonated chicken eggs. Following harvest, the virus is purified in a sucrose density gradient using continuous flow zonal 230 centrifugation. The purified virus is inactivated with beta-propiolactone, and the virus particles are disrupted using sodium taurodeoxycholate to produce a “split virion”. The disrupted virus is further purified and suspended in a phosphate buffered isotonic solution. AFLURIA QUADRIVALENT is standardized according to USPHS requirements for the 2016-2017 influenza season and is formulated to contain 60 mcg hemagglutinin (HA) per 0.5 mL dose in the recommended ratio of 15 mcg HA for each of the four influenza strains recommended for the 2016-2017 Northern Hemisphere influenza season: A/California/7/2009 (H1N1), NYMC X-181, A/Hong Kong/4801/2014 (H3N2), NYMC X-263B, B/Phuket/3073/2013 and B/Brisbane/60/2008. Thimerosal, a mercury derivative, is not used in the manufacturing process for the single dose presentation. This presentation does not contain preservative. The multi-dose presentation contains thimerosal added as a preservative; each 0.5 mL dose contains 24.5 mcg of mercury. A single 0.5 mL dose of AFLURIA QUADRIVALENT contains sodium chloride (4.1 mg), monobasic sodium phosphate (80 mcg), dibasic sodium phosphate (300 mcg), monobasic potassium phosphate (20 mcg), potassium chloride (20 mcg), and calcium chloride (0.5 mcg). From the manufacturing process, each 0.5 mL dose may also contain residual amounts of sodium taurodeoxycholate (≤ 10 ppm), ovalbumin (< 1 mcg), sucrose (< 10 mcg), neomycin sulfate (≤ 62 nanograms [ng]), polymyxin B (≤ 11 ng), and beta-propiolactone (≤ 1.5 ng). The rubber tip cap and plunger used for the preservative-free, single-dose syringes and the rubber stoppers used for the multi-dose vial were not made with natural rubber latex.

INDICATIONS AFLURIA® QUADRIVALENT 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. DOSAGE AND ADMINISTRATION 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. HOW SUPPLIED Dosage Forms And Strenghts AFLURIA QUADRIVALENT is a sterile suspension for intramuscular injection (see DESCRIPTION). AFLURIA QUADRIVALENT is supplied in two presentations: 0.5 mL pre-filled syringe (single dose). 5 mL multi-dose vial (ten 0.5 mL doses). Storage And Handling How Supplied Each product presentation includes a package insert and the following components: Presentation Carton NDC Number Components Pre-Filled Syringe 33332-316-01 Ten 0.5 mL single-dose syringes fitted with a Luer-Lok™ attachment without needles [NDC 33332-316-02] Multi-Dose Vial 33332-416-10 One 5 mL vial, which contains ten 0.5 mL doses [NDC 33332-416-11] Storage And Handling Store refrigerated at 2−8°C (36−46°F). Do not freeze. Discard if product has been frozen. Protect from light. Do not use AFLURIA QUADRIVALENT beyond the expiration date printed on the label. Between uses, return the multi-dose vial to the recommended storage conditions. Once the stopper of the multi-dose vial has been pierced the vial must be discarded within 28 days. Manufactured by: Seqirus Pty Ltd, Parkville, Victoria, 3052, Australia. Revised: Aug 2016

OVERDOSE No Information Provided CONTRAINDICATIONS AFLURIA QUADRIVALENT is contraindicated in individuals with known severe allergic reactions (e.g., anaphylaxis) to any component of the vaccine including egg protein, or to a previous dose of any influenza vaccine (see DESCRIPTION).

SIDE EFFECTS 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 (see DESCRIPTION). 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 (see Clinical Studies). 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 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 DRUG INTERACTIONS No interaction studies have been performed on interaction between influenza vaccines in general and other vaccines or medications.

WARNINGS Included as part of the "PRECAUTIONS" Section PRECAUTIONS Guillain-Barré Syndrome If Guillain-Barré Syndrome (GBS) has occurred within 6 weeks of previous influenza vaccination, the decision to give AFLURIA QUADRIVALENT should be based on careful consideration of the potential benefits and risks. The 1976 swine influenza vaccine was associated with an increased frequency of GBS. Evidence for a causal relation of GBS with subsequent vaccines prepared from other influenza viruses is unclear. If influenza vaccine does pose a risk, it is probably slightly more than one additional case per 1 million persons vaccinated. Preventing And Managing Allergic Reactions Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of the vaccine. Altered Immunocompetence If AFLURIA QUADRIVALENT is administered to immunocompromised persons, including those receiving immunosuppressive therapy, the immune response may be diminished. Limitations Of Vaccine Effectiveness Vaccination with AFLURIA QUADRIVALENT may not protect all individuals. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of Fertility AFLURIA QUADRIVALENT has not been evaluated for carcinogenic or mutagenic potential, or male infertility in animals. A developmental toxicity study conducted in rats vaccinated with AFLURIA (trivalent formulation) revealed no impact on female fertility (see Use In Specific Populations). Use In Specific Populations Pregnancy Risk Summary 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. There were no developmental toxicity studies of AFLURIA QUADRIVALENT performed in animals. The developmental effects of AFLURIA (trivalent formulation) are relevant to AFLURIA QUADRIVALENT because both vaccines are manufactured using the same process and have overlapping compositions. A developmental toxicity study of AFLURIA (trivalent formulation) has been performed in female rats administered 0.5 mL (divided) of AFLURIA (trivalent formulation) prior to mating and during gestation. This study revealed no evidence of harm to the fetus due to AFLURIA (trivalent formulation) (see 8.1 Data). Clinical Considerations Disease-associated Maternal and/or Embryo-Fetal Risk Pregnant women are at increased risk for severe illness due to influenza compared to non-pregnant women. Pregnant women with influenza may be at increased risk for adverse pregnancy outcomes, including preterm labor and delivery. Data Animal Data In a developmental toxicity study, female rats were administered 0.5 mL (divided) of AFLURIA (trivalent formulation) by intramuscular injection 21 days and 7 days prior to mating, and on gestation day 6. Some rats were administered an additional dose on gestation day 20. No vaccine-related fetal malformations or variations and no adverse effects on pre- weaning development were observed in the study. Lactation Risk Summary 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. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for AFLURIA QUADRIVALENT and any potential adverse effects on the breastfed child from AFLURIA QUADRIVALENT or from the underlying maternal condition. For preventive vaccines, the underlying maternal condition is susceptibility to disease prevented by the vaccine or the effects on milk production. Pediatric Use The safety and efficacy of AFLURIA QUADRIVALENT in persons less than 18 years has not been established in clinical trials. Administration of CSL’s 2010 Southern Hemisphere trivalent influenza vaccine was associated with increased rates of fever and febrile seizures, predominantly in children below the age of 5 years as compared to previous years, in postmarketing reports confirmed by postmarketing studies. Geriatric Use In clinical studies, AFLURIA QUADRIVALENT has been administered to, and safety information collected for, 867 subjects aged 65 years and older (see ADVERSE REACTIONS). The 65 years and older age group included 539 subjects 65 through 74 years and 328 subjects 75 years and older. After administration of AFLURIA QUADRIVALENT, hemagglutination-inhibiting antibody responses were non-inferior to comparator trivalent influenza (TIV-1 and TIV-2) in persons 65 years of age and older, but were lower than younger adult subjects (see Clinical Studies). The PharmaJet Stratis Needle-Free Injection System is not approved as a method of administering AFLURIA QUADRIVALENT to adults 65 years of age and older due to lack of adequate data supporting safety and effectiveness in this population.