NDC 49281-120 Fluzone High-dose Quadrivalent Northern Hemisphere

Influenza A Virus A/guangdong-maonan/swl1536/2019 Cnic-1909 (h1n1) Antigen (formaldehyde Inactivated), Influenza A Virus A/hong Kong/2671/2019 (h3n2) Antigen (formaldehyde Inactivated), Influenza B Virus B/phuket/3073/2013 Antigen (formaldehyde Inactivated), And Influenza B Virus B/washington/02/2019 Antigen (formaldehyde Inactivated)

NDC Product Code 49281-120

NDC CODE: 49281-120

Proprietary Name: Fluzone High-dose Quadrivalent Northern Hemisphere What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Influenza A Virus A/guangdong-maonan/swl1536/2019 Cnic-1909 (h1n1) Antigen (formaldehyde Inactivated), Influenza A Virus A/hong Kong/2671/2019 (h3n2) Antigen (formaldehyde Inactivated), Influenza B Virus B/phuket/3073/2013 Antigen (formaldehyde Inactivated), And Influenza B Virus B/washington/02/2019 Antigen (formaldehyde Inactivated) What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

NDC Code Structure

  • 49281 - Sanofi Pasteur Inc.
    • 49281-120 - Fluzone High-dose Quadrivalent Northern Hemisphere

NDC 49281-120-65

Package Description: 10 SYRINGE, GLASS in 1 PACKAGE > .7 mL in 1 SYRINGE, GLASS (49281-120-88)

NDC Product Information

Fluzone High-dose Quadrivalent Northern Hemisphere with NDC 49281-120 is a a vaccine lable product labeled by Sanofi Pasteur Inc.. The generic name of Fluzone High-dose Quadrivalent Northern Hemisphere is influenza a virus a/guangdong-maonan/swl1536/2019 cnic-1909 (h1n1) antigen (formaldehyde inactivated), influenza a virus a/hong kong/2671/2019 (h3n2) antigen (formaldehyde inactivated), influenza b virus b/phuket/3073/2013 antigen (formaldehyde inactivated), and influenza b virus b/washington/02/2019 antigen (formaldehyde inactivated). The product's dosage form is injection, suspension and is administered via intramuscular form.

Labeler Name: Sanofi Pasteur Inc.

Dosage Form: Injection, Suspension - A liquid preparation, suitable for injection, which consists of solid particles dispersed throughout a liquid phase in which the particles are not soluble. It can also consist of an oil phase dispersed throughout an aqueous phase, or vice-versa.

Product Type: Vaccine What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Fluzone High-dose Quadrivalent Northern Hemisphere Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • INFLUENZA A VIRUS A/GUANGDONG-MAONAN/SWL1536/2019 CNIC-1909 (H1N1) ANTIGEN (FORMALDEHYDE INACTIVATED) 60 ug/.7mL
  • INFLUENZA A VIRUS A/HONG KONG/2671/2019 IVR-208 (H3N2) ANTIGEN (FORMALDEHYDE INACTIVATED) 60 ug/.7mL
  • INFLUENZA B VIRUS B/PHUKET/3073/2013 ANTIGEN (FORMALDEHYDE INACTIVATED) 60 ug/.7mL
  • INFLUENZA B VIRUS B/WASHINGTON/02/2019 ANTIGEN (FORMALDEHYDE INACTIVATED) 60 ug/.7mL

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • GELATIN, UNSPECIFIED (UNII: 2G86QN327L)
  • OCTOXYNOL-9 (UNII: 7JPC6Y25QS)
  • FORMALDEHYDE (UNII: 1HG84L3525)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Intramuscular - Administration within a muscle.
  • Intramuscular - Administration within a muscle.

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Sanofi Pasteur Inc.
Labeler Code: 49281
FDA Application Number: BLA103914 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: BLA - A product marketed under an approved Biologic License Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 07-02-2020 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2021 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

* Please review the disclaimer below.

Fluzone High-dose Quadrivalent Northern Hemisphere Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1 Indications And Usage

Fluzone® High-Dose Quadrivalent is a vaccine indicated for active immunization for the prevention of influenza caused by influenza A subtype viruses and type B viruses contained in the vaccine.Fluzone High-Dose Quadrivalent is indicated for use in persons 65 years of age and older.

2 Dosage And Administration

For intramuscular use only

2.1 Dose And Schedule

Fluzone High-Dose Quadrivalent should be administered as a single 0.7 mL injection by the intramuscular route in adults 65 years of age and older.

2.2 Administration

Inspect Fluzone High-Dose Quadrivalent visually for particulate matter and/or discoloration prior to administration. If either of these conditions exists the vaccine should not be administered.Before administering a dose of vaccine, shake the prefilled syringe.The preferred site for intramuscular injection is the deltoid muscle. The vaccine should not be injected into the gluteal area or areas where there may be a major nerve trunk.Do not administer this product intravenously.Fluzone High-Dose Quadrivalent should not be combined through reconstitution or mixed with any other vaccine.

3 Dosage Forms And Strengths

Fluzone High-Dose Quadrivalent is a suspension for injection.Fluzone High-Dose Quadrivalent is supplied in prefilled syringes, 0.7 mL, for adults 65 years of age and older.

4 Contraindications

A severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine [see Description (11)], including egg protein, or to a previous dose of any influenza vaccine is a contraindication to administration of Fluzone High-Dose Quadrivalent.

5.1 Guillain-Barré Syndrome

If Guillain-Barré syndrome (GBS) has occurred within 6 weeks following any previous influenza vaccination, the decision to give Fluzone High-Dose Quadrivalent should be based on careful consideration of the potential benefits and risks.The 1976 swine influenza vaccine was associated with an elevated risk of GBS. Evidence for a causal relation of GBS with other influenza vaccines is inconclusive; if an excess risk exists, it is probably slightly more than 1 additional case per 1 million persons vaccinated. GBS has also been temporally associated with influenza disease. (See references 1 and 2.)

5.2 Preventing And Managing Allergic Reactions

Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of the vaccine.

5.3 Altered Immunocompetence

If Fluzone High-Dose Quadrivalent is administered to immunocompromised persons, including those receiving immunosuppressive therapy, the immune response may be lower than expected.

5.4 Limitations Of Vaccine Effectiveness

Vaccination with Fluzone High-Dose Quadrivalent may not protect all recipients.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse event rates observed in the clinical trial(s) of a vaccine cannot be directly compared to rates in the clinical trial(s) of another vaccine and may not reflect the rates observed in practice. One clinical study has evaluated the safety of Fluzone High-Dose Quadrivalent. Study 1 (NCT03282240, see https://clinicaltrials.gov) was a randomized, active-controlled, modified double-blind pre-licensure trial conducted in the U.S. The study compared the safety and immunogenicity of Fluzone High-Dose Quadrivalent to those of Fluzone High-Dose (trivalent formulation). The safety analysis set included 1777 Fluzone High-Dose Quadrivalent recipients, 443 Fluzone High-Dose recipients, and 450 investigational Fluzone High-Dose containing the alternate B influenza strain recipients. The most common reactions occurring after Fluzone High-Dose Quadrivalent administration were injection-site pain (41.3%), myalgia (22.7%), headache (14.4%), and malaise (13.2%). Onset usually occurred within the first 3 days after vaccination. The majority of solicited reactions resolved within three days of vaccination.Table 1 displays solicited adverse reactions for Fluzone High-Dose Quadrivalent compared to Fluzone High-Dose reported within 7 days after vaccination and collected using standardized diary cards.Table 1: Study 1NCT03282240: Frequency of Solicited Injection-Site Reactions and Systemic Adverse Events within 7 Days after Vaccination with Fluzone High-Dose Quadrivalent or Fluzone High-Dose, Adults 65 Years of Age and OlderFluzone High-Dose Quadrivalent (NN is the number of vaccinated participants with available data for the events listed=1761-1768)Fluzone High-DoseSafety results for the Fluzone High-Dose and investigational Fluzone High-Dose containing the alternate B influenza strain recipients were pooled for the analysis. (N=885-889)PercentagePercentageAnyGrade 3AnyGrade 3Local ReactionsInjection Site PainGrade 3: A type of AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention.41.30.736.40.2Injection Site ErythemaGrade 3: > 100 mm6.20.65.70.2Injection Site Swelling4.90.34.70.1Injection Site Induration3.70.23.50.1Injection Site Bruising1.30.01.10.0Systemic ReactionsMyalgia22.70.918.90.7Headache14.40.613.60.4Malaise13.20.713.40.4Shivering5.40.34.70.3FeverGrade 3: ≥ 102.1°F (39.0°C)0.40.20.90.2Based on data from Fluzone High-Dose, solicited injection site reactions and systemic adverse reactions were slightly more frequent after vaccination with Fluzone High-Dose compared to a standard-dose vaccine.Unsolicited non-serious adverse events were reported in 279 (15.7%) recipients in the Fluzone High-Dose Quadrivalent group and 140 (15.7%) recipients in the Fluzone High-Dose group. The most commonly reported unsolicited adverse event was cough.Within 180 days post-vaccination, 80 (4.5%) Fluzone High-Dose Quadrivalent recipients and 48 (5.4%) Fluzone High-Dose recipients experienced a serious adverse event (SAE). None of the SAEs were assessed as related to the study vaccines.

6.2 Postmarketing Experience

  • The following additional adverse events have been spontaneously reported during the postmarketing use of Fluzone High-Dose, Fluzone, or Fluzone Quadrivalent and may occur in people receiving Fluzone High-Dose Quadrivalent. 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 vaccine exposure. Adverse events were included based on one or more of the following factors: severity, frequency of reporting, or strength of evidence for a causal relationship to Fluzone High-Dose, Fluzone, or Fluzone Quadrivalent.Blood and Lymphatic System Disorders: Thrombocytopenia, lymphadenopathyImmune System Disorders: Anaphylaxis, other allergic/hypersensitivity reactions (including urticaria, angioedema)Eye Disorders: Ocular hyperemiaNervous System Disorders: Guillain-Barré syndrome (GBS), convulsions, febrile convulsions, myelitis (including encephalomyelitis and transverse myelitis), facial palsy (Bell's palsy), optic neuritis/neuropathy, brachial neuritis, syncope (shortly after vaccination), dizziness, paresthesiaVascular Disorders: Vasculitis, vasodilatationRespiratory, Thoracic and Mediastinal Disorders: Dyspnea, cough, wheezing, throat tightness, oropharyngeal pain, and rhinorrheaGastrointestinal Disorders: VomitingSkin and Subcutaneous Tissue Disorders: Stevens-Johnson syndromeGeneral Disorders and Administration Site Conditions: pruritus, asthenia/fatigue, chest pain, chills

8.1 Pregnancy

Fluzone High-Dose Quadrivalent is not approved for use in persons <65 years of age. There are limited human data on Fluzone High-Dose and no animal data available on Fluzone High-Dose Quadrivalent to establish whether there is a vaccine-associated risk with use of Fluzone High-Dose Quadrivalent in pregnancy.

8.2 Lactation

Fluzone High-Dose Quadrivalent is not approved for use in persons <65 years of age. No human or animal data are available to assess the effects of Fluzone High-Dose Quadrivalent on the breastfed infant or on milk production/excretion.

8.4 Pediatric Use

Safety and effectiveness of Fluzone High-Dose Quadrivalent in children younger than 18 years of age have not been established.

8.5 Geriatric Use

Safety, immunogenicity, and efficacy of Fluzone High-Dose Quadrivalent have been evaluated in adults 65 years of age and older [see Adverse Reactions (6.1) and Clinical Studies (14)].

11 Description

Fluzone High-Dose Quadrivalent for intramuscular injection is an inactivated influenza vaccine, prepared from influenza viruses propagated in embryonated chicken eggs. The virus-containing allantoic fluid is harvested and inactivated with formaldehyde. Influenza virus is concentrated and purified in a linear sucrose density gradient solution using a continuous flow centrifuge. The virus is then chemically disrupted using a non-ionic surfactant, octylphenol ethoxylate (Triton® X-100), producing a "split virus." The split virus is further purified and then suspended in sodium phosphate-buffered isotonic sodium chloride solution. The Fluzone High-Dose Quadrivalent process uses an additional concentration factor after the ultrafiltration step in order to obtain a higher hemagglutinin (HA) antigen concentration.Fluzone High-Dose Quadrivalent suspension for injection is clear and slightly opalescent in color.Neither antibiotics nor preservative are used in the manufacture of Fluzone High-Dose Quadrivalent.The Fluzone High-Dose Quadrivalent prefilled syringe presentation is not made with natural rubber latex.Fluzone High-Dose Quadrivalent is standardized according to United States Public Health Service requirements and is formulated to contain HA of each of the following four influenza strains recommended for the 2018-2019 influenza season: A/Michigan/45/2015 X-275 (H1N1), A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2), B/Phuket/3073/2013 (B Yamagata lineage), and B/Maryland/15/2016 BX-69A (a B/Colorado/6/2017-like virus, B Victoria lineage). The amounts of HA and other ingredients per dose of vaccine are listed in Table 2.Table 2: Fluzone High-Dose Quadrivalent Ingredients IngredientQuantity(per dose)Fluzone High-Dose Quadrivalent 0.7 mL DoseActive Substance: Split influenza virus, inactivated strainsper United States Public Health Service (USPHS) requirement:240 mcg HA total  A (H1N1)60 mcg HA  A (H3N2)60 mcg HA  B (Victoria Lineage)60 mcg HA  B (Yamagata Lineage)60 mcg HAOther:  Sodium phosphate-buffered isotonic sodium chloride solution QSQuantity sufficient to appropriate volume  Formaldehyde≤140 mcg  Octylphenol ethoxylate≤350 mcg  GelatinNonePreservativeNone

12.1 Mechanism Of Action

Influenza illness and its complications may follow influenza infection. Global surveillance of influenza viruses identifies yearly antigenic variants. Since 1977, antigenic variants of influenza A (H1N1 and H3N2) viruses and influenza B viruses have been in global circulation. Specific levels of hemagglutination inhibition (HI) antibody titer post-vaccination with inactivated influenza virus vaccines have not been correlated with protection from influenza virus infection. In some human studies, antibody titers ≥1:40 have been associated with protection from influenza illness in up to 50% of participants. (See references 3 and 4.)Antibodies against one influenza virus type or subtype confer limited or no protection against another. Furthermore, antibodies to one antigenic variant of influenza virus might not protect against a new antigenic variant of the same type or subtype. Frequent development of antigenic variants through antigenic drift is the virologic basis for seasonal epidemics and the reason for the usual change of one or more new strains in each year's influenza vaccine. Therefore, influenza vaccines are standardized to contain the hemagglutinins of influenza virus strains representing the influenza viruses likely to be circulating in the U.S. during the influenza season.Fluzone High-Dose Quadrivalent stimulates the immune system to produce antibodies that help prevent influenza disease.

Carcinogenesis & Mutagenesis & Impairment Of Fertility

Carcinogenesis, Mutagenesis, Impairment of FertilityFluzone High-Dose Quadrivalent has not been evaluated for carcinogenic or mutagenic potential or for impairment of fertility.

14.1 Immunogenicity Of Fluzone High-Dose Quadrivalent In Adults 65 Years Of Age And Older

Study 1 (NCT03282240, see http://clinicaltrials.gov) was a randomized, active-controlled, modified double-blind trial in adults 65 years of age and older conducted in the US. The study compared the safety and immunogenicity of Fluzone High-Dose Quadrivalent to those of Fluzone High-Dose. The objective was to demonstrate immunologic non-inferiority of Fluzone High-Dose Quadrivalent to Fluzone High-Dose, as assessed by HAI geometric mean antibody titers (GMTs) at Day 28 and seroconversion rates, to strains common to formulations of both vaccines, based on pre-specified criteria. A total of 2670 adults from 65 years of age were randomized (4:1:1) to receive one dose of either Fluzone High-Dose Quadrivalent or one of two formulations of Fluzone High-Dose (one formulation contained a B strain of the Victoria lineage [TIV-HD1] while the other contained a B strain of the Yamagata lineage [TIV-HD2]).Females accounted for 58.2% of participants in the Fluzone High-Dose Quadrivalent group and 57.4% of participants in the Fluzone High-Dose group (TIV-HD1 and TIV-HD2, pooled). The mean age was 72.9 years (range: 65 through 100 years) in the Fluzone High-Dose Quadrivalent group and the mean age was 73.0 (range: 65 through 95 years) in the Fluzone High-Dose group. The percentage of subjects 75 years of age or older was 35.4% in the Fluzone High-Dose Quadrivalent group and 35.8% in the Fluzone High-Dose group. Most participants were White (91.2% and 89.7%), followed by Black (6.8% and 8.0%), and Hispanic (2.8% and 2.6%) in the Fluzone High-Dose Quadrivalent and Fluzone High-Dose groups, respectively.The immunogenicity results of Study 1 are summarized in Table 3 and Table 4 below.Table 3: Study 1NCT03282240: Post-vaccination HAI Antibody GMTs and Analyses of Non-inferiority of Fluzone High-Dose Quadrivalent Relative to Fluzone High-Dose, Adults 65 Years of Age and Older, Per-Protocol Analysis SetInfluenza StrainGMTGMT RatioMet Predefined Non-inferiority CriteriaPredefined noninferiority criterion for the GMT ratio: the lower limit of the 95% CI of the GMT ratio (QIV-HD divided by TIV-HD) is >0.667QIV-HDTIV-HD1TIV-HD1 contained A/Michigan/45/2015 (H1N1), A/Hong Kong/4801/2014 (H3N2), and B/Brisbane/60/2008 (B1, Victoria lineage)(B1 Victoria)TIV-HD2TIV-HD2 contained A/Michigan/45/2015 (H1N1), A/Hong Kong/4801/2014 (H3N2), and B/Phuket/3073/2013 (B2, Yamagata lineage)(B2 Yamagata)QIV-HD over TIV-HD(95% CI)NN is the number of vaccinated participants with available data for the immunologic endpoint listed=1679-1680N=423N=430A (H1N1)Pooled TIV-HD group includes subjects vaccinated with either TIV-HD1 or TIV-HD2 for the A strain comparison3123740.83(0.744; 0.932)YesA (H3N2)5635940.95(0.842; 1.066)YesB1 (Victoria)516476--1.08(0.958; 1.224)YesB2 (Yamagata)578--5801.00(0.881; 1.129)YesTable 4: Study 1NCT03282240: Seroconversion Rates and Analyses of Non-inferiority of Fluzone High-Dose Quadrivalent Relative to Fluzone High-Dose, Adults 65 Years of Age and Older, Per-Protocol Analysis SetInfluenza StrainSeroconversion Rates (Percentage) Seroconversion Rates: For subjects with a pre-vaccination titer <10 (1/dil), proportion of subjects with a post-vaccination titer ≥40 (1/dil) and for subjects with a pre-vaccination titer ≥10 (1/dil), proportion of subjects with a ≥four-fold increase from pre-vaccination to post-vaccination titerDifference of Seroconversion RatesMet Predefined Non-inferiority CriteriaPredefined noninferiority criterion for seroconversion: the lower limit of the two-sided 95% CI of the difference of the seroconversion rates (QIV-HD minus TIV-HD) is >-10%QIV-HDTIV-HD1TIV-HD1 contained A/Michigan/45/2015 (H1N1), A/Hong Kong/4801/2014 (H3N2), and B/Brisbane/60/2008 (B1, Victoria lineage)(B1 Victoria)TIV-HD2TIV-HD2 contained A/Michigan/45/2015 (H1N1), A/Hong Kong/4801/2014 (H3N2), and B/Phuket/3073/2013 (B2, Yamagata lineage)(B2 Yamagata)QIV-HD minus TIV-HD(95% CI)NN is the number of vaccinated participants with available data for the immunologic endpoint listed=1668-1669N=420-421N=428A (H1N1)Pooled TIV-HD group includes subjects vaccinated with either TIV-HD1 or TIV-HD2 for the A strain comparison50.453.7-3.27(-7.37; 0.86)YesA (H3N2)49.850.5-0.71(-4.83; 3.42)YesB1 (Victoria)36.539.0---2.41(-7.66; 2.70)YesB2 (Yamagata)46.6--48.4-1.75(-7.04; 3.53)YesFluzone High-Dose Quadrivalent was as immunogenic as Fluzone High-Dose for GMTs and seroconversion rates for the common influenza strains. Fluzone High-Dose Quadrivalent induced a superior immune response, based on a pre-specified superiority criterion, with respect to the additional B strain than the immune response induced by Fluzone High-Dose formulation that did not contain the additional B strain.

14.2 Efficacy Of Fluzone High-Dose In Adults 65 Years Of Age And Older

The efficacy of Fluzone High-Dose (trivalent formulation) is relevant to Fluzone High-Dose Quadrivalent since both vaccines are manufactured according to the same process and have overlapping compositions.Study 2 (NCT01427309) was a multi-center, double-blind, post-licensure efficacy trial conducted in the U.S. and Canada in which adults 65 years of age and older were randomized (1:1) to receive either Fluzone High-Dose or Fluzone. The study was conducted over two influenza seasons (2011-2012 and 2012-2013); 53% of participants enrolled in the first year of the study were re-enrolled and re-randomized in the second year. The per-protocol analysis set for efficacy assessments included 15,892 Fluzone High-Dose recipients and 15,911 Fluzone recipients. The majority (67%) of participants in the per-protocol analysis set for efficacy had one or more high-risk chronic comorbid conditions. In the per-protocol analysis set, females accounted for 57.2% of participants in the Fluzone High-Dose group and 56.1% of participants in the Fluzone group. In both groups, the median age was 72.2 years (range 65 through 100 years). Overall, most participants in the study were White (95%); approximately 4% of study participants were Black, and approximately 6% reported Hispanic ethnicity.The primary endpoint of the study was the occurrence of laboratory-confirmed influenza (as determined by culture or polymerase chain reaction) caused by any influenza viral type/subtype in association with influenza-like illness (ILI), defined as the occurrence of at least one of the following respiratory symptoms: sore throat, cough, sputum production, wheezing, or difficulty breathing; concurrent with at least one of the following systemic signs or symptoms: temperature >99.0°F, chills, tiredness, headaches or myalgia. Participants were monitored for the occurrence of a respiratory illness by both active and passive surveillance, starting 2 weeks post-vaccination for approximately 7 months. After an episode of respiratory illness, nasopharyngeal swab samples were collected for analysis; attack rates and vaccine efficacy were calculated (see Table 5). Table 5: Study 2NCT01427309: Relative Efficacy Against Laboratory-Confirmed InfluenzaLaboratory-confirmed: culture or polymerase-chain-reaction–confirmed Regardless of Similarity to the Vaccine Components, Associated with Influenza-Like IllnessOccurrence of at least one of the following respiratory symptoms: sore throat, cough, sputum production, wheezing, or difficulty breathing; concurrent with at least one of the following systemic signs or symptoms: temperature >99.0°F, chills, tiredness, headaches or myalgia, Adults 65 Years of Age and Older Fluzone High-DoseNN is the number of vaccinated participants in the per-protocol analysis set for efficacy assessments=15,892nn is the number of participants with protocol-defined influenza-like illness with laboratory confirmation (%)FluzoneN=15,911n (%)Relative Efficacy% (95% CI)Any type/subtypePrimary endpoint227 (1.43)300 (1.89)24.2 (9.7; 36.5)The prespecified statistical superiority criterion for the primary endpoint (lower limit of the 2-sided 95% CI of the vaccine efficacy of Fluzone High-Dose relative to Fluzone >9.1%) was met.  Influenza A190 (1.20)249 (1.56)23.6 (7.4; 37.1)    A (H1N1)8 (0.05)9 (0.06)11.0 (-159.9; 70.1)    A (H3N2)171 (1.08)222 (1.40)22.9 (5.4; 37.2)  Influenza BIn the first year of the study the influenza B component of the vaccine and the majority of influenza B cases were of the Victoria lineage; in the second year the influenza B component of the vaccine and the majority of influenza B cases were of the Yamagata lineage37 (0.23)51 (0.32)27.4 (-13.1; 53.8)A secondary endpoint of the study was the occurrence of culture-confirmed influenza caused by viral types/subtypes antigenically similar to those contained in the respective annual vaccine formulations in association with a modified CDC-defined ILI, defined as the occurrence of a temperature >99.0°F (>37.2°C) with cough or sore throat. The efficacy of Fluzone High-Dose relative to Fluzone for this endpoint was 51.1% (95% CI: 16.8; 72.0).

15 References

  • 1Lasky T, Terracciano GJ, Magder L, et al. The Guillain-Barré syndrome and the 1992-1993 and 1993-1994 influenza vaccines. N Engl J Med 1998;339:1797-802.2Baxter, R, et al. Lack of Association of Guillain-Barré Syndrome with Vaccinations. Clin Infect Dis 2013;57(2):197-204.3Hannoun C, Megas F, Piercy J. Immunogenicity and protective efficacy of influenza vaccination. Virus Res 2004;103:133-138.4Hobson D, Curry RL, Beare AS, Ward-Gardner A. The role of serum haemagglutination-inhibiting antibody in protection against challenge infection with influenza A2 and B viruses. J Hyg Camb 1972;70:767-777.

16.1 How Supplied

Single-dose, prefilled syringe, without needle, 0.7 mL (NDC 49281-120-88) (not made with natural rubber latex). Supplied as package of 10 (NDC 49281-120-65).

16.2 Storage And Handling

Store Fluzone High-Dose Quadrivalent refrigerated at 2° to 8°C (35° to 46°F). DO NOT FREEZE. Discard if vaccine has been frozen.Do not use after the expiration date shown on the label.

17 Patient Counseling Information

  • See FDA-approved patient labeling (Patient Information).Inform the patient or caregiver that Fluzone High-Dose Quadrivalent contains killed viruses and cannot cause influenza.Fluzone High-Dose Quadrivalent stimulates the immune system to produce antibodies that help protect against influenza.Instruct that annual influenza vaccination is recommended.Instruct vaccine recipients and caregivers to report adverse reactions to their healthcare provider and/or to Vaccine Adverse Event Reporting System (VAERS).Give the Vaccine Information Statements to recipients or caregivers, which are required by the National Childhood Vaccine Injury Act of 1986 prior to each immunization. These materials are available free of charge at the Centers for Disease Control and Prevention (CDC) website (www.cdc.gov/vaccines).

Other

Fluzone is a registered trademark of Sanofi Pasteur Inc.Manufactured by:Sanofi Pasteur Inc.Swiftwater PA 18370 USA

Patient Information Sheetfluzone® High-Dose Quadrivalentinfluenza Vaccine

  • Please read this information sheet before getting Fluzone High-Dose Quadrivalent vaccine. This summary is not intended to take the place of talking with your healthcare provider. If you have questions or would like more information, please talk with your healthcare provider.What is Fluzone High-Dose Quadrivalent vaccine?Fluzone High-Dose Quadrivalent is a vaccine that helps protect against influenza illness (flu).Fluzone High-Dose Quadrivalent vaccine is for people 65 years of age and older.Vaccination with Fluzone High-Dose Quadrivalent vaccine may not protect all people who receive the vaccine.Who should not get Fluzone High-Dose Quadrivalent vaccine?You should not get Fluzone High-Dose Quadrivalent vaccine if you:ever had a severe allergic reaction to eggs or egg products.ever had a severe allergic reaction after getting any flu vaccine.are younger than 65 years of age.Tell your healthcare provider if you have or have had:Guillain-Barré syndrome (severe muscle weakness) after getting a flu vaccine.problems with your immune system as the immune response may be diminished.How is Fluzone High-Dose Quadrivalent vaccine given?Fluzone High-Dose Quadrivalent vaccine is a shot given into the muscle of the arm.What are the possible side effects of Fluzone High-Dose Quadrivalent vaccine?The most common side effects of Fluzone High-Dose Quadrivalent vaccine are:pain, redness, and swelling where you got the shotmuscle achetirednessheadacheThese are not all of the possible side effects of Fluzone High-Dose Quadrivalent vaccine. You can ask your healthcare provider for a list of other side effects that is available to healthcare professionals.Call your healthcare provider for advice about any side effects that concern you. You may report side effects to the Vaccine Adverse Event Reporting System (VAERS) at 1-800-822-7967 or https://vaers.hhs.gov.Why should I get Fluzone High-Dose Quadrivalent vaccine instead of a standard-dose quadrivalent influenza vaccine?Among persons 65 years of age and older, Fluzone High-Dose Quadrivalent generated a similar immune response to Fluzone High-Dose and is expected to provide better protection against influenza compared to standard-dose quadrivalent influenza vaccines.What are the ingredients in Fluzone High-Dose Quadrivalent vaccine?Fluzone High-Dose Quadrivalent vaccine contains 4 killed flu virus strains. There is no live flu virus in Fluzone High-Dose Quadrivalent. Fluzone High-Dose Quadrivalent cannot cause the flu.Inactive ingredients include formaldehyde and octylphenol ethoxylate.Manufactured by: Sanofi Pasteur Inc.Swiftwater, PA 18370 USA

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