Fluzone High-Dose Quadrivalent (Influenza Vaccine): 10 yearsa of proven protection in adults 65+1,2

 

a Trivalent formulation approved and launched in 2009. Spans trivalent and quadrivalent formulations.

Trivalent formulation:
Superior efficacy for adults 65+a

24% (95% CI: 10-37) better protection against influenza due to any lab-confirmed circulating strain compared with standard-dose Fluzone (Influenza Vaccine).2

a The pre-specified statistical superiority criterion for the primary endpoint was met

The efficacy of the trivalent formulation is relevant to Fluzone High-Dose Quadrivalent since both vaccines are manufactured according to the same process and have overlapping compositions.2

Solicited injection site reactions and systemic adverse reactions were slightly more frequent after vaccination with the HD-TIV compared with a SD-TIV.2

Full efficacy and safety data

HD-TIV=high-dose trivalent influenza vaccine
SD-TIV=standard-dose trivalent influenza vaccine

Quadrivalent formulation:
4-strain protection with 4X the antigen

Induces an immune response that is noninferior to trivalent high-dose formulations against all 4 strains2:

  • A(H3N2)
  • A(H1N1)
  • B Victoria lineage
  • B Yamagata lineage

Similar rates of injection site and systemic adverse reactions compared with the trivalent formulation2

60 micrograms (mcg) hemagglutinin (HA) per strain vs 15 mcg HA in Fluzone Quadrivalent (Influenza Vaccine)2,3

0.7-mL single-dose prefilled syringe2

Indication

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

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Safety and Immuno-bridging Study

In an immuno-bridging study, Fluzone High-Dose Quadrivalent induced a noninferior immune response compared with two HD-TIV formulations containing either influenza B Victoria or B Yamagata lineages2,4

SUBJECTS4

2,670 adults 65+ years of age

SEASON4

2017-2018

4:1:1 RANDOMIZED4

High-dose quadrivalent influenza vaccine vs HD- TIV1 vs HD-TIV2

POST VACCINATION GEOMETRIC MEAN TITER (GMT) RATIO2,4

Predefined Noninferiority Criterion:
lower limit of the 95% CI must be >0.667

POST VACCINATION SEROCONVERSION RATES2,4

Predefined Noninferiority Criterion:
lower limit of the 95% CI must be >-10%

 

Fluzone High-Dose Quadrivalent exhibited a similar safety profile compared with HD-TIV formulations2,4

Rates of any solicited local and systemic reactions, including grade 3 reactions, were similar among Fluzone High-Dose Quadrivalent and Fluzone High-Dose trivalent formulation recipients in adults 65+ years of age.2,4

HD-QIV (n=1761-1768)

HD-TIV (n=885-889)


a Grade 3: ≥102.1 °F.

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Efficacy and Safety Study

According to the primary endpoint in a randomized controlled trial, HD-TIV provided superior efficacy compared to standard-dose Fluzone

DESIGN2

Randomized (1:1), active-controlled, modified double-blind trial

STUDY SEASONS2

2011-2012 and 2012-2013

STUDY POPULATION2

31,803 community-dwelling adults 65+ years of age

PRIMARY ENDPOINT2,5,a

24%

(95% CI: 10-37)

better protection against influenza

due to any laboratory-confirmed, circulating strain

a 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.

SECONDARY ENDPOINT2,5

51%

(95% CI: 17-72)

better protection against influenza

due to strains antigenically similar to vaccine components

Safety data

In a randomized, double blind controlled immunogenicity and safety study in 65+, solicited injection site reactions and systemic adverse reactions were slightly more frequent with vaccination with HD-TIV compared with SD-TIV6

SD-TIV (n=1258-1260)

HD-TIV (n=2569-2572)


a Grade 3: ≥102.1 °F.

In an efficacy trial, HD-TIV was associated with fewer serious adverse events (SAEs) of any kind, including hospitalizations, compared with SD-TIV5,7

Study results found an 8% (95% CI: 1-15) reduced risk for SAEsa, including all-cause hospitalization.5

This result was primarily due to the lower frequency of various illness-associated complications.


a Any SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires medical hospitalization or prolongation of existing hospitalization, results in persistent disability or significant disability incapacity, is a congenital anomality/birth defect and an important medical event.5

Real-world evidence across a variety of flu-related complications

The effectiveness of the trivalent formulation is relevant to Fluzone High-Dose Quadrivalent since both vaccines are manufactured according to the same process and have overlapping compositions.

The outcomes reported in these publications contain information not included in the Prescribing Information.

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All-Cause, Cardiorespiratory, and Influenza- and Pneumonia-Related Hospitalizations8

In a 5-year study, HD-TIV was associated with fewer hospitalizations vs standard-dose influenza vaccines

STUDY METHODOLOGY:

Design: Retrospective Observational Cohort

Population: ~3.6 Million Person-Years, US Veterans 66+ Years of Age (HD-TIV: 158,636; SD-TIV: 3,480,288)

Author Affiliations: Veterans Health Administration (VHA),a Sanofi Pasteurb

Comparison: Fluzone High-Dose (HD-TIV) vs Standard-Dose Influenza Vaccines (SD-TIV)

Data Sources: VHA Electronic Medical Records, Medicare Administrative Files

a Lead author.
b Grant funding support.

Swipe to see complete results or rotate your phone to view in landscape mode

STUDY LIMITATIONS:

VHA has a 98% male population, which tends to have greater disease burden than the general population.

No diagnosis codes, whether parts of medical or billing records, could capture conditions that are difficult to measure or are unmeasured.

Reference: Young-Xu Y, et al. Vaccine. 2019;37:1484-1490.

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Influenza Hospitalization and Postinfluenza Mortality9

In a 2-year study, HD-TIV was associated with fewer postinfluenza deaths and influenza hospitalizations vs standard-dose influenza vaccines

STUDY METHODOLOGY:

Design: Retrospective Observational Cohort

Population: ~6.1 Million Adults 65+ Years of Age Immunized in Pharmacies (HD-TIV: 2,547,821; SD-TIV: 3,560,591)

Author Affiliations: US Food and Drug Administration, Centers for Disease Control and Prevention, Centers for Medicare and Medicaid Services

Comparison: Fluzone High-Dose vs Standard-Dose Influenza Vaccines

Data Sources: Medicare Fee-For-Service Claims

Swipe to see complete results or rotate your phone to view in landscape mode

aDeath within 30 days of a confirmed influenza infection
bDefined by International Classification of Diseases, Ninth Revision, Clinical Modification.
cThe mortality risk reduction in the 2013-2014 season, although positive, was not statistically significant.

STUDY LIMITATIONS:

Outcomes may not represent laboratory-confirmed influenza infections due to the lack of laboratory results in Medicare date

Results may be confounded by chronic conditions

Reference: Shay DK, et al.
J Infect Dis.2017;215:510-517.

To order Fluzone High-Dose Quadrivalent, call 1-800-VACCINE (1-800-822-2463) or click the button below.

Order fluzone high-dose quadrivalentFluzone High-Dose Quadrivalent (Influenza Vaccine)

Important Safety Information

Fluzone Quadrivalent, Flublok Quadrivalent, and Fluzone High-Dose Quadrivalent should not be administered to anyone who has had a severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine (including egg protein for Fluzone Quadrivalent and Fluzone High-Dose Quadrivalent) or after previous dose of the respective vaccine. In addition, Fluzone Quadrivalent and Fluzone High-Dose Quadrivalent should not be administered to anyone who has had a severe allergic reaction after previous dose of any influenza vaccine.

Important Safety Information

Fluzone Quadrivalent, Flublok Quadrivalent, and Fluzone High-Dose Quadrivalent should not be administered to anyone who has had a severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine (including egg protein for Fluzone Quadrivalent and Fluzone High-Dose Quadrivalent) or after previous dose of the respective vaccine. In addition, Fluzone Quadrivalent and Fluzone High-Dose Quadrivalent should not be administered to anyone who has had a severe allergic reaction after previous dose of any influenza vaccine.

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

If Guillain-Barré syndrome has occurred within 6 weeks following previous influenza vaccination, the decision to give Fluzone Quadrivalent, Flublok Quadrivalent, and Fluzone High-Dose Quadrivalent should be based on careful consideration of the potential benefits and risks.

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

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

For Fluzone Quadrivalent, in children 6 months through 35 months of age, the most common injection-site reactions were pain or tenderness, erythema, and swelling; the most common solicited systemic adverse reactions were irritability, abnormal crying, malaise, drowsiness, appetite loss, myalgia, vomiting, and fever. In children 3 years through 8 years of age, the most common injection-site reactions were pain, erythema, and swelling; the most common solicited systemic adverse reactions were myalgia, malaise, and headache. In adults 18 years and older, the most common injection-site reaction was pain; the most common solicited systemic adverse reactions were myalgia, headache, and malaise.

For Flublok Quadrivalent, in adults 18 through 49 years of age, the most common injection-site reactions were tenderness and pain; the most common solicited systemic adverse reactions were headache, fatigue, myalgia, and arthralgia. In adults 50 years of age and older, the most common injection-site reactions were tenderness and pain; the most common solicited systemic adverse reactions were headache, and fatigue.

For Fluzone High-Dose Quadrivalent, in adults 65 years of age and older, the most common injection-site reaction was pain; the most common solicited systemic adverse reactions were myalgia, headache, and malaise.

For Fluzone Quadrivalent, Flublok Quadrivalent, and Fluzone High-Dose Quadrivalent, other adverse reactions may occur.

Before administration, please see the full Prescribing Information for Fluzone Quadrivalent, Flublok Quadrivalent, or Fluzone High-Dose Quadrivalent. Also, please see complete Patient Information for Fluzone Quadrivalent or Fluzone High-Dose Quadrivalent.

Fluzone Quadrivalent Influenza Vaccine logoFlublok Quadrivalent Influenza Vaccine logoFluzone High-Dose Quadrivalent Influenza Vaccine logo

References: 1. Food and Drug Administration. December 23, 2009 Approval Letter - Fluzone High-Dose. https://wayback.archive-it.org/7993/20170723030619/https://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm195481.htm. Accessed April 29, 2021. 2. Fluzone High-Dose Quadrivalent [Prescribing Information]. Swiftwater, PA: Sanofi Pasteur Inc. 3. Fluzone Quadrivalent [Prescribing Information]. Swiftwater, PA: Sanofi Pasteur Inc. 4. Chang L-J, Meng Y, Janosczyk H, Landolfi V, Talbot HK; for the QHD00013 Study Group. Safety and immunogenicity of high-dose quadrivalent influenza vaccine in adults ≥65 years of age: a phase 3 randomized clinical trial. Vaccine. 2019;37:5825-5834. 5. DiazGranados CA, Dunning AJ, Kimmel M, et al. Efficacy of high-dose vs standard-dose influenza vaccine in older adults. N Engl J Med. 2014;371:635-645. 6. Falsey AR, Treanor JJ, Tornieporth N, et al. Randomized, double-blind controlled phase 3 trial comparing the immunogenicity of high-dose and standard-dose influenza vaccine in adults 65 years of age and older. J Infect Dis. 2009;200:172-180. 7. Sanofi Pasteur Inc. Data on file, 2021. 8. Young-Xu Y, Snider JT, van Aalst R, et al. Analysis of relative effectiveness of high-dose vs standard-dose influenza vaccines using an instrumental variable method. Vaccine. 2019;37:1484‑1490. 9. Shay DK, Chillarige Y, Kelman J, et al. Comparative effectiveness of high-dose vs standard-dose influenza vaccines among US Medicare beneficiaries in preventing postinfluenza deaths during 2012-2013 and 2013-2014. J Infect Dis. 2017;215:510-517.

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