Differentiating Between Influenza Vaccines for Adults 65 Years or Older

SupplementsJuly 2023 Influenza Supplement

Older adults are vulnerable to severe influenza-associated complications and risks, but influenza vaccines may be less effective in this population.

With pharmacists in most of the United States preparing for the warm summer months ahead, it is difficult to imagine that the fall and winter months—and influenza season—are just around the corner. Preliminary data from the CDC suggest that influenza accounted for an estimated 27 million to 54 million illnesses, 12 million to 26 million medical visits, 300,000 to 650,000 influenza hospitalizations, and 19,000 to 58,000 deaths related to the 2022-2023 influenza season.1 Older adults (those aged ≥ 65 years) are particularly susceptible to the risks of influenza and influenza-related complications, including pneumonia.2

Influenza virus. 3D illustration showing surface glycoprotein spikes hemagglutinin purple and neuraminidase orange | Image Credit: Dr_Microbe - stock.adobe.com

Dr_Microbe - stock.adobe.com

Older adults tend to have declining immune function and chronic medical conditions, and the majority of severe influenza-related illnesses, hospitalizations, and deaths occur in those at least 65 years of age.2,3 According to the National Foundation for Infectious Diseases, older adults who contract influenza are 3 to 5 times more likely to experience a heart attack and 2 to 3 times more likely to have a stroke within the first 2 weeks of influenza infection.2 These risks underscore the vulnerability of the older adult population to influenza and its consequences, and they should serve as a reminder that pharmacists must advocate for influenza vaccination in this particular demographic.

Availability of Influenza Vaccines for Adults 65 Years or Older

Older adults are vulnerable to severe influenza-associated complications and risks, but influenza vaccines may be less effective in this population.4 During the 2022-2023 influenza season, for the first time, 3 influenza vaccine formulations for use in adults 65 years or older were preferentially recommended (Table 1).5

Influenza Vaccine Products for Adults 65 Years or Older (Licensed for the 2022-2023 Influenza Season)

Table From Pharmacy Times 2023 Influenza Guide for Pharmacists

The CDC’s Advisory Committee on Immunization Practices (ACIP) usually publishes its annual influenza vaccine recommendations in August of each year, so it is not yet known whether vaccine recommendations will vary for the 2023-2024 influenza season; however, use of these same formulations likely will be recommended for the upcoming season. Readers are encouraged to visit the CDC’s Influenza ACIP Vaccine Recommendations webpage for current information and recommendations for influenza vaccination: https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html.

High-Dose Influenza Vaccines

Available higher dose or adjuvanted influenza vaccines approved for use in older adults for the 2022-2023 influenza season are discussed below.

High-Dose, Quadrivalent, Inactivated Influenza Vaccine (Fluzone High-Dose Quadrivalent)

This vaccine formulation—approved for use only in individuals 65 years or older—contains 4 times the amount of antigen as a standard-dose influenza vaccine: 60 μg for high-dose, quadrivalent, inactivated influenza vaccine (HD-IIV4) compared with 15 μg for standard-dose inactivated vaccines.5,6 The additional antigen content is intended to create higher antibody production and a greater immune response in recipients.3 Its use is contraindicated in individuals with a history of severe allergic reaction to any vaccine component (eg, egg proteins) or to any previous dose of an influenza vaccine given.6 The most common adverse events (AEs), occurring in more than 10% of adults 65 years or older in clinical trials, were injection-site pain (41.3%), myalgia (22.7%), headache (14.4%), and malaise (13.2%).6

Quadrivalent, Recombinant Influenza Vaccine (FluBlok Quadrivalent)

This vaccine contains a recombinant hemagglutinin protein and 3 times the amount of antigen as provided by a standard-dose inactivated vaccine: 45 μg for quadrivalent, recombinant influenza vaccine (RIV4) compared with 15 μg for standard-dose inactive vaccines.3,5,7 This vaccine is approved for use in adults 18 years or older; contraindications include a severe allergic reaction (eg, anaphylaxis) to any vaccine component.7 In clinical trials, the most common AEs occurring in more than 10% of adults 50 years or olderwere injection site reactions (tenderness [34%], pain [19%]), headache (13%), and fatigue (12%).7

Quadrivalent, Adjuvanted, Inactivated Influenza Vaccine (Fluad Quadrivalent)

Approved for use in those aged 65 years or older, this is a standard-dose quadrivalent, adjuvanted, inactivated influenza vaccine (aIIV4) that contains MF59, an adjuvant added to help create a stronger immune response to vaccination.3,5,8 Contraindications to this vaccine include allergic reactions to any vaccine component (eg, egg protein) or after a previous dose of influenza vaccine was given.8 The most common AEs occurring in clinical trials in 10% or more patients aged at least 65 years were injection site pain (16.3%), headache (10.8%), and fatigue (10.5%).

Evidence for High-Dose and Adjuvanted Influenza Vaccines in Adults 65 Years or Older

The preferential recommendation for use of HD-IIV4, RIV4, or aIIV4 vaccine formulations in adults aged at least 65 years is based on beneficial results noted when these products were compared with standard-dose influenza vaccines in randomized clinical trials in older adults over several influenza seasons.5,9-11 Compared with standard-dose influenza vaccines, results from observational studies and real-world evidence in adults 65 years or older given HD-IIV4, RIV4, and aIIV4 preparations suggested modest relative benefit and protection against influenza-related complications, including influenza-associated hospitalizations and deaths.5,12 Notably, there has not been a consistent benefit observed with 1 of these specific vaccine formulations over another during previous influenza seasons. Thus, if available, any formulation could be used for a patient aged at least 65 years during an immunization encounter.5 Table 1 includes information on licensed influenza vaccine products indicated for preferential use in adults 65 years or older for the 2022-2023 influenza season.5

Influenza Vaccine Recommendations for Older Adults

For the 2022-2023 influenza season, the ACIP recommended that adults 65 years or older preferentially receive any 1 of the following high-dose or adjuvanted influenza vaccines: HD-IIV4, RIV4, or aIIV4.5 However, patients could receive a standard-dose influenza vaccine if they preferred or if none of these 3 vaccines were available at an opportunity for vaccine administration. It is of paramount importance that pharmacists be aware of emerging recommendations and influenza vaccine product licensure and availability for the upcoming 2023-2024 influenza season and of updated recommendations and evidence.

Role of the Pharmacist in Vaccinating Older Adults Against Flu

Practice-based resources to help pharmacists address concerns related to influenza in older adults are included in Table 2. Pharmacists must continue to advocate for all possible strategies to reduce illness, and influenza vaccination represents a critical aspect of that conversation.

Resources About Influenza and COVID-19 for Patients and Health Care Professionals

Table From Pharmacy Times 2023 Influenza Guide for Pharmacists

According to the CDC, annual vaccination is the most important strategy for preventing influenza infection, and it is recommended for all individuals 6 months or older.5,13 A priority for pharmacists working in all care settings—and especially for those working in community and ambulatory care settings—is counseling and provision of a strong recommendation for influenza vaccination in adults 65 years or older. Influenza vaccination in older adults is associated with reduced severity of influenza illness and a lower risk of influenza-associated hospitalization.3 Older adults should be encouraged to receive their annual influenza vaccine in September or October this year. Vaccination in July and August should be avoided in this group, if possible, unless vaccination in September or October won't be feasible.14


Regardless of what they encounter during the upcoming fall and winter months, pharmacists should use influenza season as a good opportunity to discuss the importance of infection control measures—covering their mouths and noses during coughing and sneezing, self-isolating when sick or symptomatic for at least 24 hours after fever resolves, cleaning and disinfecting surfaces likely to be contaminated, not touching one’s face, observing good hand hygiene, and learning about recommendations for vaccination against influenza—with patients.13

About The Author

Mary Barna Bridgeman, PharmD, FASCP, FCCP, BCPS, BCGP, is a clinical professor at the Ernest Mario School of Pharmacy at Rutgers University in Piscataway, New Jersey, and an internal medicine clinical pharmacist at Robert Wood Johnson University Hospital in New Brunswick, New Jersey.


  1. 2022-2023 U.S. flu season: preliminary in-season burden estimates. CDC. May 26, 2023. Accessed June 3, 2023. https://www.cdc.gov/flu/about/burden/preliminary-in-season-estimates.htm
  2. Flu in adults age 65 years and older: what are the risks? National Foundation for Infectious Diseases. Accessed June 3, 2023. https://www.nfid.org/infectious-diseases/flu-in-adults-age-65-years-and-older-whatare-the-risks/#:~:text=Older%20adults%20are%20at%20higher,of%20infection%20for%20those%2065%2B
  3. People 65 years and older need a flu shot. CDC. Updated February 13, 2023.Accessed June 3, 2023. https://www.cdc.gov/flu/pdf/freeresources/seniors/seniors-vaccination-factsheet-final.pdf
  4. Past seasons’ vaccine effectiveness estimates. CDC. June 2, 2023. Accessed June 3, 2023. https://www.cdc.gov/flu/vaccines-work/pastseasons-estimates.html#2021
  5. Grohskopf LA, Blanton LH, Ferdinands JM, et al. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices — United States, 2022-23 influenza season. MMWR Recomm Rep. 2022;71(1):1-28. doi:10.15585/mmwr.rr7101a1
  6. Fluzone High-Dose Quadrivalent (influenza vaccine), suspension, for intramuscular injection 2022-2023 formula. Prescribing information. Sanofi Pasteur; 2023. https://www.vaccineshoppe.com/us/medias/Prescribing-Information.pdf
  7. Flublok Quadrivalent (influenza vaccine), sterile solution for intramuscular injection, 2022-2023 formula. Prescribing information. Sanofi Pasteur; 2023. https://www.vaccineshoppe.com/us/medias/Prescribing-Information.pdf
  8. Fluad Quadrivalent (influenza vaccine, adjuvanted) injectable emulsion for intramuscular use 2022-2023 formula. Prescribing information. Sequiris; 2023. https://www.flu360.com/medias/USA-aQIV-23-0014-Fluad-PIMarch2023
  9. DiazGranados CA, Dunning AJ, Kimmel M, et al. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med. 2014;371(7):635-645. doi:10.1056/NEJMoa1315727
  10. Keitel WA, Treanor JJ, El Sahly HM, et al. Comparative immunogenicity of recombinant influenza hemagglutinin (rHA) and trivalent inactivated vaccine (TIV) among persons > or =65 years old. Vaccine. 2009;28(2):379-385. doi:10.1016/j.vaccine.2009.10.037
  11. Dunkle LM, Izikson R, Patriarca P, et al.; PSC12 Study Team. Efficacy of recombinant influenza vaccine in adults 50 years of age or older. N Engl J Med. 2017;376(25):2427-2436. doi:10.1056/NEJMoa1608862
  12. Izurieta HS, Lu M, Kelman J, et al. Comparative effectiveness of influenza vaccines among U.S. Medicare beneficiaries ages 65 years and older duringthe 2019-2020 season. Clin Infect Dis. 2021;73(11):e4251-e4259. doi:10.1093/cid/ciaa1727
  13. Prevent seasonal flu. CDC. December 19, 2022. Accessed June 4, 2023. https://www.cdc.gov/flu/prevent/index.html
  14. 2023-2024 CDC Flu vaccination recommendations adopted. CDC. June 29, 2023. Accessed July 5, 2023. https://www.cdc.gov/flu/spotlights/2022-2023/ flu-vaccination-recommendations-adopted.htm
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