High-Dose Influenza Vaccine Recommendations

Primary Recommendations

The Advisory Committee on Immunization Practices (ACIP) recommends preferential use of higher-dose or adjuvanted influenza vaccines for adults 65 years and older 1, 2
High-dose influenza vaccine (Fluzone High-Dose) is licensed only for people 65 years and older 3, 4
The high-dose trivalent inactivated influenza vaccine (IIV3) contains a higher amount of hemagglutinin per strain compared to standard-dose vaccines 3

Patients with rheumatic and musculoskeletal diseases aged >18 and <65 years who are taking immunosuppressive medication may benefit from high-dose influenza vaccine 5, 2
Solid organ transplant recipients aged 18-64 years who are receiving immunosuppressive medications may also benefit from high-dose or adjuvanted vaccines 2
For immunocompromised individuals who have received hematopoietic cell transplantation or solid organ transplantation, clinicians could consider administering 2 doses of high-dose trivalent inactivated vaccine 6

If high-dose vaccine is not available, standard-dose influenza vaccine should be administered rather than delaying vaccination 2

Patients under 65 years without specific risk factors should receive standard-dose influenza vaccine, as high-dose formulations are not FDA-approved for this age group 3, 4
Most adults, particularly those ≥65 years, should not be immunized in July and August due to concerns about waning immunity before the peak of influenza season 6
For patients with malignant neoplasms receiving chemotherapy, influenza vaccination should generally be administered 2 weeks before cytotoxic chemotherapy when clinically possible 6
For patients who have received anti-B cell therapies, influenza vaccination should be deferred for 6 months after the last dose, ideally once there is evidence of B cell recovery 6

The high-dose influenza vaccine, Fluzone High-Dose, is specifically licensed for adults aged 65 years and older, and contains 60 μg of hemagglutinin per vaccine strain, which is four times the amount in standard-dose influenza vaccines 7, 8
Fluzone High-Dose is available as a 0.5 mL prefilled syringe with 0.0 μg mercury content, and is administered as a single dose via the intramuscular (IM) route 7, 9

The Centers for Disease Control and Prevention (CDC) recommends prescribing Fluzone High-Dose for patients aged 65 years and older, and administration is via intramuscular injection in the deltoid muscle 8, 10, 11
Only one dose (0.5 mL) of Fluzone High-Dose is required per influenza season 9, 11

The CDC reports that immunogenicity data from multiple studies have shown that Fluzone High-Dose elicits higher hemagglutination inhibition (HAI) titers against influenza virus strains compared to standard-dose vaccines in older adults 8
The Advisory Committee on Immunization Practices (ACIP) notes that while Fluzone High-Dose produces enhanced immunologic responses in adults ≥65 years, high-dose vaccine recipients may still have lower vaccine efficacy than younger adults receiving standard-dose vaccines 12, 13

The Advisory Committee on Immunization Practices (ACIP) now expresses a preferential recommendation for higher-dose or adjuvanted formulations in adults aged 65 and older 14

Fluzone High-Dose met prespecified criteria for superior efficacy compared to standard-dose vaccine in a randomized trial of 31,989 persons aged ≥65 years, with a relative efficacy of 24.2% (95% CI: 9.7%–36.5%) for preventing laboratory-confirmed influenza 14
High-dose vaccine has demonstrated consistent benefits across multiple studies in reducing hospitalizations for pneumonia and influenza, cardiorespiratory illnesses, and mortality in elderly populations 15
Among nursing home residents aged >65 years, high-dose vaccine reduced respiratory-related hospital admissions (3.4% vs. 3.9%) and mortality (17.1% vs. 18.3%) compared to standard-dose vaccine 15
The effectiveness is most pronounced in adults aged ≥75 years, though benefits extend to all individuals ≥65 years regardless of comorbidities, frailty, or prior vaccination history 15

The vaccine is available as a prefilled syringe and should not be confused with standard-dose formulations 16

High-dose vaccine is cost-effective in elderly populations and can reduce healthcare costs by 2.75% and years of life lost by over 50% 15
The benefit-to-cost ratio is most favorable in adults aged ≥75 years, though vaccination of all adults ≥65 years with high-dose formulations remains recommended 15

High-dose vaccine recipients may experience more frequent injection site reactions and systemic symptoms compared to standard-dose recipients, though the safety profile remains favorable 14

The high‑dose quadrivalent influenza vaccine (Fluzone HD‑IIV4) contains 60 µg of hemagglutinin per strain (four‑fold the standard dose) and is administered as a single 0.7 mL intramuscular injection for individuals aged ≥ 65 years. 17, 18

The MF‑59 adjuvanted quadrivalent influenza vaccine (Fluad aIIV4) includes 15 µg of hemagglutinin per strain together with the MF‑59 adjuvant to enhance the immune response in adults aged ≥ 65 years. 19