Fluzone High-dose Quadrivalent

  • Vaccines

Fluzone High-dose Quadrivalent Generic Name & Formulations

General Description

Quadrivalent inactivated "split virus" influenza vaccine (Types A and B); 0.7mL dose contains a total of 240mcg of influenza virus hemagglutinin; formulation changes annually; susp for IM inj; antibiotic- and preservative-free.

Pharmacological Class

Influenza vaccine.

How Supplied

Fluzone High-Dose Quadrivalent prefilled syringe (0.7mL)—10; Fluzone Quadrivalent prefilled syringe (0.25mL, 0.5mL)—10; single-dose vial (0.5mL)—10; multi-dose vial (5mL)—1 (contains thimerosal)


  • Store refrigerated at 2° to 8°C (35° to 46°F). Do not freeze. Discard if vaccine has been frozen.


Generic Availability


Mechanism of Action

Influenza vaccine stimulates the immune system to produce antibodies that help prevent influenza disease.

Fluzone High-dose Quadrivalent Indications


Influenza immunization for patients aged ≥65yrs.

Fluzone High-dose Quadrivalent Dosage and Administration


<65yrs: use Fluzone Quadrivalent. Give by IM inj once in the deltoid. ≥65yrs: 1 dose/season.


Use Fluzone Quadrivalent.

Fluzone High-dose Quadrivalent Contraindications


Allergy to egg proteins. Life-threatening reaction to any previous flu vaccine.

Fluzone High-dose Quadrivalent Boxed Warnings

Not Applicable

Fluzone High-dose Quadrivalent Warnings/Precautions


Use current formulation only. Guillain-Barre syndrome within 6 weeks of previous flu vaccine. Immunosuppressed. Have epinephrine inj (1:1000) available. Pregnancy. Nursing mothers.


Guillain-Barré Syndrome

  • Carefully consider the potential benefits and risks to give Fluzone High-Dose Quadrivalent if Guillain-Barré Syndrome (GBS) has occurred within 6 weeks of previous influenza vaccination.

  • 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

  • Immune response may be diminished if Fluzone High-Dose Quadrivalent is given to immunocompromised individuals, including those receiving immunosuppressive therapy.

Limitations of Vaccine Effectiveness

  • Fluzone High-Dose Quadrivalent may not protect all individuals.

Pregnancy Considerations

  • Fluzone High-Dose Quadrivalent is not approved for use in persons <65 years of age.

  • There is limited human data and no animal data available to establish whether there is a vaccine-associated risk with use of Fluzone High-Dose Quadrivalent in pregnancy.

Nursing Mother Considerations

  • Fluzone High-Dose Quadrivalent is not approved for use in persons <65 years of age.

  • No human or animal data available to assess the effects of Fluzone High-Dose Quadrivalent on the breastfed infant or on milk production/excretion.

Pediatric Considerations

  • Fluzone High-Dose Quadrivalent is not established in children younger than 18 years of age.

Fluzone High-dose Quadrivalent Pharmacokinetics

See Literature

Fluzone High-dose Quadrivalent Interactions


Immunosuppressants: may get suboptimal response.

Fluzone High-dose Quadrivalent Adverse Reactions

Adverse Reactions

Local reactions (eg, pain, tenderness, swelling, erythema), malaise, headache, myalgia, irritability.

Fluzone High-dose Quadrivalent Clinical Trials

Clinical Trials

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 which compared the safety and immunogenicity of Fluzone High-Dose Quadrivalent to Fluzone High-Dose in 2670 adults 65 years of age and older conducted in the US. 

  • Patients were randomly assigned 4:1:1 to receive 1 dose of either Fluzone High-Dose Quadrivalent or 1 of 2 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]). The objective was to demonstrate noninferiority of Fluzone High-Dose Quadrivalent to Fluzone High-Dose, as assessed by HAI geometric mean antibody titers (GMTs) at Day 28 and seroconversion rates.

  • Fluzone 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.

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.

  • 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 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.

  • The relative efficacy of Fluzone High-Dose against laboratory-confirmed influenza regardless of similarity to the vaccine components was as followed:

    • Any type/subtype: 24.2% (95% CI, 9.7-36.5)

      • Influenza A: 23.6% (95% CI, 7.4-37.1)

        • A (H1N1): 11% (95% CI, -159.9, 70.1)

        • A (H3N2): 22.9% (95% CI, 5.4-37.2)

      • Influenza B: 27.4% (95% CI, -13.1, 53.8)

  • The efficacy of Fluzone High-Dose relative to Fluzone was 51.1% (95% CI: 16.8; 72.0) for the secondary endpoint, which was the occurrence of culture-confirmed influenza caused by viral types/subtypes antigenically similar to those contained in the respective annual vaccine formulations in associated with a modified CDC-defined ILI.

Fluzone High-dose Quadrivalent Note

Not Applicable

Fluzone High-dose Quadrivalent Patient Counseling

Patient Counseling

  • 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).