Influenza Virus Vaccine Inactivated (Monograph)

Brand names: Afluria, Fluad, Fluarix, Flucelvax, Flulaval, Fluzone
Drug class: Vaccines

Medically reviewed by Drugs.com on Oct 26, 2023. Written by ASHP.

Warning

On October 15, 2021, the National Alert Network (NAN) issued an alert to make vaccine providers aware of reports of accidental mix-ups between the influenza (flu) and COVID-19 vaccines.⁶⁰⁰ The alert is based on 16 cases reported to the Institute for Safe Medication Practices (ISMP) error reporting programs. Most of the reports ISMP has received involve administration of one of the COVID-19 vaccines instead of an influenza vaccine; in 3 cases, patients received an influenza vaccine instead of a COVID-19 vaccine.

Because most of the errors were reported by consumers, details about the contributing factors were not provided in many cases. However, possible contributing factors include increased demand for vaccination services, the ability to administer the flu and COVID-19 vaccines during the same visit, syringes located next to each other, unlabeled syringes, distractions, and staffing shortages. The alert provides recommendations for preventing such vaccine mix-ups. For additional information, consult the NAN alert at [Web].

Introduction

Inactivated virus vaccine.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁶⁰ ¹⁸⁶ ¹⁹⁰ Seasonal influenza vaccine inactivated (IIV) contains noninfectious, suitably inactivated influenza virus types A and B subunits representing influenza strains likely to circulate in the US during the upcoming influenza season and is used to stimulate active immunity to influenza strains contained in the vaccine.¹⁰⁰ ¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁶⁰ ¹⁸⁶ ¹⁹⁰

Uses for Influenza Virus Vaccine Inactivated

Prevention of Seasonal Influenza A and B Virus Infections

Prevention of seasonal influenza virus infection in adults,¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁶⁰ ¹⁸⁶ ¹⁹⁰ adolescents,¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁹⁰ children,¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ and infants ≥6 months of age.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸

Influenza is an acute viral infection; influenza viruses spread from person to person mainly through large-particle respiratory droplet transmission.¹⁰⁰ ¹⁶⁶ In the US, annual epidemics of seasonal influenza occur, usually during the fall or winter.¹⁰⁰ Influenza viruses can cause illness in any age group; children have highest rate of infection.¹⁰⁰ ¹⁶⁶ Influenza can exacerbate underlying medical conditions or lead to pneumonia in certain individuals.¹⁰⁰ ¹⁶⁶ Adults ≥65 years of age, children <2 years of age, and individuals with chronic medical conditions have highest risk of influenza-related complications and death.¹⁰⁰ ¹⁶⁶

Annual vaccination is the primary means of preventing seasonal influenza and its complications.¹⁰⁰ Annual influenza vaccination necessary since immunity declines in the year following vaccination and circulating influenza strains change from year to year.¹⁰⁰

CDC Advisory Committee on Immunization Practices (ACIP), AAP, and others recommend routine influenza vaccination for all individuals ≥6 months of age using an age-appropriate seasonal influenza vaccine, unless contraindicated.¹⁰⁰ ¹¹² ¹⁹⁹ ²⁰⁰ ²³⁵ Vaccination against seasonal influenza recommended for otherwise healthy individuals as well as those who have medical conditions that put them at increased risk for influenza-related complications.¹⁰⁰ ¹¹² Seasonal influenza vaccination is particularly important for individuals at increased risk for severe influenza or influenza-related outpatient, emergency department, or hospital visits and those who live with or care for such individuals (e.g., health-care personnel, household or other close contacts).¹⁰⁰ (See Table 1.)

Table 1. ACIP and AAP Recommend Target Groups for Seasonal Influenza Vaccination Efforts Using an Appropriate Vaccine:100112
All infants and children 6 through 59 months of age
All adults ≥50 years of age
Adults, adolescents, and children ≥6 months of age with chronic pulmonary (including asthma), cardiovascular (excluding isolated hypertension), renal, hepatic, neurologic, hematologic, or metabolic disorders (including diabetes mellitus)
Adults, adolescents, and children ≥6 months of age who are immunocompromised due to any cause (including, but not limited to, immunosuppression caused by medications or HIV infection)
Women who are or will be pregnant during the influenza season
Children and adolescents 6 months through 18 years of age receiving long-term aspirin- or salicylate-containing therapy who might be at risk for Reye’s syndrome after influenza infection
Adults, adolescents, and children ≥6 months of age who are residents of nursing homes and other long-term care facilities
American Indians and Alaska Natives
Extremely obese individuals (body mass index ≥40)
Health-care personnel
Household contacts (including children ≥6 months of age) and caregivers of children <5 years of age (especially contacts of infants <6 months of age)
Household contacts (including children ≥6 months of age) and caregivers of adults ≥50 years of age
Household contacts (including children ≥6 months of age) and caregivers of individuals with medical conditions that put them at high risk for severe influenza complications

All influenza vaccines available in the US are quadrivalent formulations containing antigens representing 2 influenza A strains (H1N1 and H3N2) and 2 influenza B strains (B/Victoria lineage and B/Yamagata lineage).¹⁰⁰ ¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁸⁶ ¹⁹⁰

Several different types of influenza virus vaccines are commercially available, including an inactivated virus vaccine (influenza virus vaccine inactivated [IIV]),¹⁰⁰ ¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁶⁰ ¹⁸⁶ ¹⁹⁰ an adjuvanted inactivated virus vaccine (influenza vaccine, adjuvanted [aIIV]),¹⁰⁰ ¹⁸⁶ a recombinant vaccine (influenza vaccine recombinant [RIV]),¹⁰⁰ ¹⁸³ and a live attenuated virus vaccine (influenza vaccine live intranasal [LAIV]).¹⁰⁰ ¹⁵⁷ The various vaccine formulations also differ based on method of manufacturer (egg-based versus cell culture-based), dose (standard versus high-dose), and route of administration (e.g., parenteral versus intranasal),¹⁰⁰

Select specific influenza vaccine based on age and health status of the individual.¹⁰⁰ ¹¹² For many individuals, more than one type of influenza vaccine may be appropriate.¹⁰⁰ ¹¹²

ACIP and AAP state that there are no preferential recommendations for any specific vaccine type or trade name when more than one licensed, recommended, and age-appropriate vaccine is available, with the exception of selection of influenza vaccines for individuals ≥65 years of age.¹⁰⁰ ¹¹² If an age-appropriate vaccine is available and there are no contraindications, do not delay influenza vaccination to obtain a specific product.¹⁰⁰ ¹¹²

Although most inactivated influenza vaccines are egg-based,¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁶⁰ ¹⁸⁶ a quadrivalent cell culture-based inactivated vaccine (Flucelvax; ccIIV) also is available.¹⁹⁰

An adjuvant-containing inactivated influenza vaccine (Fluad; aIIV) is available for use only in adults ≥65 years of age.¹⁸⁶ The adjuvant is MF59C.1 (MF59), a squalene-based oil-in-water emulsion¹⁸⁶ included to increase antibody response.⁵⁶⁹

An inactivated influenza vaccine containing a higher antigen content (Fluzone High-Dose) than that contained in standard-dose inactivated influenza vaccines is available for use only in adults ≥65 years of age.¹⁰⁰ ¹⁶⁰

Seasonal influenza vaccines are not effective against all strains of influenza, but may be effective against those strains (and possibly closely related strains) represented in the vaccine.¹⁰⁰ ¹⁶⁶

Current information regarding influenza surveillance and updated recommendations for prevention and treatment of seasonal influenza is available from CDC at [Web].

Influenza Vaccination During the Coronavirus Disease 2019 (COVID-19) Pandemic

CDC and ACIP state that efforts to ensure influenza vaccination for all individuals ≥6 months of age for the upcoming (current) influenza season are of paramount importance to reduce influenza-related morbidity and mortality and reduce the impact of respiratory illnesses in the population and the resulting burdens on the health-care system.¹⁰⁰ SARS-CoV-2 (causative agent of COVID-19) is expected to circulate in the US during the influenza season; the extent of continued or recurrent SARS-CoV-2 circulation during the time influenza viruses are circulating is not known.¹⁰⁰ Vaccination against influenza can reduce prevalence of influenza illness and reduce incidence of influenza symptoms that might be confused with COVID-19 symptoms (i.e., fever, cough, dyspnea).¹⁰⁰ In addition, prevention of influenza and reduction in severity of influenza illness and associated outpatient visits, hospitalizations, and intensive care unit admissions could alleviate stress on the US health-care system.¹⁰⁰

ACIP recommends that influenza vaccination should be deferred in symptomatic individuals with moderate or severe COVID-19 until recovery and deferral also may be considered in persons with mild or asymptomatic COVID-19 illness.¹⁰⁰

Influenza Virus Vaccine Inactivated Dosage and Administration

General

Administer seasonal influenza vaccine every year before exposure to seasonal influenza.¹⁰⁰ In the US, localized influenza outbreaks indicating start of annual influenza season can occur as early as October and peak influenza activity (which often is close to the midpoint of influenza activity for the season) usually occurs in January or February or later.¹⁰⁰

ACIP recommends offering influenza vaccination by the end of October, if possible, and continuing to offer vaccination as long as influenza viruses are circulating and unexpired vaccine is available.¹⁰⁰ Although influenza vaccination by the end of October is recommended, vaccination in December or later (even if influenza activity has begun) is likely to be beneficial in the majority of influenza seasons.¹⁰⁰

When 2 doses of influenza vaccine are required in children 6 months through 8 years of age, give first dose as soon as possible after vaccine becomes available since this allows second dose to be given by the end of October.¹⁰⁰ For children and adults requiring only a single dose of influenza vaccine, there is evidence that early vaccination (i.e., in July or August) is likely to be associated with suboptimal immunity (waning immunity) before end of influenza season, particularly in older adults.¹⁰⁰ Community vaccination programs should balance maximizing likelihood of persistence of vaccine-induced protection through the season with avoiding missed opportunities for vaccination or vaccinating after influenza circulation has already started, especially in those ≥65 years of age.¹⁰⁰

Administration

Afluria (quadrivalent), Fluad (quadrivalent), Fluarix (quadrivalent), Flucelvax (quadrivalent), Flulaval (quadrivalent), Fluzone (quadrivalent), Fluzone High-Dose (quadrivalent): Administer only by IM injection.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁶⁰ ¹⁸⁶ ¹⁹⁰

Do not administer intradermally,¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁹⁰ IV,¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁶⁰ ¹⁹⁰ or sub-Q.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁹⁰

As an alternative to IM injection using a needle and syringe, Afluria (quadrivalent) may be administered IM using a PharmaJet Stratis needle-free injection system only in adults 18 through 64 years of age.¹⁰⁸ ⁵⁴³ Do not administer other commercially available inactivated influenza vaccines using a jet injector.⁵⁴³

Syncope (vasovagal or vasodepressor reaction; fainting) may occur following vaccination; such reactions occur most frequently in adolescents and young adults.¹³⁴ Take appropriate measures to decrease risk of injury if patient becomes weak or dizzy or loses consciousness (e.g., have vaccinees sit or lie down during and for 15 minutes after vaccination).¹³⁴ If syncope occurs, observe patient until symptoms resolve.¹³⁴

May be given concurrently with other age-appropriate vaccines.¹⁰⁰ ¹³⁴ When multiple vaccines administered during a single health-care visit, give each parenteral vaccine using separate syringes and different injection sites.¹³⁴ Separate injection sites by ≥1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur.¹³⁴

IM Administration

Depending on patient age, administer IM into deltoid muscle or anterolateral thigh.¹³⁴

Infants 6 through 11 months of age: Preferably give IM injection into anterolateral thigh.¹⁰⁰ ¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹³⁴ In certain circumstances (e.g., physical obstruction at other sites and no reasonable indication to defer the vaccine dose), may consider IM injection into gluteal muscle using care to identify anatomic landmarks prior to injection.¹³⁴

Infants and children 1 through 2 years of age: Preferably give IM injection into anterolateral thigh;¹³⁴ alternatively, deltoid muscle can be used if muscle mass is adequate.¹³⁴

Adults, adolescents, and children ≥3 years of age: Preferably give IM injection into deltoid muscle;¹⁰⁰ ¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹³⁴ ¹⁶⁰ ¹⁹⁰ alternatively, anterolateral thigh can be used.¹³⁴

Do not administer into gluteal region or any area where there may be a major nerve trunk.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁶⁰ ¹⁹⁰

To ensure delivery into muscle, make IM injections at a 90° angle to the skin using a needle length appropriate for individual’s age and body mass, thickness of adipose tissue and muscle at injection site, and injection technique.¹³⁴ Consider anatomic variability, especially in the deltoid; use clinical judgment to avoid inadvertent underpenetration or overpenetration of muscle.¹³⁴

Do not mix with any other vaccine or solution.¹⁰⁴ ¹³⁴ ¹⁶⁰ ¹⁸⁶ ¹⁹⁰

Shake prefilled syringe before administering a dose.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁶⁰ ¹⁸⁶ ¹⁹⁰

Shake vaccine vial before withdrawing a dose.¹⁰⁴ ¹⁰⁷ ¹⁰⁸

Discard vaccine if it contains particulates, appears discolored, or cannot be resuspended with thorough agitation.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁶⁰ ¹⁹⁰

Jet Injector (Afluria)

Afluria (quadrivalent) may be administered IM using a PharmaJet Stratis needle-free injection system in adults 18 through 64 years of age.¹⁰⁸ Do not use jet injector to administer Afluria in children and adolescents <18 years of age or geriatric adults ≥65 years of age.¹⁰⁸

Consult manufacturer’s information for the jet injector for specific information on how to administer Afluria using the PharmaJet Stratis needle-free injection system.¹⁰⁸

Dosage

Dose and dosing schedule (i.e., number of doses) for prevention of seasonal influenza depend on individual’s age, vaccination history, and specific product administered.¹⁰⁰ ¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹¹² ¹⁶⁰ ¹⁸⁶ ¹⁹⁰

Pediatric Patients

Prevention of Seasonal Influenza A and B Virus Infections

Infants and Children 6 through 35 Months of Age (Afluria)

Available in 0.25-mL single-dose syringes to provide a reduced dose for use in infants and children 6 through 35 months of age.¹⁰⁸

Has not previously received any doses of any seasonal influenza vaccine or has an uncertain history regarding influenza vaccination: Two 0.25-mL doses administered at least 1 month (4 weeks) apart.¹⁰⁰ ¹⁰⁸ ¹¹²

Did not receive a total of ≥2 doses of any seasonal influenza vaccine before July 1 of the summer prior to the upcoming (current) influenza season: ACIP and AAP recommend two 0.25-mL doses administered at least 4 weeks apart.¹⁰⁰ ¹¹²

Received a total of ≥2 doses of any seasonal influenza vaccine before July 1 of the summer prior to the upcoming (current) influenza season: ACIP and AAP recommend a single 0.25-mL dose.¹⁰⁰ ¹¹²

Infants and Children 6 through 35 Months of Age (Fluarix, Flulaval)

Has not previously received any doses of any seasonal influenza vaccine or has an uncertain history regarding influenza vaccination: Two 0.5-mL doses administered at least 1 month (4 weeks) apart.¹⁰⁰ ¹⁰⁶ ¹⁰⁷ ¹¹²

Did not receive a total of ≥2 doses of any seasonal influenza vaccine before July 1 of the summer prior to the upcoming (current) influenza season: ACIP and AAP recommend two 0.5-mL doses administered at least 4 weeks apart.¹⁰⁰ ¹¹²

Received a total of ≥2 doses of any seasonal influenza vaccine before July 1 of the summer prior to the upcoming (current) influenza season: ACIP and AAP recommend a single 0.5-mL dose.¹⁰⁰ ¹¹²

Infants and Children 6 through 35 Months of Age (Fluzone)

For infants and children 6 through 35 months of age, 0.25 mL or standard doses (0.5 mL) may be used.¹⁰⁰ ¹⁰⁴ ¹¹²

Has not previously received any doses of any seasonal influenza vaccine or has an uncertain history regarding influenza vaccination: Manufacturer recommends two 0.25-mL doses, two 0.5-mL doses, or one 0.25- and one 0.5-mL dose administered at least 1 month (4 weeks) apart.¹⁰⁰ ¹⁰⁴ ¹¹²

Did not receive a total of ≥2 doses of any seasonal influenza vaccine before July 1 of the summer prior to the upcoming (current) influenza season: ACIP and AAP recommend two 0.25-mL doses or two 0.5-mL doses administered at least 4 weeks apart.¹⁰⁰ ¹¹²

Children 6 months through 8 Years of Age (Flucelvax)

Children 3 through 8 Years of Age (Afluria, Fluarix, Flulaval, Fluzone)

Children and Adolescents 9 through 17 Years of Age (Afluria, Fluarix, Flucelvax, Flulaval, Fluzone)

Single 0.5-mL dose.¹⁰⁰ ¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹¹² ¹⁹⁰

Adults

Prevention of Seasonal Influenza A and B Virus Infections

Adults ≥18 Years of Age (Afluria, Fluarix, Flucelvax, Flulaval, Fluzone)

Single 0.5-mL dose.¹⁰⁰ ¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁹⁰

Adults ≥65 Years of Age (Fluzone High-Dose)

Single 0.7-mL dose.¹⁶⁰

Special Populations

Hepatic Impairment

No specific dosage recommendations.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁹⁰

Renal Impairment

No specific dosage recommendations.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁹⁰

Geriatric Patients

ACIP states that all adults ≥65 years of age should be vaccinated against influenza using influenza virus vaccine inactivated or influenza virus vaccine recombinant.¹⁰⁰ ACIP states a preference for the adjuvant-containing quadrivalent inactivated vaccine (Fluad), quadrivalent influenza virus vaccine inactivated (Fluzone High-Dose), or quadrivalent recombinant influenza vaccine (Flublok).¹⁰⁰ If none of these 3 vaccines are available, then adults ≥65 years of age may receive any other age-appropriate standard-dose influenza virus vaccine.¹⁰⁰ ²⁰⁰

Standard-dose Preparations (Afluria, Fluarix, Flucelvax, Flulaval, Fluzone)

Geriatric adults ≥65 years of age: Single 0.5-mL IM dose.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁹⁰

Standard-Dose, Adjuvant-containing Preparation (Fluad)

Geriatric adults ≥65 years of age: Single 0.5-mL IM dose.¹⁸⁶

Fluzone High-Dose

Geriatric adults ≥65 years of age: Single 0.7-mL IM dose.¹⁶⁰

Cautions for Influenza Virus Vaccine Inactivated

Contraindications

History of severe hypersensitivity (e.g., anaphylaxis) to previous dose of any influenza vaccine.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁶⁰ ¹⁸⁶
Egg-based influenza vaccine inactivated: History of severe hypersensitivity (e.g., anaphylaxis) to any component of the vaccine, including egg protein.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹¹² ¹⁶⁰ ¹⁸⁶
Cell culture-based influenza vaccine inactivated: History of severe allergic reactions (e.g., anaphylaxis) to any component of the vaccine.¹⁰⁰ ¹⁹⁰

Warnings/Precautions

Sensitivity Reactions

Allergic or immediate hypersensitivity reactions (e.g., urticaria, angioedema, anaphylaxis, anaphylactic shock, serum sickness, allergic asthma) reported rarely.¹⁰⁰ ¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸

Prior to administration, review patient’s history with respect to possible sensitivity reactions to the vaccine or vaccine components, including egg protein, and prior vaccination-related adverse effects and assess benefits versus risks.¹⁰⁰ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹¹²

Administer in a setting where appropriate medical treatment and supervision are available to manage possible anaphylactic reactions if they occur.¹⁰⁰ ¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹¹² ¹³⁴ ¹⁶⁰ ¹⁸⁶ ¹⁹⁰ Epinephrine and other appropriate agents should be readily available.

Egg-based influenza vaccine inactivated (Afluria, Fluad, Fluarix, Flulaval, Fluzone): ACIP states that all persons aged ≥6 months with egg allergy should receive influenza vaccine with any influenza vaccine (egg-based or nonegg-based) that is otherwise appropriate for the recipient’s age and health status.¹⁰⁰

Cell culture-based influenza vaccine inactivated (Flucelvax): ACIP states do not use in individuals who have had a severe allergic reaction (e.g., anaphylaxis) to any trivalent or quadrivalent cell culture-based influenza vaccine or to any component of the vaccine.¹⁰⁰ However, ACIP states that a history of severe allergic reaction (e.g., anaphylaxis) to any other trivalent or quadrivalent type of influenza vaccine (egg-based inactivated vaccine, recombinant vaccine, live intranasal vaccine) is a precaution to use of the cell culture-based vaccine.¹⁰⁰ If Flucelvax is used in an individual with such a history, administer the vaccine in an inpatient or outpatient medical setting supervised by a health-care provider able to recognize and manage severe allergic reactions.¹⁰⁰ Consider consultation with an allergist to help identify the vaccine component responsible for the prior reaction.¹⁰⁰

Egg Allergy

Most seasonal inactivated influenza vaccines (Afluria, Fluad, Fluarix, Flulaval, Fluzone) are produced using embryonated chicken eggs;¹⁰⁰ ¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹¹² ¹⁶⁰ ¹⁸⁶ these vaccines can contain residual egg protein (ovalbumin).¹⁰⁶ ¹⁰⁷ ¹⁸⁶

Flucelvax inactivated influenza vaccine (quadrivalent) is cell culture-based and prepared using virus propagated in Madin Darby Canine Kidney (MDCK) cells (not embryonated chicken eggs).¹⁰⁰ ¹¹² ¹⁹⁰

Manufacturers of egg-based inactivated influenza vaccines state that these vaccines are contraindicated in individuals who have had a severe allergic reaction (e.g., anaphylaxis) to egg protein.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁶⁰ ¹⁸⁶

ACIP states that all individuals aged ≥6 months with egg allergy receive influenza vaccine with any influenza vaccine (egg-based or noneggibased) that is otherwise appropriate for the recipient’s age and health status.¹⁰⁰ ACIP no longer recommends that persons who have had an allergic reaction to egg involving symptoms other than urticaria should be vaccinated in an inpatient or outpatient medical setting supervised by a health care provider who is able to recognize and manage severe allergic reactions if an egg-based vaccine is used.¹⁰⁰ Egg allergy alone necessitates no additional safety measures for influenza vaccination beyond those recommended for any recipient of any vaccine, regardless of severity of previous reaction to egg, as all vaccines should be administered in settings in which personnel and equipment needed for rapid recognition and treatment of acute hypersensitivity reactions are available.¹⁰⁰

Neomycin and/or Polymyxin B Allergy

Afluria (quadrivalent): Each 0.5-mL dose contains neomycin sulfate (≤81.8 ng) and polymyxin B (≤14 ng).¹⁰⁸

Fluad adjuvant-containing (quadrivalent): Each 0.5-mL dose may contain trace amounts of neomycin (≤0.02 mcg by calculation) and kanamycin (≤0.03 mcg by calculation).¹⁸⁶

Neomycin hypersensitivity usually manifests as a delayed-type (cell-mediated) contact dermatitis.¹³⁴

ACIP states that a history of delayed-type allergic reaction to neomycin is not a contraindication to use of vaccines containing trace amounts of neomycin.¹³⁴ However, before giving a neomycin-containing vaccine to an individual with a history of anaphylactic reaction to neomycin, have patient evaluated by an allergist.¹³⁴

Thimerosal Allergy

All multiple-dose vials of influenza vaccine inactivated (Afluria, Flucelvax, Fluzone) contain thimerosal as a preservative.¹⁰⁴ ¹⁰⁸ ¹⁹⁰

Hypersensitivity reactions to thimerosal contained in vaccines have been reported in some individuals.¹⁴⁰ ⁴⁹⁸ ⁵⁰⁰ These reactions usually manifest as local, delayed-type hypersensitivity reactions (e.g., erythema, swelling),¹⁰⁰ ¹³⁴ ¹⁴⁰ ⁴²⁷ but a generalized reaction manifested as pruritus and an erythematous, maculopapular rash on all 4 extremities has been reported rarely.⁵⁰⁰

Even when patch or intradermal tests for thimerosal sensitivity are positive, most individuals do not develop hypersensitivity reactions to thimerosal administered as a component of vaccines.¹⁰⁰ ¹³⁴ ¹⁴⁰

ACIP states that a history of delayed-type hypersensitivity to thimerosal is not a contraindication to use of vaccines that contain thimerosal.¹³⁴

Guillain-Barré Syndrome (GBS)

If GBS occurred within 6 weeks after previous influenza vaccination, manufacturers state base decision to administer influenza vaccine on careful consideration of potential benefits and risks.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁶⁰ ¹⁸⁶ ¹⁹⁰

The 1976 swine influenza vaccine was associated with increased frequency of GBS.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁶⁰ ¹⁸⁶ ¹⁹⁰ ²⁷⁸ ²⁷⁹ ³⁶⁴ ³⁶⁵ Evidence for causal relationship between other influenza vaccines and GBS inconclusive;¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁶⁰ ¹⁹⁰ if an excess risk exists, it probably is slightly more than 1 additional case of GBS per 1 million vaccinees).¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁶⁰ ¹⁸⁶ ¹⁹⁰ ³⁶⁴ ³⁶⁵

ACIP states that, as a precaution, individuals who are not at high risk for severe influenza complications and who developed GBS within 6 weeks of a previous dose of influenza vaccine generally should not receive influenza vaccination;¹⁰⁰ clinicians might consider use of antiviral prophylaxis for such individuals.¹⁰⁰ However, ACIP states that the benefits of influenza vaccine may outweigh the risks for certain individuals with a history of GBS within 6 weeks after a previous dose of influenza vaccine who are at high risk for severe complications from influenza.¹⁰⁰

Individuals with Altered Immunocompetence

May be administered to individuals immunosuppressed as the result of disease or immunosuppressive therapy.¹⁰⁰ Consider possibility that immune response to the vaccine and efficacy may be reduced in these individuals.¹⁰⁰ ¹⁶⁰ ¹⁸⁶ ¹⁹⁰

ACIP, AAP, CDC, NIH, IDSA, and others state that HIV-infected adults, adolescents, children, and infants ≥6 months of age should receive annual vaccination against seasonal influenza; use age-appropriate parenteral inactivated influenza vaccine (not intranasal live vaccine) for prevention of seasonal influenza in HIV-infected individuals.¹⁰⁰ ¹¹² ¹⁵⁶ Antibody response may be inversely correlated with severity of the disease.¹⁰⁰ ¹⁰⁵ ¹¹⁶ ²³² ²³³ ³¹⁰ ³⁷⁶ Use of an additional (i.e., booster) dose of influenza vaccine does not appear to improve immune response in HIV-infected individuals.¹¹⁶ ¹²⁴ ²³² ³¹⁰

Generally, administer prior to initiation of immunosuppressive therapy or defer until immunosuppressive therapy discontinued.¹⁰⁵ ¹³⁴

Even if previously vaccinated against influenza, ACIP recommends that hematopoietic stem cell transplant (HSCT) recipients should receive age-appropriate influenza vaccine inactivated ≥6 months after HSCT and then annually thereafter.¹³⁴ Although influenza vaccine inactivated can be given as early as 4 months after HSCT, some experts state consider a second dose in this situation.¹³⁴

Fever and Febrile Seizures

Febrile seizures reported rarely following administration of influenza vaccine inactivated.¹⁰⁰ ¹⁰⁴ ¹⁰⁸ ¹⁶⁰

Postmarketing reports of increased rates of fever and febrile seizures in infants and children 6 months through 4 years of age and increased incidence of fever in children 5–8 years of age who received a 2010 Southern Hemisphere parenteral inactivated influenza vaccine¹⁰⁰ ⁵³⁴ that was antigenically equivalent to and produced by the same manufacturer as one of the 2010–2011 seasonal parenteral inactivated influenza vaccines marketed in the US (i.e., Afluria; CSL).⁵³⁴ The 2010 Southern Hemisphere formulation apparently induced a stronger inflammatory cytokine response than that associated with previous formulations of the vaccine or with other inactivated influenza viruses and this may have been mediated by higher concentrations of residual lipid and RNA remaining in the vaccine.¹⁰⁰

Thimerosal Precautions

Although there is no convincing evidence that the low concentrations of thimerosal (a mercury-containing preservative) contained in some vaccines is harmful to vaccine recipients,¹⁰⁰ ⁴⁹³ ⁴⁹⁴ ⁴⁹⁹ ⁵⁰¹ ⁵⁰² ⁵⁰³ ⁵⁰⁴ ⁵⁰⁵ ⁵⁰⁶ efforts to eliminate or reduce the thimerosal content in vaccines is recommended as a prudent measure to reduce mercury exposure in infants and children and part of an overall strategy to reduce mercury exposures from all sources, including food and drugs.¹⁰⁰ ¹³⁴ ⁴⁰¹ ⁴⁰² ⁴⁰³ ⁴⁹²

As a result of efforts initiated in 1999 to remove or reduce thimerosal in vaccines and expedite development and approval of preservative-free formulations of vaccines, inactivated influenza vaccine now is commercially available in prefilled single-dose syringes or single-dose vials as preservative-free formulations that do not contain thimerosal.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁶⁰ ¹⁹⁰ ⁴²⁷ Only multiple-dose vials of inactivated influenza virus still contain thimerosal as a preservative (≤ 25 mcg of mercury per 0.5-mL dose).¹⁰⁴ ¹⁰⁷ ¹⁰⁸ ¹⁹⁰ ⁴²⁷

Although it was suggested that thimerosal in vaccines theoretically could have adverse effects in vaccine recipients, there is no conclusive evidence that the low levels of thimerosal contained in vaccines cause harm in vaccine recipients.¹⁰⁰ ¹³⁴ ⁴⁹² ⁴⁹³ ⁴⁹⁴ ⁴⁹⁹ ⁵⁰¹ ⁵⁰² ⁵⁰³ ⁵⁰⁴ ⁵⁰⁵ ⁵⁰⁶

Analysis of adverse effects reported to VAERS indicates that there is no difference in the incidence of injection site reactions, rash, or infections in infants 6–23 months of age who received preservative-containing (thimerosal-containing) inactivated influenza vaccine compared with those who received preservative-free preparations of the vaccine.⁴⁹⁷ To date, the only adverse effects known to be caused by thimerosal contained in vaccines are local hypersensitivity reactions.¹³⁴ ¹⁴⁰ ⁴²⁷ ⁴⁹³

USPHS, ACIP, AAP, AAFP, and other experts state that use of vaccines that contain thimerosal is preferable to withholding vaccination since failure to provide protection against vaccine-preventable diseases may represent an immediate threat, especially in infants.⁴⁰¹ ⁴⁰² ⁴⁰³ AAP states that the benefits of protecting children outweigh the hypothetical risks associated with the minute amounts of thimerosal contained in some currently available influenza vaccine preparations.⁴⁰³

Afluria (quadrivalent): Commercially available in 0.5-mL prefilled syringes as a preservative-free formulation (thimerosal not used in manufacturing process).¹⁰⁸ Also available in multiple-dose vials containing thimerosal as a preservative (24.5 mcg of mercury per 0.5-mL dose).¹⁰⁸

Fluad adjuvant-containing (quadrivalent): Commercially available in 0.5-mL prefilled syringes as a preservative-free formulation that does not contain thimerosal.¹⁸⁶

Fluarix (quadrivalent): Commercially available in 0.5-mL prefilled syringes as a preservative-free formulation that does not contain thimerosal.¹⁰⁶

Flucelvax (quadrivalent): Commercially available in 0.5-mL prefilled syringes as a preservative-free formulation (thimerosal was not used in the manufacturing process).¹⁹⁰ Also available in multiple-dose vials that contain thimerosal as a preservative (25 mcg of mercury per 0.5-mL dose).¹⁹⁰

Flulaval (quadrivalent): Commercially available in 0.5-mL prefilled syringes as a preservative-free formulation (thimerosal not used in manufacturing process).¹⁰⁷

Fluzone (quadrivalent): Commercially available in 0.5-mL prefilled syringes as a preservative-free formulation (thimerosal not used in manufacturing process).¹⁰⁴ Also available in multiple-dose vials containing thimerosal as a preservative (25 mcg of mercury per 0.5-mL dose).¹⁰⁴

Fluzone High-Dose (quadrivalent): Commercially available in 0.7-mL prefilled syringes as a preservative-free formulation.¹⁶⁰

Individuals with Bleeding Disorders

Advise individuals and/or their family about the risk of hematoma from IM injections.¹³⁴

ACIP states that vaccines may be given IM to such individuals if a clinician familiar with the patient’s bleeding risk determines that the preparation can be administered with reasonable safety.¹³⁴ In these cases, use a fine needle (23 gauge or smaller) to administer the vaccine and apply firm pressure to the injection site (without rubbing) for ≥2 minutes.¹³⁴ In individuals receiving therapy for hemophilia, IM vaccines can be scheduled for administration shortly after a dose of such therapy.¹³⁴

Concomitant Illness

Base decision to administer or delay vaccination in an individual with a current or recent acute illness on severity of symptoms and etiology of the illness.¹³⁴

ACIP states mild acute illness does not preclude vaccination.¹³⁴

ACIP states moderate or severe acute illness (with or without fever) is a precaution for vaccination;¹³⁴ defer vaccines until individual has recovered from the acute phase of the illness.¹³⁴ This avoids superimposing vaccine adverse effects on the underlying illness or mistakenly concluding that a manifestation of the underlying illness resulted from vaccine administration.¹³⁴

Individuals with Known or Suspected Coronavirus Disease 2019 (COVID-19)

ACIP states defer routine vaccinations, including influenza vaccination, in symptomatic individuals with suspected or confirmed COVID-19 until criteria for discontinuance of COVID-19 isolation have been met and the individual is no longer moderately to severely ill.¹⁰⁰ Consider deferring vaccination until the individual has fully recovered from the acute illness to avoid exposing health-care personnel and other patients to the disease.¹⁰⁰ ACIP also states that routine vaccinations, including influenza vaccination, should be deferred in patients with mild or asymptomatic COVID-19 to avoid the inability to discern between COVID-19 symptoms and postvaccination reactions.¹⁰⁰ Other considerations include the presence of risk factors for severe influenza illness and the likelihood of being able to vaccinate at a later date.¹⁰⁰

Limitations of Vaccine Effectiveness

Following seasonal influenza vaccination, up to 2 weeks may be required to develop antibody protection against infection.¹⁰⁰

May not protect all vaccine recipients against influenza.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁶⁰ ¹⁸⁶ ¹⁹⁰

Seasonal influenza vaccines are formulated annually to contain influenza A and B antigens predicted to represent strains of influenza virus likely to circulate in the US during the upcoming influenza season.¹⁰⁰ Efficacy of seasonal influenza vaccine during any given year depends on how closely viral strains represented in the vaccine match viral strains circulating during the season.¹⁰⁰ ¹⁶⁶

Seasonal influenza vaccines not expected to provide protection against human infection with animal-origin influenza viruses, including avian influenza A viruses (e.g., avian influenza A [H5N1], avian influenza A [H7N9]).¹¹⁵ ¹⁴⁹

Seasonal influenza vaccines will not provide protection against COVID-19.⁵⁸¹

Duration of Immunity

Duration of immunity usually <1 year.¹⁶⁶ Immunity declines during the year after seasonal influenza vaccination.¹⁰⁰ ¹⁰⁸ ¹⁶⁶

Although some data indicate early vaccination (e.g., in July and August) might be associated with suboptimal immunity before end of the influenza season, particularly among older adults, revaccination later in the season not recommended for individuals who already received influenza vaccine for the current influenza season.¹⁰⁰

Annual vaccination needed because of waning immunity and because circulating strains of influenza virus change from year to year.¹⁰⁰ ¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸

Do not administer influenza vaccine from a previous influenza season in an attempt to provide protection during a subsequent influenza season.¹⁰⁰

Improper Storage and Handling

Improper storage or handling of vaccines may reduce vaccine potency resulting in reduced or inadequate immune responses in vaccinees.¹³⁴

Inspect all vaccines upon delivery and monitor during storage to ensure that the appropriate temperature is maintained.¹³⁴

Do not administer vaccine that has been mishandled or has not been stored at the recommended temperature.¹³⁴

If there are concerns about mishandling, contact the manufacturer or state or local immunization or health departments for guidance on whether the vaccine is usable;¹³⁴ also can consult CDC.¹³⁴

Specific Populations

Pregnancy

Data insufficient to assess risk of administering influenza vaccine inactivated during pregnancy.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁶⁰ ¹⁸⁶ ¹⁹⁰

Animal reproduction studies have not revealed evidence of harm to fetus.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁸⁶ ¹⁹⁰

Pregnant and postpartum women are at higher risk for severe influenza and influenza-related complications, particularly during the second and third trimesters, which may lead to adverse pregnancy outcomes including preterm labor and delivery.¹⁰⁰ ¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁹⁰

ACIP, ACOG, and AAP recommend vaccination against influenza in all women who are pregnant or who might become pregnant during the influenza season;¹⁰⁰ ¹¹² ¹¹⁸ ¹³⁴ any licensed, age-appropriate, inactivated influenza vaccine (i.e., influenza vaccine inactivated or influenza vaccine recombinant) can be used.¹⁰⁰ ¹¹² These experts state that inactivated influenza vaccine can be given at any time during pregnancy (any trimester) before or during the influenza season.¹⁰⁰ ¹¹² ¹¹⁸ ¹³⁴ Encourage unvaccinated postpartum women to receive vaccination before discharge from the hospital.¹¹²

ACIP states that there is no evidence of risk to the fetus if inactivated vaccines are administered during pregnancy.¹³⁴

To monitor pregnancy outcomes and newborn health status following influenza vaccination of pregnant women, some manufacturers have established pregnancy registries.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁹⁰ Women who receive the vaccine during pregnancy or their health-care providers may contact the manufacturer at 855-358-8966 (Afluria),¹⁰⁸ 888-452-9622 (Fluarix, Flulaval),¹⁰⁶ ¹⁰⁷ or 800-822-2463 (Fluzone).¹⁰⁴

Lactation

Not known whether influenza vaccine inactivated distributed into milk.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁹⁰ Data insufficient to assess effects on the breast-fed infant or on milk production.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁸⁶ ¹⁹⁰

Consider benefits of breast-feeding and importance of the vaccine to the woman;¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁹⁰ also consider potential adverse effects on the breast-fed child from the vaccine or underlying maternal condition (i.e., susceptibility to influenza infection).¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁹⁰

ACIP and AAP state breast-feeding is not a contraindication to influenza vaccine inactivated.¹¹² ¹³⁴ These experts state that inactivated vaccines do not pose any unusual risks for the mother or her nursing infant.¹¹² ¹³⁴

Pediatric Use

Afluria, Fluarix, Flulaval, Fluzone, Flucelvax: Safety and efficacy not established in infants <6 months of age.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸

Fluad adjuvant-containing (quadrivalent): Safety and efficacy not established in pediatric patients.¹⁸⁶

Fluzone High-Dose: Safety and efficacy not established in pediatric patients.¹⁶⁰

Because seasonal influenza vaccine inactivated not indicated in infants <6 months of age, all household and other close contacts (e.g., day-care providers) of infants <6 months of age should be vaccinated against seasonal influenza using vaccine appropriate for their age and target group since this may provide some protection against seasonal influenza for these young infants.¹⁰⁰

Geriatric Use

Afluria, Fluarix, Flucelvax, Flulaval, Fluzone: No overall differences in safety relative to younger adults;¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁹⁰ may be less immunogenic in geriatric individuals.¹⁰⁰ ¹⁰⁸ ¹⁹⁰

Fluad adjuvant-containing (quadrivalent): Use only in adults ≥65 years of age.¹⁰⁰ ¹⁸⁶ Safety profile of this standard-dose, adjuvant-containing vaccine similar to that of standard-dose, non-adjuvant-containing vaccine.¹⁰⁰ Although some local and systemic adverse events reported more frequently with the adjuvant-containing vaccine, most adverse reactions have been mild in severity.¹⁰⁰

Fluzone High-Dose (quadrivalent): Use only in adults ≥65 years of age.¹⁰⁰ ¹⁶⁰ Each 0.7 mL of Fluzone High-Dose contains 4 times the amount of antigen contained in standard-dose Fluzone.¹⁰⁰ ¹⁶⁰ In adults ≥65 years of age, higher incidence of injection site reactions and systemic adverse effects reported with trivalent Fluzone High-Dose (no longer available in US) compared with standard-dose Fluzone.¹⁰⁰ Some evidence that the high-dose formulation elicits higher antibody titers and higher seroconversion rates than the standard-dose formulation in adults ≥65 years of age and may be more effective in preventing laboratory-confirmed influenza in this age group.¹⁰⁰

ACIP states that all adults ≥65 years of age should be vaccinated against influenza using influenza virus vaccine inactivated or influenza vaccine recombinant.¹⁰⁰ ACIP states a preference for Fluzone High-Dose (quadrivalent), Flublok recombinant influenza vaccine (quadrivalent), or the standard-dose quadrivalent adjuvant-containing vaccine (Fluad), but if none of these 3 vaccines are available at the time of vaccine administration, then they state that adults ≥65 years may receive a standard-dose quadrivalent preparation.¹⁰⁰ ²⁰⁰

Common Adverse Effects

Injection site reactions (i.e., tenderness, pain, redness, induration, swelling), headache, fatigue, myalgia, fever, malaise.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁸⁶ ¹⁹⁰

Drug Interactions

Immunosuppressive Agents

Immune responses to vaccines, including influenza vaccine inactivated, may be reduced in individuals receiving immunosuppressive agents.¹⁰⁴ ¹⁰⁵ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹³⁴ ¹⁶⁰ ¹⁹⁰

Generally, give inactivated vaccines ≥2 weeks prior to initiation of immunosuppressive therapy and, because of possible suboptimal response, do not give during and for certain periods of time after immunosuppressive therapy discontinued.¹⁰⁵ ¹³⁴ ¹³⁵

Time to restoration of immune competence varies depending on type and intensity of immunosuppressive therapy, underlying disease, and other factors;¹⁰⁵ optimal timing for vaccine administration after discontinuance of immunosuppressive therapy not identified for every situation.¹⁰⁵

Vaccines

Although specific studies may not be available, concurrent administration with other age-appropriate vaccines, including live virus vaccines, toxoids, or inactivated or recombinant vaccines, during same health-care visit not expected to affect immunologic responses or adverse reactions to any of the preparations.¹⁰⁰ ¹⁰⁵ ¹³⁴

Immunization with influenza vaccine inactivated can be integrated with immunization against diphtheria, tetanus, pertussis, Haemophilus influenzae type b (Hib), hepatitis A, hepatitis B, human papillomavirus (HPV), measles, mumps, rubella, meningococcal disease, pneumococcal disease, poliomyelitis, rotavirus, and varicella.¹⁰⁰ ¹⁰⁵ ¹³⁴ However, administer each parenteral vaccine using separate syringes and different injection sites.¹³⁴

Specific Drugs

Drug	Interaction	Comments
Antivirals active against influenza (baloxavir, oseltamivir, peramivir, zanamivir, amantadine, rimantadine)	Baloxavir, peramivir: No specific studies⁴⁰⁶ ⁴¹⁰ Oseltamivir: No specific studies;⁴⁰⁷ oseltamivir does not interfere with humoral antibody response to influenza infection⁴⁰⁷ Zanamivir: No interference with antibody response to inactivated influenza vaccine⁴⁰⁸ Amantadine, rimantadine: Do not appear to interfere with antibody response to inactivated influenza vaccine¹²⁰ ¹²²	Baloxavir, oseltamivir, peramivir, zanamivir: May be used concurrently with or at any interval before or after influenza vaccine inactivated¹⁰⁰ ¹¹² ¹³⁴ ⁴⁰⁶ ⁴⁰⁷
COVID-19 vaccines	Controlled studies did not identify evidence of safety concerns or any evidence of immune interference on influenza hemagglutination inhibition or SARS-CoV-2 binding antibody responses⁵⁸⁹ ⁵⁹⁰ ⁵⁹² Some studies report similar incidence of local reactions, but slightly increased systemic reactions, especially with high dose or adjuvant-containing vaccines⁵⁸⁹ ⁵⁹⁰ ⁵⁹²	Influenza vaccine inactivated may be administered concurrently with or at any interval before or after COVID-19 vaccines¹⁰⁰ ¹¹³ ⁵⁸¹ Base decisions to administer a COVID-19 vaccine concomitantly with other vaccine(s) on whether routine vaccination with the other vaccines has been delayed or missed, the individual's risk of vaccine-preventable disease (e.g., during an outbreak or occupational exposures), and reactogenicity profiles of the vaccines¹⁰⁰ ¹¹³
Hepatitis B vaccine (HepB)	Adjuvant-containing influenza vaccine inactivated (Fluad): Safety and efficacy of concomitant or sequential administration with adjuvant-containing hepatitis B vaccine recombinant (Heplisav-B) not studied¹⁰⁰	Non-adjuvant-containing influenza vaccine inactivated: May be given concurrently with any HepB vaccine using separate syringes and different injection sites¹⁰⁰ Adjuvant-containing influenza vaccine inactivated (Fluad): Consider not using concomitantly with adjuvant-containing HepB vaccine recombinant (Heplisav-B);¹⁰⁰ do not delay influenza vaccination if a non-adjuvant-containing influenza vaccine inactivated is not available¹⁰⁰
Immune globulin (immune globulin IM [IGIM], immune globulin IV [IGIV], immune globulin subcutaneous) or specific hyperimmune globulin (hepatitis B immune globulin [HBIG], rabies immune globulin [RIG], tetanus immune globulin [TIG], varicella zoster immune globulin [VZIG])	No evidence that immune globulin preparations interfere with immune response to inactivated vaccines¹³⁴	Influenza vaccine inactivated may be given concurrently with or at any interval before or after immune globulin or specific hyperimmune globulin¹³⁴
Immunosuppressive agents (e.g., alkylating agents, antimetabolites, certain biologic response modifiers, corticosteroids, cytotoxic drugs, radiation)	Potential for decreased immune responses to vaccines¹⁰⁵ ¹³⁴ ¹⁹⁰ Anti-B-cell antibodies (e.g., rituximab): Optimal time to administer vaccines after such treatment unclear¹³⁵ Corticosteroids: May reduce immune responses to vaccines if given in greater than physiologic doses¹³⁴	Chemotherapy or radiation: Give inactivated vaccines ≥2 weeks before or defer until ≥3 months after such therapy if possible;¹³⁴ ¹³⁵ if indicated based on the time of the year, IDSA states influenza vaccine inactivated can be given during or <3 months after chemotherapy discontinued¹³⁵ Anti-B-cell antibodies (e.g., rituximab): Give inactivated vaccines ≥2 weeks before or defer until ≥6 months after such treatment¹⁰⁵ ¹³⁴ ¹³⁵ Certain biologic response modifiers (e.g., colony-stimulating factors, interleukins, tumor necrosis factor [TNF] blocking agents): Give inactivated vaccines ≥2 weeks prior to initiation of such therapy;¹⁰⁵ ¹³⁴ if inactivated vaccine indicated in patient with chronic inflammatory illness receiving maintenance therapy with a biologic response modifier, some experts state do not withhold the vaccine because of concern about exacerbation of inflammatory illness¹⁰⁵ ¹³⁵ Corticosteroids: Some experts state give inactivated vaccines ≥2 weeks prior to initiation of immunosuppressive corticosteroid therapy if feasible,¹⁰⁵ ¹³⁴ but may be given to those receiving long-term corticosteroid therapy for inflammatory or autoimmune disease;¹⁰⁵ IDSA states, although it may be reasonable to delay inactivated vaccines in patients treated with high-dose corticosteroid therapy, recommendations for use of influenza vaccine inactivated in individuals receiving corticosteroid therapy (including high-dose corticosteroid therapy) generally are the same as those for other individuals¹³⁵
Pneumococcal vaccine	PCV13 (Prevnar 13): Concurrent administration with inactivated influenza vaccine in adults ≥50 years of age did not increase frequency of local adverse effects, but increased frequency of some solicited systemic reactions reported compared with administration of either vaccine alone¹⁸¹ PPSV23 (Pneumovax 23): Concurrent administration with inactivated influenza vaccine resulted in increased incidence of adverse local and systemic effects compared with administration of influenza vaccine alone;¹⁴⁶ ²⁴⁶ ACIP states concomitant administration results in satisfactory antibody responses without increasing incidence or severity of adverse reactions¹³⁴	PCV13 (Prevnar 13): May be given concurrently with influenza vaccine inactivated using separate syringes and different injection sites¹⁰⁵ ¹¹² PPSV23 (Pneumovax 23): May be administered concurrently with influenza vaccine inactivated using separate syringes and different injection sites¹⁰⁰ ¹³⁴ ³⁵² ³⁵³
Respiratory Syncytial Virus (RSV) Vaccine	Concomitant administration with seasonal influenza vaccines met noninferiority criteria for immunogenicity with the exception of the FluA/Darwin H3N2 strain when the GSK RSV vaccine was administered concomitantly with adjuvanted quadrivalent inactivated influenza vaccine.⁶⁰¹ RSV and influenza antibody titers were somewhat lower with concomitant administration; however, the clinical significance of this is unknown.⁶⁰¹	Concomitant administration of RSV vaccine with other adult vaccines during the same visit is acceptable, but might increase local or systemic reactogenicity.⁶⁰¹
Rotavirus vaccine (RV)	Concomitant use not studied¹⁶⁷	May be given concurrently with or at any interval before or after influenza vaccine inactivated¹⁶⁷
Zoster vaccine recombinant (RZV)	Non-adjuvant-containing influenza vaccine inactivated: Concurrent administration with zoster vaccine recombinant in adults ≥50 years of age does not affect immune response to either vaccine¹⁰⁶ ¹¹⁷ and not associated with any safety concerns¹¹⁷ Adjuvant-containing influenza vaccine inactivated (Fluad): Safety and efficacy of concomitant or sequential administration with zoster vaccine recombinant not studied¹⁰⁰ ¹¹⁷	Non-adjuvant-containing influenza vaccine inactivated: May be given concurrently with zoster vaccine recombinant using separate syringes and different injection sites¹⁰⁰ Adjuvant-containing influenza vaccine inactivated (Fluad): Consider not using concomitantly with zoster vaccine recombinant;¹⁰⁰ do not delay influenza vaccination if a non-adjuvant-containing influenza vaccine inactivated not available¹⁰⁰

Stability

Storage

Parenteral

Injectable Suspension, for IM Use

2–8°C; do not freeze.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁶⁰ ¹⁸⁶ ¹⁹⁰ If freezing occurs, discard vaccine.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁶⁰ ¹⁸⁶

Return multiple-dose vials to 2–8ºC between uses.¹⁰⁴ ¹⁰⁸ Manufacturer of Afluria states discard any vaccine remaining in multiple-dose vial after a total of 20 doses has been removed from the vial and discard multiple-dose vial if not used within 28 days after vial first entered.¹⁰⁸

Protect from light.¹⁰⁶ ¹⁰⁸ ¹⁸⁶ ¹⁹⁰

Single-dose syringes and single-dose vials are preservative-free.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁶⁰ ¹⁸⁶ ¹⁹⁰ Multiple-dose vials contain thimerosal as a preservative.¹⁰⁴ ¹⁰⁸ ¹⁹⁰

Actions

Inactivated influenza vaccines are noninfectious, sterile suspensions of suitably inactivated influenza virus types A and B subunits.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁹⁰
Most seasonal inactivated influenza vaccines available in the US are split-virus preparations (i.e., contain purified subvirion or purified surface antigen) prepared from formaldehyde- or propiolactone-inactivated influenza viruses harvested from allantoic fluids of chick embryos (egg-based inactivated vaccines).¹⁰⁰ ¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ An egg-based inactivated influenza vaccine that contains an adjuvant (i.e., MF59C.1) to increase antibody response also is available in the US.¹⁰⁰ ⁵⁶⁹ In addition an inactivated influenza vaccine prepared from propiolactone-inactivated influenza virus propagated in Madin Darby Canine Kidney (MDCK) cells (cell culture-based inactivated vaccine) is available in the US.¹⁰⁰ ¹⁹⁰
Seasonal influenza vaccines are formulated annually to contain antigens representative of the strains of influenza A (H1N1), influenza A (H3N2), and influenza B viruses likely to circulate in the US during the upcoming influenza season.¹⁰⁰ ⁵⁷⁸
All inactivated influenza vaccines (egg- or cell culture-based) available in the US are quadrivalent vaccines containing 2 influenza type A antigens (H1N1 and H3N2) and 2 influenza type B antigens (B/Yamagata and B/Victoria lineages).¹⁰⁰ ¹⁰⁴ ¹⁰⁶ ¹⁰⁷
Influenza vaccines stimulate active immunity to influenza virus strains represented in the vaccines.¹⁰⁰
Efficacy of influenza vaccines in preventing seasonal influenza virus infection depends on whether the virus strains represented in the vaccines are antigenically similar to influenza virus strains circulating during the influenza season.¹⁰⁰ ¹⁶⁶ When there is a good match between the vaccine formulation and circulating strains, a protective effect generally is achieved in 70–90% of healthy adults <65 years of age following IM administration of inactivated vaccine.¹⁶⁵ ²³⁵ ⁴⁸⁰
Immune response to seasonal influenza vaccine inactivated may be lower in geriatric individuals,¹⁰⁰ ²³⁵ very young children,²⁹⁵ ³⁰² ³²⁶ or individuals who are immunocompromised or have certain chronic medical conditions.¹⁰⁰ ¹⁰⁵ ²³⁵ ²⁴⁸ ²⁶¹ ²⁹⁰ ³¹⁰ ³⁷⁷
Adults ≥65 years of age: Immunogenicity of a single dose of standard-dose adjuvant-containing quadrivalent inactivated influenza vaccine (Fluad) was demonstrated in a clinical trial.¹⁸⁶
Adults ≥65 years of age: High-dose trivalent inactivated influenza vaccine (Fluzone High-Dose; no longer available in US) was superior to standard-dose Fluzone (trivalent; no longer available in US) for prevention of laboratory-confirmed influenza.¹⁶⁰ Single-dose of Fluzone High-Dose (quadrivalent) is as immunogenic as single dose of Fluzone High-Dose (trivalent).¹⁶⁰

Advice to Patients

Prior to administration of seasonal influenza vaccine inactivated, provide a copy of the appropriate CDC Vaccine Information Statement (VIS) to the patient or patient’s legal representative (VISs are available at [Web]).¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁶⁰ ¹⁹⁰ ⁴⁷⁷
Advise patient and/or patient’s parent or guardian of the risks and benefits of vaccine administration.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁶⁰ ¹⁹⁰
Advise patients that influenza vaccine inactivated contains noninfectious killed viruses and cannot cause influenza.¹⁰⁰ ¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁶⁰ ¹⁹⁰
Advise patients that influenza vaccine inactivated provides protection against illness due to influenza viruses represented in the vaccine and cannot provide protection against all respiratory illness.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁶⁰ ¹⁹⁰
Advise patient and/or patient’s parent or guardian that annual vaccination against seasonal influenza is necessary.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁶⁰ ¹⁹⁰
Importance of receiving influenza vaccine for the upcoming (current) influenza season, even if the individual received influenza vaccine for the previous influenza season.¹⁰⁰ ¹¹²
Advise patient and/or patient’s parent or guardian that a single dose of seasonal influenza vaccine is necessary each year in adults, adolescents, and children ≥9 years of age, but that 2 doses of seasonal influenza vaccine may be necessary in some infants and children 6 months through 8 years of age.¹⁰⁰ ¹¹²
Importance of informing clinicians of severe or unusual adverse effects.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁶⁰ ¹⁹⁰ Clinicians or individuals can report any adverse reactions that occur following vaccination to the Vaccine Adverse Event Reporting System (VAERS) at 800-822-7967 or [Web].¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁶⁰ ¹⁹⁰
Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses (e.g., GBS).¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁶⁰ ¹⁹⁰
Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁶⁰ ¹⁹⁰
Importance of informing patients of other important precautionary information.¹⁰⁴ ¹⁰⁶ ¹⁰⁷ ¹⁶⁰ ¹⁹⁰

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Influenza Virus Vaccine Inactivated Quadrivalent
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injectable suspension, for IM use	15 mcg hemagglutinin each of FDA-specified influenza A (H1N1), influenza A (H3N2), influenza B/Victoria lineage, and influenza B/Yamagata lineage antigens per 0.5 mL	Afluria Quadrivalent	Seqirus
		15 mcg hemagglutinin each of FDA-specified influenza A (H1N1), influenza A (H3N2), influenza B/Victoria lineage, and influenza B/Yamagata lineage antigens per 0.5 mL	Fluzone Quadrivalent	Sanofi Pasteur
		15 mcg hemagglutinin each of FDA-specified influenza A (H1N1), influenza A (H3N2), influenza B/Victoria lineage, and influenza B/Yamagata lineage antigens per 0.5 mL	Afluria Quadrivalent	Seqirus
		15 mcg hemagglutinin each of FDA-specified influenza A (H1N1), influenza A (H3N2), influenza B/Victoria lineage, and influenza B/Yamagata lineage antigens per 0.5 mL	Fluarix Quadrivalent	GlaxoSmithKline
		15 mcg hemagglutinin each of FDA-specified influenza A (H1N1), influenza A (H3N2), influenza B/Victoria lineage, and influenza B/Yamagata lineage antigens per 0.5 mL	Flucelvax Quadrivalent	Seqirus
		15 mcg hemagglutinin each of FDA-specified influenza A (H1N1), influenza A (H3N2), influenza B/Victoria lineage, and influenza B/Yamagata lineage antigens per 0.5 mL	Flulaval Quadrivalent	GlaxoSmithKline
		15 mcg hemagglutinin each of FDA-specified influenza A (H1N1), influenza A (H3N2), influenza B/Victoria lineage, and influenza B/Yamagata lineage antigens per 0.5 mL	Fluzone Quadrivalent	Sanofi Pasteur
		60 mcg hemagglutinin each of FDA-specified influenza A (H1N1), influenza A (H3N2), influenza B/Victoria lineage, and influenza B/Yamagata lineage antigens per 0.7 mL	Fluzone High-Dose Quadrivalent	Sanofi Pasteur

Influenza Virus Vaccine Inactivated Quadrivalent, Adjuvant-containing
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injectable emulsion, for IM use	15 mcg hemagglutinin each of FDA-specified influenza A (H1N1), influenza A (H3N2), influenza B/Victoria lineage, and influenza B/Yamagata lineage antigens per 0.5 mL	Fluad Quadrivalent	Seqirus

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545. . Recommended composition of influenza virus vaccines for use in the 2012–2013 northern hemisphere influenza season. Wkly Epidemiol Rec. 2012; 87:83-95. http://www.ncbi.nlm.nih.gov/pubmed/22462202?dopt=AbstractPlus

549. Centers for Disease Control and Prevention (CDC). Influenza A (H3N2) Variant Virus-Related Hospitalizations - Ohio, 2012. MMWR Morb Mortal Wkly Rep. 2012; 61:764-7. http://www.ncbi.nlm.nih.gov/pubmed/23013722?dopt=AbstractPlus

550. Centers for Disease Control and Prevention (CDC). Update: influenza activity - United States and worldwide, May 20-September 22, 2012. MMWR Morb Mortal Wkly Rep. 2012; 61:785-9. http://www.ncbi.nlm.nih.gov/pubmed/23034586?dopt=AbstractPlus

551. Centers for Disease Control and Prevention (CDC). Influenza activity--United States, 2012-13 season and composition of the 2013-14 influenza vaccine. MMWR Morb Mortal Wkly Rep. 2013; 62:473-9. http://www.ncbi.nlm.nih.gov/pubmed/23760189?dopt=AbstractPlus

552. . Recommended composition of influenza virus vaccines for use in the 2013–2014 northern hemisphere influenza season. Wkly Epidemiol Rec. 2013; 88:101-14. http://www.ncbi.nlm.nih.gov/pubmed/23544236?dopt=AbstractPlus

553. World Health Organization (WHO). Standardization of terminology of the pandemic A(H1N1)2009 virus. October 2011. From WHO website. Accessed 2013 Jul. http://www.who.int/influenza/gisrs_laboratory/terminology_ah1n1pdm09/en/

555. Centers for Disease Control and Prevention (CDC). Emergence of avian influenza A(H7N9) virus causing severe human illness - China, February-April 2013. MMWR Morb Mortal Wkly Rep. 2013; 62:366-71. http://www.ncbi.nlm.nih.gov/pubmed/23657113?dopt=AbstractPlus

556. Gao HN, Lu HZ, Cao B et al. Clinical findings in 111 cases of influenza A (H7N9) virus infection. N Engl J Med. 2013; 368:2277-85. http://www.ncbi.nlm.nih.gov/pubmed/23697469?dopt=AbstractPlus

557. Epperson S, Blanton L, Kniss K et al. Influenza activity - United States, 2013-14 season and composition of the 2014-15 influenza vaccines. MMWR Morb Mortal Wkly Rep. 2014; 63:483-90. http://www.ncbi.nlm.nih.gov/pubmed/24898165?dopt=AbstractPlus

559. . Recommended composition of influenza virus vaccines for use in the 2014-2015 northern hemisphere influenza season. Wkly Epidemiol Rec. 2014; 89:93-104. http://www.ncbi.nlm.nih.gov/pubmed/24707514?dopt=AbstractPlus

560. Rothberg MB, Haessler SD, Brown RB. Complications of viral influenza. Am J Med. 2008; 121:258-64. http://www.ncbi.nlm.nih.gov/pubmed/18374680?dopt=AbstractPlus

561. Appiah GD, Blanton L, D'Mello T et al. Influenza activity - United States, 2014-15 season and composition of the 2015-16 influenza vaccine. MMWR Morb Mortal Wkly Rep. 2015; 64:583-90. http://www.ncbi.nlm.nih.gov/pubmed/26042650?dopt=AbstractPlus

562. . Recommended composition of influenza virus vaccines for use in the 2015–2016 northern hemisphere influenza season. Wkly Epidemiol Rec. 2015; 90:97-108. http://www.ncbi.nlm.nih.gov/pubmed/25771542?dopt=AbstractPlus

563. Jhung MA, Nelson DI, Centers for Disease Control and Prevention (CDC). Outbreaks of avian influenza A (H5N2), (H5N8), and (H5N1) among birds--United States, December 2014-January 2015. MMWR Morb Mortal Wkly Rep. 2015; 64:111. http://www.ncbi.nlm.nih.gov/pubmed/25654614?dopt=AbstractPlus

564. US Centers for Disease Control and Prevention Health Alert Network. Bird infections with highly-pathogenic avian influenza A (H5N2), (H5N8), and (H5N1) viruses: recommendations for human health investigations and responses. CDCHAN-00378. June 2, 2015. From CDC website. http://emergency.cdc.gov/han/han00378.asp

565. Tan KX, Jacob SA, Chan KG et al. An overview of the characteristics of the novel avian influenza A H7N9 virus in humans. Front Microbiol. 2015; 6:140. http://www.ncbi.nlm.nih.gov/pubmed/25798131?dopt=AbstractPlus

566. United States Department of Agriculture. Avian influenza. From the USDA website. Accessed 2015 Jun 29. http://www.usda.gov

567. Davlin SL, Blanton L, Kniss K et al. Influenza Activity - United States, 2015-16 Season and Composition of the 2016-17 Influenza Vaccine. MMWR Morb Mortal Wkly Rep. 2016; 65:567-75. http://www.ncbi.nlm.nih.gov/pubmed/27281364?dopt=AbstractPlus

568. . Recommended composition of influenza virus vaccines for use in the 2016–2017 northern hemisphere influenza season. Wkly Epidemiol Rec. 2016; 91:121-32. http://www.ncbi.nlm.nih.gov/pubmed/26971356?dopt=AbstractPlus

569. US Food and Drug Administration. Center for Drug Evaluation and Research. STN:125510/0. Clinical review. From FDA website. http://www.fda.gov/downloads/BiologicsBloodVaccines/SafetyAvailability/VaccineSafety/UCM478096.pdf

570. Blanton L, Alabi N, Mustaquim D et al. Update: Influenza activity in the United States During the 2016-17 season and composition of the 2017-18 influenza vaccine. MMWR Morb Mortal Wkly Rep. 2017; 66:668-676. http://www.ncbi.nlm.nih.gov/pubmed/28662019?dopt=AbstractPlus

571. World Health Organization. Recommended composition of influenza virus vaccines for use in the 2017–2018 northern hemisphere influenza season. Wkly Epidemiol Rec. 2017; 92:117-28. http://www.ncbi.nlm.nih.gov/pubmed/28303704?dopt=AbstractPlus

572. US Centers for Disease Control and Prevention. Variant virus infections in people: interim guidance for clinicians. Aug 15, 2016. From CDC. website. https://www.cdc.gov/flu/pdf/swineflu/clinician-guidance-variant-flu-human-infections.pdf

573. Donahue JG, Kieke, BA, King JP et al. Association of spontaneous abortion with receipt of inactivated influenza vaccine containing H1N1pdm09 in 2010-11 and 2011-12. Vaccine. 2017; 35(40):5314-532. http://www.ncbi.nlm.nih.gov/pubmed/28917295?dopt=AbstractPlus

574. US Centers for Disease Control and Prevention. Flu vaccination & possible safety signal: Information & guidance for health care providers. From CDC website. Accessed 15 Sept 2017. https://www.cdc.gov/flu/professionals/vaccination/vaccination-possible-safety-signal.html

575. Garten R, Blanton L, Elal AIA et al. Update: Influenza Activity in the United States During the 2017-18 Season and Composition of the 2018-19 Influenza Vaccine. MMWR Morb Mortal Wkly Rep. 2018; 67:634-642. http://www.ncbi.nlm.nih.gov/pubmed/29879098?dopt=AbstractPlus

576. World Health Organization. Recommended composition of influenza virus vaccines for use in the 2018–2019 northern hemisphere influenza season. Wkly Epidemiol Rec. 2018; 93:133-41. http://www.ncbi.nlm.nih.gov/pubmed/29569429?dopt=AbstractPlus

577. Grohskopf LA, Sokolow LZ, Fry AM et al. Update: ACIP Recommendations for the Use of Quadrivalent Live Attenuated Influenza Vaccine (LAIV4) - United States, 2018-19 Influenza Season. MMWR Morb Mortal Wkly Rep. 2018; 67:643-645. http://www.ncbi.nlm.nih.gov/pubmed/29879095?dopt=AbstractPlus

578. Xu X, Blanton L, Elal AIA et al. Update: Influenza Activity in the United States During the 2018-19 Season and Composition of the 2019-20 Influenza Vaccine. MMWR Morb Mortal Wkly Rep. 2019; 68:544-551. http://www.ncbi.nlm.nih.gov/pubmed/31220057?dopt=AbstractPlus

579. World Health Organization. Recommended composition of influenza virus vaccines for use in the 2019–2020 northern hemisphere influenza season. February 2019. From WHO website. Accessed 2019 Aug 19. https://www.who.int/influenza/vaccines/virus/recommendations/201902_recommendation.pdf?ua=1

580. World Health Organization. Addendum to the recommended composition of influenza virus vaccines for use in the 2019–2020 northern hemisphere influenza season. March 21, 2019. From WHO website. Accessed 2019 Aug 19. https://www.who.int/influenza/vaccines/virus/recommendations/201902_recommendation.pdf?ua=1

581. US Centers for Disease Control and Prevention. Frequently asked influenza (flu) questions: 2021–2022 season. Updated August 26, 2021. From CDC website. Accessed 2021 Aug 28. https://www.cdc.gov/flu/season/faq-flu-season-2021-2022.htm

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585. World Health Organization. Recommended composition of influenza virus vaccines for use in the 2021–2022 northern hemisphere influenza season. February 2021. From WHO website. Accessed 2021 Aug 21. https://cdn.who.int/media/docs/default-source/influenza/202102_recommendation.pdf?sfvrsn=8639f

586. US Food and Drug Administration. FDA Center for Biologics Evaluation and Research (CBER) 165th Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting on March 5, 2021. Transcript. From FDA website. Accessed 2021 Sep 1. https://www.fda.gov/media/147456/download

587. US Centers for Disease Control and Prevention. CDC reports fifth U.S. human infection with variant flu virus for 2021. 2021 Jun 4. From CDC website. https://www.cdc.gov/flu/spotlights/2020-2021/human-infection-flu-variant.htm

588. US Centers for Disease Control and Prevention. Frequently asked influenza (flu) questions: 2022–2022 season. Updated September 12, 2022. From CDC website. Accessed 2022 Sept 23 https://www.cdc.gov/flu/season/faq-flu-season-2022-2023.htm

589. Izikson R, Brune D, Bolduc JS, et al. Safety and immunogenicity of a high-dose quadrivalent influenza vaccine administered concomitantly with a third dose of the mRNA-1273 SARS-CoV-2 vaccine in adults aged ≥65 years: a phase 2, randomised, open-label study. Lancet Respir Med 2022;10:392–402. Epub Feb. 21, 2022. http://www.ncbi.nlm.nih.gov/pubmed/35114141?dopt=AbstractPlus

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592. Hause AM, Zhang B, Yue X, et al. Reactogenicity of Simultaneous COVID-19 mRNA Booster and Influenza Vaccination in the US. JAMA Netw Open. 2022;5(7):e2222241.

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Influenza Virus Vaccine Inactivated (Monograph)

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Introduction

Uses for Influenza Virus Vaccine Inactivated

Prevention of Seasonal Influenza A and B Virus Infections

Influenza Vaccination During the Coronavirus Disease 2019 (COVID-19) Pandemic

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Influenza Virus Vaccine Inactivated Dosage and Administration

General

Administration

IM Administration

Jet Injector (Afluria)

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Pediatric Patients

Prevention of Seasonal Influenza A and B Virus Infections

Infants and Children 6 through 35 Months of Age (Afluria)

Infants and Children 6 through 35 Months of Age (Fluarix, Flulaval)

Infants and Children 6 through 35 Months of Age (Fluzone)

Children 6 months through 8 Years of Age (Flucelvax)

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Children and Adolescents 9 through 17 Years of Age (Afluria, Fluarix, Flucelvax, Flulaval, Fluzone)

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Prevention of Seasonal Influenza A and B Virus Infections

Adults ≥18 Years of Age (Afluria, Fluarix, Flucelvax, Flulaval, Fluzone)

Adults ≥65 Years of Age (Fluzone High-Dose)

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Hepatic Impairment

Renal Impairment

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Fluzone High-Dose

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Egg Allergy

Neomycin and/or Polymyxin B Allergy

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Guillain-Barré Syndrome (GBS)

Individuals with Altered Immunocompetence

Fever and Febrile Seizures

Thimerosal Precautions

Individuals with Bleeding Disorders

Concomitant Illness

Individuals with Known or Suspected Coronavirus Disease 2019 (COVID-19)

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