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Influenza virus vaccines (inactivated) (IIV3 and IIV4): Drug information

Influenza virus vaccines (inactivated) (IIV3 and IIV4): Drug information
(For additional information see "Influenza virus vaccines (inactivated) (IIV3 and IIV4): Patient drug information" and see "Influenza virus vaccines (inactivated) (IIV3 and IIV4): Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Afluria Quadrivalent;
  • Fluad Quadrivalent;
  • Fluad [DSC];
  • Fluarix Quadrivalent;
  • Flucelvax Quadrivalent;
  • Flulaval Quadrivalent;
  • Fluzone High-Dose Quadrivalent;
  • Fluzone Quadrivalent
Brand Names: Canada
  • Afluria Tetra;
  • Fluad;
  • Fluad Pediatric;
  • Flucelvax Quad;
  • Flulaval Tetra;
  • Fluzone High-Dose Quadrivalent;
  • Fluzone Quadrivalent;
  • Influvac Tetra
Pharmacologic Category
  • Vaccine;
  • Vaccine, Inactivated (Viral)
Dosing: Adult

Note: Influenza seasons vary in the timing and duration from year to year. In general, vaccination should preferably occur by the end of October (in the United States) to ensure optimal immunity prior to onset and for the full duration of influenza activity in the community. Early vaccination (in July or August) for an upcoming influenza season has been associated with suboptimal immunity before the end of an influenza season, particularly in older adults. Vaccination should continue throughout the influenza season as long as vaccine is available. The CDC does not recommend revaccination later in the season for those persons who have already been fully vaccinated. International considerations: Products with similar names but containing different strains may be circulating globally due to differences in recommendations between northern and southern hemisphere countries. In addition, recommendations related to use of influenza vaccines and approved ages may vary per country.

Immunization

Immunization:

Afluria Quadrivalent:

Adults ≤64 years of age: IM or via PharmaJet Stratis Needle-Free Injection System: 0.5 mL per dose as a single dose (1 dose per season).

Adults >64 years of age: IM: 0.5 mL per dose as a single dose (1 dose per season).

Fluarix Quadrivalent, Flucelvax Quadrivalent, FluLaval Quadrivalent, Fluzone Quadrivalent: IM: 0.5 mL/dose (1 dose per season).

Canadian labeling:

Afluria Tetra, FluLaval Tetra, Fluviral, Fluzone Quadrivalent: IM: 0.5 mL/dose (1 dose per season).

Influvac Tetra: IM, SubQ: 0.5 mL/dose (1 per season).

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Pediatric

(For additional information see "Influenza virus vaccines (inactivated) (IIV3 and IIV4): Pediatric drug information")

Note: Influenza seasons vary in the timing and duration from year to year. In general, vaccination should preferably occur by the end of October (in the United States) to ensure optimal immunity prior to onset and for the full duration of influenza activity in the community; patients who should receive 2 doses should begin vaccination as soon as vaccine is available so that the second dose can be given by the end of October. Vaccination should continue throughout the influenza season as long as vaccine is available. According to ACIP, doses administered ≤4 days before minimum interval or age are considered valid; however, local or state mandates may supersede this timeframe (ACIP [Kroger 2022]).

International considerations: Products with similar names but containing different strains may be circulating globally due to differences in recommendations between northern and southern hemisphere countries. In addition, recommendations related to use of influenza vaccines and approved ages may vary per country.

Immunization, annual

Immunization, annual: Note: Age is age at the time of the first dose.

Infants ≥6 months and Children <9 years: The number of doses needed per flu season is dependent upon vaccination history (see below) (AAP 2022; CDC/ACIP [Grohskopf 2022]).

One dose: If the patient received ≥2 doses of trivalent or quadrivalent influenza vaccine prior to July 1 preceding the current flu season start. The 2 doses need not have been received during the same season or consecutive seasons.

Two doses (separated by ≥4 weeks) if any of the following:

• It is the patient's first season of vaccination.

• Patient received ≤1 dose of trivalent or quadrivalent influenza vaccine prior to July 1 preceding the current flu season start.

• If vaccination history cannot be determined.

Note: A child turning 9 years of age between the first and second dose should still receive 2 doses.

Children ≥9 years and Adolescents: A single dose per season is needed.

Product-specific dosing: Note: In infants and young children, the dose volume may be different for some formulations (eg, 0.25 mL vs 0.5 mL per dose); use caution when verifying product selection and dose volume.

Afluria Quadrivalent :

Infants ≥6 months and Children ≤35 months: IM: 0.25 mL per dose for a total of 1 or 2 doses per season, dependent upon vaccination history (see Note regarding dose number).

Children 3 to 8 years: IM: 0.5 mL per dose for a total of 1 or 2 doses per season, dependent upon vaccination history (see Note regarding dose number).

Children ≥9 years and Adolescents <18 years: IM: 0.5 mL per dose as a single dose per season.

Adolescents ≥18 years: IM or via PharmaJet Stratis Needle-Free Injection System: 0.5 mL per dose as a single dose per season.

Fluarix Quadrivalent, Flucelvax Quadrivalent, FluLaval Quadrivalent:

Infants ≥6 months and Children <9 years: IM: 0.5 mL per dose for a total of 1 or 2 doses per season, dependent upon vaccination history (see Note regarding dose number).

Children ≥9 years and Adolescents: IM: 0.5 mL per dose as a single dose per season.

Fluzone Quadrivalent:

Infants ≥6 months and Children ≤35 months: IM: 0.25 mL or 0.5 mL per dose for a total of 1 or 2 doses per season, dependent upon vaccination history. If 2 doses required, the schedule can be completed as any combination of 0.25 mL or 0.5 mL doses administered ≥4 weeks apart (see Note regarding dose number).

Children 3 to 8 years: IM: 0.5 mL per dose for a total of 1 or 2 doses per season, dependent upon vaccination history (see Note regarding dose number).

Children ≥9 years and Adolescents: IM: 0.5 mL per dose as a single dose per season.

Canadian labeling:

Afluria Tetra:

Children 5 to <9 years: IM: 0.5 mL per dose (1 dose per season); a second dose should be administered 4 weeks after the first in previously unvaccinated patients.

Children ≥9 years and Adolescents: IM: 0.5 mL per dose (1 dose per season).

Fluzone Quadrivalent:

Infants and Children 6 to 35 months: IM: 0.25 mL or 0.5 mL per dose; NACI recommendation: 0.5 mL per dose (1 dose per season); a second dose should be administered 4 weeks after the first in previously unvaccinated patients (NACI 2021).

Children 3 to <9 years: IM: 0.5 mL per dose (1 dose per season); a second dose should be administered 4 weeks after the first in previously unvaccinated patients.

Children ≥9 years and Adolescents: IM: 0.5 mL per dose (1 dose per season).

Fluad Pediatric: Infants and Children 6 months to <2 years: IM: 0.25 mL per dose (1 dose per season); a second dose should be administered 4 weeks after the first in previously unvaccinated patients and in patients who were vaccinated for the first time last season and only 1 dose was received.

Flucelvax Quad:

Infants ≥6 months and Children <9 years: 0.5 mL per dose (1 dose per season); a second dose should be administered 4 weeks after the first in previously unvaccinated patients.

Children ≥9 years and Adolescents: IM: 0.5 mL per dose (1 dose per season).

FluLaval Tetra:

Infants ≥6 months and Children <9 years: IM: 0.5 mL per dose (1 dose per season); a second dose should be administered 4 weeks after the first in previously unvaccinated patients.

Children ≥9 years and Adolescents: IM: 0.5 mL per dose (1 dose per season).

Influvac Tetra:

Infants ≥6 months and Children <9 years: IM, Deep SUBQ: 0.5 mL per dose (1 dose per season); a second dose should be administered 4 weeks after the first in previously unvaccinated patients.

Children ≥9 years and Adolescents: IM, Deep SUBQ: 0.5 mL per dose (1 dose per season).

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling.

Dosing: Older Adult

Note: Influenza seasons vary in the timing and duration from year to year. In general, vaccination should preferably occur by the end of October (in the United States) to ensure optimal immunity prior to onset and for the full duration of influenza activity in the community. Early vaccination (in July or August) for an upcoming influenza season has been associated with suboptimal immunity before the end of an influenza season, particularly in older adults. Vaccination should continue throughout the influenza season as long as vaccine is available. The CDC does not recommend revaccination later in the season for those persons who have already been fully vaccinated. For persons ≥65 years of age, the ACIP recommends a higher dose or adjuvanted influenza vaccine (ie, HD-IIV4, RIV4, or aIIV4). If one of these vaccines is not available, then any other age-appropriate vaccine may be used (CDC/ACIP [Grohskopf 2022]).

Immunization: Adults ≥65 years of age:

Afluria Quadrivalent, Fluad Quadrivalent, Fluarix Quadrivalent, Flucelvax Quadrivalent, FluLaval Quadrivalent, Fluzone Quadrivalent: IM: 0.5 mL/dose (1 dose per season).

Fluzone High-Dose Quadrivalent: IM: 0.7 mL/dose (1 dose per season).

Canadian labeling:

Afluria Tetra, Fluad, FluLaval Tetra, Flucelvax Quad, Fluzone Quadrivalent: IM: 0.5 mL/dose (1 dose per season).

Fluzone High-Dose Quadrivalent: IM: 0.7 mL/dose (1 dose per season).

Influvac Tetra: IM, SubQ: 0.5 mL/dose (1 per season).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = discontinued product

Suspension, Intramuscular:

Afluria Quadrivalent: (5 mL) [contains thimerosal; may contain egg protein, neomycin sulfate]

Flucelvax Quadrivalent: (5 mL) [contains thimerosal; may contain polysorbate 80,]

Fluzone Quadrivalent: (5 mL) [contains thimerosal; may contain egg protein, formaldehyde]

Suspension, Intramuscular [preservative free]:

Fluzone Quadrivalent: (0.5 mL) [may contain egg protein, formaldehyde]

Suspension Prefilled Syringe, Intramuscular [preservative free]:

Afluria Quadrivalent: (0.25 mL, 0.5 mL) [may contain egg protein, neomycin sulfate]

Fluad: (0.5 mL [DSC]) [contains polysorbate 80; may contain egg protein, formaldehyde, neomycin]

Fluad Quadrivalent: (0.5 mL) [contains polysorbate 80; may contain egg protein, formaldehyde, neomycin]

Fluarix Quadrivalent: (0.5 mL) [contains polysorbate 80; may contain egg protein, formaldehyde, gentamicin]

Flucelvax Quadrivalent: (0.5 mL) [may contain polysorbate 80]

Flulaval Quadrivalent: (0.5 mL) [may contain egg white, formaldehyde, polysorbate 80]

Fluzone High-Dose Quadrivalent: (0.7 mL) [may contain egg protein, formaldehyde]

Fluzone Quadrivalent: (0.25 mL, 0.5 mL) [may contain egg protein, formaldehyde]

Generic Equivalent Available: US

May be product dependent

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, suspension:

Afluria Tetra: Hemagglutinin 60 mcg/0.5 mL (0.5 mL) [contains chicken egg protein, neomycin (may have trace amounts), polymyxin (may contain trace amounts), thimerosal]

Agriflu: Hemagglutinin 45 mcg/0.5 mL (0.5 mL) [contains chicken egg protein, neomycin (may have trace amounts), kanamycin (may have trace amounts), formaldehyde, polysorbate 80, thimerosal]

Flucelvax Quad: Haemagglutinin 15 mcg/0.5 mL (5 mL) [contains thimerosal]

FluLaval Tetra: (5 mL) [contains chicken egg protein, formaldehyde solution, polysorbate 80, thimerosal]

Fluviral: Hemagglutinin 45 mcg/0.5 mL (5 mL) [contains chicken egg protein, formaldehyde, polysorbate 80, thimerosal]

Fluzone Quadrivalent: Hemagglutinin 45 mcg/0.5 mL (5 mL) [contains chicken egg protein, formaldehyde, thimerosal]

Injection, suspension [preservative free]:

Agriflu: Hemagglutinin 45 mcg/0.5 mL (0.5 mL) [contains chicken egg protein, neomycin (may have trace amounts), kanamycin (may have trace amounts), formaldehyde, polysorbate 80]

Fluad: Hemagglutinin 45 mcg/0.5 mL (0.5 mL) [contains chicken egg protein, formaldehyde, neomycin (may have trace amounts), kanamycin (may have trace amounts), hydrocortisone (may have trace amounts), polysorbate 80]

Fluad Pediatric: Hemagglutinin 22.5 mcg/0.25 mL (0.25 mL) [contains chicken egg protein, formaldehyde, neomycin (may have trace amounts), kanamycin (may have trace amounts), hydrocortisone (may have trace amounts), polysorbate 80]

Flucelvax Quad: Haemagglutinin 15 mcg/0.5 mL (0.5 mL)

Fluzone High-Dose Quadrivalent: Hemagglutinin 60 mcg/0.7 mL (0.7 mL) [contains formaldehyde, ovalbumin]

Fluzone Quadrivalent: Hemagglutinin 45 mcg/0.5 mL (0.25 ml, 0.5 mL) [contains chicken egg protein, formaldehyde]

Influvac: Hemagglutinin 45 mcg/0.5 mL (0.5 mL) [contains chicken egg protein, formaldehyde, gentamicin (may have trace amounts), polysorbate 80]

Medication Guide and/or Vaccine Information Statement (VIS)

In the US, the appropriate Centers for Disease Control and Prevention (CDC)-approved Vaccine Information Statement (VIS) must be provided to the patient/caregiver before administering each dose of this vaccine; the VIS edition date and date it was provided to the patient/caregiver should be recorded as required by US law; VIS is available at http://www.cdc.gov/vaccines/hcp/vis/vis-statements/flu.html.

Administration: Adult

Suspensions should be shaken well prior to use; emulsions (Fluad Quadrivalent) should be gently shaken. Inspect for particulate matter and discoloration prior to administration. Some manufacturers recommend avoiding use if visible particles or discoloration are present in the suspension after shaking. See manufacturer labeling for specific recommendations.

Do not mix with other vaccines or injections; separate needles and syringes should be used for each injection. May administer simultaneously with other vaccines (eg, COVID-19 vaccine). If administering an influenza vaccine that may be more likely to produce an injection site reaction (eg, HD-IIV4 [Fluzone High-Dose] or adjuvanted IIV4 [Fluad Quadrivalent]) simultaneously with a COVID-19 vaccine, administer each vaccine in different limbs if possible (CDC/ACIP [Grohskopf 2022]).

To prevent syncope-related injuries, patients should be vaccinated while seated or lying down (ACIP [Kroger 2022]). US law requires that the date of administration, the vaccine manufacturer, lot number of vaccine, Vaccine Information Statement (VIS) edition date and date it was provided, and the administering person's name, title, and address be recorded.

IM: For IM administration. Use proper injection technique to inject into the deltoid muscle (eg, injecting into the central, thickest part of the muscle) to reduce the risk of shoulder injury related to vaccine administration (Cross 2016; Foster 2013). Do not inject into the gluteal region or areas where there may be a major nerve trunk.

Afluria Quadrivalent via PharmaJet Stratis Needle-free Injection System: For IM administration in adults 18 to 64 years of age only. For detailed instructions on preparation and administration of a dose, refer to the information available online at www.pharmajet.com.

Unless otherwise indicated in product labeling, jet injectors should not be used to administer inactivated influenza vaccines. Currently, Afluria Quadrivalent is the only influenza vaccine licensed in the United States with data about use with a jet-injector device.

SUBQ: Influvac Tetra (Canadian product): May administer by deep SUBQ injection; allow to warm to room temperature prior to use.

If a pediatric dose of 0.25 mL is inadvertently administered to a patient who should have received a 0.5 mL or 0.7 mL dose, the remaining volume needed to make the full dose or a full repeat dose should be administered. If the error is discovered after the patient has left the health care setting, a full dose should be given as soon as the patient can return (CDC/ACIP [Grohskopf 2022]).

Note: For patients at risk of hemorrhage following IM injection, the vaccine should be administered IM if, in the opinion of the physician familiar with the patient's bleeding risk, the vaccine can be administered by this route with reasonable safety. If the patient receives antihemophilia or other similar therapy, intramuscular vaccination can be scheduled shortly after such therapy is administered. A fine needle (≤23-gauge) can be used for the vaccination and firm pressure applied to the site (without rubbing) for at least 2 minutes. The patient should be instructed concerning the risk of hematoma from the injection. Patients on anticoagulant therapy should be considered to have the same bleeding risks and treated as those with clotting factor disorders (ACIP [Kroger 2022]).

Administration: Pediatric

To prevent syncope-related injuries, adolescents should be vaccinated while seated or lying down. Do not mix with other vaccines or injections; separate needles and syringes should be used for each injection (ACIP [Kroger 2022]). US law requires that the date of administration, the vaccine manufacturer, lot number of vaccine, Vaccine Information Statement (VIS) edition date and date it was provided, and the administering person's name, title, and address be recorded.

IM: US products: Afluria Quadrivalent, Fluarix Quadrivalent, Flucelvax Quadrivalent, FluLaval Quadrivalent, Fluzone Quadrivalent; Canadian products: Afluria Tetra, Fluad Pediatric, FluLaval Tetra, Fluzone Quadrivalent, Influvac Tetra:

For IM administration only. Inspect for particulate matter and discoloration prior to administration. Shake well prior to use; for Fluad Pediatric [Canadian product] shake gently. Jet injectors should not be used to administer inactivated influenza vaccines unless otherwise indicated in product labeling. Currently Afluria Quadrivalent is the only influenza vaccine in the US that can be given IM by a jet-injector device. Prefilled syringes should not be used to deliver smaller dose volumes (eg, do not use a 0.5 mL Fluzone prefilled syringe to deliver a 0.25 mL dose) (CDC/ACIP [Grohskopf 2022]).

Infants: IM injection in the anterolateral aspect of the thigh preferred; injection into the gluteal region or areas where there may be a major nerve trunk should generally not be used; however, ACIP indicates that the gluteal muscle can be used in certain circumstances, with care taken to define anatomic landmarks (ACIP [Kroger 2022]).

Children <3 years: IM injection in anterolateral thigh preferred; deltoid muscle can be used if muscle mass is adequate (ACIP [Kroger 2022]).

Children ≥3 years and Adolescents: IM injection in the deltoid muscle. Use proper injection technique to inject into the deltoid muscle (eg, injecting into the central, thickest part of the muscle) to reduce the risk of shoulder injury related to vaccine administration (Cross 2016; Foster 2013).

Afluria Quadrivalent via PharmaJet Stratis Needle-Free Injection System: Adolescents ≥18 years: For IM administration only. For detailed instructions on preparation and administration of a dose, refer to the information available online at www.pharmajet.com.

SUBQ: Influvac Tetra (Canadian labeling): Infants ≥6 months, Children, and Adolescents: May administer by deep SUBQ injection. Allow to warm to room temperature prior to use.

Patients at risk of bleeding (eg, patient receiving antihemophilic factor): For patients at risk of hemorrhage following IM injection, the vaccine should be administered IM if, in the opinion of the physician familiar with the patient's bleeding risk, the vaccine can be administered by this route with reasonable safety. If the patient receives antihemophilia or other similar therapy, IM vaccination can be scheduled shortly after such therapy is administered. A fine needle (23-gauge or smaller) can be used for the vaccination and firm pressure applied to the site (without rubbing) for at least 2 minutes. The patient should be instructed concerning the risk of hematoma from the injection. Patients on anticoagulant therapy should be considered to have the same bleeding risks and treated as those with clotting factor disorders (ACIP [Kroger 2022]).

If a pediatric dose of 0.25 mL is inadvertently administered to a patient ≥36 months of age who should have received a 0.5 mL dose, the remaining volume needed to make the full dose or a full repeat dose should be administered. If the error is discovered after the patient has left the health care setting, a full dose should be given as soon as the patient can return. If a 0.5 mL dose is inadvertently administered to a patient who should have received 0.25 mL, no action needs to be taken; the dose should be counted as a single dose (CDC/ACIP [Grohskopf 2022]).

Use: Labeled Indications

Influenza disease prevention: Active immunization against influenza disease caused by influenza virus subtypes A and type B contained in the vaccine in the following persons:

US labeling:

• ≥6 months of age (Afluria Quadrivalent, Fluarix Quadrivalent, Flucelvax Quadrivalent, FluLaval Quadrivalent, Fluzone Quadrivalent)

• ≥65 years of age (Fluad Quadrivalent, Fluzone High-Dose Quadrivalent)

Canadian labeling:

• 6 months to <2 years of age (Fluad Pediatric)

• ≥6 months of age (Flucelvax Quad, FluLaval Tetra, Fluzone Quadrivalent, Influvac Tetra)

• ≥5 years of age (Afluria Tetra)

• ≥65 years of age (Fluad, Fluzone High-Dose Quadrivalent)

Recommendations for annual seasonal influenza prevention:

The Advisory Committee on Immunization Practices (ACIP) recommends routine annual vaccination with the seasonal influenza vaccine for all persons ≥6 months of age who do not otherwise have contraindications to the vaccine. The ACIP and American Academy of Pediatrics (AAP) recommend use of any age and risk factor appropriate product and do not have a preferential recommendation for an influenza vaccine product for persons 6 months to <65 years of age. For persons ≥65 years of age, the ACIP recommends a higher dose or adjuvanted influenza vaccine (ie, HD-IIV4, RIV4, or aIIV4). If one of these vaccines is not available, then any other age-appropriate vaccine may be used. In addition to inactivated influenza vaccines (IIV4), the live attenuated vaccine (LAIV4) may be used for persons ≥2 years of age and recombinant influenza vaccine (RIV) can be used in persons ≥18 years of age (AAP 2022; CDC/ACIP [Grohskopf 2022]).

The Canadian National Advisory Committee on Immunization (NACI) recommends annual vaccination with seasonal influenza vaccine for all persons ≥6 months of age who do not have contraindications to the vaccine (NACI 2022). The following influenza vaccine preferences should be considered (Note: Trivalent inactivated influenza vaccines [IIV3] will not be available in Canada during the 2022-23 influenza season.)

• Persons 6 to 23 months of age: Quadrivalent inactivated influenza vaccine (IIV4) is preferred; use trivalent inactivated influenza vaccine (IIV3) if IIV4 is not available.

• Persons 2 to 17 years of age: Either IIV4-SD, LAIV4 (if appropriate), or IIV4-cc is preferred; use IIV3-SD if the other options are not available.

• Persons 18 to 64 years of age: Any age- and risk factor–appropriate product may be used.

• Persons ≥65 years of age: IIV-HD (high dose) is preferred over IIV-SD (standard dose); however, any available influenza vaccine may be used for public health program-level decision making.

• Health care workers: Either IIV4 or IIV3 are recommended; LAIV should not be used.

Prioritization when vaccine supply is limited:

When vaccine supply is limited, target groups for vaccination (those at higher risk of complications from influenza infection and their close contacts) include the following; see guidelines for details (CDC/ACIP [Grohskopf 2022]; NACI 2022):

• All infants and children 6 to 59 months of age

• Persons ≥50 years of age (≥65 years of age in Canada)

• Infants, children, and adolescents (6 months to 18 years of age) who are receiving aspirin or salicylate therapy, and therefore, may be at risk for developing Reye syndrome after influenza

• Persons who are or will be pregnant during the influenza season

• Persons with chronic pulmonary disorders (including asthma) or cardiovascular systems disorders (except isolated hypertension), renal, hepatic, neurologic, hematologic, or metabolic disorders (including diabetes mellitus). Note: The Canadian NACI excludes persons with isolated migraine or psychiatric conditions (without neurological conditions).

• Persons who have immunosuppression due to any cause (including immunosuppression caused by medications or HIV)

• Residents of nursing homes and other long-term care facilities

• Indigenous peoples (including American Indians/Alaska Natives)

• Persons with extreme obesity (BMI ≥40 for adults)

• Health care personnel, including students in these professions and other persons not directly involved in patient care who may be exposed to patients or to infectious agents (eg, clerical, housekeeping, volunteers)

• Household contacts (≥6 months of age) and caregivers of neonates, infants, and children <5 years of age (particularly neonates and infants <6 months of age) and adults ≥50 years of age

• Household contacts (≥6 months of age) and caregivers of persons with medical conditions which put them at higher risk of severe complications from influenza infection

• In addition, the NACI includes the following: persons who provide services within closed or relatively closed settings to persons at high risk; persons who provide essential community services; and persons in direct contact with poultry infected with avian influenza during culling operations

Medication Safety Issues
Sound-alike/look-alike issues:

COVID-19 vaccine may be confused with influenza virus vaccine. Medication errors have occurred when COVID-19 vaccine was inadvertently administered instead of influenza virus vaccine (and vice versa). These products may be stored in close proximity to each other. Confirm the correct vaccine has been selected prior to administration (ISMP/NAN 2021).

Fluarix may be confused with Flarex.

Influenza virus vaccine may be confused with perflutren lipid microspheres.

Influenza virus vaccine may be confused with tetanus toxoid and tuberculin products. IIV may be confused with PPD. Medication errors have occurred when tuberculin skin tests (PPD) have been inadvertently administered instead of tetanus toxoid products and influenza virus vaccine. These products are refrigerated and often stored in close proximity to each other.

Influenza virus vaccine may be confused with insulin. Medication errors have occurred when insulin was inadvertently administered instead of influenza virus vaccine. These products are refrigerated and may be stored in close proximity to each other.

Influenza virus vaccine may be confused with COVID-19 vaccines. Medication errors have occurred when COVID-19 vaccine was inadvertently administered instead of influenza virus vaccine.

International issues:

Fluarix [US and multiple international markets] may be confused with Flarex brand name for fluorometholone [US and multiple international markets] and Fluorex brand name for fluoride [France]

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adult and pediatric patients unless otherwise specified. Incidence of adverse events for the second dose of vaccine (when warranted) was typically milder than first dose.

>10%:

Gastrointestinal: Anorexia (infants, children, and adolescents: 9% to 32%; adults and older adults: 4% to 8%), diarrhea (4% to 24%), nausea (≤12%), vomiting (infants, children, and adolescents: ≤15%; adults and older adults: ≤3%)

Local: Bruising at injection site (≤11%), erythema at injection site (1% to 37%), induration at injection site (≤18%), pain at injection site (17% to 67%), swelling at injection site (≤25%), tenderness at injection site (21% to 69%)

Nervous system: Drowsiness (infants and children: 8% to 38%), fatigue (≤22%), headache (1% to 27%), irritability (infants and children: 2% to 54%), malaise (≤38%), uncontrolled crying (infants and children: 33% to 41%)

Neuromuscular & skeletal: Arthralgia (4% to 15%), myalgia (3% to 40%)

Respiratory: Cough (infants, children, and adolescents: 1% to 15%), rhinorrhea (infants and children: 1% to 11%)

Miscellaneous: Fever (infants, children, and adolescents: 1% to 16%; adults and older adults: ≤4%)

1% to 10%:

Dermatologic: Skin rash (infants and children: 1%)

Gastrointestinal: Change in appetite (children: 10%)

Nervous system: Chills (≤8%), shivering (≤9%)

Respiratory: Flu-like symptoms (infants and children: 1%), nasal congestion (infants, children, and adolescents: 2% to 6%), nasopharyngitis (infants and children: 2%), oropharyngeal pain (1% to 7%)

Frequency not defined: Local: Hematoma at injection site, itching at injection site

Postmarketing:

Cardiovascular: Chest pain, facial edema, flushing, presyncope, swelling of injected limb (lasting >1 week), syncope (shortly after vaccination), tachycardia, vasculitis (including transient renal involvement), vasodilation

Dermatologic: Diaphoresis, ecchymoses, erythema multiforme, erythema of skin, pallor, pruritus, rash at injection site, Stevens-Johnson syndrome, urticaria

Endocrine & metabolic: Hot flash

Gastrointestinal: Abdominal distress, abdominal pain, dysphagia, gastroenteritis, swollen tongue

Hematologic & oncologic: Henoch-Schönlein purpura, lymphadenopathy, thrombocytopenia

Hypersensitivity: Anaphylactic shock, anaphylaxis, angioedema, hypersensitivity reaction (including oculorespiratory syndrome, an acute, self-limited reaction with ocular and respiratory symptoms) (NACI 2022), nonimmune anaphylaxis, serum sickness, type 1 hypersensitivity reaction

Local: Abscess at injection site, cellulitis at injection site, inflammation at injection site, warm sensation at injection site

Nervous system: Bell's palsy, body pain, cranial nerve palsy, dizziness, encephalopathy, facial nerve paralysis, feeling hot, Guillain-Barre syndrome, hypoesthesia, impaired mobility (of injected limb), insomnia, myasthenia, neuralgia, neuritis, neuropathy (including brachial plexus), paralysis (including limb), paresthesia, seizure, transverse myelitis, vertigo, voice disorder

Neuromuscular & skeletal: Asthenia, hypokinesia, limb pain, musculoskeletal pain, myelitis (including encephalomyelitis), tremor

Ophthalmic: Eye pain, eyelid edema, ocular hyperemia, optic neuritis, optic neuropathy, photophobia, swelling of eye

Respiratory: Bronchospasm, dyspnea, pharyngeal edema, pharyngitis, rhinitis, tonsillitis, wheezing

Miscellaneous: Febrile seizure

Contraindications

Severe allergic reaction (eg, anaphylaxis) to any component of the formulation; see manufacturer labeling for all components of each formulation.

Additional manufacturer contraindications for Afluria Quadrivalent, Fluad Quadrivalent, Fluarix Quadrivalent, FluLaval Quadrivalent, Fluzone High-Dose Quadrivalent, Fluzone Quadrivalent: History of severe allergic reaction (eg, anaphylaxis) to egg protein.

Additional manufacturer contraindications for Canadian products: Fluad, Fluad Pediatric, FluLaval Tetra, Fluzone High-Dose Quadrivalent, Fluzone Quadrivalent, Influvac Tetra: Hypersensitivity to egg protein.

Additional contraindications from the Advisory Committee on Immunization Practices (ACIP) (CDC/ACIP [Grohskopf 2022)]:

Egg-based IIV4 vaccines: Severe allergic reaction (eg, anaphylaxis) to a previous dose of any influenza vaccine.

Cell culture-based IIV4 (Flucelvax Quadrivalent): Severe allergic reaction (eg, anaphylaxis) to a previous dose of any cell culture-based IIV.

Note: Neither the ACIP nor the Canadian National Advisory Committee on Immunization consider egg allergy a contraindication to influenza vaccination (CDC/ACIP [Grohskopf 2022]; NACI 2022).

Warnings/Precautions

Concerns related to adverse effects:

• Oculorespiratory syndrome: Oculorespiratory syndrome (ORS) is an acute, self-limiting reaction to inactivated influenza vaccine (IIV) with one or more of the following symptoms appearing within 2 to 24 hours after the dose: chest tightness, cough, difficulty breathing, facial swelling, red eyes, sore throat, or wheezing. Symptoms resolve within 48 hours of onset. The cause of ORS has not been established, but studies have suggested that it is not IgE mediated. However, because ORS symptoms may be similar to those of an IgE-mediated hypersensitivity reaction, health care providers unsure of etiology of symptoms should seek advice from an allergist/immunologist when determining whether a patient may be revaccinated in subsequent seasons (Demicheli 2018; Skowronski 2005).

• Shoulder injury related to vaccine administration: Vaccine administration that is too high on the upper arm may cause shoulder injury (eg, shoulder bursitis or tendinopathy) resulting in shoulder pain and reduced range of motion following injection. Use proper injection technique for vaccines administered in the deltoid muscle (eg, injecting in the central, thickest part of the muscle) to reduce the risk of shoulder injury related to vaccine administration (Cross 2016; Foster 2013).

• Syncope: Syncope has been reported with use of injectable vaccines and may result in serious secondary injury (eg, skull fracture, cerebral hemorrhage); typically reported in adolescents and young adults and within 15 minutes after vaccination. Procedures should be in place to avoid injuries from falling and to restore cerebral perfusion if syncope occurs (ACIP [Kroger 2022]).

Disease-related concerns:

• Acute illness: The decision to administer or delay vaccination because of current or recent febrile illness depends on the severity of symptoms and the etiology of the disease. Defer administration in patients with moderate or severe acute illness (with or without fever); vaccination should not be delayed for patients with mild acute illness (with or without fever) (ACIP [Kroger 2022]).

• Bleeding disorders: Use with caution in patients with a history of bleeding disorders (including thrombocytopenia); bleeding/hematoma may occur from IM administration; if the patient receives antihemophilia or other similar therapy, IM injection can be scheduled shortly after such therapy is administered (ACIP [Kroger 2022]).

• Febrile seizures: Based on information from the Centers for Disease Control and Prevention (CDC), an increased rate of febrile seizures has been reported in young children 6 to 23 months of age who received vaccination with IIV and the 13-valent pneumococcal conjugate vaccine (PCV13), 7-valent pneumococcal conjugate vaccine (PCV7), or diphtheria, tetanus, and pertussis (DTaP)-containing vaccines. However, due to the risks associated with delaying either vaccine, administering them at separate visits or deviating from the recommended vaccine schedule is not currently recommended (CDC/ACIP [Grohskopf 2022]). Antipyretics have not been shown to prevent febrile seizures; antipyretics may be used to treat fever or discomfort following vaccination (ACIP [Kroger 2022]). One study reported that routine prophylactic administration of acetaminophen to prevent fever prior to vaccination decreased the immune response of some vaccines; the clinical significance of this reduction in immune response has not been established (Prymula 2009).

• Guillain-Barré syndrome: Use with caution in patients with history of Guillain-Barré syndrome (GBS); patients with history of GBS have a greater likelihood of developing GBS than those without. As a precaution, the Advisory Committee on Immunization Practices (ACIP) recommends that patients with a history of GBS and who are not at higher risk for severe influenza complications, and patients known to have experienced GBS within 6 weeks following previous influenza vaccination should generally not be vaccinated (consider influenza antiviral chemoprophylaxis in these patients). The benefits of vaccination may outweigh the potential risks in persons with a history of GBS who are also at higher risk for severe complications of influenza (CDC/ACIP [Grohskopf 2022]). Studies of patients who received the trivalent inactivated influenza vaccine or the monovalent H1N1 influenza vaccine have shown the risk of GBS is lower with vaccination than with influenza infection (Baxter 2013; Greene 2013; Kwong 2013).

• Neurologic disorders: Some Canadian product labeling recommends delaying therapy in patients with active neurologic disorders.

Concurrent drug therapy issues:

• Anticoagulant therapy: Use with caution in patients receiving anticoagulant therapy; bleeding/hematoma may occur from IM administration (ACIP [Kroger 2022]).

• Vaccines: In order to maximize vaccination rates, the ACIP, as well as the Canadian National Advisory Committee on Immunization (NACI), recommends simultaneous administration (ie, >1 vaccine on the same day at different anatomic sites) of all age-appropriate vaccines (live or inactivated) for which a person is eligible at a single clinic visit, unless contraindications exist. The ACIP prefers each dose of a specific vaccine in a series come from the same manufacturer when possible; however, vaccination should not be deferred because a specific brand is unavailable (ACIP [Kroger 2022]; NACI 2022).

Special populations:

• Altered immunocompetence: Consider deferring immunization during periods of immunosuppression (eg, patients receiving chemo/radiation therapy or other immunosuppressive therapy [including high-dose corticosteroid]); may have a reduced response to vaccination. Inactivated vaccine (IIV or recombinant influenza vaccine [RIV]) is preferred over live virus vaccine (LAIV) for immunocompromised persons, household members, health care workers, and others coming in close contact with severely immunosuppressed persons requiring care in a protected environment. Refer to annual immunization schedule for additional information (ACIP [Kroger 2022]; CDC/ACIP [Grohskopf 2022]). Inactivated vaccines should be administered ≥2 weeks prior to planned immunosuppression when feasible; inactivated vaccines administered during chemotherapy should be readministered after immune competence is regained (ACIP [Kroger 2022]; IDSA [Rubin 2014]).

• Older adults: Antibody responses may be lower and decline faster in older adults ≥65 years of age compared to younger adults; however, deferral to later in the season may result in missed vaccination opportunities or early season infection (CDC/ACIP [Grohskopf 2022]). Fluzone High-Dose contains 4 times the amount of each influenza antigen compared to other inactivated virus vaccines and was shown to elicit a higher antibody response and may provide better protection against influenza illness in older adults compared to standard dose IIV3 formulations (DiazGranados 2014). For persons ≥65 years of age, the ACIP recommends a higher dose or adjuvanted influenza vaccine (ie, HD-IIV4, RIV4, or aIIV4). If one of these vaccines is not available, then any other age-appropriate vaccine may be used (CDC/ACIP [Grohskopf 2022]).

Dosage form specific issues:

• Chicken egg protein: Most products are manufactured with chicken egg protein (expressed as ovalbumin content when content is disclosed on prescribing information). The ovalbumin content may vary from season to season and lot to lot of vaccine. Allergy to eggs must be distinguished from allergy to the vaccine. Recommendations are available from the ACIP and NACI regarding influenza vaccination to persons who report egg allergies; however, ACIP states a prior severe allergic reaction to influenza vaccine, regardless of the component suspected, is a contraindication to vaccination. Per ACIP, patients with a history of egg allergy who have experienced only hives following egg exposure should receive influenza vaccine if otherwise appropriate. Patients with a history of egg allergy other than hives (eg, angioedema, respiratory distress) or who required emergency medical attention (eg, epinephrine) may receive influenza vaccine if otherwise appropriate and (for vaccines other than ccIV4 or RIV) administered in an inpatient or outpatient medical setting with health care supervision able to recognize and manage severe allergic reactions (CDC/ACIP [Grohskopf 2022]). However, the American Academy of Pediatrics (AAP); American Academy of Allergy, Asthma, and Immunology/American College of Allergy, Asthma, and Immunology; and NACI state that patients may receive vaccination regardless of severity of egg allergy and no special precautions are required (AAP 2022; Greenhawt 2018; NACI 2022). Flucelvax Quadrivalent (ccIIV4) is an inactivated influenza vaccine manufactured using cell-culture technology and provides an alternative to vaccines cultured with chicken egg protein (CDC/ACIP [Grohskopf 2022]).

• Gentamicin: Some products are manufactured with gentamicin.

• Hydrocortisone: Some products may contain hydrocortisone.

• Kanamycin: Some products are manufactured with kanamycin.

• Latex: Packaging may contain natural latex rubber.

• Neomycin: Some products are manufactured with neomycin.

• Polymyxin: Some products are manufactured with polymyxin.

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

• Thimerosal: Some products contain thimerosal; hypersensitivity reactions may occur.

Other warnings/precautions:

• Appropriate use: Use of this vaccine for specific medical and/or other indications (eg, immunocompromising conditions, hepatic or kidney disease, diabetes) is also addressed in the annual ACIP Recommended Immunization Schedules (refer to CDC schedule for detailed information). Specific recommendations for use of this vaccine in immunocompromised patients with asplenia, cancer, HIV infection, cerebrospinal fluid leaks, cochlear implants, hematopoietic stem cell transplant (prior to or after), sickle cell disease, solid organ transplant (prior to or after), or those receiving immunosuppressive therapy for chronic conditions are available from the Infectious Diseases Society of America (Rubin 2014).

• Effective immunity: Vaccination may not result in effective immunity in all patients. Response depends upon multiple factors (eg, type of vaccine, age of patient) and may be improved by administering the vaccine at the recommended dose, route, and interval. Vaccines may not be effective if administered during periods of altered immune competence (ACIP [Kroger 2022]).

• Other influenza vaccines: Influenza vaccines from previous seasons must not be used. Vaccines formulated for the northern hemisphere may differ in composition from the southern hemisphere vaccine; consult CDC Yellow Book for more information regarding travel vaccines (CDC/ACIP [Grohskopf 2022]).

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Acetaminophen: May diminish the therapeutic effect of Vaccines. Management: Consider avoiding routine prophylactic use of acetaminophen before or during vaccine administration when possible. Acetaminophen is still recommended to treat fevers and/or pain that occurs after vaccination. Risk D: Consider therapy modification

Corticosteroids (Systemic): May diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiation of systemic corticosteroids at immunosuppressive doses. Influenza vaccines administered less than 14 days prior to or during such therapy should be repeated 3 months after therapy. Risk D: Consider therapy modification

Doxofylline: Influenza Virus Vaccine (Inactivated) may increase the serum concentration of Doxofylline. Risk C: Monitor therapy

Elivaldogene Autotemcel: May enhance the adverse/toxic effect of Vaccines. Specifically, there may be a greater risk for contracting an infection from any live vaccine. Elivaldogene Autotemcel may diminish the therapeutic effect of Vaccines. Management: Administration of vaccines is not recommended in the 6 weeks before myeloablative conditioning, and until hematologic recovery after elivaldogene autotemcel treatment. Risk X: Avoid combination

Fingolimod: May diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting fingolimod. If vaccinated during fingolimod therapy, revaccinate 2 to 3 months after fingolimod discontinuation. Risk D: Consider therapy modification

Immunosuppressants (Cytotoxic Chemotherapy): May diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification

Immunosuppressants (Miscellaneous Oncologic Agents): May diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification

Immunosuppressants (Therapeutic Immunosuppressant Agents): May diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate 2 to 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification

Methotrexate: May diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating methotrexate if possible. If vaccination occurs less than 2 weeks prior to or during methotrexate therapy, revaccinate 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification

Pneumococcal Conjugate Vaccine (13-Valent): May diminish the therapeutic effect of Influenza Virus Vaccine (Inactivated). Influenza Virus Vaccine (Inactivated) may diminish the therapeutic effect of Pneumococcal Conjugate Vaccine (13-Valent). Risk C: Monitor therapy

Propacetamol: May diminish the therapeutic effect of Vaccines. Management: Consider avoiding routine prophylactic use of propacetamol before or during vaccine administration when possible. Propacetamol is still recommended to treat fevers and/or pain that occurs after vaccination. Risk D: Consider therapy modification

RiTUXimab: May diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines 2 weeks prior to starting rituximab. Vaccination of patients treated with rituximab in the past 6 months is not recommended. If vaccinated less than 2 weeks prior to rituximab, revaccinate 6 months after rituximab treatment. Risk D: Consider therapy modification

RiTUXimab: May diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of rituximab when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 6 months after therapy is complete. Risk D: Consider therapy modification

Siponimod: May diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Avoid administration of vaccines (inactivated) during treatment with siponimod and for 1 month after discontinuation due to potential decreased vaccine efficacy. Risk D: Consider therapy modification

Teplizumab: May diminish the therapeutic effect of Influenza Virus Vaccines. Management: Influenza virus vaccines are not recommended in the 2 weeks prior to teplizumab treatment, during treatment, or for 6 weeks after treatment. Reduced efficacy of the vaccine may occur if administer to patients taking teplizumab. Risk D: Consider therapy modification

Teplizumab: May diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Vaccination with inactivated or non-replicating vaccines is not recommended in the 2 weeks prior to teplizumab therapy, during treatment, or for 6 weeks following completion of therapy. Risk D: Consider therapy modification

Reproductive Considerations

Using data prospectively collected from the Pregnancy Study Online (PRESTO), an internet-based preconception cohort study of patients planning to become pregnant, use of the seasonal influenza vaccine by either partner did not adversely affect the probability of conceiving (time and date of influenza vaccination in proximity to pregnancy was self-reported) (Orta 2020).

Influenza vaccination with any licensed, recommended, age-appropriate vaccine is recommended for all patients who may become pregnant during the influenza season and who do not otherwise have contraindications to the vaccine (CDC/ACIP [Grohskopf 2022]).

Pregnancy Considerations

Inactivated influenza vaccine (IIV) has not been shown to cause fetal harm when given to pregnant patients, although information related to use in the first trimester is relatively limited (CDC/ACIP [Grohskopf 2022]).

• Outcome data following exposure to the seasonal trivalent and quadrivalent IIV are available from the GlaxoSmithKline pregnancy registry. Between 2014 and 2019, there were 507 reported US exposures with prospectively collected data (115 with outcome information); among these there were 84 first-trimester exposures (54 lost to follow-up). Also during this time period, there were 676 reports from global sources (493 with prospectively collected data; 186 with outcome information). Among the US pregnancies with known outcomes, 87.8% resulted in a live birth with no congenital anomalies. There were no live-born infants with first-trimester exposure to the seasonal IIV diagnosed with a congenital anomaly. Among the global prospectively reported exposures with known outcomes (n=186), 61.3% resulted in live birth with no congenital anomalies and 35.5% were ongoing. The registry also collected data for spontaneous abortion, fetal death/stillbirth; based on available data, no safety signals were identified (Nwoji 2022).

• Outcome data following exposure to the seasonal quadrivalent IIV is also available from the Sanofi Pasteur Fluzone Quadrivalent pregnancy registry. Between 2013 and 2019, there were 239 reported exposures from nine different countries (>85% from the United States, Australia, and Canada). Of these, 210 exposures had prospectively collected data (62 with known pregnancy/obstetrical outcomes and 15 with known neonatal outcomes) and 29 exposures with retrospectively collected data (29 with known pregnancy/obstetrical outcomes and 28 with known neonatal outcomes). No congenital anomalies were reported in the prospectively collected cases. Congenital anomalies were reported in four cases reported retrospectively (talipes n=2, atrial septal defect n=1, CNS anomaly n=1). Based on available data, the rates of all neonatal and maternal outcomes observed were similar to rates reported in the general population and no safety signals were identified (Ledlie 2022).

• Data from published studies, systematic reviews, and meta-analyses have not observed an increased risk of adverse pregnancy outcomes (including congenital anomalies, preterm birth, low birth weight, or fetal death) following maternal vaccination with IIV during pregnancy (Foo 2020; Jeong 2019; Macias Saint-Gerons 2021; Nunes 2016; Polyzos 2015).

Maternal vaccination provides passive immunization to the newborn and decreases the risk of hospitalization due to influenza in infants <6 months of age who are not eligible to be vaccinated (ACOG 2018).

The risk for severe illness and complications from influenza infection is increased during pregnancy, particularly during the second and third trimesters (CDC/ACIP [Grohskopf 2022]). Pregnant patients infected with influenza have a higher risk than nonpregnant patients of progression to pneumonia, hospitalization, and ICU admission (ACOG 2018). Influenza vaccination decreases the risk of laboratory-confirmed influenza and hospitalization in pregnant patients (Thompson 2014; Thompson 2019).

The efficacy of influenza vaccination in pregnant patients is similar to nonpregnant adults. Influenza vaccination is recommended annually and should be given to pregnant patients even if they were vaccinated in a prior pregnancy (ACOG 2018). Influenza vaccination with any licensed, recommended, age-appropriate IIV or recombinant influenza vaccine (RIV) is recommended for all patients who are pregnant during the influenza season and who do not otherwise have contraindications to the vaccine (CDC/ACIP [Grohskopf 2022]). Vaccination may be done during any trimester (ACOG 2018). Vaccination of nonpregnant patients is typically offered by the end of October; however, to decrease the risk of infection to the neonate, consider vaccination of pregnant patients who are in their third trimester in July or August, or as soon as vaccine is available (CDC/ACIP [Grohskopf 2022]).

Pregnant patients should observe the same precautions as nonpregnant patients to reduce the risk of exposure to influenza and other respiratory infections (CDC/HHS 2021). When vaccine supply is limited, focus should be given to delivering the vaccine to patients who are pregnant or will be pregnant during the flu season, as well as contacts or caregivers of children <5 years of age (particularly contacts of neonates and infants <6 months of age) (CDC/ACIP [Grohskopf 2022]).

Data collection to monitor pregnancy and infant outcomes following exposure to influenza vaccine is ongoing.

• Persons exposed to Afluria Quadrivalent vaccine during pregnancy may contact the Seqirus registry at 855-358-8966 or via email at us.medicalinformation@seqirus.com.

• Health care providers may enroll patients exposed to Fluzone Quadrivalent during pregnancy in the Sanofi Pasteur vaccination registry at 1-800-822-2463.

Breastfeeding Considerations

It is not known if the components of this vaccine are present in breast milk.

Anti-influenza IgA antibodies can be detected in breast milk following maternal vaccination with the trivalent IIV vaccine (Brady 2018; Schlaudecker 2013). Administration does not affect the safety of breastfeeding for the mother or the infant. Breastfeeding infants should be vaccinated according to the recommended schedules (ACIP [Kroger 2022]).

The risk for severe illness and complications from influenza infection is increased postpartum, and influenza vaccination decreases the risk for respiratory illness and influenza in postpartum patients (CDC/ACIP [Grohskopf 2022]). When vaccine supply is limited, focus on delivering the vaccine should be given to patients who are pregnant or who may become pregnant during the flu season, as well as contacts or caregivers of children <5 years of age (particularly contacts of neonates and infants <6 months of age) (CDC/ACIP [Grohskopf 2022]). Postpartum patients who are breastfeeding and did not receive the influenza vaccine during pregnancy may be vaccinated (ACOG 2018).

Monitoring Parameters

Monitor for anaphylaxis and syncope for 15 minutes following administration (ACIP [Kroger 2022]). If seizure-like activity associated with syncope occurs, maintain patient in supine or Trendelenburg position to reestablish adequate cerebral perfusion.

Mechanism of Action

Promotes immunity to seasonal influenza virus by inducing specific antibody production. Preparations from previous seasons must not be used.

Pharmacokinetics

Onset of action: Most adults have antibody protection within 2 weeks of vaccination (CDC/ACIP [Grohskopf 2022]).

Duration: Vaccine effectiveness declines at a variable rate, depending on virus subtypes, patient age, and other confounding factors (CDC/ACIP [Grohskopf 2022]).

Pricing: US

Prefilled Syringe (Fluad Quadrivalent Intramuscular)

0.5 mL (per 0.5 mL): $75.46

Suspension (Fluzone Quadrivalent Intramuscular)

0.5 mL (per 0.5 mL): $23.11

Suspension Prefilled Syringe (Afluria Quadrivalent Intramuscular)

0.5 mL (per 0.5 mL): $23.88

Suspension Prefilled Syringe (Fluarix Quadrivalent Intramuscular)

0.5 mL (per 0.5 mL): $22.65

Suspension Prefilled Syringe (Flucelvax Quadrivalent Intramuscular)

0.5 mL (per 0.5 mL): $33.98

Suspension Prefilled Syringe (Flulaval Quadrivalent Intramuscular)

0.5 mL (per 0.5 mL): $22.65

Suspension Prefilled Syringe (Fluzone High-Dose Quadrivalent Intramuscular)

0.7 mL (per 0.7 mL): $73.62

Suspension Prefilled Syringe (Fluzone Quadrivalent Intramuscular)

0.5 mL (per 0.5 mL): $23.11

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Afluria (HR);
  • Flivirin (BB);
  • Fluarix (AE, AR, AT, BG, CH, CL, CO, CR, CY, CZ, DK, DO, EE, ES, FI, FR, GR, GT, HN, HR, ID, IE, IL, IN, IS, IT, LB, LT, MT, MX, NI, NL, NO, NZ, PA, PE, PH, PL, PT, QA, RO, SA, SE, SI, SK, SV, TH, UY, VE, VN);
  • Fluarix Tetra (AU, CZ, ES, GB, HK, IL, MY, SK, TH);
  • Flucelvax (AU);
  • Fluquadri (SG);
  • Fluvax (AU, HK, NZ, SG);
  • Fluvirin (ZA);
  • Flyuaryks (UA);
  • Influgen (IN);
  • Influvac (AE, AR, AU, BG, BH, CH, CL, CY, CZ, DE, DK, EE, FI, FR, GR, HR, IE, IL, LT, LV, MT, MX, NL, NO, NZ, PL, QA, SA, SE, SI, SK, VN);
  • Intanza (AT, BE, CZ, DE, DK, EE, ES, GB, HR, LT, MT, NL, NZ, PL, PT, RO, SG, TH, UA);
  • Optaflu (AT, MT, SK);
  • Vepacel (IE)


For country code abbreviations (show table)
  1. Afluria Quadrivalent (influenza vaccine) [prescribing information]. Summit, NJ: Seqirus USA Inc; March 2022.
  2. Afluria Tetra (quadrivalent inactivated influenza vaccine [split virion]) [product monograph]. Kirkland, Quebec, Canada: Seqirus Canada Inc; April 2022.
  3. Afluria Tetra (quadrivalent inactivated influenza vaccine [split virion]) [product monograph]. Kirkland, Quebec, Canada: Seqirus Canada Inc; May 2022.
  4. Alade SL, Brown RE, Paquet A Jr. Polysorbate 80 and E-Ferol toxicity. Pediatrics. 1986;77(4):593-597. [PubMed 3960626]
  5. American Academy of Pediatrics (AAP) Committee on Infectious Diseases. Recommendations for prevention and control of influenza in children, 2022-2023. Pediatrics. 2022;150(4):e2022059274. doi:10.1542/peds.2022-059274 [PubMed 36065749]
  6. American College of Obstetricians and Gynecologists (ACOG). ACOG Committee Opinion No. 732: influenza vaccination during pregnancy. Obstet Gynecol. 2018;131(4):e109-e114. [PubMed 29578985]
  7. Auffret M, Béné J, Gautier S, et al. Pharmacovigilance monitoring of a cohort of pregnant women vaccinated against influenza A(H1N1) variant virus in the Nord-Pas de Calais region of northern France. Eur J Obstet Gynecol Reprod Biol. 2013;170(1):114-118. [PubMed 23810001]
  8. Baxter R, Bakshi N, Fireman B, et al. Lack of association of Guillain-Barre syndrome with vaccinations. Clin Infect Dis. 2013;57(2):197-204. [PubMed 23580737]
  9. Brady RC, Jackson LA, Frey SE, et al. Randomized trial comparing the safety and antibody responses to live attenuated versus inactivated influenza vaccine when administered to breastfeeding women. Vaccine. 2018;36(31):4663-4671. doi:10.1016/j.vaccine.2018.06.036 [PubMed 29961606]
  10. Centers for Disease Control (CDC). Unusual syndrome with fatalities among premature infants: association with a new intravenous vitamin E product. MMWR Morb Mortal Wkly Rep. 1984;33(14):198-199. http://www.cdc.gov/mmwr/preview/mmwrhtml/00000319.htm. [PubMed 6423951]
  11. Centers for Disease Control and Prevention (CDC). Immunogenicity, efficacy, and effectiveness of influenza vaccines. https://www.cdc.gov/flu/professionals/acip/2018-2019/background/immunogenicity.htm. Updated August 23, 2018. Accessed August 26, 2019.
  12. Centers for Disease Control and Prevention (CDC), "Note to Providers: Febrile Seizures Associated With TIV & PCV13." Available at http://www.cdc.gov/vaccines/pubs/vis/tiv-pcv-note.htm
  13. Centers for Disease Control and Prevention (CDC). Update on Febrile Seizures in Children Following Vaccination With Influenza Vaccines and Pneumococcal Vaccines. Updated October 2011. Available at http://www.cdc.gov/vaccinesafety/Concerns/FebrileSeizures.html
  14. Centers for Disease Control and Prevention (CDC); US Department of Health and Human Services (HHS). Flu & pregnancy. https://www.cdc.gov/flu/highrisk/pregnant.htm. Updated August 25, 2022. Accessed August 29, 2022.
  15. Centers for Disease Control and Prevention (CDC). Vaccination guidance during a pandemic. Updated October 20, 2020. Available at https://www.cdc.gov/vaccines/pandemic-guidance/index.html
  16. Centers for Disease Control and Prevention (CDC). Vaccine storage and handling. In: Hamborsky J, Kroger A, Wolfe C, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases (CDC Pink Book). 13th ed. Public Health Foundation; 2015. https://www.cdc.gov/vaccines/pubs/pinkbook/vac-storage.html Updated July 2020.
  17. Cross GB, Moghaddas J, Buttery J, Ayoub S, Korman TM. Don't aim too high: avoiding shoulder injury related to vaccine administration. Aust Fam Physician. 2016;45(5):303-306. [PubMed 27166466]
  18. 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. [PubMed 25119609]
  19. Demicheli V, Jefferson T, Ferroni E, et al. Vaccines for preventing influenza in healthy adults. Cochrane Database Syst Rev. 2018;2:CD001269. doi: 10.1002/14651858.CD001269.pub6. [PubMed 29388196]
  20. Flowers CR, Seidenfeld J, Bow EJ, et al. Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2013;31(6):794-810. [PubMed 23319691]
  21. Fluad Pediatric and Fluad (influenza vaccine) [product monograph]. Kirkland, Quebec, Canada: Seqirus Canada Inc; September 2021.
  22. Fluad Pediatric and Fluad (influenza vaccine) [product monograph]. Kirkland, Quebec, Canada: Seqirus Canada Inc; September 2022.
  23. Fluad Quadrivalent (influenza vaccine) [prescribing information]. Holly Springs, NC: Seqirus Inc; March 2022.
  24. Fluarix Quadrivalent (influenza vaccine) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; July 2022.
  25. Flucelvax Quad (influenza vaccine) [product monograph]. Kirkland, Quebec, Canada: Seqirus Canada Inc; April 2022.
  26. Flucelvax Quad (influenza vaccine) [product monograph]. Kirkland, Quebec, Canada: Seqirus Canada Inc; May 2022.
  27. Flucelvax Quadrivalent (influenza vaccine) [prescribing information]. Holly Springs, NC: Seqirus; July 2022.
  28. Flucelvax Quadrivalent (influenza vaccine) [prescribing information]. Summit, NJ: Seqirus USA Inc; October 2021.
  29. FluLaval Quadrivalent (influenza vaccine) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; July 2022.
  30. FluLaval Tetra (influenza vaccine) [product monograph]. Quebec, Quebec, Canada: ID Biomedical Corp of Quebec; April 2022.
  31. Fluzone High-Dose Quadrivalent (influenza vaccine) [prescribing information]. Swiftwater, PA: Sanofi Pasteur Inc; July 2022.
  32. Fluzone High-Dose Quadrivalent (influenza vaccine) [product monograph]. Toronto, Ontario, Canada: Sanofi Pasteur Ltd; March 2022.
  33. Fluzone Quadrivalent (influenza vaccine) [prescribing information]. Swiftwater, PA: Sanofi Pasteur Inc; July 2022.
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