Skip to Content

Influenza Virus Vaccine (Inactivated)

Medically reviewed by Drugs.com. Last updated on May 17, 2020.

Pronunciation

(in floo EN za VYE rus vak SEEN, in ak ti VAY ted)

Index Terms

  • ccIIV4 [Flucelvax Quadrivalent]
  • Cell Culture Inactivated Influenza Vaccine, Quadrivalent [Flucelvax Quadrivalent]
  • Flu Vaccine
  • H1N1 Influenza Vaccine
  • IIV
  • IIV3
  • IIV4
  • Inactivated Influenza Vaccine
  • Influenza Vaccine
  • Influenza Virus Vaccine (Purified Surface Antigen)
  • Influenza Virus Vaccine (Split-Virus)
  • QIV (Quadrivalent Inactivated Influenza Vaccine)
  • TIV (Trivalent Inactivated Influenza Vaccine)

Dosage Forms

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,]

Fluvirin: (5 mL [DSC]) [contains egg white (egg protein), neomycin, polymyxin, thimerosal]

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: (0.5 mL [DSC]) [contains neomycin sulfate]

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

Fluad: (0.5 mL) [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: (0.5 mL [DSC]) [contains polysorbate 80]

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

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

Fluvirin: (0.5 mL [DSC]) [contains egg white (egg protein), neomycin, polymyxin]

Fluzone High-Dose: (0.5 mL [DSC]) [contains formaldehyde solution]

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]

Brand Names: U.S.

  • Afluria Quadrivalent
  • Afluria [DSC]
  • Fluad
  • Fluad Quadrivalent
  • Fluarix Quadrivalent
  • Flucelvax Quadrivalent
  • Flucelvax [DSC]
  • FluLaval Quadrivalent
  • Fluvirin [DSC]
  • Fluzone High-Dose Quadrivalent
  • Fluzone High-Dose [DSC]
  • Fluzone Quadrivalent

Pharmacologic Category

  • Vaccine
  • Vaccine, Inactivated (Viral)

Pharmacology

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

Onset of Action

Most adults have antibody protection within 2 weeks of vaccination (CDC/ACIP [Grohskopf 2020]).

Duration of Action

Vaccine effectiveness declines at a variable rate, depending on virus subtypes, patient age, and other confounding factors (CDC/ACIP [Grohskopf 2020]).

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, FluLaval Quadrivalent, Fluzone Quadrivalent)

• ≥4 years of age (Flucelvax Quadrivalent)

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

Canadian labeling:

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

• ≥6 months of age (Agriflu, FluLaval Tetra, Fluviral, Fluzone Quadrivalent)

• ≥3 years of age (Influvac Tetra)

• ≥5 years of age (Afluria Tetra)

• ≥9 years of age (Flucelvax Quad)

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

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; in addition to inactivated influenza vaccines (IIV3, 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 2020; CDC/ACIP [Grohskopf 2020]).

The Canadian National Advisory Committee on Immunization (NACI) recommends the following (NACI 2020): Annual vaccination with seasonal influenza vaccine for all persons ≥6 months of age who do not have contraindications to the vaccine. The following influenza vaccine preferences should be considered:

• 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 or LAIV (if appropriate) is preferred; use IIV3 if neither IIV4 nor LAIV is available.

• Persons ≥65 years of age: IIV3-HD (high dose) is preferred over IIV3-SD (standard dose); however, any available IIV3 or IIV4 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.

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 (CDC/ACIP [Grohskopf 2020]):

• All infants and children 6 to 59 months of age

• Persons ≥50 years of age

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

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

• Patients with chronic pulmonary disorders (including asthma) or cardiovascular systems disorders (except isolated hypertension), renal, hepatic, neurologic, hematologic, or metabolic disorders (including diabetes mellitus)

• 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

• American Indians/Alaska Natives

• Persons who are extremely obese (BMI ≥40)

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

• Household contacts (including children) 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 (including children) and caregivers of persons with medical conditions which put them at higher risk of severe complications from influenza infection

In addition, the NACI also recommends vaccination of patients with neurologic or neurodevelopment conditions including neuromuscular/neurovascular/neurodegenerative conditions, seizure disorders (including febrile seizures in pediatric patients and isolated developmental delay) but excluding migraines and psychiatric conditions without neurological conditions (NACI 2020).

Contraindications

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

Additional manufacturer contraindications for Afluria Quadrivalent, Fluad, 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: Agriflu, Fluad, Fluad Pediatric, FluLaval Tetra, Fluviral, Fluzone High-Dose Quadrivalent, Fluzone High-Dose Trivalent, Fluzone Quadrivalent, Influvac Tetra: Hypersensitivity to egg protein.

Note: Both the Advisory Committee on Immunization Practices and the Canadian National Advisory Committee on Immunization do not consider egg allergy a contraindication to influenza vaccination (CDC/ACIP [Grohskopf 2020]; NACI 2020).

Dosing: Adult

Note: Immunization during coronavirus 2019 (COVID-19) pandemic: Routine vaccination should not be delayed because of the COVID-19 pandemic (CDC 2020; WHO 2020). In general, simultaneous administration of all vaccines for which a patient is eligible (according to current immunization schedules/guidelines) is recommended (ACIP [Ezeanolue 2020]). However, influenza vaccination in patients with suspected or confirmed COVID-19 infection (regardless of symptoms) should be postponed until the patient is no longer acutely ill and/or in isolation to avoid exposure to health care personnel and other patients (CDC/ACIP [Grohskopf 2020]; CDC 2020). Additional information is available from the Centers for Disease Control and Prevention (CDC), the American Academy of Pediatrics, and the Immunization Action Coalition.

Influenza seasons vary in the timing and duration from year to year. In general, vaccination should preferably occur in September and 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. Advisory Committee on Immunization Practices does not have a preference for any inactivated influenza vaccine formulation when used within their specified age indications (CDC/ACIP [Grohskopf 2020]). 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:

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, Agriflu, 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: Geriatric

Note: Immunization during coronavirus 2019 (COVID-19) pandemic: Routine vaccination should not be delayed because of the COVID-19 pandemic (CDC 2020; WHO 2020). In general, simultaneous administration of all vaccines for which a patient is eligible (according to current immunization schedules/guidelines) is recommended (ACIP [Ezeanolue 2020]). However, influenza vaccination in patients with suspected or confirmed COVID-19 infection (regardless of symptoms) should be postponed until the patient is no longer acutely ill and/or in isolation to avoid exposure to health care personnel and other patients (CDC/ACIP [Grohskopf 2020]). Additional information is available from the Centers for Disease Control and Prevention (CDC), the American Academy of Pediatrics, and the Immunization Action Coalition.

Influenza seasons vary in the timing and duration from year to year. In general, vaccination should preferably occur in September and 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. The high-dose inactivated influenza vaccine (IIV), Fluzone High-Dose Quadrivalent, contains 60 mcg of each vaccine antigen per 0.7 mL dose compared to 15 mcg of each vaccine antigen per 0.5 mL dose. The high-dose IIV formulation was shown to elicit a higher antibody response and may provide better protection against influenza illness compared to standard dose formulations. However, the Advisory Committee on Immunization Practices does not have a preference for any given IIV formulation in older adults when used within their specified age indications (CDC/ACIP [Grohskopf 2020]).

Immunization: Adults ≥65 years of age:

Afluria Quadrivalent, Fluad, 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, Agriflu, Fluad, FluLaval Tetra, Flucelvax Quad, Fluviral, Fluzone High-Dose Trivalent, 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).

Dosing: Pediatric

Note: Immunization during coronavirus disease 2019 (COVID-19) pandemic: Routine vaccination should not be delayed because of the COVID-19 pandemic (CDC 2020; WHO 2020). In general, simultaneous administration of all vaccines for which a patient is eligible (according to current immunization schedules/guidelines) is recommended (ACIP [Ezeanolue 2020]). However, influenza vaccination in patients with suspected or confirmed COVID-19 infection (regardless of symptoms) should be postponed until the patient is no longer acutely ill and/or in isolation to avoid exposure to health care personnel and other patients (CDC/ACIP [Grohskopf 2020]; CDC 2020). Additional information is available from the CDC, the American Academy of Pediatrics, and the Immunization Action Coalition.

Influenza seasons vary in the timing and duration from year to year. In general, vaccination should preferably occur in September and October (in US) 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. ACIP and AAP do not have a preference for any given inactivated influenza vaccine (IIV) formulation when used within their specified age indications and appropriate risk factor selection (if applicable) (AAP 2020; CDC/ACIP [Grohskopf 2020]). 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 [Ezeanolue 2020]).

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: 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 2020; CDC/ACIP [Grohskopf 2020]).

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 to 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.

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.

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.

Fluarix 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.

Flucelvax Quadrivalent:

Children 4 to <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.

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).

Agriflu, 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 2020).

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

FluLaval Tetra, Fluviral:

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:

Children 3 to <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).

Administration

For IM administration. Influvac Tetra [Canadian product] may also be administered by deep SubQ injection; allow to warm to room temperature prior to use. Suspensions should be shaken well prior to use; emulsions (Fluad and 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. Adults should be vaccinated in the deltoid muscle. 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.

Do not mix with other vaccines or injections; separate needles and syringes should be used for each injection. To prevent syncope related injuries, patients should be vaccinated while seated or lying down (ACIP [Ezeanolue 2020]). 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.

If a pediatric vaccine (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 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 2020]).

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 [Ezeanolue 2020]).

Storage

Store all products between 2°C to 8°C (36°F to 46°F). Do not freeze. Potency is destroyed by freezing; do not use if product has been frozen. Store in original packaging to protect from light (CDC Pink Book 2020). Storage information may vary by product; see manufacturer labeling.

Afluria Quadrivalent, Afluria Tetra [Canadian product], Flucelvax Quadrivalent, FluLaval Tetra [Canadian product]: Discard multiple-dose vials 28 days after initial entry (excluding Flucelvax Quadrivalent [US product]). Between uses, the multiple-dose vial should be stored at 2°C to 8°C (36°F to 46°F). The number of needle punctures should not exceed 10 per multiple-dose vial.

Agriflu [Canadian product]: May be used if exposed to temperatures between 8°C to 25°C for <2 hours. Discard multiple-dose vials 28 days after initial entry. Between uses, the multiple-dose vial should be stored at 2°C to 8°C (36°F to 46°F). The number of needle punctures should not exceed 10 per multi-dose vial.

Fluad (Canadian labeling), Fluad Pediatric [Canadian product]: May be used if exposed to temperatures between 8°C to 25°C for <2 hours.

Fluviral [Canadian product]: Discard multiple-dose vials 28 days after initial entry.

Drug Interactions

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

Fingolimod: May diminish the therapeutic effect of Vaccines (Inactivated). 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. Consider therapy modification

Immunosuppressants: May diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. 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). Monitor therapy

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

Venetoclax: May diminish the therapeutic effect of Vaccines (Inactivated). Monitor therapy

Adverse Reactions

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 13%), nausea (≤12%), vomiting (infants, children, and adolescents: ≤15%; adults and older adults: ≤3%)

Local: Erythema at injection site (1% to 37%), induration at injection site (≤17%), 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 (8% to 40%)

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

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%)

Local: Bruising at injection site (≤9%)

Nervous system: Chills (≤7%), 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 (adolescents and adults: 2% 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 (local), thrombocytopenia

Hypersensitivity: Anaphylactic shock, anaphylaxis, angioedema, hypersensitivity reaction (including oculorespiratory syndrome, an acute, self-limited reaction with ocular and respiratory symptoms) (CDC/ACIP [Grohskopf 2013]), nonimmune anaphylaxis, serum sickness

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, insomnia, myasthenia, neuralgia, neuritis, neuropathy (including brachial plexus), paralysis (including limb), paresthesia, seizure, transverse myelitis, vertigo, voice disorder

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

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

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

Miscellaneous: Febrile seizure

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactoid/hypersensitivity reactions: Immediate treatment (including epinephrine 1 mg/mL) for anaphylactoid and/or hypersensitivity reactions should be available during vaccine use (ACIP [Ezeanolue 2020]).

• 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 tendinitis) 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 [Ezeanolue 2020]).

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 [Ezeanolue 2020]).

• 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 [Ezeanolue 2020]).

• 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 2020]). Antipyretics have not been shown to prevent febrile seizures; antipyretics may be used to treat fever or discomfort following vaccination (ACIP [Ezeanolue 2020]). 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 at low risk for severe influenza complications, and patients known to have experienced GBS within 6 weeks following previous 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 2020]). 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 [Ezeanolue 2020]).

• 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 [Ezeanolue 2020]; NACI 2018).

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 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 [Ezeanolue 2020]; CDC/ACIP [Grohskopf 2020]). 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 [Ezeanolue 2020]; IDSA [Rubin 2014]).

• Elderly: 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 2020]). 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). However, the ACIP does not have a preference for any one vaccine (IIV [standard or high dose] or RIV4) (CDC/ACIP [Grohskopf 2020]).

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 administered in an inpatient or outpatient medical setting with health care supervision able to recognize and manage severe allergic reactions (CDC/ACIP [Grohskopf 2020]). 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 2020; Greenhawt 2018; NACI 2020). 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 2020]).

• 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 [Ezeanolue 2020]).

• 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 2020]).

Monitoring Parameters

Monitor for anaphylaxis and syncope for 15 minutes following administration (ACIP [Ezeanolue 2020]). If seizure-like activity associated with syncope occurs, maintain patient in supine or Trendelenburg position to reestablish adequate cerebral perfusion.

Reproductive Considerations

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 2020]).

Pregnancy Considerations

Inactivated influenza vaccine (IIV) has not been shown to cause fetal harm when given to pregnant women, although information related to use in the first trimester is relatively limited (CDC/ACIP [Grohskopf 2020]).

Maternal vaccination provides passive immunization to the newborn and decreases the risk of hospitalization due to influenza in infants <6 months of age (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 2020]). 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. Vaccination may be done at any time during pregnancy (CDC/ACIP [Grohskopf 2020]).

Pregnant patients should observe the same precautions as nonpregnant patients to reduce the risk of exposure to influenza and other respiratory infections (CDC/HHS 2020). When vaccine supply is limited, focus on delivering the vaccine should be given to patients who are pregnant or will be pregnant during the flu season, as well as mothers of newborns and contacts or caregivers of children <5 years of age (CDC/ACIP [Grohskopf 2020]).

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

Persons exposed to FluLaval Quadrivalent or Fluarix Quadrivalent vaccine during pregnancy or their health care provider may contact the GlaxoSmithKline registry at 888-452-9622.

Persons exposed to Afluria Quadrivalent or Flucelvax 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 800-822-2463.

Patient Education

What is this drug used for?

• It is used to prevent the flu.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Injection site pain or irritation

• Muscle pain

• Joint pain

• Loss of strength and energy

• Nausea (children)

• Vomiting (children)

• Diarrhea (children)

• Lack of appetite (children)

• Abdominal pain (children)

• Fatigue (children)

• Abnormal crying (children)

• Irritability (children)

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Burning or numbness feeling

• Facial paralysis

• Abnormal movements

• Severe dizziness

• Passing out

• Muscle weakness

• Seizures

• Severe headache

• Vision changes

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.