Influenza vaccine inactivated (IIV3) stimulates active immunity to influenza virus infection.104, 106, 107, 108, 160, 186, 190 Influenza virus vaccine inactivated contains noninfectious, suitably inactivated influenza virus types A and B subunits representing influenza strains likely to circulate in the US during the upcoming influenza season. 104, 106, 107, 108, 160, 186, 190
Prevention of Seasonal Influenza A and B Virus Infections
Influenza vaccine inactivated is used to stimulate active immunity for the prevention of disease caused by influenza virus subtypes A and B represented in the vaccine.104, 106, 107, 108, 160, 186, 190 Several different preparations of influenza vaccine inactivated are commercially available in the US; these preparations differ based on dose (standard versus high dose), method of manufacturer (cell-based versus egg-based), and indicated population.104, 106, 107, 108, 160, 186, 190 Although most inactivated influenza vaccines available in the US for use in adults and pediatric patients ≥6 months of age are egg-based vaccines (Afluria®, Fluarix®, Flulaval®, Fluzone®),104, 106, 107, 108 a cell culture-based vaccine (Flucelvax®) also is available for use in individuals ≥6 months of age.190 In addition, an egg-based vaccine (Fluzone® High-Dose)160 and adjuvant-containing egg-based vaccine (Fluad®)186 are available for use in adults ≥65 years of age.
Each year, influenza vaccines are formulated based on recommendations from the FDA, Centers for Disease Control and Prevention (CDC), and other experts.100, 101, 102, 112 All influenza vaccines available in the US for the 2025-26 season are trivalent formulations containing antigens representing influenza A (H1N1), influenza A (H3N2), and influenza B (Victoria lineage).100, 102
The US Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics (AAP) provide annual recommendations for the use of influenza vaccines in the US.100, 111, 112 These experts recommend routine annual influenza vaccination in all persons ≥6 months of age who do not have contraindications.100, 111, 112
Various preparations of influenza virus vaccines are commercially available in the US, which differ based on method of manufacturer (egg-based versus cell culture-based), dose (standard versus high-dose), and route of administration (e.g., parenteral versus intranasal).100 These preparations can be grouped into 3 broad categories: inactivated influenza vaccines (IIV3), recombinant influenza vaccine (RIV3), and live attenuated virus vaccine (LAIV3).100 Inactivated influenza vaccines (IIV3) include standard-dose egg-based vaccines, a standard-dose cell culture-based influenza vaccine (ccIIV3), a high-dose egg-based vaccine (HD-IIV3), and an adjuvanted standard-dose egg-based vaccine (aIIV3).100 For the 2025-26 season, egg-based influenza vaccines available in the US (i.e., vaccines other than ccIIV3 and RIV3) contain hemagglutinin derived from an influenza A/Victoria/4897/2022 (H1N1)pdm09-like virus; an influenza A/Croatia/10136RV/2023 (H3N2)-like virus; and an influenza B/Austria/1359417/2021 (B/Victoria lineage)-like virus.100 For the 2025-26 season, cell culture-based inactivated (ccIIV3) and recombinant (RIV3) influenza vaccines in the US contain hemagglutinin derived from an influenza A/Wisconsin/67/2022 (H1N1)pdm09-like virus; an influenza A/District of Columbia/27/2023 (H3N2)-like virus; and an influenza B/Austria/1359417/2021 (B/Victoria lineage)-like virus.100
ACIP states that all persons ≥6 months of age should receive an age-appropriate influenza vaccine with the exception of solid organ transplant recipients 18 through 64 years of age who are receiving immunosuppressive medication regimens; these individuals may receive either high-dose inactivated influenza vaccine (HD-IIV3) or adjuvanted inactivated influenza vaccine (aIIV3) as acceptable options (without a preference over other age-appropriate IIV3s or RIV3).100 ACIP states that there are no preferential recommendations for any specific vaccine type when more than one licensed, recommended, and age-appropriate vaccine is available, with the exception of selection of influenza vaccines for individuals ≥65 years of age.100 Because influenza vaccines are often less effective in older adults, the higher dose vaccines or adjuvanted vaccine is recommended in this population.100 For the 2025-26 influenza season, ACIP recommends that adults ≥65 years preferentially receive trivalent high-dose inactivated influenza vaccine (HD-IIV3), trivalent recombinant influenza vaccine (RIV3), or trivalent adjuvanted inactivated influenza vaccine (aIIV3).100 If none of these vaccines is available at an opportunity for vaccine administration, then any other age-appropriate influenza vaccine should be used.100 Live attenuated influenza vaccine (LAIV3) should not be used in immunocompromised persons, persons with certain medical conditions, or persons receiving, having recently received, or about to receive influenza antiviral medications; LAIV also should not be used during pregnancy.100 Patients should consult their healthcare provider about available flu vaccine options.100
The American College of Obstetricians and Gynecologists (ACOG) provides recommendations for annual influenza vaccine in pregnant individuals.21 Because the risks associated with influenza infection are increased in both pregnant patients and their newborns,21 ACOG recommends that individuals who are or will be pregnant during the influenza season receive an inactivated or recombinant influenza vaccine as soon as the vaccines are available.21
The Center for Infectious Disease Research and Policy (CIDRAP) has established the Vaccine Integrity Project to provide evidence-based guidance on key immunizations for the upcoming respiratory season focusing on influenza, RSV, and COVID.22 The Vaccine Integrity Project is an initiative to safeguard vaccine use in the US and disseminate evidence-based information for informed decision-making.22 A multi-disciplinary group of experts has been convened to prepare recommendations for the upcoming 2025-2026 fall-winter respiratory season.22 CIDRAP will provide updates on the initiative's progress as they become available.22 For additional information see, [Web].
Regarding the timing of influenza vaccination, ACIP states that for most individuals who need only 1 dose of influenza vaccine for the season, the vaccine should ideally be offered during September or October.100 However, vaccination should continue after October and throughout the influenza season as long as influenza viruses are circulating and unexpired vaccine is available.100 For most adults, vaccination during July and August generally should be avoided unless there is a concern that vaccination during the season might not be possible; however, vaccination during these months can be considered in children who require 2 doses, children who require only 1 dose but visit their healthcare provider during late summer before the start of the school year, and pregnant persons in the third trimester.100
Other Influenza Virus Infections
Avian Influenza A Virus Infections
Influenza vaccines used for the prevention of seasonal influenza are not expected to provide protection against infection with avian influenza A viruses, including avian influenza A (H5N1). 149 Although not commercially available, several different inactivated influenza A (H5N1) monovalent vaccines have received FDA approval and are stored in the US Strategic National Stockpile (SNS).469, 472, 473
Avian influenza A virus refers to influenza A subtypes that occur mainly in birds but also have rarely caused infection in humans (H5N1, H5N6, H5N8, H7N2, H7N4, H7N3, H7N7, H7N9, H9N2, H10N8). 149, 171 Experience to date indicates that avian influenza A viruses are not easily transmitted from wild or domestic birds, water fowl, or poultry to humans, but human infections can occur and have been linked to contact with live or dead infected birds or poultry, uncooked poultry products, or surfaces contaminated with infected poultry feces or respiratory secretions. 147, 149, 312, 316, 317, 318, 565
The best way to prevent H5N1 bird flu is to avoid sources of exposure whenever possible.149 Although seasonal influenza vaccines are not expected to provide protection against avian influenza A viruses, including avian influenza A (H5N1),149 they might reduce the risk of coinfection and thereby reduce the theoretic potential for human-avian reassortment of genes in an individual simultaneously infected with a human and avian strain.149
Information regarding treatment and prevention of avian influenza A infections is available from CDC at [Web] and WHO at [Web].
Inactivated influenza vaccines are administered by IM injection; do not administer intradermally or subcutaneously.104, 106, 107, 108, 160, 186, 190
As an alternative to IM injection using a needle and syringe, Afluria® may be administered IM using a PharmaJet® Stratis® needle-free injection system only in adults 18 through 64 years of age.108, 543 Other commercially available inactivated influenza vaccines should not be administered IM using a jet injector.543
The vaccine product should be inspected visually for particulate matter and discoloration prior to administration.104, 106, 107, 108, 160, 186, 190 Discard the vaccine if it contains particulates, appears discolored, or cannot be resuspended with thorough agitation.104, 106, 107, 160, 190
Influenza vaccine inactivated should not be mixed with any other vaccine or solution.104, 134, 160, 186, 190
Influenza vaccine inactivated should be stored at 2-8°C; do not freeze (if freezing occurs, discard vaccine).104, 106, 107, 108, 160, 186, 190 Multiple-dose vials should be returned to 2-8ºC between uses.104, 108 The manufacturer of Afluria® states to discard any vaccine remaining in multiple-dose vials after a total of 20 doses has been removed from the vial and discard the multiple-dose vial if not used within 28 days after first entry.108 The vaccine should be protected from light.106, 108, 186, 190 Single-dose vials are preservative-free.104, 106, 107, 108, 160 Multiple-dose vials contain thimerosal as a preservative.104, 108, 190
Syncope (vasovagal or vasodepressor reaction; fainting) may occur following vaccination; such reactions occur most frequently in adolescents and young adults.134 Take appropriate measures to decrease the risk of injury if a vaccine recipient becomes weak or dizzy or loses consciousness (e.g., vaccine recipients should sit or lie down during and for 15 minutes after vaccination).134 If syncope occurs, observe the individual until symptoms resolve.134
Influenza vaccine inactivated may be administered concurrently with other vaccines during the same health-care visit.134 When multiple vaccines are administered during a single health-care visit, each parenteral vaccine should be given using separate syringes and at different injection sites.134 Injection sites should be separated by at least 1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur.134
Prefilled single-dose syringes containing influenza virus vaccine inactivated for IM administration should be shaken before administering the dose.104, 106, 107, 108, 160, 186, 190
Vials containing influenza virus vaccine inactivated for IM administration should be shaken before withdrawing a dose.104, 108, 190
Depending on patient age, IM injections should be made into the anterolateral muscles of the thigh or deltoid muscle of the arm.134 Some clinicians recommend that infants and younger children be vaccinated in the anterolateral thigh because of the larger muscle muscle mass than the deltoid.134 In certain circumstances (e.g., physical obstruction at other sites and no reasonable indication to defer the vaccine dose), IM injections can be made into the gluteal muscle using care to identify anatomic landmarks prior to injection.134
In adults, adolescents, and children 3 years of age or older, IM injections should preferably be made into the deltoid muscle. 104, 106, 107, 108, 134, 160, 186, 190
To ensure delivery into muscle, IM injections should be administered at a 90° angle to the skin using a needle length appropriate for the individual's age and body mass, thickness of adipose tissue and muscle at the injection site, and injection technique.134 Anatomic variability, especially in the deltoid, should be considered and clinical judgment should be used to avoid inadvertent underpenetration or overpenetration of muscle.134
Afluria® may be administered IM using a PharmaJet® Stratis® needle-free injection system in adults 18 through 64 years of age.108 The jet injector should not be used to administer Afluria® in individuals younger than 18 years of age or geriatric adults ≥65 years of age.108
For specific information on how to administer Afluria® using the PharmaJet® Stratis® needle-free injection system, the manufacturer's information for the jet injector should be consulted.108
Dose and dosing schedule (i.e., number of doses) of influenza virus vaccine inactivated for prevention of seasonal influenza depend on the individual's age, vaccination history, and specific product administered. 104, 106, 107, 108, 160, 186, 190
Infants and Children 6 through 35 Months of Age (Afluria®)
If Afluria® is used for prevention of seasonal influenza in infants and children 6 through 35 months of age, reduced doses of 0.25 mL should be used.100, 108
Infants and children 6 through 35 months of age who did not receive a total of 2 or more doses of any seasonal influenza vaccine before July 1, 2025 or whose previous influenza vaccination history is unknown: Administer 2 doses of Afluria® at least 4 weeks apart.100, 108 Each dose consists of 0.25 mL.108
Infants and children 6 through 35 months of age who received a total of 2 or more doses of any seasonal influenza vaccine ≥4 weeks apart before July 1, 2025: Administer a single 0.25 mL dose of Afluria®.100, 108
Infants and Children 6 through 35 Months of Age (Fluarix®, Flulaval®)
For prevention of seasonal influenza in infants and children 6 through 35 months of age who did not receive a total of 2 or more doses of any seasonal influenza vaccine before July 1, 2025 or whose previous influenza vaccination history is unknown: Administer 2 doses of Fluarix® or Flulaval® at least 1 month (4 weeks) apart.100 Each dose consists of 0.5 mL.106, 107
In infants and children 6 through 35 months of age who received a total of 2 or more doses of any seasonal influenza vaccine ≥4 weeks apart before July 1, 2025, administer a single 0.5 mL dose of Fluarix® or Flulaval®.100, 106, 107
Infants and Children 6 through 35 Months of Age (Fluzone®)
If Fluzone® is used for prevention of seasonal influenza in infants and children 6 through 35 months of age, reduced doses (0.25 mL; prefilled syringes 0.25 mL no longer available) or standard doses (0.5 mL) may be used.104
For prevention of seasonal influenza in infants and children 6 through 35 months of age who did not receive a total of 2 or more doses of any seasonal influenza vaccine before July 1, 2025 or whose previous influenza vaccination history is unknown: The manufacturer recommends two 0.25-mL doses, two 0.5-mL doses, or one 0.25- and one 0.5-mL dose of Fluzone® administered at least 1 month (4 weeks) apart.100, 104
In infants and children 6 through 35 months of age who received a total of 2 or more doses of any seasonal influenza vaccine ≥4 weeks apart before July 1, 2025, administer a single 0.25- or 0.5-mL dose of Fluzone®.100, 104
Children 6 months through 8 Years of Age (Flucelvax®)
For prevention of seasonal influenza in children 6 months through 8 years of age who did not receive a total of 2 or more doses of any seasonal influenza vaccine before July 1, 2025 or whose previous influenza vaccination history is unknown: Administer 2 doses of Flucelvax® at least 1 month (4 weeks) apart.100, 190 Each dose consists of 0.5 mL.190
In children 6 months through 8 years of age who received a total of 2 or more doses of any seasonal influenza vaccine ≥4 weeks apart before July 1, 2025: Administer a single 0.5 mL dose of Flucelvax®.100, 190
Children 3 through 8 Years of Age (Afluria®, Fluarix®, Flulaval®, Fluzone®)
In children 3 through 8 years of age who did not receive a total of 2 or more doses of any seasonal influenza vaccine before July 1, 2025 or whose previous influenza vaccination history is unknown: Administer 2 doses of Afluria®, Fluarix®, Flulaval®, or Fluzone® at least 1 month (4 weeks) apart.100, 104, 106, 107, 108 Each dose consists of 0.5 mL.104, 106, 107, 108
In children 3 through 8 years of age who received a total of 2 or more doses of any seasonal influenza vaccine 4 weeks apart before July 1, 2025, administer a single 0.5 mL dose of Afluria®, Fluarix®, Flulaval®, or Fluzone®.100, 104, 106, 107, 108
Children and Adolescents 9 through 17 Years of Age (Afluria®, Fluarix®, Flucelvax®, Flulaval®, Fluzone®)
For prevention of seasonal influenza infection in children and adolescents 9 through 17 years of age, 0.5 mL of Afluria®, Fluarix®, Flucelvax®, Flulaval®, or Fluzone® should be administered IM as a single dose.100, 104, 106, 107, 108, 190
The usual dosage of Afluria®, Fluarix®, Flucelvax®, Flulaval®, or Fluzone® for prevention of seasonal influenza infection in adults 18 years of age or older is 0.5 mL administered IM as a single dose.100, 104, 106, 107, 108, 190
The usual dosage of Fluad® standard-dose adjuvant-containing vaccine for prevention of seasonal influenza infection in adults 65 years of age or older is 0.5 mL administered IM as a single dose.186
The usual dosage of Fluzone® High-Dose for prevention of seasonal influenza infection in adults 65 years of age or older is 0.5 mL administered IM as a single dose.160
The manufacturers make no specific dosage recommendations for patients with hepatic impairment.104, 106, 107, 108, 160, 186, 190
The manufacturers make no specific dosage recommendations for patients with renal impairment.104, 106, 107, 108, 160, 186, 190
For dosing in geriatric patients, see dosage recommendations for adults based on age.104, 106, 107, 108, 160, 186, 190
Allergic or immediate hypersensitivity reactions (e.g., urticaria, angioedema, anaphylaxis, anaphylactic shock, serum sickness, allergic asthma) have been reported rarely. 104, 106, 107, 108 Prior to administration, review patient's history with respect to possible sensitivity reactions to the vaccine or vaccine components, including egg protein, and prior vaccination-related adverse effects and assess benefits versus risks. 106, 107, 108 Administer influenza vaccine inactivated in a setting where appropriate medical treatment and supervision are available to manage possible anaphylactic reactions if they occur. 104, 106, 107, 108, 134, 160, 186, 190
Most seasonal inactivated influenza vaccines (Afluria®, Fluad®, Fluarix®, Flulaval®, Fluzone®) are produced using embryonated chicken eggs; these vaccines can contain residual egg protein (ovalbumin). 104, 106, 107, 108, 160, 186 Manufacturers of egg-based inactivated influenza vaccines state that these vaccines are contraindicated in individuals who have had a severe allergic reaction (e.g., anaphylaxis) to egg protein.104, 106, 107, 108, 160, 186 ACIP states that all individuals ≥6 months of age with egg allergy should receive influenza vaccine with any influenza vaccine (egg-based or nonegg-based) that is otherwise appropriate for the recipient's age and health status.100 Egg allergy alone necessitates no additional safety measures for influenza vaccination beyond those recommended for any recipient of any vaccine, regardless of severity of previous reaction to egg.100 Although egg allergy is neither a contraindication nor precaution to the use of any influenza vaccine, there are contraindications and precautions related to allergies to vaccine components, including egg protein, or following a previous administration of any influenza vaccine.100, 104, 106, 107, 108
Some preparations of influenza vaccine inactivated (e.g., Afluria®, Fluad®) contain trace amounts of neomycin, although allergies to neomycin are rare.108, 134, 186 Neomycin hypersensitivity usually manifests as a delayed-type (cell-mediated) contact dermatitis.134 ACIP states that a history of delayed-type allergic reaction to neomycin is not a contraindication to the use of vaccines containing trace amounts of neomycin; however, it is recommended that individuals with a history of anaphylactic reaction to neomycin be evaluated by an allergist prior to receiving a neomycin-containing vaccine.134
Some multi-dose vials of influenza vaccine inactivated (Afluria®, Flucelvax®, Fluzone®) contain trace amounts of thimerosal, a mercury derivative, as a preservative.104, 108, 134, 190 Hypersensitivity reactions to thimerosal contained in vaccines have been reported in some individuals.140, 498, 500 These reactions usually manifest as local, delayed-type hypersensitivity reactions (e.g., erythema, swelling), but a generalized reaction manifested as pruritus and an erythematous, maculopapular rash on all 4 extremities has been reported rarely. 134, 140, 427, 500 ACIP states that a history of local or delayed-type hypersensitivity to thimerosal is not a contraindication to use of vaccines that contain thimerosal.134
If GBS occurred within 6 weeks after previous influenza vaccination, manufacturers state to base decision to administer influenza vaccine on careful consideration of potential benefits and risks.104, 106, 107, 108, 160, 186, 190 The 1976 swine influenza vaccine was associated with increased frequency of GBS. Evidence for causal relationship between other influenza vaccines and GBS is inconclusive; if an excess risk exists, it is probably slightly more than 1 additional case of GBS per 1 million vaccinees.104, 106, 107, 108, 160, 186, 190
ACIP states that a history of GBS within 6 weeks after receipt of any influenza vaccine is a precaution to the use of all influenza vaccines.100
Individuals with Altered Immunocompetence
If influenza vaccine inactivated is administered to immunosuppressed individuals, consider the possibility that the immune response may be lower than in immunocompetent individuals. 104, 106, 107, 108, 160, 186, 190
ACIP states that all non-live vaccines can be administered safely to individuals with altered immunocompetence.134
Individuals with Bleeding Disorders
Advise individuals and/or their family about the risk of hematoma from IM injections.134
ACIP states that vaccines may be given IM to such individuals if a clinician familiar with the patient's bleeding risk determines that the preparation can be administered with reasonable safety.134 In these cases, use a fine needle (23-gauge or smaller) to administer the vaccine and apply firm pressure to the injection site (without rubbing) for ≥2 minutes.134 In individuals receiving therapy for hemophilia, IM vaccines can be scheduled for administration shortly after a dose of such therapy.134
The decision to administer or delay vaccination in an individual with a current or recent acute illness should be based on the severity of symptoms and etiology of the illness.134
ACIP states that mild acute illness does not preclude vaccination.134 Moderate or severe acute illness (with or without fever) is a precaution for vaccination; defer vaccines until the individual has recovered from the acute phase of the illness.134 This avoids superimposing vaccine adverse effects on the underlying illness or mistakenly concluding that a manifestation of the underlying illness resulted from vaccine administration.134
Limitations of Vaccine Effectiveness
Influenza vaccine inactivated may not protect all vaccine recipients against influenza.104, 106, 107, 108, 160, 186, 190
Syncope has been reported following vaccination with inactivated influenza vaccines; implement procedures to avoid injury from fainting.104, 106, 107, 108, 160, 186, 190
Data collected in a prospective pregnancy exposure registry from women vaccinated with influenza virus vaccine inactivated quadrivalent (Afluria®, Fluarix®, Flucelvax®) found no evidence of a vaccine-associated increase in the risk of major birth defects and miscarriages when administered during any trimester of pregnancy.106, 108, 190 Data for quadrivalent vaccines are relevant to trivalent products because both vaccines are manufactured using the same process and have overlapping compositions.106, 107, 108 Data are insufficient to assess the risk of use during pregnancy for other inactivated influenza vaccines (Fluzone®, Fluad®, Flulaval®).104, 107, 160, 186
Animal reproduction studies have not revealed evidence of harm to a fetus.104, 106, 107, 108, 160, 186, 190 Pregnant and postpartum women are at higher risk for severe influenza and influenza-related complications, particularly during the second and third trimesters, which may lead to adverse pregnancy outcomes including preterm labor and delivery. 104, 106, 107, 190
To monitor pregnancy outcomes and newborn health status following influenza vaccination of pregnant women, some manufacturers have established pregnancy registries.104, 106, 107, 190
It is not known whether influenza vaccine inactivated is distributed into human milk.104, 106, 107, 108, 160, 186, 190 Data are insufficient to assess effects on the breast-fed infant or on milk production.104, 106, 107, 108, 160, 186, 190 Consider the benefits of breast-feeding and importance of the vaccine to the woman; also consider potential adverse effects on the breast-fed child from the vaccine or underlying maternal condition (i.e., susceptibility to influenza infection).104, 106, 107, 108, 160, 186, 190
ACIP states that breast-feeding is not a contraindication to influenza vaccine inactivated; the vaccines do not pose any unusual risks for the mother or her nursing infant.134
Afluria®, Fluarix®, Flulaval®, Fluzone®, Flucelvax®: Safety and efficacy not established in infants <6 months of age.104, 106, 107, 108
Fluad® adjuvant-containing: Safety and efficacy not established in pediatric patients.186
Fluzone® High-Dose: Safety and efficacy not established in pediatric patients.160
Afluria®, Fluarix®, Flucelvax®, Flulaval®, Fluzone®: No overall differences in safety relative to younger adults;104, 106, 107, 190 may be less immunogenic in geriatric individuals. 108, 190
Fluad® adjuvant-containing: Use only in adults ≥65 years of age. 186
Fluzone® High-Dose: Use in adults ≥65 years of age.160 Each 0.5 mL of Fluzone® High-Dose contains 4 times the amount of antigen contained in standard-dose Fluzone®.160 In adults ≥65 years of age, higher incidence of injection site reactions and systemic adverse effects reported with Fluzone® High-Dose compared with standard-dose Fluzone®.100 Some evidence that the high-dose formulation elicits higher antibody titers and higher seroconversion rates than the standard-dose formulation in adults ≥65 years of age and may be more effective in preventing laboratory-confirmed influenza in this age group.100
ACIP states that all adults ≥65 years of age should be vaccinated against influenza using influenza virus vaccine inactivated or influenza vaccine recombinant.100 ACIP states a preference for Fluzone® High-Dose , Flublok® recombinant influenza vaccine , or the standard-dose adjuvant-containing vaccine (Fluad®), but if none of these 3 vaccines is available at the time of vaccine administration, then adults ≥65 years may receive a standard-dose preparation.100
The most common adverse effects of influenza vaccine inactivated are listed below for individual vaccine preparations.
In children 6 months through 8 years of age, the most common injection-site adverse reactions were pain or tenderness (>50%) and redness (>25%); the most common solicited systemic adverse reactions were irritability and drowsiness (>25% of children 6 months through 35 months) and myalgia (>20% of children 3 years through 8 years).104
In adults 18 through 64 years of age, the most common injection-site adverse reaction was pain (>50%); the most common solicited systemic adverse reactions were headache and myalgia (>30%).104
In adults ≥65 years of age, the most common injection-site adverse reaction was pain (>20%); the most common solicited systemic adverse reactions were headache, myalgia, and malaise (>10%).104
In adults, the most common (≥10%) solicited local adverse reactions were pain and redness; the most common systemic adverse reactions were muscle aches, fatigue, and headache.106
In children 5 through 17 years of age, the most common (≥10%) solicited local adverse reactions were pain, redness, and swelling; the most common systemic adverse reactions were muscle aches, fatigue, and headache.106
In children 3 through 4 years of age, the most common (≥10%) solicited local adverse reactions were pain, redness, and swelling; the most common systemic adverse reactions were irritability, loss of appetite (13%), and drowsiness.106
In children 6 through 35 months of age who received Fluarix QUADRIVALENT, the most common (≥10%) solicited local adverse reactions were pain and redness; the most common systemic adverse reactions were irritability, loss of appetite, and drowsiness.106
In adults, the most common (≥10%) solicited local adverse reactions were pain, redness, and swelling; the most common solicited systemic adverse reactions were fatigue, headache, and muscle aches/arthralgia.107
In children 3 through 17 years of age, the most common (≥10%) solicited local adverse reaction was pain.107
In children 3 through 4 years of age, the most common (≥10%) solicited systemic adverse reactions were irritability, drowsiness, and loss of appetite.107
In children 5 through 17 years of age, the most common (≥10%) solicited systemic adverse reactions were muscle aches, headache, and fatigue.107
In children 6 through 35 months of age who received Flulaval QUADRIVALENT, the most common (≥10%) solicited local adverse reaction was pain; most common solicited systemic adverse reactions were irritability, drowsiness, and loss of appetite.107
In adults 18 through 64 years, the most commonly reported injection-site adverse reaction was pain (≥40%).108 The most common systemic adverse reactions were myalgia and headache (≥20%).108
In adults 65 years of age and older, the most commonly reported injection-site adverse reaction was pain (≥20%).108 The most common systemic adverse reaction was myalgia (≥10%).108
In children 6 through 35 months of age, the most commonly reported injection-site reactions were pain and redness (≥20%).108 The most common systemic adverse reactions were irritability (≥30%), diarrhea, and loss of appetite (≥20%).108
In children 36 through 59 months of age, the most commonly reported injection-site reactions were pain (≥30%) and redness (≥20%).108 The most commonly reported systemic adverse reactions were malaise, fatigue, and diarrhea (≥10%).
In children 5 through 8 years of age, the most commonly reported injection-site adverse reactions were pain (≥50%), redness, and swelling (≥10%). The most common systemic adverse reaction was headache (≥10%)
In children 9 through 17 years, the most commonly reported injection-site adverse reactions were pain (≥50%), redness, and swelling (≥10%).108 The most common systemic adverse reactions were headache, myalgia, malaise, and fatigue (≥10%).108
In adults 18 through 64 years of age receiving the PharmaJet Stratis needle-free injection system, the most commonly reported injection-site adverse reactions were tenderness (≥80%), swelling, pain, redness (≥60%), itching (≥20%), and bruising (≥10%).108 The most common systemic adverse reactions were myalgia, malaise (≥30%), and headache (≥20%).108
In adults ≥65 years of age, the most common (>10%) injection-site adverse reaction was pain; the most common solicited systemic adverse reactions were myalgia, malaise, and headache.160
The most common (≥10%) local and systemic adverse reactions in adults ≥65 years of age were injection site pain, injection site tenderness, myalgia, fatigue, and headache.186
In children 6 months through 3 years of age who received FLUCELVAX QUADRIVALENT, the most commonly reported injection-site adverse reactions were tenderness (28%), erythema (26%), induration (17%), and ecchymosis (11%).190 The most common systemic adverse reactions were irritability (28%), sleepiness (27%), diarrhea (18%), and change of eating habits (17%).190
In children 4 through 8 years of age, the most commonly reported local injection-site adverse reactions were pain (29%) and erythema (11%).190 The most common systemic adverse reaction was fatigue (10%).190
In children and adolescents 9 through 17 years of age, the most commonly reported injection-site adverse reactions were pain (34%) and erythema (14%).190 The most common systemic adverse reactions were myalgia (15%) and headache (14%).190
In adults 18 through 64 years of age, the most commonly reported injection-site adverse reactions were pain (28%) and erythema (13%).190 The most common systemic adverse reactions were headache (16%), fatigue (12%), myalgia (11%), and malaise (10%).190
In adults ≥65 years of age, the most commonly reported injection-site reaction was erythema (10%).190 The most common systemic adverse reactions were fatigue (11%), headache (10%), and malaise (10%).190
Antiviral agents used for the treatment or prevention of influenza (e.g., baloxavir marboxil, oseltamivir, peramivir, zanamivir) have no effect on the immune response to inactivated vaccines, including influenza vaccine inactivated.134 Influenza vaccine inactivated may be administered to individuals receiving these antiviral drugs.100
Individuals receiving immunosuppressive therapy (e.g., alkylating agents, antimetabolites, certain biologic response modifiers, corticosteroids, radiation therapy) may have reduced immune responses to vaccines, including influenza virus vaccine inactivated.104, 106, 107, 108, 134, 160, 186, 190
Inactivated vaccines generally should be administered at least 2 weeks prior to initiation of immunosuppressive therapy and, because of possible suboptimal response, should not be administered during and for certain periods of time after immunosuppressive therapy is discontinued. 134
Inactivated vaccines should be administered at least 2 weeks prior to treatment with anti-B-cell antibodies (e.g., rituximab).134 Some experts state that administration of inactivated vaccines should be deferred until at least 6 months after treatment with anti-B-cell antibodies has been discontinued. 134
Inactivated vaccines should be administered at least 2 weeks prior to initiation of therapy with certain other immunosuppressive biologic response modifiers (e.g., colony-stimulating factors, interleukins, tumor necrosis factor [TNF; TNF-α] blocking agents).134
Corticosteroids given in greater than physiologic doses may reduce immune responses to vaccines.134 AAP states that inactivated vaccines preferably should be administered at least 2 weeks prior to initiation of corticosteroid therapy that is considered immunosuppressive.134
Concurrent administration of influenza vaccine inactivated with other age-appropriate vaccines, including live virus vaccines, toxoids, or inactivated or recombinant vaccines, during the same health-care visit is not expected to affect immunologic responses or adverse reactions to any of the preparations.134
Immunization with influenza vaccine inactivated can be integrated with immunization against diphtheria, tetanus, pertussis, Haemophilus influenzae type b (Hib), hepatitis A, hepatitis B, human papillomavirus (HPV), measles, mumps, rubella, meningococcal disease, pneumococcal disease, poliomyelitis, rotavirus, and varicella.134 However, each parenteral vaccine should be administered using separate syringes and different injection sites.134
An interim analysis of a clinical study of 296 persons ≥65 years of age comparing concomitant administration of a quadrivalent inactivated influenza vaccine (HD-IIV4) and a booster dose of an mRNA COVID-19 vaccine (administered in separate upper arm sites) with administration of either vaccine alone did not identify any safety concerns or any evidence of immune interference on influenza hemagglutination inhibition or SARS-CoV-2 binding antibody responses.589 Local reactogenicity up to 21 days postvaccination was similar between the coadministration group and the group that received the mRNA COVID-19 vaccine alone.589 Similar frequency of systemic reactions were reported in the coadministration and mRNA groups, but with lower frequencies observed in participants who received HD-IIV4 alone.589
In a multicenter, randomized clinical study, 679 adult participants were recruited to receive concomitant administration of either an age-appropriate influenza vaccine or placebo along with their second dose of a COVID-19 vaccine (either an adenovirus viral vector COVID-19 vaccine or an mRNA COVID-19 vaccine).590 Injections were administered by IM injection in the upper arm, with one injection on each side for the concomitant administration recipients.590 Analysis up to 21 days after vaccination, did not identify safety concerns or evidence of immune interference on influenza hemagglutination inhibition or SARS-CoV-2 binding antibody responses.590 The study found similar rates of local reactogenicity between the coadministration group and single vaccine administration group; however, systemic reactions were reported at similar frequencies in the coadministration and mRNA vaccine groups, with lower frequencies observed in participants who received influenza vaccine alone.590
Data from an open-label, randomized study in adults 50 years of age or older indicate that concurrent administration of quadrivalent influenza virus vaccine inactivated (Fluarix®) and zoster vaccine recombinant (Shingrix®) does not interfere with the immune response to either vaccine106, 117 and is not associated with any safety concerns.117 Although the rates of solicited systemic adverse effects (i.e., fatigue, headache, myalgia, shivering, fever) in those receiving the vaccines concurrently were similar to those observed when zoster vaccine recombinant was given alone, the rates were higher than those observed when quadrivalent influenza virus vaccine inactivated was given alone.106
Safety and efficacy of concomitant or sequential administration of adjuvant-containing influenza virus vaccine inactivated (Fluad®) and zoster vaccine recombinant have not been evaluated. 117
Inactivated influenza vaccines are noninfectious, sterile suspensions of suitably inactivated influenza virus types A and B subunits.104, 106, 107, 108, 190 Influenza virus vaccines stimulate active immunity to influenza virus infection by inducing production of specific antibodies; protection is provided only against those strains of virus from which the vaccines are prepared and possibly closely related strains.100 In healthy young adults, seasonal influenza virus vaccine inactivated has been shown to induce rapidly and simultaneously both a systemic (i.e., in serum)159, 222, 252, 253, 254 and, to a lesser extent, local (i.e., in the upper respiratory tract)222 immune response.
Local mucosal immunity in the respiratory tract (e.g., in tonsils) confers the initial line of defense against influenza.222, 252, 253, 254 It has been suggested that migration of activated B cells, particularly IgA-committed B cells, via lymphatic drainage from the injection site to the mucosal surfaces of the tonsils is responsible for the local immune response after influenza vaccination.222
Seasonal influenza vaccines are formulated annually to contain antigens representative of the strains of influenza A (H1N1), influenza A (H3N2), and influenza B viruses likely to circulate in the US during the upcoming influenza season.100 All inactivated influenza vaccines (egg- or cell culture-based) currently available in the US are trivalent vaccines containing 2 influenza type A antigens (H1N1 and H3N2) and an influenza type B antigen (B/Victoria lineages).100
Although postvaccination antibody titers initially may remain stable (e.g., hemagglutination-inhibition [HI], IgG) or decrease (e.g., IgA) with repeated annual vaccination against seasonal influenza, prevaccination titers of HI, IgG, and IgA prior to the subsequent annual dose are increased overall.380 Thus, repeated annual vaccination against seasonal influenza results in an increase in and maintenance of antibodies to seasonal influenza A (H1N1) and (H3N2) strains over time, which is beneficial for protection of vaccinees.380 Even in individuals in whom a decrease in antibody titers occurs with repeated vaccination, an increase in avidity of the antibodies for influenza antigens could prevent a decline in immune competence.380
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injectable suspension, for IM use | 15 mcg hemagglutinin each of FDA-specified influenza A (H1N1), influenza A (H3N2), and influenza B/Victoria lineage antigens per 0.5 mL | Afluria® 2025-2026 Formula | Seqirus |
15 mcg hemagglutinin each of FDA-specified influenza A (H1N1), influenza A (H3N2), and influenza B/Victoria lineage antigens per 0.5 mL | Fluarix® 2025-2026 Formula | GlaxoSmithKline | ||
15 mcg hemagglutinin each of FDA-specified influenza A (H1N1), influenza A (H3N2), and influenza B/Victoria lineage antigens per 0.5 mL | Flucelvax® 2025-2026 Formula | Seqirus | ||
15 mcg hemagglutinin each of FDA-specified influenza A (H1N1), influenza A (H3N2), and influenza B/Victoria lineage antigens per 0.5 mL | Flulaval® 2025-2026 Formula | GlaxoSmithKline | ||
15 mcg hemagglutinin each of FDA-specified influenza A (H1N1), influenza A (H3N2), and influenza B/Victoria lineage antigens per 0.5 mL | Fluzone® 2025-2026 Formula | Sanofi Pasteur | ||
60 mcg hemagglutinin each of FDA-specified influenza A (H1N1), influenza A (H3N2), and influenza B/Victoria lineage antigens per 0.5 mL | Fluzone® High-Dose 2025-2026 Formula | Sanofi Pasteur |
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injectable emulsion, for IM use | 15 mcg hemagglutinin each of FDA-specified influenza A (H1N1), influenza A (H3N2), and influenza B/Victoria lineage, antigens per 0.5 mL | Fluad® 2025-2026 Formula | Seqirus |
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions October 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
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