Influenza Virus Vaccine Inactivated

Class: Vaccines
VA Class: IM100
Brands: Afluria, Agriflu, Fluarix, Flulaval, Fluvirin, Fluzone

Introduction

Inactivated virus vaccine.^{103 143 441 463 473 533} Seasonal influenza virus vaccine inactivated is a trivalent vaccine containing noninfectious, suitably inactivated influenza virus types A and B subunits and is used to stimulate active immunity to influenza virus strains contained in the vaccine.^{103 143 441 463 473 533}

Uses for Influenza Virus Vaccine Inactivated

Prevention of Seasonal Influenza A and B Virus Infections

Prevention of seasonal influenza virus infection in adults,^{100 103 143 441 463 473 533} adolescents,^{100 103 143 441} and infants and children ≥6 months of age.^{100 103}

Influenza is an acute viral infection; influenza viruses spread from person to person mainly through large-particle respiratory droplet transmission.¹⁰⁰ In the US, epidemics of seasonal influenza occur annually, usually during late fall through early spring.¹⁰⁰ Influenza viruses can cause illness in any age group; children have highest rate of infection.¹⁰⁰ Influenza can exacerbate underlying medical conditions or lead to pneumonia in certain individuals.¹⁰⁰ Individuals ≥65 years of age, children <2 years of age, and individuals with chronic medical conditions have highest risk of influenza-related complications and death.^{100 488}

Annual vaccination is the most effective strategy for preventing seasonal influenza and its complications.¹⁰⁰

Beginning in the 2010–2011 influenza season, the US Public Health Service Advisory Committee on Immunization Practices (ACIP) recommends routine influenza vaccination for all adults, adolescents, and infants and children 6 months of age or older using an age-appropriate seasonal influenza vaccine, unless contraindicated.¹⁰⁰ However, seasonal influenza vaccination efforts should continue to target individuals at higher risk of influenza or influenza-related complications and those who live with or care for such individuals (e.g., health-care personnel, household or other close contacts).¹⁰⁰ (See Table 1.) Targeted vaccination efforts are especially important during periods when the supply of seasonal influenza vaccine is limited.¹⁰⁰

Table 1. ACIP Recommends Targeted Seasonal Influenza Vaccination Efforts in the Following Individuals Using an Appropriate Vaccine:100

Infants and children 6 months to <5 years of age (59 months)

Adults ≥50 years of age

Adults, adolescents, and children ≥6 months of age with chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, neurologic, hematologic, or metabolic disorders (including diabetes mellitus)

Adults, adolescents, and children ≥6 months of age who are immunosuppressed, including those receiving immunosuppressive drugs and those with HIV infection

Women who are or will be pregnant during the influenza season

Children and adolescents 6 months to 18 years of age receiving long-term aspirin therapy who might therefore be at risk for Reye's syndrome after influenza infection

Adults, adolescents, and children ≥6 months of age who are residents of nursing homes and other chronic-care facilities

American Indians and Alaska Natives

Morbidly obese individuals (body mass index ≥40)

Health-care personnel

Household contacts and caregivers of children <5 years of age (especially contacts of infants <6 months of age)

Household contacts and caregivers of adults ≥50 years of age

Household contacts and caregivers of individuals with medical conditions that put them at high risk for severe influenza complications

For prevention of seasonal influenza infection, 2 different types of influenza vaccine are commercially available in the US: intranasal vaccine containing live, attenuated virus^{100 157} and parenteral vaccine containing inactivated virus subunits.^{100 103 143 441 463 473 533} Both vaccine types contain influenza virus strains antigenically equivalent to the annually recommended seasonal influenza strains.¹⁰⁰ Parenteral inactivated influenza vaccine has several advantages because it can be used in a wider age group than intranasal live influenza vaccine, including infants as young as 6 months of age and adults ≥50 years.^{100 118} Parenteral inactivated vaccine can be used in some individuals who should not receive the intranasal vaccine, including pregnant women, individuals with underlying medical conditions that may predispose them to severe disease following influenza infection, children and adolescents receiving long-term aspirin therapy, and individuals who have close contact with severely immunocompromised individuals requiring a protective environment (e.g., hematopoietic stem cell transplant [HSCT] recipients).^{100 118}

Travelers who want to reduce their risk of influenza infection should receive vaccination with seasonal influenza vaccine, preferably at least 2 weeks before departure.^{100 117} The risk for exposure to seasonal influenza during travel depends on the time of year and destination.^{100 117} In the tropics, influenza can occur throughout the year; in temperate regions of the southern hemisphere, influenza activity generally occurs from April through September.^{100 117} In temperate climates, travelers also may be exposed to influenza during the summer (especially when traveling as part of large tourist groups that include individuals from areas of the world where influenza is circulating).^{100 117} ACIP recommends that travelers (especially those at high risk for influenza complications) be vaccinated against seasonal influenza before travel if they were not vaccinated during the preceding fall or winter, will be traveling to the tropics, traveling with organized tourist groups at any time of year, or traveling to the southern hemisphere between April and September.¹⁰⁰

HIV-infected individuals may be at high risk for influenza-related complications and should receive annual vaccination against seasonal influenza.^{100 112 155 156} However, antibody response may be reduced in HIV-infected individuals and is inversely correlated with severity of the disease.^{100 101 106 109 110 112 116 232 233 310 376} (See Individuals with Altered Immunocompetence under Cautions.)

Hematopoietic stem cell transplantation (HSCT) candidates should receive seasonal influenza virus vaccine inactivated during the influenza season prior to HSCT and then annually thereafter, beginning ≥6 months after HSCT.^{118 409} The vaccine may not be effective if given <6 months after HSCT.⁴⁰⁹

ACIP states that students or other persons in institutional settings (e.g., those who reside in dormitories or correctional facilities) should be encouraged to receive vaccination against seasonal influenza to minimize morbidity and disruption of routine activities during epidemics.¹⁰⁰ In addition, individuals who provide essential community services should be considered for annual vaccination against seasonal influenza to minimize disruption of essential activities during influenza outbreaks.¹⁰⁰

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

Seasonal influenza vaccines for the 2010–2011 influenza season are expected to provide protection against infection with the 2009 pandemic influenza A (H1N1) virus, previously referred to as the novel 2009 influenza A (H1N1) virus or swine-origin influenza A (H1N1) virus.¹⁰⁰

Individuals who received the influenza A (H1N1) 2009 monovalent vaccine during the 2009–2010 influenza season should still receive the 2010–2011 seasonal influenza vaccine, unless contraindicated.¹⁰⁰ The 2009 pandemic influenza A (H1N1) virus is expected to continue to circulate during the 2010–2011 season, and the duration of protection after receipt of the monovalent vaccine is unknown and likely declines over time.¹⁰⁰ In addition, the seasonal vaccine also provides protection against influenza A (H3N2) and influenza B.¹⁰⁰ ACIP states that there is no harm in administering 2010–2011 seasonal influenza vaccine to an individual who was previously infected with the 2009 pandemic influenza A (H1N1) virus.¹⁰⁰

Seasonal influenza vaccines are not expected to provide protection against infection with avian influenza A viruses, including avian influenza A (H5N1).¹⁰⁰ Although an inactivated influenza A (H5N1) monovalent vaccine has been approved by the FDA,⁴⁷⁰ the vaccine is not available commercially but has been purchased by the US Federal Government for inclusion in the National Stockpile.⁴⁷⁰

Information regarding influenza surveillance and updated recommendations for prevention and treatment of seasonal influenza is available from CDC at .

Influenza Virus Vaccine Inactivated Dosage and Administration

Administration

IM Administration

Administer by IM injection.^{100 103 143 441 463 473 533}

Do not administer IV,^{441 463} sub-Q,⁴⁶³ or intradermally.⁴⁶³

Administer every year before exposure to seasonal influenza.^{100 103 143 441 463 473 533} Optimum time for annual vaccination against seasonal influenza cannot be determined since influenza seasons vary in timing and duration and more than one outbreak might occur in a single community in a single year.¹⁰⁰ In the US, localized outbreaks indicating start of the annual influenza season can occur as early as October; peak influenza activity often occurs in January or February, but has occurred as late as April or May.¹⁰⁰ Begin vaccination efforts each year by October or as soon as the seasonal vaccine is available; continue vaccination efforts throughout influenza season, even after influenza activity has begun in the community.¹⁰⁰

Shake vaccine vial before withdrawing a dose.^{103 119 143 463 473} Shake prefilled syringe before administering a dose.^{103 119 143 441 473 533} Discard vaccine if it contains particulates, appears discolored, or cannot be resuspended with thorough agitation.^{103 119 143 441 463 473 533}

To ensure delivery into muscle, IM injections should be made at a 90° angle to the skin using a needle length appropriate for the individual's age and body mass.¹¹⁸ For adults and adolescents, administer IM into the deltoid muscle.^{100 103 118 143 441 463 473 533} In children ≥3 years of age, IM injections should be made into the deltoid muscle if muscle mass is adequate; alternatively, the anterolateral thigh can be used.^{103 118 441} In children 6 months to 2 years of age, IM injections should preferably be made in the anterolateral aspect of the thigh.^{100 103 118}

Do not administer into buttock muscle because of potential for injection-associated injury to sciatic nerve.^{103 118 143 441 463 533} Do not administer into any area where there may be a major nerve trunk.^{103 143 441 463 533}

Since syncope may occur following vaccination, observe vaccinees for approximately 15 minutes after the dose.^{112 105} Syncope occurs most frequently in adolescents and young adults,^{112 105} and may be averted if vaccinees sit or lie down for 15 minutes after vaccination.¹¹² If syncope occurs, observe patient until symptoms resolve.^{112 105}

Do not mix with any other vaccine or solution.^{103 118 143 441 463 473 533}

May be given simultaneously with other age-appropriate vaccines during same health-care visit.^{100 118} (See Interactions.) When multiple vaccines are administered during a single health-care visit, each parenteral vaccine should be given with a different syringe and at different injection sites.¹¹⁸ Separate injection sites by at least 1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur.¹¹⁸

Dosage

Dose and dosing schedule for prevention of seasonal influenza depend on individual’s age, vaccination status, and specific product administered.^{100 103 105 143 441 463 473 533}

A single-dose regimen of seasonal influenza vaccine is used in adults, adolescents, and children ≥9 years of age.^{100 103 105 143 200 441 463 473 533}

ACIP and AAP state that a single-dose regimen of 2010–2011 seasonal influenza vaccine can be used in infants and children 6 months through 8 years of age who received 2 doses of any type of seasonal influenza vaccine during the 2009–2010 influenza season and received at least 1 dose of any type of influenza A (H1N1) 2009 monovalent vaccine during the 2009–2010 season.^{100 105} A single-dose regimen also can be used in infants and children 6 months through 8 years of age who were vaccinated against seasonal influenza prior to the 2009–2010 influenza season and received at least 1 dose of any type of influenza A (H1N1) 2009 monovalent vaccine during the 2009–2010 season.^{100 105}

However, ACIP and AAP state that a 2-dose regimen of 2010–2011 seasonal influenza vaccine should be used in infants and children 6 months through 8 years of age who did not receive any doses of influenza A (H1N1) 2009 monovalent vaccine during the 2009–2010 influenza season or have an uncertain history regarding vaccination with the influenza A (H1N1) 2009 monovalent vaccine.^{100 105}

A 2-dose regimen of 2010–2011 seasonal influenza vaccine also is necessary in infants and children 6 months through 8 years of age who have not previously received any type of seasonal influenza vaccine,^{100 103 105 143 441 473} received seasonal influenza vaccine for the first time during the 2009–2010 season but received only a single dose,^{100 105} or have an uncertain history regarding vaccination with seasonal influenza vaccine.^{100 105}

ACIP states that there is no harm in administering 2 doses of 2010–2011 seasonal influenza vaccine to a child who was previously infected with the 2009 pandemic influenza A (H1N1) virus.¹⁰⁰ However, at the clinician's discretion, children with a history of laboratory-confirmed 2009 pandemic H1N1 virus infection (i.e., confirmed with reverse transcription polymerase chain reaction [PCR] testing or virus culture specific for 2009 pandemic influenza A [H1N1] virus) can be considered to have been vaccinated against this virus when determining whether a single- or 2-dose regimen of seasonal influenza vaccine is needed.¹⁰⁰ Infants and children 6 months through 8 years of age who had a febrile respiratory illness during 2009–2010 and did not receive specific diagnostic testing for the 2009 pandemic influenza A (H1N1) virus (i.e., were not tested or were tested with a rapid antigen test) cannot be assumed to have had influenza A (H1N1) virus infection and, therefore, should receive 2 doses of 2010–2011 seasonal influenza vaccine.¹⁰⁰

Agriflu and Flulaval are used only in adults ≥18 years of age.^{463 533}

Fluzone may be used in adults, adolescents, and infants and children ≥6 months of age.¹⁰³

Fluzone High-Dose should be used only in adults ≥65 years of age.¹⁰³ (See Geriatric Use under Cautions.)

Fluvirin may be used in adults, adolescents, and children ≥4 years of age.¹⁴³ Fluarix may be used in adults, adolescents, and children ≥3 years of age.⁴⁴¹

Although Afluria was labeled for use in adults, adolescents, and infants and children ≥6 months of age,⁴⁷³ ACIP recommends that this vaccine only be used in adults, adolescents, and children ≥9 years of age.⁵³⁴ (See Pediatric Use under Cautions.)

Pediatric Patients

Prevention of Seasonal Influenza A and B Virus Infections

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

IM

Received 2 doses of any type of seasonal influenza vaccine during the 2009–2010 influenza season and received at least 1 dose of any type of influenza A (H1N1) 2009 monovalent vaccine during the 2009–2010 season^{100 105} : Single 0.25-mL dose.^{100 103 105}

Received any type of seasonal influenza vaccine prior to the 2009–2010 influenza season and received at least 1 dose of any type of influenza A (H1N1) 2009 monovalent vaccine during the 2009–2010 season^{100 105} : Single 0.25-mL dose.^{100 103 105}

Did not previously receive any type of seasonal influenza vaccine or received only a single dose of any type of seasonal influenza vaccine during the 2009–2010 season: Two 0.25-mL doses administered at least 1 month apart.^{100 103 105}

Did not receive any doses of influenza A (H1N1) 2009 monovalent vaccine during the 2009–2010 influenza season: Two 0.25-mL doses administered at least 1 month apart.^{100 103 105}

Uncertain history of previous vaccination with any type of seasonal influenza vaccine and/or uncertain history regarding vaccination with influenza A (H1N1) 2009 monovalent vaccine during the 2009–2010 season: Two 0.25-mL doses administered at least 1 month apart.^{100 103 105}

Children 3 through 8 Years of Age (Fluarix, Fluzone) or Children 4 through 8 Years of Age (Fluvirin)

IM

Received 2 doses of any type of seasonal influenza vaccine during the 2009–2010 influenza season and received at least 1 dose of any type of influenza A (H1N1) 2009 monovalent vaccine during the 2009–2010 season^{100 105} : Single 0.5-mL dose.^{100 103 143 441}

Received any type of seasonal influenza vaccine prior to the 2009–2010 influenza season and received at least 1 dose of any type of influenza A (H1N1) 2009 monovalent vaccine during the 2009–2010 season^{100 105} : Single 0.5-mL dose.^{100 103 143 441}

Did not previously receive any type of seasonal influenza vaccine or received seasonal influenza vaccine for the first time during the 2009–2010 season and received only a single dose: Two 0.5-mL doses administered at least 1 month apart.^{100 103 105 143 441}

Did not receive any doses of influenza A (H1N1) 2009 monovalent vaccine during the 2009–2010 influenza season: Two 0.5-mL doses administered at least 1 month apart.^{100 103 105 143 441}

Uncertain history of previous vaccination with any type of seasonal influenza vaccine and/or uncertain history regarding vaccination with influenza A (H1N1) 2009 monovalent vaccine during the 2009–2010 season: Two 0.5-mL doses administered at least 1 month apart.^{100 103 105 143 441}

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

IM

Single 0.5-mL dose.^{103 143 441 473}

Adults

Prevention of Seasonal Influenza A and B Virus Infections

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

IM

Single 0.5-mL dose.^{100 103 143 441 463 473 533}

Special Populations

Hepatic Impairment

No specific dosage recommendations.^{103 143 441 463 473 533}

Renal Impairment

No specific dosage recommendations.^{103 143 441 463 473 533}

Geriatric Patients

A standard-dose preparation or Fluzone High-Dose may be used.¹⁰⁰ (See Geriatric Use under Cautions.)

Standard-dose Preparations (Afluria, Agriflu, Fluarix, Flulaval, Fluvirin, Fluzone)

No special dosage recommendations.^{103 143 441 463 473 533}

Fluzone High-Dose

Geriatric adults ≥65 years of age: Single 0.5-mL IM dose.^{100 103}

Cautions for Influenza Virus Vaccine Inactivated

Contraindications

• 
  

  Hypersensitivity to egg or egg proteins or any vaccine component.^{100 103 143 441 463 473 533} (See Sensitivity Reactions under Cautions.)

  
  


• 
  

  Life-threatening reaction to previous dose of any influenza vaccine.^{103 143 441 463 473 533}

  
  


• 
  

  Afluria: Hypersensitivity to neomycin or polymyxin.⁴⁷³ (See Neomycin, Kanamycin, and/or Polymyxin B Allergy under Cautions.)

  
  


• 
  

  Agriflu: Hypersensitivity to kanamycin or neomycin.⁵³³ (See Neomycin, Kanamycin, and/or Polymyxin B Allergy under Cautions.)

  
  

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Immediate, presumably allergic reactions (e.g., urticaria, angioedema, anaphylaxis, anaphylactic shock, allergic asthma) reported rarely.^{100 117 143 441 463 473 533} Reactions may result from sensitivity to some vaccine component; the majority of reactions most likely are related to residual egg protein.^{100 117 441 463 473}

Seasonal parenteral inactivated influenza vaccine is produced using embryonated chicken eggs^{100 143 441 463 473 533} and can contain residual egg protein that may induce immediate hypersensitivity reactions, including anaphylaxis, in individuals with severe egg allergy.^{100 118} AAP states that less severe or local manifestations of allergy to eggs or feathers are not contraindications to routine administration of influenza vaccine.¹⁰⁵ ACIP states asking patients if they can eat eggs without adverse effects is a reasonable way to identify those who may be at risk for allergic reactions if they receive the vaccine.^{100 118} Those who are able to eat eggs or egg products safely usually can receive influenza vaccine; those with a history of anaphylactic or other immediate hypersensitivity reaction (e.g., hives, angioedema, allergic asthma) to eggs or egg proteins should not receive the vaccine.¹¹⁸ (See Contraindications under Cautions.)

Prior to administration, review patient’s history with respect to possible hypersensitivity to vaccine components, including egg and egg products.^{143 441 463} Epinephrine^{441 463} and other appropriate agents should be readily available in case anaphylaxis occurs.^{103 143 441 463 473 533}

Do not administer additional vaccine doses to any individual who experienced life-threatening reactions to a previous dose.^{103 143 441 463 473 533} (See Contraindications under Cautions.)

Neomycin, Kanamycin, and/or Polymyxin B Allergy

Afluria: Each 0.5-mL dose may contain trace amounts of neomycin sulfate (≤0.2 picograms) and polymyxin B (≤0.03 picograms).⁴⁷³ Manufacturer states the vaccine is contraindicated in individuals hypersensitive to neomycin or polymyxin.⁴⁷³

Agriflu: Each 0.5-mL dose may contain trace amounts of neomycin (≤0.02 mcg) and kanamycin (≤0.03 mcg).⁵³³ Manufacturer states the vaccine is contraindicated in individuals hypersensitive to neomycin or kanamycin.⁵³³

Fluvirin: Each 0.5-mL dose may contain neomycin (≤2.5 mcg) and polymyxin B (≤3.75 mcg).¹⁴³

Neomycin allergy usually results in delayed-type (cell-mediated) hypersensitivity reactions manifested as contact dermatitis.¹¹⁸ ACIP and AAP state that vaccines containing trace amounts of neomycin should not be used in individuals with a history of anaphylactic reaction to neomycin, but may be considered in those with a history of delayed-type neomycin hypersensitivity if benefits of vaccination outweigh risks.^{112 118}

Thimerosal Allergy

All multiple-dose vials of influenza virus vaccine contain thimerosal as a preservative;^{103 143 463 473} some preparations of the vaccine in prefilled syringes are preservative-free but contain trace amounts of thimerosal from the manufacturing process.¹⁴³ (See Thimerosal Precautions under Cautions.) Hypersensitivity reactions to thimerosal contained in vaccines have been reported in some individuals.^{100 140 427 498 500} These reactions usually manifest as local, delayed-type hypersensitivity reactions (e.g., erythema, swelling),^{100 118 140 427} but a generalized reaction manifested as pruritus and an erythematous, maculopapular rash on all 4 extremities has been reported rarely.⁵⁰⁰ Even when patch or intradermal tests for thimerosal sensitivity are positive, most individuals do not develop hypersensitivity reactions to thimerosal administered as a component of vaccines.^{100 118 140}

ACIP states that a history of delayed-type hypersensitivity to thimerosal is not a contraindication to use of vaccines that contain thimerosal.¹¹⁸

Latex Sensitivity

Agriflu, Fluarix, Fluvirin: Some components (i.e., tip cap) of the single-dose prefilled syringes contain dry natural latex.^{143 441 533}

Some individuals may be hypersensitive to natural latex proteins.^{143 356 357 441 533} Take appropriate precautions if this preparation is administered to individuals with a history of latex sensitivity.^{355 356 357}

Guillain-Barré Syndrome

Carefully consider possible benefits and potential risks of influenza vaccine in individuals who experienced Guillain-Barré syndrome (GBS) within 6 weeks of previous influenza vaccination.^{143 441 463 473 533}

Unclear whether influenza vaccination increases risk of recurrence of GBS.^{100 105} AAP states that influenza vaccines should not be used in children who developed GBS within 6 weeks after a dose of any influenza vaccine.¹⁰⁵ ACIP states that benefits of influenza vaccine may outweigh risks in individuals with a history of GBS who are at high risk for severe influenza-related complications.¹⁰⁰ However, it may be prudent to avoid influenza vaccine in individuals who are not at high risk for severe influenza complications if they experienced GBS within 6 weeks after previous influenza vaccination.¹⁰⁰

Individuals with Altered Immunocompetence

May be administered to individuals immunosuppressed as the result of disease or immunosuppressive therapy.¹⁰⁰ Consider possibility that immune response to the vaccine and efficacy may be reduced in these individuals.^{103 143 441 463 473 533}

CDC, National Institutes of Health (NIH), IDSA, AAP, and other experts state that HIV-infected children, adolescents, and adults should receive annual vaccination against seasonal influenza; however, the parenteral inactivated influenza vaccine (not the intranasal live vaccine) should be used for prevention of seasonal influenza in HIV-infected individuals.^{155 156} Data are limited regarding safety of parenteral inactivated influenza vaccine in HIV-infected individuals, but there is no evidence that use of the vaccine has any clinically important effect on HIV infection or immunocompetence.¹⁰⁰ An adequate antibody response to parenteral inactivated influenza vaccine may be attained in HIV-infected individuals with minimal or no AIDS-related symptoms.¹⁰⁰ Antibody response may be inversely correlated with severity of the disease.^{100 101 106 109 110 112 116 232 233 260 310 375 376} Although parenteral inactivated influenza vaccine has been highly effective in preventing symptomatic, laboratory-confirmed influenza infection in HIV-infected individuals with mean CD4⁺ T-cell counts of 400/mm³, the vaccine may be less effective in those with more advanced disease and lower CD4⁺ T-cell counts (e.g., <100/mm³).¹⁰⁰ A second dose of influenza vaccine does not appear to improve immune response in these individuals.¹⁰⁰

May not be effective if given <6 months after HSCT.⁴⁰⁹

Limited data indicate the vaccine does not appear to adversely affect allograft function or cause rejection episodes in kidney, heart, or liver transplant recipients.¹⁰⁰ However, the vaccine may be less immunogenic in some solid organ transplant recipients, especially those vaccinated within 4 months after liver transplant.¹⁰⁰

Fever and Febrile Seizures

Postmarketing reports indicate an increased incidence of fever and febrile seizures in infants and children 6 months through 4 years of age and an increased incidence of fever in children 5–8 years of age who received a 2010 southern hemisphere parenteral inactivated influenza vaccine^{473 534} that is antigenically equivalent to and produced by the same manufacturer as one of the 2010–2011 seasonal parenteral inactivated influenza vaccines marketed in the US (i.e., Afluria; CSL).⁵³⁴

In a study evaluating safety and efficacy of the 2009–2010 formulation of Afluria, the incidence of fever within 7 days after the first dose was 37% in infants and children 6 months to <3 years of age, 32% in those 3 to <5 years of age, and 16% in those 5 to <9 years of age compared with 14, 11, and 9%, respectively, in children in these age groups who received a comparator vaccine.⁴⁷³

Based on available data, ACIP states Afluria should not be used in infants and children 6 months through 8 years of age.⁵³⁴ (See Pediatric Use under Cautions.)

Thimerosal Precautions

Although there is no convincing evidence that the low concentrations of thimerosal (a mercury-containing preservative) contained in some vaccines is harmful to vaccine recipients,^{100 493 494 499 501 502 503 504 505 506} efforts to eliminate or reduce the thimerosal content in vaccines is recommended as a prudent measure to reduce mercury exposure in infants and children and part of an overall strategy to reduce mercury exposures from all sources, including food and drugs.^{100 118 401 402 403 492}

As a result of efforts initiated in 1999 to remove or reduce thimerosal in vaccines and expedite development and approval of preservative-free formulations of vaccines, inactivated influenza vaccine now is commercially available in prefilled syringes as preservative-free formulations that do not contain thimerosal^{103 427 441 473 533} and in prefilled syringes as preservative-free formulations that contain only trace amounts of thimerosal from the manufacturing process (≤1 mcg of mercury per 0.5-mL dose),^{143 427} FDA states that trace amounts of thimerosal from the manufacturing process are not considered clinically important.⁴²⁷ Only multiple-dose vials of inactivated influenza virus still contain thimerosal as a preservative (≤ 25 mcg of mercury per 0.5-mL dose).^{103 143 427 463 473} Intranasal live influenza vaccine does not contain thimerosal.^{100 157}

Although it was suggested that thimerosal in vaccines theoretically could have adverse effects in vaccine recipients, there is no conclusive evidence that the low levels of thimerosal contained in vaccines cause harm in vaccine recipients.^{100 118 492 493 494 499 501 502 503 504 505 506} A link between thimerosal in vaccines and neurodevelopmental disorders in children (autism, attention deficit/hyperactivity disorder [AHDH], speech or language delay) possibly related to mercury neurotoxicity has been theorized; however, considerable evidence has accumulated that supports the absence of substantial risk for neurodevelopmental disorders or other harm resulting from exposure to thimerosal-containing vaccines.^{100 493 494 499 501 502 503 504 505 506} In 2004, the Immunization Safety Review Committee of the IOM examined the hypothesis that thimerosal-containing vaccines are causally associated with autism and concluded that the body of epidemiologic evidence favors rejection of a causal relationship between these vaccines and autism.⁵⁰⁶

Analysis of adverse effects reported to the Vaccine Adverse Event Reporting System (VAERS) indicates that there is no difference in the incidence of injection site reactions, rash, or infections in infants 6–23 months of age who received preservative-containing (thimerosal-containing) inactivated influenza vaccine compared with those who received preservative-free preparations of the vaccine.^{100 497} To date, the only adverse effects known to be caused by thimerosal contained in vaccines are hypersensitivity reactions.^{100 118 140}