Influenza Vaccine Recombinant

Class: Vaccines
VA Class: IM100
Brands: Flublok

Medically reviewed by Drugs.com. Last updated on Sep 7, 2020.

• Uses
• Dosage
• Cautions
• Interactions
• Patient advice
• Preparations

Introduction

Recombinant influenza vaccine.¹⁸³ Seasonal influenza vaccine recombinant (RIV; RIV4) contains recombinant hemagglutinin (HA) proteins representing influenza virus types A and B likely to circulate in the US during the upcoming season and is used to stimulate active immunity to influenza strains contained in the vaccine.^{100 183}

Uses for Influenza Vaccine Recombinant

Prevention of Seasonal Influenza A and B Virus Infections

Prevention of seasonal influenza virus infection in adults ≥18 years of age.¹⁸³

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

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

CDC Advisory Committee on Immunization Practices (ACIP), AAP, and others recommend routine influenza vaccination for all adults, adolescents, children, and infants ≥6 months of age using an age-appropriate seasonal influenza vaccine, unless contraindicated.^{100 112 199 200} Vaccination against seasonal influenza recommended for otherwise healthy individuals as well as those who have medical conditions that put them at increased risk for influenza-related complications or at higher risk for influenza-related outpatient, emergency department, or hospital visits.^{100 112}

Several different types of influenza vaccines may be available in the US for prevention of seasonal influenza: influenza virus vaccine inactivated (IIV), influenza vaccine recombinant (RIV), and influenza vaccine live intranasal (LAIV).¹⁰⁰ All 3 vaccine types are available as quadrivalent formulations containing antigens representing 2 influenza A strains (H1N1 and H3N2) and 2 influenza B strains (B/Victoria lineage and B/Yamagata lineage).¹⁰⁰ Influenza virus vaccine inactivated may also be available as a trivalent formulation containing antigens representing 2 influenza A strains (H1N1 and H3N2) and a single influenza B strain (B/Victoria lineage).¹⁰⁰

Select specific seasonal influenza vaccine based on individual’s age and whether they have certain underlying medical conditions that put them at increased risk of influenza complications (e.g., pregnancy, immunocompromising disease or therapy), are in close contact with severely immunocompromised individuals, or have a personal history that contraindicates use of certain vaccines.^{100 112} For many individuals, more than one vaccine type may be appropriate.^{100 112}

ACIP states there are no preferential recommendations for any specific vaccine type or trade name, provided an age-appropriate vaccine is chosen based on FDA-labeled indications and contraindications.¹⁰⁰ ACIP does not state a preference for a quadrivalent or trivalent formulation.¹⁰⁰ If an age-appropriate vaccine is available and there are no contraindications, do not delay influenza vaccination to obtain a specific product.¹⁰⁰

Travelers: All travelers (including those at high risk for influenza complications) who were not vaccinated with the current seasonal influenza vaccine should consider vaccination against seasonal influenza ≥2 weeks before travel.^{100 115} Revaccination not recommended for travelers who received influenza vaccine during the preceding fall and will be traveling during the summer.¹¹⁵ Risk for exposure to seasonal influenza during travel depends on time of year and destination.¹¹⁵ In temperate regions, influenza typically circulates at higher levels during colder winter months (i.e., October to May in Northern Hemisphere and April to September in Southern Hemisphere).^{100 115} In many tropical and subtropical areas, influenza can occur throughout the year.^{100 115}

Seasonal influenza vaccines not effective against all possible strains of influenza, but may be effective against influenza strains (and possibly closely related strains) represented in the vaccines.^{100 166} (See Limitations of Vaccine Effectiveness under Cautions.)

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

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

CDC and ACIP state that efforts to ensure influenza vaccination for all individuals ≥6 months of age for the 2020–2021 influenza season are of paramount importance to reduce influenza-related morbidity and mortality and reduce the impact of respiratory illnesses in the population and the resulting burdens on the health-care system.^{100 583} SARS-CoV-2 (causative agent of COVID-19) is expected to circulate in the US during the 2020–2021 influenza season; the extent of continued or recurrent SARS-CoV-2 circulation during the time influenza viruses are circulating is not known.¹⁰⁰ Vaccination against influenza can reduce prevalence of influenza illness and reduce incidence of influenza symptoms that might be confused with COVID-19 symptoms (i.e., fever, cough, dyspnea).¹⁰⁰ In addition, prevention of influenza and reduction in severity of influenza illness and associated outpatient visits, hospitalizations, and intensive care unit admissions could alleviate stress on the US health-care system.¹⁰⁰

Health-care providers should use every opportunity to communicate the importance of influenza vaccination and to administer an age-appropriate influenza vaccine to all eligible individuals for the 2020–2021 influenza season.^{100 583} This includes essential workers (e.g., health-care personnel such as nursing home, long-term care facility, and pharmacy staff, and other critical infrastructure workforce personnel), those at increased risk for severe illness due to COVID-19 (e.g., adults ≥65 years of age, residents in nursing homes or long-term care facilities, individuals with certain underlying medical conditions), and those at high risk for influenza complications (e.g., infants and young children, children with neurologic conditions, pregnant women, adults ≥65 years of age).⁵⁸³

Stay-at-home orders and social distancing strategies aimed at reducing SARS-CoV-2 transmission have led to decreased use of routine preventive medical services, including immunization services.⁵⁸³ Routine vaccination is an essential preventive care service for children, adolescents, and adults (including pregnant women) that should not be delayed because of the COVID-19 pandemic.⁵⁸³ Ensuring that immunization services are maintained or reinitiated is essential for protecting individuals and communities from vaccine-preventable diseases and outbreaks and reducing the burden of respiratory illness during the 2020–2021 influenza season.⁵⁸³ Some settings usually used to provide influenza vaccination (e.g., workplaces) may not be available as a result of strategies used to limit spread of COVID-19⁵⁸¹ and influenza vaccination programs may need to adapt and consider different or additional vaccination strategies for the 2020–2021 influenza season.^{100 583} (See General under Dosage and Administration.)

Guidance for vaccination planning and interim guidance for administering routine immunizations, including influenza vaccine, during the COVID-19 pandemic is available at [Web].⁵⁸³

Influenza Vaccine Recombinant Dosage and Administration

General

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

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

There is some evidence that early influenza vaccination (i.e., in July or August) in individuals requiring only a single dose of influenza vaccine is likely to be associated with suboptimal immunity (waning immunity) before the end of influenza season, particularly in older adults.¹⁰⁰ Community vaccination programs should balance maximizing likelihood of persistence of vaccine-induced protection through the influenza season with avoiding missed opportunities for vaccination or vaccinating after influenza circulation has already started, especially in those ≥65 years of age.¹⁰⁰

Because SARS-CoV-2 (causative agent of COVID-19) is expected to be circulating in the US at the same time influenza viruses are circulating, it is important that health-care providers use every opportunity to communicate the importance of influenza vaccination and to administer an age-appropriate influenza vaccine to all eligible individuals for the 2020–2021 influenza season.^{100 583} (See Influenza Vaccination During the Coronavirus Disease 2019 [COVID-19] Pandemic under Uses.) Some settings usually used to provide influenza vaccination (e.g., workplaces) may not be available as a result of strategies used to limit spread of COVID-19.⁵⁸¹ In addition, organized influenza vaccination programs may need to adapt and consider different or additional vaccination strategies for the 2020–2021 influenza season, including starting vaccination campaigns early to allow sufficient time to vaccinate the population and avoid missed opportunities for influenza vaccination, using alternative vaccination sites (e.g., drive-through, curbside, mobile outreach units, home visits), and extending the duration of vaccination campaigns.^{100 583}

Guidance for vaccination planning and interim guidance for administering routine immunizations, including influenza vaccine, during the COVID-19 pandemic is available at [Web].⁵⁸³

Administration

Administer only by IM injection.¹⁸³ Do not administer sub-Q, intradermally, or IV.¹⁸³

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

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

IM Administration

Administer by IM injection preferably into the deltoid muscle in adults.¹⁸³

To ensure delivery into muscle, make IM injections 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 injection site, and injection technique.¹³⁴

Vaccine should appear clear and colorless;¹⁸³ do not use if it appears discolored or contains particles.¹⁸³

Gently invert single-dose prefilled syringes of the vaccine prior to affixing appropriate size needle.¹⁸³

Do not mix with any other vaccine or solution.¹⁸³

Dosage

Adults

Prevention of Seasonal Influenza A and B Virus Infections

Adults ≥18 Years of Age

IM

Single 0.5-mL dose.¹⁸³

Special Populations

Hepatic Impairment

No specific dosage recommendations.¹⁸³

Renal Impairment

No specific dosage recommendations.¹⁸³

Geriatric Patients

Single 0.5-mL dose.¹⁸³ (See Geriatric Use under Cautions.)

Cautions for Influenza Vaccine Recombinant

Contraindications

• History of severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine.¹⁸³ (See Sensitivity Reactions under Cautions.)

Warnings/Precautions

Sensitivity Reactions

Anaphylaxis, anaphylactoid reactions, allergic reactions, and other forms of hypersensitivity reported during postmarketing experience.¹⁸³

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

Appropriate medical treatment and supervision must be available for immediate use in case an anaphylactic reaction occurs.¹⁸³

Guillain-Barré Syndrome (GBS)

If GBS occurred within 6 weeks after previous influenza vaccination, manufacturer states base decision to administer influenza vaccine recombinant on careful consideration of potential benefits and risks.¹⁸³

The 1976 swine influenza vaccine was associated with increased frequency of GBS.¹⁸³ Evidence for causal relationship between other influenza vaccines and GBS inconclusive;¹⁸³ if an excess risk exists, it probably is slightly more than 1 additional case of GBS per 1 million vaccinees.¹⁸³

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

Individuals with Altered Immunocompetence

May be administered to individuals immunosuppressed as the result of disease or immunosuppressive therapy.¹⁸³ Consider possibility that immune response to the vaccine and efficacy may be reduced in such individuals.^{100 134 183}

ACIP states that recombinant vaccines can be administered safely to individuals with altered immunocompetence.¹³⁴

HIV-infected adults: Use influenza virus vaccine inactivated or influenza vaccine recombinant (not influenza vaccine live intranasal).^{100 155}

Individuals with Bleeding Disorders

Advise individuals who have bleeding disorders or are receiving anticoagulant therapy and/or their family members about the risk of hematoma from IM injections.¹³⁴

ACIP states that IM vaccines may be given to individuals who have bleeding disorders or are receiving anticoagulant therapy if a clinician familiar with the patient’s bleeding risk determines that the IM injection 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 injection site (without rubbing) for ≥2 minutes.¹³⁴ In individuals receiving therapy for hemophilia, give IM vaccine shortly after a scheduled dose of such therapy.¹³⁴

Concomitant Illness

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

ACIP states mild acute illness generally does not preclude vaccination.¹³⁴

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

Individuals with Coronavirus Disease 2019 (COVID-19)

CDC states defer influenza vaccination in individuals with suspected or confirmed COVID-19, regardless of symptoms, until criteria for discontinuance of COVID-19 isolation have been met.⁵⁸³ Although mild illness usually not considered a contraindication to vaccination, postpone vaccination in such individuals with suspected or confirmed COVID-19 to avoid exposing health-care personnel and other patients to the disease.⁵⁸³

Limitations of Vaccine Effectiveness

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

May not protect all vaccine recipients from influenza.¹⁸³

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

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

Seasonal influenza vaccines will not provide protection against COVID-19.⁵⁸¹

Duration of Immunity

Immunity declines during the year after seasonal influenza vaccination.¹⁰⁰ In addition, circulating strains of seasonal influenza virus change from year to year.¹⁰⁰ Annual vaccination is needed for prevention of seasonal influenza.¹⁰⁰

Do not administer influenza vaccine from a previous influenza season (e.g., 2019–2020) in an attempt to provide protection during a subsequent influenza season.¹⁰⁰

Improper Storage and Handling

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

Inspect all vaccines upon delivery and monitor during storage to ensure that the appropriate temperature is maintained.¹³⁴ (See Storage under Stability.)

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

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

Specific Populations

Pregnancy

Manufacturer states data insufficient to assess risk of influenza vaccine recombinant in pregnant women.¹⁸³

ACIP, ACOG, AAP, and others recommend vaccination against influenza in all women who are pregnant or who might become pregnant during the influenza season and state that any licensed, age-appropriate, inactivated influenza vaccine (i.e., influenza virus vaccine inactivated or influenza vaccine recombinant) can be used.^{100 112} These experts state that inactivated influenza vaccines can be administered at any time during pregnancy (any trimester) before or during influenza season.^{100 112 134}

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

Pregnancy registry at 800-822-2463.¹⁸³ Clinicians or vaccinees should report any exposure to the vaccine that occurs during pregnancy.¹⁸³

Lactation

Not known whether influenza vaccine recombinant is distributed into milk.¹⁸³ Data insufficient to assess effects on breast-fed infant or on milk production.¹⁸³

Consider benefits of breast-feeding and importance of the vaccine to the woman;¹⁸³ also consider potential adverse effects on the breast-fed child from the vaccine or underlying maternal condition (i.e., susceptibility to influenza infection).¹⁸³

ACIP states recombinant vaccines do not pose any unusual risks for women who are breast-feeding or their breast-fed infants.¹³⁴

Pediatric Use

Safety and efficacy not established in individuals <18 years of age.¹⁸³

Study using trivalent influenza vaccine recombinant (no longer available in US) indicates recombinant vaccine may not be effective in children <3 years of age†.¹⁸³

Geriatric Use

Insufficient experience using influenza vaccine recombinant in adults ≥65 years of age to determine whether geriatric patients respond differently than younger adults.¹⁸³

ACIP states use influenza virus vaccine inactivated or influenza vaccine recombinant in adults ≥65 years of age.(r100)

Common Adverse Effects

Adults ≥18 years of age: Injection site reactions (e.g., local tenderness, pain), headache, fatigue, myalgia, arthralgia.¹⁸³

Interactions for Influenza Vaccine Recombinant

Immunosuppressive Agents

Immune responses to vaccines may be reduced in individuals receiving immunosuppressive agents.^{134 183}

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

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

Vaccines

Although specific studies may not be available,¹⁸³ ACIP states influenza vaccine recombinant may be administered concurrently or sequentially with other age-appropriate vaccines, including live virus vaccines, toxoids, or inactivated or recombinant vaccines.^{100 134}

Specific Drugs

Stability

Storage

Parenteral

Injectable Solution, for IM Use

2–8°C; do not freeze.¹⁸³ If freezing occurs, discard vaccine.¹⁸³

Protect from light.¹⁸³

Does not contain thimerosal or any other preservatives.¹⁸³

Actions

• Influenza vaccine recombinant contains recombinant hemagglutinin (HA) proteins from suitable strains of influenza viruses.¹⁸³ The vaccine is prepared using recombinant DNA technology and a continuous insect cell line (expresSF+) derived from Sf9 cells of the fall armyworm (Spodoptera frugiperda) and a baculovirus vector.¹⁸³ Manufacturing process does not involve live influenza viruses and does not involve eggs.¹⁸³

• Seasonal influenza vaccines are formulated annually to contain antigens representative of the influenza A (H1N1), influenza A (H3N2), and influenza B viruses likely to circulate during the upcoming influenza season.¹⁰⁰

• Influenza vaccines for the 2020–2021 influenza season contain different influenza A (H1N1), influenza A (H3N2), and influenza B (B/Victoria lineage) antigens, but the same influenza B (B/Yamagata lineage) antigen, contained in vaccines used for the 2019–2020 influenza season.^{100 581}

• Influenza vaccines stimulate active immunity to influenza virus strains represented in the vaccines.^{100 183}

• Following IM administration of influenza vaccine recombinant, the recombinant HA proteins contained in the vaccine act as antigens and induce a humoral immune response that can be measured by HA inhibition antibody.¹⁸³

• Following a single IM dose of trivalent influenza vaccine recombinant (no longer available in US) in adults 18 through 49 years of age during the 2007–2008 influenza season, an immune response to the H1N1, H3N2, and B components of the vaccine was achieved in 78, 81, and 52% of vaccine recipients, respectively;²³³ estimated vaccine effectiveness was 75% against influenza strains that closely matched vaccine strains and 45% without regard to match (96% of isolates did not match vaccine strains).²³³ In adults ≥50 years of age, antibody responses at 28 days after a single IM dose of trivalent influenza vaccine recombinant met predefined success criterion for all 3 vaccine antigens when compared with a single IM dose of trivalent influenza vaccine inactivated.²³⁴

• Immune response to a single IM dose of quadrivalent influenza vaccine recombinant in adults 18 through 49 years of age during the 2014–2015 influenza season met the success criterion for GMTs for 3 of the 4 antigens, but not the B/Victoria lineage antigen;¹⁸³ however, HI response to the B/Victoria lineage antigen also was low in the active-control group that received quadrivalent influenza virus vaccine inactivated.¹⁸³ In a study in adults ≥50 years of age during the 2014–2015 influenza season, quadrivalent influenza vaccine recombinant was noninferior to standard-dose quadrivalent influenza virus vaccine inactivated.^{183 574}

• Efficacy of influenza vaccines in preventing seasonal influenza virus infection depends on whether the virus strains represented in the vaccines are antigenically similar to influenza virus strains circulating during the influenza season.^{100 166} (See Limitations of Vaccine Effectiveness under Cautions.)

Advice to Patients

• Prior to administration of seasonal influenza vaccine recombinant, provide a copy of the appropriate CDC Vaccine Information Statement (VIS) to the patient or patient’s legal representative (VISs are available at [Web]).^{183 477}

• Advise patient of the risks and benefits of influenza vaccine recombinant.¹⁸³

• Advise patient that influenza vaccine recombinant contains noninfectious proteins that cannot cause influenza.¹⁸³

• Advise patient that annual vaccination against seasonal influenza is necessary.^{100 183} Importance of receiving a 2020–2021 seasonal influenza vaccine, even if the individual received a 2019–2020 seasonal influenza vaccine.^{100 183}

• Advise patient that influenza vaccine recombinant provides protection against illness due to influenza viruses represented in the vaccine and cannot provide protection against all respiratory illness.¹⁸³

• Importance of informing clinicians of any severe or life-threatening allergies, including any history of severe reaction after prior influenza vaccination.¹⁸³

• Importance of informing clinicians of adverse effects.¹⁸³ Clinicians or individuals can report any adverse reactions that occur following vaccination to the Vaccine Adverse Event Reporting System (VAERS) at 800-822-7967 or [Web].^{100 183}

• Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses (e.g., GBS).¹⁸³

• Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.¹⁸³

• Importance of informing patients of other important precautionary information.¹⁸³ (See Cautions.)

Preparations

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

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

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