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Influenza Vaccine Recombinant

Class: Vaccines
VA Class: IM100
Brands: Flublok

Medically reviewed on Nov 19, 2018

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.100 183 575

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.100 183

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

US Public Health Service 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.100 112 199 200 235 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

For the 2018–2019 influenza season, 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 Influenza virus vaccine inactivated is available as trivalent formulations containing influenza antigens representing 2 influenza A strains (H1N1 and H3N2) and an influenza B strain (Victoria lineage) and quadrivalent formulations containing antigens representing these 3 influenza strains and another influenza B strain (Yamagata lineage).100 Influenza vaccine recombinant and influenza vaccine live intranasal are only available as quadrivalent formulations.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

For prevention of seasonal influenza in adults ≥18 years of age, 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 In addition, ACIP does not state a preference for a trivalent or quadrivalent formulation for the 2018–2019 influenza season.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 during the preceding fall or winter should consider vaccination against seasonal influenza ≥2 weeks before departure if they will be traveling to the tropics, traveling to the Southern Hemisphere from April through September, or traveling with organized tourist groups at any time of the year.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 the Northern Hemisphere, influenza season may begin as early as October and extend until May;115 in the Southern Hemisphere, influenza season may begin in April and last through September.115 In many tropical and subtropical areas, influenza viruses generally circulate throughout the year.115

Seasonal influenza vaccines not effective against all possible strains of influenza, but may be effective against those 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 Vaccine Recombinant Dosage and Administration

Administration

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

Administer seasonal influenza vaccine every year before exposure to seasonal influenza.100 112 In the US, localized outbreaks indicating start of the annual influenza season can occur as early as October;100 112 peak influenza activity (which often is close to the midpoint of influenza activity for the season) usually occurs in January through March;100 112 and influenza activity can continue until late spring (end of May).112

Offer influenza vaccination by the end of October, if possible, and continue to offer vaccination as long as influenza viruses are circulating and unexpired vaccine is available.100 112 To avoid missed opportunities for vaccination, offer influenza vaccination to unvaccinated individuals during routine health-care visits and hospitalizations when vaccine is available.100 Although vaccination in the fall 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

Syncope (vasovagal or vasodepressor reaction; fainting) may occur following vaccination; such reactions occur most frequently in adolescents and young adults.134 Syncope and secondary injuries may be averted if 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

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

Temporal association was noted between administration of 1976 swine influenza vaccine and GBS.100 183 Investigations to date suggest no large increase in GBS associated with influenza vaccine (other than 1976 swine influenza vaccine) and if influenza vaccine does pose a risk it probably is quite small (i.e., approximately 1 additional case of GBS per 1 million vaccinees).100 183

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 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 generally can be administered safely to individuals with altered immunocompetence.134

Recommendations for use of recombinant vaccines in HIV-infected individuals usually the same as those for individuals without HIV infection.100 155

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 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 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 the 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

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.100 575 Efficacy of seasonal 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

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., 2017–2018) 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

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 generally 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 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

Common Adverse Effects

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

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.100 183 575 For the 2018–2019 season, antigenic components recommended by FDA for US formulations of seasonal influenza vaccines are the same as those recommended by WHO (Northern Hemisphere).575 576

  • For the 2018–2019 influenza season, influenza vaccine recombinant for the US is a quadrivalent vaccine containing A/Michigan/45/2015 (H1N1), A/Singapore/INFIMH-16-0019/2016 (H3N2), B/Maryland/15/2016 (B/Victoria lineage), and B/Phuket/3073/2013 (B/Yamagata lineage) HA antigens.183 575

  • Influenza vaccines stimulate active immunity to influenza virus strains represented in the vaccines.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 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 2018–2019 seasonal influenza vaccine, even if the individual received a 2017–2018 seasonal influenza vaccine.100 112 183

  • 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.

Influenza Vaccine Recombinant Quadrivalent (2018–2019)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IM use

45 mcg recombinant hemagglutinin each of A/Michigan/45/2015 (H1N1), A/Singapore/INFIMH-16-0019/2016 (H3N2), B/Maryland/15/2016, and B/Phuket/3073/2013 per 0.5 mL

Flublok Quadrivalent

Sanofi Pasteur

AHFS DI Essentials™. © Copyright 2018, Selected Revisions November 19, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

100. Grohskopf LA, Sokolow LZ, Broder KR et al. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices-United States, 2018-19 Influenza Season. MMWR Recomm Rep. 2018; 67:1-20. http://www.ncbi.nlm.nih.gov/pubmed/30141464?dopt=AbstractPlus

105. American Academy of Pediatrics. Red Book: 2015 Report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015.

112. Committee on Infectious Diseases. Recommendations for Prevention and Control of Influenza in Children, 2018-2019. Pediatrics. 2018; http://www.ncbi.nlm.nih.gov/pubmed/30177511?dopt=AbstractPlus

115. Centers for Disease Control and Prevention. CDC health information for international travel, 2018. Atlanta, GA: US Department of Health and Human Services. Updates may be available at CDC website. http://wwwnc.cdc.gov/travel/page/yellowbook-home

134. Kroger AT, Duchin J, Vazquez M. General best practice guidelines for immunization. Best practices guidance of the Advisory Committee on Immunization Practices (ACIP). From CDC website. Accessed 2018 Aug 15. Updates may be available at CDC website. https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/downloads/general-recs.pdf

135. Rubin LG, Levin MJ, Ljungman P et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014; 58:309-18. http://www.ncbi.nlm.nih.gov/pubmed/24421306?dopt=AbstractPlus

155. Panel on Opportunistic Infection in HIV-infected Adults and Adolescents, US Department of Health and Human Services (HHS). Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Accessed August 1, 2018. Updates may be available at HHS AIDS Information (AIDSinfo) website. http://www.aidsinfo.nih.gov

166. Centers for Disease Control and Prevention. Epidemiology and prevention of vaccine-preventable diseases. 13th ed. Washington DC: Public Health Foundation; 2015. Updates may be available at CDC website. http://www.cdc.gov/vaccines/pubs/pinkbook/flu.html

183. Sanofi Pasteur. Flublok Quadrivalent (influenza vaccine 2018–2019 formula) sterile solution for intramuscular injection prescribing information. Bridgewater, NJ;; 2018 Jun.

199. Centers for Disease Control and Prevention. Advisory Committee on Immunization Practices (ACIP) recommended immunization schedules for children and adolescents aged 18 years or younger, United States, 2018. Updates may be available at CDC website. http://www.cdc.gov/vaccines/schedules/index.html

200. Centers for Disease Control and Prevention. Recommended immunization schedule for adults aged 19 years or older, United States, 2018. Updates may be available at CDC website. http://www.cdc.gov/vaccines/schedules/index.html

233. Treanor JJ, El Sahly HM, King J, et al. Protective efficacy of a trivalent, insect cell-expressed, recombinant hemagglutinin protein vaccine (FluBlok) against culture confirmed influenza in healthy adults: a randomized, placebo-controlled trial. Vaccine. 2011; 29 (44): 7733-9. http://www.ncbi.nlm.nih.gov/pubmed/21835220?dopt=AbstractPlus

234. Baxter R, Patriarca PA, Ensor K et al. Evaluation of the safety, reactogenicity and immunogenicity of FluBlok trivalent recombinant baculovirus-expressed hemagglutinin influenza vaccine administered intramuscularly to healthy adults 50-64 years of age. Vaccine. 2011; 29:2272-8. http://www.ncbi.nlm.nih.gov/pubmed/21277410?dopt=AbstractPlus

235. Advisory Committee on Immunization Practices, Centers for Disease Control and Prevention (CDC). Immunization of health-care personnel: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011; 60(RR-7):1-45.

470. US Food and Drug Administration. FDA approves first U.S. vaccine for humans against the avian influenza virus H5N1. April 19, 2007. From FDA web site. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm108892.htm

477. Centers for Disease Control and Prevention. Influenza vaccine (flu vaccine, inactivated or recombinant) vaccine information statement. 2015 Aug 7. From CDC website. http://www.cdc.gov/vaccines/hcp/vis/vis-statements/flu.pdf

574. Dunkle LM, Izikson R, Patriarca P et al. Efficacy of Recombinant Influenza Vaccine in Adults 50 Years of Age or Older. N Engl J Med. 2017; 376:2427-2436. http://www.ncbi.nlm.nih.gov/pubmed/28636855?dopt=AbstractPlus

575. Garten R, Blanton L, Elal AIA et al. Update: Influenza Activity in the United States During the 2017-18 Season and Composition of the 2018-19 Influenza Vaccine. MMWR Morb Mortal Wkly Rep. 2018; 67:634-642. http://www.ncbi.nlm.nih.gov/pubmed/29879098?dopt=AbstractPlus

576. World Health Organization. Recommended composition of influenza virus vaccines for use in the 2018–2019 northern hemisphere influenza season. Wkly Epidemiol Rec. 2018; 93:133-41. http://www.ncbi.nlm.nih.gov/pubmed/29569429?dopt=AbstractPlus

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