Influenza Vaccine Recombinant

Class: Vaccines
VA Class: IM100
Brands: Flublok

Introduction

Recombinant influenza vaccine.¹ Seasonal influenza vaccine recombinant 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.^{1 558 561}

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.^{1 558}

Influenza is an acute viral infection; influenza viruses spread from person to person mainly through large-particle respiratory droplet transmission.^{100 105 166} 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.^{100 105 166} Influenza can exacerbate underlying medical conditions or lead to pneumonia in certain individuals.^{100 105 166} 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.^{100 105 166}

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, and infants and children ≥6 months of age using an age-appropriate seasonal influenza vaccine, unless contraindicated.^{112 199 200 235 558} 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.^{100 112}

For the 2015–2016 influenza season, 3 different types of influenza vaccines are commercially available in the US for prevention of seasonal influenza: parenteral inactivated influenza vaccine (IIV),^{103 104 106 107 186 187 189 190 558} intranasal live attenuated influenza vaccine (LAIV),^{157 558} and parenteral recombinant influenza vaccine (RIV).^{1 558} Some of these are available as trivalent formulations containing 2 influenza A antigens and a single influenza B antigen^{1 103 160 186 187 189 190 558} and some are available as quadrivalent formulations containing 2 influenza A antigens and 2 influenza B antigens.^{104 106 107 157 161 558}

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 (e.g., egg allergy).^{100 112 558} For many individuals, more than one vaccine type may be appropriate.^{100 112 558}

ACIP and AAP state 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.^{100 112} In addition, these experts do not state a preference for a trivalent or quadrivalent formulation for the 2015–2016 influenza season.^{112 558} If an age-appropriate vaccine is available and there are no contraindications, do not delay influenza vaccination to obtain a specific product.^{112 558}

Because influenza vaccine recombinant contains recombinant HA proteins (not attenuated, live influenza viruses), it can be used in age-appropriate individuals (i.e., adults ≥18 years of age) who cannot receive the intranasal live vaccine (e.g., pregnant women, individuals with underlying medical conditions that may predispose them to severe disease following influenza infection, individuals immunocompromised because of disease or immunosuppressive therapy, individuals caring for severely compromised individuals).¹⁰⁰ In addition, the recombinant vaccine is egg-free^{1 112 558} and can be used in age-appropriate individuals (i.e., adults ≥18 years of age) who have a history of any degree of egg allergy, including those who have had severe reactions after eating eggs or egg-containing foods.^{112 558}

Travelers (including those at high risk for influenza complications) who were not vaccinated during the preceding fall or winter should receive seasonal influenza vaccine ≥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 tropical and subtropical areas, influenza viruses usually circulate throughout the year, but influenza activity may peak during rainy or dry seasons.¹¹⁵

Safety and efficacy of seasonal influenza vaccine recombinant not established in children or adolescents <18 years of age;¹ use age-appropriate parenteral inactivated seasonal influenza vaccine^{103 104 106 107 186 187 189 190 199 200 558} or age-appropriate intranasal live influenza vaccine in this age group.^{157 199 200 558}

Seasonal influenza vaccines not effective against all strains of influenza, but may be effective against those strains (and possibly closely related strains) represented in the vaccines.^{100 166}

Seasonal influenza vaccines for the 2015–2016 influenza season are expected to provide protection against the influenza A (H1N1)pdm09 virus and influenza A (H3N2) and influenza B viruses represented in the vaccines.^{112 558 561}

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

Influenza Vaccine Recombinant Dosage and Administration

Administration

IM Injection

Administer by IM injection, preferably into deltoid.¹ Do not administer IV, sub-Q, or intradermally.¹

Shake vaccine vial gently before withdrawing dose.¹ Vaccine should appear clear and colorless.¹

To ensure delivery into muscle, make IM injections at a 90° angle to the skin using a needle length appropriate for individual's age and body mass.¹³⁴

Do not mix with any other vaccine or solution.¹

Administer seasonal influenza vaccine every year before exposure to seasonal influenza.⁵⁵⁸ In the US, localized outbreaks indicating start of the annual influenza season can occur as early as October;^{100 112} peak influenza activity usually occurs in January and February, but has occurred in March, April, or May.¹⁶⁶

Offer influenza vaccination by October, if possible, and continue to offer vaccination as long as influenza viruses are circulating.⁵⁵⁸

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

Dosage

Adults

Prevention of Seasonal Influenza A and B Virus Infections

Adults ≥18 Years of Age

IM

Single 0.5-mL dose.¹

Special Populations

Hepatic Impairment

No specific dosage recommendations.¹

Renal Impairment

No specific dosage recommendations.¹

Geriatric Patients

Single 0.5-mL dose.¹ (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.¹ (See Sensitivity Reactions under Cautions.)

Warnings/Precautions

Sensitivity Reactions

Anaphylaxis, anaphylactoid reactions, allergic reactions, and other forms of hypersensitivity reported during postmarketing experience.¹

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.^{100 112}

Appropriate medical treatment and supervision must be available for immediate use in case an anaphylactic reaction occurs.¹

Guillain-Barré Syndrome (GBS)

If GBS occurred within 6 weeks after previous influenza vaccination, manufacturer states base decision to administer influenza vaccine on careful consideration of potential benefits and risks.¹

Unclear whether influenza vaccination increases risk of recurrence of GBS.¹⁰⁰ Temporal association was noted between administration of 1976 swine influenza vaccine and GBS.^{1 100} 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).^{1 100}

ACIP states that, as a precaution, individuals who are not at high 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 high 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.¹ Consider possibility that immune response to the vaccine and efficacy may be reduced in these individuals.¹

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.¹

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.^{1 100 558 561} 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}

Influenza vaccine recombinant for the 2015–2016 influenza season is expected to provide protection against influenza A (H1N1)pdm09 virus and influenza A (H3N2) and influenza B strains represented in the vaccine.^{1 100 112 558 561}

Concomitant Illness

Delay administration in individuals with moderate to severe acute illness (with or without fever) until symptoms have subsided.¹³⁴

ACIP states that mild diarrhea or mild upper respiratory tract illness or other acute illness (with or without fever) does not preclude vaccination.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 vaccines may be given IM to such individuals if a clinician familiar with the patient's bleeding risk determines that the 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 If patient is receiving antihemophilia therapy, administer the IM vaccine shortly after a scheduled dose of such therapy.¹³⁴

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

Category B.¹

Manufacturer states use in pregnant women only when clearly needed.¹

Pregnancy registry at 888-855-7871.¹ Clinicians or vaccinees should report any exposure to the vaccine that occurs during pregnancy.¹

Lactation

Not known whether influenza vaccine recombinant is distributed into milk.¹ Manufacturer recommends caution.¹

Pediatric Use

Safety and efficacy not established in children or adolescents <18 years of age.¹

Some evidence that influenza vaccine recombinant may not be effective in children <3 years of age†.¹

Geriatric Use

Some evidence that antibody responses are lower in adults ≥65 years of age compared with younger adults.¹

Common Adverse Effects

Adults ≥18 years of age: Injection site reactions (e.g., pain), headache, fatigue, myalgia.¹

Interactions for Influenza Vaccine Recombinant

Immunosuppressive Agents

Immune response may be decreased in individuals receiving immunosuppressive agents.¹

Vaccines

Safety and immunogenicity of influenza vaccine recombinant administered concomitantly with age-appropriate inactivated or live vaccines not specifically studied.¹

Stability

Storage

Parenteral

Injectable Solution, for IM Use

2–8°C; do not freeze.¹ If freezing occurs, discard vaccine.¹

Protect from light.¹

Does not contain thimerosal or any other preservatives.¹

Actions

• Influenza vaccine recombinant contains recombinant hemagglutinin (HA) proteins from 3 suitable strains of influenza viruses.¹ 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.¹ Manufacturing process does not involve live influenza viruses or eggs.¹

• 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.^{1 561} For the 2015–2016 season, antigenic components recommended by FDA for US formulations of seasonal influenza vaccines are the same as those recommended by WHO (Northern Hemisphere).^{561 562}

• Influenza vaccine recombinant for the 2015–2016 influenza season is a trivalent vaccine containing 2 influenza type A antigens (H1N1 and H3N2) and a single influenza type B antigen (B/Yamagata lineage).^{1 558} The 2015–2016 seasonal recombinant influenza vaccine for the US contains A/California/7/2009 (H1N1), A/Switzerland/9715293/2013 (H3N2), and B/Phuket/3073/2013 (B/Yamagata lineage) HA antigens.¹

• Influenza vaccines stimulate active immunity to influenza virus strains represented in the vaccines.¹

• 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.¹

• 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).^{1 100 233} 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.¹

• 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}

• Seasonal influenza vaccines for the 2015–2016 influenza season are expected to provide protection against the influenza A (H1N1)pdm09 virus and influenza A (H3N2) and influenza B strains represented in the vaccines.^{112 558 561} (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 ).^{1 477}

• Advise patient of the risks and benefits of vaccine administration.¹

• Advise patient that influenza vaccine recombinant contains noninfectious proteins that cannot cause influenza.¹

• Advise patient that annual vaccination against seasonal influenza is necessary.^{1 558} Importance of receiving a 2015–2016 seasonal influenza vaccine, even if the individual received a 2014–2015 seasonal influenza vaccine.^{100 112}

• 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.¹

• Importance of informing clinicians of any severe or life-threatening allergies, including any history of severe reaction after prior influenza vaccination.¹

• Importance of informing clinicians of adverse effects.¹ 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 .^{1 100}

• Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant medical problems (e.g., Guillain-Barré syndrome).¹

• Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.¹

• Importance of informing patients of other important precautionary information.¹ (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 (2015–2016)

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection, for IM use	45 mcg recombinant hemagglutinin each of A/California/7/2009 (H1N1), A/Switzerland/9715293/2013 (H3N2), and B/Phuket/3073/2013 per 0.5 mL	Flublok	Protein Sciences