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Influenza Vaccine Recombinant

Class: Vaccines
VA Class: IM100
Brands: Flublok

Medically reviewed by Drugs.com on Oct 18, 2021. Written by ASHP.

Warning

Special Alerts:

On October 15, 2021, the National Alert Network (NAN) issued an alert to make vaccine providers aware of reports of accidental mix-ups between the influenza (flu) and COVID-19 vaccines. The alert is based on 16 cases reported to the Institute for Safe Medication Practices (ISMP) error reporting programs. Most of the reports ISMP has received involve administration of one of the COVID-19 vaccines instead of an influenza vaccine; in 3 cases, patients received an influenza vaccine instead of a COVID-19 vaccine.

Because most of the errors were reported by consumers, details about the contributing factors were not provided in many cases. However, possible contributing factors include increased demand for vaccination services, the ability to administer the flu and COVID-19 vaccines during the same visit, syringes located next to each other, unlabeled syringes, distractions, and staffing shortages. The alert provides recommendations for preventing such vaccine mix-ups. For additional information, consult the NAN alert at [Web].

Introduction

Recombinant influenza vaccine. 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.

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.

Influenza is an acute viral infection; influenza viruses spread from person to person mainly through large-particle respiratory droplet transmission. In the US, annual epidemics of seasonal influenza occur, usually during the fall or winter. Influenza viruses can cause illness in any age group; children have highest rate of infection. Influenza can exacerbate underlying medical conditions or lead to pneumonia in certain individuals. 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.

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

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. 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.

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). 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).

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. For many individuals, more than one vaccine type may be appropriate.

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. If an age-appropriate vaccine is available and there are no contraindications, do not delay influenza vaccination to obtain a specific product.

Travelers: All unvaccinated travelers who want to reduce their risk for influenza should consider vaccination against seasonal influenza, preferably ≥2 weeks before travel. Revaccination not recommended in those who received influenza vaccine during the fall and will be traveling during the summer. Risk for exposure to seasonal influenza during travel depends on time of year and destination. In temperate climate regions, influenza activity is seasonal, typically occurring during colder winter months (i.e., October to May in Northern Hemisphere and April to September in Southern Hemisphere). In the tropics, influenza can occur throughout the year. Additional information on influenza vaccination for travelers and risk of exposure to influenza during travel is available at [Web].

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. (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 upcoming (current) 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. SARS-CoV-2 (causative agent of COVID-19) is expected to circulate in the US during the influenza season; the extent of continued or recurrent SARS-CoV-2 circulation during the time influenza viruses are circulating is not known. 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). 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.

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. This includes essential workers (e.g., staff at post-acute or long-term care facilities, 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 post-acute or long-term care facilities, individuals with certain underlying medical conditions), and those at high risk for influenza complications (e.g., infants ≥6 months of age, young children, children with neurologic conditions, pregnant women, adults ≥65 years of age, individuals with certain underlying medical conditions).

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. 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. 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 influenza season. 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 and influenza vaccination programs may need to adapt and consider different or additional vaccination strategies. (See General under Dosage and Administration.)

CDC recommends deferring influenza vaccination in symptomatic individuals with suspected or confirmed COVID-19 and asymptomatic and presymptomatic individuals who have tested positive for SARS-CoV-2. (See Individuals with Known or Suspected Coronavirus Disease 2019 [COVID-19] under Cautions.)

Guidance for influenza vaccination during the COVID-19 pandemic for individuals in health-care facilities and congregate settings is available from CDC at [Web].

Influenza Vaccine Recombinant Dosage and Administration

General

Administer seasonal influenza vaccine every year before exposure to seasonal influenza. 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.

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. 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.

There is 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. 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.

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 upcoming (current) influenza season. (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. In addition, organized influenza vaccination programs may need to adapt and consider different or additional vaccination strategies, 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.

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

Administration

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

Syncope (vasovagal or vasodepressor reaction; fainting) may occur following vaccination; such reactions occur most frequently in adolescents and young adults. 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). If syncope occurs, observe patient until symptoms resolve.

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

IM Administration

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

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.

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

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

Do not mix with any other vaccine or solution.

Dosage

Adults

Prevention of Seasonal Influenza A and B Virus Infections
Adults ≥18 Years of Age
IM

Single 0.5-mL dose.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

Single 0.5-mL dose. (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.

  • History of severe allergic reactions (e.g., anaphylaxis) to a previous dose of any recombinant influenza vaccine (quadrivalent or trivalent formulation).

Warnings/Precautions

Sensitivity Reactions

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

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

ACIP states that a history of severe allergic reaction (e.g., anaphylaxis) to any other type of influenza vaccine (egg-based influenza virus vaccine inactivated, cell culture-based influenza vaccine inactivated, influenza vaccine live intranasal) is a precaution to use of influenza vaccine recombinant. If influenza vaccine recombinant used in an individual with such a history, administer the vaccine in an inpatient or outpatient medical setting supervised by a health-care provider able to recognize and manage severe allergic reactions. Consider consultation with an allergist to help identify the vaccine component responsible for the prior reaction.

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.

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

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; clinicians might consider use of antiviral prophylaxis for such individuals. 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.

Individuals with Altered Immunocompetence

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

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

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.

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. 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. In individuals receiving therapy for hemophilia, give IM vaccine shortly after a scheduled dose of such therapy.

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.

ACIP states mild acute illness generally does not preclude vaccination.

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

Individuals with Known or Suspected Coronavirus Disease 2019 (COVID-19)

CDC states defer routine vaccinations, including influenza vaccination, in symptomatic individuals with suspected or confirmed COVID-19 until criteria for discontinuance of COVID-19 isolation have been met and the individual is no longer moderately or severely ill. Consider deferring vaccination until the individual has fully recovered from the acute illness to avoid exposing health-care personnel and other patients to the disease.

CDC states defer routine vaccinations, including influenza vaccination, in asymptomatic and presymptomatic individuals who have tested positive for SARS-CoV-2 until criteria for discontinuance of COVID-19 isolation have been met.

Individuals who are not considered fully vaccinated against COVID-19 and have a known exposure to an individual with COVID-19 should not seek outpatient care solely for routine vaccination, including influenza vaccination, until criteria for discontinuance of COVID-19 isolation have been met.

Guidance for influenza vaccination during the COVID-19 pandemic for individuals in various health-care facilities and congregate settings is available at [Web].

Limitations of Vaccine Effectiveness

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

May not protect all vaccine recipients from influenza.

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. (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.

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]).

Seasonal influenza vaccines will not provide protection against COVID-19.

Duration of Immunity

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

Do not administer influenza vaccine from a previous influenza season in an attempt to provide protection during a subsequent influenza season.

Improper Storage and Handling

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

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

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

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; also can consult CDC.

Specific Populations

Pregnancy

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

Pregnant and postpartum women are at higher risk for severe influenza and complications from influenza, particularly during second and third trimesters.

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. These experts state that inactivated influenza vaccines can be administered at any time during pregnancy before or during influenza season. Encourage postpartum women who did not receive influenza vaccination during pregnancy to receive vaccination (e.g., before hospital discharge).

Pregnancy registry at 800-822-2463. Clinicians or vaccinees should report any exposure to the vaccine that occurs during pregnancy.

Lactation

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

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

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

Pediatric Use

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

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

Geriatric Use

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

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

Common Adverse Effects

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

Interactions for Influenza Vaccine Recombinant

Immunosuppressive Agents

Immune responses to vaccines may be reduced in individuals receiving immunosuppressive agents.

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.

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.

Vaccines

Although specific studies may not be available, 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.

Specific Drugs

Drug

Interaction

Comments

Antivirals active against influenza (baloxavir, oseltamivir, peramivir, zanamivir)

No effect on immune response to inactivated vaccines, including influenza vaccine recombinant

Influenza vaccine recombinant may be given to individuals receiving an influenza antiviral

COVID-19 vaccines

Data not available to date regarding concomitant administration of COVID-19 vaccines with other vaccines; not known whether reactogenicity of COVID-19 vaccines is increased if administered concomitantly with other vaccines, including those known to be more reactogenic (e.g., adjuvanted vaccines, live vaccines)

Influenza vaccine recombinant may be administered concurrently with or at any interval before or after COVID-19 vaccines

Base decisions to administer a COVID-19 vaccine concomitantly with other vaccine(s) on whether routine vaccination with the other vaccines has been delayed or missed, the individual's risk of vaccine-preventable disease (e.g., during an outbreak or occupational exposures), and reactogenicity profiles of the vaccines

Stability

Storage

Parenteral

Injectable Solution, for IM Use

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

Protect from light.

Does not contain thimerosal or any other preservatives.

Actions

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

  • 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.

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

  • 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.

  • 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; 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). 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.

  • 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; however, HI response to the B/Victoria lineage antigen also was low in the active-control group that received quadrivalent influenza virus vaccine inactivated. 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.

  • 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. (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]).

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

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

  • Advise patient that annual vaccination against seasonal influenza is necessary. Importance of receiving influenza vaccine for the upcoming (current) influenza season, even if the individual received influenza vaccine for the previous influenza season.

  • 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.

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

  • Importance of informing clinicians of adverse effects. 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].

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

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

  • Importance of informing patients of other important precautionary information. (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

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IM use

45 mcg recombinant hemagglutinin each of FDA-specified influenza A (H1N1), influenza A (H3N2), influenza B/Victoria lineage, and influenza B/Yamagata lineage antigens per 0.5 mL

Flublok Quadrivalent

Sanofi Pasteur

AHFS DI Essentials™. © Copyright 2022, Selected Revisions October 18, 2021. 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.

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