b'FASENRA (benralizumab) injection, for subcutaneous use 4 FASENRA (benralizumab) injection, for subcutaneous use 2Initial U.S. Approval: 2017 Injectallofthemedicationbypushingin Brief Summary of Prescribing Information. For complete prescribing information consultthe plunger all the way until the plunger 28-Week TrialLactation official package insert.head is completely between the needle guardAdversereactionsfromTrial3with28weeksoftreatmentwithFASENRA(n=73)orplaceboRisk Summaryactivation clips. This is necessary to activate (n=75)inwhichtheincidencewasmorecommoninFASENRAthanplaceboinclude INDICATIONS AND USAGEthe needle guard. headache (8.2% compared to 5.3%, respectively) and pyrexia (2.7% compared to 1.3%,Thereisnoinformationregardingthepresenceofbenralizumabinhumanoranimalmilk,andFASENRA is indicated for the add-on maintenance treatment of patients with severe asthmarespectively) [see Clinical Studies (14) in the full Prescribing Information]. The frequenciestheeffectsofbenralizumabonthebreastfedinfantandonmilkproductionarenotknown.aged 12 years and older, and with an eosinophilic phenotype [see Clinical Studies (14) in thefortheremainingadversereactionswithFASENRAweresimilartoplacebo. However,benralizumabisahumanizedmonoclonalantibody(IgG1/-class), and immuno-full Prescribing Information]. globulinG(IgG)ispresentinhumanmilkinsmallamounts.Ifbenralizumabistransferred Limitations of use: 5 Injectionsitereactionsinto human milk, the effects of local exposure in the gastrointestinal tract and potential Afterinjection,maintainpressureontheInTrials1and2,injectionsitereactions(e.g.,pain,erythema,pruritus,papule)occurred limitedsystemicexposureintheinfanttobenralizumabareunknown.Thedevelopmentaland FASENRAisnotindicatedfortreatmentofothereosinophilicconditions. plunger head and remove the needle from theat a rate of 2.2% in patients treated with FASENRA compared with 1.9% in patients treatedhealthbenefitsofbreastfeedingshouldbeconsideredalongwiththemothersclinicalneed FASENRAisnotindicatedforthereliefofacutebronchospasmorstatusasthmaticus. skin. Release pressure on the plunger head towithplacebo. forbenralizumabandanypotentialadverseeffectsonthebreast-fedchildfrombenralizumabDOSAGE AND ADMINISTRATIONallow the needle guard to cover the needle. Immunogenicity or from the underlying maternal condition.Recommended Dose Do not re-cap the prefilled syringe. As with all therapeutic proteins, there is potential for immunogenicity. The detection ofPediatric Use FASENRAisforsubcutaneoususeonly. antibodyformationishighlydependentonthesensitivityandspecificityoftheassay.Therewere108adolescentsaged12to17withasthmaenrolledinthePhase3exacerbationAdditionally,theobservedincidenceofantibody(includingneutralizingantibody)positivitytrials(Trial1:n=53,Trial2:n=55).Ofthese,46receivedplacebo,40receivedFASENRAeveryThe recommended dose of FASENRA is 30 mg administered once every 4 weeks for the firstinanassaymaybeinfluencedbyseveralfactorsincludingassaymethodology,sample4weeksfor3doses,followedbyevery8weeksthereafter,and22receivedFASENRAevery 3doses,andthenonceevery8weeksthereafterbysubcutaneousinjectionintotheupper 6Discard the used syringe into a sharps container. handling, timing of sample collection, concomitant medications, and underlying disease. For4weeks.Patientswererequiredtohaveahistoryof2ormoreasthmaexacerbations arm,thigh,orabdomen. Instructions for Administration of FASENRA PEN thesereasons,comparisonoftheincidenceofantibodiestobenralizumabinthestudies requiring oral or systemic corticosteroid treatment in the past 12 months and reduced lung General Administration Instructions RefertotheFASENRAPENInstructionsforUseformoredetailedinstructionsonthe describedbelowwiththeincidenceofantibodiesinotherstudiesortootherproductsmay functionatbaseline(pre-bronchodilatorFEV 1 90%) despite regular treatment with medium FASENRA is intended for use under the guidance of a healthcare provider. In line with clinicalpreparationandadministrationofFASENRAPEN[See Instructions for Use in the fullbemisleading. or high dose ICS and LABA with or without OCS or other controller therapy. The pharmaco- practice,monitoringofpatientsafteradministrationofbiologicagentsisrecommendedPrescribing Information].Apatientmayself-injectorthepatientcaregivermayadminister Overall,treatment-emergentanti-drugantibodyresponsedevelopedin13%ofpatientskineticsofbenralizumabinadolescents12to17yearsofagewereconsistentwithadults[see Warnings and Precautions (5.1) in the full Prescribing Information]. FASENRAPENsubcutaneouslyafterthehealthcareproviderdeterminesitisappropriate. treated with FASENRA at the recommended dosing regimen during the 48 to 56 weekbasedonpopulationpharmacokineticanalysisandthereductioninbloodeosinophilcountsAdministerFASENRAintothethighorabdomen.TheupperarmcanalsobeusedifaCONTRAINDICATIONStreatmentperiod.Atotalof12%ofpatientstreatedwithFASENRAdevelopedneutralizingwassimilartothatobservedinadultsfollowingthesameFASENRAtreatment.Theadversehealthcareproviderorcaregiveradministerstheinjection.Priortoadministration,warm FASENRAiscontraindicatedinpatientswhohaveknownhypersensitivitytobenralizumabor antibodies. Anti-benralizumab antibodies were associated with increased clearance ofeventprofileinadolescentswasgenerallysimilartotheoverallpopulationinthePhase3FASENRAbyleavingcartonatroomtemperatureforabout30minutes.Visuallyinspect any of its excipients [see Warnings and Precautions (5.1) in the full Prescribing Information].benralizumabandincreasedbloodeosinophillevelsinpatientswithhighanti-drugantibody studies [see Adverse Reactions (6.1) in the full Prescribing Information]. The safety and FASENRA for particulate matter and discoloration prior to administration. FASENRA is clearWARNINGS AND PRECAUTIONS titerscomparedtoantibodynegativepatients.Noevidenceofanassociationofanti-drug efficacyinpatientsyoungerthan12yearsofagehasnotbeenestablished.to opalescent, colorless to slightly yellow, and may contain a few translucent or white toHypersensitivity Reactions antibodieswithefficacyorsafetywasobserved. Geriatric Use off-white particles. Do not use FASENRA if the liquid is cloudy, discolored, or if it containsHypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, rash) have occurredThedatareflectthepercentageofpatientswhosetestresultswerepositiveforantibodiesto Ofthetotalnumberofpatientsinclinicaltrialsofbenralizumab,13%(n=320)were65andlarge particles or foreign particulate matter. following administration of FASENRA. These reactions generally occur within hours ofbenralizumabinspecificassays. over, while 0.4% (n=9) were 75 and over. No overall differences in safety or effectiveness Prefilled Syringe administration,butinsomeinstanceshaveadelayedonset(i.e.,days).Intheeventofa Postmarketing Experience wereobservedbetweenthesepatientsandyoungerpatients,andotherreportedclinical hypersensitivityreaction,FASENRAshouldbediscontinued[see Contraindications (4) in theexperiencehasnotidentifieddifferencesinresponsesbetweentheelderlyandyounger Theprefilledsyringeisforadministrationbyahealthcareprovider. full Prescribing Information]. In addition to adverse reactions reported from clinical trials, the following adverse reactionspatients,butgreatersensitivityofsomeolderindividualscannotberuledout.Autoinjector (FASENRA PEN) havebeenidentifiedduringpostapprovaluseofFASENRA.BecausethesereactionsareAcute Asthma Symptoms or Deteriorating Disease reportedvoluntarilyfromapopulationofuncertainsize,itisnotalwayspossibletoreliably OVERDOSAGE FASENRAPENisintendedforadministrationbypatients/caregivers.Patients/caregiversFASENRAshouldnotbeusedtotreatacuteasthmasymptomsoracuteexacerbations.Donot estimatetheirfrequencyorestablishacausalrelationshiptodrugexposure.Theseevents Dosesupto200mgwereadministeredsubcutaneouslyinclinicaltrialstopatientswithmayinjectafterpropertraininginsubcutaneousinjectiontechnique,andafterthehealthcare useFASENRAtotreatacutebronchospasmorstatusasthmaticus.Patientsshouldseekmedicalhavebeenchosenforinclusionduetoeithertheirseriousness,frequencyofreporting,or eosinophilic disease without evidence of dose-related toxicities.provider determines it is appropriate. advice if their asthma remains uncontrolled or worsens after initiation of treatment with FASENRA. causalconnectiontoFASENRAoracombinationofthesefactors. Thereisnospecifictreatmentforanoverdosewithbenralizumab.Ifoverdoseoccurs,theInstructions for Administration of FASENRA Prefilled Syringe (Healthcare Providers) Reduction of Corticosteroid DosageImmune System Disorders: Hypersensitivity reactions, including anaphylaxis. patientshouldbetreatedsupportivelywithappropriatemonitoringasnecessary.Refer to Figure 1 to identify the prefilled syringe components for use in the administration steps. DonotdiscontinuesystemicorinhaledcorticosteroidsabruptlyuponinitiationoftherapyDRUG INTERACTIONS PATIENT COUNSELING INFORMATION withFASENRA.Reductionsincorticosteroiddose,ifappropriate,shouldbegradualand Figure 1 Needle guard Syringe Label with performed under the direct supervision of a physician. Reduction in corticosteroid dose mayNoformaldruginteractionstudieshavebeenconducted. Advisethepatientsand/orcaregiverstoreadtheFDA-approvedpatientlabeling(Patient activation clips body expiration date Needle cover beassociatedwithsystemicwithdrawalsymptomsand/orunmaskconditionspreviously USE IN SPECIFIC POPULATIONSInformationandInstructionsforUseforFASENRAPEN)beforethepatientstartsusingsuppressedbysystemiccorticosteroidtherapy. FASENRAandeachtimetheprescriptionisrenewedastheremaybenewinformationtheyParasitic (Helminth) Infection Pregnancyneed to know.Eosinophilsmaybeinvolvedintheimmunologicalresponsetosomehelminthinfections. PregnancyExposureRegistry Providepropertrainingtopatientsand/orcaregiversonpropersubcutaneousinjection Plunger Patientswithknownhelminthinfectionswereexcludedfromparticipationinclinicaltrials.Itis There is a pregnancy exposure registry that monitors pregnancy outcomes in womentechniqueusingtheFASENRAPEN,includingaseptictechnique,andthepreparationandhead unknownifFASENRAwillinfluenceapatientsresponseagainsthelminthinfections. exposed to FASENRA during pregnancy. Healthcare providers can enroll patients or encourageadministrationofFASENRAPENpriortouse.Advisepatientstofollowsharpsdisposal Treatpatientswithpre-existinghelminthinfectionsbeforeinitiatingtherapywithFASENRA. patientstoenrollthemselvesbycalling1-877-311-8972orvisitingmothertobaby.org/Fasenra. recommendations[see Instructions for Use in the full Prescribing Information].IfpatientsbecomeinfectedwhilereceivingtreatmentwithFASENRAanddonotrespondto Risk Summary Hypersensitivity Reactionsanti-helminth treatment, discontinue treatment with FASENRA until infection resolves. The data on pregnancy exposure from the clinical trials are insufficient to inform on drug-Inform patients that hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, ADVERSE REACTIONSassociatedrisk.Monoclonalantibodiessuchasbenralizumabaretransportedacrosstherash) have occurred after administration of FASENRA. These reactions generally occurred Plunger Thefollowingadversereactionsaredescribedingreaterdetailinothersections: placentaduringthethirdtrimesterofpregnancy;therefore,potentialeffectsonafetusarewithinhoursofFASENRAadministration,butinsomeinstanceshadadelayedonset(i.e.,Finger Viewing NeedleHypersensitivityReactions[see Warnings and Precautions (5.1) in the full Prescribinglikelytobegreaterduringthethirdtrimesterofpregnancy.Inaprenatalandpostnataldays). Instruct patients to contact their healthcare provider if they experience symptoms of flange window Information] development study conducted in cynomolgus monkeys, there was no evidence of fetalan allergic reaction [see Warnings and Precautions (5.1) in the full Prescribing Information].Do not touch the needle guard activation clips to prevent premature activation of the needleClinical Trials Experience harmwithIVadministrationofbenralizumabthroughoutpregnancyatdosesthatproducedNot for Acute Symptoms or Deteriorating Disease Lorem ipsum safety guard. Because clinical trials are conducted under widely varying conditions, adverse reaction ratesexposures up to approximately 310 times the exposure at the maximum recommendedInformpatientsthatFASENRAdoesnottreatacuteasthmasymptomsoracute 1Grasp the syringe body, not the plunger, to remove prefilled syringe from the tray. Checkobservedintheclinicaltrialsofadrugcannotbedirectlycomparedtoratesintheclinical humandose(MRHD)of30mgSC[seeData]. exacerbations.Informpatientstoseekmedicaladviceiftheirasthmaremainsuncontrolledtheexpirationdateonthesyringe.Thesyringemaycontainsmallairbubbles;thisis trialsofanotherdrugandmaynotreflecttheratesobservedinpractice. IntheU.S.generalpopulation,theestimatedbackgroundriskofmajorbirthdefectsand or worsens after initiation of treatment with FASENRA [see Warnings and Precautions (5.2) normal. Do notexpeltheairbubblespriortoadministration. Across Trials 1, 2, and 3, 1,808 patients received at least 1 dose of FASENRA [see Clinicalmiscarriageinclinicallyrecognizedpregnanciesis2%to4%and15%to20%,respectively. in the full Prescribing Information].NEEDLE GUARD Studies (14) in the full Prescribing Information].Thedatadescribedbelowreflectexposure WINGS Clinical ConsiderationsReduction of Corticosteroid Dosage 2 Donotremoveneedlecoveruntilreadytoinject.to FASENRA in 1,663 patients, including 1,556 exposed for at least 24 weeks and 1,387Disease-associated maternal and/or embryo/fetal risk: Inform patients to not discontinue systemic or inhaled corticosteroids except under the Holdthesyringebodyandremovetheneedleexposedforatleast48weeks.ThesafetyexposureforFASENRAisderivedfromtwoPhase3 In women with poorly or moderately controlled asthma, evidence demonstrates that there isdirect supervision of a physician. Inform patients that reduction in corticosteroid dose may coverbypullingstraightoff.Donotholdthe placebo-controlledstudies(Trials1and2)from48weeksduration[FASENRAevery4weeks beassociatedwithsystemicwithdrawalsymptomsand/orunmaskconditionspreviouslyplunger or plunger head while removing the (n=841),FASENRAevery4weeksfor3doses,thenevery8weeks(n=822),andplacebo anincreasedriskofpreeclampsiainthemotherandprematurity,lowbirthweight,andsmall suppressedbysystemiccorticosteroidtherapy[see Warnings and Precautions (5.3) in the needle cover or the plunger may move. If the(n=847)]. While a dosing regimen of FASENRA every 4 weeks was included in clinical trials,forgestationalageintheneonate.Thelevelofasthmacontrolshouldbecloselymonitoredin full Prescribing Information].prefilled syringe is damaged or contaminated FASENRA administered every 4 weeks for 3 doses, then every 8 weeks thereafter is the recom- pregnantwomenandtreatmentadjustedasnecessarytomaintainoptimalcontrol.(for example, dropped without needle cover inmended dose [see Dosage and Administration (2.1) in the full Prescribing Information]. TheData PregnancyExposureRegistry place), discard and use a new prefilled syringe. population studied was 12 to 75 years of age, of which 64% were female and 79% were white.Animal DataInform women there is a pregnancy exposure registry that monitors pregnancy outcomes 3 Adverse reactions that occurred at greater than or equal to 3% incidence are shown in Table 1. In a prenatal and postnatal development study, pregnant cynomolgus monkeys receivedinwomenexposedtoFASENRAduringpregnancyandthattheycanenrollinthePregnancy Gently pinch the skin and insert the needle Table 1. Adverse Reactions with FASENRA with Greater than or Equal to 3% IncidencebenralizumabfrombeginningonGD20toGD22(dependentonpregnancydetermination),ExposureRegistrybycalling1-877-311-8972orbyvisitingmothertobaby.org/Fasenra attherecommendedinjectionsitein Patients with Asthma (Trials 1 and 2) on GD35, once every 14 days thereafter throughout the gestation period and 1-month[see Use in Specific Populations (8.1) in the full Prescribing Information].(i.e.,upperarm,thigh,orabdomen). Adverse Reactions FASENRA Placebo postpartum (maximum 14 doses) at doses that produced exposures up to approximatelyManufacturedby(N=822)(N=847)310timesthatachievedwiththeMRHD(onanAUCbasiswithmaternalIVdosesuptoAstraZeneca AB% % 30mg/kgonceevery2weeks).BenralizumabdidnotelicitadverseeffectsonfetalorSdertlje,SwedenSE-15185Headache 8 6 neonatalgrowth(includingimmunefunction)upto6.5monthsafterbirth.Therewasno USLicenseNo.2059Pyrexia 3 2 evidenceoftreatment-relatedexternal,visceral,orskeletalmalformations.Benralizumabwas DistributedbyPharyngitis* 5 3 notteratogenicincynomolgusmonkeys.Benralizumabcrossedtheplacentaincynomolgus AstraZenecaPharmaceuticalsLP,Hypersensitivity reactions3 3 monkeys.Benralizumabconcentrationswereapproximatelyequalinmothersandinfants Wilmington, DE 19850*Pharyngitiswasdefinedbythefollowingterms:Pharyngitis,Pharyngitisbacterial,Viralpharyngitis, onpostpartumday7,butwerelowerininfantsatlatertimepoints.Eosinophilcountswere FASENRA is a trademark of the AstraZeneca group of companies.Pharyngitisstreptococcal. suppressedininfantmonkeyswithgradualrecoveryby6monthspostpartum;however, AstraZeneca 2019HypersensitivityReactionsweredefinedbythefollowingterms:Urticaria,Urticariapapular,andRash recoveryofeosinophilcountswasnotobservedforoneinfantmonkeyduringthisperiod.[see Warnings and Precautions (5.1) in the full Prescribing Information]. Rev.02/21US-510163/21US-79891_US-51016 Fasenra US Medicine 2024 Directory of Federal Medical Treatment Facilities.indd 2 11/22/23 12:04 PM US-79891_US-51016 Fasenra US Medicine 2024 Directory of Federal Medical Treatment Facilities.indd 3 11/22/23 12:04 PM'