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2016NHIAAnnualConference&ExpositionSession13-D.NewDrugsandBiologics2015

Zarxio®-filgrastim-sndzResidentName AmyLee,PharmD DrugName-Trade Zarxio® Manufacturer:Sandoz OrphanDrug?NDrugName—generic filgrastim-sndz DateApproved:March6,2015 BiologicEntity?Y

Element ProvidetheInformationintheColumnBelow:DiagnosticCategory Hematology

Indication(s)Patientswithcancerreceivingmyelosuppressivechemotherapy,patientswithacutemyeloidleukemia(AML)receivingorconsolidationchemotherapy,patientswithcancerundergoingbonemarrowtransplantation,patientsundergoingautologousperipheralbloodprogenitorcellcollectionandtherapyandpatientswithseverechronicneutropenia.

ClinicalTrialSummary

Trialscomparedfilgastimtoplacebotodetermineincidenceanddurationoffebrileneutropenia,numberofdaysofplatelettransfusionsandadverseeffects.Variousdosesoffilgastimwereusedinthevarioustrialswithnoheadtoheadtrialscomparingsimilaragents.

DiseaseSummary: Neutropeniamaybecharacterizedbyinfection,feverandoropharyngealulcers.Neutropeniamaybecausedbymyelosuppressiveagents,autosomaldominantdisorderwithmutationforneutrophilelastase,andunknownetiology.

TherapeuticGoals Reduceincidenceofinfection,timetoneutrophilrecovery,durationoffever,andneutropenia-relatedclinicalsequelae.

Prevalence

About1inamillionpersonsinthegeneralpopulationexperienceneutropenia.Riskfactorsforpatientsreceivingchemotherapyorradiationinclude:preexistingneutropenia,historyofneutropeniawithcurrentorprevioustherapies,tumorinthebonemarrow,useofhighlymyelosuppressiveagents,poorimmunefunction,malnutrition,hepaticorrenaldysfunction,chemoradiation,comorbidities,advancedage,poorperformancestatus.Riskfactorsforpatientswithanautosomaldominantdisorderincludepositivefamilyhistory.

Morbidity/Mortality

Febrileneutropeniaisalife-threateningtreatment-relatedconditionthatoftenleadstohospitalization,dosereductionsandtreatmentdelays,andincreasetheriskofseriousinfectionsassociatedwitha12to42percentmortality.

MechanismofAction

Granulocytecolony-stimulatingfactor;bindstothespecificcellsurfacereceptorandstimulatesproliferation,differentiation,activationofneutrophilstoincreasebothmigrationandcytotoxicity.

Dosing

Patientswithcancerreceivingmyelosuppressivechemotherapyorinductionand/orconsolidationchemotherapyforAML:5mcg/kg/daySubQorIVPatientswithcancerundergoingbonemarrowtransplantation:10mcg/kg/dayIVPatientsundergoingautologousperipheralbloodprogenitorcellcollectionandtherapy:10mcg/kg/daySubQ.Patientswithcongentialneutropenia:6mcg/kgSubQtwicedaily.

HowSupplied 300mcg/0.5mLsingle-useprefilledsyringe480mcg/0.8mLsingle-useprefilledsyringe

Preparation/Storage

Maybedilutedin5%DextroseInjection,USPtoconcentrationsbetween5mcg/mLand15mcg/mL.DilutedconcentrationsshouldbeprotectedfromadsorptiontoplasticmaterialsbytheadditiononAlbumin(Human)tofinalconcentrationof2mg/mL.Thiscombinationiscompatibleinthefollowingcontainers:glass,polyvinylchloride,polyolefinandpolypropylene.

AdministrationPatientswithcancerreceivingmyelosuppressivechemotherapyorinductionand/orconsolidationchemotherapyforAML:SubQinjection,shortIVinfusionover15to30minutesorcontinuousIVinfusion.Patientswithcancerundergoingbonemarrowtransplantation:IVinfusionnolongerthan24hours.


Zarxio®-filgrastim-sndzPatientsundergoingautologousperipheralbloodprogenitorcellcollectionandtherapy:SubQinjection.Patientswithcongentialneutropenia:6mcg/kgSubQinjection.

AdverseEvents Pyrexia,pain,rash,cough,dyspnea,epistaxis,headache,bonepain,anemia,diarrhea,hypoesthesiaandalopecia.Drug-drugordrug-foodInteractions Noknowninteractions.

Contraindications Priorhypersensitivitytohumangranulocytecolony-stimulatingfactorproducts.

Warnings

Evaluatepatientsforpotentialfatalsplenicrupture.Discontinueinpatientswithacuterespiratorydistresssyndrome(ARDS).Permanentlydiscontinueinpatientswithseriousadverseallergicreactions.Reportedfatalcasesofsicklecellcrisis.Reportedcasesofalveolarhemorrhageandhemoptysis,capillaryleaksyndrome,severechronicneutropenia,thrombocytopeniaandleukocytosis.Simultaneoususewithchemotherapyandradiationtherapyisnotrecommended.

PatientEducation/CarePlanningConsiderations

Reviewstepsfordirectpatientadministrationwithpatientsandcaregivers.Advisepatientsofthepotentialrisksofruptureorenlargementofspleen,hypersensitivityreactions,symptomsofARDS,sicklediseasecrisisinpatientswithsicklecelldisease,andcutaneousvasculitis.

Monitoring CBCwithdifferentialandhypersensitivity.Studies Assessthesafetyandefficacyoffilgrastim-mobilizedPBSCinunrelateddonorhematopoieticstemcelltransplantrecipients.

Cost 300mcg/0.5mLsingle-useprefilledsyringe:$330.79480mcg/0.8mLsingle-useprefilledsyringe:$529.78

References

1. Zarxio[packageinsert].Princeton,NJ:SandozInc.;2015March.2. Lexi-Comp,Inc.(Lexi-Drugs®).Lexi-Comp,Inc.;December4,2015.3. Lexi-Comp,Inc.(5-MinuteClinicalConsult®).Lexi-Comp,Inc.;December4,2015.4. LymanGH,AbellaE,PettengellR.Riskfactorsforfebrileneutropeniaamongpatientswithcancerreceivingchemotherapy:A

systematicreview.CritRevOncolHematol2014;90(3):190-199.5. GünalpM1KoyunoğluM,GürlerS,etal.Independentfactorsforpredictionofpooroutcomesinpatientswithfebrileneutropenia.

MedSciMonit2014;20:1826-1832.6. Searchresults.ClinicalTrials.govWebsite.Availableat:https://clinicaltrials.gov/ct2/results?term=zarxio&recr=Open.Accessed

December4,2015.


Praluent®-alirocumabResidentName AlexandreIvanov,PharmD

DrugName-Trade Praluent® Manufacturer:RegeneronPharmaceuticals,Sanofi

OrphanDrug?No

DrugName—generic Alirocumab DateApproved:7/24/2015 BiologicEntity?MonoclonalAntibody Element DiagnosticCategory • MetabolicDisease

Indication(s)• Asanadjuncttodietandmaximallytoleratedstatintherapyforthetreatmentofadultswithheterozygousfamilial

hypercholesterolemia(HeFH)orclinicalatheroscleroticcardiovasculardisease(ASCVD),whorequireadditionalloweringofLDL-cholesterol(LDL-C).


• Fivedouble-blindplacebo-controlledtrialsthatenrolled3499patients,36%withHeFHand54%withnon-FHASCVD,investigatedalirocumabefficacy.Allpatientswerereceivingamaximallytolerateddoseofstatin,withorwithoutotherlipidmodifyingtherapies(LMTs).Alltrialswereatleast52weeksindurationwiththemeanpercentchangeinLDL-Cfrombaselineastheprimaryefficacyendpointmeasuredatweek24.Allstudiesmettheirprimaryefficacyendpointatweek24.

• Noheadtoheadtrialscomparingsimilaragents(i.e.,monoclonalantibodiesthatinhibitproproteinconvertasesubtilisinkexin9(PCSK9)].

• Arandomized,double-blind,active-controlled,parallel-grouptrialevaluatedtheefficacyandsafetyofalirocumabtoezetimibeinhypercholesterolemicpatientsatmoderatecardiovascularriskonnoLMTsover24weeks,anddemonstratedasignificantlygreaterLDL-Cloweringeffectwithalirocumabversusezetimibewithadverseeventratessimilarbetweengroups.

• Thesafetyofalirocumabwasevaluatedin9placebo-controlledtrialsthatincluded2476patients,37%withHeFHand66%withnon-FHASCVD,withmediantreatmentdurationof65weeks.Themostcommonadversereactions(i.e.,occurringin≥5%ofpatientsonalirocumabandmorefrequentlythanplacebo)werenasopharyngitis,injectionsitereactions,andinfluenza.Adversereactionsleadtodiscontinuationoftreatmentin5.3%ofpatientstreatedwithalirocumaband5.1%ofpatientstreatedwithplacebo.

DiseaseSummary:

• Atherosclerosisisapathologicprocessthatcausesdiseaseofthecoronary,cerebral,andperipheralarteries.• Multiplefactorscontributetothepathogenesisofatherosclerosis,includingelevatedlevelsofLDL-C,whichwhenoxidized,may

disruptendothelialcellsurfaces,promoteinflammatorychanges,andincreaseplateletaggregation.• TheLDLreceptoristheprimaryreceptorthatclearscirculatingLDL-C.• Familialhypercholesterolemia(FH)isassociatedwithadefectintheLDLreceptorandtheresultantimpairmentleadstoreduced

clearanceofLDLparticlesfromthecirculationandelevationinplasmaLDL-C.• InadditiontoLDLreceptordefects,thephenotypeofFHcanbeseenwithmutationsinthePCSK9genethatleadtodestruction

ofLDLreceptorsinsidelivercells.• FHisanautosomaldominantdisorderassociatedwithhighLDL-Cfrombirthandearlyonsetofcoronaryheartdisease(CHD).• Outofthetwoformsoffamilialhypercholesterolemia(i.e.,homozygousandheterozygous),HeFHisthemorecommonandless

severeform.TherapeuticGoals • PreventCVdiseaseandimprovethemanagementofpeoplewhohavethedisease.Prevalence • About26.6millionAmericansarediagnosedwithheartdisease.


Praluent®-alirocumab

• Majorriskfactorsincludefamilyhistory,olderage,femalesex,andrace(non-Hispanicwhites,non-Hispanicblacks,andAmericanIndians).

• Thesymptomsofheartdiseasecanbedifferentinwomenandmen,andareoftenmisunderstood.

Morbidity/Mortality• CVdiseaseisthenumberonecauseofdeathintheU.S.andworldwideforbothmenandwomen.• Everyyearabout735,000Americanshaveaheartattack.• Since1984,morewomenthanmenhavediedeachyearfromheartdisease.

MechanismofAction

• Alirocumabisahumanmonoclonalantibody(IgG1isotype)thattargetsandinhibitsPCSK9,aserineproteasemainlyexpressedintheliverandtheintestine.

• PCSK9bindstoLDLreceptorsonthesurfaceoflivercellstopromotereceptordegradationwithintheliver.• ThedecreasedlevelofLDLreceptorsbyPCSK9resultsinhigherLDL-Clevels.• ByinhibitingthebindingofPCSK9toLDLreceptors,alirocumabincreasesthenumberofLDLreceptorsavailabletoclearLDL,

resultinginlowerLDL-Clevels.

Dosing

• Recommendedstartingdose:o 75mgSubQonceevery2weeks.o 150mgSubQonceevery2weeks(maximumdosage)withinadequateresponse.

• Useinspecialpopulations:• Pregnancy:noavailabledatatoinformadrug-associatedrisk.• Lactation:noinformationregardingthepresenceofalirocumabinhumanmilk,theeffectsonthebreastfedinfant,orthe

effectsonmilkproduction.• Pediatricuse:safetyandefficacynotestablished.• Geriatricuse:nooveralldifferencesinsafetyoreffectivenessobservedbetweenelderlyandyoungerpatients.• Renalimpairment:nodoseadjustment,nodataareavailableinsevererenalimpairment.• Hepaticimpairment:nodoseadjustmentwithmild-to-moderateimpairment.Nodataareavailableinpatientswithsevere

hepaticimpairment.

HowSupplied

• Aclear,colorlesstopaleyellowsolution,suppliedinsingle-dosepre-filledpensandsingle-dosepre-filledglasssyringes.• Eachpre-filledpenorpre-filledsyringeisdelivers1mLof75mg/mLor150mg/mLsolution.

Preparation/Storage • Storeinarefrigeratorat36°Fto46°F(2°Cto8°C)intheoutercartontoprotectfromlight.• Donotfreeze,exposetoextremeheat,and/orshake.

Administration

• SubQinjectionintothethigh,abdomen,orupperarmusingasingle-dosepre-filledpenorpre-filledsyringeonceevery2weeks.• Maytakeupto20secondstoinject.• Rotatetheinjectionsitewitheachinjection.• Donotinjectintoareasofactiveskindiseaseorinjury,inflammation,skinrashes,orskininfections.


Praluent®-alirocumab

• Donotco-administerwithotherinjectabledrugsatthesameinjectionsite.• Ifadoseismissed,administerwithin7daysfromthemisseddose,thenresumeoriginalschedule.• Ifthemisseddoseisnotadministeredwithin7days,waituntilthenextdoseontheoriginalschedule.• Allowalirocumabtowarmtoroomtemperaturefor30to40minutespriortouse.Donotuseifstoredatroomtemperature

[77°F(25°C)]for24hoursorlonger.• Inspectvisuallyforparticulatematteranddiscolorationpriortoadministration.• Ifthesolutionisdiscoloredorcontainsvisibleparticulatematter,thesolutionshouldnotbeused.• Followasepticinjectiontechniqueeverytimedrugisadministered.

AdverseEvents• Themostcommonadversereactions(i.e.,occurringin≥5%ofpatientsonalirocumabandmorefrequentlythanplacebo)were

nasopharyngitis,injectionsitereactions,andinfluenza.

Drug-drugordrug-foodInteractions

• Thehalf-lifeofalirocumabisreducedto12dayswhenadministeredwithastatin;however,thisdifferencedoesnotimpactdosingrecommendations.

Contraindications • Historyofaserioushypersensitivityreactiontoalirocumab.• Reactionshaveincludedhypersensitivityvasculitisandhypersensitivityreactionsrequiringhospitalization.

Warnings

• Hypersensitivityreactions(e.g.,pruritus,rash,urticaria),includingseriouseventsasdescribedabove,havebeenreportedwithtreatment.

• Ifsignsorsymptomsofseriousallergicreactionsoccur,discontinuetreatment,treataccordingtothestandardofcare,andmonitoruntilsignsandsymptomsresolve.


• Educateforsignsofallergicreactions.• Advisetodiscontinuetherapyandseekpromptmedicalattentionifanysignsorsymptomsofseriousallergicreactionsoccur.• Cautionnottore-usethepre-filledpenorpre-filledsyringeandeducatetodisposeofinapuncture-resistantcontainerthatis

nottoberecycled.• Discussbenefitsversusrisksofusingalirocumabifpregnant,planningtobecomepregnant,orbreastfeeding.

Monitoring • LDL-Cwithin4to8weeksofinitiationordosetitrations.• Monitorforhypersensitivityreactions.

Studies

• Recruitingtoevaluatetheefficacyandsafetyofalirocumabversusplaceboontopofmaximallytoleratedlipidloweringtherapyinpatientswithhypercholesterolemiawhohavetype1ortype2diabetesandaretreatedwithinsulin.

• RecruitingtoevaluatealirocumabinpatientswithHeFHundergoingLDLapheresistherapy.

Cost

• ThroughtheMyPRALUENTPatientAssistanceProgram,uninsuredorunderinsuredpatientsmaybeeligibletoreceive60-daysuppliesofPRALUENTfreeofchargeforupto12months.Eligiblepatientsmaysubmitforrenewal.

• Eligibilitycriteria:o UninsuredorlackcoverageforPRALUENT,includinglackofcoveragethroughanappealdenial(followinganinitial

coveragerequestdenial)o Demonstratefinancialneed(basedonatotalannualhouseholdincomethatdoesnotexceed400%oftheFederal


Praluent®-alirocumabPovertyLevel)

o Are18yearsofageoroldero AreprescribedPRALUENTforanapprovedindicationo ArearesidentoftheUnitedStatesorPuertoRico

References

• Praluent(alirocumab)[prescribinginformation].Bridgewater,NJ:Sanofi-AventisUSLLC;July2015.• RothEM,McKenneyJM.ODYSSEYMONO:effectofalirocumab75mgsubcutaneouslyevery2weeksasmonotherapyversus

ezetimibeover24weeks.FutureCardiol.2015;11(1):27-37.• VinkH,ConstantinescuAA,SpaanJA.Oxidizedlipoproteinsdegradetheendothelialsurfacelayer:implicationsforplatelet-

endothelialcelladhesion.Circulation.2000;101(13):1500-1502.• HobbsHH,RussellDW,BrownMS,GoldsteinJL.TheLDLreceptorinfamilialhypercholesterolemia:mutationalanalysisofa

membraneprotein.AnnuRevGenet.1990;24:133-170.• HortonJD,CohenJC,HobbsHH.PCSK9:aconvertasethatcoordinatesLDLcatabolism.JLipidRes.2009;50:S172-177.• CentersforDiseaseControlandPrevention.HeartDiseaseFacts.Availablefromhttp://www.cdc.gov/heartdisease/facts.htm.

Lastaccessed02December2015.


Vistogard®–uridinetiracetateResidentName AlexandreIvanov,PharmD DrugName-Trade Vistogard® Manufacturer:WellstatTherapeutics OrphanDrug?YesDrugName—generic Uridinetriacetate DateApproved:12/11/2015 BiologicEntity?No

Element ProvidetheInformationintheColumnBelow:DiagnosticCategory • Oncology

Indication(s)

• Apyrimidineanalogindicatedfortheemergencytreatmentofadultandpediatricpatients:o Followingfluorouracil(FU)orcapecitabineoverdoseregardlessofthepresenceofsymptoms.o Withearly-onset,severe,orlife-threateningtoxicityaffectingthecardiacorcentralnervoussystem,and/orsevereadverse

reactions(e.g.,gastrointestinaltoxicityand/orneutropenia)within96hoursfollowingFUinfusionorcapecitabineadministration.

• Limitationsofuse:

o Notrecommendedfornon-emergenttreatmentofadversereactionsassociatedwithFUorcapecitabineduetoriskofdiminishingdrugeffect.

o Safetyandefficacywithinitiation>96hourspostFUorcapecitabineadministrationhasnotbeenestablished.


• Vistogardsafetyandefficacywasassessedintwosingle-arm,open-label,multi-centertrialsthatenrolled135patientscombined.Vistogardwasadministeredat10gramsorallyevery6hoursfor20dosesoratbodysurfaceareaadjusteddosageof6.2grams/m2/dosefor20dosesinfourpatientsbetween1and7yearsofage.

• Thecombinedmedianageinbothstudieswas59years(range:1to83),and95%ofpatientshadacancerdiagnosis.• Ofthe135patients,117receivedVistogardfollowinganoverdoseofFU(n=112)orcapecitabine(n=5),and18patientsreceived

treatmentwithin96hoursafterexhibitingsevereorlife-threateningtoxicitiesfollowingtheendofFUadministration.• Thesevereorlife-threateningtoxicitiesinvolvedthecentralnervoussystem(e.g.,encephalopathy,acutementalstatuschange),

cardiovascularsystem,gastrointestinalsystem(e.g.,mucositis),andbonemarrow.• OverdosewasdefinedasadministrationofFUatadose,orinfusionrate,greaterthantheintendeddoseormaximumtolerateddose

forthepatient’sintendedregimen.• Efficacy:

o Themajorefficacyoutcomewassurvivalat30daysoruntiltheresumptionofchemotherapyifpriorto30days.Ofthe112patientsoverdosedwithFU,94%wereoverdosedbyinfusionrateonly,4%wereoverdosedbydoseonly,and3%wereoverdosedbybothdoseandrate.Survivalat30dayswas97%forpatientstreatedforanoverdoseand89%forpatientstreatedforearly-onsetorlife-threateningtoxicity.Additionally,33%ofpatientsresumedchemotherapyinlessthan30days.

• Safetyo Themediandurationofexposurewas4.8days,withamedianof20doses.o Discontinuationduetoadversereactionsoccurredintwo(1.4%)patients.Adversereactionsoccurringin>2%ofpatients

(n=135)includedvomiting(10%),nausea(5%),anddiarrhea(3%).


Vistogard®–uridinetiracetateo FivedeathswereattributedtoFUorcapecitabinetoxicity,andtwoofthefivepatientsweretreated96hoursfollowingthe

endofFUadministration.o Long-termstudiesinanimalshavenotbeenperformedtoevaluatethecarcinogenicpotentialofuridinetriacetate.

• Therearenoheadtoheadtrialscomparingsimilaragents.

DiseaseSummary:

• Fluorouracil(FU),anantineoplasticfluorinatedpyrimidineanalog,isasterile,nonpyrogenicinjectablesolutionforintravenousadministration.Eitherasasingleagentoraspartofamulti-drugregimen,FUisusedinthemanagementofcarcinomaofthecolon,rectum,breast,stomachandpancreas.Throughitscytotoxicintermediates(i.e.,FdUMPandFUMP),FUimpairsDNAandRNAsynthesis.FdUMPinhibitsthymidylatesynthetase,depletingthymidinetriphosphate,anecessarycomponentofDNA.FUMPincorporatesintoRNAtoreplaceuracil(pyrimidineanalog),whichinhibitscellgrowth.Patientsshouldbecarefullysupervisedduetoitshighlytoxicnatureandnarrowmarginofsafety.Therapyshouldbediscontinuedpromptlywheneveroneofthefollowingsingsoftoxicityappears:stomatitisoresophagopharyngitis,gastrointestinalulcerationandbleeding,intractablevomiting,diarrhea,leukopenia(WBC<3500),orhemorrhagefromanysite.TheadministrationofFUhasalsobeenassociatedwiththeoccurrenceofhand-footsyndrome,andwithearly-onset,severe,orlife-threateningtoxicityaffectingthecardiacorcentralnervoussystem.Neurologicalsideeffectsincludeacutecerebellarsyndrome,encephalopathy,opticneuropathy,cerebrovasculardisorders,andseizures.Aspectrumofcardiaceffectshavebeenreported,includingacutecoronarysyndrome,arrhythmias,heartfailure,cardiogenicshock,andsuddendeath.

• Capecitabine,anorallyactivefluorinatedpyrimidineanalogue,metabolizedtotheactivemoiety,FU,isindicatedforthemanagementofcolorectalandbreastcancer,eitherasasingleagent,oraspartofamulti-drugregimen.Mostcommonadversereactionsincludediarrhea,hand-footsyndrome,nausea,vomiting,abdominalpain,fatigue,andhyperbilirubinemia.Cardiotoxicityobservedwithcapecitabineincludesmyocardialinfarction,angina,dysrhythmias,cardiacarrest,cardiacfailure,cardiomyopathy,andsuddendeath.Mucocutaneous,hematological,andneuroglialtoxicitieshavealsobeenreported.

• Dihydropyrimidinedehydrogenease(DPD),anenzymeencodedbytheDPYDgene,istherate-limitingstepinpyrimidinecatabolismanddeactivatesmorethan80%ofstandarddosesofFUandcapecitabine,.PartialorfulldeficiencyoftheDPDenzymeincreasesthehalf-lifeofthedrug,resultinginexcessdrugaccumulationandtoxicity.

TherapeuticGoals • FirstandonlyemergencytreatmentavailableintheUStoreverseeffectsofandpreventdeathwithin96hoursfollowingtheendofFUorcapecitabineadministration.

Prevalence

• Distinguishingdiseasepathologyfromtheadversechemotherapeuticeffectsischallenging,andcessationofexposureisoftennecessarytomanageseveretoxicity.

• Dose-limitingtoxicitiesassociatedwithdailyFUadministrationareprimarilymucositis(24%)andneutropenia(29%),whereasaspredominanttoxicityseeninpatientsontheweeklyFUregimenisdiarrhea(32%).Cardiotoxicityandneurotoxicityhavebeenobservedin2%-5%ofpatientstreatedwithFU.

• CapecitabinedemonstratesclinicallymeaningfulbenefitsoverFUintermsofscheduleflexibility,administrationcosts,andtoxicity-relatedhospitalizations.Patientstreatedwithcapecitabineexperiencelessdiarrhea,stomatitis,nausea,vomiting,alopecia,andneutropenia.Therateofcardiotoxicityissimilarbetweenagents,whereasneurotoxicityappearstobelesscommon.

• PatientswithDPDdeficiencywhoaretreatedwithFUorcapecitabineareatsignificantlyincreasedriskfordrug-relatedtoxicity.Inonereport,theattributablerisktosufferfromseveredrug-adverseeffectsduetoDPDdeficiencywas56.9%.BasedonwhatisknowntodateabouttheroleofDPDinFUandcapecitabinemetabolism,patientswithknownDPDdeficiencyand/orfamilyhistoryofknown


Vistogard®–uridinetiracetatemutationsshouldavoidtherapywiththeseagents.

Morbidity/Mortality

• CanceristhesecondmostcommoncauseofdeathintheUS,exceededonlybyheartdisease,andaccountsfornearly1ofevery4deaths.

• ThefrequencyofFU/capecitabinetreatment-relatedsuddendeathvariesfrom0%to8%butclustersaround0.5%inlargerstudieswith>400patients.

• Basedonretrospectivehistoricalcasereportsof25patientswhowereoverdosedwithFUandreceivedsupportivecareonly,allwereoverdosedbyraterangingfrom1.9to64timestheplannedinfusionrate,and84%died.

MechanismofAction

• Uridinetriacetateisanacetylatedpro-drugofuridine(pyrimidineanalog).Followingoraladministration,nonspecificesterasesreleaseuridineincirculation.

• ExcesscirculatinguridinederivedfromVistogardisconvertedintouridinetriphosphate(UTP),whichcompeteswithFUTPforincorporationintoRNA.

• InFUoverexposure,uridinetriacetateactsasdirectchemicalantagonistagainstFUtoxicity.

Dosing

• Adults:o 10gm(1packet)orallyevery6hoursfor20doses.

• Pediatric:o 6.2grams/m2ofbodysurfacearea(max:10gm/dose)orallyevery6hoursfor20doses.

• Useinspecialpopulations:o Pregnancy:limitedevidencetoinformofadrug-associatedriskofbirthdefectsandmiscarriage.o Breastfeeding:notknownifVistogardisexcretedintobreastmilk.o Geriatricuse:limitedevidencetodetermineiftheelderlyresponddifferently.

HowSupplied • 10gramsoforange-flavored,white-to-off-white,oralgranules(95%w/w)insingle-dosepackets.

Preparation/Storage

• Oralpreparation:mixeachVistogarddosewith3to4ouncesofsoftfoods(applesauce,puddingoryogurt)foradministrationwithin30minutesofpreparation.

o Note:forpediatricdosing,measuredosewithascaleaccuratetoatleast0.1gm,oragraduatedteaspoon(tsp)accurateto¼tsp.

o Donotusegranulesleftintheopenpacketforsubsequentdosing.• Nasogastric(NG)orgastric(G-tube)administration:

o Prepare4ouncesofafoodstarch-basedthickeningproductinwaterandstiruntilthickenerdissolves.o Crushthecontentsofonefull10gmpacketgranulestoafinepowder.o Addcrushedgranulestothe4ouncesofreconstitutedstarchproduct.o Note:forpediatricpatientsreceiving<10gm,preparemixtureataratioofnogreaterthan1gmper10mLofreconstituted

thickeningproductandmixthoroughly.• Storage

o Atcontrolledroomtemperature,25°C(77°F);excursionspermittedto15°C-30°C(59°F-86°F).

Administration• Administerorallywithin96hoursofanoverdoseorearly-onsettoxicityfollowingFUorcapecitabineadministration.• Ifpatientvomitswithin2hoursofadministration,initiateanothercompletedose,withthenextdoseprovidedattheregularscheduled

time.


Vistogard®–uridinetiracetate

• Ifpatientmissesadose,administerassoonaspossible,withthenextdoseprovidedattheregularscheduledtime.• FollowingNGorG-tubeadministration,flushfeedingtubewithwater.

AdverseEvents • Adversereactionsoccurringin>2%ofpatientsincludedvomiting(10%),nausea(5%),anddiarrhea(3%).Drug-drugordrug-foodInteractions • Therearenosignificantdrug-drugordrug-foodinteractions.

Contraindications • NoneWarnings • None


• Importanceoftakingall20doses,evenwithsymptomimprovement.• Vistogardcanbetakenmixedinfood(applesauce,puddingoryogurt).• Nottochewgranulesanddrinkatleast4ouncesofwaterwitheachdose.• Administrationinstructionsinthecaseofvomitingwithin2hoursofadministrationorwithamisseddose.

Monitoring • FUorcapecitabineoverdose/toxicity

Studies• Active(notrecruiting)open-labeltrialofuridinetriacetateinpediatricpatientswithhereditaryoroticaciduria.• Recruitingforanopen-labeltrialfortheuseofuridinetriacetateasanantidotetotreatpatientsatexcessriskofFUtoxicitydueto

overdoseorimpairedelimination.Cost • Notavailableatthistime.

References

• Vistogard(uridinetriacetate)[prescribinginformation].WestConshohocken,PA:WellstatTherapeutics;December2015.• Fluorouracil[prescribinginformation].Princeton,NJ:Sandoz;May2015.• Capecitabine[prescribinginformation].Durham,NC:AccordHealthcare;March2015.• PolkA,Vaage-NilsenM,VistisenK,NielsenDL.Cardiotoxicityincancerpatientstreatedwith5-fluorouracilorcapecitabine:asystematic

reviewofincidence,manifestationsandpredisposingfactors.CancerTreatRev.2013;39(8):974-984.• Malet-MartinoM,MartinoR.Clinicalstudiesofthreeoralprodrugsof5-fluorouracil(capecitabine,UFT,S-1):areview.Oncologist.

2002;7(4):288-323.• GrossE,BusseB,RiemenschneiderM,etal.Strongassociationofacommondihydropyrimidinedehydrogenasegenepolymorphism

withfluoropyrimidine-relatedtoxicityincancerpatients.PLosOne.2008;3(12):e4003.


Jadenu®-deferasiroxResidentName RossWoods DrugName-Trade Jadenu® Manufacturer:Novartis OrphanDrug?NoDrugName—generic Deferasirox DateApproved:March30,2015 BiologicEntity?No Element ProvidetheInformationintheColumnBelow:DiagnosticCategory Hematology

Indication(s)

Chronicironoverloadresultingfrombloodtransfusioninpatients≥2yearsold.Chronicironoverloadinpatientswithnon-transfusion-dependentthalassemia(NTDT)syndromeswithliverironconcentration(LIC)of≥5mgFe/gramdryweightandserumferritin>300mcg/Linpatients≥10yearsold

ClinicalTrialSummary Onlyevaluatedinhealthysubjects.NoclinicaldatainpatientswithJadenu®.ApprovalwasbasedoffclinicaltrialsconductedwithExjade®,whichcontainsthesameactiveingredientasJadenu®.

DiseaseSummary:

IronOverloadisaduetoaltereddynamicsinironregulation.Intransfusioninducedironoverload,plasmairon-bindingproteintransferrinbecomesoversaturatedandexcessironcirculatesasfreenon-transferrin-boundiron(NTBI).TheliverandothertissuesrapidlyuptakesNTBI.NTDTcancauselowhepcidinlevels,increasedintestinalabsorptionofiron,andincreasedreleaseofrecycledironformthereticuloendothelialsystem.Commonsymptomsofironoverloadincludeweightloss,fatigue,bronze/grayskin,arthralgias,andhematologic,cardiac,gastrointestinal,andendocrineissues.Excessironcandamagetissuesincludingmajororgans.Theseincludetheheart,lungs,liverandendocrineglands.Thiscancausehypertrophyanddilationoftheheartandleadtoabnormalcardiacfunction.Overloadcanalsoleadtorestrictivelungfunction,earlycirrhoticchanges,andendocrinedysfunction.

TherapeuticGoals Reductioninserumferritin,LICreductions,reductionsinsymptomsofironoverload,reductionofcardiomyopathy,morbidityandmortality.

Prevalence

Thereareanestimated15,000peoplewithsicklecelldisorderand5,000withmyelodysplasticsyndromesorotherrefractoryanemiasthatrequirebloodtransfusions.Approximately23%havedocumentedironoverload.Thalassemiaoccursinaround68,000childrenworldwidewith80to90millionindividualsthatarecarriersworldwide.NTDThasarelativelylowprevalenceandvariesineverypopulation.

Morbidity/Mortality

TransfusionRelatedIronOverloadMortality3timeshigherinchronicallyinfusedpatientswiththalassemiaandsicklecelldiseaseinUSthangeneralpopulation.Cardiomyopathyinducedbyironoverloadisthemostcommonmorbiditycause(approximately30%).Morbiditiescaninvolveseveralorgansandincidenceincreaseswithincreasingage.Complicationsincludesilentcerebralischemia,pulmonaryhypertension,right-sidedheartfailure,cirrhosisandlivercancer,splenomegaly,gallstones,osteoporosis,venousthrombosis,andlegulcers.Theratesarevariableamountthedifferentformsofthalassemia.

MechanismofAction Orallyactivechelator;selectiveforiron(Fe3+);tridentateligandwithironbindingaffinityratio2:1;lowaffinityforzincandcopper

Dosing

TransfusionalIronOverload:• Initialdose14mg/kg(roundedtonearestwholetablet)oncedaily• Adjustmentsmadeevery3to6monthsbasedonserumferritintrends• Adjustinstepsof3.5or7mgperKgtailoredtoresponseandgoals• Doses>28mg/kgnotrecommended


Jadenu®-deferasirox

• Interrupttherapyinserumferritin<500mcg/LNTDTsyndromes:

• Initialdose7mg/kg(roundedtonearestwholetablet)oncedaily• Considerincreasingto14mg/kgat4weeksifLIC>15mgFe/gdw• AdjustdosebasedonLIC• Interrupttherapyifserumferritin<300mcg/LorLIC<3mgFe/gdw

ConversionfromExjade®• Reducedoseby30%• Jadenu®has36%greaterbioavailabilitythanExjade®

HepaticImpairment• Moderate(Child-PughB)

o Reducestartingdoseby50%• Severe(Child-PughC)

o DonotuseRenalImpairment

• CrCl40to60mL/mino Reducestartingdoseby50%

• CrCl<40mL/mino Donotuse

DoseModificationsTransfusionalIronOverload

• ≥16y/oo SCrincrease≥33%averagebaseline

§ RepeatSCrwithin1week§ Remainselevatedby≥33%

• Reducedoseby7mg/kg• 2to15y/o

o SCr≥33%aboveaveragebaselineand>ULN§ Reducedoseby7mg/kg

• Allpatientso SCr>2timesULNorCrCl<40mL/min

§ DiscontinueNTDTsyndromes:

• ≥16y/oo SCrincrease≥33%averagebaseline

§ RepeatSCrwithin1week


Jadenu®-deferasirox§ Remainselevatedby≥33%

• Interrupttherapyif3.5mg/kg• Reduceby50%if7or14mg/kg

• 10to15y/oo SCr≥33%aboveaveragebaselineand>ULN

§ Reducedoseby3.5mg/kg• Allpatients

o SCr>2timesULNorCrCl<40mL/min§ Discontinue

Allpatients• UDP-glucuronosyltransferases(UGT)inducers

o Avoidwithpotentinducerso ConsiderreducingJadenu®by50%ifusedconcomitantly

• BileAcidSequestrantso DecreaseJadenu®exposureo Avoidconcomitantuseo ConsiderincreasingJadenu®by50%ifusedconcomitantly

HowSupplied 90mg,180mg,and360mgtabletsPreparation/Storage Storeat25°C(77°F);excursionpermittedto15to30°C(59to86°F);shouldbeprotectedfrommoisture

Administration Oncedailywithwaterorotherliquid;Giveonemptystomachorwithlightmeal(<7%fatandapprox.250calories);DonottakewithantacidproductscontainingAluminum;maybecrushedandmixedwithsoftfoodsimmediatelypriortouseandadministeredorally

AdverseEvents

BlackBoxWarnings:RenalFailure,HepaticFailure,Gastrointestinal(GI)HemorrhageADRs:≥10%Skinrash,abdominalpain,diarrhea,nausea,vomiting,proteinuria,serumcreatinineincreaseOthersofnote:bonemarrowsuppression,SJS,erythemamultiform,auditoryandoculardisturbances


Antacidscontainingaluminum;CYP3A4,CYP2C8,andCYP1A2metabolizedagents;UDP-glucuronosyltransferase(UGT)inducers;Bileacidsequestrants

Contraindications

SCr>2timesULNorCrCl<40mL/minPoorperformancestatusHigh-riskmyelodysplasticsyndromesAdvancedmalignanciesPlateletcount<50x109/LHypersensitivitytodeferasiroxorcomponentofJadenu®

WarningsRenaltoxicity,failure,andproteinuriaHepatictoxicityandfailureGIulceration,hemorrhage,andperforation


Jadenu®-deferasiroxBonemarrowsuppressionElevatedtoxicityriskinElderlyHypersensitivitySevereSkinReactionsSkinRashAuditoryandOculardisturbancesOverchelation


Educateforsignsofhypersensitivityreactions,infection,renalimpairment,visionchanges,hepaticimpairment,hemorrhaging,severenauseaand/ordiarrhea,auditorychanges,intolerabledyspepsia,andSJS/TEN.AdvisepatientstoavoidAluminumcontainingantacids,reportallmedicationstoHCPtoscreenforpotentialdruginteractions,andavoiddriving/operatingmachineryifexperiencedizziness.

Monitoring

Baseline:TransfusionalIronOverload:

• Serumferritinlevel• SCrinduplicate(determinetheCrClviaCockcroft-Gaultmethod)• Serumtransaminasesandbilirubin• Auditoryandophthalmicexaminations

NTDTsyndromeIronOverload:• LICvialiverbiopsyorotherFDAapprovedmethod• Serumferritin(atleast2measurements1monthapart)• SCrinduplicate(determinetheCrClviaCockcroft-Gaultmethod)• Serumtransaminasesandbilirubin• Auditoryandophthalmicexaminations

DuringTherapy:TransfusionalIronOverload:

• Weight(particularlyinchildren)• Serumferritinmonthly• CBCwithdifferential• SCrandCrClmonthly• Urineproteinmonthly• Serumtransaminasesandbilirubineverytwoweeksformonth1,thenmonthly• Auditoryandophthalmicexaminationsannually• s/sGIhemorrhage• cumulativeRBCunitsreceived

NTDTsyndromeIronOverload:


Jadenu®-deferasirox

• Weight(particularlyinchildren)• Serumferritinmonthly• CBCwithdifferential• SCrandCrClmonthly• Urineproteinmonthly• Serumtransaminasesandbilirubineverytwoweeksformonth1,thenmonthly• Auditoryandophthalmicexaminationsannually• S/sGIhemorrhage• LICevery6months(adjustdosebasedoffresults)

Studies Nonecurrentlyforthisformulationofdeferasirox.

Cost AWPof$1000to$4000per30tabletsdependingonstrength.AssistanceProgramavailablethroughNovartis.Coversupto$20,000percalendarforthosewithcommercialInsurance.

References

1. JADENU®[packageinsert].EastHanover,NJ:Novartis;October2015.2. JADENU®.JADENU®website.https://www.jadenu.com.AccessedDecember21st,2015.3. Jadenu®,Oral.In:DrugFactsandComparisons(FactsandComparisonseAnswers)[VCMIntranet].St.Louis:WoltersKluwer

Health[updatedSeptember2015cited2015December].[about22p.].Availablefromhttp://online.factsandcomparisons.com4. RedBookOnline.In:Micromedex®System.Version2.0GreenwoodVillage,CO:ThomsonReuters(Healthcare)Inc.[updated

2015,cited2015Dec].[about4p.].Availablefromhttp://www.micromedexsolutions.com/5. Emedicine.medscape.com.Transfusion-InducedIronOverload:Background,Pathophysiology,Epidemiology.2016.Available

at:http://emedicine.medscape.com/article/1389732-overview.AccessedJanuary15,2016.6. TaherA,CappelliniM.ManagementofNon-Transfusion-DependentThalassemia:APracticalGuide.Drugs.2014;74(15):1719-

1729.doi:10.1007/s40265-014-0299-0.

2016NHIAAnnualConference&ExpositionSession13-D.NewDrugsandBiologics2015Technivie®–ombitasvir/paritaprevir/ritonivir

ResidentName RossWoods DrugName-Trade Technivie® Manufacturer:AbbVieInc. OrphanDrug?No

DrugName—generic ombitasvir,paritaprevir,andritonavir

DateApproved:July24th,2015 BiologicEntity?No

Element ProvidetheInformationintheColumnBelow:DiagnosticCategory InfectiousDiseaseIndication(s) Foruseincombinationwithribavirintotreatgenotype4chronichepatitisCvirus(HCV)infectionswithoutcirrhosis


Trialwasanopen-labeltrialevaluatingtreatmentnaïvesubjectswithTechnivie®withandwithoutribavirinandPEGylatedinterferon/ribavirintreatment-experiencedsubjectswithTechnivie®withribavirin.Overallsustainedvirologicresponse(SVR12),on-treatmentvirologicfailure,andrelapseaftertreatmentfor12weeks.SVR12wasmeasuredatweek24.Noheadtoheadtrialscomparingsimilaragents.

DiseaseSummary:

HepatitisCisaninfectiousliverdiseasecausedbytheblood-bornehepatitisCvirus.Around70to85%ofthoseacutelyinfectedbecomealongtermchronicinfectiondefinedasHCVRNA≥6months.Itismostoftenacquiredthroughinjectiondruguse,butcanalsospreadviasexualcontact,hemodialysis,oroccupational,household,orperinatalexposure.Commonsymptomsincludefever,fatigue,darkurine,abdominalpain,appetiteloss,nausea,vomiting,clay-coloredstool,jointpain,andjaundice.Complicationsincludechronicliverdisease,cirrhosis,HCVtransmission,livercancer,anddeath.HCVistheleadingindicationforlivertransplants.

TherapeuticGoals Virologiccure(12weeksafterendoftreatment),sustainedvirologicresponse(SVR12),HCVRNA<25IU/mL,normalizationofliverfunction,reductionofinfectivityandtransmission,reductioninmorbidityandmortality

Prevalence

Estimated3.5millioncurrentlyinfectedinUSand130to150millionpeopleworldwide.Approximately29,718acutecasesin2013intheUS.Around75to85%ofthoseacutelyinfectedbecomeinfectedchronically.Mostcommoninthose20to29yearsold,ratessimilarbygender,andmorecommoninAmericanIndians/AlaskanNativesandWhite,non-Hispanicsthanotherraces.Genotypes1,2,and3aremostcommoninEuropeandNorthAmerica.HCVgenotype4ismostcommonHCVinfectionintheMiddleEastandAfrica,mainlyEgypt.

Morbidity/MortalityOfthoseinfected,asignificantnumberdeveloplivercirrhosisorlivercancerworldwide.Approximately1to5%dieofcomplications,5to20%developcirrhosisovera20to30yearperiod,and60to70%developchronicliverdiseaseintheUS.Worldwide,approximately500,000diefromhepatitisCrelateddiseaseseachyear.

MechanismofActionParitaprevir:inhibitorofHCVNS3/4Aprotease(essentialforproteolyticcleavageofHCVencodedpolyproteinandviralreplication).Ombitasvir:HCVNS5Ainhibitor(essentialforviralRNAreplicationandvirionassembly)Ritonavir:potentCYP3A4inhibitor,increasespeakandtroughplasmadrugconcentrationsofparitapreviranddrugexposure.

Dosing

TwoTechnivie®tablets(ombitasvir12.5mg,paritaprevir75mg,ritonavir50mgfixeddosecombinationtablets)oncedailywithfoodfor12weeks.Recommendribavirindose:

• WeightBasedo <75kg

§ 1000mg/dayo ≥75kg


§ 1200mg/dayo Administeredtwicedailyindivideddoseswithfood

Mayconsideradministrationwithoutribavirinfortreatment-naïvepatientsandthoseunabletotolerateribavirin.Nodataonsafetyandefficacyinchildren.Discontinuationoftherapy

• ConsiderifpersistentelevationsofALT>10timesupperlimitofnormal(ULN)• DiscontinueifALTelevationswithsignsandsymptomsofliverinflammation,increasingdirectbilirubin,alkalinephosphatase,

orinternationalnormalizedratio(INR).

HowSuppliedOmbitasvir12.5mg,paritaprevir75mg,ritonavir50mgfixeddosecombinationtablets;suppliedinmonthlycartonstotaling28daysoftherapyandcontains4weeklycartons;eachweeklycartoncontains7dailydosepacks;eachdailydosepackcontainstwoTechnivie®tablets

Preparation/Storage Storeatorbelow30°C(86°F)

Administration TwoTechnivie®tabletsorallyoncedailyinthemorningwithameal.Administerincombinationwithweightbaseddosingofribavirintwicedailyindivideddoseswithfood.

AdverseEvents≥10%:asthenia,fatigue,nausea,andinsomniaOthers:pruritus,skinreactions,ALTelevations,bilirubinelevations,anemia,hemoglobinreductions,hypersensitivityreactions,hepaticdecompensation,hepaticfailure


Digoxin,antiarrhythmics,ketoconazole,voriconazole,quetiapine,amlodipine,fluticasone,furosemide,atazanavir,atazanavir/ritonavir,darunavir/ritonavir,lopinavir/ritonavir,rilpivirine,pravastatin,cyclosporine,tacrolimus,salmeterol,buprenorphine/naloxone,omeprazole,alprazolam

Contraindications

ModeratetoseverehepaticimpairmentHighlyCYP3A4metabolizeddrugsModeratetostrongCYP3A4inducersKnownhypersensitivitytoritonavirHypersensitivitytocomponentsofTechnivie®

Certainmedicationswiththeclassofalpha-1-adrenoreceptorantagonists,anti-gout,anticonvulsants,antimycobacterial,ergotderivatives,ethinylestradiol-containingproducts,St.John’sWort,HMG-CoAReductaseInhibitors,Non-nucleosidereversetranscriptaseinhibitor,Phosphodiesterase-5-inhibitor,andsedatives/hypnotics.

Warnings

RiskofhepaticdecompensationRiskofALTelevationsRisksassociatedwithribavirincombinationtherapyAdversereactionsorreducedtherapeuticeffectduetodruginteractionsRiskofHIV-1proteaseinhibitordrugresistanceinHCV/HIV-1co-infections


Educateforsignsandsymptomsofhypersensitivityreactions,liverimpairment,severeasthenia,skinreactions.Advisetoreadmedicationguide,avoidduringpregnancy,potentialfordruginteractions,andwhentotakeifdoseismissed.

Monitoring Baseline:Hepaticfunctiontests


SerumHCV-RNADuringTherapy:Hepaticfunctiontestswithinfirst4weeksoftherapythenperiodically.SerumHCV-RNAattheendoftherapy,duringfollowup,thenasclinicallyindicated.

Studies Recruitingforuseingenotype1or4andtreatedearlystagecarcinomawithcompensatedcirrhosis.Ongoingstudyingenotype4anddecompensatedcirrhosis.

Cost AWP:$1095.04per2tabletsAssistanceprogramthroughpartnershipforprescriptionassistance.https://www.pparx.org/

References

1. Technivie®.Technivie®website.https://www.technivie.com.AccessedDecember30th,2015.2. Technivie®[packageinsert].NorthChicago,IL:AbbVieInc;October2015.3. Technivie®,Oral.In:DrugFactsandComparisons(FactsandComparisonseAnswers)[VCMIntranet].St.Louis:WoltersKluwer

Health[updatedDecember2015cited2015December].[about30p.].Availablefromhttp://online.factsandcomparisons.com4. RedBookOnline.In:Micromedex®System.Version2.0GreenwoodVillage,CO:ThomsonReuters(Healthcare)Inc.[updated2015,

cited2015Dec].[about5p.].Availablefromhttp://www.micromedexsolutions.com/5. Hepchope.com.HepCHopeOfficialSite-HepatitisCInformation.2016.Availableat:http://www.hepchope.com/.Accessed

January5,2016.6. Cdc.gov.HCVFAQsforHealthProfessionals|DivisionofViralHepatitis|CDC.2016.Availableat:

http://www.cdc.gov/hepatitis/hcv/hcvfaq.htm#a5.AccessedJanuary5,2016.7. Who.int.WHO|HepatitisC.2016.Availableat:http://www.who.int/mediacentre/factsheets/fs164/en/.AccessedJanuary5,2016.


Repatha®-evolocumabResidentName NoreenChan DrugName-Trade Repatha® Manufacturer:Amgen OrphanDrug?YesDrugName—generic evolocumab DateApproved:August27,2015 BiologicEntity?No Element ProvidetheInformationintheColumnBelow:DiagnosticCategory Cardiovascular

Indication(s)

Alongwithdietandmaximallytoleratedstatintherapyinadultswithheterozygousfamilialhypercholesterolemiaoratheroscleroticheartorbloodvesselproblems,whoneedadditionalloweringofLDLcholesterolAlongwithdietandotherLDLloweringtherapies,inpeoplewithhomozygousfamilialhypercholesterolemiawhoneedadditionalloweringofLDLcholesterol


8placebo-controlledtrialsthatincluded2651patients,including557exposedfor6monthsand515exposedfor1year(mediantreatmentdurationof12weeks).Meanagewas57years,49%ofthepopulationwerewomen,85%white.Themostcommonadversereactionina52-weekcontrolledtrialthatledtoRepatha®treatmentdiscontinuationandoccurredatarategreaterthanplacebowasmyalgia(0.3%vs0%forRepatha®andplacebo,respectively).Adversereactionsledtodiscontinuationoftreatmenton2.2%ofRepatha®-treatedpatientsand1%orplacebo-treatedpatients.

DiseaseSummary:

Individualswithfamilialhypercholesterolemiaareunabletorecyclethenaturalsupplyofcholesterolthattheirbodiesareconstantlyproducing.Therefore,thecholesterollevelsareexceedinglyhigh.Thereare2formsofFH.Ifyouhaveinheritedthisgeneticmutationfromoneparent,thenyouwillhaveheterozygousFH.IfyouinheritFHfrombothparents,itismuchmoresevereinitsconsequences.Ifleftuntreated,menhavea50%riseofhavingaheartattackbyage50.Untreatedwomenhavea30%riskbyage60.Homozygousfamilialhypercholesterolemiaisararebyexceedinglyaggressiveformoffamilialhypercholesterolemia.Itleadstoaggressiveatherosclerosis.Thisprocessstartsevenbeforebirthandprogressesrapidly.Ifleftuntreated,heartattackorsuddendeatharelikelytooccurasearlyastheteenageyears.

TherapeuticGoalsNearly100%ofpeoplewithFHwillrequirecholesterol-loweringmedications.ForsomepeoplewithFH,moreaggressivemeasuresareneeded,includingLDL-apheresis(averysimpleprocedureinwhichLDL-Ccholesterolisremovedfromthebloodonaweeklyorbiweeklybasis).

PrevalenceAbout1in200to1in500peopleworldwidehavefamilialhypercholesterolemia.IntheUSalone,anestimated1.3millionpeoplelivewithFH.Yetonly10%ofthemarediagnosed.1in160,000to1in1millionpeoplehavehomozygousfamilialhypercholesterolemia.

MechanismofAction

PCSK9inhibitorHumanmonoclonalIgG2thatbindstoandpreventscirculatingproproteinconvertasesubtilistin/kexintype9(PCSK9)bindingtotheLDLreceptor(LDLR)onlivercells,therebypreventingPCSK9-mediateddegradation.ReductionsinserumLDL-CareassociatedwithincreasedliverLDLRcells.

Dosing

Repatha®isgivenasaninjectionundertheskin(subcutaneously)every2weeksor1timeeachmonth.Familialhypercholesterolemia-homozygous,incombinationwithotherlipid-loweringtherapies-420mgSQoncemonthlyPrimaryheterogygousfamilialhypercholesterolemia,incombinationwithastatin


Repatha®-evolocumab-140mgSQevery2weeksor420mgSQoncemonthlyPrimaryhypercholesterolemia,atheroscleroticcardiovasculardiseaseincombinationwithastatin-140mgSQevery2weeksor420mgSQoncemonthlyFamilialhypercholesterolemia-homozygous,incombinationwithotherlipid-loweringtherapies-(13yearsorolder)420mgSQoncemonthlyNoadjustmentnecessaryonrenalorhepaticimpairment

HowSuppliedRepatha®comesasasingle-use(1time)pre-filledautoinjector(SureClickautoinjector),orasasingle-usepre-filledsyringe.140mg/mlsubcutaneoussolution

Preparation/Storage StoreRepatha®intherefrigerator.Priortouse,Repatha®canbekeptatroomtemperatureintheoriginalcartonforupto30dayswithoutrefrigeration.

Administration

Repatha®isself-injectedundertheskinwithapre-filled,single-useSureClickAutoinjector.Removefromrefrigeratorandallowtowarmatroomtemperatureforatleast30minutesbeforeuse.InjectSQintoabdomen,thigh,orupperarm;rotateinjectionsitesanddonotinjectintoareaswheretheskinistender,bruised,redorhard.The420mgdoseshouldbeadministeredusing3prefilledsyringesgivenconsecutivelywithin30minutes.

AdverseEvents Possiblesideeffects:allergicreactions,runnynose,sorethroat,symptomsofthecommoncold,fluorflu-likesymptoms,backpain,redness,painorbruisingattheinjectionsite

Drug-drugordrug-foodInteractions Unknown

Contraindications DonotuseRepatha®ifyouareallergictoevolocumabortoanyoftheingredientsinRepatha®.

Warnings Discontinueifseriousallergicreactionsoccur.Latexallergy:Needlecovercontainsdrynaturalrubber(alatexderivative)andmaycauseallergicreaction.


Forsubcutaneoususeonly,patientmustlearnpropertechniqueandplacementofinjection.Instructpatienttoadministeramisseddoseassoonaspossibleiftherearemorethan7daysbeforethenextscheduleddose.If7daysorlessremain,skipthemisseddose.

Monitoring LDL-C,inpatientswithhomozygousfamilialhypercholesterolemia,4to8weeksaftertherapyinitiation

Studies

Amgenhascompletedenrollmentina27500patientstudyseekingtoclarifywhethertheeffectsofRepatha®onLDLcholesterollevelstranslateintocardiovascularbenefits,withresultsfromthetrialexpectedin2017.ItisnotknownifRepatha®issafeandeffectiveinchildrenwithhomozygousfamilialhypercholesterolemiawhoareyoungerthan13yearsofageorinchildrenwhodonothavehomozygousfamilialhypercholesterolemia.

Cost EligiblepatientscangethelppayingforRepatha®withtheRepathacopaycardCall1-844-REPATHAtolearnmoreabouttheprogramandenroll

Referenceswww.repatha.compackageinserthttp://pi.amgen.com/united_states/repatha/repatha_pi_hcp_english.pdfhttps://thefhfoundation.org/about-fh/what-is-fh/


Cresemba®–isavuconazoniumsulfateResidentName MichaelAnderson DrugName-Trade Cresemba® Manufacturer:AstellasPharmaUS OrphanDrug?NDrugName—generic isavuconazoniumsulfate DateApproved:March6,2015 BiologicEntity?N Element ProvidetheInformationintheColumnBelow:DiagnosticCategory InfectiousDiseaseIndication(s) Invasiveaspergillosisandmucormycosis


InvasiveaspergillosisComparedCresemba®andvoriconazoleinarandomized,double-blindcomparisonclinicaltrial(n=516)fortreatmentofinvasiveaspergillosisfoundthattheefficacyofisavuconazolewasnoninferiortothatofvoriconazole.InvasivemucormycosisAnopen-labeltrial(n=74)thatstudiedprimaryaswellassalvagetherapyofinvasivemucormycosisshowedefficacywithCresemba®thatwassimilartothatreportedforamphotericinBandposaconazole.

DiseaseSummary:

AspergillosisisafungalinfectioncausedbyacommonmoldcalledAsergillus.Thisfunguslivesbothindoorsandoutdoors.Itiscommontobreatheinthesporeseverydaywithoutgettingsick,butpatientsthatimmunocompromisedhaveahigherchanceofbecominginfectedwiththespores.Patientswillexperienceaseriesofsymptomssuchasfever,chestpain,cough,coughingupblood,SOBandothersympotomsmayoccurifinfectionspreadsfromthelungstootherpartsofthebody.

TherapeuticGoals Eradicatefungalinfection

Prevalence Invasiveaspergillosisisuncommonandoccursprimarilyinpatientsthatareimmunocompromised.Thereisayearlyrateof1to2casesper100,000populations.

Morbidity/MortalityInvasiveaspergillosisaffectspatientsthathaveweakenedimmunesystemssuchascancerpatients,stemcellorsolidorgantransplant,andpatientsthattakehighdosecorticosteroidsforlongperiodsoftime.Althoughinvasiveaspergillosisisuncommon,ithasahighmortalityrateinsoildorgantransplantpatientsat58%(one-yearsurvival)andstemcelltransplantpatientsat25%(one-yearsurvival).

MechanismofAction Itisanactivemetaboliteofisavuconazonium.Exertsitsantifungalactivitybyinhibitingthesynthesisofergosterol(fungalcellmembrane)

Dosing

Oral:Loadingdoseof372mgPOevery8hoursfor6doses.Maintenancedoseof372mgPOoncedaily.(Initiatemaintenancedosing12—24hoursafterthelastloadingdose)IV:Loadingdoseof372mgIVevery8hoursfor6doses.Maintenancedoseof372mgIVoncedaily.(Initiatemaintenancedosing12—24hoursafterthelastloadingdose)(nodosingadjustmentsneedtobemadeforrenalorhepaticimpairment)

HowSupplied 186mgcapsules372mgpowderforinjection


Cresemba®–isavuconazoniumsulfate

Preparation/Storage Reconstitutewith5mLofSWI.Dissolvecontentsbygentlemixingorswirling.Avoidshakingvials.Completeinfusionwithin6hoursofdilutionifkeptatroomtemperatureorwithin24hoursifkeptunderrefrigeration.

Administration IVmustbeadministeredoveraminimumof1hour.

AdverseEvents

Common:Cardiovascular:Peripheraledema(15.2%)Endocrinemetabolic:Hypokalemia(19.1%)Gastrointestinal:Constipation(14%),Diarrhea(23.7%),Nausea(27.6%),Vomiting(25%)Musculoskeletal:Backache(10.1%)Neurologic:Headache(16.7%)Respiratory:Cough(12%),Dyspnea(17.1%)Serious:Hepatic:Cholestasis,Hepatitis(Upto5%),Increasedliverfunctiontest(17.1%),Liverfailure(Upto5%)Immunologic:Hypersensitivityreaction(Upto5%)Renal:Renalfailure(10.1%)Respiratory:Acuterespiratoryfailure(7.4%)Other:Infusionreaction(6.2%)

Drug-drugordrug-foodInteractions Ketoconazole,lopinavir/ritonavir,andrifampin.

Contraindications

HypersensitivitytoCresemba®StrongCYP3A4inhibitorsStrongCYP3A4inducersShortQTsyndrome

Warnings

HepaticdiseaseInfusionrelatedreactionsHypersensitivitytoCresemba®Pregnancy/Breastfeeding(CatC)


Cresemba®canbetakenwithorwithoutfoodPatientsshouldinformtheirphysicianiftheyaretakinganyothermedicationsorOTCproductsCresemba®canincreaseordecreasetheefficacyofotherdrugsPatientsneedtoinformtheirphysicianiftheyarepregnant

Monitoring ResolutionoffungalinfectionLiverrelatedtests

Studies Noneatthistime

Cost 186mgcapsules:AWP-$1176(14capsules)372mgIV:AWP$286.20(1vial)

References KontoyiannisDP,GiladiM,LeeMetal.Aphase3,randomized,double-blind,non-inferioritytrialtoevaluateefficacyandsafetyofisavuconazoleversusvoriconazoleinpatients


Cresemba®–isavuconazoniumsulfatewithinvasivemolddisease(SECURE):outcomesininvasiveaspergillosispatients[abstract1211].In:ProgramandabstractsofIDWeek,Philadelphia,PA,2014.

FalciDR,PasqualottoAC.Profileofisavuconazoleanditspotentialinthetreatmentofsevereinvasivefungalinfections.Infectionanddrugresistance.2013;6:163-174

MicromedexHealthcareSeries[Internet].GreenwoodVillage(CO):TruvanHealthAnalytics.c2012-.Cresemba®;[cited2015November28].Availablefromhttp://www.micromedex.comRegistrationandloginrequiredClinicalPharmacology[Internet].Tampa(FL):GoldStandard,Inc.;c2013.Cresemba®;[cited2015November28].Availablefrom:http://www.clinicalpharmacology.comRegistrationandloginrequired.


Orkambi®-lumacaftorResidentName MarleeAndis DrugName-Trade Orkambi® Manufacturer:VertexPharmInc. OrphanDrug?YDrugName—generic lumacaftor/ivacaftor DateApproved:July2,2015 BiologicEntity?N Element ProvidetheInformationintheColumnBelow:DiagnosticCategory PulmonaryIndication(s) Cysticfibrosis


Twotrials(totaling1108participants)comparedtreatmentdifferencebetweenORKAMBI®(400mg/250mgq12hours)andplaceboforthemeanabsolutechangeinpercentpredictedFEV1frombaselineatWeek24(assessedastheaverageofthetreatmenteffectsatWeek16andatWeek24)was:

• 2.6percentagepoints[95%CI(1.2,4.0)]inTrial1(P=0.0003)• 3.0percentagepoints[95%CI(1.6,4.4)]inTrial2(P<0.0001)

ParticipantswithCFwhotookOrkambi®,twopillstakenevery12hours,demonstratedimprovedlungfunctioncomparedtothosewhotookplacebo.

DiseaseSummary2:

Genemutationsinthetransmembraneconductanceregulator(CFTR),whichispresentinthelungairwaysandsubmucosalglands,causesmucosalobstructionanddysregulationofchloridetransportacrosscellmembranes.ThemostcommonmutationidentifiedinCFpatientsisΔF508.Additionally,geneproteinsassociatedwithinflammatoryresponses,iontransport,andcellsignalingareaffected,resultinginvarietyofseverityamongstindividualswithaCFTRmutation.BecauseCFTRisaltered,chloridefailstobereabsorbed,impactingsodiumreabsorptionaswell.Thisfailedprocessproduces2-3timestheamountofsaltinanaffectedperson’ssweat.Complications:Thisoverlyingprocesscanaffectmanyorgans,suchasintestinalobstructionatbirth,blockageofpancreaticduct,bileductobstruction,andobstructionofthevasdeferensinutero.

TherapeuticGoals Improvedlungfunction,decreasedsymptoms

Prevalence Cysticfibrosis(CF)occursinapproximately1in3,500newborns.Allnewbornsaretestedatbirth.CFisanautosomalrecessivedisease.CFaffectsabout30,000peopleintheUnitedStatescurrently.

Morbidity/Mortality Inthe1970s,patientsonlysurvivedintotheirteenyears.By2006,progressincarehadextendedsurvivalto36years.

MechanismofAction

LumacaftorimprovestheconformationalstabilityofF508del-CFTR,resultinginincreasedprocessingandtraffickingofmatureproteintothecellsurface.IvacaftorisaCFTRpotentiatorthatfacilitatesincreasedchloridetransportbypotentiatingthechannel-openprobability(orgating)oftheCFTRproteinatthecellsurface

Dosing Lumacaftor400mg/ivacaftor250mgevery12hoursHowSupplied Lumacaftor200mg/ivacaftor125mgtablet,oralPreparation/Storage Storeatcontrolledroomtemperature

Administration Administer2tabletsbymouthevery12hours.


Orkambi®-lumacaftorAlwaystakeORKAMBI®tabletswithfat-containingfoodssuchaseggs,avocados,nuts,butter,peanutbutter,cheesepizza,andwhole-milkdairyproducts(suchaswholemilk,cheese,andyogurt).

AdverseEvents Mostcommon:Shortnessofbreath,upperrespiratorytractinfection,nausea,diarrhea,rash,fatigue,menstrualirregularities,increasedCPK

Drug-drugordrug-foodInteractions Drug-Food:increasesexposuretolumacaftorandivacaftor(clinicaltrialadministeredwithfattymeal)

Contraindications None

Warnings

• Worseningofliverfunctionforthosewithliverdisease• UsewithcautioninpatientswithCrCl<30mL/min• Cataractshavebeenreported• Increasedincidenceofrespiratoryevents

PatientEducation/CarePlanningConsiderations Educateforadministrationconsiderations,adverseeffectrecognition,providemedicationguide.

Monitoring

• CFmutationtest(priortotherapyifgenotypeisunknown)• Ophthalmologicalexaminations• ALT,AST,andbilirubin(baseline,every3monthsforthefirstyearoftherapy,andannuallythereafter• Signsandsymptomsofrespiratoryeffects(inpatientswithapercentpredictedFEV1<40)

Studies Cost $213/tabletAWP;VertexGPS:Guidance&PatientSupportavailable.

References

LumacaftorandIvacaftor.Lexi-Drugs.Lexicomp.WrightCC,VeraYY.Chapter18.CysticFibrosis.In:DiPiroJT,TalbertRL,YeeGC,MatzkeGR,WellsBG,PoseyL.eds.Pharmacotherapy:APathophysiologicApproach,9e.NewYork,NY:McGraw-Hill;2014.http://accesspharmacy.mhmedical.com/www.orkambi.com


Nucala®-mepolizumabResidentName MarleeAndis DrugName-Trade Nucala® Manufacturer:GlaxoSmithKline,LLC OrphanDrug?NDrugName—generic Mepolizumab DateApproved:November4,2015 BiologicEntity?Y Element DiagnosticCategory Pulmonary;Interleukin-5ReceptorAntagonist;MonoclonalAntibody,Anti-AsthmaticIndication(s) Add-onmaintenancetreatmentofsevereasthmainadultsandchildren12yearsandolderwithaneosinophilicphenotype


3placebocontrolledtrials(DREAM,MENSA,SIRIUS)testinguseofmepolizumabonpatientswithsevereasthmaonavailabletreatmentandidentifyingphenotypiccharacteristicsalsoprovedthatmepolizumabresultedin:

• fewerexacerbationsrequiringhospitalizationand/oremergencydepartmentvisits• Longertimetothefirstexacerbation• Greaterreductionsindailymaintenanceoralcorticosteroiddose• Nosignificantimprovementinlungfunction,asmeasuredbythevolumeofairexhaledbypatientsinonesecond

DiseaseSummary2:

Asthmaisamixofairflowobstruction,bronchohyper-responsiveness,andairwayinflammation.Symptomsbeginasanacute-phasereactionwhichisinitiatedbyactivationofIgEinselectcellswhilesimultenouslyactivatingmastcellsandmacrophageswhichreleaseproinflammatorymediatorsresultingincontractionofairwaysmoothmuscle,mucussecretionandvasodilation.Alatephasereactionwillsometimesfollowtheacute-phase6-9hourslaterandisindicativeofchronicasthma.Thisprocessisactivebyrecruitmentandactivationofeosinophils,T-cells,basophils,neutrophils,andmacrophages.Eosinophilsspecificallyinteractwithselectingsandintegrinsinordertoadheretoendothelium,releaseproinflammatorymediators,cytotoxicmediators,andcytokineswhichinjureairwaytissue.Chronicinflammationfollowedbyhealingmayresultinpermanentremodelingoftheairways.Ashtmaisadiseaseofcontinuousexacerbationandremission.Duringexacerbation,itoftenpresentsasdyspnea,wheezing,chesttightness,cough(oftenatnight).Itistriggeredbymanydifferentallergens,exercise,orspontaneously.Laboratorytestingshowingdropin15%ofFEV1following6minutesofmaximalexercise,elevatedeosinophilcountandIgEconcentrationintheblood.

TherapeuticGoals Reducesymptoms,induce/maintainremission,reduceneedforcorticosteroids,reducehospitalizations,increasequalityoflife

Prevalence

25.7millionpeopleintheUnitedStates(8.4%ofthepopulation.ItisthemostcommonchronicdiseaseinchildrenintheUnitedStates.(9.5%from0-17yearsold)3rdleadingcauseofpreventablehospitalization.Fromages0-10riskisgreaterinmales,becomesequalduringpuberty,andisgreaterinadultwomenvs.adultmen.AfricanAmericanshavehighesthospitalizationstatisticsandHispanicshavethelowest.Thereisastronggeneticcorrelation.

Morbidity/Mortality Deathratehasbeendecreasing,butiscurrently0.14per1,000personswithasthmareportedin2009;80-90%ofthosedeathsarepreventable.Keytopreventioniseducationofseverityofsymptoms.

MechanismofAction IL-5antagonist(IgG1kappa);IL-5isthecytokinemostresponsibleforgrowthanddifferentiation,recruitment,activation,andsurvivalofeosinophilswhichareassociatedwiththeinflammationpathogenesisofasthma.

Dosing 100mgsubcutaneouslyonceevery4weeks;nodosageadjustmentinrenalorhepaticimpairment


Nucala®-mepolizumab

HowSupplied 100mgsingle-dosevial(NDC0173-0881-01)(sterile,preservative-free,lyophilizedpowderforreconstitution)

Preparation/Storage

Reconstitutewith1.2mLSWFIresultinginafinalconcentration100mg/mL.Dissolvecontentsbygentlyswirlingthevialfor10secondsatatimeuntilthepowderisdissolved.Donotshakethevial.Thisprocessmaytakeupto5minutes.Thereconstitutedsolutionshouldbecleartoopalescent,colorlesstopaleyelloworpalebrown.Pleasediscardthesolutionifparticulatematterispresentorifthesolutionappearscloudyormilky.Discardifnotusedwithin8hoursofreconstitution.

Administration SubQinjectionintotheupperarm,thigh,orabdomen.Donotshakethereconstitutedsolution.

AdverseEvents Systemicallergicreactions,injectionsitereaction(8%),headache(19%),fatigue(5%),backpain(5%),musclespasm(3%),eczema(3%),pruritus(3%),Upperabdominalpain(3%),urinarytractinfection(3%),andinfluenza(3%),immunogenicity(6%;neutralizing<1%)

Drug-drugordrug-foodInteractions Noknownsignificantdrug-druginteractions

Contraindications Hypersensitivitytomepolizumaboranycomponentoftheformulation

Warnings

• Immediateanddelayedhypersensitivityreactionshavebeenreported• Herpeszosterinfluenzamayresult;considervaccinationpriortotherapy• Notindicatedforacuteasthmasymptoms;ifsymptomsworsenamonginitiation,seekmedicalattention• Patientswithexistinghelminthinfectionsshouldbetreatedforinfectionpriortostartingmedication;ifpatientscontract

helminthinfectionduringtherapy,mepolizumabtherapyshouldbediscontinueduntilinfectionresolves• Donotdiscontinuecorticosteroidssuddenlyuponinitiationofmepolizumab;Reductionincorticosteroiddoseshouldbe

gradualifnecessary• Thismedicationisnotindicatedforothereosinophilconditions


Educateforsignsofhypersensitivityreactions,educateforsignsofhelminthinfections,providepatientmedicationguide;currentlyforadministrationbyhealthcareprofessional

Monitoring FEV1,peakflow,and/orotherpulmonaryfunctiontests.Monitorforincreaseduseofshort-actingbeta2-agonistinhalers;maybeamarkerofadeterioratingasthmacondition.

Studies300mgSCtrialcurrentlyinprogresstodetermineefficacyvs.placeboinEosinophilicGranulomatosiswithPolyangiitis(EGPA);RecruitingforPharmacokineticsandPharmacodynamicsinSCAdministrationinChildren;OmalizumabSwitchtoMepolizumabisnotyetrecruiting;RecruitingforcompassionateuseinHypereosinophilicSyndrome(HES)

Cost 100mgvial:$3000.00

References

Mepolizumab.Lexi-Drugs.Lexicomp.Mepolizumabpackageinsert.KellyH,SorknessCA.Chapter15.Asthma.In:DiPiroJT,TalbertRL,YeeGC,etal.Pharmacotherapy:APathophysiologicApproach,9e.NewYork,NY:McGraw-Hill;2014.FDAapprovesNucala®totreatsevereasthma.FDANewsRelease.LastupdatedNov6,2015.


Cosentyx®-secukinumabResidentName ElizabethLagasse DrugName-Trade Cosentyx® Manufacturer:Novartis OrphanDrug?Y/NDrugName—generic Secukinumab DateApproved:January21,2015 BiologicEntity?Y/N Element DiagnosticCategory ImmunologyIndication(s) Moderatetosevereplaquepsoriasisinadultpatientswhoarecandidatesforsystemictherapyorphototherapy.

ClinicalTrialSummaryTwotrialscomparedsecukinumab300mg,secukinumab150mg,andplacebotodeterminereductioninPsoriasisAreaandSeverityIndex(PASI)scoreover52weeks.Twotrialsassessedsafety,tolerability,andusabilityoftheprefilledsyringesandtheSensoreadypenfor12weeks.

DiseaseSummary:Psoriasisisacommonskinconditionthateffectsthelifecycleofskincells.Skincellsbegintobuilduprapidlyonthesurfaceoftheskinformingthick,silveryscalesanditchy,dry,redpatchesthatcanbepainful.Psoriasiscanoccuranywhereonthebodyandmaycoversmallareasorverylargeareas.

TherapeuticGoals Stopskincellsfromrapidlygrowing,reduceinflammation,andpreventplaqueformation.

Prevalence Plaquepsoriasisoccursworldwide.About1-2%ofthepopulationintheUShasplaquepsoriasisanditeffectsmalesandfemalesequally.Onsettypicallyoccursbetween16-22yearsand57-60years.

Morbidity/MortalityMortalityisveryrarewithplaquepsoriasisandisusuallyassociatedwithreactionstotherapy.Thereisahighdegreeofmorbidityinthesepatientsincluding:pruritus,dryandpeelingskin,fissuring,self-consciousnessandembarrassment.Comorbidityiscommonwithobesityandcardiovasculardiseases.

MechanismofActionSecukinumabisahumanIgG1monoclonalantibodythatselectivelybindstotheinterleukin-17A(IL-17A)cytokineandinhibitsitsinteractionwiththeIL-17receptor.IL-17Aisanaturallyoccurringcytokinethatisinvolvedinnormalinflammatoryandimmuneresponses.Secukinumabinhibitsthereleaseofproinflammatorycytokinesandchemokines.

Dosing 300mgSCatweeks0,1,2,3,and4followedby300mgSCevery4weeks.

HowSupplied

• Cartonoftwo150mg/mL(300mgdose)Sensoreadypens(injection)• Cartonofone150mg/mLsingle-useSensoreadypen(injection)• Cartonoftwo150mg/mL(300mgdose)single-useprefilledsyringes(injection)• Cartonofone150mg/mLsingle-useprefilledsyringe(injection)• Cartonofone150mglyophilizedpowderinasingle-usevial(forinjection)(forhealthcareprofessionaluseonly)

Preparation/StorageCOSENTYX®Sensoreadypens,prefilledsyringesandvialsmustberefrigeratedat2ºCto8ºC(36ºFto46ºF).Keeptheproductintheoriginalcartontoprotectfromlightuntilthetimeofuse.Donotfreeze.Toavoidfoamingdonotshake.COSENTYX®doesnotcontainapreservative;discardanyunusedportion.

Administration SubcutaneousAdverseEvents Nasopharyngitis,diarrhea,andupperrespiratorytractinfectionDrug-drugordrug-foodInteractions LiveVaccines

Contraindications SerioushypersensitivityreactionstosecukinumabortoanyofitsexcipientsWarnings • Infections:Seriousinfectionshaveoccurred.CautionshouldbeexercisedwhenconsideringtheuseofCOSENTYX®in


Cosentyx®-secukinumab

patientswithachronicinfectionorahistoryofrecurrentinfection.Ifaseriousinfectiondevelops,discontinueCOSENTYX®untiltheinfectionresolves.

• Tuberculosis(TB):PriortoinitiatingtreatmentwithCOSENTYX®,evaluateforTB• Crohn’sDisease:Exacerbationsobservedinclinicaltrials.CautionshouldbeexercisedwhenprescribingCOSENTYX®topatientswithactiveCrohn’sdisease.

• HypersensitivityReactions:Ifananaphylacticreactionorotherseriousallergicreactionoccurs,discontinueCOSENTYX®immediatelyandinitiateappropriatetherapy

PatientEducation/CarePlanningConsiderations Educateforsignsofinfectionandhypersensitivityreactions.

Monitoring Monitorfors/sofTB,infection,andexacerbationsofCrohn’sdisease.

Studies Activetrials:ModeratetoSevereNailPsoriasis,ActiveAnkylosingSpondylitis,ModeratetoSeverePalmoplantarPsoriasis,JapanesesubjectswithGeneralizedPustularPsoriasis(GPP),PatientswithPsoriasis

Cost Cosentyx®Connectprogramprovidesco-payassistance.References Cosentyx®packageinsert,PlaquepsoriasisMedscape


Kanuma®-sebelipasealfaResidentName CollinChan DrugName-Trade Kanuma® Manufacturer:Alexion OrphanDrug?YDrugName—generic Sebelipasealfa DateApproved:12/8/15 BiologicEntity?Y

Element ProvidetheInformationintheColumnBelow:DiagnosticCategory Endocrine

Indication(s) LysosomalAcidLipasedeficiency


1) TrialinChildrenwithGrowthFailureDuetoEarlyOnsetysosomalAcidLipaseDeficiency/WolmanDisease- Multicenter,open-label,single-armstudyof9infants(1-6months)withLALdeficiencywhoreceived0.35mg/kgqWeeklyx2weeks

then1mg/kgqWeekly.Doseescalatedto3mg/kgqWeeklyuponclinicalresponse,asearlyas1monthandupto20monthsafterstarting1mg/kg.Thisstudycomparedthesurvivalexperienceofpatientspast12monthsforthisstudycomparedtoahistoricalcorhort(21patients).Inthehistorical,0/21patientssurvivedbeyond8months.Inthisstudy,6/9patientssurvivedbeyond12months,with1patientsurvivingto15months.

- 1mg/kgqWeeklyimprovedAST,ALT,andweightgainwithinfirstseveralweeksoftreatment2) APhase3TrialofSebelipaseAlfainLysosomalAcidLipaseDeficiency

- Multicenter,double-blind,placebo-controlledstudyof66childrenandadults(4-58years)withLALdeficiency,followedbyanopen-labeltreatmentforall.Patientsreceived1mg/kg(n=36)orplacebo(n=30)everyotherweekx20weeks.ALTwasnormalizedin31%ofthesebelipasealfagroupand7%intheplacebo.Treatmentwithsebelipasealfaduringtheopen-labelforplacebopatientsresultedinrapidimprovementsinALTandlipidparameters.

DiseaseSummary:

Theliposomalacidlipaseplaysaroleinbreakingcholesterylestersandtriglycerides.InindividualswithLALdeficiency,anaccumulationofthesesubstratescanoccurthroughoutthebody,suchasintheliver,spleen,andintestinalwall.Accumulationinthelivercanresultinhepatomegaly,fibrosis,andcirrhosis.Accumulationinthespleencanresultinanemia,thrombocytopenia,andsplenomegaly.Accumulationintheintestinalwallcanleadtogrowthfailureandmalabsorption.Also,withtheincreaseddyslipidemia,patientsareatincreasedriskforcardiovasculardiseaseandartherosclerosis.

TherapeuticGoals ProlongsurvivalandreducetheaccumulationofcholesterylestersandtriglyceridesthroughoutthebodyPrevalence 1:500,000;fewerthan200,000individualsintheUShavethisdiseaseMorbidity/Mortality

ForindividualswithnoenzymaticactivityforLAL-D,thelifeexpectancyisbetween4-6months.DiseaseseverityisdeterminedbyhowdeficienttheLALis.

MechanismofAction Recombinanthumanlysosomalacidlipase.Sebelipasealfacatalysesthelysosomalhydrolysisofcholesterylestersandtriglycerides

Dosing

ForRapidlyProgressiveLALDeficiencywithinfirst6monthsoflife:1mg/kgIVqWeeklyandupto3mg/kgQWeeklyForPediatric/AdultswithLAL-D:


Kanuma®-sebelipasealfa1mg/kgIVeveryotherweek

HowSupplied 20mg/10mLvial

Preparation/Storage

Remove#ofvialsfromtherefrigerator.CalculatetherequiredvolumeofKanuma®needed.Refertothepackageinsert’scharttoseehowmuchSodiumChloride0.9%isneededtodilutetheKanuma®.Dilutedsolutionmaybestoredupto24hoursintherefrigerator.Protectfromlight

Administration Infuseoveratleast2hours.Inpatientsusing1mg/kgandwhotolerateit,patientsmayinfuseover1hourAdverseEvents Headache,Diarrhea,vomiting,fever,rhinitis,anemia,cough,nasopharyngitis,urticariaDrug-drugordrug-foodInteractions Nonenoted

Contraindications NoneWarnings HypersensitivitytoanycomponentofKanuma®.HypersensitivitytoeggsoreggproductsPatientEducation/CarePlanningConsiderations

Hypersensitivityreactions

Monitoring NoneStudies NoneasofnowCost $12,000per20mg/10mLvial

References

1. Sebelipasealfaforinjection[packageinsert].AlexionPharmaceuticalsInc.Dec2015.2. BurtonBK,etal.APhase3TrialofSebelipaseAlfainLysosomalAcidLipaseDeficiency.NEnglJMed.2015Sep10;373(11):1010-20.3. TrialinChildrenWithGrowthFailureDuetoEarlyOnsetLysosomalAcidLipase(LAL)Deficiency/WolmanDisease.<

https://clinicaltrials.gov/ct2/show/study/NCT01371825>Mar2015.

2016NHIAAnnualConference&ExpositionSession13-D.NewDrugsandBiologics2015Coagadex®-CoagulationFactorX(Human)

ResidentName CollinChan DrugName-Trade Coagadex® Manufacturer:BioProductsLaboratory OrphanDrug?YDrugName—generic CoagulationFactorX(Human) DateApproved:10/20/15 BiologicEntity?N

Element ProvidetheInformationintheColumnBelow:DiagnosticCategory Hematology

Indication(s)

Usedinadultsandchildren(12yearsandabove)withhereditaryFactorXdeficiencyfor:- On-demandtreatmentandcontrolofbleedingepisodes- PerioperativemanagementofbleedinginpatientswithmildhereditaryFactorXdeficiency(Patientswithmoderate-severedeficiency

hasnotbeenstudied)


Multi-center,non-randomizedstudyof18patientsweregivenatleast1dosefortreatmentofspontaneous,traumatic,andheavymenstrualbleedingepisodes.Drugwasshowntobeeffectiveincontrollingbloodlossduringandaftersurgeryinmilddeficiencies.Drugalsodemonstratedeffectivenessincontrollingbleedingepisodes.

DiseaseSummary:Inthecoagulationcascade,FactorXisneededtoconvertProthrombintoThrombin.Withoutthisconversion,thrombinwouldnotbeabletoconvertfibrinogentofibrin,whichultimatelyformstheclot.Asaresult,individualswithFactorXdeficiencywillbeunabletoclotaseasilyasothers.Symptomsofspontaneousbleedinganduncontrolledbleedingistobeexpected.Patientsareatriskofexcessivebloodloss.

TherapeuticGoals Treatmentgoalsaretostopandcontrolbleedingepisodes.

Prevalence TheincidenceofFactorXdeficiencyisestimatedat1:500,000–1:1,000,000people.Itisanautosomoalrecessivediseasethataffectsmenandwomenequally.

Morbidity/Mortality

FactorXDeficiencyisalife-longdisease.Morbidityandmortalitydependsontheseverityofdisease,withtheclassificationrangingfrommildtosevere.Thosewithasevereformofthediseaseareathigherriskofmorefrequentandseverebleedingepisodes.

MechanismofAction

Coagadex®temporarilyreplacesFactorXinpatientstorestorehemostasis.TheadministeredFactorXcanbeactivatedbyFactorIXaorVIIaintoFactorXa,whichcanthenconvertprothrombintothrombin.

Dosing

OnDemandTreatment:25IU/kgwhenthefirstsignofbleedingoccurs,repeatq24hrsuntilbleedingstopsPerioperativeManagementofBleedingDose=BodyWeight(kg)xDesiredFactorXRise(IU/dL)x0.5

- Pre-surgerygoal:70-90IU/dL- Post-surgerygoal:≥50IU/dL

- RepeatdoseasnecessarytomaintainplasmalevelsatgoalForboth:maxof60IU/kg/day

HowSupplied ~250IU(with2.5mLSterileWaterDiluent)~500IU(with5mLSterileWaterDiluent)

2016NHIAAnnualConference&ExpositionSession13-D.NewDrugsandBiologics2015Coagadex®-CoagulationFactorX(Human)

Preparation/Storage

- Protectfromlight- Storeinrefrigeratororroomtemp(36–86F)- UsereconstitutedCoagadex®within1hourofreconstitution

Administration AdministerIV@10mL/min,withamaxof20mL/minAdverseEvents Infusionsiteerythema,Infusionsitepain,Fatigue,BackPainDrug-drugordrug-foodInteractions

- UsewithcautioninpatientsreceivingotherplasmaproductsthatmaycontainFactorX- Coagadex®islikelytobecounteractedbyFactorXainhibitors

Contraindications PriorhypersensitivitytoCoagadex®oranyofitscomponentsWarnings Hypersensitivityreactions,FormationofNeutralizingAntibodies,Transmissionofblood-borneinfectiousagentsPatientEducation/CarePlanningConsiderations

EducateforsignsofhypersensitivityreactionsandtothatinhibitorstoFactorXcanbedeveloped.Also,educationthatCoagadex®ismadefromhumanbloodandmaycontaininfectiousagents

Monitoring - MonitorFactorXactivitybyperformingavalidatedtest- Nijmegen-BethesdaInhibitorAssay

Studies RecruitingpatientsforProphylaxisofBleedinginchildren<12yearsCost Unavailable

References

1.Coagadex®(CoagulationFactorX[Human])[packageinsert].Durham,NC27701:BioProductsLaboratory;2015.2.APhaseIIIOpen,MulticentreStudytoInvestigatetheSafety,PharmacokineticsandEfficacyofBPL'sHighPurityFactorXintheProphylaxisofBleedinginFactorXDeficientChildrenUndertheAgeof12Years.In:ClinicalTrials.gov[Internet].Bethesda(MD):NationalLibraryofMedicine(US).2000-[cited2015Dec3].Availablefrom:https://clinicaltrials.gov/show/NCT01721681.NLMIdentifier:NCT01721681.


Unituxin®-dinutuximabResidentName JesseS.Peterson DrugName-Trade Unituxin® Manufacturer:UnitedTherapeutics OrphanDrug?YESDrugName—generic dinutuximab DateApproved:March10th,2015 BiologicEntity?YES

Element DiagnosticCategory Oncology

Indication(s)Dinutuximabisindicatedincombinationwithgranulocyte-macrophagecolony-stimulatingfactor(GM-CSF),interleukin-2(IL-2),and13-cis-retinoicacid(isotretinoin)forthetreatmentofpediatricpatientswithhigh-riskneuroblastomawhopreviouslyachievedatleastapartialresponsetofirst-linemultiagent,multimodalitytherapy(surgery,chemotherapy,radiation)


Thesafetyandefficacyofdinutuximabwereevaluatedinarandomized(1:1)cohortofasingle,open-label,multicenterclinicaltrialconductedinpediatricpatientswithhighriskneuroblastoma.Atotalof226patientswererandomizedtodinutuximab,13-cis-retinoicacid,GM-CSF,andIL-2(n=113)or13-cis-retinoicacidalone(n=113).3yearsaftertreatmentassignment63%ofUnituxin®groupaliveandfreeoftumorgrowthorrecurrencecomparedto46%withisotretinoinalone.Themostcommonsevereandlife-threateningadversereactionsofdinutuximabareneuropathicpain(51%),pyrexia(40%),infusion-relatedreactions(25%),capillaryleaksyndrome(23%),hypotension(16%),sepsis(16%),devicerelatedinfection(16%),diarrhea(13%),urticaria(13%)andhypoxia(12%).Thebenefitsofdinutuximaboutweightheseseriousandsometimesfatalrisks,whicharecommonlyacceptedinthepediatriconcologycommunitybybothhealthcareproviders,patients,andtheirparents,asthepriceofimprovementinoverallsurvivalanddelayingtimetorelapse.

DiseaseSummary:

Neuroblastomatypicallyoccursinchildrenyoungerthanfiveyearsofage.Neuroblastomaisararecancerthatformsfromimmaturenervecells.Itusuallybeginsintheadrenalglands(40%)butmayalsodevelopintheabdomen(25%),thoracic(15%),cervical(5%),pelvicganglia(5%),andlesscommonlyintheCNS.Mostcommonlypresentsasalocalizedmassandsignsandsymptomsarearesultoftumormassandmetastases.

TherapeuticGoals

Goal:Event-freesurvival.Threeyearsaftertreatmentassignment,63percentofparticipantsreceivingtheUnituxin®combinationwerealiveandfreeoftumorgrowthorrecurrence,comparedto46percentofparticipantstreatedwithisotretinoinalone.Inanupdatedanalysisofsurvival,73percentofparticipantswhoreceivedtheUnituxin®combinationwerealivecomparedwith58percentofthosereceivingisotretinoinalone

Prevalence AccordingtotheNationalCancerInstitute,neuroblastomaoccursinapproximatelyoneoutof100,000childrenandisslightlymorecommoninboys.Thereareanestimated650newcasesofneuroblastomadiagnosedintheUnitedStateseachyear.

Morbidity/ Patientswithhigh-riskneuroblastomahavea40to50percentchanceoflongtermsurvivaldespiteaggressivetherapy


Unituxin®-dinutuximabMortality

MechanismofAction

DinutuximabbindstotheglycolipidGD2.Thisglycolipidisexpressedonneuroblastomacellsandonnormalcellsofneuroectodermalorigin,includingthecentralnervoussystemandperipheralnerves.DinutuximabbindstocellsurfaceGD2andinducescelllysisofGD2expressingcellsthroughantibody-dependentcell-mediatedcytotoxicity(ADCC)andcomplement-dependentcytotoxicity(CDC).

Dosing

TherecommendeddoseofUnituxin®is17.5mg/m2/dayadministeredasanintravenousinfusionover10to20hoursfor4consecutivedaysforamaximumof5cycles.Initiateataninfusionrateof0.875mg/m2/hourfor30minutes.Theinfusionratecanbegraduallyincreasedastoleratedtoamaximumrateof1.75mg/m2/hour.

HowSupplied Unituxin®issuppliedinacartoncontainingone17.5mg/5mL(3.5mg/mL)single-usevial.Preparation/Storage

StoreUnituxin®vialsunderrefrigerationat2°Cto8°Cuntiltimeofuse.Donotfreezeorshakethevial.Keepthevialintheoutercartoninordertoprotectfromlight.

Administration

Pretreatmentwithantihistamines,analgesics,antipyretics,andIVhydrationisrequiredpriortoeachdoseofdinutuximab.

IntravenousHydration:Administer0.9%SodiumChlorideInjection,USP10mL/kgasanintravenousinfusionoveronehourjustpriortoinitiatingeachUnituxin®infusion.

Analgesics:Administermorphinesulfate(50mcg/kg)intravenouslyimmediatelypriortoinitiationofUnituxin®andthencontinueasamorphinesulfatedripataninfusionrateof20to50mcg/kg/hourduringandfortwohoursfollowingcompletionofUnituxin®.Administeradditional25mcg/kgto50mcg/kgintravenousdosesofmorphinesulfateasneededforpainuptoonceevery2hoursfollowedbyanincreaseinthemorphinesulfateinfusionrateinclinicallystablepatients.Considerusingfentanylorhydromorphoneifmorphinesulfateisnottolerated.Ifpainisinadequatelymanagedwithopioids;consideruseofgabapentinorlidocaineinconjunctionwithintravenousmorphine.

AntihistaminesandAntipyretics:Administeranantihistaminesuchasdiphenhydramine(0.5to1mg/kg;maximumdose50mg)intravenouslyover10to15minutesstarting20minutespriortoinitiationofUnituxin®andastoleratedevery4to6hoursduringtheUnituxin®infusion.Administeracetaminophen(10to15mg/kg;maximumdose650mg)20minutespriortoeachUnituxin®infusionandevery4to6hoursasneededforfeverorpain.Administeribuprofen(5to10mg/kg)every6hoursasneededforcontrolofpersistentfeverorpain.

AdverseEvents

Themostcommonadversereactionsobservedatarateofatleast25%inclinicaltrialsincludedpain,pyrexia,thrombocytopenia,lymphopenia,infusionreactions,hypotension,hyponatremia,increasedALT,anemia,vomiting,diarrhea,hypokalemia,capillaryleaksyndrome,neutropenia,urticaria,hypoalbuminemia,increasedAST,andhypocalcemia.Boxedwarning:


Unituxin®-dinutuximab

Drug-drugordrug-foodInteractions Natalizumab,TNF-blockers,livevaccines Nodrug-druginteractionstudieshavebeenconductedwith

dinutuximab.

Contraindications Reasonspatientsshouldnotreceivethedrug Priorhypersensitivitytovedolizumab

HistoryofanaphylaxistodinutuximabWarnings

Avoiduseinpatientswithactiveinfections.


Informationtoprovidetopatients,potentialinterventions,treatmentendpoints

Educateforsignsofhypersensitivityreactions,infection,neurologicalsymptoms,liverdamage.Providepatientmedicationguide.

1.) PremedicationSection2.) MonitoringSection

MonitoringRoutinetests(labs,x-ray,etc),physicalassessment,REMSprogramrequirements

TBscreening,hypersensitivity,s/sPML,noREMS

Monitorforsignsandsymptomsofinfusionreactions(eg,hypotension,dyspnea,edema)duringdinutuximabadministrationandatleast4hourspostexposure.Pretreatpatientspriortoeachdoseofdinutuximabwithantihistamines,analgesics,antipyretics,andIVhydration.Monitorpatientsforsignsandsymptomsofcapillaryleak


Unituxin®-dinutuximabsyndrome,systemicinfection,andneurologicaldisordersoftheeye.Monitorforsignsofatypicalhemolyticuremicsyndrome.Permanentlydiscontinuedinutuximabandinitiatesupportivemeasuresinthepresenceofhemolyticuremicsyndrome.Monitorforsignsandsymptomsofpainand/orperipheralneuropathy.Appropriatelymanagepainwithanalgesicsanddosereductions,asneeded.Monitorperipheralbloodcountscloselythroughouttherapyandmonitorserumelectrolytesdailyduringdinutuximabtherapy.

StudiesCurrentclinicaltrialstoexpandusestootherdiseasesorspecialpopulations?

RecruitingforSCadministrationtrial PhaseII:treatmentofrecurrentosteosarcomawith

Unituxin®+sargramostimhttps://clinicaltrials.gov/ct2/results?term=Unituxin®&Search=Search

CostPublicsourcesonly–noproprietaryinformation,manufacturerco-payassistanceprogramsifavailable

EntyvioConnectprogramprovidesco-payassistance.

EstimateviaReuters@150,000/yearhttp://in.reuters.com/article/2015/03/10/united-therapeutics-fda-idINL4N0WC4J320150310

References Listallreferences

PackageInsert:http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125516s000lbl.pdfCancer.gov:http://www.cancer.gov/types/neuroblastoma/hp/neuroblastoma-treatment-pdq#section/all


Natpara®-parathyroidhormoneResidentName JoshuaJaussi DrugName-Trade Natpara® Manufacturer:NPSPharmaceuticals OrphanDrug?YDrugName—generic parathyroidhormone DateApproved:January23,2015 BiologicEntity?Y

Element ProvidetheInformationintheColumnBelow:DiagnosticCategory Endocrine

Indication(s) HypocalcaemiasecondarytohypoparathyroidismClinicalTrialSummary

Evaluatedina24-week,randomized,double-blind,placebo-controlled,multicentertrial.patientswithestablishedhypoparathyroidismreceivingcalciumandactiveformsofvitaminD(vitaminDmetaboliteoranalogs)wererandomized(2:1)toNATPARA(n=84)orplacebo(n=40).

DiseaseSummary:

Ionizedcalciumisthenecessaryplasmafractionfornormalphysiologicprocesses.Intheneuromuscularsystem,ionizedcalciumfacilitatesnerveconduction,musclecontraction,andmusclerelaxation.Calciumisnecessaryforbonemineralizationandisanimportantcofactorforhormonalsecretioninendocrineorgans.PTHstimulatesosteoclasticbonereabsorptionanddistaltubularcalciumreabsorptionandmediates1,25-dihydroxyvitaminD(1,25[OH]2D)intestinalcalciumabsorption.Commonsymptomsofhypocalcemiainclude:musclespasms,numbnessandtinglinginthehands,feet,face,anddepression.

TherapeuticGoalsThegoalofNatpara®treatmentistoachieveserumcalciumwithinthelowerhalfofthenormalrange.

Prevalence

Hypoparathyroidismisrare,withanestimated59,000individualsintheUnitedStatessufferingfromthedisorder.Themostcommoncauseisinadvertentremovalorirreversibledamagetotheparathyroidglandsduringthyroidorothernecksurgery.OthercausesincludeautoimmunediseaseandraregeneticdisorderssuchasDiGeorgesyndrome,familialisolatedhypoparathyroidism,autoimmunepolyglandularsyndrometype1andautosomaldominanthypocalcemia.

Morbidity/Mortality

Hypoparathyroidpatientsoftendescribesymptomsof“brainfog”andotherneurocognitivecomplaints.hypoparathyroidpatientsonconventionaltherapyhavecompromisedqualityoflifecomparedtonormalsubjectsdespiteeucalcemia.

MechanismofAction

Parathyroidhormoneraisesserumcalciumbyincreasingrenaltubularcalciumreabsorption,increasingintestinalcalciumabsorptionbyconverting25-OHvitaminDto1,25-OH2vitaminD.Parathyroidhormonealsoincreasesboneturnoverwhichreleasescalciumintothecirculation.

Dosing

Therecommendedinitialdoseis50mcgoncedailyadministeredsubcutaneouslyinthethigh(alternatingthighsdaily).Fordosetitration,thefollowingisrecommended:forserumcalciumlessthan8mg/dL,increasethedoseinincrementsof25mcgsubcutaneouslyevery4weeks.Maximumdose:100mcgsubcutaneouslyoncedaily.

HowSupplied

25mcgpowderforinjection50mcgpowderforinjection75mcgpowderforinjection100mcgpowderforinjection


Natpara®-parathyroidhormone

Preparation/Storage

UnmixedNATPARA®medicinecartridges:RefrigerateNATPARAbetween36°Fto46°F(2°Cto8°C).Donotfreeze.•MixedNATPARA®medicinecartridges:Refrigeratebetween36°Fto46°F(2°Cto8°C).Donotfreeze.YoucanusetheQ-Cliqpenforupto14daysaftermixingthemedicinecartridge.ThrowawaythemixedNATPARA®medicinecartridges14daysaftermixingthemedicinecartridge.•StoreNATPARA®awayfromheatandlight.•DonotfreezeorshakeNATPARA®.DonotuseNatpara®ifitwasfrozenorshaken.

Administration Patientcanself-administerviaSQinjection

AdverseEvents

Gastrointestinaladverseeventsreportedwiththeuseofparathyroidhormoneinpatientswithhypoparathyroidismincludenausea(18%),diarrhea(12%),vomiting(12%),andupperabdominalpain(7%).Sensory/nervoussystemadverseeventsreportedwiththeuseofparathyroidhormoneinpatientswithhypoparathyroidismincludeparesthesias(31%),headache(25%),hypoesthesia(14%),andfacialhypoesthesia(6%).Musculoskeletaladverseeventsreportedwiththeuseofparathyroidhormoneinpatientswithhypoparathyroidismincludearthralgia(11%),musculoskeletalpainintheextremity(10%),andneckpain(6%).

Drug-drugordrug-foodInteractions Alendronateanddigoxin

Contraindications HypersensitivitytoNatpara®

Warnings Thereisapotentialriskofosteosarcoma(osteogenicsarcoma)withtheuseofparathyroidhormone.Safetyandefficacyofparathyroidhormonehavenotbeenestablishedinpediatricpatients.


Natpara®isavailableonlythrougharestrictedprogramcalledtheNATPARA®REMSProgram,becauseofthepotentialriskofosteosarcoma.

Monitoring

Serum25(OH)DconcentrationsSerumalbuminandcalciumSerumintactparathyroidhormoneconcentrations(iPTH)

Studies N/ACost Discountdrugcardavailable

References

Parathyroidhormone(Natpara®)forinjectionpackageinsert.Bedminster,NJ:NPSPharmaceuticals,Inc.;2015Jan.ParathyroidhormonetherapyforhypoparathyroidismCusano,NatalieE.etal.BestPractice&ResearchClinicalEndocrinology&Metabolism,Volume29,Issue1,47-55ClinicalPharmacology[Internet].Tampa,(FL):Elsevier/GoldStandard,Inc.c2015.Natpara®[updated2015Oct23;cited2015Nov15].


Avycaz®-ceftazidime/avibactamResidentName AlfredOlumba DrugName-Trade Avycaz® Manufacturer:Allergan(Actavis) OrphanDrug?NDrugName—generic CeftazidimeandAvibactam DateApproved:02/25/2015 BiologicEntity?N

Element ProvidetheInformationintheColumnBelow:DiagnosticCategory InfectiousDisease

Indication(s) • ComplicatedIntra-abdominalInfections(cIAI)whenusedconcomitantlywithmetronidazole• ComplicatedUrinaryTractInfections,includingpyelonephritis


EfficacypartiallysupportedonpreviousstudiesceftazidimeintreatmentsforcIAIandcUTI.Avibactamcomponentefficacy&safetywasestablishedinvitro&animalstudy.Followingtrialsnotdesignedwithanyformalhypothesesforinferentialtestingagainsttheactivecomparators.Phase2Trials:

• 203cIAIpatientscomparedwithmeropenem-similarratesofadverseeventsbetweenAvycazandplacebo(Nausea&vomitingmostcommon)

• 135cUTIpatientscomparedwithImipenem-cilastatinfoundsimilarratesofadverseeventsbetweenavycaz(Anxiety&Constipationmostcommon)

Phase3Trial:• cIAIDeathin2.5%ofavycaz+metronidazolevs1.5%meropenem• 25.8%ofdeathinavycaz+metronidazolepatientswithCrCl30to50mL/min

DiseaseSummary:

cIAIsarecausedbyawidevarietyofoftenresistantbacteriabothgrampositiveandnegativeanddifferentiatedfromuncomplicatedIAIbytheinfectiousprocessgoingfrominfectingoneorgantomanyabdominalorgansandcausingperitonitis.Symptomsincludedgastrointestinaldistress,fever,tendernessofarea,anddecreasedappetiteandfatigueasinfectionprogresses.cIAIcanbecausedbysurgicalprocedurestoorganruptures&trauma.cUTIischaracterizedbythetractinfectionbeingassociatedwithriskfactorssuchasdiabetesorindwellingcatheterthatwillincreasethechanceofinfection.cUTIpatientswillalsopresentwithoneormoreofthefollowing:multi-drugresistantbacteria,immunocompromised,orabnormalGUtract(i.e.kidneystone).Symptomsincludedysuria,flankpain,backandsuprapubicpain,andfever.

TherapeuticGoals Improvesymptomsstemmingfromresistantbacterialinfectionsintheeventtherearefewornoothertreatmentoptionsleft

Prevalence About150millionUTIsoccuryearly.WomenaremoresoaffectbyUTIswith1in2experiencingatleastoneintheirlifetime.OverallIntra-abdominalinfectionsprevalenceandratesarehardtoestablishduetoverityofcausesandunderlyingdiseaseprocessthatcausethem.

Morbidity/Mortality

Mortalityratesassociatedwithintra-abdominalinfectionsrangefrom3.5%tomorethan60%dependinghowearlytheinfectionisdiagnosedandtheamountofdamagecausedbyinfection.40%ofnosocomialinfectionsareUTI’swithroughly40%ofthoseleadingtogramnegativebacteremia.UTIhavea3.2%mortalityratewhichcanincreasetoroughly10%ifitbecomesbacteremiaorsepsis.

MechanismofAction

3rdgenerationcephalosporin/non-betalactambetalactamaseinhibitorcombination;Ceftazidimeisbactericidalbybindingtopenicillin-bindingproteins(PBPs)inhibitingcellwallsynthesis.Avibactaminhibitsseveralbeta-lactamaseslikeKlebsiellapneumoniaecarbapenemasesthusprotectingCeftazidimefromdestructionwithoutaffectingantibioticactivity.


Avycaz®-ceftazidime/avibactam

DosingcIAI:2.5gIVevery8hoursinconjunctionwithmetronidazolefor5to14dayscUTI:2.5gIVevery8hoursfor7to14days

HowSupplied 2.5gramsingledosevial(2gmCeftazidime&0.5gramAvibactam)

Preparation/Storage

Reconstitutewith10mL(SWI,NS,D5W,&LR).Dissolvecontentsbygentlymixingorswirling.Dissolvedsolutioncannotsitformorethan30minutes.Oncedissolvedwithdrawcontentsandfurtherdilutewith50-250mLofchosendiluent.BUD:12hours(roomtemperature),24hours(refrigerated).Storeatroomtemperatureandprotectfromlightpriortomixing&administration.

Administration IVintermittentinfusionover2hours,flushwithsalinepreandpostinfusionwithpossibleheparinpostsecondsalineflush.

AdverseEventscIAI:Nausea&vomitingmostcommoncUTI:Anxiety&Constipationmostcommon

Drug-drugordrug-foodInteractions Probenecid&false-positivesforglucoseinurine

Contraindications Hypersensitivitytoceftazidime,avibactam,orotherdrugsofthecephalosporinclass.

Warnings • DecreasedClinicalresponsewithbaselineCrCL30to≤50• PossibleClostridiumdifficileassociatedDiarrhea


EducateonsignsofHypersensitivity(i.e.wheezing,facialswelling,itching),possibilityofseriousdiarrhea,neurologicalsymptoms,andfinishingfullcourseofdrugandantibacterialresistance.

Monitoring Signsofhypersensitivitywithfirstdose,reductionininfectionsymptoms,renalfunctionparticularlyinrenallyimpaired

Studies2trials

• Phase1safety&tolerabilityforPediatricpatients-recentlyconcluded• PharmacokineticsstudyinCysticFibrosishasbeenproposedandslatedtostart

Cost One2.5gramvialwillcost$342.00.NoCo-payassistance/hardshipprogramsavailableatthistime

References

1) "AdultUTI:AmericanUrologicalAssociation."AdultUTI:AmericanUrologicalAssociation.AmericanUrologicalAssociation,n.d.Web.22Jan.2016.

2) Avycazceftazidime/avibactam[prescribinginformation].Cincinnati,OH:ForestPharmaceuticals;September2015.3) CeftazidimeandAvibactam."LexiComp.N.d.Lexicomp.Web.05Jan.2016.4) SafetyandTolerabilityofCeftazidime-AvibactamforPediatricPatientsWithSuspectedorConfirmedInfections."Safetyand

TolerabilityofCeftazidime-AvibactamforPediatricPatientsWithSuspectedorConfirmedInfections.AstraZeneca&ForestLaboratories,11June2015.Web.22Jan.2016.<https://clinicaltrials.gov/ct2/show/NCT01893346?term=avycaz&rank=4>

5) Steady-statePharmacokineticsofCeftazidime/AvibactaminCysticFibrosis."Steady-statePharmacokineticsofCeftazidime/AvibactaminCysticFibrosis.ClinicalTrials.gov/UniversityofSouthernCalifornia,20July2015.Web.05Jan.2016.<https://clinicaltrials.gov/ct2/show/NCT02504827?term=avycaz&rank=3>

6) UTIandCAUTI."UTIandCAUTI.VirginaDepartmentOfHealth,2016.Web.22Jan.2016<http://www.vdh.virginia.gov/epidemiology/surveillance/hai/uti.htm>

7) ClinicalUpdatesinInfectiousDiseases:IntraabdominalInfections-ASurgicalPerspective."ClinicalUpdatesinInfectiousDiseases.


Avycaz®-ceftazidime/avibactamNationalFoundationforInfectiousDiseases,1996.Web.22Jan.2016.http://www.nfid.org/content-conversion/idarchive/intraabdominal.html

8) Bowen,Ashley,andWayneJ.Hellstorm,MD."UrinaryTractInfections:APrimerforClinicians."UrinaryTractInfections:APrimerforClinicians.Medscape,n.d.Web.22Jan.2016.<http://www.medscape.org/viewarticle/556040>

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