AccesstoNaloxone:Evidence-BasedOverdoseResponseStrategy

ErinL.Winstanley,Ph.D.AssistantProfessorUCCollegeofPharmacy,DivisionofPharmacyPrac8ce&Administra8veSciences

UCCollegeofMedicine,DepartmentofPsychiatry&BehavioralNeuroscience

ObjecDves

1)  Iden(fystrategiestopreventanopioidoverdose

2)  Understandthesafetyandefficacyofnaloxoneinreversinganopioidoverdose

3)  Describehowpoliciescanbeusedtoexpandaccesstonaloxone

DefiningAnOpioidOverdose

• Hallmarksymptomofanopioidoverdoseisrespiratorydepression• Respiratorydepressiondefinedas<13breathsperminute• Signsofopioidtoxicity:apnea,stupor,andmiosis

SOURCE:Boyer(2012)NEJM

DrugOverdose•  AccordingtotheCDC,thereisanepidemicofdrugoverdosefatali(es

•  DrugoverdoseistheleadingcauseofinjurydeathintheU.S.,surpassingdeathsfrommotorvehicleaccidentsin2007

•  Prevalenceamongdrugusers:73%havewitnessedanoverdose&45%experiencedanon-fataloverdose

•  Inlong-termfollow-upstudiesofpa(entswhoreceivedaddic(ontreatment,overdoseisaleadingcauseofdeath

•  Overdoseises(matedtocost$20.4billionin2009

SOURCES:Walleyetal.(2013)JSubstAbuseTreat;Hseretal.(2006)JSubstAbuseTreat;Saitzetal.(2007)JUrbanHealth;Martensetal.(2016)APHA

OverdoseDeathsinU.S.

SOURCE:NYTimesJan.19,2016:hdp://www.ny(mes.com/interac(ve/2016/01/07/us/drug-overdose-deaths-in-the-us.html

StateswithHighestRatesofOverdose(2014)

1.  WestVirginia(35.5deathsper100,000)2.  NewMexico(27.3)3.  NewHampshire(26.2)4.  Kentucky(24.7)5.  Ohio(24.6)

2014hadthehighestrateofoverdosefatali(eseverrecordedintheUnitedStates

SOURCE:MMWRJan2016

CausesofOverdoses

16,235

8,257

•  74%weredeemeduninten(onal&17%weresuicides•  Approximately61%ofoverdosedeathsinvolvedanopioid

Hydrocodone&oxycodone

SOURCES:CDChLp://www.cdc.gov/nchs/data/databriefs/db190.htm;MMWRJan2016

Fentanyl-relatedDeaths•  In2013therewere84fentanyl-relatedoverdosesinOhio,in2014thatnumbergrewto502

HeroinAdulterants&Diluents•  Benzodiazepines•  Cocaine•  Procaine–localanesthe(c•  Quinine–an(paras(c(treatsMalaria)•  Caffeine-s(mulant•  Paracetamol–acetaminophen•  Lidocaine-anesthe(c/an(arrhythmic•  Mannitol-diure(c•  Lactose-filler•  Starch-filler•  Dextrose-filler•  Diphenhydramine/Caffeine-An(histamine•  Diphenhydramine/Thiamine

SOURCE:Brosusetal.(2016)ForensicScienceInterna(onal

Asklocaltoxicologist/coronersforlocaldata

NovelSynthe(cOpioids:ü  Fentanylü  Fentanylanalogsü W-18ü  U-4700ü  AH-7921ü MT-45

RiskFactorsforFatalRxOpioidOverdose

Demographic•  Male•  Middle-aged(Rx

opioids:45-54yrs;heroin:25-34yrs)

•  Livinginnon-metropolitanareas(Heroinmetroareas)

•  Low-income(RR:2.1-5.7)

•  Non-Hispanicwhite

BehavioralHealth•  Historyof

substanceabuse(60-78%)

•  Historyofmentalillness(42-57%)

•  IVdruguse(22%)•  Previousoverdose

(17%)

PhysicalHealth•  Historyofchronic

pain(82%)•  Havingaprescrip(on

(75%prescrip(onopioidvs29%formethadone)

•  Signs of non-medical use (51%)

•  Greaternumberofprescribers(RR:2.8)

•  Greaternumberofprescrip(ons(RR:8.2)

•  Highdailydose(>80mgmorphineequivalentdose)

SOURCES: Paulozzi, FDA, 2012; Hall et al, JAMA, 2008; Lanier et al, CDC, 2010 ; Jones et al. (2013) JAMA

SOURCE:Binswangeretal.(2007)NEJM

DrugOverdoseistheLeadingCauseofDeathAmongFormerInmates

12.7greaterriskofdeath

OVERDOSEPREVENTION

OverdoseEducaDonDelivery

•  Delivery:– 1:1in-person– Group– Video– Educa(onalmaterials/brochures

•  Lengthvariesfrom10-60minutes•  Maybelegisla(verequirementsthatoverdosepreven(oneduca(onisrequiredtodistributenaloxone

SOURCE:Clark,Wilder,Winstanley(2014)JAddictMed

Goodtodiscussineffec(veresponsestooverdose

SymptomsofanOpioidOverdose

•  Breathingisslow&shalloworhasstopped•  Vomi(ng•  Faceispale&clammy•  Blueorgrayishlips&fingernails•  Slow,erra(cornopulse•  Chokingorloudsnoringnoises(“deathradle”)•  Willnotrespondtoshakingorsternumrub•  Skinmayturngray,blueorashen

OverdosePrevenDon•  Donotmixopioids,benzodiazepines&alcohol•  Peoplewhohavestoppedusingforaperiodof(me&trytouseagain

•  Quality&adulterants(forexample,fentanyl)•  Usingalone•  Makeanoverdoseplanwithafriend•  Age&physicalhealth(forexample,respiratoryproblemslikeasthmaorCOPD)

•  Learntorecognizeoverdoseasdecreasedrespira(on•  Call911andadministernaloxone

EducaDononFentanyl

WhenisitanOverdose?

SOURCE: Boston Department of Public Health

ResponsestoanOverdose

•  Clientsmayhavemisunderstandingofhowtorespondtoanoverdose

•  Anecdotalexperiencesthathaveworkedtoreverseanoverdose

•  Unresponsivepersonrequiress(mulus

76%ofclientshadwitnessedorexperiencedanoverdose,butonly53%hadheardofnaloxone

OverdoseEducaDonAmongDrugUsersAmongclientsinaddic(ontreatmentforopioidusedisorders,overdosepreven(oneduca(onlargestimprovementsin:•  Sternumrub(52%improvement)•  Placingpeopleintherecoveryposi(on(37%)•  Notgivings(mulants(29%)•  Snore-likegurglingnoisesymptomofoverdose(29%)•  Performrescuebreathing(27%)•  Donotwalksomeonearoundtheroom(25%)•  Administernaloxone(24%)•  Donotinjectthemwithsalineorwater(22%) SOURCE:Winstanleyetal.(2015)unpublishedreport

OverdoseReversal•  Naloxonehydrochloride(brandnameNarcan),FDA-approved

in1971,isashort-ac(ngcompe((vemuopioid-receptorantagonist,andtheonlyagentthatcanreverseanopioidoverdose

•  Firstsynthesizedin1960

•  Well-establishedefficacyandsafety

•  UsedbyEMS&hospitalsforover40years

•  Veryspecificmechanismofac(on

•  Doseupto700/xrecommendeddosewithoutseeingadverseevents

SOURCES:Boyeretal.2012;Buajordetetal.2004;Clarkeetal.2005;Dahanetal.2010

NaloxoneDosingMedicalsesng:•  Recommendedstart0.04mg,increaseevery2-3minutesatrate0.5mg,2mg,4mg,10mg,15mg–un(ladequaterespira(on

•  Onsetwithin2minutes,dura(on20-90minutes;administeredIV/IM/IO/IN

•  Observe4-6hoursstandard,atleast8hoursiflong-ac(ngopioidused(methadone,fentanylpatch)

Communitysesng:•  Twodosesperclient•  Moredosesmaybenecessaryinareaswhereheroinisknown

tobeadulteratedwithfentanyl

SOURCES:Boyeretal.2012;Buajordetetal.2004;Clarkeetal.2005;Dahanetal.2010

•  Confusion•  Headache•  Gastrointes(nalproblems•  Aggressiveness•  Tachycardia•  Shivering

Naloxone Side Effects? •  Swea(ng•  Tremor•  Seizures•  Naloxonesensi(vity•  Cardiacarrest•  Pulmonaryedema•  Renarco(za(on

•  Manysymptomsthoughttobeadributabletonaloxoneresultfromopioidwithdrawal

•  Long-termdrugusemayincreasetheprobabilityofanadverseevent(AE),reflec(nganunderlyingmorbidity–NOTnaloxoneAE

NaloxoneAdministraDon•  FDAapprovedIV/IMadministra(onofnaloxone•  April2014FDAapprovedauto-injector(0.4mg/0.4mL)Evzio(~$575)withaudioinstruc(ons

•  November2015FDAapprovedanasaldevice(4mg/1mL)fromAdaptPharma($75)

•  Basedonnaloxonedistribu(onto20%ofheroinusers

•  Es(mated6%overdosedeathsaverted•  1saveper227naloxonekitsdistributed•  Incrementalcost$53•  Eachdeathpreventedbydistribu(onofnaloxonekitswillcost$438(ICER)

•  HIGHLYCOSTEFFECTIVE

NaloxoneCostEffecDveness

SOURCE:Coffin&Sullivan(2013)AnnalsofInternalMedicine

ModeofNaloxoneAdministraDon

ModeofNaloxoneAdministraDonNasalnaloxoneorAuto-Injector:

•  Non-druguserswithoutmedicaltraining•  Peopleinrecoveryfromopioidaddic(on,avoidneedleasapoten(al“trigger”

Intramuscular:•  Individualwithmedicaltraining•  Ac(veinjec(ondrugusers•  Par(cularlyimportantifheroinknowntobeadulteratedwithfentanyl

Intramuscular/IV:•  Medicalsesngsonly(ambulance,emergencydepartment)•  Par(cularlyimportantifheroinknowntobeadulteratedwithfentanyl

OverdosePrevenDon

The only evidenced-based intervention that has demonstrated to prevent heroin overdose, is medication assisted treatment with methadone or buprenorphine

SOURCES: Darke & Hall, 2003; Sporer & Kral 2007.

SOURCES: Schwartz et al. (2013) American Journal of Public Health

OpioidOverdosePrevenDonProgramsBeganin1996&thekeycomponentsare:

1)  trainingonhowtoiden(fythesymptomsofanopioidoverdose

2)  howtorespond,includingadministra(onofnaloxone(bystanderadministra(on)

SOURCES:Sporer&Kral2007;Enteenetal.2010;Baca&Grant2007

Whyimportant:•  Manypeopledon’tcall911•  EMT-Basics&firstresponderscannot

administernaloxoneinsomejurisdictions

•  InruralOhio,itcantakeEMS17-18minutestorespond

SOURCE:MMWR6/19/15

DistribuDonofOOPPsbyStateMajority of programs are nested within

harm reduction programs

1)  Laypersonscanandwilladministernaloxone2)  Overdosesarecommonamongac(vedrugusers,aswellas

peopleseekingtreatmentfordrugusedisorders3)  Mixedevidenceregardingwhetherpeople,asaresultof

overdoseeduca(on,aremorelikelytocall9-1-14)  Noevidencetosuggestthatnaloxoneencouragesdruguse5)  Non-medicalpersonscanincreasetheirknowledgeofthe

signsandsymptomsofanoverdose

ReviewofOOPPs

OOPPsinOhio

SOURCE:Winstanleyetal.(2015)SubstAbus

BarrierstoOOPPsImplementaDon

SOURCE:Winstanleyetal.(2015)SubstAbus

Improving&ExpandingOverdosePrevenDon

•  Affordability&accesstonaloxone•  Point-of-caredistribu(onofnaloxone•  Tailoringeduca(ontodifferentat-riskpopula(ons•  Co-prescribingofnaloxoneforpersons:1)highdoseofopioids,2)

co-prescribedbenzodiazepines,&3)opioids+an(depressants•  Medica(onsafetyforallpa(entsreceivingopioids•  Outreach&educa(onforac(vedrugusers(e.g.,syringeexchange

programs)•  Increaseaccesstomedica(onstotreatopioidusedisorders•  Naloxonedistribu(ontoallpa(entsleavingAMAfromresiden(al

addic(ontreatmentprograms

POLICYISSUES

LegalIssuesinPrescribing/AdministeringNaloxone

SOURCE:hdp://lawatlas.org/query?dataset=laws-regula(ng-administra(on-of-naloxone

LegalIssuesState-levelvaria(oninwhether:

1.  Immunityforpersonwhocalls9-1-1and/oradministersnaloxone

2.  Civil&criminalprotec(onsforphysiciansthatprescribenaloxone

3.  Protec(onforlaypersonscarryingnaloxone

NewMexicowasthe1ststateinU.S.topasslegislaDonin

2007

SOURCE: Davis et al. (2013) Journal of Law, Medicine & Ethics

RegulatoryIssues

•  RhodeIslandBoardofPharmacyapprovedacollabora(veprescrip(onagreement

•  Massachusedsexpandedaccessbyusingastandingorder

•  BasiclevelfirstrespondersmaynotbeabletoadministerIV/IMmedica(onswhichispar(cularlyproblema(cinruralareas

•  Somestatesdonotallownaloxonetobeprescribedtoathirdparty

OhioHB4

•  Expandedaccesstonaloxone– 3rdpartyprescribing– Pharmaciescanadoptastandingordertoprovidenaloxonetocommunitymemberswithoutaprescrip(on

MythsVersusFacts

Myth:PeoplewillusemoreheroinbecausetheyknowNarcancanbeusedtosavethemiftheyoverdose.

Fact:PeoplewilluseheroinwhetherornotNarcanisavailable.Themajorityofpeopleusingdrugsdonotwanttodie,theyarestrugglingwithaddic(on.AdministeringNarcanmeansthatsomeonemayhaveanotherchancetoentertreatment.

ConcludingRemarks•  Overdoseisapreventable

causeofdeath•  Educa(on&provisionofMAT

canpreventanoverdosefromoccurring

•  Naloxoneisasafe,efficaciousandcost-effec(vemedica(onthatcanpreventanoverdosefatality

•  Furtherregulatoryandlegalchangesareneededtoexpandaccesstonaloxone&ensure911iscalled