Agenda
• Introduction• Probuphine(buprenorphine)implant
– Indication
• ProbuphineREMSProgram– GoalofREMSProgram– MitigatingPotentialRisks– Roles/ResponsibilitiesofHealthcareProviders(HCPs)– CertificationProcessforHCPs– PatientCounseling
• ProbuphineInsertion/RemovalProcedures– StepbyStepInsertion/RemovalProcedures– ComplicationsandRisksofInsertion/RemovalProcedures
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Probuphine(Buprenorphine)Implant
4
EVA polymer Buprenorphine
Blended&
Extruded
Probuphine®
• Probuphineisanimplantableformulationofbuprenorphine• Eachimplantcontains74.2mgofbuprenorphine,uniformlydistributedthroughouttheethylenevinylacetateco-polymer(EVA)matrix
• 4Probuphineimplantsareinsertedsubdermallyintheupperarminanofficeprocedureanddelivercontinuous,stablebloodlevelsofbuprenorphinefor6months
• ProbuphinesurgicalprocedurescanonlybeperformedbyHCPswhohavesuccessfullycompletedthelivetrainingprogram
• Dosagewillbe4Probuphineimplants• Suppliedinakitcontaining4individuallypackagedimplantsandsteriledisposableapplicator
26 mm long,2.5mm diameter
ProbuphineIndicationProbuphineisindicatedforthemaintenancetreatmentofopioiddependenceinpatientswhohaveachievedandsustainedprolongedclinicalstabilityonlow-tomoderatedosesofatransmucosalbuprenorphine-containingproduct(i.e.,dosesofnomorethan8mgperdayofSubutexorSuboxonesublingualtabletorgenericequivalent).
Probuphineshouldbeusedaspartofacompletetreatmentprogramtoincludecounselingandpsychosocialsupport.
Probuphineisnotappropriatefornewentrantstotreatmentandpatientswhohavenotachievedandsustainedprolongedclinicalstability,whilebeingmaintainedonbuprenorphine8mgperdayorlessofSubutexorSuboxonesublingualtabletorgenericequivalent.
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REMS
• ARiskEvaluationandMitigationStrategy(REMS)isastrategytomanageknownorpotentialseriousrisksassociatedwithadrugproductandisrequiredbytheFoodandDrugAdministration(FDA)toensurethebenefitsofadrugoutweighitsrisks.
• BraeburnPharmaceuticalshasworkedwiththeFDAtodeveloptheProbuphineREMSProgramtomitigatetheriskofcomplicationsofmigration,protrusion,expulsion,andnervedamageassociatedwiththeinsertionandremovalofProbuphineandtherisksofaccidentaloverdose,misuseandabuseifanimplantcomesoutorprotrudesfromtheskin.
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GoalofProbuphineREMSThegoaloftheProbuphineREMSistomitigatetheriskofcomplicationsofmigration,protrusion,expulsionandnervedamageassociatedwiththeinsertionandremovalofProbuphineandtherisksofaccidentaloverdose,misuseandabuseby:
• Ensuringthathealthcareprovidersareeducatedonthefollowing:– ProperinsertionandremovalofProbuphine– Riskofcomplicationsofmigration,protrusion,expulsionandnervedamage
associatedwiththeinsertionandremovalofProbuphine– Risksofaccidentaloverdose,misuseandabuseifanimplantcomesoutor
protrudesfromtheskin• Informingpatientsabouttherisksofcomplicationsofmigration,
protrusion,expulsionandnervedamageassociatedwithinsertionandremoval,aswellas,therisksofaccidentaloverdose,misuseandabuseifanimplantcomesoutorprotrudesfromtheskin
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WhatistheProbuphineREMSProgram?
• ProbuphineisonlyavailablethroughthisREMSProgram– HealthcareProviders(HCPs)WhoPrescribemustbecertifiedto
placeanorderforProbuphine– HCPswhoinsertProbuphinemustbecertifiedtoperformthe
procedure– OnlyHCPwhoarecertifiedtoinsertProbuphinecanperform
removalprocedures– ProbuphinewillbedistributedthroughaClosedDistribution
SystemONLYtoHCPsWhoPrescribeProbuphineandeither(i)arecertifiedtoinsertor(ii)makearrangementsforacertifiedHCPWhoInsertstoperformtheprocedures
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ProbuphineREMS:MitigatingPotentialRisks1. Mitigatingcomplicationsassociatedwiththeinsertion/removal
– InformHCPsonrisksassociatedwiththeinsertion/removal• Migration• Protrusion• Expulsion• Nervedamage
– HCPsWhoPrescribewillbeeducated/trainedon:• Properandasepticinsertion/removalprocedures• Appropriatecareoftheincision/removalsite• Managingcomplicationsassociatedwithinsertion/removal• Referringpatientswhenthereareconcernsregardingtheincision/insertion
site
– HCPswhoperformProbuphinesurgicalprocedureswillbeeducated,trainedanddemonstrateproficiencyon:
• Properandasepticinsertion/removalprocedures• Appropriatecareoftheincision/removalsite• Managingcomplicationsassociatedwithinsertion/removal
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Probuphine REMS:MitigatingPotentialRisks,continued2. Mitigatingtherisksofaccidentaloverdose,misuse,andabuseassociated
withProbuphine ifanimplantcomesoutorprotrudesfromtheskin– MedicationinProbuphine canbeextractedandthenabusedinamanner
similartootheropioids– HCPsmustbeproperlyeducated,trained,passtheknowledgeassessment,
andbecertifiedintheProbuphine REMSProgramtoprescribeanddispenseProbuphine
– Probuphine shouldnotbedispensedtopatientsforself-administration– PrescribersmustgivepatientsWhatYouNeedtoKnowAboutProbuphine:
APatient’sGuide counselingtooltoinformpatientsabout:– Therisksofinsertion/removalofProbuphine– Therisksofaccidentaloverdose,misuse,andabuse,ifanimplantcomesoutor
protrudesfromtheskin– Theimportanceofappropriatewoundcare
– HCPswhoperformProbuphine surgicalproceduremustgivepatientstheProbuphineMedicationGuideateachinsertionprocedureandcounselpatientsabout:
– Therisksofinsertion/removalofProbuphine– Therisksofaccidentaloverdose,misuse,andabuse,ifanimplantcomesoutor
protrudesfromtheskin– Theimportanceofappropriatewoundcare
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HCPswhoPrescribeProbuphine:RolesandResponsibility
• TobecomecertifiedtoprescribeProbuphineintheREMSProgram,HCPmust:1. ReviewthePrescribingInformationforProbuphine.2. CompletetheProbuphineREMSProgramLiveTraining:LectureandPracticum,
andsuccessfullycompletetheProbuphineREMSProgramKnowledgeAssessment.
3. EnrollintheProbuphineREMSProgrambycompletingtheProbuphineREMSProgramPrescriberEnrollmentForm.
• Afterenrollment,prescribermust:o CounselpatientsusingWhatYouNeedtoKnowaboutProbuphine:APatient’s
Guide.o EnsureProbuphinesurgicalproceduresareperformedinyourhealthcaresettingbya
HCPwhoiscertifiedtoinsertProbuphine.PatientsmustbemonitoredtoensureProbuphineisremovedbyaHCPwhoiscertifiedtoinsert.
o Maintaindocumentationofinsertion/removalofProbuphineineachpatient’smedicalrecord.UsetheProbuphineREMSProgramInsertion/RemovalLogoranothermethod/system(e.g.,electronichealthrecord)specifictoHCP’spractice
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HCPswhoPerformProbuphine SurgicalProcedures:RolesandResponsibility
• TobecomecertifiedtoperformProbuphine surgicalproceduresintheProbuphineREMSProgram,HCPsmust:1. ReviewthePrescribingInformationforProbuphine.
2. Attesttoperformingasurgicalprocedureinthe3monthsimmediatelyprecedingenrollmentintheProbuphine REMSProgram.
3. CompletetheProbuphineREMSProgramLiveTraining:LectureandPracticum,andsuccessfullycompletetheProbuphineREMSProgramKnowledgeAssessment,aswellasmeettheProbuphineREMSProgramCriteriaforProceduralCompetency.
4. EnrollintheProbuphineREMSProgrambycompletingtheProbuphineREMSProgramHCPWhoPerformsProbuphineSurgicalProceduresEnrollmentForm orProbuphineREMSProgramHCPDualEnrollmentForm.
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HCPswhoPerformProbuphine SurgicalProcedures:RolesandResponsibility(cont.)• Afterenrollment,HCPswhoperformProbuphine surgical
proceduresmust:o Ensurethatthefacilitywheretheprocedureisbeingconductedhas
appropriateequipmenttoperforminsertions/removalsofProbuphine.PatientsmustbemonitoredtoensureProbuphineisremovedbyaHCPwhoiscertifiedtoinsert.
o CounseleachpatientonrisksassociatedwithProbuphineandprovideeachpatientacopyoftheProbuphineMedicationGuide.
o Documenttheinsertion/removalofProbuphine,usingtheProbuphineREMSProgramInsertion/RemovalLogorbyothermethod/system(e.g.,electronichealthrecord)specifictoHCP’spractice
o RecertifyintheProbuphine REMSProgramannually.
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Probuphine REMSProgramRecertificationRequirements1
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I have current operating privileges at hospitals or out-patient surgical centers:(Select the “yes” or “no” Column below that Applies)
If YESâ
If NOâ
I must review the Probuphine REMS Program Surgical Procedures Recertification Videofound on the Probuphine REMS website every year.
Number of Probuphine procedures in the past 12 months
(Select the Row that applies)
≥10
Performed 10 or more successful2
procedures (comprised of at least five insertions and five removals) à
I must review the Probuphine REMS Program Surgical Procedures Recertification Video found on the Probuphine REMS website every year.
I understand that I should keep documentation of all successfully completed procedures on the Probuphine REMS Program Procedure Record for Recertification or another record of my choosing - which must be provided to the Probuphine REMS Program if I am audited.
<10
Performed less than 10 successful2
procedures (comprised of at least five implantations and five removals) à
I must (annually):• attend a Probuphine REMS Program Live Training:
Lecture and Practicum session• successfully complete the Probuphine REMS Program
Knowledge Assessment test• meet the Probuphine REMS Program Criteria for
Procedural Competency
1 Denotes the minimal requirements. Healthcare Providers should utilize the tools provided for recertification as needed to ensureproper insertion/ removal of Probuphine is conducted in accordance with the Probuphine REMS Program.2 “Successful” implantation and removal procedures exclude attempted procedures that require assistance of other surgical specialties for completion. Removal procedures assisted by imaging studies prior to completion can be included, provided thatthe healthcare provider successfully removes all implants identified by imaging without involving additional surgical consultants.
ProbuphineREMSRecertificationRequirements• OnlyHCPswhoperformProbuphine surgicalprocedures needtoberecertified
every12months,byobtainingtheProbuphineREMSProgramHealthcareProviderWhoPerformsProbuphineSurgicalProceduresRecertificationFormfromtheProbuphineREMSProgramwebsiteandsubmittingviaFaxprovidedintheform.
• HCPswhoperformProbuphine surgicalprocedureswillbenotified60dayspriortorecertificationdeadline.
• HCPswhoperformProbuphine surgicalprocedureswillbesubjecttoauditiftheydonothaveoperatingprivilegesandchoosetorecertifybyattestingtocompletingtensuccessful proceduresinthepastyear.
– Successfulinsertionandremovalproceduresexcludeattemptedproceduresthatrequireassistanceofothersurgicalspecialtiesforcompletion.
– Removalproceduresassistedbyimagingpriortocompletioncanbeincluded,providedtheHCPsuccessfullyremovalallimplantsidentifiedbyimagingwithoutinvolvingadditionalsurgicalconsultations.
• HCPswhoperformProbuphine surgicalproceduresmayusetheProbuphineREMSProgramProcedureRecordforRecertification (foundintheProbuphine REMSProgramwebsite)todocumenteachInsertion/Removalprocedureshouldtheybeaudited 16
REMSMaterials
• ListofMaterialsforHCPs:– ProbuphineREMSProgramHealthcareProviderWhoPrescribesEnrollmentForm– ProbuphineREMSProgramHealthcareProviderWhoPerformsProbuphineSurgicalProceduresEnrollment
Form– ProbuphineREMSProgramHealthcareProviderDualEnrollmentForm– ProbuphineREMSProgramHealthcareProviderWhoPerformsProbuphineSurgicalProcedures
RecertificationForm– WhatYouNeedtoKnowAboutProbuphine:APatient’sGuide– ProbuphineREMSProgramInsertion/RemovalLog– ProbuphineREMSProgramProcedureRecordforRecertification– ProbuphineREMSProgramLiveTraining:LectureandPracticum– ProbuphineREMSProgramSurgicalProceduresRecertificationVideo(availableinlate2016)– ProbuphineREMSProgramKnowledgeAssessment– ProbuphineREMSProgramCriteriaforProceduralCompetency– ProbuphineMedicationGuide– ProbuphineInstructionsforUse– ProbuphineREMSWebsite
• ListofMaterialsforPatients– WhatYouNeedtoKnowaboutProbuphine:APatient’sGuide– ProbuphineMedicationGuide– ProbuphineREMSWebsite
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PatientCounseling
• AllHCPswillprovidepatientcounseling
• Tworesourceswillbeutilizedforpatientcounseling:– WhatYouNeedtoKnowaboutProbuphine :APatient’sGuide– ProbuphineMedicationGuide
• HCPswhoPrescribeProbuphinewillcounselpatientsusingWhatYouNeedtoKnowaboutProbuphine:APatient’sGuide priortoprescribingitforpatients
• HCPswhoperformProbuphine surgicalprocedureswillcounselpatientsusingtheProbuphineMedicationGuidepriortoeachinsertionprocedure(TheMedicationGuideispartofeachProbuphineInsertionKit)
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PatientEducationonPotentialRisks:InsertionandRemovalofProbuphine
• TherearerisksassociatedwithProbuphineimplants,including:– Animplantmaycomeoutbyitself,oranendofanimplantmaybegin
stickingoutoftheskin.– Animplantmaymove(migrate).Probuphineorpiecesofitcanmove
intothebloodvesselsandtoyourlung,andcouldleadtodeath.– Injuryordamagetonervesorbloodvesselscouldoccur.– Implantsmaybedifficulttofindif:
• Theyaretoodeepforadoctortofeel• Apatienttriestomovethemaroundundertheskin• Apatienthasgainedalotofweightsincetheywereinserted
– Specialprocedures,tests,orareferraltoaspecialistmaybeneededtoremovetheimplantsiftheyaredifficulttolocate.
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PatientEducationonPotentialRisks:InsertionandRemovalofProbuphine
• Followingaresomecommonrisksassociatedwithanyminorsurgicalprocedure– Itching,pain,irritationorredness,swelling,bleeding,orbruisingattheinsertion
site– Scarringaroundtheinsertionsite
• AppropriatecareoftheincisionisimportanttoreducetheriskofcomplicationsassociatedwiththeinsertionandremovalofPROBUPHINE
• WhentocallaHCPrightaway:– Iftheimplantscomeoutortheendoftheimplantstartsstickingoutoftheskin– Iftherearesymptomsofinfectionatthesiteafterinsertionorremoval,including
excessiveorworseningitching,pain,irritation,redness,orswelling– Anynumbnessoranyweaknessinthearmaftertheinsertionorremoval
procedure– Iftherearesymptomssuggestingtheimplanthasmigrated,suchasweaknessor
numbnessinthearm,orshortnessofbreath
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PatientEducationonPotentialRisks:CareoftheIncisionInstructions
Explainpropercareoftheincisiontothepatient:• Keeptheincisionsitecleanasdirectedbyyourphysician.• Keeptheincisionsitecleananddry foratleast24hoursaftertheinsertionor
removalofimplants.Thisincludesavoidingshowers/bathsforthefirst24hourstokeepthepressuredressingandinsidebandagedry.Avoidanyactivitiessuchasswimmingorstrenuousactivitiesforthefirstweekaftertheimplantsareinsertedorremoved.
• Applyanicepackoracoldcompresstoyourarmfor40minuteseverytwohoursforthefirst24hoursandasneededafteryourproceduretoreducebruisingandswelling.
• Removethepressuredressing,butnottheinsidebandage24hoursaftertheprocedure.
• Removetheinsidebandage3-5daysaftertheprocedure.• Afterremovaloftheinsidebandage,youshouldgentlywashthewoundarea
(insertionandremovalsitearea)withsoapandwaterandpatdry.• Donotscratch,rub,orpickattheincisionsite,orputanyliquids,ointment
medicationsoranyotherproductontheincisionsite. 22
PatientEducationonPotentialRisks:CareoftheIncisionInstructions,continued• Protecttheincisionsitefromprolongedexposuretosunlightortanninglamps
whiletheincisionishealing.• Checkforanysignsandsymptomsofinfection,suchas:increasedpain,swelling,
redness,fever,drainageofpusorpus-likematerialfromtheinsertionandremovalsite.Ifanyofthesesignsorsymptomsappears,oriftheincisionsiteseemstobeopeningup,immediatelycontactthedoctorwhoperformedtheinsertionorremovalprocedure,thedoctorwhoprescribedProbuphine foryou,oranotherhealthcareprovider.
• AftertheInsertionProcedure:Keepsteri-strips(thethinbandagesstickingtoyourskin)onfor7daysaftertheprocedure.
• AftertheRemovalProcedure:Returntothephysician’soffice7daysaftertheproceduretohaveyourstichesremoved.Ifyouhaveabsorbablestiches,returntohaveyourincisioncheckedtomakesureitishealingwell.
Patientsmayreturnthenextdaytocheckthewound.Whenthepatientcomesback:
– Checkforsignsofinfection:heat,redness,pain,pus– Checkforsuturecomplications:knotfailure,wounddehiscence 23
PatientEducation:RiskofAccidentalOverdose,Abuse,Misuse
Thereisariskofaccidentaloverdose,abuseandmisuseforothersiftheimplantscomeoutandothersareexposedtothem• DonottrytoremoveProbuphineimplantsyourself
– Improperremovalcarriestheriskofimplantsiteinfection– Ifyouremovetheimplants,thismaycauseopioidwithdrawalsyndrome
• IftheProbuphineimplantscomeout:– WashyourhandsifyouhavetouchedtheProbuphineimplants– Covertheareawheretheywereinsertedwithacleanbandage– DonotallowotherstotouchorusetheProbuphineimplants,sincethis
couldbeverydangerous– Puttheminaplasticbagandbringthemtoyourdoctorrightaway– Keeptheimplantsinasafeandsecureplace,awayfromothers,
especiallychildren– Protecttheimplantsfromtheftuntilyoucanreturnthemtoyourdoctor
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InsertionandRemoval
• Itmaybeofbenefitduringtheinsertion/removalprocesstohaveanassistantatalltimes.
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ProbuphineKit
• Only a certified prescriber is allowed to order the Probuphine Kit.• The only equipment from the kit that are needed for the insertion procedure are the
Probuphine implants and the Probuphine Applicator.
Probuphine Kits contain:– Four Probuphine Implants– Probuphine Applicator– Patient ID Card – Patient Chart Sticker – Instruction for Use Booklet– Probuphine Prescribing Information– Probuphine Medication Guide
NOTE: The Serial Number for the kit is located on the back of the kit, in the bottom left hand corner. The Serial Number should be recorded in the Probuphine REMS Program Insertion/Removal Log for tracking and accountability (including, for example, to track adverse events).
Insertion/RemovalProcedureTrainingObjectives
• Reviewanatomyofthebrachium• InsertionProcedure• ImplantLocalization• RemovalProcedure• CareoftheIncision• AvoidingComplications&ImportantPotentialRisksof:
– Migration,protrusion,expulsion,andnervedamage– Insertion/Removalprocedures– Accidentaloverdose,misuse,abuseassociatedifimplantexpulsionandprotrusionoccurs
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BrachiumCrossSection
It is important to avoid the neurovascular bundle that underlies the subcutaneous plane.
CorrectSubdermalInsertion
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Carefulandcorrectsubdermalinsertionisoneofthekeystosuccessfulplacementandwillfacilitateremoval.
ProbuphineInsertionProcedureEquipment• Anexaminationtableforthepatient
tolieon• Instrumentstand,steriletray• Adequatelighting(e.g.,headlamp)• Sterilefenestrateddrape• Latexandtalc-freesterilegloves• EtOHprep• Surgicalmarker• Antisepticsolution(e.g.,
chlorhexidine)• Localanesthetic(1%lidocainewith
epinephrine1:100,000)• 5mLsyringewith1.5inch25gneedle
• Adsonsingletoothtissueforceps• #15bladescalpel• ¼inchthinadhesivestrip(butterfly
strip)(e.g.Steri-stripskinclosures)• 4X4sterilegauze• Adhesivebandages• 3inchpressurebandages• Liquidadhesive(e.g.,Matisol)• 4Probuphineimplants(includedin
theProbuphineKit)• 1Probuphinedisposableapplicator
(includedintheProbuphineKit)
NOTE: Insertion kits contain all of the equipment, except for exam table, instrument stand, a headlamp, 4 Probuphine implants and 1 Probuphine applicator. Insertion kits are available from Braeburn upon request
InsertionProcedure
Step1.Havethepatientlieonhis/herback,withtheintendedarmflexedattheelbowandexternallyrotated,sothatthehandispositionednexttothehead.
Step2.Identifytheinsertionsite,whichisattheinnersideoftheupperarmabout8-10cm(3-4inches)abovethemedialepicondyleofthehumerusinthesulcusbetweenthebicepsandtricepsmuscle.Havingthepatientflexthebicepsmusclemayfacilitateidentificationofthesite.
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InsertionProcedure
Theclosertheimplantslietoeachotherattimeofinsertion,themoreeasilytheycanberemoved.Thereshouldbeatleast5mmbetweentheincisionandtheimplantwhentheimplantisproperlypositioned.
Step3.Cleantheinsertionsitewithalcoholpreppadpriortomarkingtheskin.
Step4.Marktheinsertionsitewiththesurgicalmarker.Theimplantswillbeinsertedthroughasmall2.5mm- 3mmsubdermal incision.
Step5.Usingthesurgicalmarker,markthechanneltrackswhereeachimplantwillbeinsertedbydrawing4lineswitheachline4cminlength.Theimplantswillbepositionedinaclosefanshapedistribution4-6mmapartwiththefanopeningtowardstheshoulder.
InsertionProcedureStep6.Putonsterilegloves.
Step7.Usingaseptictechnique,placethesterileequipment,PROBUPHINEimplants,andtheapplicatoronthesterilefieldoftheinstrumentstand.Oneapplicatorisusedtoinsertallfourimplants.
Step8.Checkapplicatorfunctionbyremovingtheobturatorfromthecannulaandrelockingit.
Step9.Cleantheinsertionsitewithanantisepticsolution(e.g.,chlorhexidine)usinggentlerepeatedback-and-forthstrokesfor30seconds.Whenusingthetripleswabstickapplicators,useeachswabsticksequentiallywithinthe30seconds.Allowtheareatoairdryforapproximately30secondsanddonotblotorwipeaway.
Step10.Applythesteriledrapetothearmofthepatient.
InsertionProcedureStep11.Anesthetizetheinsertionareaattheincisionsiteandjustundertheskinalongtheplannedinsertionchannelsusinglocalanesthetic(forexample,byinjecting5mLlidocaine1%withepinephrine1:100,000).
Step12.Afterdeterminingthatanesthesiaisadequateandeffective,makeashallowincisionthatis2.5-3mminlength.
InsertionProcedureStep13.Lifttheedgeoftheincisionopeningwithatoothedforceps.Whileapplyingcounter-tractiontotheskin,insertonlythetipoftheapplicatorataslightangle(nogreaterthan20degrees)intothesubdermalspace(depthof3-4mmbelowtheskin),withthebevel-upstopmarkingonthecannulafacingupwardsandvisiblewiththeobturatorlockedfullyintothecannula. (Figure1)
Step14.Lowertheapplicatortoahorizontalposition,lifttheskinupwiththetipoftheapplicatorbutkeepthecannulainthesubdermalconnectivetissue (Figure2).Whiletenting(lifting)gentlyadvancetheapplicatorsubdermally alongthechannelmarkingontheskinuntiltheproximalmarkingonthecannulajustdisappearsintotheincision(Figure3).
Figure 1
Figure 2
Figure 3
InsertionProcedureStep15.Whileholdingthecannulainplace,unlocktheobturatorandremovetheobturator.
Step16.Insertoneimplantintothecannula,re-inserttheobturator,andgentlypushtheobturatorforward(mildresistanceshouldbefelt)untiltheobturatorstoplineislevelwiththebevel-upstopmarking,whichindicatestheimplantispositionedatthetipofthecannula.Donotforcetheimplantbeyondtheendofthecannulawiththeobturator.Thereshouldbeatleast5mmbetweentheincisionandtheimplantwhentheimplantisproperlypositioned.
InsertionProcedureStep17.Whileholdingtheobturatorfixedinplaceonthearm,retractthecannulaalongtheobturator,leavingtheimplantinplace.Note:donotpushtheobturator.Byholdingtheobturatorfixedinplaceonthearmandbyretractingthecannula,theimplantwillbeleftinitscorrectsubdermalposition.
Step18.Withdrawthecannulauntilthehubisflushwiththeobturator,andthentwisttheobturatorclockwisetolockontothecannula.Retracttheapplicator,bevel-up,untilthedistalmarkingofthecannulaisvisualizedattheincisionopening(thesharptipremaininginthesubcutaneousspace).
InsertionProcedureStep19.Redirecttheapplicatortothenextchannelmarkingwhilestabilizingthepreviouslyinsertedimplant,withyourindexfinger,awayfromthesharptip.Followsteps13through16fortheinsertionofthethreeremainingimplantsthroughthesameincision,placingimplantsinaclosefan-shapeddistribution4-6mmapartatthetopoftheimplant.Theapplicatorcannowberemoved.
InsertionProcedureStep20.Alwaysverifythepresenceofeachimplantinthepatient’sarmbypalpationofthearmimmediatelyaftertheinsertion.Bypalpatingbothendsoftheimplant,youshouldbeabletoconfirmthepresenceofthe26mmimplant.Ifyoucannotfeeleachofthefourimplants,orareindoubtofeachoftheirpresence,useothermethodstoconfirmthepresenceoftheimplant.
Suitablemethodstolocateare:Ultrasoundwithahighfrequencylineararraytransducer(10MHzorgreater),orMagneticResonanceImaging(MRI).PleasenotethatPROBUPHINEimplantsarenotradiopaqueandcannotbeseenbyX-rayorCTscan.IfultrasoundandMRIfail,pleasecall1-844-859-6341.
InsertionProcedureStep21.Applypressuretotheincisionsiteforapproximatelyfiveminutesifnecessary.
Step22.Cleantheincisionsite.Applyliquidadhesivetotheskinmarginsandallowtodrybeforeclosingtheincisionwiththe1⁄4inchthinadhesivestrip(butterflystrip)(forexampleSteri-stripskinclosures).
Step23.Placeasmalladhesivebandageovertheinsertionsite.
Step24.Applyapressurebandagewithsterilegauzetominimizebruising.Thepressurebandagecanberemovedin24hoursandtheadhesivebandagecanberemovedinthreetofivedays.
Step25.CompletethePATIENTIDENTIFICATIONCARDandgiveittothepatienttokeep.Also,completethePATIENTCHARTSTICKERandaffixittothepatientmedicalrecordorscanorinputintoelectronicmedicalrecord.ProvidethepatientwiththeMedicationGuideandexplainpropercareoftheinsertionsite.
InsertionProcedureStep26.Theapplicatorisforsingleuseonly.DisposeoftheapplicatorinaccordancewiththeCentersforDiseaseControlandPreventionguidelinesforhazardouswaste.
Step27.Instructthepatienttoapplyanicepackonhis/herarmfor40minuteseverytwohoursforfirst24hoursandasneeded.
Step28.CompletethePROBUPHINEREMSProgramInsertion/RemovalLogForm.
– TheSerialNumberfromtheProbuphineKitshouldbeincluded fortrackingandaccountabilitypurposes (forexample,totrackAEs)intheProbuphineREMSProgramInsertion/RemovalLogFormandincludetheloginthepatient’schart– orbyusinganothermethodorsystem(e.g.electronichealthrecord)
– RecordtheprocedureintheProbuphineREMSProgramProcedureRecordforRecertification todocumenteachinsertion/removalprocedureshouldtheybeaudited
PatientEducationonPotentialRisks:CareoftheIncisionInstructionsExplainpropercareoftheincisiontothepatient:• Keeptheincisionsitecleanasdirectedbyyourphysician.• Keeptheincisionsitecleananddry foratleast24hoursaftertheinsertionor
removalofimplants.Thisincludesavoidingshowers/bathsforthefirst24hourstokeepthepressuredressingandinsidebandagedry.Avoidanyactivitiessuchasswimmingorstrenuousactivitiesforthefirstweekaftertheimplantsareinsertedorremoved.
• Applyanicepackoracoldcompresstoyourarmfor40minuteseverytwohoursforthefirst24hoursandasneededafteryourproceduretoreducebruisingandswelling.
• Removethepressuredressing,butnottheinsidebandage24hoursaftertheprocedure.
• Removetheinsidebandage 3-5days aftertheprocedure.• Afterremovaloftheinsidebandage,youshouldgentlywashthewoundarea
(insertionandremovalsitearea)withsoapandwaterandpatdry.• Donotscratch,rub,orpickattheincisionsite,orputanyliquids,ointment
medicationsoranyotherproductontheincisionsite.
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PatientEducationonPotentialRisks:CareoftheIncisionInstructions,continued• Protecttheincisionsitefromprolongedexposuretosunlightortanninglamps
whiletheincisionishealing.• Checkforanysignsandsymptomsofinfection,suchas:increasedpain,swelling,
redness,fever,drainageofpusorpus-likematerialfromtheinsertionandremovalsite.Ifanyofthesesignsorsymptomsappears,oriftheincisionsiteseemstobeopeningup,immediatelycontactthedoctorwhoperformedtheinsertionorremovalprocedure,thedoctorwhoprescribedProbuphineforyou,oranotherhealthcareprovider.
• AftertheInsertionProcedure:Keepsteri-strips(thethinbandagesstickingtoyourskin)onfor7daysaftertheprocedure.
Patientsmayreturnthenextdaytocheckthewound.Whenthepatientcomesback:• Checkforsignsofinfection:heat,redness,pain,pus• Checkforsuturecomplications:knotfailure,wounddehiscence
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Probuphine Localization
• IdentifythelocationoftheimplantsbyconsultingthePATIENTIDENTIFICATIONCARDand/orTHEPATIENTCHARTSTICKER.– TheProbuphine REMSProgramInsertion/RemovalLoginthepatient’schartorelectronichealthrecordcanalsobeusedtoidentifythelocationoftheimplants.
• Theexactlocationofallimplantsinthearm(patientswillhavefourimplants)shouldbeverifiedbypalpation.
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InabilitytoPalpateProbuphine• Ifalloftheimplantsarenotpalpable,useothermethodstoconfirmthe
presenceoftheimplant(s).Non-palpableimplantsshouldalwaysbelocatedpriortoattemptedremoval.
• Suitablemethodstolocateimplantsare:– Ultrasoundwithahighfrequencylineararraytransducer(10MHzorgreater);or– MagneticResonanceImagine(MRI)
• NotethatProbuphineimplantsarenotradiopaqueandcannotbeseenbyX-rayorCTscan.Call1-844-267-8675ifyouareunabletolocatenon-palpableimplantsusingMRIorultrasound.
• Afterlocalizationofanon-palpableimplant,removalshouldbeperformedunderultrasoundguidance.
– Ifimplant(s)orimplantfragment(s)arenotremovedduringremovalattempt,thepatientshouldundergoimagingforlocalizationassoonasfeasible.
– Subsequentremovalattemptshouldbeperformedonthesamedayoflocalization.– Iflocalizationandasecondremovalattemptarenotperformedonthesamedayasthe
initialremovalattemptthatnecessitatedimagingforlocalization,thewouldshouldbeclosedwithsuturesintheinterim.
• Exploratorysurgerywithoutknowledgeoftheexactlocationofallimplantsisstronglydiscouraged
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ProbuphineRemoval• Indicationsforremoval
– Attheendof6monthsoftreatment– Patientrequest– Medicalindication
• Beforeinitiatingtheremovalprocedure,readtheinstructionsforremoval.
• Counselpatientsaboutremovalprocedure• Donotattemptremovaluntilthelocationoftheimplants
havebeenverifiedbypalpationorimaging• Confirmnoallergiestoantisepticandanesthetic• Prepareasepticconditions• Allow45minutesforremovals
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ProbuphineRemovalProcedureEquipment• Anexaminationtableforthepatientto
lieon• InstrumentstandandSteriletray• Adequatelighting(e.g.,headlamp)• Sterilefenestrateddrape• Latexandtalc-freesterilegloves• EtOHprep• Antisepticsolution(e.g.,chlorhexidine)• Surgicalmarker• Localanesthetic(1%lidocainewith
epinephrine1:100,000)• 5mLsyringewith1.5inch25g• Adsonsingletoothtissueforceps
• Mosquitoforceps• TwoX-plantclamps(vasectomy
fixationclampswith2.5mmringdiameter)
• IrisScissors• Needledriver• #15bladescalpel• Sterileruler• 4x4sterilegauze• Adhesivebandages• 3-inchpressurebandages• Sutures(e.g.,4-0ProleneTM with
anFS-2cuttingneedle)– Maybeabsorbable
NOTE: Removal kits contain all of the equipment, except for exam table, instrument stand, and a headlamp Removal kits are available from Braeburn upon request
RemovalProcedureStep1.Havethepatientlieonhis/herback,withtheimplantarmflexedattheelbowandexternallyrotated,sothatthehandispositionednexttothehead.
Step2.Reconfirmthelocationoftheimplantsbypalpation.
Step3.Cleanremovalsitewithalcoholpreppadpriortomarkingtheskin.
Step4.Markthelocationoftheimplantswithasurgicalmarker.Inaddition,markthelocationoftheincision,paralleltotheaxisofthearm,betweenthesecondandthirdimplants.
RemovalProcedureStep5.Putonsterilegloves.
Step6.Usingaseptictechnique,placethesterileequipmentonthesterilefieldoftheinstrumentstand.
Step7.Cleantheremovalsitewithanantisepticsolution(e.g.,chlorhexidine)usinggentlerepeatedback-and-forthstrokesfor30seconds.Whenusingtripleswabstickapplicators,useeachswabsticksequentiallywithinthe30seconds.Allowtheareatoairdryforapproximately30secondsanddonotblotorwipeaway.
Step8.Applythesteriledrapetothearmofthepatient.
Step9.Anesthetizetheincisionsiteandthesubcutaneousspacecontainingtheimplants(forexample,byinjecting5-7mLlidocaine1%withepinephrine1:100,000).Separateneedles maybeusedfortheincisionsiteandthesubcutaneousinjections.NOTE:Besuretoinjectthelocalanestheticjustbeneaththeimplants;thiswilleffectivelylifttheimplantstowardtheskin,facilitatingremovaloftheimplants.
Step10.Afterdeterminingthatanesthesiaisadequateandeffective,makea7-10mmincisionwithascalpel,paralleltotheaxisarm,betweenthesecondandthethirdimplants.
RemovalProcedureStep11.PickuptheskinedgewithAdsonsingle-toothedtissueforcepsandseparatethetissuesaboveandbelowthefirstvisualizedimplantusinganirisscissorsoracurvedmosquitoforceps.GraspthecenteroftheimplantwiththeX-plantclampandapplygentletraction.Usethetechniqueofspreadingandclosingwitheithertheirisscissorsormosquitoforcepstoseparatethefibroustissue.Iftheimplantisencapsulatedusethescalpeltoshavethetissuesheathandcarefullydissectthetissuearoundtheimplant.Theimplantcanthenberemoved.
RemovalProcedureStep12.Retractthenextvisibleimplanttowardtheincisionalopening.Youmayseetentingoftheskinatthispointifthesurroundingtissueisstilladheringtotheimplant.Maintaingentletractionontheimplantwhileyoucontinuetodissectproximallyanddistallyuntiltheimplantisfreeofalladheringtissue.Atthispoint,youmayrequiretheuseofyoursecondX-plantclamptoremovetheimplant.Iftheimplantisencapsulatedusethescalpeltoshavethetissuesheathandcarefullydissectthetissuearoundtheimplant.Theimplantcanthenberemoved.
Step13.Afterremovalofeachimplant,confirmthattheentireimplant,whichis26mmlong,hasbeenremovedbymeasuringitslength.Ifapartialimplant(lessthan26mm)isremoved,theremainingpieceshouldberemovedbyfollowingthesameremovalinstructions.Followsteps11through13fortheremovaloftheremainingimplantsthroughthesameincision.Visualidentificationofwhetheranentireimplanthasbeenremovedisunreliable.Therefore,itisimportanttomeasuretheimplanttoensuretheentireimplanthasbeenremoved.
NOTE:arulershouldbeutilizedtomeasuretheremovedimplant
RemovalProcedureStep14.Afterremovalofallfourimplants,cleantheincisionsite.
Step15.Closetheincisionwithsutures.
Step16.Placeanadhesivebandageovertheincision.
Step17.Usethesterilegauzeandapplygentlepressureforfiveminutestotheincisionsitetoensurehemostasis.
Step18.Applyapressurebandagewithsterilegauzetominimizebruising.Thepressurebandagecanberemovedin24hoursandtheadhesivebandageinthreetofivedays.
Step19.Counselthepatientonproperasepticwoundcare.Instructthepatienttoapplyanicepacktohis/herarmfor40minuteseverytwohoursforfirst24hoursandasneeded.
RemovalProcedureStep20.Scheduleanappointmentforthesuturestoberemoved
Step21.Theremovedimplant,containsasignificantamountofresidualbuprenorphine,andmustbehandledwithadequatesecurity,accountability,andproperdisposal,perfacilityprocedureforaScheduleIIIdrugproduct,andperapplicablefederal,state,andlocalregulations.DisposalofPROBUPHINEimplantsshouldalsobeinkeepingwithlocalstateandfederalregulationsgoverningthedisposalofpharmaceuticalbiohazardouswaste.
Step22.CompletethePROBUPHINEREMSProgramInsertion/RemovalLogForm.
PatientEducationonPotentialRisks:CareoftheIncisionInstructionsExplainpropercareoftheincisiontothepatient:• Keeptheincisionsitecleanasdirectedbyyourphysician.• Keeptheincisionsitecleananddry foratleast24hoursaftertheinsertionor
removalofimplants.Thisincludesavoidingshowers/bathsforthefirst24hourstokeepthepressuredressingandinsidebandagedry.Avoidanyactivitiessuchasswimmingorstrenuousactivitiesforthefirstweekaftertheimplantsareinsertedorremoved.
• Applyanicepackoracoldcompresstoyourarmfor40minuteseverytwohoursforthefirst24hoursandasneededafteryourproceduretoreducebruisingandswelling.
• Removethepressuredressing,butnottheinsidebandage24hoursaftertheprocedure.
• Removetheinsidebandage3-5days aftertheprocedure.• Afterremovaloftheinsidebandage,youshouldgentlywashthewoundarea
(insertionandremovalsitearea)withsoapandwaterandpatdry.• Donotscratch,rub,orpickattheincisionsite,orputanyliquids,ointment
medicationsoranyotherproductontheincisionsite.
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PatientEducationonPotentialRisks:CareoftheIncisionInstructions,continued
• Protecttheincisionsitefromprolongedexposuretosunlightortanninglampswhiletheincisionishealing.
• Checkforanysignsandsymptomsofinfection,suchas:increasedpain,swelling,redness,fever,drainageofpusorpus-likematerialfromtheinsertionandremovalsite.Ifanyofthesesignsorsymptomsappears,oriftheincisionsiteseemstobeopeningup,immediatelycontactthedoctorwhoperformedtheinsertionorremovalprocedure,thedoctorwhoprescribedProbuphineforyou,oranotherhealthcareprovider.
• AftertheRemovalProcedure:Returntothephysician’soffice7daysaftertheproceduretohaveyourstichesremoved.Ifyouhaveabsorbablestiches,returntohaveyourincisioncheckedtomakesureitishealingwell.
Patientsmayreturnthenextdaytocheckthewound.Whenthepatientcomesback:• Checkforsignsofinfection:heat,redness,pain,pus• Checkforsuturecomplications:knotfailure,wounddehiscence
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Continuation of Therapy: Subsequent Insertion in the Contralateral Arm• ThereisnoclinicalexperiencewithinsertionofProbuphine beyonda
singleinsertionineacharm.
• Ifcontinuedtreatmentisdesiredattheendofthefirstsix-monthtreatmentcycle,Probuphineimplantsmaybereplacedbynewimplantsatthetimeofremovalinthecontralateralarm,followingtheinsertionstepsintheinstructionsforusetolocatetheappropriateinsertionsite.
• Ifnewimplantsarenotinsertedonthesamedayastheremoval,patientsshouldbemaintainedontheirpreviousdoseoftransmucosalbuprenorphine(i.e.,thedosefromwhichtheyweretransferredtoProbuphine treatment)priortoadditionalProbuphine treatment.
• Thereisnoexperiencewithinsertingadditionalimplantsintoothersitesinthearmtorecommendanapproachtoasecondinsertionintoapreviously-usedarm.
• Neitherre-insertionintopreviously-usedadministrationsites,norintositesotherthantheupperarm,havebeenstudied.
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ContinuationofTherapy:SubsequentInsertionintheContralateralArm
• Itisimportanttoavoidpreviously-implantedsitesbecausetheeffectofscarringandfibrosisinpreviously-usedinsertionsitesoneithertheeffectivenessofProbuphine orthesafetyofinsertionhavenotbeenevaluated.
• Afteroneinsertionineacharm,additionalcyclesoftreatmentshouldonlybeconsideredifthepotentialbenefitsofcontinuingProbuphine outweighthepotentialriskofadditionalinsertionandremovalprocedures,takingintoaccounttheexperienceofthehealthcareproviderwithProbuphine proceduresandrelatedprocedures,andtheclinicalneedofthepatientforongoingtreatmentwithsubdermal medication.
• Inmostcases,patientsshouldbetransitionedbacktoatransmucosal buprenorphine-containingproductforcontinuedtreatment.
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MitigationofComplicationsAssociatedwithInsertion/RemovalProcedure
• Therearerisksassociatedwithinsertion/removalofProbuphinesuchas:– Migration– Protrusion– Expulsion– Nervedamage
• Propertrainingandeducationisneededtoavoidcomplicationsassociatedwithinsertion/removal– Ensuringproperasepticinsertion/removalprocedures
• NOTE:HCPsWhoperformProbuphine surgicalprocedure mustdemonstrateproficiencyonpropertechniqueforcertification
– Providingappropriatecareoftheinsertion/removalsiteandinstructionstopatients
– Appropriatemanagementofcomplications
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PreventionofDeepInsertion
• InsertonlytheTIPoftheapplicator,slightlyanglednogreaterthan(~20°)topreventneurovascularinjury,atadepthof3-4mmbelowtheskin
• Lowertheapplicatortoahorizontalposition
• Gentlyinsert,whileliftingtheskin(tenting),theapplicatoruntiltheproximalmarking justdisappearsintotheincision,withoutusingforce
• Keeptheapplicatorparalleltothesurfaceoftheskin
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PreventionofaFractured/BentImplant• Duringinsertion:
– Avoidpushingthe beyondthebevel-upmarkingonthecannula
– Withdrawcannulauntilhubisflushwithobturator,twist theobturatorclockwisetolockintothecannula
• Duringremoval:– ApplygentletractionwithX-plantclamp,useanassistantifneeded.– Donotgrasptheimplantwithhemostat
• Ifimplant(s)orimplantfragment(s)arenotremovedduringaremovalattempt,thefollowingstepsshouldbetaken:– Thepatientshouldundergoimagingforlocalization.Thesubsequent
removalattemptshouldbeperformedonthesamedayoflocalization– Iflocalizationandasecondremovalattemptarenotperformedonthe
samedayastheinitialremovalattempt(thatnecessitatedimagingforlocalization),thewoundshouldbeclosedwithsuturesintheinterim
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PreventionofWoundInfection
• Adheretoaseptictechnique• Prepskinwithantisepticsolution(e.g.,chlorhexidine)perproductguidelines.
• Instructpatientonpropercareoftheincision
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HowtoAddressSpontaneousExpulsionofImplant1. Scheduletwoappointmentsforthepatienttoreturntotheofficeofthe
insertingHCPassoonaspossibleandtotheofficeoftheprescribingHCP.2. Instructthepatienttoplacetheimplantinaplasticbag,storeitsafelyoutof
reachofchildren,andtobringittotheHCPofficetodeterminewhetherthefullimplanthasbeenexpelled.
3. Ifthepatientreturnstheexpelledimplant,measureittoensurethattheentireimplantwasexpelled(26mm).
4. Disposeoftheremovedimplantinkeepingwithlocal,state,andfederalregulationsgoverningthedisposalofpharmaceuticalbiohazardwaste,aftermeasuring.
5. Examinetheincisionsiteforinfection.Ifinfected,treatappropriatelyanddetermineifremainingimplantsneedtoberemoved.
6. Iftheexpelledimplantisnotintact,palpatetheinsertionlocationtoidentifythelocationofanyremainingpartialimplant.Removetheremainingpartialimplantusingthetechniquesdescribedintheinstructionsforuseforremovalprocedure.
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HowtoAddressSpontaneousExpulsionofImplant
7. Call1-844-859-6341 toobtainanewkitthatwillincludefourimplantsandreturninstructionsforanyunusedimplants.
8. TheprescribingHCPmustcarefullymonitorpatientuntiltheimplantisreplacedtoevaluateforwithdrawalorotherclinicalindicatorsthatsupplementaltransmucosal buprenorphinemaybeneeded.
9. Scheduleanappointmenttoinsertreplacementimplant(s).10. Insertthereplacementimplant(s)inthesamearmeithermediallyor
laterallytoin-situimplants.Alternatively,replacementimplantmaybeinsertedinthecontralateralarm.
11. RecordtheserialnumberontheProbuphineREMSProgramInsertion/RemovalLog.
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AvoidingComplications:InsertionandRemoval
InSummary:Properattentiontotechniqueandfollowingtheinstructionswillminimizepotentialproblemsandcomplications
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ProbuphineREMSResources
• ForanyadditionalinformationaboutthePROBUPHINEREMSProgram,please call1-866-397-8939;OR
• Visitwww.PROBUPHINEREMS.com• ToReportanysuspectedadversereactions,pleasecall1-844-859-6341(pleaseremembertoprovidetheserialnumberofthekitwhenreportinganadverseevent)
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