Download A Literature Review Examining the Use of Combina9on Inhaler Tiotropium/Olodaterol in COPD

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Category:HealthSciences
DegreeLevel:PharmDStudent
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ALiteratureReviewExaminingtheUseofCombina9onInhalerTiotropium/OlodaterolinCOPD
LaurenMoDoPharmacyStudent,AlexaCarlsonPharmD,BCPS,TaylaRosePharmD
NortheasternUniversitySchoolofPharmacy
Abstract
Objec9ves:ToevaluatetheappropriateuseofSPolto™Respimat®
(Potropium/olodaterol)inchronicobstrucPvepulmonarydisease(COPD)
baseduponpharmacokinePcandclinicaltrialdatatodetermineadverse
eventsanddruginteracPonsaswellasdiscussdosage,administraPon,
andformularyconsideraPonsofthiscombinaPoninhaler.
Methods:Atotalof15randomizedcontroltrials,literaturereviews,
analyses,andongoingtrialswerefoundusingPubMed,ClinicalKey,
ClinicalTrials.gov,andPotropium/olodaterol'swebsite.Clinicaltrials
comparingPotropium/olodateroltoothermedicaPonsinsimilardrug
classesandmonitoringtheinhalerforsafetywereincluded.Opinion
arPcleswereexcluded.
Results:ThePotropium/olodaterolinhalerdosedat5mcg/5mcg
demonstratedincreasedforcedexpiratoryvolumein1second(FEV1),
troughFEV1,andqualityoflife(QOL)withminimallyincreasedincidence
ofadverseeffectscomparedtomonotherapyinhalersinthesamedrug
class.EvidencesuggeststheuseofPotropium/olodaterolmaybe
preferredinplaceofmonotherapyforpaPentswithmoderatetovery
severeCOPD.Currentlyevidenceislackingintermsoftheinhaler'seffects
oncardiacandrenalfuncPon;howeverongoingresearchshowsno
increaseincardiovascularorrenalrisk.
Conclusions:Earlyresultsofpost-markePngresearchindicatePotropium/
olodaterolissafeandoffersimprovedefficacyasacombinaPonagent
comparedtosimilarinhalers.ThecombinaPontherapyhasbeneficial
advantagesandhasbeensuccessfulattreaPngmoderatetoverysevere
COPD.
Background
•  COPDaffectsover200millionpaPentsacrosstheglobeandis
characterizedbynonreversibleprogressiveairflowlimitaPon.1
TreatmentuPlizesinhaledtherapyincludinglong-acPngbeta2adrenoreceptoragonists(LABA)orlong-acPngmuscarinicreceptor
antagonists(LAMA).1
•  SPoltoRespimat(Potropium/olodaterol)isacombinaPoninhalerof
PotropiumbromidewhichisaLAMAandolodaterolwhichisaLABA.2It
isindicatedformoderatetoverysevereCOPDaslongacPveoncedaily
maintenancetherapy.2
•  Tiotropium/olodaterolascombinaPontherapyhasbeenshownto
achievebeDerclinicaloutcomesintermsofpeakFEV1,troughFEV1,
andQOLcomparedtoPotropiumorolodaterolalone.3
•  ThisliteraturereviewanalyzestheuseofPotropium/olodaterolin
COPDcomparedtomedicaPonsinthesameclassintermsof
pharmacology,pharmacokinePcsandpharmacodynamics,
administraPon,dosing,efficacy,andsafety.
Discussion
Structural
formulaof
Potropium
bromide:
Structural
formulaof
olodaterol:
2
Pharmacokine1cs/Pharmacodynamics
•  PharmacokinePcparametersforthecombinaPontherapyadministered
byinhalaPonweresimilartothosethatPotropiumandolodaterol
displayedwhenadministeredindividually.2
•  OlodateroldisplayslinearpharmacokinePcsandreachesitsmaximum
plasmaconcentraPonwithin10to20minutesofdoseadministraPon.2
ItisesPmatedtohave30%bioavailability.2Olodaterolundergoesdirect
glucuronidaPonandO-demethylaPonatthemethoxymoietyfollowed
byconjugaPonmetabolism.2
•  Tiotropiumisadministeredaseitheradrypowderinhaler(DPI)ora
soa-mistinhaler(SMI).WhenadministeredasaDPIamajorityofthe
PotropiumdoseisunintenPonallydeliveredintothegastrointesPnal
tractinsteadofthelungs.2Itsbioavailabilityis19.5%aaerdrypowder
inhalaPonandishighlyabsorbedinthelungswhilepoorlyabsorbedin
thegastrointesPnaltract.2Inyounghealthyvolunteers74%of
intravenousPotropiumwasexcretedintheurineasunchangeddrug
while25%ismetabolizedbycytochromeP450-dependentoxidaPonand
glutathioneconjugaPontoseveralPhaseIImetabolites.2
•  Inarandomized,double-blindtrialofpaPentswithCOPD,cardiac
electrophysiologywasassessedwithpost-doseelectrocardiography
(ECG)readings.PooledanalysisshowedaQTintervalincreasegreater
than30msecbutcorrecPonofQTwasnodifferentfromthe
comparisongroupsofolodaterolandPotropiumbothdosedat5mcg.2
Results:SafetyandAdverseEvents
•  IntheTOnado1and2studiesgreaterthan3%oftheindividualevents
recordedwereCOPDexacerbaPonsandinfecPons.4Tiotropium/
olodaterolhadthehighestincidenceofcoughanddyspneawhen
comparedtothemonotherapytreatmentarms.4Generally,the
combinaPontherapyhassimilaradverseeventstoPotropiumand
olodaterolusedindependently.4
•  IntheVIVACITOinvesPgaPonalstudyadverseeventswereofsimilar
incidentratesacrossthetreatmentarmswiththemostcommonevents
beingnasopharyngiPsandCOPDworsening.5
•  ANHELTO1and2arereplicate,doubleblind,randomized,12-week
studiesthatsawsignificantimprovementsintheareaunderthecurve
from0-3hoursofforcedexpiratoryvolumein1second(FEV1AUC0-3)
andtroughFEV1measurementswhencomparingPotropium/olodaterol
toPotropiumwithplacebo.6ThestudyfoundthecombinaPontobewell
toleratedandmoreefficaciousthanthemonotherapyinhaler.6
•  Tiotropium/olodaterol’sfixeddoseof5mcg/5mcgwasrecommended
tobeusedaaerphaseIIclinicaltrialsduetoincreasedefficacyinterms
ofmeantroughFEV1withoutasignificantincreaseinadverseevents
comparedtothelowerdoseofPotropium2.5mcg.7
•  AsystemaPcreviewthatevaluated11differentmedicaPonsincluding
Potropium/olodaterol,umeclidinium/vilanterol,aclidinium/formoterol,
andPotropiumalonefoundsimilarresultsintermsofefficacy,
disconPnuaPonrates,andexacerbaPons,suggesPngthatPotropium/
olodaterolhasasimilarefficacyandsafetyprofilecomparedtoother
LAMA/LABAcombinaPonsinitsclass.8
•  Tiotropium/olodaterolissuppliedasaRespimatinhalerwhichdelivers
medicaPonasafinemistandallowsfordecreasedpaPentcoordinaPon
comparedtostandardmeterdoseinhalers.9Themistalsoallowsfor
moreuniformdeliverytothesmallerairwaysinthelungs.9Studies
evaluaPngthecardiovascularrisksoftheRespimatformulaPonhave
shownmixedresultsandthereforefurtherresearchisrequired.9
Conclusion
•  Earlyresultsofpost-markePngresearchindicatePotropium/olodaterol
issafeandoffersimprovedefficacyasacombinaPonagentcompared
tosimilarinhalersandmonotherapy.
•  Whilecurrentevidenceislackingintermsoftheinhaler'seffectson
cardiacandrenalfuncPonongoingresearchshowsnoincreasein
cardiovascularorrenalrisk.AddiPonalresearchissPllneededonthe
Respimatinhalerintermsofcardiovascularrisk.
•  ThecombinaPontherapyhasbeneficialadvantagesandhasbeen
successfulattreaPngmoderatetoverysevereCOPD.
Disclosure
•  Theauthorshavenothingtodisclose.
References
1. PelaiaG,VatrellaA,BuscePMT,CalabreseC,TerraccianoR,etal.PharmacologicraPonaleunderlyingthetherapeuPceffectsof
Potropium/olodaterolinCOPD.TherClinRiskManag[Internet].2015Oct8[cited2016Mar13];11:1563-72.Availablefrom:hDps://
www.dovepress.com/pharmacologic-raPonale-underlying-the-therapeuPc-effects-of-Potropi-peer-reviewed-fulltext-arPcle-TCRM
2. BoehringerIngelheimPharmaceuPcals.HighlightsofprescribinginformaPonSPoltoRespimat(Potropiumbromideand
olodaterol)inhalaPonspray,fororalinhalaPonuse[Internet].USFoodandDrugAdministraPon;2015[cited2016Mar12].Available
from:hDp://www.accessdata.fda.gov/drugsapda_docs/label/2015/206756s001lbl.pdf
3. SinghD,FergusonGT,BolitschekJ,GrönkeL,HallmannC,BenneDN,etal.Tiotropium+olodaterolshowsclinicallymeaningful
improvementsinqualityoflife.RespirMed.2015Oct[cited2016Mar15];109(10):1312-9.Availablefrom:hDp://
www.sciencedirect.com/science/arPcle/pii/S0954611115300342
4. DhillonS.Tiotropium/olodaterol:areviewinCOPD.Drugs[Internet].2016Jan[cited2016Mar13];76(1):135-46.Availablefrom:
hDp://link.springer.com/arPcle/10.1007%2Fs40265-015-0527-2
5. BuhlR,MaltaisF,AbrahamsR,BjermerL,DeromE,FergusonG,etal.Tiotropiumandolodaterolfixed-dosecombinaPonversus
mono-componentsinCOPD(GOLD2-4).EurRespirJ[Internet].2015[cited2016Mar13];45(4):969–79.Availablefrom:hDps://
hcp.sPolto.com/assets/Tiotriopium-and-olodaterol-fixed-dose-combinaPon-versus-mono-components-in-COPD-(GOLD-2-4).pdf
6. ZuWallackR,AllenL,HernandezG,TingN,AbrahamsR.EfficacyandsafetyofcombiningolodaterolrespimatandPotropium
handihalerinpaPentswithCOPD:resultsoftworandomized,double-blind,acPve-controlledstudies.IntJChronObstructPulmon
Dis.2014Oct14[cited2016Mar15];9:1133-44.Availablefrom:hDps://www.dovepress.com/efficacy-and-safety-of-combiningolodaterol-respimatreg-and-Potropium-peer-reviewed-fulltext-arPcle-COPD
7. AalbersR,Maleki-YazdiMR,HamiltonA,Waitere-WijkerS,ZhaoY,AmaDoVC,etal.Randomized,double-blind,dose-findingstudy
forPotropiumwhenaddedtoolodaterol,administeredviatherespimatinhalerinpaPentswithchronicobstrucPvepulmonary
disease.AdvTher.2015Sep[cited2016Mar15];32(9):809-22.Availablefrom:hDps://link.springer.com/arPcle/
10.1007%2Fs12325-015-0239-8
8. SchlueterM,Gonzalez-RojasN,BaldwinM,GroenkeL,VossF,ReasonT.ComparaPveefficacyoffixed-dosecombinaPonsoflongacPngmuscarinicantagonistsandlong-acPngβ2-agonists:asystemaPcreviewandnetworkmeta-analysis.TherAdvRespirDis.2016
Apr[cited2016Mar15];10(2):89-104.Availablefrom:hDp://tar.sagepub.com/content/10/2/89.long
9. MuruganandanS,JayaramL.Profileofafixed-dosecombinaPonofPotropium/olodaterolanditspotenPalinthetreatmentof
COPD.IntJChronObstructPulmonDis[Internet].2015Jun18[cited2016Mar12];10:1179-1189.Availablefrom:hDp://
www.ncbi.nlm.nih.gov/pmc/arPcles/PMC4476436/