-20090312134628-00001 mpairedmentat‘physCalabllteS
Cautionmustbeusedwthpotentaliv haardousactVjbes55
SelZureS UsewlthcautlOninpatlentSWithahlStOryOselZureSr57
SerotoninSvndrome’Potentlaytifethreatenngcondtl10nCOUldrestlh
omconcomlttSerOtOnergicadminStration58
brTRAIENAMETM
DVERSEREACT10NSγ NDICAT10NSANDUSGE
ThemostcommonadverseeventswerenauseadizzinessVOmlttngand
TRADENAMETMISanOplOIdanagesICindlCatedfortheTelzefcdmoderateto
severeaculePalnlnpatlentSi8yeaOrageOrOlderl
orTRADENAME’ndshouIdbetndivlduaIizedaccordlngtOtheseverOr
pambelngtTeatedthepreviousexperIenCeWtthslrmardrugsandthe
ab11jtytomonltOrthepatent2
∴COITRDICAT10NS∴…
lmparedpulmonaTyfunctionSignificantrespiratorydepressIOnaCuteOr
DRUGINTERACllO≠
USEINSPECLFICPOPUAT10NSM
1boranddelVerYShouldnotuseduTlngandimmediatelypnortotaboT
yearsorageS4
CNSeffects’AdditiveCNSdepressiveefrectswhenusedincounCt10n
w11halcobo0eroplOidsOrillicitd52
ElevatIOnOfintracranalpressureMaybemarkedlyexaggeratedinthe
presenceofheadiruuryOtherintracranlalIesions53
82 LaborandDetive 83 Nursin9Mothers 84 Pedi8tricUse 85 GethcUe 86
Renampalrment 87 Hepaticlmpalment
9 DRUGA8USEANDDEPENDENCE 91 ConOlledSubstance 92 Abuse 93
Depdence
lO OVERDO5GE lO1 umIExpelence lO2 Mana9ementOfOverdose
ll DESCRIPT10N 12 CLrNCALPNARMACOLOGY
121 MedlanisOfOn 122 PhanOdymics 123 Phan¶aCOkinetics
13 NONCuNICALTOXICOLOGY 131
CarcinogeSisMutagenesislmpalmentOf
Fel 132 Anima0lo⊆lyandOrPhamacoIogy
14 CLICALTUDIES 141 010PedicSuelγ8unjonectomy 142
EndStageDe9enereJointDiseae
16 HOVVSUFIFIuED′STOFuGEANDHANDLING 17
PATIENTCOLJNELINGINFOFuATlON
171 1nmSUse 172 MisueandAbue 173
1nterencevdthCognitjveandMotor
PemarICe 174 Prnanq 175 Nur∩9 176 MonoamineOxaselnhibitors
177 SZu†eS 178 StOninSyndrome
179 AIcohoi 710 MediαonGuide
Section5 0r
1 1HDICA¶ONSNDUSGE 2 DOAEANDADtlRA¶ON
21 Rempment 22 Ha“Clmpment 23 EldeyPients
3 DOSAEFORMSAl5TRENGS 4 CONTRAINDICAT10NS
1 lmpairedPutmonaFunction 42 PaCtleus 43
MonoamineOxidaselnhibitors
5 WARlNGSAllDPR∈CAU¶ONS 51 RespiratoryDepression 52 CNSDepression
53 HeadUryandlncaSedlntCnial
Pressure 54 MisusoandAbuse 55 DringandOpeIingMadlinelY 56
1nteractionswithAcohoandDrugsofAbuse 57 Seizures 58
SetOninSyndromeRisk 59 WdrawaI 510 epticImpment 511
UseinPancTeaticniliaryTractDisease
8 ADVERS∈REACT10S 61 ComrnonJyObservedTreatmentEmergent
AdverseEventsinDoubleBlindControlled ClinicalTri∈S
T DRUGINTERACT10NS 71 DrugsMetaboIizedbyCytochromeP450
EnmeS 72 DrugsThatlnhibhorInduceCytochrDme
8 USEINPEClCPOPUL¶Ol 81 P9nanCy
1 1 1
FULLPRESCRIBNGNFORMATlON
2 DOSAGEANDADMINISTRAT10N
As with many centra1yaCtlng analgesic medicationsthe dosing reglmen
Shoud be
individualized accordingtothe severlty Ofpain beingtreatedthe
previous experience with
sihlilardrugSandtheabilitytomonitorthepatient
OthersideandlOOmgoftapentadolOrangewith”0M”ononesideand“100”ontheother
Side
LikeotherdrugSwithmuOpioidagonistactivityTRADENAMETMiscontraindicatedinpatients
accompanicdbyhypoxiahypercapnlaOrupperairwayobstruCtioninwhomevenmoderate
byhypoxiahypercapnlaOrdecreasedrespiratoryreserveSuChasaSthmaChronicobstruCtive
Pulmonary disease or cor pulmonaleSeVere ObesitySleep apnea
syndromemyXedema
kyphoscoliosisCentralnervoussystemCNSdepressionOrCOmahsuchpatientseVenuSual
therapeuticdosesofTRADENAMETMmaylnCreaSeairwayresistanceanddecreaseresplratOry
4
with TRADENAMETM may exhibit additive CNS depressionInteractive
efcts resutingln
resplratOrydepressionhypotensionprOfbundsedationCOmaOrdeathmayresutifthesedrugs
COurSe Ofpatients with headirtjury due to ects on
pupillaryresponseand consciousness
TRADENAMETMshouldbeusedwithcautioninpatientswithheadi‡tiury1ntraCranialesions
Tapentadolis amuOpioid agonistSuch drugS are SOughtbydrug abusers
and peoplewith
addictiondisorders
addictionSinceuseofmuOpioidagonistanalgesicproductscarrytheriskofaddictioneven
underappropriatemedicaluseieeDrAbuseandDqpennceP2H
55 DrivingandOperatingMachinery
Patients should be cautionedat TRADENAMETM mayJmPair the mentaandor
physical
abilitiesrequired fbrtheperformanceofpotentiallyhazardoustasks
suchasdrivingacaror
5
InhibitorsSSRIsSNRIstricyclicantidepressantsTCAsMAOIsandtriptanSandwithdrugS
thatimpair metabolism of serotoninincluding MAOIsThis may occur
within the
recommended doseSerotonin syndromemayincludementalStatuS
Changesegagitation
ha11ucinationsCOmaautOnOmicinstabilityegtaChycardialabile blood
pressure
hyperthermianeurOmuSCular
aberrationseghyperreflexiaincoordinationandor
gastrointestinalsymptomsegnauSeaVOmitingdiarrhea
59 Withdrawal
mayincludeanXietySWeatinginsomniarigorspainnauSeatremOrSdiaJTheauPper
resplratOrySymptOmSpiloerectionandrarelyhallucinationsWithdrawalsymptOmSmaybe
reducedbytaperingTRADENAMETMJee∂rAbuseandDqpendbnceP3H
510Hopaticlmpalnent
A study of TRADENAMETM insubjects with hepaticimpalrment Showed
higher serum
COnCentrationsthaninthosewithnormalhepaticfunctionTRADENAMETMshouldbeusedwith
Because clinicalstudies are conducted underwidely varylng
COnditionsadverse eventrates
observedintheclinicalstudiesofadrugcannotbedirectlycomparedtoratesintheclinical
studies of another drug and may not reflect the rates observedin
clinicaipracticeA
treatmentemergentadverseeventreftrstoanyuntowardmedicaleventassociatedwiththeuse
OfthedruginhurnansWhetherornotconsidereddrugrelated
Based on data om nine Phase 23 studies that administered multiple
dosesSeVen
placeboandoractiveCOntrOlledOnenOnCOntrOlledandonePhase3activeCOntrO11edsaftty
studythemostcommonadverseeventsreportedby10inanyTRADENAMETMdosegroup
WerenauSeadizzinessVOmltlngandsomnolence
The most common reasonsfor discontinuation due to adverse eventsin
the studies described
abovereportedby1inanyTRADENAMETMdosegroupweredizziness26vs05
nausea23vs06VOmiting14vs02SOmnOlence13vs02andheadache
09vs02forTRADENAMETMandplacebotreatedpatientsreSpeCtively
SeventySix percentofTRADENAMETMtreated patientsfromthe nine studis
experienced
adverseevents
TRADENAMETM was studiedin multipledoseaCtiveOr placeboCOntrOlled
studiesOr
noncontrolledstudiesn2178insingledosestudiesn870inopen1abelstudyextension
n483andinPhaselstudiesn597Ofthese2034patientsweretreatedwithdosesof
50mgtolOOmgofTRADENAMETMdosedevery4to6hours
449exposedfor45daysTRADENAMETM was studied prlmarilyln placeboand
active
contro11edstudiesn2266andn2944reSpeCtivelyThepopulationwas18to85yearsold
meanage46years68werefbmale75whiteand67werepostoperativeMostpatients
receivedTRADENAMETMdosesof50mg75mgOrlOOmgevery4to6hours
withacutemoderatetoseverepaininthepooledsaftydataomninePhase23studiesthat
administeredmultipledosesSeVenplaceboandoractiveCOntrOlledOnenOnCOntrOlledandone
MedDRAPrefbrredTerm
AtreatmentemeTgentadverseeventrefrstoanyuntowardmedicaleventassociatedwiththeuseofthedrugin
humansWhetherornotconsidereddrugrelated
Thefo1iowlngadversedrugreaCtionsoccurredniofTRADENAMETMtreatedpatieritSn
Study
Syndromefteingdrunk
dysarthriadepressedlevelofconsciousnessmemOrylmpalrmentataXiapreSynCOPeSynCOpe
COOrdinationabnormalSeizure
thinkingabnormal
dyspneareSPratOrydepression
SkiJlandsubcttaneOuStissuedisordersurticaria
The pharmacokinetics oftapentadoIwere not acted when gastric pH or
gastrointestinal
motility wereincreased by omeprazole and metoclopramidereSpeCtivey
hee Clinical
αr7αCO′27
tapentadol13byCYP2C9andCYP2C19tohydroxytapentadol2byCYP2D6Whichare
further metabolized by coqugationSince only aminor amount of
TRADENAMETMis
metabolized via the oxidative pathway clinically relevant
interactions mediated by the
CytOChromeP450systemareunlikelytooccurieeClinicalPharmacology2
73 CentraJJyActingDrugsandAIcohoI
antiemetic0ther tranquilizersSedativeshypnoticsOr Other CNS
depressantSincluding
alcoholconcomitantly with TRADENAMETM may exhibit an additive CNS
depression
InteractiveefftctsresultinglnreSpiratorydepressionhypotensionprOfoundsedationOrCOma
4 MonoamineOxidaselnhibitors
j
t ′ 1 L T t t †
8 USE IN SPEClFlC POPULATIBNS
81Pregnancy
intravenousandsubcutaneousexposureduringtheperiodofembryofttalorganogenesisWhen
tapentadoIwas administered twice dailybythe subcutaneous TOutein
rats atdoselevels of
lO20Or40mgn’gdayproducing up toltimes the plasma exposure at the
maximum
recommended human doseMRHDof700mgdaybased on am area underthe
timeCurVe
AUCcomparisonnOteratOgenic ectswere
observedEvidenceofembryofbtaltoxjcjty
includedtransientdelaysin
skeietalmaturationiereducedossicationatthe40mgngday
dosewhichwasassociatedwithsignincantmatemaltoxicityAdministrationoftapentadoHCt
inrabbitsatdosesof410Or24mgngdaybysubcutaneousinjectionproducingO206and
l85times the plasma exposuTe at the MRHD based on an AUC
comparisonrevealed
embryofttaltoxicityatdoses10rnkgdayFindingsincludedreducedfttalviabiitySkeetaJ
gastroschisisthoracogastroschjsisameJiaphocomeliaandcepaJateatdoses10mgkgday
andaboveandablephariaenCePhalopathyandspinabdaatthehighdoseof24mggday
Embryofbtaltoxicityincludingmalfbrmationsmaybe secondarytothe
signincantmaternal
postnatalperiodresultinginuptol7timesthepIasmaexposureattheMRHDonanAUC
basisdidnotinnuencephysicalorrenexdevelopmenttheoutcomeof’neurobehavioraltestsor
incompleteosscationandsignificantreductionsinpupbodyweightsandbodyweightgainsat
doses150mgkgdayadoserelatedincreaseinpupmortalitywasobservedthroughpostnatal
Day4
There are no adequate and wellcontrolled studies ofTRADENAMETMin
pregnant women
TRADENAMETM should be used duringpregnancy onlyifthe
potentialbenefitjustiesthe
potentialrisktothefttus
taking TRADENAMETM should be monitoredfor resplratOry depressionA
specc opioid
antagonistSuCh as naloxoneShould be available
fbrreversalofopioidinduced respiratory
depressionintheneonate 1l
breastmilkPhysicochemicalandavailablepharmacodynamictoxicologlCaldataontapentadol
polnt tO eXCretionin breastmilk and risk to the suckling child
cannot be excluded
TRADENAMETMshouldnotbeusedduringbreastfteding
TRADENAMETM19were65andoverWhile5were75andoverNooveral1difftrencesin
ectiveness were observed between these patientsand younger
patientsThe rate of
COnStipationwashigherinsuectsgreaterthanorequalto65yearsthanthoselessthan65years
mαCOJy2
86 Renallmpment
PJ
9 DRUGABUSEANDDEPENDENCE
91 ControTIedSubstance
TRADENAMETM corLtains tapentadola muOpioid agonistTRADENAMETM has
an abuse
potentialsimilartohydromorphoneQanbeabusedandissubjecttocriminaldiversion
Addictionis a pmmaryChronicneurObiologic diseasewith
geneticPSyChosocialand
environmentafhctorsinnuenclngits development and maniftstations‡tis
characterized by
behaviorsthatincludeoneormoreofthefb1lowlng1mpairedcontrooverdruguseCOmpulsive
multidisciplinaryapproachbutrelapseiscommon
Concems about abuse and addiction should not preventthe proper
management Of paln
Howeverallpatientstreatedwith opioids requlre
CarefhlmonitorlngforslgnS Ofabuse and
addictionbecause use ofopioid analgesic products carriesthe risk
ofaddiction even under
appropnatemedicaluse
includeemergencycallsorvisitsneartheendofofncehoursrefusato
undergoapproprlate
PreSCrlPt10nSandreluctancetoprovidepnormedicalrecordsorcontactinfbrmationfbrother
treating physicianS“Doctor shopping”visiting multiple prescribersto
obtain additiona
PreSCrlPtlOnSis common among drugabusers and people sufringom
untreated addiction
Preoccupationwithachievingadequatepalnreliefcanbeapproprlatebehaviorinapatientwith
poorpalnCOntrOl
Abuse and addiction are separate and distinctfrom physical
dependence and tolerance
Physiciansshouldbeawarethataddictionmaynotbeaccompaniedbyconcurrenttoleranceand
OCCurintheabsenceoftrueaddictionandischaracterizedbymisusefornonmedicalpurposes
COnCurrentabuseofTRADENAMETMwithalcoholandothersubstancesInadditionParenteral
mayexhibitrespiratorydifficultiesandwithdrawalsymptOmShee
WdrningsandPrecautions
PLuUse of TRADENAMETMin this population has not been
characterizedAs
TRADENAMETM has muOpioid agonist activityinfants whose mothers have
taken
TRADENAMETMShouldbecarefu11ymonitored
