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資料3-② タペンタドール(七apen七ado監)

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-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

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