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KetamineParenteralandOralDoseRecommendations • Pharmacology o InhibitsglutamatebindingtoNMDA-Rreceptor;activityatnorepinephrine,serotonin, andmuscariniccholinergic,kappaopioid,andvoltage-sensitivecalciumchannel receptors • Pharmacokinetics o Lipophilic;Crossesbloodbrainbarrier o Proteinbinding:47% o Onsetofaction:1-5minIV/IM,15-30minSC;30min o Plasmahalf-life:1-3hrs(ketamine);12hrs(norketamine o Durationofaction:4-12hrs(oral);10-15minIV o Metabolism:N-demethylationviaCYP2B6,CYP2C8/9,CYP3A4substratestonorketamine (primarymetabolite);norketaminemetabolizedviahydroxylationandconjugation o Elimination:Primarilyhydroxylatedorconjugatednorketaminemetabolitesinurine;4% unchangedketamineornorketamine;<5%eliminationinfeces • DrugInteractions o IncreasedketaminelevelswithconcurrentuseofCYP2B6orCYP2C8/9inhibitors • Adverseeffects o Centralnervoussystem:Alterationsinbodyimage/mood,floatingsensations,vivid dreams,hallucinations,delirium,purposelessmovement,drowsiness,increased intraocularpressure,increasedintracranialpressure,increasedmuscletone,memory impairment(long-termuse) o Gastrointestinal:Nauseaandvomiting,hepaticdamage(long-termoraluse) o Cardiovascular:HTN,tachyarrhythmias o Misc:lacrimation,salivation,ulcerativecystitis(longtermoraluse) Routeof Administration Oral AvailableProduct Compounded capsules Howproductisstocked 30mg,60mgcapsules UsualDoses 1mgPOKetamine=1mgIVKetamine • ReportedRange:0.3mg–1.15mgPO Ketamine=1mgIVKetamine AdministerindivideddosesQ8h • ReportedRange:Q4htoQ12h IfconvertingpatientsfromKetamineinfusionto oral,administerfirstoraldose4to8hrsafter infusionstopped • Maytitrateevery48-72hrs • Typicalstartingdoseinketaminenaïve patient:10mg-30mgPOQ8h o MaximumReportedOralDose: 800mg/day Routeof Administration Intravenousor Subcutaneous AvailableProduct Compounded Infusion Howproductisstocked UsualDoses Concentration:2mg/ml Bolus:0.1mg/kg-0.4mg/kgSlowIVpush Volume:500mg/250mlin MaintenanceInfusion:0.1mg/kg/hr– dextrose5% 1mg/kg/hr • Oncepainstabilized,maytitrate maintenanceinfusionby0.050.1mg/kg/hrevery24hrs Duetolackofconcretedata,recommend conservativeinitialdosesanddosetitrations MaximumReportedParenteralDose: 3600mg/day ExampleofanIV toOralKetamineConversion 70kgpatientonaketamineinfusionat0.2mg/kg-hr 70kg(ketamineIV0.1mg/kg-hr)(24hrs/day)=336mgIVketamine/day 336mgIVketamine/day(1mgPOketamine/1mgIVketamine)=336mgPOketamine/day336mgPO ketamine/day(3doses/day)=112mg[Roundtoavailablecapsulesize60mg]Finaloralregimen:Ketamine 120mgPOQ8h References 1. OkonT.Ketamine:anintroductionforthepainandpalliativemedicinephysician.PainPhysician. 2007:10:493-500. 2. FitzgibbonEJ,HallP,SchroderC,SeelyJ,ViolaR.Lowdoseketamineasananalgesicadjuvantin 3. 4. 5. 6. 7. difficultpainsyndromes:astrategyforconversionfromparenteraltooralketamine.JPain SymptomManage.2002;23(2):165-170. Benitez-RosarioMA,FeriaM,Salinas-MartinA,etal.Aretrospectivecomparisonofthedose ratiobetweensubcutaneousandoralketamine.JPainSymptomManage.2003;25(5):400-401. BroadleyKE,KurowskaA,TookmanA.Ketamineinjectionusedorally.PalliatMed.1996;10:247250. BlonkMI,KoderBG,BemtPM,HuygenFJ.Useoforalketamineinchronicpainmanagement:a review.EurJPain.2010;14(5):466-72. Benitez-RosarioMA,Salinas-MartinA,Gonzalez-GuillermoT,FeriaM.Astrategyforconversion fromsubcutaneoustooralketamineincancerpainpatients:effectofa1:1ratio.JPain SymptomManage.2011;41(6):1098-1105. QuibellR,PrommerEE,MihalyoM,TwycrossR,WilcockA.Therapeuticreviews:ketamine.J PainSymptomManage.2011;41(3):640-649. Preparedby:KatherineJuba,PharmD,BCPS Reviewedby:TimothyQuill,MD,5/12