Download Ketamine Parenteral and Oral Dose Recommendations

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