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VariableUnitsorAllowedValuesEnterValueAgeYearsHeightCentimeters(cm)WeightKilograms(kg)VKORC1genotypeA/AA/GG/GU((forUnknown)CYP2C9genotype*1/*1*1/*2*1/*3*2/*2*2/*3*3/*3U(forUnknown)RaceA(forAsian)B(forBlackorAfricanAmerican)C(forCaucasianorWhite)U(forUnknownorMixedRace)TakingEnzymeInducerY(forYes)N(forNoornotknown)TakingAmiodaroneY(forYes)N(forNoornotknown)ERROR*1/*1*1/*2*1/*3*2/*2*2/*3ComputedWeeklyStartingDose(mg/week):IWPCWarfarinDoseCalculatordetailedinstructionsandexamplescanbefoundattheInstructionstab*3/*3UErrorMessages/WarningsValidationResultEnteranumericalvalueforageinyears,suchas65ErrorEnteranumericalvalueforHeightincmErrorBMIcalcassumingmetricObesityDescriptorEnteranumericalvalueforWeightinkgError#DIV/0!#DIV/0!EnteragenotypeforVKORC1-1639AGSNP,usingoneoftheallowedvaluesshownincolumnB,orenterthesingleletter'U'forunknowngenotypeErrorEnteragenotypeforCYP2C9,usingoneoftheallowedvaluesshownincolumnB,orenterthesingleletter'U'forunknowngenotype,Notethatallelesotherthan*1,*2,and*3arenotallowedintheIWPCalgorithmErrorEnterpatient'srace,usingsingelettervaluesA,B,C,orU,asshownincolumnBErrorEntereitherY(patienttakingCYP2C9inducer)orN(patientnottakingCYP2C9inducer).TheinducersconsideredindevelopmentoftheIWPCalgorithmwererifampin,phenytoin,andcarbamazepineErrorEntereitherY(patienttakingamiodarone)orN(patientnottakingamiodorone).ErrorThereare8errorsinthedatayouhaveentered.Adosecannotbecalculateduntiltheerrorsarefixed.8Errorcount0WarningcountCYP2C9lookuptable*1/*10*1/*2-0.5211*1/*3-0.9357*2/*2-1.0616*2/*3-1.9206IWPCWarfarinDoseCalculatordetailedinstructionsandexamplescanbefoundattheInstructionstab*3/*3-2.3312U-0.2188Variablesrequiredforthecomputationareasfollows:VariableUnitsorAllowedValuesAgeYearsHeightCentimeters(cm)WeightKilograms(kg)VKORC1genotypeA/AA/GG/GU((forUnknown)CYP2C9genotype*1/*1*1/*2*1/*3*2/*2*2/*3*3/*3U(forUnknown)RaceA(forAsian)B(forBlackorAfricanAmerican)C(forCaucasianorWhite)U(forUnknownorMixedRace)ThisisthegenotypeforCYP2C9.Onlygenotypescomposedofcombinationsofthe*1,*2and*3allelesintheexactformatshownareallowed.TheseweretheonlyallelesthatoccurredintheIWPCpatientpopulationathighenoughfrequenciestoreliablyestimatetheircontributiontoWarfarindose.Ifyouhavegenotypedotheralleles,youmaywishtoenteranallowedgenotypethatisclosestinenzymeactivitytoyouractualgenotype,basedonthepharmacologicliterature.Ifgenotypeisunknown,enterthesingleletterU.Anyvalueotherthantheallowedvalueswillstopthecomputationandmustbecorrected.ThiscalculatorprovidesapredictedstartingdoseforWarfarinbasedonapharmacogeneticalgorithmdevelopedbytheIWPC(InternationalWarfarinPharmacogeneticsConsortium),asdescribedinN.Engl.J.Med.360:753-764(2009).Thealgorithmonlyusesageatthegranularityofdecades,butyoumustenterageinyearsandthecalculatorwillconverttodecadesHeightmustbeenteredincentimeters,notfeetorinches.Verylargeorverysmallvaluesofheightwillresultinawarning,asthesemayindicatedataentryerrors,buttheywillnotstopthecomputation.Ifawarningappears,pleasecheckthatheightwasenteredcorrectly.Thisisthegenotypeatthe-1639AGSNPintheVKORC1promoter.Onlythevaluesshownintheexactformatshownareallowed;anyothervalueswillstopthecomputationandmustbecorrected.Ifgenotypeisunknown,enterthesingleletterU.IfyouhavegenotypedadifferentVKORC!SNPwhichyouknowtobeinhighLinkageDisequilibriumwiththe-1639SNPintheracialgrouptowhichyourpatientbelongs,youmaywishtosubstituteanallowedvaluethatrepresentsthehaplotypesindicatedbytheSNPyoutyped.Consulttheliteratureforappropriatesubstitutions.Weightmustbeenteredinkilograms,notpounds.Toflagpotentialdataentryerrors,HeightandWeightareusedtocomputeBMI,andverylargeorverysmallvaluesofBMIresultinawarning,butwillnotstopthecomputation.Ifawarningappears,pleasecheckthatweightwasenteredcorrectly.Toobtainapredictedstartingdose,enterdataforyourpatientinthecolumnlabeledEnterValueontheCalculatortabofthisExcelWorkbook.AnentryisrequiredforeachvariablelistedintheCalculator.Thepredicteddoseisgivenbelowthelastlineinthedataentrytable.PleasenotethatthisisaWeeklydose,notadailydose.Dividethisdoseasevenlyaspossibleinto7partstoobtaindailydoses.CommentsEntersinglelettercodes(A,BorC)foroneofthethreebroadracialgroupingsthatwereusedintheIWPCalgorithm(Asian,Black,andCaucasian).TheselargelycorrespondtotheUSOMBracialcategories,althoughHispanicswereincludedintheCaucasiancategoryintheIWPCdataset.OtherracialgroupsoccurredintheIWPCdatasetinnumberstoosmalltoprovidereliableestimatesofeffectonWarfarindose,andwereincludedintheUnknowngroup.EnterthesingleletterUforunknownormixedrace.Anyothervaluewillstopthecomputationandmustbecorrected.TakingEnzymeInducerYorNTakingAmiodaroneYorNExamplecalculationsVariableUnitsorAllowedValuesEnterValueAgeYears70HeightCentimeters(cm)180WeightKilograms(kg)75VKORC1genotypeA/AA/GG/GU((forUnknown)A/GCYP2C9genotype*1/*1*1/*2*1/*3*2/*2*2/*3*3/*3U((forUnknown)*1/*1RaceA(forAsian)B(forBlackorAfricanAmerican)C(forCaucasianorWhite)U(forUnknownorMixedRace)CTakingEnzymeInducerYorNNTakingAmiodaroneYorNN30ComputedWeeklyStartingDose(mg/week):Inthefirstexample,alldataa