FDA基因检测用药指南

1、TableofPharmacogenomicBiomarkersinDrugLabelingPharmacogenomicscanplayanimportantroleinidentifyingrespondersandnon-responderstomedications,avoidingadverseevents,andoptimizingdrugdose.Druglabelingmaycontaininformationongenomicbiomarkersandcandescribe:DrugexposureandclinicalresponsevariabilityRiskforad

2、verseeventsGenotype-specificdosingMechanismsofdrugactionPolymorphicdrugtargetanddispositiongenesThetablebelowlistsFDA-approveddrugswithpharmacogenomicinformationintheirlabeling.Thelabelingforsome,butnotall,oftheproductsincludesspecificactionstobetakenbasedonthebiomarkerinformation.Pharmacogenomicinf

3、ormationcanappearindifferentsectionsofthelabelingdependingontheactions.Formoreinformation,pleaserefertotheappropriatelabelingguidance.Biomarkersinthetableincludebutarenotlimitedtogerm-lineorsomaticgenevariants,functionaldeficiencies,expressionchanges,andchromosomalabnormalities;selectedproteinbiomar

4、kersthatareusedtoselectpatientsfortreatmentarealsoincluded.Thistabledoesnotincludenon-humangeneticbiomarkers(e.g.,microbialvariantsthatinfluencesensitivitytoantibiotics),orbiomarkersthatareusedsolelyfordiagnosticpurposes(e.g.,forgeneticdiseases)unlesstheyarelinkedtodrugactivityorusedtoidentifyaspeci

5、ficsubsetinwhomprescribinginformationdiffers.Fordrugsthatareavailableinmultipledosageforms,salts,orcombinations,asinglerepresentativeproductislisted.Inthecaseofcombinationproducts,thesingleagentassociatedwiththebiomarkerislistedunlesstheagentisonlyapprovedasacombinationproduct,inwhichcaseallagentsar

6、elisted.PharmacogenomicBiomarkersinDrugLabelingDrugTherapeuticArea*Biomarker?ReferencedSubgroup?LabelingSectionsAbacavirAdo-TrastuzumInfectiousDiseasesiHLA-BHLA-B*5701allelecarriersHER2proteinBoxedWarning,Contraindications,WarningsandPrecautionsIndicationsandUsage,abEmtansineOncologyERBB2overexpress

7、ionorgeneamplificationpositive,WarningsandPrecautions,AfatinibOncologyEGFRAlectinibOncologyALKAlirocumabEndocrinologLDLRyAmitriptylinePsychiatryAnastrozoleOncologyArformoterol(1)AdverseReactions,ClinicalPharmacology,ClinicalStudiesIndicationsandUsage,DosageandAdministration,AdverseReactions,Clinical

8、Pharmacology,ClinicalStudiesIndicationsandUsage,AdverseALKgenerearrangementReactions,positiveClinicalPharmacology,ClinicalStudiesIndicationsandUsage,LDLreceptormutationAdverseheterozygotesReactions,ClinicalStudiesEGFRexon19deletionexon21substitution(L858R)positiveCYP2D6CYP2D6poormetabolizersPrecauti

9、onsESR1,PGRHormonereceptorpositivePulmonaryUGT1A1IndicationsandUsage,AdverseReactions,DrugInteractions,ClinicalStudiesUGT1A1poormetabolizersClinicalPharmacologyCYP2D6intermediateorpoormetabolizersArformoterolAripiprazolePulmonaryPsychiatryAripiprazoleLauroxilPsychiatryArsenicTrioxideOncologyAtomoxet

10、inePsychiatryCYP2D6CYP2D6CYP2D6PML-RARARheumatologTPMTyAzathioprinepositiveClinicalPharmacologyDosageandAdministration,UseinSpecificCYP2D6poormetabolizersPopulations,DrugInteractions,ClinicalPharmacologyDosageandAdministration,UseinCYP2D6poormetabolizersSpecificPopulations,ClinicalPharmacologyClinic

11、alPML-RARxtranslocationPharmacology,IndicationsandUsageDosageandAdministration,WarningsandCYP2D6CYP2D6poormetabolizersPrecautions,DrugInteractions,ClinicalPharmacologyClinicalPharmacology,Warnings,Precautions,TPMTintermediateorpoorDrugmetabolizersInteractions,AdverseReactions,DosageandAdministratioD

12、rugTherapeuticArea*Biomarker?ReferencedSubgroup?LabelingSectionsnDosageandBelinostatOncologyUGT1A1UGT1A1*28allelehomozygotesAdministration,ClinicalPharmacologyIndicationsBlinatumomabOncologyBCR-ABL1PhiladelphiachromosomenegativeandUsage,ClinicalStudiesBoceprevirInfectiousDiseasesIFNL3IL28Brs12979860

13、Tallelecarriers(C/TandT/Tgenotype)ClinicalPharmacologyIndicationsandUsage,AdverseBosutinibOncologyBCR-ABL1PhiladelphiachromosomepositiveReactions,UseinSpecificPopulations,ClinicalStudiesDosageandAdministration,DrugBrexpiprazolePsychiatryCYP2D6Interactions,CYP2D6poormetabolizersUseinSpecificPopulatio

14、ns,ClinicalPharmacologyBusulfanOncologyBCR-ABL1PhiladelphiachromosomenegativeClinicalStudiesCabozantinibOncologyRETRETmutationpositiveClinicalStudiesWarningsandPrecautions,CapecitabineOncologyDPYDDPDdeficientPatientCounselingInformationBoxedCarbamazepineNeurologyHLA-BHLA-B*1502allelecarriersWarning,

15、Warnings,PrecautionsCarbamazepinK1,顷eNeurologyHLA-AHLA-A*3101allelecarriersWarningsInbornErrorsCarglumicAcidofNAGSN-acetylglutamatesynthasedeficientIndicationsandUsage,WarningsandPrecautions,UseinSpecificPopulations,ClinicalPharmacology,ClinicalStudiesCYP2D6poormetabolizersInteractions,ClinicalCaris

16、oprodolRheumatologCYP2C19CarvedilolCardiologyCYP2D6UseinSpecificCYP2C19poorPopulations,metabolizersClinicalPharmacologyDrugCelecoxibRheumatologCYP2C9yCeritinibOncologyALKPharmacologyDosageandAdministration,UseinCYP2C9poormetabolizersSpecificPopulations,ClinicalPharmacologyIndicationsandUsage,Adverse

17、ALKgenerearrangementReactions,positiveClinicalPharmacology,ClinicalStudiesIndicationsandUsage,Cetuximab(1)OncologyEGFREGFRproteinexpressionDosageandpositiveAdministration,WarningsandCetuximab(2)OncologyKRASCevimelineDentalCYP2D6InfectiousChloroquineDiseasesG6PDChlorpropamidEndocrinologG6PDeyAKR1D1,I

18、nbornErrorsHSD3B7,CholicAcidofCYP27A1,MetabolismAMACR,CYP7A1CisplatinOncologyTPMTCitalopram(1)PsychiatryCYP2C19Precautions,AdverseReactions,ClinicalPharmacology,ClinicalStudiesIndicationsandUsage,DosageandAdministration,WarningsandPrecautions,AdverseReactions,ClinicalPharmacology,ClinicalStudiesCYP2

19、D6poormetabolizersPrecautionsG6PDdeficientPrecautionsG6PDdeficientPrecautionsIndicationsandUsage,WarningsandPrecautions,AdverseBileacidsynthesisenzymeReactions,deficientUseinSpecificPopulations,ClinicalPharmacology,ClinicalStudiesTPMTintermediateorpoorAdversemetabolizersReactionsCYP2C19poorClinicalm

20、etabolizersPharmacologyKRAScodon12and13mutationnegativeDrugTherapeuticArea*Biomarker?ReferencedSubgroup?LabelingSections,Warnings,DosageandAdministrationCitalopramPsychiatryCYP2D6ClinicalCYP2D6poormetabolizersPharmacologyDosageandAdministratioClobazamNeurologyCYP2C19CYP2C19poormetabolizersn,UseinSpe

21、cificPopulations,ClinicalPharmacologyClomipraminePsychiatryCYP2D6CYP2D6poormetabolizersPrecautionsBoxedWarning,DosageandClopidogrelCardiologyCYP2C19CYP2C19intermediateorpoormetabolizersAdministration,WarningsandPrecautions,ClinicalPharmacologyDosageandAdministration,UseinClozapinePsychiatryCYP2D6CYP

22、2D6poormetabolizersSpecificPopulations,ClinicalPharmacologyIndicationsandUsage,DosageandAdministratioCobimetinibOncologyBRAFBRAFV600E/Kmutationpositiven,AdverseReactions,ClinicalPharmacology,ClinicalStudiesCodeineAnesthesioloCYP2D6CYP2D6ultrarapidBoxedgyCrizotinibOncologyALKDabrafenib(1)OncologyBRAF

23、Dabrafenib(2)OncologyG6PDmetabolizersWarning,WarningsandPrecautions,UseinSpecificPopulations,PatientCounselingInformationIndicationsandUsage,DosageandAdministratioALKgenerearrangementn,AdversepositiveReactions,ClinicalPharmacology,ClinicalStudiesIndicationsandUsage,DosageandAdministration,Warningsan

24、dPrecautions,BRAFV600E/KmutationAdversepositiveReactions,ClinicalPharmacology,ClinicalStudies,PatientCounselingInformationWarningsandPrecautions,AdverseG6PDdeficientReactions,PatientCounselingInformationDrugTherapeuticArea*Biomarker?LabelingReferencedSubgroup?SectionsDapsone(1)DermatologyG6PDWarning

25、sandPrecautions,UseinSpecificG6PDdeficientPopulations,Dapsone(2)InfectiousG6PDPatientCounselingInformationPrecautions,AdverseG6PDdeficientDasatinibDiseasesOncologyBCR-ABL1Reactions,OverdosageIndicationsandUsage,DosageandAdministration,WarningsPhiladelphiachromosomeandpositive,T315ImutationPrecaution

26、s,DenileukinDiftitoxOncologyIL2RApositiveAdverseReactions,ClinicalPharmacology,ClinicalStudiesIndicationsandUsage,WarningsandCD25antigenpositivePrecautions,DesipraminePsychiatryCYP2D6ClinicalStudiesCYP2D6poormetabolizersPrecautionsDexlansoprazolGastroenterolCYP2C19DrugCYP2C19poorInteractions,eogymet

27、abolizersClinicalDextromethorphanandNeurologyCYP2D6PharmacologyWarningsandPrecautions,CYP2D6poormetabolizersClinicalQuinidineDiazepamNeurologyCYP2C19PharmacologyCYP2C19poorClinicalmetabolizersPharmacologyDinutuximabDolutegravirDoxepin(1)Doxepin(2)DrospirenoneandEthinylEstradiolOncologyInfectiousDise

28、asesPsychiatryPsychiatryMYCNUGT1A1CYP2D6CYP2C19GynecologyCYP2C19EliglustatInbornErrorsoMfetabolismCYP2D6ElosulfaseInbornErrorsoMfetabolismGALNSMYCNamplificationClinicalpositiveStudiesUGT1A1poormetabolizersClinicalPharmacologyCYP2D6poormetabolizersCYP2C19poormetabolizersCYP2C19intermediatemetabolizer

29、sCYP2D6ultrarapid,intermediateorpoormetabolizersClinicalPharmacologyClinicalPharmacologyClinicalPharmacologyIndicationsandUsage,DosageandAdministration,Contraindications,WarningsandPrecautions,DrugInteractions,UseinSpecificPopulations,ClinicalPharmacology,ClinicalStudiesIndicationsandUsage,Warningsa

30、ndPrecautions,Eltrombopag(1)EltrombopagHematologyF5HematologySERPINC1N-acetylgalactosamine-6-sUseinSpecificulfatasedeficientPopulations,ClinicalPharmacology,ClinicalStudiesWarningsandFactorVLeidencarriersPrecautionsAntithrombinIIIdeficientWarningsandTherapeuticArea*Biomarker?ReferencedSubgroup?Label

31、ingSectionsPrecautionsOncologyEGFREGFRproteinexpressionpositiveClinicalStudiesIndicationsandUsage,DosageandEGFRexon19deletionorAdministration,AdverseReactions,ClinicalOncologyEGFRexon21substitution(L858R)positivePharmacology,ClinicalStudiesPsychiatryCYP2D6DrugCYP2D6poormetabolizersInteractionsPsychi

32、atryCYP2C19CYP2C19poormetabolizersAdverseReactionsDrugGastroenterolCYP2C19CYP2C19poorInteractions,ogymetabolizersClinicalPharmacologyIndicationsandUsage,DosageandAdministration,WarningsandPrecautions,OncologyERBB2HER2proteinoverexpressionnegativeAdverseReactions,DrugInteractions,UseinSpecificPopulat

33、ions,ClinicalPharmacology,ClinicalStudiesOncologyESR1EstrogenreceptorpositiveClinicalStudiesEndocrinologLDLRLDLreceptormutationIndicationsErlotinibErlotinibEscitalopramEscitalopramEsomeprazoleEverolimus(1)Everolimus(2)EvolocumabheterozygotesandhomozygotesandUsage,DosageandAdministration,AdverseReact

34、ions,UseinSpecificPopulations,ClinicalStudiesIndicationsandUsage,ExemestaneOncologyESR1EstrogenreceptorpositiveDosageandAdministration,ClinicalStudiesExemestaneOncologyPGRProgesteronereceptorClinicalpositiveStudiesDrugFesoterodineUrologyCYP2D6CYP2D6poormetabolizersInteractions,ClinicalPharmacologyFl

35、uorouracil(1)DermatologyDPYDFluorouracil(2)OncologyDPYDFluoxetinePsychiatryCYP2D6FlurbiprofenRheumatologCYP2C9FluvoxaminePsychiatryCYP2D6DPDdeficientContraindications,WarningsDPDdeficientWarningsWarningsandPrecautions,CYP2D6poormetabolizers?：，.Interactions,ClinicalPharmacologyCYP2C9poormetabolizersC

36、linicalPharmacologyDrugCYP2D6poormetabolizersInteractionsIndicationsandUsage,FulvestrantClinicalOncologyESR1,PGRHormonereceptorpositive,Pharmacology,ClinicalStudiesDrugTherapeuticArea*Biomarker?ReferencedSubgroup?LabelingSectionsGalantamineNeurologyCYP2D6ClinicalCYP2D6poormetabolizersPharmacologyInd

37、icationsandUsage,GefitinibOncologyEGFREGFRexon19deletionsorDosage+andAdministratioexon21substitutionn,Clinical(L858R)mutationpositive二,Pharmacology,ClinicalStudiesWarningsandGlimepirideEndocrinologyG6PDG6PDdeficientPrecautions,AdverseReactionsGlipizideEndocrinologyG6PDG6PDdeficientPrecautionsGlyburi

38、deEndocrinologyG6PDG6PDdeficientPrecautionsHydralazineCardiologyNAT1-2NAT1-2slowacetylatorsClinicalPharmacologyIndicationsIbrutinibOncologydel(17p)Chromosome17pdeletionpositiveandUsage,ClinicalStudiesDosageandAdministration,WarningsandIloperidonePsychiatryCYP2D6CYP2D6poormetabolizersPrecautions,Drug

39、Interactions,ClinicalPharmacologyIndicationsandUsage,Imatinib(1)OncologyKITKITproteinexpressionpositive,c-KITD816VmutationnegativeDosageandAdministration,WarningsandPrecautions,AdverseImatinibOncologyPhiladelphiachromosomeBCR-ABL11positiveImatinib(3)OncologyPDGFRgenePDGFRB,.厂rearrangementpositiveIma

40、tinib(4)ImipramineIndacaterolIrinotecanOncologyPsychiatryPulmonaryOncologylcccFIP1L1-PDGFRfusionFIP1L1-PDGFRACYP2D6UGT1A1UGT1A1Reactions,UseinSpecificPopulations,ClinicalPharmacology,ClinicalStudiesIndicationsandUsage,DosageandAdministration,WarningsandPrecautions,AdverseReactions,UseinSpecificPopul

41、ations,ClinicalPharmacology,ClinicalStudiesIndicationsandUsage,DosageandAdministration,ClinicalStudiesIndicationsandUsage,Dosageandkinase(orCHIC2deletion)Administratiopositiven,ClinicalStudiesCYP2D6poormetabolizersPrecautionsUGT1A1*28alleleClinicalhomozygotesPharmacologyDosageandAdministratioUGT1A1*

42、28allelecarriersn,WarningsandDrugTherapeuticArea*Biomarker?ReferencedSubgroup?LabelingSectionsPrecautions,ClinicalPharmacologyIndicationsandUsage,CFTRG551D,G1244E,AdverseG1349D,G178R,G551S,Reactions,IvacaftorPulmonaryCFTRS1251N,S1255P,S549N,S549R,R117HmutationUseinSpecificPopulations,positive,F508de

43、lmutationClinicalhomozygotesPharmacology,ClinicalStudiesLacosamideNeurologyCYP2C19CYP2C19poormetabolizersClinicalPharmacologyLansoprazoleGastroenterologyCYP2C19CYP2C19intermediateorpoormetabolizersDrugInteractionsIndicationsandUsage,DosageandAdministration,AdverseLapatinib(1)OncologyERBB2HER2protein

44、overexpressionpositiveReactions,UseinSpecificPopulations,ClinicalPharmacology,ClinicalStudiesLapatinib(2)OncologyHLA-DQA1,HLA-DRB1HLA-DQA1*0201orHLA-DRB1*0701allelecarriersClinicalPharmacologyBoxedWarning,IndicationsLenalidomideHematologydel(5q)Chromosome5qdeletionpositiveandUsage,AdverseReactions,U

45、seinSpecificPopulations,ClinicalIvacaftorandLumacaftorPulmonaryCFTRMafenideInfectiousDiseasesG6PDMercaptopurineOncologyTPMTStudiesLesinuradRheumatologCYP2C9CYP2C9poormetabolizersCyPharmacologyIndicationsandUsage,AdverseLetrozoleReactions,OncologyESR1,PGRHormonereceptorpositiveClinicalPharmacology,Cl

46、inicalStudiesIndicationandUsage,WarningsandLomitapideEndocrinologLDLRLDLreceptormutationPrecautions,yhomozygotesAdverseReactions,ClinicalStudiesIndicationsandUsage,AdverseCFTRF508delmutationReactions,homozygotesClinicalPharmacology,ClinicalStudiesWarnings,G6PDdeficientAdverseMethyleneBlueHematologyG

47、6PDG6PDdeficientnPrecautionsReactionsClinicalPharmacology,Warnings,Precautions,TPMTintermediateorpoorAdversemetabolizersReactions,DosageandAdministratioDrugTherapeuticArea*Biomarker?LabelingReferencedSubgroup?SectionsMetoclopramiGastroenterolCYB5R1-4NADHcytochromeb5Precautionsdeogyreductasedeficient

48、MetoclopramideMetoprololGastroenterologyCardiologyG6PDCYP2D6G6PDdeficientPrecautionsClinicalCYP2D6poormetabolizersPharmacologyMipomersenEndocrinologyLDLRIndicationsandUsage,WarningsandLDLreceptormutationPrecautions,AnVPrQPheterozygotesandReactions,ModafinilPsychiatryCYP2D6homozygotesUseinSpecificPop

49、ulations,ClinicalStudiesClinicalCYP2D6poormetabolizersPharmacologyMycophenolicTransplantatiHPRT1,PrecautionsWarningsandHGPRTdeficientx.AcidonPrecautionsNalidixicAcidInfectiousG6PDPrecautions,G6PDdeficientAdverseNefazodoneDiseasesPsychiatryCYP2D6ReactionsCYP2D6poormetabolizersPrecautionsNilotinib(1)O

50、ncologyBCR-ABL1IndicationsandUsage,DosageandAdministration,AdversePhiladelphiachromosomeReactions,Nilotinib(2)OncologyUGT1A1positiveUseinSpecificPopulations,ClinicalPharmacology,ClinicalStudiesUGT1A1*28alleleClinicalNitrofurantoinInfectiousG6PDhomozygotesPharmacologyG6PDdeficientWarnings,DrugTherape

51、uticArea*Biomarker?ReferencedSubgroup?LabelingSectionsDiseasesAdverseReactionsIndicationsandUsage,Nivolumab(1)OncologyBRAFBRAFV600mutationpositiveAdverseReactions,ClinicalStudiesNivolumabOncologyCD274PD-L1proteinexpressionpositiveClinicalPharmacologyNortriptylinePsychiatryCYP2D6CYP2D6poormetabolizer

52、sPrecautionsObinutuzumabOncologyMS4A1CD20antigenpositiveClinicalStudiesIndicationsandUsage,DosageandAdministration,WarningsandOlaparibOncologyBRCA1-2BRCA1-2mutationpositivePrecautions,AdverseReactions,ClinicalPharmacology,ClinicalStudiesClinicalOmacetaxineOncologyBCR-ABL1Philadelphiachromosomepositi

53、vePharmacology,ClinicalStudiesOmbitasvir,Paritaprevir,Ritonavir,andDasabuvirInfectiousDiseasesIFNL3IL28Brs12979860Tallelecarriers(non-C/Cgenotype)ClinicalStudiesOmeprazoleGastroenterologyCYP2C19CYP2C19poormetabolizersDrugInteractionsIndicationsOsimertinibOncologyEGFREGFRT790MmutationpositiveandUsage

54、,DosageandAdministration,AdversePalbociclib(1)OncologyESR1PalbociclibPalonosetronPanitumumab(1)OncologyERBB2Reactions,ClinicalPharmacology,ClinicalStudiesIndicationsandUsage,AdverseReactions,EstrogenreceptorpositiveClinicalPharmacology,ClinicalStudiesIndicationsandUsage,HER2proteinAdverseoverexpressionnegativeReactions,ClinicalStudiesGastroenterologyCYP2D6ClinicalCYP2D6poormetabolizersPharmacologyClinicalOncologyEGFREGFRproteinexpressionpositivePharmacology,Cli