FDA基因检测用药的指引

1、Table of Pharmacogenomic Biomarkers in Drug LabelingPharmacogenomics can play an important role in identifying responders and non-responders to medications, avoiding adverse events, and optimizing drug dose. Drug labeling may contain information on genomic biomarkers and can describe: Drug exposure

2、and clinical response variability Risk for adverse eventsGenotype-specific dosing Mechanisms of drug action Polymorphic drug target and disposition genesThe table below lists FDA-approved drugs with pharmacogenomic information in their labeling. The labeling for some, but not all, of the products in

3、cludes specific actions to be taken based on the biomarker information. Pharmacogenomic information can appear in different sections of the labeling depending on the actions. For more information, please refer to the appropriate labeling guidance. Biomarkers in the table include but are not limited

4、to germ-line or somatic gene variants, functional deficiencies, expression changes, and chromosomal abnormalities; selected protein biomarkers that are used to select patients for treatment are also included.This table does not include non-human genetic biomarkers (e.g., microbial variants that infl

5、uence sensitivity to antibiotics), or biomarkers that are used solely for diagnostic purposes (e.g., for genetic diseases) unless they are linked to drug activity or used to identify a specific subset in whom prescribing information differs. For drugs that are available in multiple dosage forms, sal

6、ts, or combinations, a single representative product is listed. In the case of combination products, the single agent associated with the biomarker is listed unless the agent is only approved as a combination product, in which case all agents are listed. Pharmacogenomic Biomarkers in Drug LabelingDr

7、ugTherapeuticArea*Biomarker? Referenced Subgroup?LabelingSectionsBoxedWarning,AbacavirInfectiousDiseasesHLA-BHLA-B*5701 allele carriersContraindicati ons, WarningsandPrecautionsERBB2Indications and Usage, Warnings and Precautions,Ado-TrastuzumOncology ab EmtansineHER2 protein overexpression or gene

8、amplification positiveDrugTherapeuticArea*Biomarker? Referenced Subgroup?LabelingSectionsAdverse Reactions, Clinical Pharmacology , Clinical StudiesAfatinib Oncology EGFRAlectinib Oncology ALKAlirocumabEndocrin010gLDLRyIndications and Usage, Dosage and Administratio n, Adverse Reactions, Clinical Ph

9、armacology , Clinical StudiesIndications and Usage, AdverseALK gene rearrangement Reactions, positiveClinicalPharmacology , Clinical StudiesIndications and Usage, LDL receptor mutationAdverseheterozygotesReactions,Clinical StudiesEGFR exon 19 deletion exon 21 substitution (L858R) positiveAmitriptyli

10、ne PsychiatryCYP2D6 CYP2D6 poor metabolizersPrecautionsIndicationsand Usage, AdverseAnastrozole OncologyESR1, PGR Hormone receptor positiveReactions, Drug Interactions,Arformoterol(1)PulmonaryClinicalStudiesClinical UGT1A1 UGT1A1 poor metabolizers_,.PharmacologyDrugArformoterol AripiprazoleTherapeut

11、icArea*PulmonaryPsychiatryBiomarker? Referenced Subgroup?CYP2D6CYP2D6LabelingSectionsAripiprazoleLauroxilPsychiatryCYP2D6ArsenicTrioxideOncologyPML-RARAAtomoxetinePsychiatryCYP2D6AzathioprineRheumatolog TPMT yCYP2D6 intermediate or poor metabolizersClinical Pharmacology Dosage and Administratio n, U

12、se in SpecificCYP2D6 poor metabolizersPopulations, Drug Interactions, Clinical Pharmacology Dosage and Administratio n, Use inCYP2D6 poor metabolizersSpecificPML-RARx translocationpositivePopulations, Clinical Pharmacology Clinical Pharmacology , Indications and Usage Dosage and Administratio n, War

13、nings andCYP2D6 poor metabolizersPrecautions, Drug Interactions, Clinical Pharmacology Clinical Pharmacology ,Warnings, Precautions,TPMT intermediate or poor DrugmetabolizersInteractions, Adverse Reactions, Dosage and AdministratioDrugBelinostatBlinatumomabBoceprevirBosutinibTherapeuticArea*Biomarke

14、r? Referenced Subgroup?Oncology UGT1A1Oncology BCR-ABL1Infectious IFNL3DiseasesOncology BCR-ABL1LabelingSectionsDosage and UGT1A1*28 alleleAdministratiohomozygotesn, ClinicalPharmacology IndicationsPhiladelphia chromosome and Usage, negativeClinicalStudiesIL28B rs12979860 T allele carriers (C/T and

15、T/T genotype)ClinicalPharmacologyIndicationsand Usage, Adverse Philadelphia chromosome Reactions, positiveUse in SpecificPopulations, Clinical StudiesDosage andAdministration, DrugBrexpiprazoleBusulfanCabozantinibCapecitabineCarbamazepin ePsychiatry CYP2D6Oncology BCR-ABL1Oncology RETOncology DPYDNe

16、urology HLA-BCYP2D6 poor metabolizersInteractions, Use in SpecificPopulations, ClinicalPharmacologyPhiladelphia chromosome Clinical negativeStudiesRET mutation positiveClinicalStudiesWarnings and Precautions,DPD deficientPatientCounseling Information BoxedHLA-B*1502 allele carriers Warning, Warnings

17、, PrecautionsDrugTherapeuticArea*Biomarker? Referenced Subgroup?LabelingSectionsIndicationsN-acetylglutamateand Usage, Warnings and Precautions, Use in Specificsynthase deficientPopulations,CYP2C19 poorClinicalPharmacology , Clinical StudiesUse in Specific Populations,metabolizersClinicalPharmacolog

18、yDrugInteractions,CYP2D6 poor metabolizersClinicalHLA-A*3101 allele carriers WarningsCarbamazepin Z ,e (2)Neurology HLA-AInborn ErrorsCarglumic Acid ofNAGSCarisoprodol RheumatologCYP2c19Carvedilol Cardiology CYP2D6CelecoxibRheumat010g CYP2C9yCeritinib Oncology ALKCetuximab (1) OncologyEGFRPharmacolo

19、gy Dosage and Administratio n, Use in CYP2C9 poor metabolizersSpecificPopulations, ClinicalPharmacology Indications and Usage, AdverseALK gene rearrangement Reactions, positiveClinicalPharmacology , Clinical StudiesIndications and Usage, EGFR protein expression Dosage and positiveAdministration, War

20、nings andDrugTherapeuticArea*Biomarker? Referenced Subgroup?LabelingSectionsPrecautions, Adverse Reactions, Clinical Pharmacology ,Clinical StudiesIndications and Usage, Dosage and AdministratioCetuximab (2) OncologyKRASKRAS codon 12 and 13 mutation negativen, Warnings and Precautions, Adverse React

21、ions, Clinical Pharmacology , Clinical StudiesCevimelineDentalInfectiousChloroquineDiseasesCYP2D6 CYP2D6 poor metabolizersPrecautionsG6PD G6PD deficientPrecautionsG6PDChlorpropamid Endocrinolog eyAKR1D1, Inborn Errors HSD3B7, Cholic Acid ofCYP27A1,Metabolism AMACR, CYP7A1G6PD deficientPrecautionsInd

22、ications and Usage, Warnings and Precautions, AdverseBile acid synthesis enzyme Reactions, deficientUse in SpecificPopulations, ClinicalPharmacology ,Clinical StudiesCisplatinOncology TPMTTPMT intermediate or poor AdversemetabolizersReactionsCitalopram (1) PsychiatryCYP2C19CYP2C19 poor metabolizersC

23、linicalPharmacologyDrugTherapeuticArea*Biomarker? Referenced Subgroup?LabelingSections,Warnings, Dosage and Administratio nCitalopram (2)Psychiatry CYP2D6CYP2D6 poor metabolizersClobazamNeurology CYP2C19CYP2C19 poor metabolizersClinical Pharmacology Dosage and Administratio n, Use in Specific Popula

24、tions, Clinical PharmacologyClomipraminePsychiatry CYP2D6ClopidogrelCardiology CYP2C19ClozapinePsychiatry CYP2D6CobimetinibOncology BRAFCYP2D6 poor metabolizersPrecautions Boxed Warning, Dosage and AdministratioCYP2C19 intermediate or n, Warnings poor metabolizers and Precautions, ClinicalPharmacolo

25、gy Dosage and Administratio n, Use in CYP2D6 poor metabolizersSpecific Populations, Clinical Pharmacology Indications and Usage, Dosage and AdministratioBRAF V600E/K mutation n, AdversepositiveReactions, Clinical Pharmacology , Clinical StudiesCodeineAnesthesiolo CYP2D6CYP2D6 ultrarapidBoxedDrugCriz

26、otinibTherapeuticArea*Biomarker? Referenced Subgroup?LabelingSectionsgymetabolizersWarning, Warnings and Precautions, Use in Specific Populations, Patient Counseling InformationIndications and Usage, Dosage and AdministratioOncologyALKALK gene rearrangement positiven, Adverse Reactions, Clinical Pha

27、rmacology ,Clinical StudiesIndications and Usage, Dosage and Administratio n, Warnings and Precautions,OncologyBRAFBRAF V600E/K mutation positiveAdverse Reactions, Clinical Pharmacology ,Clinical Studies, Patient Counseling Information Warnings and Precautions, AdverseOncologyG6PDG6PD deficientReact

28、ions, Patient Counseling InformationDabrafenib (1)Dabrafenib (2)DrugTherapeuticArea*Biomarker? Referenced Subgroup?LabelingSectionsDapsone (1)DermatologyG6PDDapsone (2)InfectiousDiseasesG6PDG6PD deficientG6PD deficientDasatinib Oncology BCR-ABL1Philadelphia chromosome positive, T315I mutation positi

29、veWarnings and Precautions, Use in Specific Populations, Patient Counseling Information Precautions, Adverse Reactions, Overdosage Indications and Usage, Dosage and Administratio n, Warnings and Precautions, Adverse Reactions, ClinicalDenileukinDiftitoxOncologyIL2RADesipraminePsychiatryCYP2D6Dexlans

30、oprazolGastroenterolCD25 antigen positiveCYP2c19eogyPharmacology , Clinical StudiesIndications and Usage, Warnings and Precautions, Clinical StudiesCYP2D6 poor metabolizersPrecautions DrugCYP2C19 poorInteractions,metabolizersClinicalPharmacologyDextromethorphan andNeurologyCYP2D6QuinidineDiazepamNeu

31、rologyCYP2C19Warnings andCYP2D6 poor metabolizersPrecautions, ClinicalCYP2C19 poor metabolizersPharmacologyClinicalPharmacologyDrugTherapeuticArea*Biomarker? Referenced Subgroup?LabelingSectionsDinutuximabOncologyMYCNMYCN amplificationClinicalpositiveStudiesDolutegravirInfectiousDiseasesUGT1A1Clinic

32、alUGT1A1 poor metabolizersPharmacologyDoxepin (1)PsychiatryCYP2D6ClinicalCYP2D6 poor metabolizersPharmacologyDoxepin (2)PsychiatryCYP2C19CYP2C19 poor metabolizersClinicalPharmacologyDrospirenoneGynecologyCYP2C19CYP2C19 intermediateClinicaland Ethinyl EstradiolmetabolizersPharmacologyIndications and

33、Usage, Dosage and Administratio n, Contraindicati ons, WarningsInborn ErrorsCYP2D6 ultrarapid,andEliglustatofCYP2D6intermediate or poorPrecautions,MetabolismmetabolizersDrug Interactions, Use in Specific Populations, Clinical Pharmacology , Clinical Studies Indications and Usage, Warnings and Precau

34、tions,Inborn ErrorsElosulfaseofGALNSN-acetylgalactosamine-6-s Use in SpecificMetabolismulfatase deficientPopulations, Clinical Pharmacology , Clinical StudiesEltrombopagHematologyF5Factor V Leiden carriersWarnings and(1)PrecautionsEltrombopagHematologySERPINC1Antithrombin III deficientWarnings andTh

35、erapeuticArea*Biomarker? Referenced Subgroup?LabelingSectionsPrecautionsOncologyEGFREGFR protein expression positiveClinicalStudiesIndications and Usage, Dosage andEGFR exon 19 deletion orAdministratio n, Adverse Reactions, ClinicalOncologyEGFRexon 21 substitution (L858R) positivePharmacology, Clini

36、cal StudiesPsychiatryCYP2D6DrugCYP2D6 poor metabolizersInteractionsPsychiatryCYP2c19CYP2C19 poor metabolizersAdverse Reactions DrugGastroenterolCYP2C19CYP2C19 poorInteractions,ogymetabolizersClinical Pharmacology Indications and Usage, Dosage and Administratio n, Warnings and Precautions,OncologyERB

37、B2HER2 protein overexpression negativeAdverse Reactions, Drug Interactions, Use in Specific Populations, Clinical Pharmacology , Clinical StudiesOncologyESR1Estrogen receptor positiveClinicalStudiesEndocrinolog LDLRLDL receptor mutationIndicationsDrugErlotinib Erlotinib Escitalopram Escitalopram Eso

38、meprazoleEverolimus (1)Everolimus (2)EvolocumabDrugTherapeuticArea*Biomarker? Referenced Subgroup?LabelingSectionsheterozygotes and homozygotesExemestane OncologyESR1Estrogen receptor positiveExemestane OncologyPGRProgesterone receptor positiveFesoterodineUrologyCYP2D6CYP2D6 poor metabolizersFluorou

39、racil (1) DermatologyDPYDDPD deficientFluorouracil (2) OncologyDPYDDPD deficientFluoxetinePsychiatryCYP2D6CYP2D6 poor metabolizersFlurbiprofenRheumatolog CYP2C9 yCYP2C9 poor metabolizersFluvoxaminePsychiatry CYP2D6CYP2D6 poor metabolizersFulvestrantOncology ESR1, PGR Hormone receptor positiveand Usa

40、ge, Dosage and Administratio n, Adverse Reactions, Use in Specific Populations, Clinical Studies Indications and Usage, Dosage and Administratio n, Clinical Studies Clinical StudiesDrug Interactions, Clinical Pharmacology Contraindicati ons, Warnings Warnings Warnings and Precautions, Drug Interacti

41、ons, Clinical Pharmacology Clinical Pharmacology Drug Interactions Indications and Usage, Clinical Pharmacology , Clinical StudiesDrugTherapeuticArea*Biomarker? Referenced Subgroup?LabelingSectionsGalantamineNeurology CYP2D6ClinicalCYP2D6 poor metabolizersPharmacologyIndicationsand Usage,GefitinibOn

42、cology EGFREGFR exon 19 deletions orDosage .and Administratio exon 21 substitutionZl.匚.口、. n, Clinical(L858R) mutation positive ,Pharmacology,Clinical StudiesWarnings andGlimepirideEndocrinolog G6PD yG6PD deficientPrecautions, Adverse ReactionsGlipizideEndocrinolog G6PD yG6PD deficientPrecautionsGly

43、burideEndocrinolog G6PD yG6PD deficientPrecautionsHydralazineCardiology NAT1-2NAT 1-2 slow acetylatorsClinical Pharmacology IndicationsIbrutinibOncology del (17p)Chromosome 17p deletion positiveand Usage, ClinicalStudiesDosage and Administratio n, Warnings andIloperidonePsychiatry CYP2D6CYP2D6 poor

44、metabolizersPrecautions,Drug Interactions, Clinical Pharmacology Indications and Usage,Imatinib (1)Oncology KITKIT protein expression positive, c-KIT D816V mutation negativeDosage and Administratio n, Warnings and Precautions, AdverseDrugTherapeuticArea*Biomarker? Referenced Subgroup?LabelingSection

45、sReactions, Use in Specific Populations, Clinical Pharmacology ,Clinical StudiesIndicationsand Usage, Dosage and Administratio n, Warnings andImatinib (2)OncologyBCR-ABL1Philadelphia chromosome positivePrecautions, Adverse Reactions, Use in Specific Populations, ClinicalPharmacology , Clinical Studi

46、esImatinib (3)OncologyPDGFR genePDGFRB ,.rearrangement positiveIndications and Usage, Dosage and Administratio n, Clinical StudiesImatinib (4)ImipramineIndacaterolIrinotecanOncologyPsychiatryPulmonaryOncologyccFIP1L1-PDGFR fusion FIP1L1-PDGIndications and Usage, Dosage andFRA kinase (or CHIC2 deleti

47、on) Administratio positiven, ClinicalStudiesCYP2D6UGT1A1UGT1A1CYP2D6 poor metabolizersPrecautionsUGT1A1*28 alleleClinicalhomozygotesPharmacologyUGT1A1*28 allele carriersDosage andAdministratio n, WarningsandDrugTherapeuticArea*Biomarker? Referenced Subgroup?LabelingSectionsIvacaftorLacosamideLansopr

48、azoleLapatinib (1)Lapatinib (2)LenalidomidePrecautions,clinicalPharmacologyIndicationsand Usage,CFTR G551D, G1244E,AdverseG1349D, G178R, G551S,Reactions,cic-cS1251N, S1255P, S549N,Use in SpecificPulmonary CFTR'S549R, R117H mutationPopulations,positive, F508del mutationclinicalhomozygotesPharmaco

49、logy,ClinicalStudiesCYP2C19 poorClinicalNeurology CYP2C19metabolizersPharmacologyGastroenterolCYP2C19 CYP2c19 intermediate orDrugogypoor metabolizersInteractionsIndicationsand Usage,Dosage andAdministration, AdverseHER2 proteinReactions,Oncology ERBB2overexpression positive,Use in SpecificPopulation

50、s,ClinicalPharmacology,ClinicalStudies八HLA-DQA1*0201 orHLA-DQA1ClinicalOncology A ,HLA-DRB1*0701 alleleHLA-DRB1carriersPharmacologyBoxedWarning,Indicationschromosome 5q deletionand Usage,Hematology del (5q)positiveAdverseReactions,Use in SpecificPopulations,ClinicalDrugTherapeuticLabelingArea*Biomarker? Referenced Subgroup? Secti0nsLesinuradRheumatologC CYP2c9CYP2c9 poor metabolizersyLetrozoleOncologyESR1, PGR Hormone receptor positiveLomitapideEndocrinolog yLDLRLDL receptor mutation homozygotesIvacaftor and LumacaftorPulm