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FDA公布的药品说明书中药物基因组学相关生物标志物列表

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2021-02-27 23:37
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2021年2月27日发(作者:课程表英语)


Table of Pharmacogenomic Biomarkers in Drug


Labeling


Pharmacogenomics 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 and clinical response variability


?



?



?



?



Risk for adverse events


Genotype-specific dosing


Mechanisms of drug action


Polymorphic drug target and disposition genes


The table below lists FDA- approved drugs with pharmacogenomic information in their labeling. The labeling for


some, but not all, of the products includes 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 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 influence 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, salts, 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 Labeling



Drug


Therapeutic


Area*


Biomarker?



Referenced Subgroup?



Labeling Sections


Abacavir



Infectious


Diseases


HLA-B


HLA-B*5701 allele


carriers


Boxed Warning,


Contraindications,


Warnings and


Precautions


Ado- Trastuzumab


Emtansine



Oncology


ERBB2


HER2 protein


Indications


and


Usage,


overexpression or gene


Warnings and


Drug


Therapeutic


Area*


Biomarker?



Referenced Subgroup?



Labeling Sections


amplification positive


Precautions, Adverse


Reactions, Clinical


Pharmacology,


Clinical Studies


Afatinib



Oncology


EGFR


EGFR


exon


19


deletion


or


Indications


and


Usage,


exon 21 substitution


Dosage and


(L858R) positive


Administration,


Adverse Reactions,


Clinical


Pharmacology,


Clinical Studies


ALK gene rearrangement


Indications


and


Usage,


positive


Adverse Reactions,


Clinical


Pharmacology,


Clinical Studies


LDL receptor mutation


heterozygotes


Indications


and


Usage,


Adverse Reactions,


Clinical Studies


Precautions


Alectinib



Oncology


ALK


Alirocumab



Endocrinology


LDLR


Amitriptyline



Psychiatry


CYP2D6


CYP2D6 poor


metabolizers


Hormone receptor


positive


Anastrozole



Oncology


ESR1, PGR


Indications


and


Usage,


Adverse Reactions,


Drug Interactions,


Clinical Studies


Clinical Pharmacology


Arformoterol (1)



Pulmonary


UGT1A1


UGT1A1 poor


metabolizers


Arformoterol (2)



Pulmonary


CYP2D6


CYP2D6 intermediate or


Clinical Pharmacology


poor metabolizers


CYP2D6 poor


metabolizers


Dosage and


Administration,


Use


in


Specific Populations,


Aripiprazole



Psychiatry


CYP2D6


Drug


Therapeutic


Area*


Biomarker?



Referenced Subgroup?



Labeling Sections


Drug Interactions,


Clinical Pharmacology


Aripiprazole Lauroxil



Psychiatry


CYP2D6


CYP2D6 poor


metabolizers


Dosage and


Administration,


Use


in


Specific Populations,


Clinical Pharmacology


Arsenic Trioxide



Oncology


PML-RARA


PML-RAR


α



translocation


Clinical


positive


Pharmacology,


Indications and Usage


CYP2D6 poor


metabolizers


Dosage and


Administration,


Warnings and


Precautions, Drug


Interactions,


Clinical Pharmacology


Clinical


Pharmacology,


Warnings,


Precautions, Drug


Interactions, Adverse


Reactions, Dosage and


Administration


Dosage and


Administration,


Clinical Pharmacology


Atomoxetine



Psychiatry


CYP2D6


Azathioprine



Rheumatology


TPMT


TPMT intermediate or


poor metabolizers


Belinostat



Oncology


UGT1A1


UGT1A1*28 allele


homozygotes


Blinatumomab



Oncology


BCR-ABL1


Philadelphia


chromosome


Indications


and


Usage,


negative


Clinical Studies


IL28B rs12979860 T


Clinical Pharmacology


allele


carriers


(C/T


and


T/T genotype)


Philadelphia


chromosome


Indications


and


Usage,


positive


Adverse


Reactions,


Use


Boceprevir



Infectious


Diseases


IFNL3


Bosutinib



Oncology


BCR-ABL1


Drug


Therapeutic


Area*


Biomarker?



Referenced Subgroup?



Labeling Sections


in Specific


Populations, Clinical


Studies


Brexpiprazole



Psychiatry


CYP2D6


CYP2D6 poor


metabolizers


Dosage and


Administration, Drug


Interactions, Use in


Specific Populations,


Clinical Pharmacology


Busulfan



Oncology


BCR-ABL1


Philadelphia


chromosome


Clinical Studies


negative


RET mutation positive


DPD deficient


Clinical Studies


Warnings and


Precautions, Patient


Counseling


Information


Boxed Warning,


Warnings, Precautions


Warnings


Cabozantinib



Capecitabine



Oncology


Oncology


RET


DPYD


Carbamazepine (1)



Neurology


HLA-B


HLA-B*1502 allele


carriers


HLA-A*3101 allele


carriers


N-acetylglutamate


synthase deficient


Carbamazepine (2)



Neurology


HLA-A


Carglumic Acid



Inborn Errors


of Metabolism


NAGS


Indications


and


Usage,


Warnings and


Precautions, Use in


Specific Populations,


Clinical


Pharmacology,


Clinical Studies


Use in Specific


Populations, Clinical


Pharmacology


Drug Interactions,


Clinical Pharmacology


Carisoprodol



Rheumatology


CYP2C19


CYP2C19 poor


metabolizers


Carvedilol



Cardiology


CYP2D6


CYP2D6 poor


metabolizers


Drug


Therapeutic


Area*


Biomarker?



Referenced Subgroup?



Labeling Sections


Celecoxib



Rheumatology


CYP2C9


CYP2C9 poor


metabolizers


Dosage and


Administration,


Use


in


Specific Populations,


Clinical Pharmacology


Ceritinib



Oncology


ALK


ALK gene rearrangement


Indications


and


Usage,


positive


Adverse Reactions,


Clinical


Pharmacology,


Clinical Studies


EGFR protein expression


Indications


and


Usage,


positive


Dosage and


Administration,


Warnings and


Precautions, Adverse


Reactions, Clinical


Pharmacology,


Clinical Studies


KRAS codon 12 and 13


mutation negative


Indications


and


Usage,


Dosage and


Administration,


Warnings and


Precautions, Adverse


Reactions, Clinical


Pharmacology,


Clinical Studies


Precautions


Cetuximab (1)



Oncology


EGFR


Cetuximab (2)



Oncology


KRAS


Cevimeline



Dental


CYP2D6


CYP2D6 poor


metabolizers


G6PD deficient


Chloroquine



Infectious


Diseases


Endocrinology


Inborn Errors


of Metabolism


G6PD


Precautions


Chlorpropamide



Cholic Acid



G6PD


AKR1D1,


HSD3B7,


G6PD deficient


Bile acid synthesis


enzyme deficient


Precautions


Indications


and


Usage,


Warnings and


Drug


Therapeutic


Area*


Biomarker?



Referenced Subgroup?



Labeling Sections


CYP27A1,


AMACR,


CYP7A1


Precautions, Adverse


Reactions, Use in


Specific Populations,


Clinical


Pharmacology,


Clinical Studies


TPMT intermediate or


poor metabolizers


CYP2C19 poor


metabolizers


Adverse Reactions


Cisplatin



Oncology


TPMT


Citalopram (1)



Psychiatry


CYP2C19


Clinical


Pharmacology,


Warnings, Dosage and


Administration


Clinical Pharmacology


Citalopram (2)



Psychiatry


CYP2D6


CYP2D6 poor


metabolizers


CYP2C19 poor


metabolizers


Clobazam



Neurology


CYP2C19


Dosage and


Administration,


Use


in


Specific Populations,


Clinical Pharmacology


Precautions


Clomipramine



Psychiatry


CYP2D6


CYP2D6 poor


metabolizers


Clopidogrel



Cardiology


CYP2C19


CYP2C19 intermediate or


Boxed Warning, Dosage


poor metabolizers


and Administration,


Warnings and


Precautions, Clinical


Pharmacology


CYP2D6 poor


metabolizers


Dosage and


Administration,


Use


in


Specific Populations,


Clinical Pharmacology


Indications


and


Usage,


Dosage and


Administration,


Clozapine



Psychiatry


CYP2D6


Cobimetinib



Oncology


BRAF


BRAF V600E/K mutation


positive


Drug


Therapeutic


Area*


Biomarker?



Referenced Subgroup?



Labeling Sections


Adverse Reactions,


Clinical


Pharmacology,


Clinical Studies


Codeine



Anesthesiolog


y


CYP2D6


CYP2D6 ultrarapid


metabolizers


Boxed Warning,


Warnings and


Precautions, Use in


Specific Populations,


Patient Counseling


Information


Crizotinib



Oncology


ALK


ALK gene rearrangement


Indications


and


Usage,


positive


Dosage and


Administration,


Adverse Reactions,


Clinical


Pharmacology,


Clinical Studies


BRAF V600E/K mutation


positive


Indications


and


Usage,


Dosage and


Administration,


Warnings and


Precautions, Adverse


Reactions, Clinical


Pharmacology,


Clinical Studies,


Patient Counseling


Information


Warnings and


Precautions, Adverse


Reactions, Patient


Counseling


Information


Warnings and


Precautions, Use in


Dabrafenib (1)



Oncology


BRAF


Dabrafenib (2)



Oncology


G6PD


G6PD deficient


Dapsone (1)



Dermatology


G6PD


G6PD deficient


Drug


Therapeutic


Area*


Biomarker?



Referenced Subgroup?



Labeling Sections


Specific Populations,


Patient Counseling


Information


Dapsone (2)



Infectious


Diseases


Oncology


G6PD


G6PD deficient


Precautions, Adverse


Reactions, Overdosage


Dasatinib



BCR- ABL1


Philadelphia


chromosome


Indications


and


Usage,


positive, T315I


Dosage and


mutation positive


Administration,


Warnings and


Precautions, Adverse


Reactions, Clinical


Pharmacology,


Clinical Studies


CD25 antigen positive


Indications


and


Usage,


Warnings and


Precautions, Clinical


Studies


Precautions


Denileukin Diftitox



Oncology


IL2RA


Desipramine



Psychiatry


CYP2D6


CYP2D6 poor


metabolizers


CYP2C19 poor


metabolizers


CYP2D6 poor


metabolizers


Dexlansoprazole



Gastroenterol


ogy


Neurology


CYP2C19


Drug Interactions,


Clinical Pharmacology


Warnings and


Precautions, Clinical


Pharmacology


Clinical Pharmacology


Dextromethorphan and


Quinidine



CYP2D6


Diazepam



Neurology


CYP2C19


CYP2C19 poor


metabolizers


MYCN amplification


positive


UGT1A1 poor


metabolizers


Dinutuximab



Oncology


MYCN


Clinical Studies


Dolutegravir



Infectious


Diseases


UGT1A1


Clinical Pharmacology


Drug


Therapeutic


Area*


Biomarker?



Referenced Subgroup?



Labeling Sections


Doxepin (1)



Psychiatry


CYP2D6


CYP2D6 poor


metabolizers


CYP2C19 poor


metabolizers


CYP2C19 intermediate


metabolizers


CYP2D6 ultrarapid,


intermediate or poor


metabolizers


Clinical Pharmacology


Doxepin (2)



Psychiatry


CYP2C19


Clinical Pharmacology


Drospirenone


and


Ethinyl


Gynecology


Estradiol



Eliglustat



Inborn Errors


of Metabolism


CYP2C19


Clinical Pharmacology


CYP2D6


Indications


and


Usage,


Dosage and


Administration,


Contraindications,


Warnings and


Precautions, Drug


Interactions, Use in


Specific Populations,


Clinical


Pharmacology,


Clinical Studies


Indications


and


Usage,


Warnings and


Precautions, Use in


Specific Populations,


Clinical


Pharmacology,


Clinical Studies


Elosulfase



Inborn Errors


of Metabolism


GALNS < /p>


N-acetylgalactosamine-


6-sulfa tase deficient


Eltrombopag (1)



Hematology


F5


Factor


V


Leiden


carriers


Warnings and


Precautions


Antithrombin III


deficient


Warnings and


Precautions


Eltrombopag (2)



Hematology


SERPINC1


Erlotinib (1)



Oncology


EGFR


EGFR protein expression


Clinical Studies


positive


EGFR


exon


19


deletion


or


Indications


and


Usage,


exon 21 substitution


Dosage and


Erlotinib (2)



Oncology


EGFR


Drug


Therapeutic


Area*


Biomarker?



Referenced Subgroup?



Labeling Sections


(L858R) positive


Administration,


Adverse Reactions,


Clinical


Pharmacology,


Clinical Studies


Drug Interactions


Escitalopram (1)



Psychiatry


CYP2D6


CYP2D6 poor


metabolizers


CYP2C19 poor


metabolizers


CYP2C19 poor


metabolizers


Escitalopram (2)



Psychiatry


CYP2C19


Adverse Reactions


Esomeprazole



Gastroenterol


ogy


Oncology


CYP2C19


Drug Interactions,


Clinical Pharmacology


Everolimus (1)



ERBB2


HER2 protein


Indications


and


Usage,


overexpression


negative


Dosage and


Administration,


Warnings and


Precautions, Adverse


Reactions, Drug


Interactions, Use in


Specific Populations,


Clinical


Pharmacology,


Clinical Studies


Estrogen receptor


positive


LDL receptor mutation


heterozygotes and


homozygotes


Clinical Studies


Everolimus (2)



Oncology


ESR1


Evolocumab



Endocrinology


LDLR


Indications


and


Usage,


Dosage and


Administration,


Adverse


Reactions,


Use


in Specific


Populations, Clinical


Studies


Indications


and


Usage,


Exemestane (1)



Oncology


ESR1


Estrogen receptor


Drug


Therapeutic


Area*


Biomarker?



Referenced Subgroup?



Labeling Sections


positive


Dosage and


Administration,


Clinical Studies


Clinical Studies


Exemestane (2)



Oncology


PGR


Progesterone receptor


positive


CYP2D6 poor


metabolizers


DPD deficient


Fesoterodine



Urology


CYP2D6


Drug Interactions,


Clinical Pharmacology


Contraindications,


Warnings


Warnings


Warnings and


Precautions, Drug


Interactions,


Clinical Pharmacology


Clinical Pharmacology


Fluorouracil (1)



Dermatology


DPYD


Fluorouracil (2)



Fluoxetine



Oncology


Psychiatry


DPYD


CYP2D6


DPD deficient


CYP2D6 poor


metabolizers


Flurbiprofen



Rheumatology


CYP2C9


CYP2C9 poor


metabolizers


CYP2D6 poor


metabolizers


Hormone receptor


positive


Fluvoxamine



Psychiatry


CYP2D6


Drug Interactions


Fulvestrant



Oncology


ESR1, PGR


Indications


and


Usage,


Clinical


Pharmacology,


Clinical Studies


Clinical Pharmacology


Galantamine



Neurology


CYP2D6


CYP2D6 poor


metabolizers


EGFR exon 19 deletions


or exon 21 substitution


(L858R) mutation


positive


Gefitinib



Oncology


EGFR


Indications


and


Usage,


Dosage and


Administration,


Clinical


Pharmacology,


Clinical Studies


Drug


Therapeutic


Area*


Biomarker?



Referenced Subgroup?



Labeling Sections


Glimepiride



Endocrinology


G6PD


G6PD deficient


Warnings and


Precautions, Adverse


Reactions


Precautions


Precautions


Glipizide



Glyburide



Hydralazine



Ibrutinib



Endocrinology


Endocrinology


Cardiology


Oncology


G6PD


G6PD


NAT1-2


del (17p)


G6PD deficient


G6PD deficient


NAT


1-2


slow


acetylators


Clinical Pharmacology


Chromosome 17p deletion


Indications


and


Usage,


positive


Clinical Studies


CYP2D6 poor


metabolizers


Dosage and


Administration,


Warnings and


Precautions, Drug


Interactions,


Clinical Pharmacology


Iloperidone



Psychiatry


CYP2D6


Imatinib (1)



Oncology


KIT


KIT protein expression


Indications


and


Usage,


positive, c-KIT D816V


Dosage and


mutation negative


Administration,


Warnings and


Precautions, Adverse


Reactions, Use in


Specific Populations,


Clinical


Pharmacology,


Clinical Studies


Philadelphia


chromosome


Indications


and


Usage,


positive


Dosage and


Administration,


Warnings and


Precautions, Adverse


Reactions, Use in


Specific Populations,


Clinical


Imatinib (2)



Oncology


BCR-ABL1

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