Adverse Drug Reactions in the Emergency Department: Is There a Role for Pharmacogenomic Profiles at Risk?—Results from the ADRED Study

Individual differences in required drug dosages exist based on the pharmacogenomic (PGx) profiles. This study aimed to assess associations between PGx profiles and adverse drug reactions (ADR) that lead to admissions to the emergency department (ED). ADR cases of the prospective multi-center observa...

Full description

Bibliographic Details
Main Authors: Katja S. Just, Harald Dormann, Marlen Schurig, Miriam Böhme, Jochen Fracowiak, Michael Steffens, Catharina Scholl, Thomas Seufferlein, Ingo Gräff, Matthias Schwab, Julia C. Stingl
Format: Article
Language:English
Published: MDPI AG 2020-06-01
Series:Journal of Clinical Medicine
Subjects:
Online Access:https://www.mdpi.com/2077-0383/9/6/1801
id doaj-11bfc3bf8a7f4e5a825bdb398dc3dbaa
record_format Article
spelling doaj-11bfc3bf8a7f4e5a825bdb398dc3dbaa2020-11-25T03:17:50ZengMDPI AGJournal of Clinical Medicine2077-03832020-06-0191801180110.3390/jcm9061801Adverse Drug Reactions in the Emergency Department: Is There a Role for Pharmacogenomic Profiles at Risk?—Results from the ADRED StudyKatja S. Just0Harald Dormann1Marlen Schurig2Miriam Böhme3Jochen Fracowiak4Michael Steffens5Catharina Scholl6Thomas Seufferlein7Ingo Gräff8Matthias Schwab9Julia C. Stingl10Institute of Clinical Pharmacology, University Hospital of RWTH Aachen, 52074 Aachen, GermanyCentral Emergency Department, Hospital Fürth, 90766 Fürth, GermanyResearch Department, Federal Institute for Drugs and Medical Devices, 53175 Bonn, GermanyResearch Department, Federal Institute for Drugs and Medical Devices, 53175 Bonn, GermanyResearch Department, Federal Institute for Drugs and Medical Devices, 53175 Bonn, GermanyResearch Department, Federal Institute for Drugs and Medical Devices, 53175 Bonn, GermanyResearch Department, Federal Institute for Drugs and Medical Devices, 53175 Bonn, GermanyInternal Medicine Emergency Department, Ulm University Medical Centre, 89081 Ulm, GermanyInterdisciplinary Emergency Department (INZ), University Hospital of Bonn, 53127 Bonn, GermanyDr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, 70376 Stuttgart, GermanyInstitute of Clinical Pharmacology, University Hospital of RWTH Aachen, 52074 Aachen, GermanyIndividual differences in required drug dosages exist based on the pharmacogenomic (PGx) profiles. This study aimed to assess associations between PGx profiles and adverse drug reactions (ADR) that lead to admissions to the emergency department (ED). ADR cases of the prospective multi-center observational trial in EDs (ADRED study) were analyzed (<i>n</i> = 776) together with the relevant PGx phenotypes of the enzymes CYP2D6, CYP2C19, CYP2C9, and VKORC1. Overall, the allele frequency distribution in this cohort did not differ from the population frequencies. We compared the frequencies of phenotypes in the subgroups with the drugs suspected of certain ADR, in the remaining cases. The frequency distribution of CYP2C19 differed for the ADR bleeding cases suspected of clopidogrel (<i>p</i> = 0.020). In a logistic regression analysis, higher CYP2C19 activity (OR (95% CI): 4.97 (1.73−14.27)), together with age (1.05 (1.02−1.08)), showed an impact on the clopidogrel-suspecting ADRs, when adjusting for the clinical parameters. There was a trend for an association of phenprocoumon-risk profiles (low VKORC1 or CYP2C9 activity) with phenprocoumon-suspecting ADRs (<i>p</i> = 0.052). The PGx impact on serious ADRs might be highest in drugs that cannot be easily monitored or those that do not provoke mild ADR symptoms very quickly. Therefore, patients that require the intake of those drugs with PGx variability such as clopidogrel, might benefit from PGx testing.https://www.mdpi.com/2077-0383/9/6/1801adverse drug reactionspharmacogenomicsclopidogrelCYP2C19phenprocoumon
collection DOAJ
language English
format Article
sources DOAJ
author Katja S. Just
Harald Dormann
Marlen Schurig
Miriam Böhme
Jochen Fracowiak
Michael Steffens
Catharina Scholl
Thomas Seufferlein
Ingo Gräff
Matthias Schwab
Julia C. Stingl
spellingShingle Katja S. Just
Harald Dormann
Marlen Schurig
Miriam Böhme
Jochen Fracowiak
Michael Steffens
Catharina Scholl
Thomas Seufferlein
Ingo Gräff
Matthias Schwab
Julia C. Stingl
Adverse Drug Reactions in the Emergency Department: Is There a Role for Pharmacogenomic Profiles at Risk?—Results from the ADRED Study
Journal of Clinical Medicine
adverse drug reactions
pharmacogenomics
clopidogrel
CYP2C19
phenprocoumon
author_facet Katja S. Just
Harald Dormann
Marlen Schurig
Miriam Böhme
Jochen Fracowiak
Michael Steffens
Catharina Scholl
Thomas Seufferlein
Ingo Gräff
Matthias Schwab
Julia C. Stingl
author_sort Katja S. Just
title Adverse Drug Reactions in the Emergency Department: Is There a Role for Pharmacogenomic Profiles at Risk?—Results from the ADRED Study
title_short Adverse Drug Reactions in the Emergency Department: Is There a Role for Pharmacogenomic Profiles at Risk?—Results from the ADRED Study
title_full Adverse Drug Reactions in the Emergency Department: Is There a Role for Pharmacogenomic Profiles at Risk?—Results from the ADRED Study
title_fullStr Adverse Drug Reactions in the Emergency Department: Is There a Role for Pharmacogenomic Profiles at Risk?—Results from the ADRED Study
title_full_unstemmed Adverse Drug Reactions in the Emergency Department: Is There a Role for Pharmacogenomic Profiles at Risk?—Results from the ADRED Study
title_sort adverse drug reactions in the emergency department: is there a role for pharmacogenomic profiles at risk?—results from the adred study
publisher MDPI AG
series Journal of Clinical Medicine
issn 2077-0383
publishDate 2020-06-01
description Individual differences in required drug dosages exist based on the pharmacogenomic (PGx) profiles. This study aimed to assess associations between PGx profiles and adverse drug reactions (ADR) that lead to admissions to the emergency department (ED). ADR cases of the prospective multi-center observational trial in EDs (ADRED study) were analyzed (<i>n</i> = 776) together with the relevant PGx phenotypes of the enzymes CYP2D6, CYP2C19, CYP2C9, and VKORC1. Overall, the allele frequency distribution in this cohort did not differ from the population frequencies. We compared the frequencies of phenotypes in the subgroups with the drugs suspected of certain ADR, in the remaining cases. The frequency distribution of CYP2C19 differed for the ADR bleeding cases suspected of clopidogrel (<i>p</i> = 0.020). In a logistic regression analysis, higher CYP2C19 activity (OR (95% CI): 4.97 (1.73−14.27)), together with age (1.05 (1.02−1.08)), showed an impact on the clopidogrel-suspecting ADRs, when adjusting for the clinical parameters. There was a trend for an association of phenprocoumon-risk profiles (low VKORC1 or CYP2C9 activity) with phenprocoumon-suspecting ADRs (<i>p</i> = 0.052). The PGx impact on serious ADRs might be highest in drugs that cannot be easily monitored or those that do not provoke mild ADR symptoms very quickly. Therefore, patients that require the intake of those drugs with PGx variability such as clopidogrel, might benefit from PGx testing.
topic adverse drug reactions
pharmacogenomics
clopidogrel
CYP2C19
phenprocoumon
url https://www.mdpi.com/2077-0383/9/6/1801
work_keys_str_mv AT katjasjust adversedrugreactionsintheemergencydepartmentistherearoleforpharmacogenomicprofilesatriskresultsfromtheadredstudy
AT haralddormann adversedrugreactionsintheemergencydepartmentistherearoleforpharmacogenomicprofilesatriskresultsfromtheadredstudy
AT marlenschurig adversedrugreactionsintheemergencydepartmentistherearoleforpharmacogenomicprofilesatriskresultsfromtheadredstudy
AT miriambohme adversedrugreactionsintheemergencydepartmentistherearoleforpharmacogenomicprofilesatriskresultsfromtheadredstudy
AT jochenfracowiak adversedrugreactionsintheemergencydepartmentistherearoleforpharmacogenomicprofilesatriskresultsfromtheadredstudy
AT michaelsteffens adversedrugreactionsintheemergencydepartmentistherearoleforpharmacogenomicprofilesatriskresultsfromtheadredstudy
AT catharinascholl adversedrugreactionsintheemergencydepartmentistherearoleforpharmacogenomicprofilesatriskresultsfromtheadredstudy
AT thomasseufferlein adversedrugreactionsintheemergencydepartmentistherearoleforpharmacogenomicprofilesatriskresultsfromtheadredstudy
AT ingograff adversedrugreactionsintheemergencydepartmentistherearoleforpharmacogenomicprofilesatriskresultsfromtheadredstudy
AT matthiasschwab adversedrugreactionsintheemergencydepartmentistherearoleforpharmacogenomicprofilesatriskresultsfromtheadredstudy
AT juliacstingl adversedrugreactionsintheemergencydepartmentistherearoleforpharmacogenomicprofilesatriskresultsfromtheadredstudy
_version_ 1724629633329004544