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https://www.readbyqxmd.com/read/28198005/clinical-pharmacogenetics-implementation-consortium-cpic-guideline-for-pharmacogenetics-guided-warfarin-dosing-2017-update
#1
Julie A Johnson, Kelly E Caudle, Li Gong, Michelle Whirl-Carrillo, C Michael Stein, Stuart A Scott, Ming Ta Michael Lee, Brian F Gage, Stephen E Kimmel, Minoli A Perera, Jeffrey L Anderson, Munir Pirmohamed, Teri E Klein, Nita A Limdi, Larisa H Cavallari, Mia Wadelius
This document is an update to the 2011 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2C9 and VKORC1 genotypes and warfarin dosing. Evidence from the published literature is presented for CYP2C9, VKORC1, CYP4F2, and rs12777823 genotype-guided warfarin dosing to achieve a target international normalized ratio of 2-3 when clinical genotype results are available. In addition, this updated guideline incorporates recommendations for adult and pediatric patients that are specific to continental ancestry...
February 15, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28090649/-the-pharmacogenomics-research-network-translational-pharmacogenetics-program-outcomes-and-metrics-of-pharmacogenetic-implementations-across-diverse-healthcare-systems
#2
Jasmine A Luzum, Ruth E Pakyz, Amanda R Elsey, Cyrine E Haidar, Josh F Peterson, Michelle Whirl-Carrillo, Samuel K Handelman, Kathleen Palmer, Jill M Pulley, Marc Beller, Jonathan S Schildcrout, Julie R Field, Kristin W Weitzel, Rhonda M Cooper-DeHoff, Larisa H Cavallari, Peter H O'Donnell, Russ B Altman, Naveen Pereira, Mark J Ratain, Dan M Roden, Peter J Embi, Wolfgang Sadee, Teri E Klein, Julie A Johnson, Mary V Relling, Liewei Wang, Richard M Weinshilboum, Alan R Shuldiner, Robert R Freimuth
Numerous pharmacogenetic clinical guidelines and recommendations have been published, but barriers have hindered the clinical implementation of pharmacogenetics. The Translational Pharmacogenetics Program (TPP) of the NIH Pharmacogenomics Research Network was established in 2011 to catalog and contribute to the development of pharmacogenetic implementations at eight US healthcare systems, with the goal to disseminate real-world solutions for the barriers to clinical pharmacogenetic implementation. The TPP collected and normalized pharmacogenetic implementation metrics through June 2015, including gene-drug pairs implemented, interpretations of alleles and diplotypes, numbers of tests performed and actionable results, and workflow diagrams...
January 16, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28046094/analysis-of-genetic-variation-in-cyp450-genes-for-clinical-implementation
#3
Liuh Ling Goh, Chia Wei Lim, Wey Cheng Sim, Li Xian Toh, Khai Pang Leong
BACKGROUND: Genetic determinants of drug response remain stable throughout life and offer great promise to patient-tailored drug therapy. The adoption of pharmacogenetic (PGx) testing in patient care requires accurate, cost effective and rapid genotyping with clear guidance on the use of the results. Hence, we evaluated a 32 SNPs panel for implementing PGx testing in clinical laboratories. METHODS: We designed a 32-SNP panel for PGx testing in clinical laboratories...
2017: PloS One
https://www.readbyqxmd.com/read/28044932/ubiquitous-pharmacogenomics-u-pgx-the-time-for-implementation-is-now-an-horizon2020-program-to-drive-pharmacogenomics-into-clinical-practice
#4
Erika Cecchin, Rossana Roncato, Hendrik Jan Guchelaar, Giuseppe Toffoli, and for the Ubiquitous Pharmacogenomics Consortium
Although the clinical validity of a number of pharmacogenetic markers is nowadays a matter of fact, and led authoritative scientific consortia as the Dutch Pharmacogenetic Working Group (DPWG) and the Clinical Pharmacogenomics Implementation Consortium (CPIC) to publish pharmacogenetic guidelines, the clinical implementation in the real life remains challenging. Ubiquitous Pharmacogenomics (U-PGx) program is a coordinated effort that put together scientific and clinical expertise in the pharmacogenomic field, to implement the pre-emptive pharmacogenomic approach in the clinical practice in Europe, and to demonstrate its benefit in both patients clinical outcome and quality of life, with an economic advantage for the healthcare system...
January 2, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28002639/clinical-pharmacogenetics-implementation-consortium-cpic-guideline-for-cyp2d6-genotype-and-use-of-ondansetron-and-tropisetron
#5
G C Bell, K E Caudle, M Whirl-Carrillo, R J Gordon, H Hikino, C A Prows, A Gaedigk, Jag Agundez, S Sadhasivam, T E Klein, M Schwab
No abstract text is available yet for this article.
December 21, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27997040/clinical-pharmacogenetics-implementation-consortium-guideline-cpic%C3%A2-for-cyp2d6-and-cyp2c19-genotypes-and-dosing-of-tricyclic-antidepressants-2016-update
#6
J Kevin Hicks, Katrin Sangkuhl, Jesse J Swen, Vicki L Ellingrod, Daniel J Müller, Kazutaka Shimoda, Jeffrey R Bishop, Evan D Kharasch, Todd C Skaar, Andrea Gaedigk, Henry M Dunnenberger, Teri E Klein, Kelly E Caudle, Julia C Stingl
CYP2D6 and CYP2C19 polymorphisms affect the exposure, efficacy and safety of tricyclic antidepressants (TCAs), with some drugs being affected by CYP2D6 only (e.g., nortriptyline and desipramine) and others by both polymorphic enzymes (e.g., amitriptyline, clomipramine, doxepin, imipramine, and trimipramine). Evidence is presented for CYP2D6 and CYP2C19 genotype-directed dosing of TCAs. This document is an update to the 2012 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants...
December 20, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27981572/clinical-pharmacogenetics-implementation-consortium-cpic-guidelines-for-cyp2c19-and-voriconazole-therapy
#7
B Moriyama, A Owusu Obeng, J Barbarino, S R Penzak, S A Henning, S A Scott, Jag Agúndez, J R Wingard, H L McLeod, T E Klein, S J Cross, K E Caudle, T J Walsh
Voriconazole, a triazole antifungal agent, demonstrates wide interpatient variability in serum concentrations, due in part to variant CYP2C19 alleles. Individuals who are CYP2C19 ultrarapid metabolizers have decreased trough voriconazole concentrations, delaying achievement of target blood concentrations; whereas poor metabolizers have increased trough concentrations and are at increased risk of adverse drug events. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for the use of voriconazole for treatment based on CYP2C19 genotype (updates at https://cpicpgx...
December 16, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27864205/evidence-and-resources-to-implement-pharmacogenetic-knowledge-for-precision-medicine
#8
Kelly E Caudle, Roseann S Gammal, Michelle Whirl-Carrillo, James M Hoffman, Mary V Relling, Teri E Klein
PURPOSE: The current state of pharmacogenetic data curation and dissemination is described, and evidence-based resources for applying pharmacogenetic data in clinical practice are reviewed. SUMMARY: Implementation of pharmacogenetics in clinical practice has been relatively slow despite substantial scientific progress in understanding linkages between genetic variation and variability of drug response and effect. One factor that has inhibited the adoption of genetic data to guide medication use is a lack of knowledge of how to translate genetic test results into clinical action based on currently available evidence...
December 1, 2016: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/27643672/pharmacogenomics-and-global-precision-medicine-in-the-context-of-adverse-drug-reactions-top-10-opportunities-and-challenges-for-the-next-decade
#9
Marco Alessandrini, Mamoonah Chaudhry, Tyren M Dodgen, Michael S Pepper
In a move indicative of the enthusiastic support of precision medicine, the U.S. President Barack Obama announced the Precision Medicine Initiative in January 2015. The global precision medicine ecosystem is, thus, receiving generous support from the United States ($215 million), and numerous other governments have followed suit. In the context of precision medicine, drug treatment and prediction of its outcomes have been important for nearly six decades in the field of pharmacogenomics. The field offers an elegant solution for minimizing the effects and occurrence of adverse drug reactions (ADRs)...
October 2016: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/27603572/advances-and-challenges-in-hereditary-cancer-pharmacogenetics
#10
REVIEW
Ingolf Cascorbi, Anneke Nina Werk
Cancer pharmacogenetics usually considers tumor-specific targets. However, hereditary genetic variants may interfere with the pharmacokinetics of antimetabolites and other anti-cancer drugs, which may lead to severe adverse events. Areas covered: Here, the impact of hereditary genes considered in drug labels such as thiopurine S-methyltransferase (TPMT), UDP-glucuronosyltransferase 1A1 (UTG1A1) and dihydropyrimidine dehydrogenase (DPYD) are discussed with respect to guidelines of the Clinical Pharmacogenetics Implementation Consortium (CPIC)...
January 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27537706/assessing-the-capability-of-massively-parallel-sequencing-for-opportunistic-pharmacogenetic-screening
#11
David Ng, Celine S Hong, Larry N Singh, Jennifer J Johnston, James C Mullikin, Leslie G Biesecker
PURPOSE: The aim of the study was to assess exome data for preemptive pharmacogenetic screening for 203 clinically relevant pharmacogenetic variant positions from the Pharmacogenomics Knowledgebase and Clinical Pharmacogenetics Implementation Consortium and identify copy-number variants (CNVs) in CYP2D6. METHODS: We examined the coverage and genotype quality of 203 pharmacogenetic variant positions in 973 exomes compared with five genomes and with five genotyping chip data sets...
March 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/27441996/standardizing-terms-for-clinical-pharmacogenetic-test-results-consensus-terms-from-the-clinical-pharmacogenetics-implementation-consortium-cpic
#12
Kelly E Caudle, Henry M Dunnenberger, Robert R Freimuth, Josh F Peterson, Jonathan D Burlison, Michelle Whirl-Carrillo, Stuart A Scott, Heidi L Rehm, Marc S Williams, Teri E Klein, Mary V Relling, James M Hoffman
INTRODUCTION: Reporting and sharing pharmacogenetic test results across clinical laboratories and electronic health records is a crucial step toward the implementation of clinical pharmacogenetics, but allele function and phenotype terms are not standardized. Our goal was to develop terms that can be broadly applied to characterize pharmacogenetic allele function and inferred phenotypes. MATERIALS AND METHODS: Terms currently used by genetic testing laboratories and in the literature were identified...
February 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/27388693/prediction-of-cyp2d6-phenotype-from-genotype-across-world-populations
#13
Andrea Gaedigk, Katrin Sangkuhl, Michelle Whirl-Carrillo, Teri Klein, J Steven Leeder
PURPOSE: Owing to its highly polymorphic nature and major contribution to the metabolism and bioactivation of numerous clinically used drugs, CYP2D6 is one of the most extensively studied drug-metabolizing enzymes and pharmacogenes. CYP2D6 alleles confer no, decreased, normal, or increased activity and cause a wide range of activity among individuals and between populations. However, there is no standard approach to translate diplotypes into predicted phenotype. METHODS: We exploited CYP2D6 allele-frequency data that have been compiled for Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines (>60,000 subjects, 173 reports) in order to estimate genotype-predicted phenotype status across major world populations based on activity score (AS) assignments...
January 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/27311679/comparison-of-genome-sequencing-and-clinical-genotyping-for-pharmacogenes
#14
W Yang, G Wu, U Broeckel, C A Smith, V Turner, C E Haidar, S Wang, R Carter, S E Karol, G Neale, K R Crews, J J Yang, C G Mullighan, J R Downing, W E Evans, M V Relling
We compared whole exome sequencing (WES, n = 176 patients) and whole genome sequencing (WGS, n = 68) and clinical genotyping (DMET array-based approach) for interrogating 13 genes with Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. We focused on 127 CPIC important variants: 103 single nucleotide variations (SNV), 21 insertion/deletions (Indel), HLA-B alleles, and two CYP2D6 structural variations. WES and WGS provided interrogation of nonoverlapping sets of 115 SNV/Indels with call rate >98%...
October 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27170790/the-impact-of-community-engagement-on-health-social-and-utilization-outcomes-in-depressed-impoverished-populations-secondary-findings-from-a-randomized-trial
#15
Christine A Lam, Cathy Sherbourne, Lingqi Tang, Thomas R Belin, Pluscedia Williams, Angela Young-Brinn, Jeanne Miranda, Kenneth B Wells
BACKGROUND: Disparities in depression care exist among the poor. Community Partners in Care (CPIC) compared a community coalition model with technical assistance to improve depression services in under-resourced communities. We examine effects on health, social, and utilization outcomes among the poor and, non-poor depressed, and poor subgroups. METHODS: This study analyzed clients living above (n = 268) and below (n = 750) the federal-poverty level and, among the poor, 3 nonoverlapping subgroups: justice-involved (n = 158), homeless and not justice-involved (n = 298), and other poor (n = 294)...
May 2016: Journal of the American Board of Family Medicine: JABFM
https://www.readbyqxmd.com/read/27026620/developing-knowledge-resources-to-support-precision-medicine-principles-from-the-clinical-pharmacogenetics-implementation-consortium-cpic
#16
James M Hoffman, Henry M Dunnenberger, J Kevin Hicks, Kelly E Caudle, Michelle Whirl Carrillo, Robert R Freimuth, Marc S Williams, Teri E Klein, Josh F Peterson
To move beyond a select few genes/drugs, the successful adoption of pharmacogenomics into routine clinical care requires a curated and machine-readable database of pharmacogenomic knowledge suitable for use in an electronic health record (EHR) with clinical decision support (CDS). Recognizing that EHR vendors do not yet provide a standard set of CDS functions for pharmacogenetics, the Clinical Pharmacogenetics Implementation Consortium (CPIC) Informatics Working Group is developing and systematically incorporating a set of EHR-agnostic implementation resources into all CPIC guidelines...
July 2016: Journal of the American Medical Informatics Association: JAMIA
https://www.readbyqxmd.com/read/26807054/evaluation-of-popular-drug-information-resources-on-clinically-useful-and-actionable-pharmacogenomic-information
#17
Jennifer S Chang, Duyen-Anh Pham, Maithao T Dang, Yiting Lu, Sheri VanOsdol, Jaekyu Shin
BACKGROUND: Pharmacogenomics is the study of how genes affect a person's response to drugs. This descriptive study assessed whether popular drug information resources provide clinically useful pharmacogenomic (PGx) information. METHODS: Four resources (package inserts, Lexicomp, Micromedex 2.0, and Epocrates) were evaluated for information about twenty-seven drugs. RESULTS: There was wide variability of PGx information. Whereas Lexicomp included relevant PGx biomarker information for all 27 drugs, Epocrates did in less than 50% of the drugs...
January 2016: Journal of the Medical Library Association: JMLA
https://www.readbyqxmd.com/read/26417955/clinical-pharmacogenetics-implementation-consortium-cpic-guideline-for-ugt1a1-and-atazanavir-prescribing
#18
REVIEW
R S Gammal, M H Court, C E Haidar, O F Iwuchukwu, A H Gaur, M Alvarellos, C Guillemette, J L Lennox, M Whirl-Carrillo, S S Brummel, M J Ratain, T E Klein, B R Schackman, K E Caudle, D W Haas
The antiretroviral protease inhibitor atazanavir inhibits hepatic uridine diphosphate glucuronosyltransferase (UGT) 1A1, thereby preventing the glucuronidation and elimination of bilirubin. Resultant indirect hyperbilirubinemia with jaundice can cause premature discontinuation of atazanavir. Risk for bilirubin-related discontinuation is highest among individuals who carry two UGT1A1 decreased function alleles (UGT1A1*28 or *37). We summarize published literature that supports this association and provide recommendations for atazanavir prescribing when UGT1A1 genotype is known (updates at www...
April 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/26094938/clinical-pharmacogenetics-implementation-consortium-cpic-guidelines-for-human-leukocyte-antigen-b-hla-b-genotype-and-allopurinol-dosing-2015-update
#19
Y Saito, L K Stamp, K E Caudle, M S Hershfield, E M McDonagh, J T Callaghan, W Tassaneeyakul, T Mushiroda, N Kamatani, B R Goldspiel, E J Phillips, T E Klein, M T M Lee
The Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for HLA-B*58:01 Genotype and Allopurinol Dosing was originally published in February 2013. We reviewed the recent literature and concluded that none of the evidence would change the therapeutic recommendations in the original guideline; therefore, the original publication remains clinically current. However, we have updated the Supplemental Material and included additional resources for applying CPIC guidelines into the electronic health record...
January 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/25974703/clinical-pharmacogenetics-implementation-consortium-cpic-guideline-for-cyp2d6-and-cyp2c19-genotypes-and-dosing-of-selective-serotonin-reuptake-inhibitors
#20
REVIEW
J K Hicks, J R Bishop, K Sangkuhl, D J Müller, Y Ji, S G Leckband, J S Leeder, R L Graham, D L Chiulli, A LLerena, T C Skaar, S A Scott, J C Stingl, T E Klein, K E Caudle, A Gaedigk
Selective serotonin reuptake inhibitors (SSRIs) are primary treatment options for major depressive and anxiety disorders. CYP2D6 and CYP2C19 polymorphisms can influence the metabolism of SSRIs, thereby affecting drug efficacy and safety. We summarize evidence from the published literature supporting these associations and provide dosing recommendations for fluvoxamine, paroxetine, citalopram, escitalopram, and sertraline based on CYP2D6 and/or CYP2C19 genotype (updates at www.pharmgkb.org).
August 2015: Clinical Pharmacology and Therapeutics
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