Challenges of development and implementation of point of care pharmacogenetic testing

Haga, Susanne B.

doi:10.1080/14737159.2016.1211934

Cited by 30 publications

(28 citation statements)

References 129 publications

(111 reference statements)

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“…Several institutions have already implemented pre-emptive pharmacogenetic testing, and some patients may have results readily available 67 . Point-of-care pharmacogenetic tests are available but generally the potential variants of relevance in COVID-19 therapies are not available on this type of testing platform 68 .…”

Section: Resultsmentioning

confidence: 99%

Pharmacogenomics of COVID-19 therapies

et al. 2020

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A new global pandemic of coronavirus disease 2019 (COVID-19) has resulted in high mortality and morbidity. Currently numerous drugs are under expedited investigations without well-established safety or efficacy data. Pharmacogenomics may allow individualization of these drugs thereby improving efficacy and safety. In this review, we summarized the pharmacogenomic literature available for COVID-19 drug therapies including hydroxychloroquine, chloroquine, azithromycin, remdesivir, favipiravir, ribavirin, lopinavir/ritonavir, darunavir/cobicistat, interferon beta-1b, tocilizumab, ruxolitinib, baricitinib, and corticosteroids. We searched PubMed, reviewed the Pharmacogenomics Knowledgebase (PharmGKB ®) website, Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines, the U.S. Food and Drug Administration (FDA) pharmacogenomics information in the product labeling, and the FDA pharmacogenomics association table. We found several drug-gene variant pairs that may alter the pharmacokinetics of hydroxychloroquine/chloroquine (CYP2C8, CYP2D6, SLCO1A2, and SLCO1B1); azithromycin (ABCB1); ribavirin (SLC29A1, SLC28A2, and SLC28A3); and lopinavir/ritonavir (SLCO1B1, ABCC2, CYP3A). We also identified other variants, that are associated with adverse effects, most notable in hydroxychloroquine/chloroquine (G6PD; hemolysis), ribavirin (ITPA; hemolysis), and interferon β-1b (IRF6; liver toxicity). We also describe the complexity of the risk for QT prolongation in this setting because of additive effects of combining more than one QT-prolonging drug (i.e., hydroxychloroquine/chloroquine and azithromycin), increased concentrations of the drugs due to genetic variants, along with the risk of also combining therapy with potent inhibitors. In conclusion, although direct evidence in COVID-19 patients is lacking, we identified potential actionable genetic markers in COVID-19 therapies. Clinical studies in COVID-19 patients are deemed warranted to assess potential roles of these markers.

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Section: Resultsmentioning

confidence: 99%

Pharmacogenomics of COVID-19 therapies

et al. 2020

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“…Guidelines have become available for a number of medications with applicable PGx testing through the Clinical Pharmacogenetics Implementation Consortium [7][8][9]. Although physicians may perceive a benefit to using PGx [3,5,[9][10][11][12], many barriers exist that have prevented implementation on a larger scale such as: physicians lacking sufficient knowledge and finding time to keep up-to-date; uncertainty surrounding clinical utility; lack of confidence or comfort in ordering PGx testing; lack of comfort interpreting results; uncertainty in how to communicate results to patients and having sufficient time to do so; difficulty in managing changes to workflow; determining how to incorporate results into the electronic medical record (EMR); and uncertainty about level of coverage by insurance and reimbursement [3,5,6,[9][10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Primary Care Physician Experiences with Integrated Pharmacogenomic Testing in a Community Health System

et al. 2017

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Aim: To explore primary care physicians' views of the utility and delivery of direct access to pharmacogenomics (PGx) testing in a community health system. Methods: This descriptive study assessed the perspectives of 15 healthcare providers utilizing qualitative individual interviews. Results: Three main themes emerged: perceived value and utility of PGx testing; challenges to implementation in practice; and provider as well as patient needs. Conclusion: While providers in this study viewed benefits of PGx testing as avoiding side effects, titrating doses more quickly, improving shared decision-making and providing psychological reassurance, challenges will need to be addressed such as privacy concerns, cost, insurance coverage and understanding the complexity of PGx test results.

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“…Haga has summarized the challenges of development and implementation of POCTs related to pharmacogenetic testing [91]. One of the major issues is provider training.…”

Section: Expert Opinionmentioning

confidence: 99%

Arylamine N-acetyltransferase acetylation polymorphisms: paradigm for pharmacogenomic-guided therapy- a focused review

Hein

Millner²

2020

Expert Opinion on Drug Metabolism & Toxicology

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Introduction: The N-acetylation polymorphism has been the subject of comprehensive reviews describing the role of arylamine N-acetyltransferase 2 (NAT2) in the metabolism of numerous aromatic amine and hydrazine drugs. Areas covered: We describe and review data that more clearly defines the effects of NAT2 haplotypes and genotypes on the expression of acetylator phenotype towards selected drugs within human hepatocytes in vitro, within human hepatocyte cultures in situ, and clinical measures such as bioavailability, plasma metabolic ratios of parent to N-acetyl metabolite, elimination rate constants and plasma half-life, and/or clearance determinations in human subjects. We review several drugs (isoniazid, hydralazine, sulfamethazine, amifampridine, procainamide, sulfasalazine, amonafide and metamizole) for which NAT2 phenotype-guided therapy may be important. The value of pharmacogenomics-guided isoniazid therapy for the prevention and treatment of tuberculosis is presented as a paradigm for NAT2 phenotype-dependent dosing strategies. Expert opinion: Studies in human subjects and cryopreserved human hepatocytes show evidence for rapid, intermediate and slow acetylator phenotypes, with further data suggesting genetic heterogeneity within the slow acetylator phenotype. Incorporation of more robust NAT2 genotype/phenotypes relationships, including genetic heterogeneity within the slow acetylator phenotype, should lead to further advancements in both health outcomes and cost benefit for prevention and treatment of tuberculosis.

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Challenges of development and implementation of point of care pharmacogenetic testing

Cited by 30 publications

References 129 publications

Pharmacogenomics of COVID-19 therapies

Pharmacogenomics of COVID-19 therapies

Primary Care Physician Experiences with Integrated Pharmacogenomic Testing in a Community Health System

Arylamine N-acetyltransferase acetylation polymorphisms: paradigm for pharmacogenomic-guided therapy- a focused review

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