Dosing recommendations for pharmacogenetic interactions related to drug metabolism

Objective Pharmacogenomic studies have established the important contribution of drug-metabolizing enzyme genotype toward drug toxicity and treatment failure; however, clinical implementation of pharmacogenomics has been slow. The aim of this study was to systematically review the information on drug-metabolizing enzyme pharmacogenomics available in the US drug labeling, practice guidelines, and recommendations. Methods Drug-metabolizing enzyme genotype and phenotype information was assessed in US FDA drug labeling, clinical practice guidelines, and independent technology assessors to evaluate the consistency in information sources for healthcare providers. Results Eighty four gene–drug pairs were identified as having drug-metabolizing enzyme genotype or phenotype information within the label. The manner in which pharmacogenomic information was presented was heterogeneous both within the label and between clinical practice recommendations. Conclusion For proper implementation of pharmacogenomics in clinical practice, information sources for healthcare providers should relay consistent and clear information for the appropriate use of biomarkers.

[1]  S. Teutsch,et al.  Recommendations from the EGAPP Working Group: testing for cytochrome P450 polymorphisms in adults with nonpsychotic depression treated with selective serotonin reuptake inhibitors , 2007, Genetics in Medicine.

[2]  Guidance for Industry Clinical Pharmacogenomics : Premarket Evaluation in Early-Phase Clinical Studies and Recommendations for Labeling , 2013 .

[3]  R. Verbrugge,et al.  Adoption of Pharmacogenomic Testing by US Physicians: Results of a Nationwide Survey , 2012, Clinical pharmacology and therapeutics.

[4]  S. Teutsch,et al.  The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) initiative: methods of the EGAPP Working Group , 2009, Genetics in Medicine.

[5]  S. Paugh,et al.  Cancer Pharmacogenomics , 2011, Clinical pharmacology and therapeutics.

[6]  U. Amstutz,et al.  Pharmacogenetic Testing: Time for Clinical Practice Guidelines , 2011, Clinical pharmacology and therapeutics.

[7]  J. Hirsh,et al.  Antiplatelet drugs: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. , 2012, Chest.

[8]  T. Klein,et al.  CPIC: Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network , 2011, Clinical pharmacology and therapeutics.

[9]  S. Teutsch,et al.  Recommendations from the EGAPP Working Group: can UGT1A1 genotyping reduce morbidity and mortality in patients with metastatic colorectal cancer treated with irinotecan? , 2009, Genetics in Medicine.

[10]  F. Innocenti,et al.  Clinical Implementation of Germ Line Cancer Pharmacogenetic Variants During the Next‐Generation Sequencing Era , 2014, Clinical pharmacology and therapeutics.

[11]  R. Sorelle US Department of Health and Human Services gives states wider latitude in choosing services to be covered by Medicaid. , 2001, Circulation.

[12]  M. Pirmohamed Acceptance of Biomarker‐Based Tests for Application in Clinical Practice: Criteria and Obstacles , 2010, Clinical pharmacology and therapeutics.

[13]  J J Swen,et al.  Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants , 2013, Clinical pharmacology and therapeutics.

[14]  D. Christiani,et al.  Germline genetic variation, cancer outcome, and pharmacogenetics. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  E. Clayton,et al.  Operational Implementation of Prospective Genotyping for Personalized Medicine: The Design of the Vanderbilt PREDICT Project , 2012, Clinical pharmacology and therapeutics.

[16]  B. Tarini,et al.  Primary-care providers’ perceived barriers to integration of genetics services: a systematic review of the literature , 2014, Genetics in Medicine.

[17]  Aniwaa Owusu Obeng,et al.  Clinical pharmacogenetics implementation: Approaches, successes, and challenges , 2014, American journal of medical genetics. Part C, Seminars in medical genetics.

[18]  G. Levine,et al.  2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. , 2011, Circulation.

[19]  Jeffrey L. Anderson,et al.  2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. , 2011, Circulation.