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Implementation of CYP2C19 Genotyping for Clopidogrel

Implementation of CYP2C19 Genotyping for Clopidogrel. Gwen McMillin, PhD, DABCC (CC,TC) July 27, 2010. Outline. Demand for CYP2C19 genotyping Laboratory considerations Reporting considerations Other uses for CYP2C19 genotyping. CYP2C19 Orders July 2009 – June 2010.

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Implementation of CYP2C19 Genotyping for Clopidogrel

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  1. Implementation of CYP2C19 Genotyping for Clopidogrel Gwen McMillin, PhD, DABCC (CC,TC) July 27, 2010

  2. Outline • Demand for CYP2C19 genotyping • Laboratory considerations • Reporting considerations • Other uses for CYP2C19 genotyping

  3. CYP2C19 Orders July 2009 – June 2010 ~40-fold increase in Q4 vs Q1 test volumes

  4. CYP2C19 Patients (Q4) • Average age: 70 yrs (median 72 yrs) • 55% male • 37 states

  5. Distribution of alleles detected (Q4) Predicts PM Predicts UM

  6. Laboratory Considerations • Specimen: blood, saliva, buccal swab • Guidelines and standards: CAP, NYDOH, ACMG • Quality control: no template, and previously characterized samples or commercial sources • Proficiency testing: CAP Pharmacogenetics

  7. Report Content • Collection, specimen, and patient details • Results (genotype), evidence of review • Analytical • Method • List of all variants detected, using standard nomenclature • Limitations of testing • ASR status (if applicable) • Clinical • Interpretation • Suggestions for additional or alternative testing • References (if applicable) • Access to consultation (genetic counselor, director)

  8. MOL.3600, CAP, Molecular Pathology, 2009 “Laboratory reports should be designed to convey patient results effectively to a non-expert physician. This includes documentation of the analytical procedure used or the commercial kit version accompanied by an interpretation of findings”

  9. Possible algorithm for clopidogrel Two PM variants Alternate drug (e.g., prasugrel) Monitor response Genotype CYP2C19 One PM variant No PM Variants or CYP2C19*17 only Consider alternate drug Consider escalated dose Monitor response Active drug expected Drug-drug interactions? Monitor response

  10. Turnaround Time? Clinical need Laboratory and cost efficiency

  11. Other uses for CYP2C19 Genotyping • Drug substrate examples • Antidepressants: amitriptyline, imipramine, trimipramine, citalopram, sertraline • Anxiolytic: diazepam • Anticonvulsant: phenytoin • Muscle relaxant: carisoprodol • Gastrointestinal: omeprazole, lansoprazole • Infection: voriconazole, nelfinavir, proguanil • Oncology: tamoxifen, cyclophosphamide • Cardiology: r-warfarin, propranolol • Define role of CYP2C19 in metabolism • Content of CYP2C19 testing

  12. Possible Scenarios for Utility • CYP2C19 is a major pathway • Inactivates drug • Activates drug • CYP2C19 is a minor pathway • Inactivates drug • Activates drug • Must consider potential for drug-gene interactions and drug-drug interactions Impairment could interfere with expected drug activation or inactivation CYP2C19*17 could “accelerate” PK or convert CYP2C19 from a minor to a major pathway

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