Implementation of CYP2C19 Genotyping for Clopidogrel Gwen McMillin, PhD, DABCC (CC,TC) July 27,...
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Transcript of Implementation of CYP2C19 Genotyping for Clopidogrel Gwen McMillin, PhD, DABCC (CC,TC) July 27,...
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
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
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)
Possible algorithm for clopidogrel
GenotypeCYP2C19
No PMVariantsor CYP2C19*17 only
Active drug expected Drug-drug interactions?Monitor response
One PM variant
Two PM variantsAlternate drug(e.g., prasugrel)Monitor response
Consider alternate drugConsider escalated doseMonitor response
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
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
CYP2C19*17 could “accelerate” PK or convert CYP2C19 from a minor to a major pathway
CYP2C19*17 could “accelerate” PK or convert CYP2C19 from a minor to a major pathway
Impairment could interfere with
expected drug activation or inactivation
Impairment could interfere with
expected drug activation or inactivation