Pharmacogenomics

1. Pharmacogenomics Rita Leone, RN, MSN, CMSRN

2. Objectives • Define Pharmacogenomics/Pharmacogenetics • Describe how genetics is used to tailor drug therapies • Discuss the RN’s role (r/t pharmacogenomics) • Identify barriers to integrating pharmacogenomics into practice • Explore current pharmacogenetic testing that affects selection/dosing of drug therapies (Warfarin/Coumadin & Trastuzumab/Herceptin)

3. What is Pharmacogenomics? • Pharmacogenomics is a rapidly growing field of research into the ways in which genetic variation affects drug response • Identifying genetic markers for differences in the way people metabolize drugs • Developing genetic tests that predict how individual patients will respond to drugs (i.e. statins, cancer therapies). • Goal… • To develop precisely targeted, optimal drug therapy • Minimizing drug related adverse events

4. Pharmacogenetics: Your Doctors New Genetic Tools http://learn.genetics.utah.edu/content/health/pharma/intro/

5. Pharmacogenomics: Role of the RN • Explaining rationale for genetic testing • Provide appropriate patient teaching regarding drug selection • Understand drug dosing variances between patients

6. Barriers • Who pays for the genetic testing if not already standard of care? • FDA • Insurers (i.e. KRAS) • Professional Organizations

7. Warfarin (Coumadin): Factors Affecting Dose/Response • Age • Increased age = decreased dose • Height and Weight • taller and/or weight more = higher warfarin dose • Ethnicity • Ancestry plays an important role • Asians: may need lower doses than Caucasians • African Americans: may need higher doses. • Diet • Warfarin works by inhibiting vitamin K. • consuming large amounts of vitamin K (through foods or supplements) = higher warfarin doses. • Other Medications, Herbs, or Supplements • Many prescription and over-the-counter medications interact with warfarin. • Inform prescribing physician of all medications, herbs, & supplements taking • Other Health Conditions • Some diseases affect how our bodies respond to medications

8. 2 more…introducing the CYP2C9 and VKORC1 Genotypes 1) CYP2C9 gene variant • Instructs body how to make an enzyme that metabolizes warfarin—an enzyme converts one chemical to another • Changes in the CYP2C9 gene can your ability to metabolize or clear warfarin from the body • When the body cannot metabolize warfarin at the usual rate, drug level builds up to a potential overdose • People with these CYP2C9 variants generally need warfarin doses. 2) VKORC1 gene variant • Contains instructions for making an enzyme called vitamin K epoxide reductase, (or VKOR) which plays an important part in making blood-clotting factors. • Warfarin stops blood clots by decreasing the effectiveness of VKOR=lowering the amount of VKOR produced • Since people with this gene variant have enzyme levels to start with, taking an average warfarin dose may their blood clotting factors too much--putting them at a higher risk for adverse events (bleeding)

9. HER2 + Breast Cancer: Target Therapies Affecting Tumor Growth • Aggressive form of breast CA • Associated with genetic variation leading to overproduction of protein called HER2 • Tumor samples tested for high levels of HER2 • If yes…Herceptin (Trastuzumab) is indicated

10. Using Genetics to Tailor Drug Therapy https://atlantichealth.dnadirect.com/grc/patient-site/warfarin-response/what-affects-warfarin-response.html

11. Where are we at?

12. To summarize…

13. Thank you! • Questions?