Pharmacogenomics Rita Leone, RN, MSN, CMSRN

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)

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

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

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

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

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

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)

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

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

Where are we at?

To summarize…

Thank you! Questions?