Pharmacogenetics . Simplified

How Effective are Medications?

How Can I Know What & How Much to Prescribe? Order a Pharmacogentics (PGx) test.

Who is Already Using (or teaching) PGx Testing? Harvard Medical School & Beth Israel Deaconess Vanderbilt Georgetown Medical School Stanford University - Center for Genomics and Personalized Medicine Scripps-Howard Columbia Presbyterian Weill Cornell Precision Medical Institute NIH & FDA Drug Manufactures – Tailored Therapeutics Cardiology & Anesthesiology Boards

Benefits of PGx Testing Right Drug at the Right Dose for the Right Patient for the First Time! Precision prescribing is better medicine than “Trial and Error Prescribing.” Decrease ADE’s (adverse drug events) Less hospitalizations as a result of ADE’s Healthcare cost savings

What is Pharmacogenetics (PGx)? It is the study of Genetic Differences in Metabolic Pathways which can affect Individual Responses to drugs, both in terms of therapeutic affect as well as adverse effects (how genetics influence a patient’s response to medications).

What is Pharmacogenetics (PGx)? Genes affect Patient Drug Metabolism and Response Predict in Advance = Better Medicine/Outcomes Genomic Differences Influence Efficacy – Therapeutic Window Increase Risk of serious Drug Side Effects Increase risk of Drug-Drug Interaction

Personalized Medicine Adds Precision to Prescribing Tailoring Medical Treatment to Individual Patient Sophisticated Molecular Tools Better Outcomes with Fewer Adverse Events Personal Medicine is a shift from what works for a “typical” patient to what works for the “Individual” patient. Right Drug for the Right Patient at the Right Dose

The Future is PGx Testing “The point of personalized medicine is to develop better efficacy, better outcomes, fewer adverse affects and lower systemic costs.” Dr. Edward Abrahams Personalized Medicine Coalition – The Boston Globe January 25, 2010

Why Utilize PGx Testing? Identify likelihood of Adverse Drug Event (ADE) 25-50% have polymorphism 2.2 Million ADE’s occur annually with 106,000 deaths Increase Drug Efficacy Only 58% of Pain Management Patients receive Relief Cardiac patients with Reduced Function Alleles have 3.5 – 8 times greater risk for major CV Event 30% of Psychiatric disorders have severe ADE’s 50% of Urology drugs have No Therapeutic Affect Increase Patient Compliance and Retention Standard of Care – Specialty Boards Market Practice, Mitigate Risk, Reduce Healthcare Costs

PGx Dynamics

Patient’s Genetic Profile Metabolizer Phenotype Drug Type Active Drugs Prodrugs Poor Metabolizer (PM) Reduced Elimination Increased Toxicity Risk Decreased Effectiveness Decreased Activation Intermediate Metabolizer (IM) Increased Drug-to-Gene and Drug-t0-Drug Interaction Risk Possible Increased Toxicity Risk Normal/Extensive Metabolizer (NM,EM) Performs according to FDA label specifications Rapid or Ultra Rapid Metabolizer (RM,URM) Reduced Effectiveness Increased Elimination Increased Activation

Reports: Simple & Informative CARDIAC PHARMACOGENTIC MARKERS Drug Gene Result Implications Therapeutic Recommendations Clopidogrel Plavix® CYP2C19 *1/*1 Normal metabolizer Normal Metabolizer of Clopidogrel *Start Clopidogrel at 300 mg (loading dose) and continue with 75 mg daily (maintenance dose). *Avoid using Clopidogrel with Omeprazole, a CYP2C19 inhibitor. Warfarin (Coumadin®) CYP2C9 VKORC1 *1/*1 *B/*B Normal metabolizer Low Sensitivity Normal inhibition of vitamin K reductase *Consider 5-7 mg/day to achieve therapeutic INR using the Warfarin product insert approved by the USFDA. Additonal information at www.warfarindosing.org. Beta Blockers Propranolol (Inderal®) CYP2D6 *1/*41 Normal metabolizer Normal Metabolism of Beta Blockers *Consider Drug Label-Recommended Dosage and Administration Ticagrelor CYP3A4 CYP3A5 *1/*1B, *1/*3 Intermediate metabolizer Intermediate Metabolism of Ticagretor *Consider Ticagrelor Label Recommended Dosage and Administration *Avoid use with Potent CYP3A Inducers (see Table 3 of CYP3A Report) *Avoid us of Strong Inhibitors of CYP3A (see Table 3 of CYP3A Report)

Cardiac & Pain Panels Plavix* (Clopidogrel bisulfate) Factor II B-Blockers Factor V Leiden Warfarin MTHFR APO-E   Codeine Methadone Hydrocodone Meperidine Oxycodone Buprenorphine Fentanyl Sufentanil

Psychiatric & Urology Panels MEDICATION UROLOGY MEDICATION Alprazolam Fluvoxamine Amitriptyline Haloperidol Aripriprazole Mirtazapine Atomoxetine Nortriptyline Buspirone Olanzapine Citalopram Paroxetine Clomipramine Pimozide Clonazepam Quetiapine Diazepam Risperidone Doxepin Sertraline Duloxetine Trazodone Escitalopram Venlafaxine Fluoxetine Ziprasidone Benign Prostatic Hyperplasia (BPH) Drugs Terazosin (Hytrin) Silodosin (Rapaflo*) Doxazosin (Cardura) Dutasteride (Avodart) Alfuzosin (Uroxatral) Dutasteride/Tamsulosin (Jalyn) Tamsulosin (Flomax) Finasteride (Proscar) Overactive Bladder Oxybutynin (Ditropan*) Trospium (Sanctura*) Solifenacin (Vesicare) Tolteradine (Detrol*) Darifenacin (Enablex*) Fesoterodine fumarate (Toviaz) Erectile Dysfunction Sildenafil (Viagra*) Tadalafil (Cialis*) Vardenafil (Levitra*)  

Tailored Therapeutics “The power in tailored therapeutics is for us to say more clearly to payers, providers, and patients – ‘this drug is not for everyone, but it is for you.’ That is exceedingly powerful.” John C. Lechleiter, Ph.D President and Chief Executive Officer, Eli Lilly and Company

Goals “Today, one of our biggest goals is to cut the cost of sequencing an entire human genome to $1,000 or less. This advance will pave the way for each person’s genome to be sequenced as part of the standard of care, leading to a revolution in the practice of medicine.” Francis S. Collins, M.D., Ph.D. Director, National Institute of Health

Implement PGx in Your Practice Buccal Swabs - Simple, Non-invasive, Quick, Convenient No Costs - Test Kit & On-site Pickup free to practice Clinically Actionable Results – Easy to Read & Electronically Delivered Insurance Paid – Covered by Medicare & most major Commercial Payers New Revenue Source - Physician Reimbursed for Interpretation Pharm-D - Available for Consultation

Pharmacogenetics . Simplified Richard G. Orchard 916.759.7883 rorchard@vantagerx.com