3 How Can I Know What & How Much to Prescribe? Order a Pharmacogentics (PGx) test.
4 Who is Already Using (or teaching) PGx Testing? Harvard Medical School & Beth Israel DeaconessVanderbiltGeorgetown Medical SchoolStanford University - Center for Genomics and Personalized MedicineScripps-HowardColumbia PresbyterianWeill Cornell Precision Medical InstituteNIH & FDADrug Manufactures – Tailored TherapeuticsCardiology & Anesthesiology Boards
5 Benefits of PGx Testing Right Drug at the Right Dose for the Right Patientfor 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’sHealthcare cost savings
6 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).
7 What is Pharmacogenetics (PGx)? Genes affect Patient Drug Metabolism and ResponsePredict in Advance = Better Medicine/OutcomesGenomic DifferencesInfluence Efficacy – Therapeutic WindowIncrease Risk of serious Drug Side EffectsIncrease risk of Drug-Drug Interaction
8 Personalized Medicine Adds Precision to Prescribing Tailoring Medical Treatment to Individual PatientSophisticated Molecular ToolsBetter Outcomes with Fewer Adverse EventsPersonal 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
9 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 AbrahamsPersonalized Medicine Coalition – The Boston GlobeJanuary 25, 2010
10 Why Utilize PGx Testing? Identify likelihood of Adverse Drug Event (ADE)25-50% have polymorphism2.2 Million ADE’s occur annually with 106,000 deathsIncrease Drug EfficacyOnly 58% of Pain Management Patients receive ReliefCardiac patients with Reduced Function Alleles have 3.5 – 8 times greater risk for major CV Event30% of Psychiatric disorders have severe ADE’s50% of Urology drugs have No Therapeutic AffectIncrease Patient Compliance and RetentionStandard of Care – Specialty BoardsMarket Practice, Mitigate Risk, Reduce Healthcare Costs
12 Patient’s Genetic Profile Metabolizer PhenotypeDrug TypeActive DrugsProdrugsPoor Metabolizer (PM)Reduced EliminationIncreased Toxicity RiskDecreased EffectivenessDecreased ActivationIntermediate Metabolizer (IM)Increased Drug-to-Gene and Drug-t0-Drug Interaction RiskPossible Increased Toxicity RiskNormal/Extensive Metabolizer (NM,EM)Performs according to FDA label specificationsRapid or Ultra Rapid Metabolizer (RM,URM)Reduced EffectivenessIncreased EliminationIncreased Activation
13 Reports: Simple & Informative CARDIAC PHARMACOGENTIC MARKERSDrugGeneResultImplicationsTherapeutic RecommendationsClopidogrelPlavix®CYP2C19*1/*1NormalmetabolizerNormal 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®)CYP2C9VKORC1*1/*1 *B/*BNormal metabolizerLow SensitivityNormal 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 atBeta Blockers Propranolol (Inderal®)CYP2D6*1/*41Normal metabolizerNormal Metabolism of Beta Blockers*Consider Drug Label-Recommended Dosage and AdministrationTicagrelorCYP3A4CYP3A5*1/*1B, *1/*3Intermediate metabolizerIntermediate 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)
14 Cardiac & Pain Panels Plavix* (Clopidogrel bisulfate) Factor II B-BlockersFactor V LeidenWarfarinMTHFRAPO-ECodeineMethadoneHydrocodoneMeperidineOxycodoneBuprenorphineFentanylSufentanil
16 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.DPresident and Chief Executive Officer, Eli Lilly and Company
17 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
18 Implement PGx in Your Practice Buccal Swabs - Simple, Non-invasive, Quick, ConvenientNo Costs - Test Kit & On-site Pickup free to practiceClinically Actionable Results – Easy to Read & Electronically DeliveredInsurance Paid – Covered by Medicare & most major Commercial PayersNew Revenue Source - Physician Reimbursed for InterpretationPharm-D - Available for Consultation
19 Pharmacogenetics . Simplified Richard G. Orchard