1. Pharmacogenetics . Simplified

2. How Effective are Medications?

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 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

5. 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

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 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

8. 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

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 Abrahams
Personalized Medicine Coalition – The Boston Globe
January 25, 2010

10. 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

11. PGx Dynamics

12. 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

13. 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
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)

14. 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

15. 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*)

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.D
President 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, 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

19. Pharmacogenetics . Simplified
Richard G. Orchard