Pharmcogenetics Simplified
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Transcript Pharmcogenetics Simplified
Pharmacogenetics . Simplified
How Effective are Medications?
How Can I Know What & How Much
to Prescribe?
Order a Pharmacogentics (PGx) test.
Who is Already Using
PGx Testing?
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(or teaching)
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
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The Future is PGx Testing
“The point of personalized medicine is to develop better
efficacy, better outcomes, fewer adverse affects and
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
Poor Metabolizer (PM) Reduced Elimination
Increased Toxicity Risk
Intermediate
Metabolizer (IM)
Prodrugs
Decreased Effectiveness
Decreased Activation
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
Reduced Effectiveness
Metabolizer (RM,URM) Increased Elimination
Increased Activation
Increased Toxicity Risk
Reports:
Simple & Informative
CARDIAC PHARMACOGENTIC MARKERS
Drug
Gene
Result
Implications
Clopidogrel
Plavix®
CYP2C19
*1/*1
Normal
metabolizer
Normal Metabolizer
of Clopidogrel
Warfarin
(Coumadin®)
CYP2C9
VKORC1
*1/*1 *B/*B
Beta Blockers
Propranolol
(Inderal®)
CYP2D6
Ticagrelor
CYP3A4
CYP3A5
Normal metabolizer
Low Sensitivity
*1/*41
Normal
metabolizer
*1/*1B, *1/*3
Intermediate
metabolizer
Therapeutic Recommendations
*Start Clopidogrel at 300 mg (loading dose) and continue with 75 mg daily
(maintenance dose).
*Avoid using Clopidogrel with Omeprazole, a CYP2C19 inhibitor.
Normal inhibition of *Consider 5-7 mg/day to achieve therapeutic INR using the Warfarin product insert
vitamin K reductase approved by the USFDA. Additonal information at www.warfarindosing.org.
Normal Metabolism
of Beta Blockers
*Consider Drug Label-Recommended Dosage and Administration
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
Codeine
Methadone
B-Blockers
Factor V Leiden
Hydrocodone
Meperidine
Warfarin
MTHFR
Oxycodone
Buprenorphine
Fentanyl
Sufentanil
APO-E
Psychiatric & Urology Panels
UROLOGY
MEDICATION
PSYCHIATRIC
MEDICATION
Alprazolam
Fluvoxamine
Amitriptyline
Haloperidol
Terazosin (Hytrin)
Silodosin (Rapaflo*)
Aripriprazole
Mirtazapine
Doxazosin (Cardura)
Dutasteride (Avodart)
Atomoxetine
Nortriptyline
Alfuzosin (Uroxatral)
Dutasteride/Tamsulosin (Jalyn)
Buspirone
Olanzapine
Tamsulosin (Flomax)
Finasteride (Proscar)
Citalopram
Paroxetine
Clomipramine
Pimozide
Clonazepam
Quetiapine
Diazepam
Risperidone
Doxepin
Sertraline
Duloxetine
Trazodone
Escitalopram
Venlafaxine
Sildenafil (Viagra*)
Fluoxetine
Ziprasidone
Vardenafil (Levitra*)
Benign Prostatic Hyperplasia (BPH) Drugs
Overactive Bladder
Oxybutynin (Ditropan*)
Trospium (Sanctura*)
Solifenacin (Vesicare)
Tolteradine (Detrol*)
Darifenacin (Enablex*)
Fesoterodine fumarate (Toviaz)
Erectile Dysfunction
Tadalafil (Cialis*)
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
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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
[email protected]