• Pharmacogenomics is the study of how an individual's genetic
inheritance affects the body's response to drugs.
• The goal of these test results could be used to optimize drug
choice and/or dose earlier for more effective therapy, avoid
serious adverse effects, and decrease medical costs.
• CYP450 tests provide information on how quickly or slowly the
patient will metabolize a certain drug (ex: warfarin or
clopidogrel). This allows one to assess the likely risk of adverse
drug reactions, drug toxicity, decreased effectiveness or drug
failure when using a specific drug in one particular individual.
Understanding Cytochrome P450
• Cytochrome P450 (CYP450) is a large enzyme family mostly found
in the liver that is involved in the metabolism and processing of
many drugs and chemicals in our body.
• Since the CYP450 enzymes have more than 50 variations, their
activity may vary from person to person. Individual differences of
cytochrome P450 activity can mean that certain drugs aren’t
metabolized at all, are metabolized slowly, or are metabolized
• These results can lead to adverse drug reactions or a lack of
therapeutic effect under standard therapy conditions.
• Essential for production of cholesterol, steroids, prostacyclins, and
• Necessary for detoxification of foreign chemicals and metabolism of drugs
• CYP450 – cell (cyto)+heme pigment (chrome and P)+ absorbs light at
wavelength of 450 when exposed to CO
• Over 50 CYP450 enzymes
• CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5 metabolize 90% of
• For each drug test requested, The Pgx Lab provides an analysis of the
patient’s genetic response to that specific drug, classifying them as:
• Normal Metabolizers (NM)
• Poor Metabolizers (PM)
• Intermediate Metabolizers (IM)
• Rapid Metabolizers (RM)
• Ultra Rapid Metabolizers (URM)
• Key Point to Remember: Each person responds to drug treatments
Genetic Enzymes Tested
• Enzymes Associated with Cytochrome P450:
• CYP2D6 – responsible for the metabolism or elimination of approx.
25% of clinically used drugs.
• CYP2C19 – primary enzyme for the metabolism of Plavix
• CYP3A4 & 3A5 – primarily functions in metabolism of pain drugs.
Active in nearly 50% of all pain drugs used today.
• CYP2C9 – Nearly 100 therapeutic drugs are metabolized by this
Breaking Down Pain Management
CYP450 2C19, 2C9, 2D6, 3A4, 3A5:
Key Factors in Effective Pain Management
Breaking Down Pain Management
• Drugs are the “first line” of treatment for most forms of pain.
• Goal of successful pain management is to effectively control
patient pain without causing excess side effects from the
• However, only 58% of those who took prescription medication
received any form of pain relief.
• Less than 41% of patients taking over-the-counter pain
medication reported relief.
• The incidence of unintentional
(and preventable) overdose-
related deaths is growing
• Of all drug-related deaths in
the U.S., 43% are due to pain
• 80% of all pain management
drugs are prescribed by the
general practitioner or the
Codeine and FDA Guidance 2007
• Evidence suggests that individuals who are ultrarapid
metabolizers (those with a specific CYP2D6 genotype) may
convert codeine to its active metabolite, morphine, more
rapidly and completely than other people.
• In nursing mothers, this metabolism can result in higher
than expected serum and breast milk morphine levels.
• In a nursing mother known to be or suspected to be an
ultra-rapid metabolizer of codeine, consider other options
for relieving pain or persistent cough.
Cardiac Molecular Testing
CYP2C19 and its Relationship to the Cardiac Response
• CYP450 includes a gene (CYP2C19) that codes for numerous liver
enzymes involved in the metabolism of toxins, metabolic
intermediates, lipids, sterols and xenobiotic substances such as drugs.
• These enzymes account for 75% of the metabolic processes involved in
the metabolism and bioactivation of all drugs.
• Detecting these genetic variations helps clinicians predict how a
patient will respond to these types of drugs, such as Plavix.
• Patients with reduced function alleles have ~3.5x greater risk for major
adverse cardiovascular events – with the greatest risk for poor
metabolizers of CYP2C19.1
• People of African and Asian ancestry have a greatly increased
prevalence of Poor Metabolizer status of CYP2C19.2
Adverse Drug Reactions
• “appreciably harmful or unpleasant reaction, resulting from an
intervention related to the use of a medicinal product, which
predicts hazard from future administration and warrants
prevention or specific treatment, or alteration of the dosage
regimen, or withdrawal of the product.”
• 100,000 Americans die due to medication-related problems every
• 10.7% of hospital admissions in older adults are associated with
adverse drug reactions
• Four medications accounted for more than two thirds of these
oral antiplatelet agents (13%)
oral hypoglycemic agents (11%)
Cardiac Molecular Testing
Factor II and its Relationship to Cardiac Events
• The increased risk of venous thrombosis in patients who
are heterozygous for the prothrombin gene polymorphosis
is 3X greater than normal.
• Patients with a previous or current thrombotic event that
have the prothrombin gene polymorphism are at increased
risk for a re-occurrence.
Factor II Mutation
• Prothrombin 20212 mutation
• Having a heterozygous prothrombin mutation
increases the risk of developing a first DVT by
about 2 to 3 times the background
• May increase risk of heart attacks in young
women, particularly those who smoke
• MTHFR is an abbreviation for the gene that codes for an
enzyme called methyltetrahydrofolate reductase. The MTHFR
enzyme helps the body to manufacture proteins. Two
mutations are the most studied: 677 and 1298, although there
are more than 50 known MTHFR variants.
• Mutations in the 677T variant is associated with
thromboembolic and cardiovascular disease, which can lead
to blood clots, strokes, embolisms, and heart attacks.
• Mutations in the 1298C variant are associated with a number
of chronic diseases, including fibromyalgia, irritable bowel
syndrome, migraines, and other conditions.
• Studies have found that 98% of autistic children have an
Elevated homocysteine levels increase risk of:
• Having a child with a neural tube defect (i.e. spina
• Increased risk of pregnancy complications
(preeclampsia, placental abruption, pregnancy loss)
We consider the MTHFR genetic test one of the most
important to your health. MTHFR is involved in processing
folic acid. Small changes in this chemical process can be
associated with any of the following conditions:
Stillbirths, as well as
other birth defects
Simple Testing Process
Collect the buccal swab
Ship Lab processes
• Requisition form completion and non-invasive
buccal swab collection under 5 minutes
• INCLUDE patient’s current medications list,
demographic face sheet, copy of front and
back of insurance card.
• Ship to lab overnight
• Results back to provider typically within 10
business days from receipt
Test Requisition Form
medications list, demographic
face sheet, copy of front and
back of insurance card.
sign in order for test
to be run
Barcode stickers for
• If PGx Lab is an out of network lab.
• Total cost of comprehensive test charged to insurance: $7195.
• Noridian LCD limits PGX payment to CV and Psych.
• Growing utilization of PGX in Pain and Geriatrics.
• Cash Price program to continue supplying the need within markets other
than CV and Psych:
• List Price example of $600
• Option 1- One time payoff by Check or Credit-$600 – 25%=$450.00
• Option 2- 3 installments (1 every 2 months) of $175.00 over 6
months. 3 X $175= $525 or a 12.5% discount.
• Option 3- 12 month installments of $50.00. 12 X $50=$600
• Medicare covers:
• Cardiovascular panel
• Psychiatric panel
• Thrombosis/Anti-Clotting panel
How To Start
1. Complete New Client paperwork
for each new account/physician
office and fax to (888) 865-8954.
2. Once New Client paperwork is
received, start up materials are
then sent out to physician office
including test kits, return shipping
labels, personalized test request
a. Test request forms will be
prepopulated with provider
information and then printed for
ordering and signature.