1.
G e n o P A T H
2 0 9 L o n g w o o d D r i v e , S W
H u n t s v i l l e , A L 3 5 8 0 1
8 5 5 - G E N O P A T H
w w w . g e n o p a t h . c o m
Pharmacogenomics:
The Case for Provider
Practice Integration

2. 2
Pharmacogenomics:
The
Case
for
Provider
Practice
Integration
Introduction
Personalized medicine is becoming a reality in today’s healthcare environment. The
successful milestone of mapping the human genome was achieved through the Human
Genome Project in 2003 and marked the beginning of a new “normal” for how we think
about diagnosing, understanding, and treating diseases in the human species. This area of
science is expanding to cover a wide variety of challenges and opportunities. One specific
subset of the broader context of personalized medicine is Pharmacogenomics.
Pharmacogenomics is the study of how genes affect a person’s response to medications.
This field combines pharmacology and genomics to both develop and administer effective,
safe medications and doses that are tailored to a person’s genetic makeup. Clinicians can tap
into a substantial knowledge base about how certain genetic variations are predictors for
how a patient will respond to a wide variety of very commonly prescribed medications for
immediately relevant clinical applications today. Available insights with respect to how
patients uniquely respond to common prescriptions such as statins, blood thinners, blood
pressure medications, pain medications, oral diabetic meds, anti-inflammatories and
heartburn medications, to name a few, offer an alternative to “trial-and-error” prescription
and the sometimes harmful side effects it can yield.
The imperatives to take advantage of the insights of pharmacogenomics are well justified
given the challenges to our healthcare system, not to mention the costs, suffering and/or
fatalities attributed to ADE’s (Adverse Drug Events). It is estimated that ADE’s add an
estimated costs of $3.5B/year in the US according to the US CDC.1
Estimates also suggest
that if medication issues were classified as a disease, they would represent the 3rd
or 4th
largest cause of death in the United States. Certain patient populations are at a greater risk
of suffering from these events and as such are the most likely to benefit from this type of
personalized medicine.
Providers face a myriad of challenges in today’s increasingly complex healthcare environment.
It is important that this type of personalized medicine be introduced to practices in a way
that is beneficial to the provider practice in order to be ultimately beneficial to patients.
Successful integration requires understanding of the complicated workflow requirements of
the practice and a partner who provides the practice with expertise, education, support and
consultation.
With the right approach and partnership, the integration of this type of personalized
medicine into clinical practice can begin to deliver upon the promise of enhancing patient
outcomes.
1
http://www.cdc.gov/medicationsafety/basics.html

3. Pharmacogenomics:
The
Case
for
Provider
Practice
Integration
3
Why
is
Pharmacogenomics
Important?
According to the FDA (Food and Drug Administration), “Pharmacogenomics can play an
important role in identifying responders and non-responders to medications, avoiding
adverse events, and optimizing drug dosages.” Adverse Drug Events (ADE’s) are a serious
public health problem and it is anticipated that it will likely get worse as the population in
the US ages.
Pharmacogenomics utilized in personalized medicine can shift the emphasis in medicine
from reaction to prevention, significantly reduce trial and error prescribing, help reduce the
overall costs of healthcare, and improve the quality of care and outcomes for your patients.
Furthermore, adverse drug reactions are a cost leader contributing to continued escalation
of expense for malpractice. Adverse Drug Reactions are prominent in malpractice payouts
by providers.

4. 4
Pharmacogenomics:
The
Case
for
Provider
Practice
Integration
Pharmacogenomics
Basics
Genetic factors are estimated to account for between 20-95% of the patient variability with
respect to responses to individual medications. Although humans share about 99% of the
exact same exact genetic material, it is the 1% differences that make us unique. It is also
some of these differences that determine how an individual will respond to a medication.
When a drug is taken, there are two main processes that occur in the body:
1) Pharmacokinetics: How a drug moves
through your body and gets metabolized
or “absorbed” by the body’s systems.
2) Pharmacodynamics: How a drug
changes the physiology of the body as it
meets its “target” (e.g. the pain, or
inflammation as examples.)
In the case of how these processes occur, it is the
Cytochrome P450 (CYP) system of genes that
include the encoding enzymes that control the
metabolism of more than 70% of prescription
drugs.2
The variations that naturally occur through
genetic inheritance predict whether a patient will be either a poor, intermediate, normal, or
rapid/ultra-rapid metabolizer of certain medications. Medications and associated
recommended dosages are typically determined based on “average” success in clinical
trials. With certain enzymes in the CYP450 family, however, the variations from normal
metabolism are significant across our population. Greater than 75% of patients have
significant variations falling outside of “normal metabolizers.”
As an example, known population variances for these three enzymes exists as noted in the
table below and can have significant implications for common prescription drugs such as
Plavix, Coumadin, Warfarin, certain Beta Blockers, common pain medications
and anti-depressants.
2
Pharmacogenomics: Increasing the Safety and Effectiveness of drug therapy; American Medical Association
Percentages of Population By Variation of Metabolism1
Poor
Metabolizer
Intermediate
Metabolizer
Normal
Metabolizer
Rapid
or
Ultra
Rapid
Metabolizer
MetabolicVariations

5. Pharmacogenomics:
The
Case
for
Provider
Practice
Integration
5
Genetic tests can uncover information with respect to these enzyme variations that suggest
for specific drugs what type of metabolizer an individual will be. Genetic testing assays for
particular genes and enzymes can disclose very critical information with respect to the
efficacy of certain drugs for the patient and the dosing levels that will be appropriate.
Just one example of available insights specific to one particular medication when a patient’s
genetic tests highlight particular metabolizer variations is shown below:
Clopidogrel
(pro
drug)
Efficacy
Poor
Metabolizer
Population:
3-­‐5%
Whites;
13-­‐19%
Asians;
10-­‐20%
African
Americans
Potential
Outcomes:
-­‐
Not
Likely
to
receive
full
beneKit;
-­‐
Increased
Risk
of
stent
thrombosis
heart
attack
or
stroke.
Intermediate
Metabolizer
Population:
24-­‐36%
Potential
Outcomes:
-­‐
May
not
receive
full
beneKit;
-­‐
Increased
risk
of
stent
thrombosis
heart
attack
or
stroke;
-­‐
Recommended
to
consider
alternative
therapy.
Normal
Metabolizer
Population:
43-­‐73%
Expected
to
beneKit
from
standard
dose;
Rapid
/
Ultra
Rapid
Metabolizer
Population:
5%
Potential
Outcomes:
-­‐
Expected
to
process
medication
more
quickly;
-­‐
Possible
increased
beneKits;
Possible
increased
risk
for
bleeding/
bruising.
* Note: People with Asian and African ancestry tend to have an increased prevalence of
poor metabolizer status.
Enzymes Normal Intermediate Poor Ultra Rapid
CYP2D6 48% 35% 10% 7%
CYP2C9 60% >35% 2-4% N/A
CYP2C19 14-44% 24-36% 2-20% 30%

6. 6
Pharmacogenomics:
The
Case
for
Provider
Practice
Integration
Which
Patients
Tend
to
Benefit
the
Most
From
Pharmacogenomics?
A large and diverse group of patients
may benefit from a combination of
pharmacogenomics and
comprehensive medication
reconciliation. Commonly prescribed
statins, chronic pain medications,
chronic beta-blockers, SSRI, or anti-
arrhythmic therapy meds are known
to produce responses with significant
variations based on the genetic
characteristics of the patient.
The growing population of aging
adults in the US who are living
longer, but often while managing
multiple chronic conditions are prime
beneficiaries of this type of medicine.
Patients who are over 55 years of age and are taking two or more chronic medications
frequently benefit from this type of personalized medicine. Additionally, the number of
individuals who are taking five or more medications are very good candidates for this type of
medication management.
Primary care physicians are often the ones who are called upon to work with patients who
are suffering from issues such as heartburn or pain management. Medications prescribed
for these situations, not generally deemed as serious as chronic conditions, can in fact have
unintended consequences for the patient because of other medications and/or their genetic
predispositions with respect to metabolism. For these reasons, primary care provider
practices often see tremendous benefits in integration of this type of personalized medicine
into their practices.
Certain medications, over 120 in total, actually have been deemed to be so potentially
harmful due to known issues in patients with specific genetic alleles that they are required by
the U.S. FDA (United States Food and Drug Administration) to carry “black box labels,” or
pharmacogenomics biomarkers information in their labels.3
Some medications commonly
3
www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378.htm

7. Pharmacogenomics:
The
Case
for
Provider
Practice
Integration
7
prescribed by cardiologists fall into this category including medications such as Coumadin ®
(Warfarin) and simvastatins.
Finally, as the number of medications an individual takes increases, the situations in which a
combination of pharmacogenomics and comprehensive medication reconciliation can
provide excellent decision support also becomes more prevalent. Genetic traits provide
predictable insights into how a patient will metabolize drugs and when drugs can become
inhibitors or inducers in an individual providing valuable insight for identifying potentially
harmful drug-to-drug interactions or situations in which the beneficial effects of one
medication are diluted or altered by other medications.
CDC research conducted in 2010 showed that 66.2% of patients between the ages of 45-64
years have taken at least (1) prescription medicine in the last 30 days. The same study
suggests that 16.8% of those individuals have taken (5) or more. The numbers for
individuals who have taken (5) or more prescription drugs more than doubles for the 65
years or older demographic. Genetic pathways information combined with comprehensive
medication reconciliation can provide a physician with significant decision support insights
for these types of patients taking multiple medications.

8. 8
Pharmacogenomics:
The
Case
for
Provider
Practice
Integration
The benefits to the patients who fit in the profiles shown above can be significantly life
altering at times. Expenses associated with ineffective treatments can be reduced. Adverse
reactions and problematic side effects can be reduced. Ultimately, the efficacy of the
treatment regime can be improved, yielding better outcomes for these patients.

9. Pharmacogenomics:
The
Case
for
Provider
Practice
Integration
9
Provider
Practice
Considerations
The decision to integrate pharmacogenomics and personalized medicine into your
practice can be a very positive one. The decision can have immediate and substantial
benefits for your patients inclusive of:
• Saving your patients money on ineffective medications;
• Preventing your patients from experiencing avoidable unpleasant or even fatal
experiences which can be attributed to certain medications;
• Improving the efficacy of their comprehensive treatment plans, thus improving
their quality of life.
Guidance from clinicians who have successfully implemented these programs often
begin with these basic considerations for making the transition in your practice go
smoothly:
1.
Integrate
pharmacogenomics
combined
with
increased
rigor
around
basic
comprehensive
medication
reconciliation
practices.
2.
As
much
as
possible,
work
across
the
continuum
of
providers
for
your
patients
and
include
pharmacy
in
the
process.
3.
Embrace
a
partner
in
the
process
who
is
qualified
and
willing
to
aide
in
educating
you,
your
staff,
and
your
patients
throughout
the
process.
For more information on how your practice can implement pharmacogenomics and
produce better outcomes for your patients, contact GenoPATH at 1-855-GenoPATH
(1-855-436-6728) or contact us at info@genopath.com.