Pharmacogenomics:

Using a Patient’s Genetic Blueprint to Determine Best Medication Regimen

Lotricia Guerrier, ARNP/CNS, CCNS, FNP-BC, CCRN

Objectives The learner will be able to:

o Define pharmacogenomicso Define pharmacogeneticso Discuss potential use of pharmacogenomics with

prescribing and medication management.o Identify resources for interpreting results of genetic drug

testing.o Discuss implications of pharmacogenomics for future

healthcare research.

Disclosures No conflicts of interest have been disclosed by

the presenters or planning committee of this activity

Current Medication Management

“One size fits all” and “trial and error” Difficult to determine who will respond and how Adverse drug reactions and allergies are a

significant cause of hospitalization and death in the US

Personalized Medicine Providers base the majority of their drug

prescriptions on clinical factors, such as a patient’s age, weight, sex, and liver and kidney function.

For a small subset of drugs, researchers have identified genetic variations that influence how people respond.

Patients for Whom Drug Therapy is Ineffective

Patient Response to Medications

Variation in Drug Response

Genetic factors may account for 20-95% of the observed variation in drug response

Five Stages of Pharmacokinetics-o Absorption into the bodyo Distribution to the their site of action in the bodyo Target interaction-binding to cellular receptorso Metabolic processing -using the drug and giving off

byproduct o Excretion from the body-getting rid of the byproduct

Overview

Other Factors That Impact Drug Response

Gender Age Body Mass Diet Other medications Exposure to certain

chemicals/toxins (ie cigarette smoking)

Particular disease states.

Pharmacogenetics vs Pharmacogenomics

PharmacoGENETICs- the study of genetic influences on an individual’s response to drugs.o Analysis of a specific gene or group of geneso Use to predict responses to a specific drug or class of drugs

PharmocoGENOMICs-refers collectively to all the genes that influence a drugs responseo Examines the entire genome

New field that combines pharmacology (the science of drugs) with genomics (the study of genes and their functions)

Genetic differences will be used to predict whether a medication will be effective for a particular person and to help prevent adverse drug reactions.

2 Groups of Genes to Monitor

Pharmocokinetic-o Impacts drug metabolizing enzymes and drug

transporterso How the drug is handled by the body

Pharmacodynamic-o Impacts drug targets such as enzymes, receptors, ion

channels, and their associated pathways. o How the body is effected by the drug.

Personalized Medicine Approach

Why is it Significant?

In the future, pharmacogenomics will allow the development of tailored drugs to treat a wide range of health problems, including cardiovascular disease, depression, Alzheimer’s, cancer, HIV/AIDS, and asthma.

The Ideal Formula for Prescribing

Efficacy-maximum benefit or therapeutic response that a drug can produce

Toxicity-the extent to which a drug induces unwanted or harmful health effects.

High Efficacy + Low toxicity= most ideal drug regimen

Examples of Pharmacogenetics Being Used Today

CYP2D6 gene -This enzyme acts on a quarter of all prescription drugs, including the painkiller codeine, which it converts into the drug’s active form, morphine.

Some people have hundreds or even thousands of copies of the CYP2D6 gene (typically, people have two copies of each gene). Those with extra copies of this gene manufacture an overabundance of CYP2D6 enzyme molecules and metabolize the drug very rapidly.

As a result, codeine may be converted to morphine so quickly and completely that a standard dose of the drug can be an overdose.

On the other end of the spectrum, some variants of CYP2D6 result in a nonfunctional enzyme. People with these variants metabolize codeine slowly, if at all, so they might not experience much pain relief.

Examples of Pharmacogenetics Being Used Today

HIV-Before prescribing Abacavir an antiviral drug, routine testing of the genetic variant that increases likelihood of adverse reaction

Breast Cancer- Trastuzumab - this drug only works for women whose tumors have a particular genetic profile that leads to the overproduction of a protein called HER2

Acute Lymphoblastic Leukemia (ALL)- Mercaptopurine- Genetic variant interferes with ability to process the drug, causing severe side effects and increased risk of infection

How Will Pharmacogenetics Impact Prescribing?

The Food and Drug Administration, which monitors the safety of all drugs in the United States, has included pharmacogenomic information on the labels of more than 150 medications.

This information—which can cover dosage guidance, possible side effects or differences in effectiveness for people with certain genomic variations—can help providers tailor their drug prescriptions for individual patients.

How Will it Affect Drug Design and Development?

Pharmaceutical companies are beginning to use pharmacogenomic knowledge to develop and market drugs for people with specific genetic profiles.

Studying a drug only in those likely to benefit from it could speed up and streamline its development and maximize its therapeutic benefit. 

Additionally, if scientists can identify the genetic basis for certain serious side effects, drugs could be prescribed only to people who are not at risk for them.

As a result, potentially lifesaving medications, which otherwise might be taken off the market because they pose a risk for some people, could still be available to those who could benefit from them.

Who Should Receive Pharmacogenetic Testing?

Pharmacogenetic testing should only be performed based upon medical necessity. o Patients taking a large number of medications with the

potential for serious adverse effects. o Patients taking medications with a high risk of drug

interactions. o When patients do not respond to drug treatment and

options are limited. o Patients with an unexpected pattern of side effects to

medications.

Improved Cost, Efficiency, and Quality of Life

Reduced number of clinic visits to titrate medications or select new medications.

Reduced total medication cost because fewer pills are “wasted” because they are not effective.

Improved efficiency and time savings in managing patients. Reduced risk of drug interactions and adverse events.

Increased medication adherence. Studies show that 38% of Americans do not

metabolize antidepressants properly and 50% of Americans are poor metabolizers of arthritis medications.

Cost and Reimbursement

Average costs range from $250-$500 FDA approved list is generally reimbursed by

most insurance companies. Most insurance companies consider the vast

majority of these test “experimental” because of lack of high quality research results with each one.

What are the Major Trends in Pharmacogenetic Testing?

Some laboratories are offering a larger number of gene tests

Some laboratories are only offering tests that are “reimbursed” by insurance and they are ignoring the value of broader gene testing.

The changing reimbursement landscapes by Medicare and other payers is making it difficult for laboratories to provide “all inclusive” testing that is not based on medical necessity.

Reports are getting better, and easier to interpret and implement. Improved reports are less intimidating to providers and helps them embrace pharmacogenetic testing faster

How is Testing Done? 

The test is a simple specimen collection via a buccal (q-tip) swab. It is non-invasive and the provider receives the results generally within 48 hours.

It is a ONE TIME test with a lifetime impact. Repeat testing is not needed unless additional

genes are available in the future.

Not Sure What Test to Order?

Genetic Test Registry (GTR)

How to Use the Genetic Test Registry

Find tests for a condition or drug responseo Query for a test by clicking on the Tests tab on the home page or by selecting 'Tests'  from the pull-down

menu to the left of the Search button on any other page,o Start typing the name of the condition or drug.o If you see the name of the disorder in which you are interested appear under the query bar, click on it,

otherwise click on Search o If you used Search, the result page will probably list multiple disorders in the left column. Click on the one

you wanto If there are multiple tests listed for the condition in which you are interested, you can focus on those of

most interest to you by selecting from filter options in the left column, such as method used in the test, certifications of the offerer, and location of the laboratory.

Find tests using words in the test nameo Query for tests with one or more words in the test name within the Tests tab.o Use double quotation marks around the word(s) and an asterisk after the last word, e.g.

"mitochondrial*"[testname]" or "respiratory chain*"[testname]. Click Search. Find a laboratory

o Query for a laboratory by clicking on the Labs tab on the home page or by selecting 'Labs'  from the pull-down menu to the left of the Search button on any other page

o You can query on any of the following: name of tests, conditions, genes, proteins, laboratories, staff, or services.

o Start typing your queryo If you see the value in which you are interested appear under the query bar, click on it, otherwise click on

Search.o If there are multiple laboratories listed in the result set, you can focus on those of most interest to you by

selecting from filter options in the left column, such as certifications, special services, and location of the laboratory.

Interpreting The Results

Clinical Pharmacogenetics Implementation Consortium (CPIC) Dosing Guidelines

FDA- drug labeling Lab Pharmacist

Drug Labeling Drug labeling may contain information on

genomic biomarkers and can describe:o Drug exposure and clinical response variabilityo Risk for adverse eventso Genotype-specific dosingo Mechanisms of drug actiono Polymorphic drug target and disposition genes

FDA LABELED DRUGS (selected)

Amitriptyline Aripiprazole Atomexetine Carvedilol Celecoxib Citalopram Clopidogrel Codeine Diazepam Phenytoin

Exomeprazole Imipramine Metoprolol Pantoprazole Risperidone Tolterodine Tramadol Warfarin Nitrofurantoin

Future Implications More research

o Various medicationso When used a tool, not exclusively, will it truly impact

overall outcomes.

Resources The National Institute of General Medical Sciences offers a list of Frequently Asked Questions about

Pharmacogenomics. . http://www.nigms.nih.gov/education/Pages/factsheet-pharmacogenomics.aspx

Additional information about pharmacogenetics is available from the Centre for Genetics Education http://www.genetics.edu.au/Publications-and-Resources/Genetics-Fact-Sheets/FactSheet25

GTR: Genetic Test Registry-is a single location to learn more about genetic tests, including those used for pharmacogenomics. http://www.ncbi.nlm.nih.gov/gtr/

The Smithsonian National Museum of Natural History’s exhibit ‘Genome: Unlocking Life’s Code’ discusses the utility of pharmacogenomics http://unlockinglifescode.org/explore/genomic-medicine/pharmacogenomics.

The Genetic Science Learning Center at the University of Utah offers an interactive introduction to pharmacogenomics. http://learn.genetics.utah.edu/content/pharma/

The American Medical Association explains what pharmacogenomics is and provides a list of practical applications. http://www.ama-assn.org/ama/pub/physician-resources/medical-science/genetics-molecular-medicine/current-topics/pharmacogenomics.page

The National Genetics and Genomics Education Centre of the National Health Service (UK) provides information about predicting the effects of drugs. http://www.geneticseducation.nhs.uk/genomics-in-health/predict-drug-effects

PharmGKB is a pharmacogenomics resource sponsored by the National Institutes of Health that collects information on human genetic variation and drug responses also includes CPIC Guidelines. https://www.pharmgkb.org/

The EndQuestions/Comments?