DMEx Genotype Panel

Make Better Treatment Decisions for Your Patients

The vast majority of drugs are metabolized through the liver. The liver's primary mechanism for metabolizing drugs is the P450 cytochrome system of enzymes which include CYP2C9, CYP2C19, CYP2D6, CYP3A4 and CYP1A2. Over 50% of the most commonly prescribed medications today are metabolized through the P450 System. Not all patients respond appropriately to a standard, One Size Fits All dose. DNA testing provides a lifetime of protection against drug toxicity or lack of drug efficacy. This simple genetic test, which looks at liver enzymes, will determine your patient's drug sensitivity.

How Cytochrome P450 Gene Variants
Alter Enzyme Function, Drug Metabolism

A Primer on Gene Variation
and Cytochrome P450 Enzymes


Pharmacogenomics is the study of how genetic variations affect the response to drugs. All enzymes, including enzymes in the cytochrome P450 family, are produced by specific genes. The gene contains a DNA code for the construction of the enzyme. It is common for an enzyme's DNA code to have a variation. Typically, this is caused by a change in one nucleotide in the code. Such a change is called a single nucleotide polymorphism (SNP). A gene (also called an allele) with a SNP is called a variant gene or variant allele.

Why should I know my
patients' DME genotype?


Many patients have a gene variant that affects the function of one or more drug metabolizing enzymes (DMEs)--the cytochrome P450 enzymes. The altered enzyme function can change the rate of drug metabolism.8,9 Patients with gene variants are more likely to experience drug toxicity or lack of efficacy.6 Most variants cause a loss of enzyme function. Patients who have these variants are poor or intermediate metabolizers. A few people have variants that increase enzyme function. These patients are ultra-rapid metabolizers.9 Patients on multiple drugs (polypharmacy) have the highest risk for adverse drug reactions (ADRs). Taking multiple medications increases the likelihood that one or more will not be metabolized correctly.10

Genetic variants and prodrugs


A prodrug is a chemical substance that is inactive until it is metabolized by enzymes in the body. Enzyme metabolism converts the substance into its active (drug) form. For example, codeine is a prodrug that is metabolized into morphine. A genetic variant that slows the rate of prodrug metabolism can result in lower than expected blood levels of the active drug. A genetic variant that speeds up prodrug metabolism can lead to a higher concentration of the drug in the blood. This could be toxic, depending on the drug.

In Drug Dosing, Not All Patients Respond to the Standard Dose


Plasma drug levels can vary up to 1000-fold between patients who weigh the same amount.4 Variations in metabolism can cause life-threatening toxicity in one patient and reduce drug effectiveness in another.5

In 40 to 75 percent of patients, drug therapy is less effective than expected.6 With 3.9 billion prescriptions filled in 2009, millions of patients are under- or over-treated.7 Genetic testing helps you personalize drug therapy to avoid ADRs and maximize treatment efficacy.

Adverse Drug Reactions: A Leading
Cause of Morbidity and Mortality


Adverse drug reactions (ADRs) cause an estimated 7,000 outpatient deaths per year.1 More than 2 million serious ADRs and 100,000 deaths occur annually in hospitals, with another 350,000 ADRs in nursing homes.2 Adverse drug reactions cost an estimated $177 billion each year--more than cardiovascular diseases.3

To Avoid ADRs, Look to Your Patient's Genes


Our genes determine characteristics from the obvious eye color and heightto less apparent, such as how much the body makes of certain enzymes. These distinct traits are caused by variations in genes, called alleles.

The cytochrome P450 liver enzymes are among the most important metabolizers affected by individual gene variations. This family of enzymes is responsible for metabolizing more than 80 percent of drugs.8

Because genes come in pairs--one from each parent--a patient can have two normal genes (no variants), one variant, or two. Patients with no variants have normal cytochrome P450 enzymes, but patients with one or two variants have enzymes that metabolize less or more than normal enzymes. This affects how the body metabolizes drugs, which in turn affects the levels of a medication in the blood. Levels that are too high can cause ADRs, and levels that are too low can make treatment ineffective.6

DME Panel Helps You Make Better
Treatment Decisions for Your Patients


Genetic variations play a role in every step of drug metabolism. The DME Genotype Panel helps you personalize prescribing by revealing these variations. Benefits include:
  • Better initial dosing estimates to personalize treatment
  • Greater confidence in prescribing standard dosages
  • Reduced clinical risk from ADRs
  • Better clinical results due to improved drug efficacy


Know Before You Prescribe


A few enzymes are responsible for metabolizing most drugs. This test can tell you how your patients may respond. The basic panel covers CYP2D6, CYP2C9 and CYP2C19. This group metabolizes drugs like warfarin, clopidogrel, codeine, tamoxifen and some antidepressants. The basic test can find:
  • CYP2C9 variations that affect response to warfarin (Coumadin) and other drugs.
  • CYP2C19 variations affect response to clopidogrel (Plavix) and other drugs.
  • CYP2D6 variations that affect codeine response--recent FDA reports caution against potentially lethal codeine effects in children.
Our new Extended DME Genotype Panel covers the above enzymes, plus:
  • CYP3A4 variant (*22) affects the response to Atorvastatin (Lipitor), Simvastatin and Lovastatin.
  • CYP1A2, which can affect response to acetaminophen and Haldol.
  • VKORC1 affects a patient's sensitivity to warfarin (Coumadin). COMT metabolizes catecholamine drugs such as dopamine, methyldopa and levodopa.
The Extended DME Panel from Iverson Genetics is the only cytochrome P450 test to include COMT. To order the basic or new extended DME Genotype Panel, simply select your preferred option on Iverson's requisition form.
References

1. Committee on Quality of Health Care in America. To err is human: building a safer health system. Washington, D.C.: National Academy Press; 2000.
2. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA. 1998;279:1200-1205.
3. Ernst FR, Grizzle AJ. Drug-related morbidity and mortality: updating the cost-of-illness model. J Am Pharm Assoc (Wash). 2001;41:192-199.
4. Ingelman-Sundberg M. Pharmacogenetics: an opportunity for a safer and more efficient pharmacotherapy. J Intern Med. 2001;250:186-200.
5. Ingelman-Sundberg M, Rodriguez-Antona C. Pharmacogenetics of drug-metabolizing enzymes: implications for a safer and more effective drug therapy. Philos Trans R Soc Lond B Biol Sci. 2005;360:1563-1570.
6. Wilkinson GR. Drug metabolism and variability among patients in drug response. N Engl J Med. 2005;352:2211-2221.
7. Kaiser Family Foundation. Prescription Drug Trends, May 2010. 2009; http://www.kff.org/rxdrugs/upload/3057-08.pdf. Accessed November 18, 2012.
8. Matchar DB, Thakur M. Is genetic testing for cytochrome P450 polymorphisms ready for implementation? Am Fam Physician. 2007; 76:348-351.
9. Pharmagenomics Knowledgebase. Available at: http://www.pharmgkb.org/
10. Hohl CM, Dankoff J, Colacone A, Afilalo M. Polypharmacy, adverse drug-related events, and potential adverse drug interactions in elderly patients presenting to an emergency department. Ann Emerg Med. 2001;38:666-671.


Plavix® is a registered trademark owned by Bristol-Myers Squibb/Sanofi-Aventis Pharmaceuticals Partnership. There is no affiliation, sponsorship or endorsement by Bristol-Myers Squibb/Sanofi-Aventis Pharmaceuticals and Iverson Genetic Diagnostics, Inc. Effient® is a registered trademark owned by Eli Lilly and Company. There is no affiliation, sponsorship or endorsement by Eli Lilly and Company and Iverson Genetic Diagnostics, Inc .

Any other trademarks or service marks listed without identification of companies are the property of their respective owners. Quotations made by third parties represent their views only. The naming of a company is not a representation of the company's interaction with the FDA, nor are any comments an endorsement or advertisement for such companies. No further reproductions, alterations or representations of this document by any third party are authorized or endorsed by Iverson Genetic Diagnostics, Inc.

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option on the Req form:

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Testing can be important for medications prescribed to treat even the most common conditions:



• Mental Health conditions
• Post MI Surgery
• Acid Reflux
• Cancer
• Organ Transplant
• Pregnancy
• Heart Failure
• High Blood Pressure
• Migraine Headaches
• Peptic Ulcer
• High Cholesterol
• Enlarged Prostate
• Asthma/COPD
• Depression

One Test For a
Lifetime of Better Health


The DME Genotype Panel is a once-in-a lifetime test. A person's genetic makeup does not change, so each patient only needs testing once. Iverson provides a handy wallet card you can give patients with their results.

Does Insurance
Cover the DME Panel?


Medicare, Tricare and VA have covered the cost of testing when a physician judges it medically necessary. Private insurers cover the cost of testing for some patients. The main reason for private insurance denials is that genetic testing in general is not covered. However, your patient can check with the insurer if cost is a concern.

Additional
Resources


We know you always use your best clinical judgment in making prescribing decisions. Additional information is available at:
PharmGKB.com
Epocrates.com