Pharmacogenomics in Clinical Practice: Where Do We Go From Here?

In an interview with Medscape, Mark J. Ratain, MD, Professor of Medicine at the University of Chicago and Founding Director of the University's Center for Personalized Therapeutics, pointed out that pharmacogenomic testing needs to move from the realm of reflex lab testing to part of the physical exam….

“I think we need to take genetic testing out of the domain of laboratory testing and move it to the domain of physical examination. It can then be one more piece of information for the physician to consider and we wouldn't need to focus on the cost.”

“There are a lot of things we do during a physical examination that have never been demonstrated to be cost-effective. Physicians look at their patients' toes as part of an annual physical. Have you ever seen a study that shows that looking at your toes is cost-effective?”“We need to conceptualize genetic testing as a part of the physical exam rather than as a laboratory test that needs to be ordered so you can have the information at the time you are seeing the patient. For example, if you're starting a patient on warfarin, or you are considering whether to start him on warfarin, and you already know that he is going to metabolize warfarin a lot more slowly or that he's going to be a lot more sensitive to it, you can take that into account in the same way you would probably use a lower dose if your patient were frail or elderly. That is where I think the field needs to move.”

“The solution is one that we are piloting here, which is to genotype all patients for all polymorphisms that may affect drug response. You'll then have the results when you need them and your costs will be much lower than doing each test as a one-off laboratory test.
In the current system, you see the patient and want to prescribe a drug, and you say to yourself, ‘Maybe I should order a pharmacogenetic test. But I don't know how to do that, I don't know how long it is going to take to get results, and I don't know if my patient is going to get reimbursed for it. Oh, who cares. I am just going to prescribe the drug.'

“Unless someone says that you can't prescribe the drug without doing the test, or unless we change the way we look at how pharmacogenomic testing should be incorporated into clinical practice, the system is unlikely to change.”

Bringing Personalized Prescribing to the Community Pharmacy

An interview with Brian Hocum, PharmD of Wasem’s Pharmacy who has recently made personalized prescribing available to at-risk customers.

Why do you think genetics is important?
I tell my patients that through DNA technology, we are able to determine what type of drug metabolizer they are. I explain how this information can be used to help predict if they are at risk of having bad reactions to drugs (too much drug exposure) or poor response to drugs (too little exposure to the medication). Genetics is important because it allows Health Care Providers, like myself, to predict who will have “bad reactions” or “poor responses” to medications.

How would you define personalized prescribing in your own words?
‘Personalized prescribing” is the analysis and incorporation of patient specific factors (i.e. CYP450 metabolizing capacity–derived from DNA testing) prior to prescribing, dispensing and/ or choosing new medications (including OTC, vitamins, herbals) and doses. While we typically think of “prescribing” as something only Physicians do, I feel “personalized prescribing” is something we can all embrace; Physician, Pharmacist & Patient.

Why did you decide to launch this program at Wasem’s?
As a Pharmacist working in a community pharmacy, my number one goal is to serve the patients of the community. Our services are what bring patients into the store and they are what keep them coming back for years. Keeping patients safe through more informed medication and dose choices is the best service we can provide and “personalized prescribing” is the best tool I know of to do so.

What efforts have you made to educate physicians and patients in your community about personalized prescribing?
We have in the past and continue to educate the community through newspaper advertisements, co-marketing posters and speaking with community volunteer groups like the Rotary, Lion’s club and retirement centers.

Since pharmacists are able to order laboratory tests in Washington State for the purpose of monitoring drug therapy, I often find that the prescribers are unacquainted with “personalized prescribing.” I send them a fax describing what the genetic results mean, and any alternate medications or dose adjustments that they might considered based on the results. The response has been all positive. Doctors are noting the recommendations in their patient charts. I plan to host a dinner soon for Health Care Providers to educate them about “personalized prescribing.”

You have now made several successful interventions on a patient’s behalf; can you share one of these stories?
Yes, here is one of the first testimonials I received after a successful pharmacogenetic intervention. This patient struggled with adverse drug reactions her whole life, and was relieved that science and technology are finally beginning to understand and incorporate “personalized prescribing:”

“Thank you so much for guiding me through the new way to approach medication. Armed with the letter to my health care provider, I feel confident that finally my doctor will be able to adjust some of my medications. Maybe some day genetic testing will be a routine procedure before prescribing meds. How much misery and money could be saved if we get it right the first time…”

Personalized Prescribing: Making the Most of Medicare Preventive Services

Many people don’t realize that personalized prescribing based on DNA testing is covered by most public and private insurers if a healthcare provider believes it is medically necessary. Be sure to ask about personalized prescribing at your next annual wellness visit.

Medicare offers a number of preventive services, including a free annual wellness visit so your doctor can identify health risk factors and recommend steps you can take to reduce those risks. Your doctor will evaluate your personal and family medical history, as well as current medications, and order tests. (See page 3 for complete description.) The goal of these visits is to prevent disease and to improve your overall health and well-being.

More and more physicians are including medication risk assessments to identify drug side-effects and interactions that may be causing problems along with the standard risk assessments for depression, heart disease, and cancer. If you’re taking four or more prescription drugs or one, such as Plavix, with a warning about genetics on the label, your doctor may order DNA Drug Sensitivity Testing to help optimize your prescriptions. Typically covered by insurance if ordered by a qualified healthcare provider, personalized prescribing helps doctors determine both “drug-to-drug” and “drug-to-DNA” interaction risk.

The comprehensive personalized prescribing program analyzes all the prescription drugs, herbal preparations, and over-the-counter medicines patients are taking for their combined interaction risk, and for their compatibility with a patient’s unique DNA profile.

“With this tool, no longer is it a trial and error proposition as to what drug and dose to prescribe; we can now do it scientifically with a much better outcome for the patient.”

- J.E. Block, MD, FACP, Tulsa, Oklahoma

As the number of drugs an individual is taking goes up, so do the risks of a serious or even fatal reaction. If these drugs are being prescribed by more than one doctor, are self-prescribed, such as herbals, or purchased from more than one source, the risks go up even more.

A questionnaire is now available that allows patients to quickly calculate their risk for adverse drug reactions and treatment failures to help determine if they are a candidate for DNA Drug Sensitivity Testing and a Personalized Prescribing evaluation. Based on information compiled from NIH, the FDA, and www.medsandaging.org, you can download the questionnaire at www.HealthandDNA.com/risk.pdf or request copies for yourself or a medical office by calling 800-523-3080 now.

Sources: U.S. Centers for Disease Control and Journal of the American Medical Association

New Plavix Study Confirms Importance of Genetic Testing

Almost all of the deaths and major cardiovascular events observed in Plavix patients occurred in poor metabolizers of a liver enzyme called CYP2C19, according to data from the GIFT sub study of GRAVITAS presented at American College of Cardiology 2011 annual meeting. Poor metabolizers are people who lack the DNA coding required for their bodies to make CYP2C19, which acts on about 10% of medications. Approximately 2-4% of European origin individuals, 10% of Africans, and up to 20% of Asians are CYP2C19 poor metabolizers. Plavix is a prodrug, taken in an inactive form that requires CYP2C19 to activate it. Additionally, the study found that doubling Plavix dose from 75 to 150 mg improved platelet reactivity results in the one-third of patients who are intermediate metabolizers, but had no impact on poor metabolizers of CYP2C19.

“The thing that hit me in the face was that virtually all of the events were in those [poor
metabolizers].”

- Dr. Gibson, Duke University

Dr. C. Michael Gibson and Dr. Ajay Kirtane from Duke University discussed the study, and both commented that the FDA boxed warning about Plavix genetics was premature until seeing this data. Dr. Kirtane stated, “I’m wondering if maybe we should spend more effort trying to find these non responders for the homozygous gene [poor metabolizers].

Watch the Duke cardiologists discuss the study at www.vimeo.com/22008430

Read details of the study at: www.theheart.org/article/1208199.do

Coming Home to Die of Drug Interactions

The wars in Iraq and Afghanistan have returned 40,000 wounded soldiers to the US, the highest number, compared to combat deaths, of any war in history. Another 300,000 or more troops have returned with traumatic brain injury, P.T.S.D. (post traumatic stress disorder), depression, or chronic pain; difficult to treat conditions our troops will likely suffer from for many years. As a result, psychiatric drugs, central nervous system depressants, and narcotic painkillers have been used by military doctors more than in any previous war. But those medications are being increasingly linked to a rising tide of other problems, among them drug dependency, suicide, and fatal accidents—sometimes from the interaction of the drugs themselves. An Army report on suicide released last year noted that medications were involved in one-third of the record 162 suicides by active-duty soldiers in 2009. An additional 101 soldiers died accidentally from the toxic mixing of prescription drugs from 2006 to 2009. DNA testing can help improve this situation because almost all of the drugs contributing to the drug interactions afflicting our troops are affected by DNA status. When prescribers know the DNA status of their patients, they’re in a better position know when drugs or combinations of drugs will work or when they might be unsafe. Adapted from “For Some Troops, Powerful Drug Cocktails Have Deadly Results,” The New York Times, Feb. 12, 2011

A Family Battle to Overcome Bad Genes for Drug Metabolism

This is an abridged version of an article Tom Carlson, owner of HostasDirect and IdealGardenMarkers, is sending to all of his subscribers because he is a staunch advocate for personalized medicine based upon almost tragic personal experiences.

It has been known for years that people react differently to medications. There is more than a 50% chance that you have an easily diagnosed drug metabolizing enzyme problem, a genetic mutation that causes 100,000 deaths and 2,200,000 serious drug reactions in the U.S. every year. If you know and understand your enzyme situation, you can learn which prescription drugs are best and worst for you. A simple genetic test can mean the difference between a drug that makes you well and one that gives you a toxic reaction or has no effect at all. Despite these tests being around for the last few years, a recent study found that only "1 in 4 physicians had any education in the use of genetic testing to guide medical decisions,” and many people are unaware of how far personalized medicine has come.

My family and I have experienced first-hand how pivotal this information is. We have all been tested, and it has been very influential in improving our health care. Members of my family have suffered and almost died from being prescribed medications that did not match their unique and genetically determined drug metabolizing enzymes. I am not in any way affiliated with the genetic testing industry; this is simply something I am passionate about and I feel that it is my responsibility to share this knowledge with you.

My dad almost died from a bad drug-gene interaction in 2008 caused by a common prescription pain killer. Even though he explained to his outstanding health care providers that, like 10% of the population, he is a poor metabolizer of the CYP2D6 enzyme, he was still prescribed the wrong pain medication after surgery. His caregivers did not understand the drug-metabolizing enzyme information he provided and he was prescribed a medication that is solely metabolized by CYP2D6. He rapidly became very sick, and experienced no pain relief. I thought he was going to die in front of me. As he was suffering, I went on the web and learned that thousands have died from the combination of drugs and being a CYP2D6 poor metabolizer.

My mother also had a problem with Coumadin, a common blood thinner, which could have been very serious. Like 35% of the population, she is an intermediate metabolizer of the CYP2C9 enzyme, which metabolizes the blood thinner. She told her caregivers about her enzyme deficiency, but they did not know of the tests or what my mom’s meant. Worse yet, they did not tell her they did not understand what she told them. These caring, smart, hardworking people proceeded to give her way too much blood thinner for her enzyme situation. When she returned to get her blood checked, they discovered that her blood had become dangerously thin, and there was a risk that she could bleed to death.

These incidences–and others I can’t name here–could have, and should have, been prevented!

Please realize I am not a physician and take no liability for your decisions. Talk to your doctors, pharmacists, and nurses and find out if they are familiar with this testing. I have talked to many highly regarded physicians that were not familiar with these tests. They greatly appreciated the information I shared, and some even changed how they prescribed medications to members of my family. One physician told me, “Of course we have seen different results in patients given the same medications, but we have never understood why–this makes total sense. Thanks for letting me know.”

Please pass this information along–knowledge and understanding of these tests needs to get to the public and medical community. You might save or improve a life!

Genelex has created a new web page at http://www.healthanddna.com/drug-safety-dna-testing/stories.html called Real People, Real Stories to help raise awareness.

Do you have a story to share? Email info@genelex.com.

Genelex Corporation Launches Tamoxitest which can improve survial rates for thousands of breast cancer patients

One hundred eighty thousand women will be diagnosed with breast cancer this year. Eighty thousand will

start taking the drug tamoxifen to prevent the recurrence of their ER (estrogen receptor) positive breast

cancers. The treatment is successful in two-thirds of the women who take it. Genelex Corporation (Seattle)

is now offering Tamoxitest™ that could improve this success rate to greater than 90% by addressing both

of the common causes of tamoxifen treatment failure.
Ten-percent of women are unable to produce the enzyme CYP 2D6 essential for tamoxifen effectiveness

and need an alternative treatment. Another 35% have reduced functioning so their physician should

consider a higher dose or other treatments. DNA testing identifies both classes of patients.
Even with the right genetics, interactions with prescription, over-the-counter, and herbal remedies can also

reduce tamoxifen effectiveness. To prevent this, Tamoxitest™ includes access to GeneMedRx. This

interpretive software warns patients and physicians if tamoxifen benefit is at risk and offers safer

alternatives.

“Five years is a long time to take a medicine that may have little to no effect in preventing cancer

recurrence,” states Genelex Corporation’s CEO, Howard Coleman.

Tamoxitest™ is advocated by the National Foundation for Cancer Research and is based on research

completed at the University of Indiana and Mayo Clinic. This simple, but powerful test requiring only a few

cheek swabs is steadily gaining ground with the mainstream medical community.

Los Angeles oncologist Dr. Michael Benjamin, MD is one of the first physicians to embrace this

technology. "The Genelex gene profiling technology is a powerful tool to help my patients. With tamoxifen

testing, we can appropriately individualize treatment based on patients' ability to process the medicine.”
Benjamin regularly advises his patients to take Tamoxitest™.“ Genelex tamoxifen testing helps me be

smarter about who I treat with tamoxifen, and why. I can take the discoveries made in their labs right to the

patient’s bedside,” states Benjamin. “I see it as the wave of the future in medicine.”

Maura, a breast cancer patient, says that she ordered Tamoxitest™ after she was diagnosed. Found to

be an intermediate metabolizer, the patient and her doctor have opened a dialogue about her dose of

tamoxifen. “It was worth the information – and peace of mind – I received,” she concluded. Most

insurance companies cover the test.

Breast cancer patients and healthcare providers can learn more about Tamoxitest™ at

www.Tamoxitest.com.

Dr. Michael Benjamin’s website is www.interactMD.com