YouScript: Life Changing Analysis

Elise Astleford was afraid that she was developing Alzheimer’s disease. Moments of confusion and forgetfulness plagued her to the point where simple joys like playing a card game became daunting. “I would have to put the cards down so carefully, it was impossible to focus.”

As new prescriptions frequently made her feel worse, whenever doctors prescribed a new drug, Elise would prepare herself for another trial and error experience by scheduling days off from her life as a retired Episcopal priest, to give herself time to see what would happen.

Often, her system couldn’t tolerate the new drug and would experience what felt like an extreme allergic reaction. Medications prescribed for even the most common conditions gave her terrible side effects.

Unable to function as she once had, Elise resigned herself to the idea that these symptoms were a sign of getting older, and feared her episodes of dementia were early signs of Alzheimer’s disease.

After seeing an ad in a local publication, Elise sent a DNA sample to Genelex for drug sensitivity testing.

When her pharmacist ran her results and a list of the medications and over-the-counter drugs she was taking through the YouScript™ Personalized Prescribing System software, the problem became immediately clear. Astleford learned that she is an intermediate metabolizer of the cytochrome 2D6 and 2C19 enzymes.

The over-the-counter antihistamines Elise was taking contained the active ingredient, chlorpheniramine. Chlorpheniramine is metabolized by the CYP2D6 enzyme, and continued use would result in increased levels of the drug in her system, exposing her to possible adverse drug reactions that affect the central nervous system, such as dizziness, sedation, and altered mental states.

Her pharmacist advised she discontinue taking any medicines containing chlorpheniramine. She did, and the results were life changing. “It was like night and day. I feel like I got my life back.”

Now Elise runs everything by her pharmacist who uses YouScript™, “It is wonderful having a gifted pharmacist who understands that I am an intermediate metabolizer through two pathways and what that means.” Elise’s doctors, including her cardiologist, have now also received reports on which medications are safe or unsafe for Elise and what her proper dose is.

In September, Elise came to Seattle for a Genelex press conference where she told her story to TV and newspaper reporters. National and local news organizations covered the story, “All of a sudden I realized I wasn’t an old lady who was destined for a nursing home. My thinking is clearer and I have unexpected energy.”

Elise carries her YouScript™ card in her wallet, ready to tell her cautionary tale and encourages all healthcare providers to make pharmacogenetic testing the standard of care so fewer people will have to suffer through adverse drug reactions like hers.

These days, it’s not unusual to find Elise briskly walking along a park trail, playing a lively card game with friends or creating art. Her paintings are made into greeting cards which brighten the days of their recipients. It’s a far cry from the diminished quality of life she once thought she was destined for. □

Did You Know?

While dieticians, nurse practitioners, physician assistants, nurse midwives, and clinical social workers are recognized as healthcare providers under the Social Security Act, pharmacists are not, despite overwhelming evidence of their positive impact on patient health.

Change.Org is hosting a petition to correct this crucial oversight in healthcare policy.

Learn more and weigh in at: http://chn.ge/OyZcOS

Personalized Medicine May Fuel Economic Growth

The concept of personalized medicine isn’t new, but the public awareness campaign is only just picking up momentum, partly on the heels of the Patient Protection and Affordable Care Act (PPACA). While the overhaul of the American healthcare system is surrounded by considerable debate, biotech companies are finding fresh optimism in bringing the science of pharmacogenomics into the mainstream.

Though physicians and pharmacists are just beginning to adopt gene-based prescribing, it has already caught the eye of Eddie Yoon, a research analyst for Fidelity Investments and the company’s health care fund manager.

“We are entering the era of Biotech 2.0, in which targeted diagnostic tests are accelerating advances in the truly life-changing therapies of personalized medicine,” according to a recently published Fidelity Viewpoint article. “With an estimated 90% of prescription drugs working only about 50% of the time, prescribing physicians could use molecular diagnostics to test for specific genetic mutations that might cause one drug to be harmful, while another might be safe.”

Fidelity considers genetic-based medicine regimes a game-changing innovation that can drive considerable growth in the health care sector. And at a current estimate of 770,000 injuries and deaths from adverse drug reactions, Fidelity suggests,“this could not only save 50% of drug costs, but also help prevent a leading cause of unintended death.”

All this suggests that the cost savings introduced by personalized medicine and genetic-based prescribing practices might well become the prevailing catalyst to an entirely more patient-centric approach to healthcare. □

Whether it will be improved patient care goals or impressive profit-and-loss ratios that fuel the move to personalized medicine, all indicators point to a win-win scenario.

Source:  https://www.fidelity.com/viewpoints/personalized-medicine-revolution

Codeine For Kids? FDA Says Maybe Not

On August 15th, 2012, the FDA issued a Drug Safety Communication cautioning against the use of codeine in children following surgery. Four recent cases of severe adverse drug reactions prompted this communication.

In these cases doctors used the opioid narcotic codeine as a pain-killer following nose and throat surgery in children suffering from sleep apnea. Their ages ranged from 2-5 years old. All of the children received normal doses of codeine, however, respiratory symptoms developed within two days of starting the regimen. Three of the four cases proved fatal. 

Evidence suggests that all four children possessed the CYP2D6 Ultra-Rapid Metabolizer phenotype. Enzymes within the liver naturally convert codeine into morphine. However, in these particular cases the children’s livers would have converted the codeine more rapidly than expected, leading to dangerously high blood-morphine levels.

Recent studies have shown some aspects of opioid sensitivity (including decreased respiratory rate, sedation, and addiction risk) can be genetically inherited. It’s estimated that 7% of the population possess the aforementioned Ultra-Rapid Metabolizer phenotype, although its estimated to be as high as 29% of North African and Ethiopian populations.

Conversely, individual genetics may also cause opioids to be processed more slowly than expected. The FDA reminds readers that the only way to know if someone is an Ultra-Rapid Metabolizer is to do a genetic test that determines an individual’s CYP2D6 phenotype.

Codeine, along with other related opioids such as methadone and oxycodone, forms a cornerstone of advanced pain management, and is also used as a cough suppressant. Adverse reactions to codeine typically manifest as sleepiness, confusion, or breathing difficulty. Nausea is also common, affecting approximately one out of every three patients taking codeine post-surgery. Even non-serious side effects can be problematic, extending hospital stays and increasing likelihood of readmissions.

The FDA is currently investigating to determine if additional cases of severe adverse drug reactions have occurred in children. They advise healthcare professionals to be conservative in their prescribing regimens and remind parents to monitor their children’s health for any adverse drug reactions whenever taking new medications. □

Source: http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm315497.htm

Washington Family Reunited

The Republic of the Union of Myanmar has been in political and economic turmoil for decades. Formerly known as Burma, the country had been under military rule until the beginning of 2011.

In 2008, Aum Phe attempted to smuggle his family out of the country, to escape religious persecution. Though he and his wife were able to get out of the country, Thailand border agents discovered the van transporting their five children and sent them back to Myanmar.
 

Since their separation, Aum and his wife, Shwe Pai, have been living in Washington state where he had, at least, found peace tending his backyard garden.

All of that changed on the night of Tuesday, July 18th when the couple’s children landed at the Tri-Cities Airport in Pasco, Washington. The children were greeted with hugs, strawberries, and bottles of Sprite and Coca Cola.

The two boys and three girls range in age from 7 to 16 years old. Om Phe, the oldest son, is now nearly as tall as his father. Speaking through a translator, Aum Phe, thanked everyone who made the reunion possible.

Before escaping, Aum Phe had to work for years to save enough money to get his family out of the country. He worked in India and Malaysia, taking whatever work he could find, including working for a pig farmer, where he slept in a field inside a makeshift tent made of newspapers and plastic tarps while earning little to no money.

When his children were prevented from fleeing the country, he had to bribe border agents to learn where they were and again to buy the release of his children, so they could return to their uncle’s farm.

Fortunately, Aum Phe’s story is uncommon with fewer than 6 percent of families becoming separated during their relocation, according to World Relief. The process to reunite the family took years of paperwork, an immigration attorney, DNA relationship testing, and a lot of worrying.

Over the years, the Phe’s sent money to Myanmar for their children to rent a home and for the two oldest to go to school and take English lessons. Now they look forward to sending all their children to school, and if all goes as planned, Aum wants to send Om Phe, 16, to college, and maybe take classes himself. □

FDA Reaffirms Plavix Black Box Label Decision

The US Food and Drug Administration (FDA) is standing by its original decision to update the Plavix label with pharmacogenetic information. A meta-analysis published last year in the Journal of the American Medical Association led by Michael Holmes of the University College of London, raised questions about whether the label changes were premature.

The FDA black box warnings are the strongest type of printed warnings put on prescription drugs. Many pharmaceutical companies and physicians believe black box warnings stigmatize a drug and lead to a decline in prescription rates. However, to date, there is no evidence of a meaningful relationship between the warning labels and any changes in demand.

The CYP2C19 enzyme converts Plavix into its active form. Pharmacogenetic testing identifies the amount of the enzyme a person creates and assigns a value ranging from poor to rapidmetabolizers. The FDA updated the label to inform doctors that poormetabolizers experienced a diminished response to the drug. In 2010, the FDA added the black box warning to highlight that poor metabolizers exhibited a higher cardiovascular risk following acute coronary syndrome or percutaneous coronary intervention (PCI) than normal metabolizers. Both warnings emphasized that pharmacogenetic tests could help guide therapeutic strategies, with the black box advising doctors to "consider alternative treatment strategies" in poor metabolizers.

Holmes et al noted “evidence of small-study bias” in the data collected by the original meta-analysis, and restricted their analysis to only four studies with 200 or more events. These four studies, plus six randomized trials, failed to identify any significant associations between CYP2C19 genotypes and Plavix efficacy in terms of cardiovascular events and bleeding.

According to Lawrence Lesko, former director of the Office of Clinical Pharmacology at FDA's Center for Drug Evaluation and Research, emerging data has shown that the FDA was right in updating the Plavix label. He noted that two other meta-analyses, published before the Holmes et al study, found that poor metabolizers were at heightened risk for cardiac events. Jessica Mega, a cardiologist at Brigham and Women’s Hospital authored a meta-analysis two years ago reporting Plavix-treated patients who were poor to intermediate metabolizers had a “significantly increased risk of major adverse cardiovascular events, particularly stent thrombosis.”

Scripps Health Chief Academic Officer, Eric Topol, has repeatedly argued that CYP2C19 pharmacogenetic testing is most useful in patients who have undergone PCI and are at risk of stent thrombosis. Many agree that these studies have been positive and that the resulting dialogue continues to be extremely valuable to doctors and patients. Ultimately, conversations like the Plavix/FDA debate continue to underpin the value of pharmacogenetic testing in treatment strategies.  

Did You Know?

More than 50% of the most commonly prescribed drugs are processed by enzymes whose levels vary due to genetic factors. This genetic variability is a leading cause of adverse reactions.

There are over 2 million severe adverse drug reactions every year.

Every day more than 5,000 Americans have  an adverse drug reaction serious enough to require hospitalization.

In 2001, the direct healthcare costs associated with adverse drug reactions were estimated at $177 billion.