Pharmacists called to take lead 
in pharmacogenomics—the bridge 
to personalized medicine


Health-System Edition

In a case series published this September in JAMA, genetic testing in 91 children and young adults with refractory or relapsed cancer led to actionable findings that changed cancer treatment for almost one-half of the patients. Genetic testing to predict how a patient will respond to a given medication is improving patient safety and outcomes in numerous conditions.


Pharmacogenomics uses a patient’s genetic information—or that of a patient’s cancer tissue—to aid prescribers in selecting the right drug and the right dose for the patient. Genetic data can reveal a patient’s risk for adverse effects or toxicity from a particular drug or the likelihood that the drug will have any effect at all. Currently, fewer than 10% of U.S. hospitals use pharmacogenomic testing, but the American Society for Health-System Pharmacists (ASHP) Foundation predicts that most U.S. regions will have a formal hospital pharmacogenomics program within the next 5 years.


“As genotyping methods have become easier, more available, and less expensive, and we’ve organized more of the clinical information needed to apply pharmacogenomics to patient care, we’ve reduced barriers to its implementation,” said James Hoffman, PharmD, medication outcomes and safety officer at St. Jude Children’s Research Hospital in Memphis, TN. “We are seeing various indicators that pharmacogenomics is poised to take off.” 


Anticipating expansion in the field, ASHP released a statement earlier this year describing pharmacists’ unique positioning to lead development of pharmacogenomics initiatives. 


What is pharmacogenomics?


Researchers have identified some 200 drug–gene pairs in which a particular gene mutation has implications for how a patient will respond to a given drug. The genes involved may be the patient’s own genes (germline) or, in the case of cancer, those found in a tumor (somatic). The National Institutes of Health (NIH)–funded Clinical Pharmacogenetics Implementation Consortium (CPIC) has compiled these pairs into a list along with clinical guidelines. FDA offers a list of drugs for which pharmacogenomic markers are included in the labeling. 


In addition to cancer drugs, medications for HIV, heart disease, depression, and chronic pain, among many other conditions, are associated with genes that can modulate the drugs’ effects or the adverse effects they bring. 


Take codeine, for example. The cytochrome P450 (CYP) 2D6 gene produces a protein that converts codeine into morphine in the body. The morphine then has its pain-relieving effect. Some people have a mutation in CYP2D6, however, that causes the body to convert codeine too slowly or not at all, rendering the drug ineffective. Another possible mutation in the gene can cause dangerously high levels of morphine to accumulate in the body after a standard dose of codeine. 


“There’s been cases where children have died from having too much morphine because the conversion by that gene is ramped up,” said Hoffman.


Why pharmacogenomics?


Just as a patient’s age, lifestyle, existing comorbidities, and other medications figure into a prescriber’s selection of a drug, genetic predisposition to do well or poorly on that drug is a crucial clinical factor that health care providers can now consider. 


“If you’re a patient newly diagnosed with depression, we have 10 or 15 drugs that we know will work in the population, but we need to know which one to pick for you,” said Mark Dunnenberger, PharmD, director of the pharmacogenomics program at NorthShore University HealthSystem in Evanston, IL. “Up until today we might ask the patient, ‘Has somebody in your family had this problem before? What medications worked for them?’ That really is a genetic question.”


Physicians might try patients on numerous drugs before finding one that works. Each drug can bring new potential risks, and the time it takes to find the right drug is time that the condition goes untreated. Genotyping can increase the odds that prescribers try the right drug first. 


“We believe it will lead to safer, more effective medication therapy by reducing the probability that patients accumulate side effects and by increasing the probability that the patient receives the benefit we expect from the medication,” said Dunnenberger. 


Pharmacists and other health care providers should not see pharmacogenomics as an esoteric bench science, Hoffman added, but as a tool for optimizing medication safety. 


Rather than removing codeine from formularies, for example, in response to mortalities associated with the drug, “it allows us to still use codeine safely in our patient population,” Hoffman said. “[Codeine] is a good application for pharmacogenomics because it leaves this therapeutic option that can be used safely. More therapeutic options are usually better.”


Putting pharmacogenomics 
into practice


Because an individual’s genetic makeup doesn’t change, the ideal time to test someone for genetic variations that may affect drug metabolism is before they ever take a drug.


“If you’ve already been taking the drug for 6 months, I know how you are responding to it, and it doesn’t matter whether it’s your genotype that’s causing that response,” said Dunnenberger.


As hospitals roll out pharmacogenomics programs in the coming years, patients will likely undergo tests for genetic variants known to play a role in the metabolism of a drug their physician plans to prescribe. But as genetic testing becomes less expensive, more accessible, and generally more common, Dunnenberger envisions a near future when many patients’ medical records will already include a patient’s raw genetic data. 


“You’ll have gotten your whole genome sequenced for one reason or another—maybe it’s to determine your risk for a certain cancer, cardiovascular or endocrine disease, or a neurological condition,” Dunnenberger said. “And there’s going to be this treasure trove of data in your medical record.”


To make this information actionable and to fully integrate pharmacogenomics into systemwide prescribing practices, health systems need informatics platforms that can interpret and apply the genetic data to recommendations offered by decision aids. Just as decision aids now alert prescribers that the patient takes a supplement that may interact with a prescription, these tools would alert the prescriber that the patient is a poor metabolizer of a particular drug. 


“We need to build a system that allows us to pull out what we need at the moment that we need it and make clinical recommendations,” Dunnenberger said. “That changes the question from ‘Should I test you for this or for that?’ to ‘Let me go find that piece of data.’ That’s going to be really powerful if we build the informatics tools to support that.” 


Bridge to precision medicine


The term “precision medicine” echoed through American households when President Barack Obama announced his administration’s Precision Med-icine Initiative during the State of the Union address early this year. Pharmacogenomics could be many Americans’ first experience with precision medicine. 


“Patients are used to having their medications adjusted on clinical factors, and that’s what pharmacogenomics is. It’s just another clinical factor,” Dunnenberger said. “Patients understand and grasp that.”


Patients might feel less comfortable at first with the idea of making a preemptive health decision today based on the genetic probability of developing a particular disease in the future. “That’s about a future problem, whereas pharmacogenomics is about a current problem and coming up with the best possible treatment for it.” 


Acting on genetic data in the selection of medications today could lead patients to better understand the value of genetic information for other health decisions in the future. Pharmacists have a significant role to play in laying that groundwork.


Opportunities for pharmacists


In its statement, ASHP charges pharmacists with the task of “spearhead[ing] the clinical application of pharmacogenomics” as part of safe, effective, and cost-efficient medication practices. 


“As drug therapy experts, we can lead implementation of this cutting-edge area,” Hoffman said. 


To prepare all pharmacists to provide care that will increasingly include pharmacogenomic recommendations, the organization calls colleges of pharmacy and the Board of Pharmacy Specialties to include curricula on this growing field. ASHP advises that basic understanding of pharmacogenomics enables pharmacists to recommend appropriate genetic testing, design a drug therapy regimen based on a patient’s genetic information, educate others on pharmacogenomics, communicate pharmacogenomic-driven drug therapy recommendations to the care team, and interpret results in the patient’s medical record. 


Experts foresee a health care landscape in which all pharmacists have a working understanding of pharmacogenomics and some pharmacists are specialists in the field. 


“The requirement for a specialist in this area might be like specialists in infectious disease [ID]. A hospital generally has an ID specialist, but every pharmacist in the hospital practices ID in some way. The same thing is going to be true with pharmacogenomics, and actually, this is how it works at our hospital,” Dunnenberger said. 


ASHP calls pharmacists who specialize in the field to develop clinical decision support tools in electronic health records that guide prescribers in the use of pharmacogenomic information, a process and materials for patient education, and institutional guidelines for pharmacogenomic im-plementation, among numerous other high-level tasks. 


In a field primed for continued growth, opportunities await pharmacists. “Pharmacogenomics integrates diverse perspectives and aspects of pharmacy practice, from informatics to patient education, interprofessional collaboration with various groups, applying drug knowledge, genomic knowledge,” Hoffman said. “It’s a unique area where pharmacists can apply a lot of different skill sets.”