Physicians have long used genetic tests to identify genes that cause rare diseases among family members or to screen for or diagnose birth defects during pregnancy. More recently, researchers have begun using genetic tests to map cancer tumor genomes and pair patients with targeted treatments that will be effective against particular types of cancer.
“Now, we’re looking at more and more human genes and using that pharmacogenomic information to tailor [drug] treatment,” said Mary Roederer, PharmD, BCPS, Assistant Professor at the Institute for Pharmacogenomics and Individualized Therapy at the University of North Carolina (UNC) Eshelman School of Pharmacy and UNC Department of Family Medicine. “Pharmacists caring for patients use the core elements of medication therapy management such as good drug selection, proper dosing, and monitoring for adverse effects. I like to think of pharmacogenomic testing as an additional piece of information that can help us come up with the best treatment plan for patients, rather than a science that exists in exclusion.”
Advances in medicine and technology show that genetics play an important role in identifying responders and nonresponders to medications, avoiding adverse events, and optimizing drug doses. In fact, more than 100 FDA-approved drugs now have pharmacogenomic information in their labeling. Institutions presented with genetic information about medications often aren’t equipped with methods to incorporate genotype data into clinical decision making practices, however. In a recent survey of more than 10,000 physicians in clinical practice in the United States, 98% agreed that a patient’s genetic profiles may influence drug therapy, but only around 10% of physicians surveyed believed they are adequately informed about the availability, use, and applicability of pharmacogenomics testing when prescribing drug therapy for patients.
As medication experts, pharmacists can recognize opportunities for pharmacogenomic testing and interpret test results for the clinical team. Pharmacogenomic consults provided by pharmacists, coupled with clinical decision support for drug-specific alerts, “are integral for clinical implementation of pharmacogenetics,” said Kristine R. Crews, PharmD, BCPS, during a session on pharmacogenomics at the 2011 American Society of Health-System Pharmacists (ASHP) Midyear Clinical Meeting & Exhibition. “Pharmacists should take a leadership role in the therapeutic applications of pharmacogenomics,” added Crews, Director of the Translational Research Laboratory at St. Jude Children’s Research Hospital in Memphis, TN.
Medco, a large pharmacy benefit manager, is already using pharmacists’ expertise in pharmacogenomics. In 2010, the company launched a new program in which pharmacists act as liaisons among patients, physicians, and the laboratory to help manage the genetic testing process.
According to Crews, the pharmacogenetics service at St. Jude grew out of the hospital’s longstanding clinical pharmacokinetics service. About 6 years ago, the St. Jude team identified drugs metabolized by polymorphic enzymes on the hospital’s formulary, Crews said. For example, the enzyme thiopurine methyltransferase (TPMT) is responsible for the metabolism of thiopurine medications, including 6-mercaptopurine, which is the backbone of St. Jude’s pediatric leukemia therapy.
“This is a classic example of a polymorphic gene, because about 90% of the population has inherited normally functioning alleles for the gene TPMT, which results in normal [enzyme] activity,” explained Crews. “With a normal dose of 6-mercaptopurine, there is a fairly low accumulation of these metabolites.”
Patients with intermediate levels of TPMT activity need a small dose adjustment to avoid toxicity. About 1 in 400 patients have deficient levels of TPMT, however, and a normal dose of 6-mercaptopurine can cause potentially fatal toxicity in this population. These patients need only about 10% of a normal dose of the drug.
“For these reasons, we thought it was important to genotype patients for TPMT before they receive their first dose of a drug in this class,” Crews explained. “Doing your test before you give this drug and having it in place in the medical record at the time the decision needs to be made” allows the right dose of the drug to be given to a patient.
Institutions must also provide education to pharmacists to establish competencies in pharmacogenetic consults and provide direction to pharmacists and laboratory staff on the ordering and reporting of pharmacogenetic test results, Crews said. She also discussed St. Jude’s PGEN4Kids project, a pilot program designed to migrate pharmacogenetic tests from the laboratory to routine patient care for preemptive availability. “Ideally, preemptive [genetic] testing helps identify patients with a high [risk of] toxicity or lack of benefit for certain drugs,” said Crews.
Vanderbilt University Medical Center is also focused on implementing pharmacogenomics into practice strategies. “Pharmacogenomics will become a compelling part of the medical process, but the limiting factor right now is that oftentimes, if you’re ready to write a prescription, you don’t want to wait a week to find out [the patient’s] genotype,” said Leslie R. Mackowiak, BSPharm, Director of Clinical Informatics at the Vanderbilt University Medical Center in Nashville during the ASHP pharmacogenomic session.
In 2010, Vanderbilt launched a personalized medicine initiative called Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment (PREDICT), which puts genetic information in patients’ electronic medical records to help physicians identify the drug and dose that is best for them.
The launch of PREDICT was particularly timely. In March 2010, FDA mandated a black box label for clopidogrel (Plavix—Bristol-Myers Squibb/Sanofi) to alert physicians and patients of the role of CYP2C19 (cytochrome P450 2C19) gene variants in response to this drug. More than 3,000 patients at Vanderbilt have undergone CYP2C19 gene testing, and as of last year, more than 600 were found to have one or two copies of a genetic variant that makes them poor responders to clopidogrel.
Vanderbilt also offers testing for the SLCO1B1 gene, which affects muscle toxicity in patients prescribed simvastatin. Researchers are currently working on algorithms for analyzing the two significant polymorphisms associated with warfarin dosing, and Vanderbilt plans to add many more drugs to the PREDICT program.
We have a “vision for highly personalized medicine,” said Mackowiak. “We give you the drugs you absolutely need at Vanderbilt—nothing more, nothing less.”