Making Genotype a Routine Part of Drug Prescribing

Perhaps the boldest move to date to apply genotype information to drug prescribing, and to do it in a timely way to optimize the treatment a patient receives, launched in September at Vanderbilt University Medical Center in Nashville.

Vanderbilt physicians began routinely asking patients scheduled for coronary catheterization if they’d agree to have a small cell specimen genotyped using a commercially available chip that screens for 184 genetic polymorphisms that help determine the way a person metabolizes various prescription drugs. They decided to start with patients undergoing coronary cath, because many of these patients wind up getting a coronary stent and then require prolonged treatment with antiplatelet drugs, usually including clopidogrel. Some patients have a polymorphism in the gene for a protein involved in clopidogrel activation that impairs efficacy. Those patients either get a boosted clopidogrel dose or the pricier alternative, prasugrel. By mid November, 300 patients had undergone genotyping, with 10 poor metabolizers identified who received an alternate regimen.

image courtesy of Flickr user JaypeeOnline

Next up for expanding the program are patients scheduled for hip or knee replacement, because after surgery they’ll all go on an anti-coagulant drug, traditionally warfarin. Genotyping can help guide warfarin dosing during the first few days of treatment. (Since October, though, many patients began receiving dabigatran instead, an anti-coagulant that sidesteps the genotyping issue.)  Future patients to add to the genotyping list include those who are on or may soon start tamoxifen, azathioprine, 6-mercaptopurine, abacavir, codeine, or “virtually every antidepressant and most antipsychotics,” said Dr. Dan M. Roden, assistant vice-chancellor for personalized medicine at Vanderbilt and a driver and shaper of the program.

Although during rollout the program targets patients with a specific, imminent need for a certain drug, the broader concept is to have genetic information about variations in drug metabolism embedded in each patient’s medical record, so that it can automatically come into play whenever the patient gets prescribed a drug. “In the long perspective, it’s every 50-year-old,” because over the rest of ther lives they all stand a decent chance to receive some drug that carries a pharmacogenetic backstory, said Dr. Roden when I spoke with him last month in Chicago at the annual Scientific Sessions of the American Heart Association. Vanderbilt put “a huge amount of money into this,” he added, and it’s hoping to eventually persuade payers to foot the bill. So far Vanderbilt has supplied all the funding, because it believes this will improve outcomes and is also a great marketing tool.

A key element of Vanderbilt’s launch, which it says is the world’s first such program, was the careful wording of the alert that physicians get when their electronic pad identifies a patient with clopidogrel-activation deficiency. The pop-up’s text followed “a year of negotiations between lawyers, pharmacologists, pharmacists, and interventional cardiologists,” Dr. Roden said.

—Mitchel Zoler (on Twitter @mitchelzoler)

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Filed under Cardiovascular Medicine, Drug And Device Safety, Family Medicine, Genomic medicine, Health Policy, Hospital and Critical Care Medicine, IMNG, Infectious Diseases, Internal Medicine, Medical Genetics, Oncology, Practice Trends, Primary care, Psychiatry, Surgery

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