October 2007 Clinical Laboratory News: FDA Takes a Step Toward Widespread Personalized Medicine

October 2007: Volume 33, Number 10

FDA Takes a Step Toward Widespread Personalized Medicine

Warfarin Label Now Recommends Genetic Testing

By Deborah Levenson


For the first time, FDA has recommended pharmacogenomic testing for patients who are newly prescribed a common medication. An August update to the label for warfarin (Coumadin) makes clinicians aware that patients with certain genetic variants probably need lower initial doses, but it stops well short of directing clinicians to order pharmacogenomic tests to identify those patients who have problematic variations of the CYP2C9 and VKORC1 genes, which metabolize warfarin and determine the effectiveness of circulating doses.

“Personalized medicine has moved into the mainstream,” proclaimed Larry Lesko, MD, PhD, Director of FDA’s Office of Clinical Pharmacology, Center for Drug Evaluation and Research (CDER) during an August press conference. However, some officials and pharmacogenomics experts call the recommendation weak because the label never specifically discusses clinicians ordering the tests—which FDA officials said are available from most major labs as home-brew tests at costs ranging from $125 to $500. Instead, the label implies they are beneficial. “The lower initiation doses should be considered for patients with certain genetic variations in CYP2C9 and VKORC1 enzymes as well as for elderly and/or debilitated patients and patients with potential to exhibit greater than expected PT/INR responses to Coumadin,” the dosage and administration section states. A longer section on pharmacogenomics presents results of three studies on the genetic variations, but does not specifically discuss use of the test in clinical settings. “The relabeling isn’t directive to physicians that they should use these tests. For that type of label, we need more data. This label is more informational to physicians and is intended to stimulate study of the role of genetics in warfarin therapy,” explained Janet Woodcock, MD, FDA’s Deputy Commissioner and Chief Medical Officer, during the press conference. Added Dwaine Reeves, MD, acting director, Division of Medical Imaging and Hematology products, Center for Drug Evaluation and Research, “We’re not quite at the point where we can say physicians must use these tests, but we want physicians to know they are available.”

“This could be a huge volume test,” predicted Thomas Monroe, PhD, Director of Molecular Diagnostics at Spectrum Health, Grand Rapids, Mich. “So many adverse drug events are related to warfarin.” Some laboratorians have called dosing algorithms the key to making the tests viable tools for physicians. Monroe identified about six that have been developed for Caucasians and Asians. The label makes no mention of these algorithms, but cites other research in overwhelmingly Caucasian cohorts. Lesko noted that FDA has asked researchers to expand their algorithms to other populations.

Several companies have submitted 510(k) applications for warfarin tests to the FDA. One of the companies, Nanosphere (Northbrook, Ill.), told CLN it expects FDA approval of its Verigene Warfarin Metabolism Nucleic Acid Test “at any time.”

Efforts to educate physicians about pharmacogenomics and warfarin are underway. FDA’s Critical Path Initiative and the American Medical Association (AMA) are working on a brochure about pharmacogenomics, and a new AMA online continuing medical education course covers the genetic control of drug metabolism and response, clinical examples, and pharmacogenomic information on drug labels. AMA and FDA are also developing a video on pharmacogenomics and warfarin for the Web.

For More Information

FDA information on new warfarin label language 

American Medical Association (AMA) continuing medical education course 

Additional AMA information on pharmacogenomics 

March 2007 CLN article on pharmacogenomics and warfarin

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