Biotechnology Healthcare - July/August 2008 - (Page 54)

PERSONALIZED MEDICINE Declaring War on Warfarin Misdosing Bob Carlson, MHA, Senior Contributing Editor A bout 20 million Americans are on warfarin, and another 2 million start taking the drug each year. So, chances are, you know someone who is on Coumadin, Jantoven, Marevan, or Waran. If that’s the case, chances are you also know that getting the dose just right is a tricky business involving frequent office visits for blood tests and dosage adjustments. This monitoring is important. Too much warfarin and you can bleed to death. Too little, and a blood clot may get you. The widespread use of warfarin and the hassle of getting the dose just right makes this drug an ideal candidate for pharmacogenetic research to find out if a person’s genes can help predict his or her best initial dose. THE OPTIMAL DOSE Warfarin is an anticoagulant, indicated after major surgery, such as hip replacement, and for people with artificial heart valves, or for those with conditions such as chronic atrial fibrillation or deep vein blood clots. A synthetic derivative of coumarin, a chemical found in many plants, warfarin is available in tablet form and is effective in preventing or eliminating clots. Warfarin’s drawbacks are its narrow therapeutic range and the fact that the optimal dose varies greatly from person to person. Some A WIN FOR EVERYONE people metabolize warfarin slowly, while others do so One of the experts who testified before the FDA in supquickly. port of genotyping patients for warfarin dosing was Throughout most of warfarin’s 50year history, physicians have tried to calculate the optimal dose for individuals by using algorithms that factor into account gender, age, height, weight, race, evidence of liver disease, other drugs being taken, and the baseline International Normalized Ratio (INR), a measure of how quickly a person’s blood clots. But that approach leaves a lot of room for improvement. More than a third of patients do not respond to their initial dose of warfarin as expected and end up in the emergency room. In 2004 and 2005, according to a study published in JAMA the following year, warfarin was implicated in an annual average of 43,000 ER visits for adverse drug One of the simplest applications of personalized medicine could prevent events (ADEs). That’s second only to more than 17,000 strokes a year: genetic testing for warfarin metabolism. 54 BIOTECHNOLOGY HEALTHCARE · JULY/AUGUST 2008 ADEs involving insulin, and it doesn’t include warfarin-related ADEs in hospitals, nursing homes, clinics, offices, or homes. Because of the high rate of ADEs associated with it, warfarin is underprescribed. A few years ago, when researchers began figuring out which genes do what, they discovered that cytochrome P450 liver enzymes are responsible for metabolizing many drugs, including warfarin. Within this family, one gene, CYP2C9, explains about 10 percent of the variation in warfarin dosing. In 2005, the vitamin K epoxide reductase enzyme, encoded by the VKORC1 gene, was found to explain another 30 percent of dose variations. Together with clinical variables such as gender, age, height, and weight, the CYP2C9 and VKORC1 genes account for about 54 percent of the variation in how individuals respond to warfarin. Numerous companies have developed commercially available tests to detect variations in the CYP2C9 and VKORC1 genes. Last year, the U.S. Food and Drug Administration updated labeling information for warfarin and suggested that physicians order these new genetic tests to help them establish more precise warfarin doses in patients. Jim Varney/Photo Researchers Inc.

Table of Contents Feed for the Digital Edition of Biotechnology Healthcare - July/August 2008

Biotechnology Healthcare - July/August 2008 Openers Contents Editorial/David B. Nash, MD, MBA Drug Track Health Plan Confidential Rheumatoid Arthritis A Decade of Trial, Error, False Starts, and Hope What Path Will Comparative Effectiveness Research Take? RA Therapies in Development: A New Generation of Relief Assessing the Full Impact of RA on Employers and Payers Stem Cells: Health Insurance You Can Bank On Specialty Pharmacy Employer to Employer Personalized Medicine Trends Clinical Briefs

Biotechnology Healthcare - July/August 2008

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