New Plavix Warning: Plavix May Not Work for Some People

The U.S. Food and Drug Administration (FDA) recently required the makers of Plavix, the second-best selling drug in the world, to carry a new "black box" warning on its label that alerts patients and doctors the popular blood thinning drug may not work for up to one in seven patients who use Plavix to prevent blood clots that can cause heart attacks and strokes. Like the color red in the U.S. Homeland Security terrorist alert system, the new "black box" warning for drugs is the strongest warning the FDA issues for medications, a level of concern that is dramatized by the warning being framed by a black border.

FDA Raises Level of Plavix Warning

The FDA had previously mandated a less stringent warning for Plavix in May 2009 that did not appear in a black framed box, but the pharmaceutical watchdog agency raised the alert level of the Plavix warning to "black box" status in March 2010 because of new data that suggested the risk of taking Plavix is potentially fatal for the 2% to 14% of the populations whose genes hamper the drug's effectiveness.

Why Is Plavix Ineffective for Some People and Not Others?

Unlike a drug like aspirin that enters the body in its active form, Plavix requires patients to convert the heart attack prevention drug to its active form by metabolizing it with a special liver enzyme called CYP2C19. The catch is, not all people produce enough of this liver enzyme to convert Plavix to its active form, and "poor metabolizers"-people with a special gene that causes them to produce insufficient levels of CYP2C19-are vulnerable to platelets in their blood clumping together like sticky rice and forming potentially deadly blood clots that could result in heart attacks or strokes.

Chinese at Highest Risk Taking Plavix

The risk of taking Plavix is highest for people of Chinese descent and lowest for Caucasians, according to FDA scientist Mary Ross Southworth, PharmD, at the news conference where the new Plavix warning was announced. "The frequency is about 2% of Caucasians, 4% of blacks, and 14% of Chinese," said Ross.

Genetic Test for Plavix Users

A genetic test is available for Plavix candidates to determine if they carry the gene that does not allow them to create enough of the liver enzyme that converts Plavix to its active form. So far the FDA has approved only one lab test to spot the gene, an indentification process that costs about $500, according to FDA scientist Courtney Harper, PharmD. Aside from the steep cost of the genetic test for potential Plavix users, it can take up to a few weeks for test results to come back, cautioned Harper at the FDA press conference. During that time, the patient and doctor cannot be sure that Plavix is doing its job to prevent blood clots that could potentially result in a fatal heart attack or paralyzing stroke.

The new Plavix warning comes on the heels of a November 2009 Plavix warning that taking certain heartburn relief drugs like Prilosec and Nexium with Plavix can decrease the effectiveness of Plavix by half because it reduces production of the same liver enzyme that converts Plavix to its active form.

Loss of Plavix Sales Could be Heart Breaking for Bristol-Myers

The two pharmaceutical companies that partner to market Plavix, Sanofi-Aventis and Bristol-Myers Squibb, stand to lose a major cash cow if doctors switch their Plavix patients to alternative blood-thinning medications. According to pharmaceutical intelligence firm IMS health, in 2008 Plavix enjoyed whopping sales of $8.6 billion, second only to cholesterol drug Lipitor from Pfizer.

Sources:
http://www.webmd.com/heart-disease/news/20100312/new-plavix-warning-lack-of-effect-in-gene-carriers
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm203888.htm1
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm204253.htm
http://www.usatoday.com/news/health/2010-03-12-fda-plavix_N.htm
http://blogs.wsj.com/health/2010/03/12/a-black-box-warning-for-plavix-confusion-may-follow/tab/article/