March 12, 2010 — The US Food and Drug Administration (FDA) today announced it is requiring a boxed warning for the anticoagulant clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership) to caution that poor metabolizers of the drug may not receive full protection from heart attacks, stroke, and cardiovascular death.
The boxed warning also states that tests are available to determine the genetic profile of a key liver enzyme and predict whether a patient will ineffectively convert clopidogrel to its active form. It advises clinicians to consider other antiplatelet medications or alternative dosing strategies for clopidogrel in patients who are poor metabolizers.
However, the FDA noted that although higher doses of clopidogrel increase antiplatelet response in poor metabolizers, an appropriate dose regimen for these patients has not been established in a clinical outcome trial.
The liver enzyme CYP2C19 is primarily responsible for converting clopidogrel into an active metabolite that will protect patients from blood clots. Some patients, however, have alleles, or variations, of this enzyme and cannot metabolize the drug to its active form.
Roughly 3% of the population are poor clopidogrel metabolizers, according to a press release issued today by Sanofi-Aventis and Bristol-Myers Squibb. However, this metabolism inefficiency varies significantly by race.
snip
Roche Diagnostics Test of Key Liver Enzyme Would Be an Off-Label Use
At an FDA press conference today, Courtney Harper, PhD, director of the Division of Chemistry and Toxicology Devices at the FDA's Center for Devices and Radiological Health, said that genetic tests to determine a patient's CYP2C19 status are widely available, and usually cost less than $500. Depending on the particular test, said Dr. Harper, the results may come back in a few hours or a few weeks.
Dr. Harper noted that Roche Diagnostics sells a test that can identify the most common alleles of the CYP2C1P enzyme that cannot metabolize clopidogrel. Because the FDA has not yet cleared the test for clopidogrel dosing, physicians would need to employ it on an off-label basis, she said. "At this point, we would leave it up to the physician's discretion."
More information is available on the FDA Web site.
http://www.medscape.com/viewarticle/718408?sssdmh=dm1.601203&src=nldne&uac=146086BX
The boxed warning also states that tests are available to determine the genetic profile of a key liver enzyme and predict whether a patient will ineffectively convert clopidogrel to its active form. It advises clinicians to consider other antiplatelet medications or alternative dosing strategies for clopidogrel in patients who are poor metabolizers.
However, the FDA noted that although higher doses of clopidogrel increase antiplatelet response in poor metabolizers, an appropriate dose regimen for these patients has not been established in a clinical outcome trial.
The liver enzyme CYP2C19 is primarily responsible for converting clopidogrel into an active metabolite that will protect patients from blood clots. Some patients, however, have alleles, or variations, of this enzyme and cannot metabolize the drug to its active form.
Roughly 3% of the population are poor clopidogrel metabolizers, according to a press release issued today by Sanofi-Aventis and Bristol-Myers Squibb. However, this metabolism inefficiency varies significantly by race.
snip
Roche Diagnostics Test of Key Liver Enzyme Would Be an Off-Label Use
At an FDA press conference today, Courtney Harper, PhD, director of the Division of Chemistry and Toxicology Devices at the FDA's Center for Devices and Radiological Health, said that genetic tests to determine a patient's CYP2C19 status are widely available, and usually cost less than $500. Depending on the particular test, said Dr. Harper, the results may come back in a few hours or a few weeks.
Dr. Harper noted that Roche Diagnostics sells a test that can identify the most common alleles of the CYP2C1P enzyme that cannot metabolize clopidogrel. Because the FDA has not yet cleared the test for clopidogrel dosing, physicians would need to employ it on an off-label basis, she said. "At this point, we would leave it up to the physician's discretion."
More information is available on the FDA Web site.
http://www.medscape.com/viewarticle/718408?sssdmh=dm1.601203&src=nldne&uac=146086BX