Posted on 03/12/2010 4:50:36 PM PST by neverdem
FDA NEWS RELEASE
For Immediate Release: March 12, 2010
Media Inquiries: Sandy Walsh, 301-796-4669,
sandy.walsh@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA
FDA Announces New Boxed Warning on Plavix
Alerts patients, health care professionals to potential for reduced effectiveness
The U.S. Food and Drug Administration today added a boxed warning to the anti-blood clotting drug Plavix (clopidogrel), alerting patients and health care professionals that the drug can be less effective in people who cannot metabolize the drug to convert it to its active form.
Plavix reduces the risk of heart attack, unstable angina, stroke, and cardiovascular death in patients with cardiovascular disease by making platelets less likely to form blood clots. Plavix does not have its anti-platelet effects until it is metabolized into its active form by the liver enzyme, CYP2C19.
People who have reduced functioning of their CYP2C19 liver enzyme cannot effectively convert Plavix to its active form. As a result, Plavix may be less effective in altering platelet activity in those people. These “poor metabolizers” may not receive the full benefit of Plavix treatment and may remain at risk for heart attack, stroke, and cardiovascular death.
“We want to highlight this warning to make sure health care professionals use the best information possible to treat their patients,” said Mary Ross Southworth, Pharm.D., a clinical analyst in the Division of Cardiovascular and Renal Products in the FDA’s Center for Drug Evaluation and Research.
In May 2009, the FDA added this warning to the drug’s label. After reviewing more data, the agency felt it was important to highlight this risk in a boxed warning.
It is estimated that 2 percent to 14 percent of the U.S. population are poor metabolizers. The FDA recommends that health care professionals consider alternative dosing of Plavix for these patients, or consider using other anti-platelet medications. Tests are available to assess CYP2C19 genotype to determine if a patient is a poor metabolizer.
Patients should not stop taking Plavix unless told to do so by their health care professional. They should talk with their health care professional if they have any concerns about Plavix.
Plavix is made under a Bristol-Myers Squibb - Sanofi Pharmaceuticals partnership.
For information: FDA Drug Safety Communication: Reduced effectiveness of Plavix (clopidogrel) in patients who are poor metabloizers of the drug http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm203888.htm
The loss-of-function CYP2C19*2 genotype is common in diverse populations. In white populations, approximately 24% have at least 1 CYP2C19*2 allele. The frequency of this allele is somewhat lower in Mexican Americans ( 18% with at least 1 CYP2C19*2 allele), higher in African Americans ( 33% with at least 1 copy), and markedly higher in Asian populations ( 51% with at least 1 copy).36-38 Thus, clopidogrel resistance due to this variant may be particularly important in Asian and African American populations. However, the strength of effect of CYP2C19*2 genotype on clopidogrel response may depend on other factors such as genetic background or environmental exposures, which may differ among ethnic groups. Unfortunately, our sample size was not sufficient to examine ethnicity-specific differences in CYP2C19 genotype effects on clopidogrel response. Additional studies in diverse populations will be necessary.
FDA Drug Safety Communication: Reduced effectiveness of Plavix (clopidogrel) in patients who are poor metabolizers of the drug
Safety Announcement
Additional Information for Patients
Additional Information for Healthcare Professionals
Data Summary
Safety Announcement
[03-12-2010] The U.S. Food and Drug Administration (FDA) has added a Boxed Warning to the label for Plavix, the anti-blood clotting medication. The Boxed Warning is about patients who do not effectively metabolize the drug (i.e. “poor metabolizers”) and therefore may not receive the full benefits of the drug.
The Boxed Warning in the drug label will include information to:
Warn about reduced effectiveness in patients who are poor metabolizers of Plavix. Poor metabolizers do not effectively convert Plavix to its active form in the body.
Inform healthcare professionals that tests are available to identify genetic differences in CYP2C19 function.
Advise healthcare professionals to consider use of other anti-platelet medications or alternative dosing strategies for Plavix in patients identified as poor metabolizers.
Plavix is given to reduce the risk of heart attack, unstable angina, stroke, and cardiovascular death in patients with cardiovascular disease. Plavix works by decreasing the activity of blood cells called platelets, making platelets less likely to form blood clots.
For Plavix to work, enzymes in the liver (particularly CYP2C19) must convert (metabolize) the drug to its active form. Patients who are poor metabolizers of the drug, do not effectively convert Plavix to its active form. In these patients, Plavix has less effect on platelets, and therefore less ability to prevent heart attack, stroke, and cardiovascular death. It is estimated that 2 to 14% of the population are poor metabolizers; the rate varies based on racial background.
Healthcare professionals should be aware that a subgroup of patients are poor metabolizers and do not metabolize Plavix effectively; this can result in reduced effectiveness of Plavix. Healthcare professionals should consider use of other anti-platelet medications or alternative dosing strategies for Plavix in these patients.
Patients should not stop taking Plavix unless told to do so by their healthcare professional. They should talk with their healthcare professional if they have any concerns about Plavix, or to find out if they should be tested for being a poor metabolizer.
In May 2009, FDA added information about poor metabolizers of Plavix to the drug label. However, based on additional data reviewed by the agency (see Data Summary below) the Boxed Warning is now being added to highlight the reduced effectiveness of Plavix in these patients and to recommend that healthcare professionals consider use of other anti-platelet medications or alternative dosing strategies for Plavix in patients identified as poor metabolizers.
Additional Information for Patients
Patients currently taking Plavix should:
Be aware that some patients do not convert Plavix to its active form as well as other patients. These patients may not get the same benefit from Plavix and are known as poor metabolizers.
Not stop taking Plavix unless told to do so by their healthcare professional.
Talk with their healthcare professional if they have any concerns about Plavix.
Talk with their healthcare professional to see if testing to determine their metabolizer status is appropriate.
Additional Information for Healthcare Professionals
FDA recommends that healthcare professionals should:
Be aware that some patients may be poor metabolizers of Plavix. They do not effectively convert Plavix to its active form because of low CYP 2C19 activity.The effectiveness of Plavix as a preventive therapy is reduced in these patients.
Be aware that tests are available to determine patients’ CYP2C19 status.
Consider use of other anti-platelet medications or alternative dosing strategies for Plavix in patients who have been identified as poor metabolizers.
Be aware that although a higher dose regimen (600 mg loading dose followed by 150 mg once daily) in poor metabolizers increases antiplatelet response, an appropriate dose regimen for poor metabolizers has not been established in a clinical outcome trial.
Review the newly approved Plavix drug label for complete information on the use of Plavix
Data Summary
The liver enzyme CYP2C19 is primarily responsible for the formation of the active metabolite of Plavix. Pharmacokinetic and antiplatelet tests of the active metabolite of Plavix show that the drug levels and antiplatelet effects differ depending on the genotype of the CYP2C19 enzyme. The following represent the different alleles of CYP2C19 that make up a patient’s genotype:
The CYP2C19*1 allele has fully functional metabolism of Plavix.
The CYP2C19*2 and *3 alleles have no functional metabolism of Plavix. These two alleles account for most of the reduced function alleles in patients of Caucasian (85%) and Asian (99%) descent classified as poor metabolizers.
The CYP2C19*4, *5, *6, *7, and *8 and other alleles may be associated with absent or reduced metabolism of Plavix, but are less frequent than the CYP2C19*2 and *3 alleles.
A patient with two loss-of-function alleles (as defined above) will have poor metabolizer status.
The pharmacokinetic and antiplatelet responses to Plavix were evaluated in a crossover trial in 40 healthy subjects. Ten subjects in each of the four CYP2C19 metabolizer groups (ultrarapid, extensive, intermediate and poor) were randomized to two treatment regimens: a 300 mg loading dose followed by 75 mg per day, or a 600 mg loading dose followed by 150 mg per day, each for a total of 5 days. After a washout period, subjects were crossed over to the alternate treatment. Decreased active metabolite exposure and decreased platelet aggregation were observed in the poor metabolizers compared to the other groups. When poor metabolizers received the 600 mg loading dose followed by 150 mg daily, active metabolite exposure and antiplatelet response were greater than with the 300 mg/75 mg regimen. Healthcare professionals should note that an appropriate dose regimen for patients who are poor metabolizers has not been established in clinical outcome trials.
its the only drug with the name ‘dog’ in its name.
ping
I picked up a re-fill prescription for plavix today. Thirty (30) tablets for $172.72 at a Wal-Mart pharmacy!!! That is $5.757 per tablet!!! The pharmaceutical house has requested an extension on their patent. Maybe by the time generics can be sold, 30 plavix tables will cost patients $20.00 per tablet!! I take plavix because I had a triple by-pass and am allergic to aspirin, so need it to keep red cells from sticking together to form clots. And that is only ONE of twelve prescribed medications. Yes, I have prescription insurance, but that is expensive too. With Obama’s health care I probably won’t need medicine because everyone like me will be dead.
Under obamacare you’ll get aspirin and LIKE IT!
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