CYP2C19 and Clopidogrel (Plavix®) Response
What is clopidogrel (Plavix®)?
Clopidogrel, sold under the brand name Plavix®, is an anti-platelet
medication that prevents platelets, a type of cell found in the blood, from sticking
together. When platelets stick together they can form clots which block the flow
of blood.
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Clopidogrel
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Plavix®
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Image from: www.drugs.com
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Plavix® is prescribed for any of the following reasons:
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To prevent strokes and heart attacks in people at increased risk due to:
° hardening of the arteries (also called atherosclerosis)
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° narrowing of the arteries outside the heart such as arteries in the pelvis
and legs (also called peripheral artery disease)
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° sudden, reduced blood flow to the heart (also called acute coronary syndrome)
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° a recent heart attack or stroke.
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To reduce the risk of blood clots in people who:
° are having a coronary artery stent placed
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° have an artificial heart valve
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° have mitral valve disease (a condition that affects the control of blood
flow between the top and bottom chambers of the left side of the heart).
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Plavix® is the 3rd most commonly prescribed brand name drug, with
over 25 million prescriptions written in the year 2009.1
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Plavix® is a brand name for the drug clopidogrel bisulfate.
Other brand names of this drug include: Clopilet® and Ceruven®
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What is CYP2C19?
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Some medications are metabolized (broken down or activated) by enzymes. Variants
in the genes coding for these enzymes may cause your body to metabolize a medication more quickly or more
slowly than normal. These variants can affect how well the medication works, and
the risk of side effects. CYP2C19 is a gene that contains the instructions for making
an enzyme which metabolizes many different types of drugs. Some examples of drugs
that are affected by CYP2C19 include the anti-platelet drug clopidogrel and the
anti-ulcer, proton pump inhibitor drug, omeprazole, commonly known as Prilosec.
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For CYP2C19 and many other genes involved in drug response, there are multiple genetic
variants that impact the way the body responds to a drug.
Your response to clopidogrel is determined by your specific combination
of genetic variants, not simply by the number of variants that you have. Each combination
of genetic variants in or near a gene is called a “haplotype”. There can be many
different combinations of variants for each gene. To distinguish one combination
of variants from another, scientists sometimes use a numbering system. For example:
one combination of variants within the CYP2C19 gene may be called “star 2”, written
as *2, while another combination is *1.
Since we have two copies of each gene, one from our mother and one from our father,
each person will have a combination of variants (called a haplotype) from each parent.
When genetic testing is performed the results are noted as two numbers (one representing
each combination of variants in that gene), separated by a slash. For example, someone
who inherited the combination of variants from their mother known as *2 and the
combination known as *3 from their father would be a *2/*3 for the gene tested.
Some people have combinations of variants that are rare and have not been studied
or named. Sometimes, the genetic test that is performed cannot determine a person’s
result with certainty.
Different combinations of variants in the CYP2C19 gene can be used to predict how
a person will respond to a particular drug, like clopidogrel. A person’s predicted
response, called a “metabolizer type” is based on the two CYP2C19 haplotypes they
inherited from their parents.
CYP2C19 metabolizer status categories and predicted response to clopidogrel:
Reduced CYP2C19 activity
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Poor Metabolizer
Not likely to receive full benefit of clopidogrel. Increased
risk for heart attack and stroke.
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Intermediate Metabolizer
May not receive full benefit of clopidogrel. Possible increased risk for heart attack and stroke.
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Typical CYP2C19 activity
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Extensive Metabolizer
Expected to benefit from standard clopidogrel dose.
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Increased CYP2C19 activity
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Ultra-Rapid Metabolizer
Expected to process medication more quickly. Possible
increased benefit. Possible increased risk for bleeding.
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Uncertain CYP2C19 activity
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Metabolizer Status Uncertain
Not enough data to determine clopidogrel response.
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In some cases the expected response to clopidgrel is not known and cannot be predicted.
In some cases the expected genetic testing provides enough information to determine
the general response category (e.g. reduced activity) but the specific metabolizer
type cannot be predicted.
The frequency of each metabolizer group can be different in each racial or ethnic
group. Your personal CPMC results will show how common each metabolizer group is
in your racial or ethnic group. You can view this information in your personal report
by clicking on the ABOUT tab and then the HOW COMMON tab. Information is not available
for all racial or ethnic groups. If data is not available for your race or ethnicity
your report will include information for the Caucasian population.
Example:
Are there other factors that can affect how clopidogrel (Plavix®)
works?
Many factors affect how your body will respond to a medication. Non-genetic factors
include interactions between different drugs you may be taking, interactions between
drugs and your medical history, and interactions between drugs and your lifestyle.
Some drugs (both prescription and over the counter) may decrease the effect of clopidogrel
or increase the risk for side effects.
Talk to your health care provider if you are taking clopidogrel in addition to any
of the following drugs:
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Nonsteroidal anti-inflammatory drugs (NSAIDS). These drugs, commonly prescribed
for analgesic
(pain reducing),
antipyretic (fever-reducing), and anti-inflammatory effects can cause gastrointestinal
bleeding when taken with clopidogrel. Common types of NSAIDS include: aspirin,
ibuprofen (Motrin, Advil), and naproxen (Alleve).
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Proton Pump Inhibitors (PPIs). Commonly used to treat heartburn, peptic ulcers and
other gastrointestinal conditions, PPIs can reduce the effect of clopidogrel, making
it less effective at preventing blood clots. Examples of PPIs include: Prilosec,
Zegerid, and Prevacid.
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Warfarin. When taken in combination with clopidogrel, warfarin (Coumadin) has been
shown to increase the risk for bleeding.
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For a list of medications that interact with clopidogrel, click here.
It is important that you talk to your healthcare providers about all of the medications
(both over-the-counter and prescription) as well as supplements that you are taking,
as they may interact with clopidogrel. Do NOT make any changes to ANY medications
without talking to your healthcare providers.
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There are no known food interactions with clopidogrel.
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Can CYP2C19 affect my response to any other drugs?
In addition to clopidogrel, your genetic results for CYP2C19 can affect your response
to other drugs. Different drugs can be processed in different ways by the body.
Because of these differences, the metabolizer status does not always predict the
same response for all drugs, even when those drugs are metabolized by that same
gene.
Example:
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CYP2C19 metabolizes clopidogrel. Poor metabolizers may not respond to that drug
and may need an alternative treatment.
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CYP2C19 metabolizes many other drugs in addition to clopidogrel. Metabolizer status
for one drug may not predict the same response to other drugs.
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For a list of other drugs that may interact with CYP2C19 click here.
Talk to your healthcare providers about all of the medications (both over the counter
and prescription) as well as any supplements that you are taking.
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What does the CPMC Test for?
The CPMC tests for 8 variants in the CYP2C19 gene. Your personal result will be
displayed in the form of a table on the RESULT tab within your personal report.
Your result interpretation can be found on a separate INTERPRETATION tab.
As you can see from the sample results table below, each variant tested
is listed by its “rs number”, the number used by scientists to name genetic variants.
In the next column of the table you will find your results. Because we have two
copies of every gene, one from mom and one from dad, everyone tested will have two
results, represented by letters (example: CT) for each variant tested. In the last
column, we display the reference value. The reference value shows the result for
someone who is expected to have a normal or ‘typical’ response to clopidogrel. Since
it is your personal combination of variants that is important in interpreting your
results, you will be provided with the common name for your combination of results.
For example, in the sample table below, the combination of variants in the CYP2C19
gene are also referred to as CYP2C19*1/*17. People who have a CYP2C19*1/*17 result
are ultra-rapid metabolizers. For more information on ultra rapid metabolizers and
other CYPC2C19 metabolizer types see “The Impact of CYP2C19 Gene Variants on Clopidogrel
Response” (above).
SAMPLE REPORT:
In addition to the RESULT tab which will show your personal result for each variant
tested, you will be provided with an interpretation (found on the INTERPRETATION
tab). The interpretation will give you information about how your personal result
will impact how your body metabolizes clopidogrel. In some cases this information
will not be known.
SAMPLE REPORT:
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It is important to note that CPMC testing alone cannot fully predict your response
to Plavix® or any other drug. Other factors like body weight, other
health conditions, and other medications may also influence the way a person will
respond to Plavix® and other drugs. It is possible that you may have
other genetic variants that occur in the CYP2C19 gene that are not tested by the
CPMC. Also, it is possible that you may have variants in other genes that influence
your response to Plavix®.
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For More Information?
References
1. http://drugtopics.modernmedicine.com/drugtopics/data/articlestandard/drugtopics/252010/674969/article.pdf
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