Recommendations for cardiovascular indications were clear, concise, and given with a ‘strong’ classification; clopidogrel should be avoided in intermediate or poor CYP2C19
Individuals may be classified as poor, intermediate, extensive, or ultrarapid metabolizers, based on whether they carry wild type or polymorphic CYP2C19 alleles
In white participants, those with CYP 2C19 intermediate or poor metabolizer status had higher odds of recurrent stroke (odds ratio 5
The bioavailability of active clopidogrel in poor metabolizers is very low
This active thiol metabolite inhibits adenosine diphosphate (ADP)-induced platelet aggregation by blocking the platelet P2Y 12 receptor, resulting in
If the genotype is *17*17, and/or *1*17, (known as ultra-metabolizer),11 a higher drug metabolite level is expected, and consequently a lower clopidogrel dose is indicated, whereas if the genotype has one allele *17 or *1 in combination with *2 or *3 (which are known as intermediate metabolizers) a lower drug metabolite level is
Rapid metabolizers – These patients have slightly higher CYP2C19 function compared to normal
The poor metabolizer (PM, 2 LOF alleles) and intermediate metabolizer (IM, one LOF allele) phenotypes were assigned in accordance with CPIC guidelines
19 [95% CI 1
Adjustments to citalopram or escitalopram therapy are not warranted based on CYP2C19 status for those who are CYP2C19 extensive metabolizers
The CYP2C19 (sounds like “sip-2-see-19”) gene encodes the CYP2C19 enzyme, which is a member of the cytochrome P450 enzyme family
Some people have CYP2C19 enzyme that does not work well (Intermediate and Poor Metabolizers) while others have CYP2C19 enzyme that works better than average
Normal (Extensive) Metabolizer Normal metabolizers effectively convert the drug to an active metabolite
The CYP2C19 gene is important in how your body responds to medications and breaks down toxins
The prevalence of poor metabolizers carrying 2 CYP2C19 loss-of-function alleles is 13%, which is higher than that in previously studied European (2
CYP2C19 intermediate and poor metabolizers who receive clopidogrel experience an increased risk for major adverse cardiovascular and cerebrovascular events
08 to 24
10 A meta-analysis demonstrated that poor metabolizers receiving clopidogrel had an HR of 3
Antidepressants, amitriptyline, clomipramine, doxepin, imipramine, trimipramine, clopidogrel, voriconazole, proton pump inhibitors Created Date: 9/21/2016 12:05:23 PM However, in the CHANCE trial, the rate of stroke was 9
About 3% of Caucasians exhibit a CYP2C19 PM phenotype, whereas the frequency is much higher in Asians, e