The goal of pharmacogenetic testing is to use a patient’s genetic profile to predict a drug’s efficacy, guide drug dosing and reduced adverse reactions. The Food and Drug Administration (FDA) recognizes the importance of pharmacogenetic information when deciding appropriate treatments for patients have included this information in the labeling for over 100 drugs [1].
Available Pharmacogenetic Tests
CYP2C19/Clopidogrel
Clopidogrel is an antiplatelet drug commonly prescribed following percutaneous coronary intervention (PCI). Patients with genetic variants that results in reduced function of CYP2C19 have lower exposure to the active metabolite of clopidogrel, decreased antiplatelet response and greater cardiovascular event rates following a coronary stent procedure than patients with normal CYP2C19 function [2,3].
Interpretation of Results
The Clinical Pharmacogenetic Consortium (CPIC) provides guidance on interpretation of pharmacogenetic test results into drug treatment decisions [4]. Table 1, based on published CPIC guidelines, provides recommendations for antiplatelet drugs according to the CYP2C19 genotype [5].
Table 1. Antiplatelet Therapy Recommendations Based on CYP2C19 Genotype
| Genotype |
Phenotype |
Description |
Treatment |
CYP2C19
*1/*1
|
Normal metabolizer |
Two normal function alleles |
Clopidogrel (Plavix) 75 mg per day |
CYP2C19
*1/*17 |
Rapid metabolizer |
One normal function and one increased function allele |
Clopidogrel (Plavix) 75 mg per day |
CYP2C19
*17/*17 |
Ultra-rapid metabolizer |
Two increased function alleles |
Clopidogrel (Plavix) 75 mg per day |
CYP2C19
*1/*2 |
Intermediate metabolizer |
One normal function allele and one no function allele |
Prasugrel (Effient) 10 per day
Or Ticagrelor (Brilinta) 90 mg twice daily
See contraindications (Table 2) |
CYP2C19
*1/*3 |
Intermediate metabolizer |
One normal function allele and one no function allele |
Prasugrel (Effient) 10 per day
Or Ticagrelor (Brilinta) 90 mg twice daily
See contraindications (Table 2) |
CYP2C19
*2/*17 |
Intermediate metabolizer |
One increased function allele and one no function allele |
Prasugrel (Effient) 10 per day
Or Ticagrelor (Brilinta) 90 mg twice daily
See contraindications (Table 2) |
CYP2C19
*3/*17 |
Intermediate metabolizer
|
One increased function allele and one no function allele |
Prasugrel (Effient) 10 per day
Or Ticagrelor (Brilinta) 90 mg twice daily
See contraindications (Table 2) |
CYP2C19
*2/*2 |
Poor metabolizer |
Two no function alleles |
Prasugrel (Effient) 10 per day
Or Ticagrelor (Brilinta) 90 mg twice daily
See contraindications (Table 2) |
CYP2C19
*3/*3 |
Poor metabolizer |
Two no function alleles |
Prasugrel (Effient) 10 per day
Or Ticagrelor (Brilinta) 90 mg twice daily
See contraindications (Table 2) |
CYP2C19
*2/*3 |
Poor metabolizer |
Two no function alleles |
Prasugrel (Effient) 10 per day
Or Ticagrelor (Brilinta) 90 mg twice daily
See contraindications (Table 2) |
Please consider all clinical contraindications before prescribing prasugrel or ticagrelor (Table 2).
Table 2. Clinical Contraindications to Prasugrel or Ticagrelor
| Prasugrel |
Ticagrelor |
- Do not use prasugrel in patients with active bleeding or a history of transient ischemic attack or stroke.
- Individual risks/benefits of prasugrel must be carefully considered in patients over age 75.
- Do not start prasugrel in patients likely to undergo urgent coronary bypass graft surgery (CABG).
- Consider prasugrel 5 mg per day for patients <60 kg.
|
- Do not use ticagrelor in patients with active bleeding or a history of transient ischemic attack or stroke.
- Do not start ticagrelor in patients likely to undergo urgent coronary bypass graft surgery (CABG).
- Do not use maintenance aspirin dose above 100 mg in combination with ticagrelor.
- Avoid with strong CYP3A inhibitors or inducers.
|
References
- United States Food and Drug Administration. Table of pharmacogenomics biomarkers in drug labels. Table of Pharmacogenomic Biomarkers in Drug Labeling Accessed March 9, 2016.
- Shuldiner AR, O'Connell JR, Bliden KP, Gandhi A, Ryan K, Horenstein RB, et al. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA. 2009; 302 (8):849-857.
- Mega JL, Simon T, Collet JP, Anderson JL, Antman EM, Bliden K, et al. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA. 2010; 304 (16):1821-1830.
- CPIC: Clinical pharmacogenetics implementation consortium. Clinical Pharmacogenetics Implementation Consortium (accessed March 8, 2016).
- Scott SA, Sangkuhl K, Stein CM, Hulot JS, Mega JL, Roden DM, et al. Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C19 Genotype and Clopidogrel Therapy: 2013 Update. Clin Pharmacol Ther (CPIC Update). 2013; 94 (3):317-323.
Additional Resources
- The Pharmacogenomics Knowledgebase. https://www.pharmgkb.org/
- Vanderbilt University. Drug Genome Interactions (DGIs)
- Mayo Clinic. DRUG-GENE TESTING
- St. Jude’s Children’s Research Hospital. Clinical Pharmacogenetics at St. Jude