Pharmacogenomic Testing Optimizes Patient Outcomes

JUNE 03, 2016
In daily clinical assessments and decisions, dosage adjustments are made based on renal function, hepatic function, and other clinical parameters. However, a patient’s genetic makeup isn’t usually considered in dosing or therapy recommendations because that information isn’t normally available.
 
But, what if we were provided that information? Could we use it to optimize treatment?

Pharmacogenomics is the study of how genes affect a person’s response to drugs.1 Treatment recommendations are always patient-specific, so why not take the patient’s genetic profile into consideration to make the best possible selection? 
 
Pharmacogenomics is very important to understand because it can optimize patient care. However, the cost of pharmacogenomic testing may hinder the process of providing this care. Further research on the testing’s clinical validity and utility could help improve patient care and outcomes.
 
Because the metabolism of medications differs from patient to patient, there’s always some degree of uncertainty in terms of whether a medication with a proven indication will provide optimal benefits to a patient. A patient’s race or ethnicity can also play a role in a medication’s metabolism rate. One patient may require a higher dose of a medication to obtain the same results as another patient taking a lower dose. 
 
For instance, dosing requirements for warfarin in anticoagulation are higher for African-Americans than Caucasians, while those of Asian descent require lowering dosing of warfarin than Caucasians. The enzyme involved in warfarin metabolism is CYP2C9, and deviations of CYP2C9 genotypes are associated with increased risk of hemorrhaging.2 Each race has various enzymes that differ in performance levels. 

As an another example, clopidogrel, which is commonly prescribed for acute coronary syndrome, myocardial infarction, or stroke, is metabolized through CYP2C19, and the FDA recommends genetic testing prior to prescribing the drug to determine whether the patient is a poor CYP2C19 metabolizer. Because clopidogrel relies on activation of an active metabolite through CYP2C19, patients who have a loss of function allele of the CYP2C19 enzyme are more likely to experience cardiovascular events than those with a normal functioning CYP2C19 enzyme.
 
In situations dealing with the cardiovascular system, it’s important to provide the patient with the best therapy. Therefore, performing pharmacogenomic testing before prescribing clopidogrel could potentially save a patient’s life.

Finally, carbamazepine (Tegretol), which is commonly prescribed for epilepsy, requires genetic testing for the presence of HLA-B*1502 allele prior to its use.3 Patients with ancestry of Asian descent are more likely to have this allele, so it’s highly recommended that this population receives pharmacogenetic testing, as anyone with the allele is at increased risk for Steven-Johnson syndrome or other hypersensitivity reactions with the use of carbamazepine. 

Those are just a few of the medications that require or are recommended for genetic testing. Sometimes, it’s impossible to know whether a certain medication is appropriate for a particular patient. The medication may treat the indication that it’s approved for, but it may not be safe or effective in all patient populations.
 
Pharmacogenomic testing can help provide additional information that will be beneficial for patients and the pharmacist making drug therapy recommendations.
 
References
1. National Library of Medicine. What is pharmacogenomics? Genetics Home Reference. ghr.nlm.nih.gov/primer/genomicresearch/pharmacogenomics. Published May 31, 2016. Accessed June 1, 2016.
2. SU Yasuda, L Zhang, S-M Huang. The role of ethnicity in variability in response to drugs: focus on clinical pharmacology studies. Clin Pharmacol Ther. 2008 Sep;84(3):417-23. doi: 10.1038/clpt.2008.141. Epub 2008 Jul 9.
3. FDA label information for carbamazepine and HLA-B. PharmGKB. pharmgkb.org/view/drug-label.do?id=PA166104780. Updated March 21, 2016. Accessed May 28, 2016. 


Shivam Patel, Pharm.D.
Shivam Patel, Pharm.D.
Dr. Shivam Patel has graduated from Lake Erie College of Osteopathic Medicine (LECOM) School of Pharmacy with a Doctor of Pharmacy degree. He is a PGY1 Pharmacy Resident at Martinsburg VA Medical Center. His professional interests include critical care, infectious disease, and ambulatory care. After completion of his PGY1 residency, Dr. Patel hopes to continue to serve veterans and become a Clinical Pharmacy Specialist.
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