“Kate” greeted me with a pleasant but constrained smile. Her hands tightly clenched her black purse. Although she was courteous, I sensed she was anxious, confused or both.
Kate, a 41-year-old software engineer, had come to see me about her pharmacogenomic test results. She was referred to Mayo Clinic’s Center for Individualized Medicine by her primary care physician because she’d had bad reactions to multiple medications. These reactions started in her 20s but became more frequent and intense over the years. In addition, she started taking omeprazole (Prilosec), a medication for acid reflux, but felt it was not helping her symptoms. She often had to take double the recommended dose.
As a clinical pharmacist with expertise in pharmacogenomics, I often see patients like Kate. And she’s not alone in her uncertainty and confusion about how pharmacogenomics can help her.
What is pharmacogenomics?
Pharmacogenomics — also known as pharmacogenetics or PGx — uses your genetics to help predict the way you will react to a drug. It combines the sciences of pharmacology (study of drugs) and genetics (study of DNA).
Deoxyribonucleic acid (DNA) is responsible for traits such as height, eye color and susceptibility to disease. These traits are passed on through genes. Humans have over 20,000 genes. People typically inherit two copies of each gene: one copy from each parent. Genes give instructions to make proteins, also known as enzymes, which serve many functions. For example, the CYP2D6 gene makes the CYP2D6 enzyme that breaks down some commonly used drugs such as antidepressants, blood pressure medications and pain medications.
Almost 99% of genes are identical among all people. However, that 1% difference in the form of gene variations is what makes each person unique. It also means that a drug can affect each of us differently.
PGx studies these variations and their impact on drug metabolism and efficacy. With a simple cheek swab or blood draw, medical experts can look at genes associated with drug responses to help predict how you may react to a drug. PGx can also tell you if you are at risk of serious drug reactions.
There are currently about 200 drugs with pharmacogenomics information in their Food and Drug Administration (FDA) drug label. This number is expected to rise because almost every new drug that enters the market goes through pharmacogenetic studies.
Why is pharmacogenomics important?
People react differently to drugs, partly due to their genetics. Have you or someone you know taken a correctly prescribed medication that was not a good fit? This may mean:
- Severe or intolerable side effects. Some people experience side effects so severe they have to stop taking a drug. Women are at especially increased risk due to biological differences that impact how a drug is metabolized, distributed and eliminated. This can make women more susceptible to increased levels of drugs in their bodies, which is linked to more side effects. It is never a good day when a patient tells me that the side effects of a medication are worse than the disease symptoms!
- Drugs not working as well. Some people may report limited benefits from their medications — like Kate with omeprazole.
- Death. Did you know that adverse drug events are the fourth-leading cause of death in the U.S.? Studies estimate that over 100, 000 patients die every year from serious adverse drug reactions.
PGx can reduce the risk of bad reactions by helping predict how people will respond to a drug even before they take it. Consider these examples:
- Testing HLA genes can identify those at risk of drug hypersensitivity reactions to medications such as the HIV drug abacavir (Ziagen) and the anti-seizure medications carbamazepine (Carbatrol, Equetro, others) and phenytoin (Dilantin).
- Testing the CYP2D6gene can predict whether the pain relievers tramadol (ConZip, Qdolo, Ultram) and codeine and the breast cancer drug tamoxifen (Soltamox) will work for you or produce intolerable side effects.
- Testing the CYP2C19 gene can predict whether the antidepressant citalopram (Celexa), the blood-thinning medication clopidogrel (Plavix) and the acid-reducing medication omeprazole (Prilosec) will work for you or produce intolerable side effects.
How does pharmacogenomics testing work?
Most testing requires either a cheek swab or a blood draw. If you elect cheek swab testing, be sure to avoid putting anything in your mouth, including tobacco, smoking, chewing gum, liquids, foods or medications, for at least 30 minutes before the swab. If you’re giving a blood sample, these rules do not apply.
Once the results are back, you may meet with a pharmacist or a physician trained in pharmacogenomics to help interpret the results in the context of your medications or conditions.
Insurance companies have gotten better about covering the cost of PGx, but I advise you to check your insurance before testing. Some people hesitate to get PGx testing for fear of being discriminated against by their health insurance companies or employers. The Genetic Information Nondiscrimination Act, passed in 2008, prevents such discrimination. However, it does not apply to military insurance or to life, long-term care or disability insurance.
What about Kate? Her PGx testing showed her to be a CYP2D6 poor metabolizer, which meant she could not metabolize many drugs. This shed light on why she reacted badly to metoprolol extended release (Toprol-XL) for blood pressure and to certain antidepressants. Simply put, they remained longer in her body, causing concerning side effects. Interestingly, Kate was also a CYP2C19 rapid metabolizer, which meant she was clearing omeprazole from her body faster than is typical, so it could not work as long. We recommended that she switch to esomeprazole (Nexium). A couple of weeks later, she was happy to report that her symptoms were better.
To learn more about pharmacogenomics testing, visit https://www.cdc.gov/genomics/disease/pharma.htm.
