Pharmacogenomics is a growing field that examines how one’s genes affect how they respond to medications. A 2021 study found that pharmacogenomic testing, if it had been conducted, would have predicted abnormal responses to medication in 25% of subjects who received a medication. (8)
When medications are not appropriately prescribed, treatment failure (TF) or new medical problems (NMP) can commonly occur. Both TF and NMP originate from non-optimized medication use and cost the United States approximately $290 billion USD or 13% of annualized medical costs. (13)
Given that 90% of the $4.1 trillion USD annualized health costs come from chronic and mental health conditions, (3) and most people require medications to manage their diagnosis, delivery of the right medication at the right dose is critical to improve patient outcomes, support adherence, and decrease medication side effects. (12)
What is pharmacogenomics?
Pharmacogenomics, also called pharmacogenetics, is a field of genetics that examines an individual’s genes and provides information on how their body breaks down or transports different medication. (8)
Individuals receive genes from both their mother and father. Depending on the results of these genes, medications may:
- Cause side effects
- Increase toxicity
- Not have an effect on their condition
How does pharmacogenomics work?
Medications work in three different ways as outlined below.
Binding to the receptor
A receptor acts as a “lock” for your medication “key.” Patients need the right key for the right lock. The medication attaches to the receptor and the effect of the medication is determined by how many receptors the body makes, which comes from DNA instructions.
A common medication class affected by receptor binding is anti-estrogens. (4)
Some medications must be transported into the cell or tissue to work. Individuals range from excellent to poor transport systems. One’s DNA affects these transporters.
A common medication class affected by different medication transporters is statins. (4)
Medication metabolism (breakdown)
All medications must be broken down so the body can eliminate the waste products. Some drugs exert their effect during the metabolism process. If someone breaks their medication down rapidly, they may not have enough medication to target their condition. Others may break down their medication slowly, increasing the chance of side effects or toxicity.
A common medication class affected by drug metabolism is opiates. (4)
Benefits of pharmacogenomics testing
Typical pharmacogenomic testing involves a simple saliva test that will provide information to providers about approximately 44 different drug classes (approximately 130 drugs), which highlighted by both the U.S. Food and Drug Association (FDA) and Clinical Pharmacogenetics Implementation Consortium (CPIC) as medications that either require pharmacogenomic testing or for which testing is highly recommended prior to starting the medication. (2)(6)
Additional benefits include:
- Assisting providers with patients who have polypharmacy
- Helping elderly patients avoid duplicate medication therapy or side effects
- Increasing confidence in selected drug therapy regimens
- Increasing safety and optimization of drug therapy
- Preventing adverse drug interactions (ADRs) caused by gene-drug interactions
In May 2022, Oregon Health and Science Center (OHSU) settled a lawsuit with the family of a man who received capecitabine for bile duct cancer. Because a pharmacogenomic test was not performed, neither the family nor the oncologist knew the husband carried a rare genetic dihydropyrimidine dehydrogenase deficiency (DPD) enzyme deficiency. As a result, the husband could not clear the capecitabine and developed toxic levels, ultimately leading to a painful death. (10)
A large-scale study with close to eight million veterans (VHA) was conducted to determine the utility of pharmacogenomic testing. Researchers estimated that 99% of veterans would have one or more genes that would impact their medication. The most common medications prescribed and under pharmacogenomic control included:
All four of these medications are very commonly prescribed for chronic conditions.
Researchers concluded that “clinically important pharmacogenetic variants are highly prevalent in the VHA population. Almost all veterans would carry an actionable variant, and more than half of the population had been exposed to a drug affected by these variants.” (1)
The largest pharmacogenomic study based on approximately 500,000 individuals found that 99.5% of participants could have an abnormal response to at least one medication from 14 well known CPIC genes, and typically, the average person had an divergent response to 10.3 medications. (8)
Given that the average 65+ year old takes at least five medications or more, the chance they will be prescribed a medication that is affected by pharmacogenomics is high. (5)
A pharmacogenomic test must be ordered through a provider who can prescribe your medications.
The test is typically a saliva test, but some companies still use a blood test.
Reputable U.S. labs that complete clinically based pharmacogenomic testing will be accredited by the College of American Pathologists (CAP) and have Clinical Laboratory Improvement Amendments (CLIA). Some direct-to-consumer testing companies provide pharmacogenomic results; however, unless the results have undergone clinical validation, the results might be false negative or false positive. (9)
Limitations of pharmacogenomic testing
There are some limitations of pharmacogenomic testing to be considered, including:
- Nutrition sufficiency can be key for medication success or minimizing side effects, such as ensuring adequate methylated folate intake to maximize selective serotonin reuptake inhibitor (SSRI) medications. (11)
- Pharmacogenomics plays one component in a medications journey.
- Pharmacogenomics does not look at the role of epigenetics (turning genes on and off). An individual’s environment and thoughts can easily influence medication success or failure (e.g., placebo effect).
- Genes cannot be viewed as an individual instrument but instead as one instrument in an entire orchestra. Genes affect one another and exert their own epigenetic effects.
The bottom line
With the introduction of new legislation in Congress, the “Right Drug Dose Now Act,” (7) pharmacogenomic testing will become more mainstream and may begin to affect standard of care prescribing. Early-adopting clinicians are uniquely positioned to leverage pharmacogenomic testing to bring new and novel testing to their patients leading to improved medication adherence, decreased side effects, and increased patient satisfaction.
Disclosure: This article was written in partnership with ToolBox Genomics. All integration partnerships have been approved by doctors on our Integrative Medical Advisory team, and this content adheres to all guidelines outlined in our content philosophy. Fullscript has not been compensated financially for the publication of this article.
- Catherine Chanfreau-Coffinier, P. D. (2019). Prevalence of actionable pharmacogenetic variants and level A drugs prescribed among US veterans. JAMA Network Open.
- Center for Devices and Radiological Health. (2022). Table of pharmacogenetic associations. U.S. Food and Drug Administration. https://www.fda.gov/medical-devices/precision-medicine/table-pharmacogenetic-associations
- Centers for Disease Control and Prevention. (2022). Health and economic costs of chronic diseases. Centers for Disease Control and Prevention. https://www.cdc.gov/chronicdisease/about/costs/index.htm
- Centers for Disease Control and Prevention. (2022). Pharmacogenomics: What does it mean for your health? Centers for Disease Control and Prevention. https://www.cdc.gov/genomics/disease/pharma.htm
- Charlesworth, C.J., Smit, E., Lee, D.S., Alramadhan, F., Odden, M.C. (n.d.). Polypharmacy among adults aged 65 years and older in the United States: 1988-2010. The journals of gerontology. Series A, Biological sciences and medical sciences.
- Clinical pharmacogenetics implementation consortium. CPIC. (2022). https://cpicpgx.org/
- H.R.6875 – 117th Congress (2021-2022): Right Drug Dose Now 5 Act. (2022). https://www.congress.gov/bill/117th-congress/house-bill/6875/text
- McInnes, G., Lavertu, A., Sangkuhl, K., Klein, T.E., Whirl-Carrillo, M., Altman, R.B. (2020). Pharmacogenetics at scale: An analysis of the UK Biobank. Clinical pharmacology and therapeutics.
- Nicholson, W.T., Formea, C.M., Matey, E.T., Wright, J.A., Giri, J., Moyer, A.M. (2020). Considerations when applying pharmacogenomics to your practice. Mayo Clinic proceedings.
- Oregonian/OregonLive, F. Z. | T. (2022). OHSU to pay $1 million, promises change to settle lawsuit from widow of cancer patient. oregonlive. https://www.oregonlive.com/health/2022/05/ohsu-to-pay-1-million-promises-change-to-settle-lawsuit-from-widow-of-cancer-patient.html
- Papakostas, G.I., Shelton, R.C., Zajecka, J.M., Bottiglieri, T., Roffman, J., Cassiello, C., Stahl, S.M., Fava, M. (2014). Effect of adjunctive L-methylfolate 15 mg among inadequate responders to ssris in depressed patients who were stratified by biomarker levels and genotype: Results from a randomized clinical trial. The Journal of clinical psychiatry.
- Rodis, J., Sevin, A., & Magdi, A. (2017). Improving Chronic Disease Outcomes Through Medication Therapy Management in Federally Qualified Health Centers.
- Watanabe, J. H., McInnis, T., & Hirsch, J. D. (2018). Cost of prescription drug-related morbidity and mortality. The Annals of pharmacotherapy.