Improve pain management with precision pharmacotherapy

Taking advantage of pharmacogenomic evidence, simultaneous analysis of multiple drugs may help prevent drug interactions that affect pain control.

In 2020, according to the CDC, an average of 44 people died every day from prescription opioid overdoses.1 Opioid overdoses can be due to a variety of factors, including adverse events caused by drug-gene or multiple drug-gene interactions. The traditional trial-and-error prescription leaves patients vulnerable to these interactions, but precision-tailored drug therapy can improve clinicians’ ability to identify risks and prevent medication-related harm.

Precision pharmacotherapy incorporates pharmacogenomic (PGx) testing and advanced drug decision support tools that provide simultaneous analysis of multiple drugs. The PGx test identifies an individual’s genotype, which provides information about how the individual might respond to certain medications based on the individual’s genes.

According to the CDC, the most commonly prescribed opioids include hydrocodone, oxycodone, oxymorphone, morphine, codeine, fentanyl, hydromorphone, tapentadol, and methadone.two Some of these opioids must be metabolized into more active metabolites in order to relieve pain. An example is the metabolism of hydrocodone via the CYP2D6 enzyme. An individual’s genetic makeup determines their CYP2D6 metabolism, and they may be a poor, intermediate, normal, or ultra-rapid metabolizer.

With poor or intermediate metabolizers, opioids may not be fully activated in the body and people may continue to experience pain. These people may be prescribed a higher dose of opioids, but this will not change their CYP2D6 metabolism, and the opioids will continue to move through the body without being fully activated. In addition to providing limited or no pain relief, higher doses of opioids may worsen side effects, increase the risk of toxicity, and even unintentional overdose. Ultra-extensive metabolizers may also experience adverse events related to opioid gene interactions.3 Ultra-rapid metabolizers produce more active metabolites and may encounter a higher risk of toxicity as a result.

In addition to genes, opioid-related interactions can involve other medications. For example, when normal CYP2D6 metabolizers take hydrocodone with other medications, they may function as poor metabolizers. PGx testing combined with pharmacist-led simultaneous multidrug testing can shed light on multidrug-gene interactions. Simultaneous multi-drug analysis analyzes an individual’s medication regimen as a whole rather than a series of 1:1 drug interactions. This more comprehensive analysis provides pharmacists with more information about a patient’s risk of adverse drug events and how they can be prevented.

Research published in the Personalized Medicine Journal highlights the drugs that interact with CYP2D6 that are most frequently prescribed with common opioids. Some drugs included in the study, such as orphenadrine, terbinafine, and amiodarone, prevent the metabolism of CYP2D6. Other drugs, such as bupropion, fluoxetine, and aripiprazole, have priority for CYP2D6 metabolism, preventing opioids from being converted to active metabolites and relieving pain.4 Research results show that participants who took at least 1 common opioid and at least 1 CYP2D6-interacting drug were at increased risk of adverse drug events compared to participants who took at least 1 opioid but no interacting drug. .4 Those with at least 1 possible opioid-related multidrug interaction also had higher mean daily dose of opioids and higher mean annual medical costs ($7,841 vs. $5,625).4

Using pharmacogenomic testing with advanced drug decision support tools that provide simultaneous multi-drug analysis, pharmacists can not only assess how a patient might metabolize opioids based on their genotype, but can also examine how other drugs could further affect this metabolism. Given this information, pharmacists can alert prescribers to potential risk before patients take a new medication, eliminating trial-and-error prescribing and reducing multidrug-gene interactions that can lead to inadequate pain relief. or other adverse drug events, such as unintentional overdose. . As a result, pharmacists, with the help of advanced medication decision support, can play a critical role in reducing unwanted overdoses of prescription opioids.


1. Prescription opioid overdose death maps. Centers for Disease Control and Prevention. Reviewed June 6, 2022. Accessed September 22, 2022.

2. Get informed. Centers for Disease Control and Prevention. Reviewed May 24, 2022. Accessed September 30, 2022.

3. Ballinghoff T, Bain KT, Matos A, Bardolia C, Turgeon J, Amin NS. Opioid response in an individual with altered cytochrome P450 2D6 activity: implications of a pharmacogenomics case. Clin Case Rep J. 2020;1(6):1-4. doi:10.2254/au.2020.1596

4. Michaud, V, Bikmetov R, Smith MK, et al. Using drug claims data and a drug risk score to assess the impact of CYP2D6 drug interactions among opioid users on healthcare costs. J Pers Med. 2021;11(11):1174. doi:10.3390/jpm11111174

About the Author

Veronique Michaud, BPharm, PhD, is director of operations for Tabula Rasa HealthCare’s Precision Pharmacotherapy Research and Development Institute. He has published more than 70 articles in peer-reviewed journals and his research includes drug metabolizing enzymes, the role of pharmacogenomics, and drug interactions.

Improve pain management with precision pharmacotherapy

Leave a Reply

Your email address will not be published.

Scroll to top