Improve Pain Management With Precision Pharmacotherapy

In 2020, according to the CDC, an average of 44 people died every day from overdoses involving prescription opioids.¹ Opioid overdoses can result from a variety of factors, including adverse drug events caused by drug-gene or multi–drug-gene interactions. Traditional trial-and-error prescribing leaves patients vulnerable to these interactions, but personalized, precision pharmacotherapy can improve clinicians’ ability to identify risk and prevent medication-related harm.

Precision pharmacotherapy incorporates pharmacogenomic (PGx) testing and advanced medication decision support tools that provide simultaneous multidrug analyses. PGx testing identifies an individual’s genotype, which provides insight into how the individual might respond to certain medications based on their genes.

According to the CDC, the most commonly prescribed opioids include hydrocodone, oxycodone, oxymorphone, morphine, codeine, fentanyl, hydromorphone, tapentadol, and methadone.² Some of these opioids must be metabolized to be transformed into more active metabolites so they can provide pain relief. One example is the metabolism of hydrocodone through the enzyme CYP2D6. An individual’s genetic makeup determines their CYP2D6 metabolism, and they can be a poor, intermediate, normal, or ultra-rapid metabolizer.

With poor or intermediate metabolizers, the opioids might not become fully activated in the body and individuals may continue to experience pain. These individuals might be prescribed a higher dosage of the opioids, but this will not change their CYP2D6 metabolism, and the opioids will continue to move through the body without becoming fully activated. In addition to providing limited or no pain relief, higher doses of the opioids could lead to worsened side effects, heightened risk for toxicities, and even unintentional overdoses. Ultra-rapid metabolizers can also experience adverse drug events related to opioid-gene interactions.³ Ultra-rapid metabolizers produce more active metabolites and, as a result, may encounter heightened risk for toxicities.

In addition to genes, opioid-related interactions can involve other medications. For example, when normal metabolizers of CYP2D6 take hydrocodone with certain other medications, they can function as poor metabolizers. PGx testing paired with pharmacist-driven simultaneous multidrug analysis can shed light on multi–drug-gene interactions. Simultaneous multidrug analysis looks at 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 insight into a patient’s risk of adverse drug events and how they can be prevented.

Research published in the Journal of Personalized Medicine highlights medications that interact with CYP2D6 that were most frequently prescribed with common opioids. Some medications included in the study, such as orphenadrine, terbinafine, and amiodarone, prevent CYP2D6 metabolism. Other medications, like bupropion, fluoxetine, and aripiprazole, take priority for CYP2D6 metabolism, blocking the opioids from transforming into active metabolites and providing pain relief.⁴ The research results show that participants who took at least 1 common opioid and at least 1 medication that interacts with CYP2D6 had a higher risk of adverse drug events compared with participants who took at least 1 opioid but no interacting medication.⁴ Those with at least 1 potential opioid-related multidrug interaction also had a higher average daily dosage of opioids and higher average yearly medical costs ($7841 vs $5625).⁴

By using pharmacogenomic testing with advanced medication decision support tools that provide simultaneous multidrug analysis, pharmacists can not only evaluate how a patient might metabolize opioids according to their genotype, but they can also examine how other medications might further impact this metabolism. Given this insight, pharmacists can alert prescribers to potential risk before patients take a new medication, eliminating trial-and-error prescribing and reducing multi–drug-gene interactions that can lead to inadequate pain relief or other adverse drug events, such as unintentional overdoses. As a result, pharmacists, with the help of advanced medication decision support, can play a critical role in reducing unintended overdoses from prescription opioids.

Reference

1. Prescription opioid overdose death maps. Centers for Disease Control and Prevention. Reviewed June 6, 2022. Accessed September 22, 2022. https://www.cdc.gov/drugoverdose/deaths/prescription/maps.html

2. Get informed. Centers for Disease Control and Prevention. Reviewed May 24, 2022. Accessed September 30, 2022. https://www.cdc.gov/rxawareness/information/index.html

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. Use of drug claims data and a medication 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 chief operating officer of Tabula Rasa HealthCare’s Precision Pharmacotherapy Research and Development Institute. She has published over 70 peer-reviewed journal articles and her research includes drug-metabolizing enzymes, the role of pharmacogenomics, and drug-drug interactions.