Patient Engagement May Help Prevent Drug Interactions, Related Opioid Overdoses

Patient engagement can support pharmacists in discovering a wider range of potential drug interactions while promoting medication safety.

Sixty two percent of adults report currently taking prescription medicine and a quarter note they take at least 4 prescription medicines, according to a KFF Health Tracking Poll.1 When patients take multiple medications, the drugs can interact in unintended ways. These interactions may result in a range of negative consequences, from falls to inadequate drug efficacy.

Drug interactions are a common problem. In our study published in The American Journal of Managed Care, pharmacists noted 9716 drug interactions among 36,455 medication-related problems.2 In fact, “drug interaction” was the most prevalent medication-related problem for several drugs, including atorvastatin (Lipitor), metoprolol, warfarin, and simvastatin, as well as others.2

These drug interactions can be one-to-one or can include interactions between several medications simultaneously. For example, if a patient takes 3 or 4 medications that cause sedation, the total sedative burden could spur negative outcomes, such as falls, which can lead to broken bones and surgeries.

It’s also important to consider how certain drugs work in the body. To work as intended, common opioids, such as hydrocodone, oxycodone, codeine, and tramadol, must be metabolized by the enzyme cytochrome P450 2D6 (CYP2D6). Other medications such as bupropion, fluoxetine, and duloxetine also need this enzyme, and they can take priority over the opioids. For this reason, hydrocodone, oxycodone, codeine, or tramadol could fail to be properly metabolized when taken with these other medications that could take priority during CYP2D6 metabolization.

Furthermore, taking a higher dose of the opioid would not solve the underlying problem relating to its metabolism by CYP2D6, as bupropion, fluoxetine, or duloxetine will continue to impact the opioid’s successful metabolism. However, if the patient stops taking bupropion, fluoxetine, or duloxetine, the enzyme will begin to metabolize the opioid. In this situation, a higher dose of the opioid could cause an unintended overdose.

Our research published in the Journal of Personalized Medicine demonstrates some of the potential impacts of drug interactions on opioid intake. The findings compared opioid intake for patients who took at least 1 of the common opioids mentioned (hydrocodone, oxycodone, codeine, and tramadol) plus at least 1 additional drug that also needs the CYP2D6 enzyme versus patients who took at least 1 of the opioids without any additional CYP2D6 interacting drugs. The results show the former generally had a larger average daily opioid intake.3

While enzymes can play a role in drug interactions, so can over-the-counter medications, supplements, and herbals. Prilosec, a common over-the-counter medication, serves as an example. It prevents the body from activating Plavix, a blood thinner.

For these reasons, pharmacists’ engagement with patients is key. Not only is it necessary to determine which over-the-counter medications, supplements, and herbals a patient takes, but it can support interventions as well.

In our study in The American Journal of Managed Care, the results demonstrated that pharmacists could recommend patients change the time of medication intake in response to over half the 9716 drug interactions noted.2 While shifting a medication to a different time of day may seem like a trivial change, it could be a significant adjustment for a patient, especially if they are in the habit of taking all their medications at a specific time of day. Patient engagement can help pharmacists recognize and address this potential issue.

When pharmacists engage with patients, the impact can be incredible. Pharmacists can get a more complete picture of potential drug interactions and ensure recommendations align with patients from an adherence perspective. The end result is greater attention to medication safety.

About the Author

Jacques Turgeon, BPharm, PhD, is chief scientific officer of Tabula Rasa HealthCare (TRHC) and CEO of TRHC’s Precision Pharmacotherapy Research and Development Institute. Throughout his career, he has authored over 150 peer-reviewed articles. His expertise includes the cytochrome P450 system, the role of pharmacogenetics in cardiovascular drug actions, drug-induced Long QT syndrome, and the development of clinical decision support systems and medication risk scores.


  1. Hamel L, Lopes L, Kirzinger A, et al. Public opinion on prescription drugs and their prices. Published October 18, 2021. Accessed December 29, 2021.
  2. Bankes D, Pizzolato K, Finnel S, et al. Medication-related problems identified by pharmacists in an Enhanced Medication Therapy Management model. Am J Manag Care. 2021;27(suppl 16):S292-S299. doi:10.37765/ajmc.2021.88754
  3. 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