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Drug Diversion Prevention Beyond Controlled Substance Medications

Problem: While controlled substance medications are most often thought of as being associated with substance use disorder and are the most common targets for diversion detection programs, medication diversion by practitioners can involve non-controlled substances as well. Medications may be targets of diversion for financial gain due to their high value and/or ease and ability to be sold illegally. Another possibility is that they may be diverted for self-use or for family/friends to self-medicate, or for those who cannot afford the cost of these life-saving medications. 

Non-controlled medication targets include high-value medications such as antiretroviral agents and certain cancer medications; performance-enhancing agents like erythropoietin; psychoactive medications (e.g., cyclobenzaprine, QUEtiapine, traZODone); and medications associated with opioid use disorder such as diphenhydrAMINE (to reduce histamine-induced pruritis), ondansetron (to control nausea and vomiting related to opioid withdrawal), and naloxone (in case of an overdose).1-4 

The drug diversion program manager, Mary Nelson, from HonorHealth in Phoenix/Scottsdale, AZ, presented information on this topic during a November 2023 Medication Safety Officers Society (MSOS) member briefing. She noted that organizations often do not include non-controlled substances as part of their diversion detection programs because they may not understand the rationale as to why practitioners may be diverting non-controlled substances, or they might not know how to monitor them. In turn, practitioners may perceive non-controlled medications as easier to divert because they know that most organizations do not have processes in place to monitor them as closely.

Practitioners who divert non-controlled substances may be self-treating medical conditions (e.g., depression, anxiety) or selecting medications that have a synergistic effect to enhance the effect of other drugs (e.g., sedation, euphoria, dissociation). Practitioners may also dilute or swap patients’ controlled drugs for non-controlled drugs (e.g., oxyCODONE for acetaminophen) so that the controlled drugs could be kept for self-use or distribution, or use the non-controlled drug as a substitute for controlled waste adjudication. As a result, patients may experience lapses in care (e.g., untreated pain, therapeutic failure), or suffer harm (e.g., side effects, adverse reactions) from unknowingly receiving medication that was not prescribed. There is also the serious risk of patient harm from receiving substandard care from an impaired practitioner and/or the risk of bloodstream infection from compromised vials and syringes. 

Potential non-controlled substance diversion scenarios 

When reviewing a report that captured medications removed via override in an automated dispensing cabinet (ADC), a pharmacist noticed a trend with injectable diphenhydrAMINE. When a pharmacist investigated further, it was discovered that a specific nurse had several “override canceled” transactions for diphenhydrAMINE that occurred before the start of each shift. The pharmacist and nurse manager reviewed the nurse's transactions via surveillance videos, which showed that the nurse removed a vial with each canceled transaction. The diversion response team was consulted, and the investigation confirmed the nurse was diverting diphenhydrAMINE.

A pharmacy technician could not locate a bottle of oral ondansetron that had been set aside to be placed in unit dose packages. After searching the pharmacy and inquiring with staff, the technician contacted the pharmacy purchaser to order a replacement bottle. The purchaser recalled that this was not the first time ondansetron had been missing and notified the pharmacy manager. Video surveillance revealed that a pharmacist had been diverting the medication for self-use. 

Safe Practice Recommendations: To prevent non-controlled medication diversion, organizations should start by reviewing Part I of our previous publication, Controlled substance drug diversion by healthcare workers as a threat to patient safety, which highlights the widespread scope of diversion in healthcare, barriers to recognition, at-risk behaviors, and other signs associated with possible diversion; and Part II, which includes tools for preventing, identifying, reporting, and responding to diversion. Use this information as a starting point for drug diversion response programs and then incorporate medications beyond controlled substances by considering the following recommendations:

List non-controlled drugs at risk for diversion. Based on your organization’s formulary, an interdisciplinary diversion response team, ideally led by a dedicated diversion officer, should develop a list of non-controlled substances that organizations should monitor or treat similarly to controlled substances (examples in the second paragraph of this article). Use this list to address storage configurations of non-controlled substances at risk of diversion. Consider treating these drugs like controlled substances, requiring a blind count (meaning that staff are not aware of the quantity in the inventory system prior to performing counts).

Monitor pharmacy inventory. Use data from pharmacy inventory management systems and monitor the potential for non-controlled substance diversion within the pharmacy. Consider excessive restocking and unexpected stockouts when monitoring procurement, current inventory, and usage. 

Consider diversion analytics technology. For rapid identification of suspected diversion, consider machine learning diversion monitoring and advanced analytics software programs. These programs use consolidated data sets from multiple informatics technology systems (e.g., ADCs, electronic health records [EHRs], attendance software, inventory systems, wholesalers) to reconcile stock movement and waste documentation, compare clinical data (e.g., pain scores) with dispensing patterns, detect when staff are accessing ADCs in areas where they do not normally work or are not scheduled to work that day, and trend behavior against other users on the same unit. If using diversion analytics technology, include transactions of both controlled and non-controlled substances.

Evaluate the override list. Through the Pharmacy and Therapeutics (P&T) Committee or equivalent interdisciplinary group, review and approve all medications allowed via ADC override, clinical locations where staff can remove the medications via override, practitioner types who can remove medications via override, and associated policies. During the evaluation process, special attention should be paid to medications that are on the organization’s non-controlled substance diversion list. Review the list of medications available by override at least annually and adjust as needed. 

Monitor ADC data. Evaluate dedicated targeted reports with a regular cadence (e.g., daily, weekly, monthly) and designate an individual responsible for the review. Based on the organizational non-controlled drug diversion list, analyze ADC data such as canceled transactions, overrides, inventory counts, and discrepancies for unusual or repetitive transactions. If a staff member is identified as an outlier when it comes to high usage of a non-controlled substance on the organizational list (e.g., diphenhydrAMINE), this may be the first sign of potential diversion and should be further investigated. 

Drug diversion reporting program. Establish a reporting platform and maintain confidentiality of staff who report concerns about drug diversion to protect them from retaliation. 

Investigate and respond. If diversion is suspected, review the “all transaction” report from the ADC, EHR, surveillance videos, and badging access system. Discuss the findings of the initial investigation with an interdisciplinary diversion response team to determine the next steps. Depending on the team’s recommendation, staff may need to be interviewed. Findings should be reported back to the team. While there may be a need to comply with reporting to relevant state and federal agencies, establish a culture of recovery, not solely punishment, for a healthcare worker who is diverting drugs. Include a process to determine the worker’s employment disposition, and provide resources, such as access to employee assistance programs, for staff who may have a substance use disorder.

Educate staff. During orientation and at least annually, educate staff about the non-controlled substances that are commonly diverted. Outline the steps implemented to prevent drug diversion, the signs of drug diversion, and how to report and respond to drug diversion. Encourage staff to speak up when it comes to any medication they suspect is being diverted. To alleviate reporting concerns, educate staff on how to report using the reporting platform, and that confidentiality will be maintained to protect them from retaliation.

Evaluate. Organizations should immerse the drug diversion program in continuous process improvement. Gather feedback from staff, review internal and external data, and adjust processes as needed. 

We thank Mary Nelson, MSN, RN, CCPS, for sharing a systematic review of HonorHealth's drug diversion program, as well as helping to write this article. Email ISMP ([email protected]) with questions for HonorHealth.


  1. National Institute on Drug Abuse (NIDA). Misuse of prescription drugs research report. What classes of prescription drugs are commonly misused? National Institute on Drug Abuse. June 2020. Updated June 12, 2023. Accessed December 19, 2023. 

  2. Knight T. Is your organization protected from diversion of high-value drugs? Healthcare Business Today. December 9, 2021. Accessed December 19, 2023. 

  3. Dinwiddie AT, Tanz LJ, Bitting J. Notes from the field: antihistamine positivity and involvement in drug overdose deaths - 44 jurisdictions, United States, 2019-2020. MMWR Morb Mortal Wkly Rep. 2022;71(41):1308-10. 

  4. Kurtz SP, Buttram ME, Margolin ZR, Wogenstahl K. The diversion of nonscheduled psychoactive prescription medications in the United States, 2002 to 2017. Pharmacoepidemiol Drug Saf. 2019;28(5):700-6.


Suggested citation:

Institute for Safe Medication Practices (ISMP). Drug diversion prevention beyond controlled substance medications. ISMP Medication Safety Alert! Acute Care. 2024;29(5):1-3.