Drug Diversion Red Flags by Drug Class

The short answer

The warning signs of diversion are not the same for every drug. An injectable opioid is diverted by tampering with a syringe, so the signs are in waste records, patient pain and infection surveillance. A benzodiazepine or a stimulant is usually an oral solid, so the signs are in counts, prescriptions and ordering. Propofol is not a federally controlled substance at all, so there is often no count to check unless you create one. In a nursing home the drug is the same but the records are different, and the surveyor reads them against CMS rules rather than DEA rules.

This page takes each class in turn: what federal rules fix for it, the red flags documented for it, and the one control that closes the usual gap. The behavioral signs that apply to every class, such as frequent incorrect counts, large or inconsistent waste, and a mismatch between a patient's reported pain and the doses charted, are listed in 15 red flags of drug diversion and are not repeated here.

What the schedule changes

Federal rules do not mention drug classes. They work by schedule, and the schedule decides how exact your records have to be. That is why the same loss is easy to see for one drug and nearly invisible for another.

Schedules as listed by DEA on October 21, 2026: fentanyl, hydromorphone, morphine, oxycodone, hydrocodone, methadone and meperidine are Schedule II; amphetamine, methylphenidate and lisdexamfetamine are Schedule II; buprenorphine and ketamine are Schedule III; tramadol, alprazolam, lorazepam, midazolam, diazepam, clonazepam and temazepam are Schedule IV. Propofol is not on the list (DEA, Controlled Substances by alphabetical order).

Opioids

Opioids are the most common drugs diverted inside health care facilities (Berge et al., 2012). For injectables, the method is tampering: a fraction of the dose is given and the rest kept, or the drug is drawn off and the syringe refilled with saline or tap water. The signs follow from that.

• Patients in more pain than the chart says. Post-operative patients who seem undermedicated despite documentation of adequate doses were the trigger in documented cases (Berge et al., 2012). ISMP lists the same mismatch between reported pain and recorded administration as a diversion signal (Grissinger, 2018).
• Waste that is late, large or unwitnessed. ASHP says controlled substances should be wasted immediately or as close to administration as possible, with an independent witness for every waste (ASHP, 2022). Partial doses left in syringes and sharps containers are a documented source of diversion (Grissinger, 2018). Colleagues signing for disposal they did not watch is how one diverter was enabled (Berge et al., 2012).
• Cabinet access out of line with peers. In a 2017 to 2018 hepatitis C cluster in a Washington emergency department, the nurse responsible had accessed the automated dispensing system more often than other staff, more than three standard deviations above the staff mean. At least 12 patients were infected and 2,762 were offered testing (Njuguna et al., MMWR 2019). ASHP's standard is that dispensing-cabinet activity is compared with peers who have similar duties, and override reports are reviewed daily (ASHP, 2022).
• Infections that should not be there. A CDC review of 2004 to 2013 found six hospital outbreaks caused by tampering with injectable controlled substances. Two involved opioids in patient-controlled analgesia pumps and caused gram-negative bacteremia in 34 patients. Four involved fentanyl syringes or vials and caused hepatitis C in 84 patients. Nearly 30,000 patients were notified for testing (Schaefer and Perz, 2014). An unexplained bloodstream infection or a new hepatitis C diagnosis in a patient without risk factors is a diversion signal, not only an infection-control one.
• Fentanyl patches. A used patch keeps a substantial amount of fentanyl, and CMS says disposal in trash cans or sharps containers does not prevent diversion (CMS, Appendix PP, F755). ASHP calls for specific wasting procedures for patches (ASHP, 2022).

The control that closes the gap: reconcile the amount removed against the amount charted as given and the amount charted as wasted, for each dose, and resolve any discrepancy by the end of the shift. ASHP sets that interval, with unresolvable discrepancies escalated and closed within 24 to 72 hours (ASHP, 2022). Operating rooms and post-operative units are covered in anesthesia and OR diversion prevention and auditing post-op analgesia orders.

Benzodiazepines

Alprazolam, lorazepam, diazepam, clonazepam, temazepam and midazolam are Schedule IV. Federally that means an estimated count at inventory and records that can sit with everything else. A pharmacy that counts its Schedule II stock to the tablet can lose benzodiazepines for months without a record showing it.

• Losses that only a count would show. California's Board of Pharmacy added alprazolam 1 mg and 2 mg to the products that need a yearly reconciliation report because they were among the four non-Schedule II products with the highest reported losses to the board (Board of Pharmacy, 2021; rule adopted April 2022). If your state has no such rule, nothing federal requires you to count a benzodiazepine more than once every two years.
• Prescriptions that pair them with opioids. For a community pharmacy ASHP lists the red flags to check before dispensing: concomitant prescribing of opioids and benzodiazepines, high daily doses, cash-only claims and doctor shopping (ASHP, 2022). The pharmacist's duty on those prescriptions is covered in corresponding responsibility.
• Midazolam in procedural areas. As an injectable it carries the same waste and witness risks as the opioids above, and it is wasted alongside them in endoscopy, sedation and the OR.
• Liquid forms. Oral liquids are hard to reconcile. CMS lists the signs for liquid controlled medications: a visible gap between the written balance and the amount in the bottle, a change in viscosity or color, reports of spills, and a patient saying the medication is not working (CMS, Appendix PP, F755).

The control that closes the gap: a periodic physical count of the benzodiazepines you stock most, on a schedule your policy sets, with the review of acquisitions and dispositions that a Schedule II reconciliation already gets. What federal and state rules fix for count intervals is set out in how often controlled substances have to be counted.

Stimulants

Amphetamine, methylphenidate and lisdexamfetamine are Schedule II, so the federal rules are as strict as for oxycodone: an exact count, separate records, and a Form 222 or CSOS order. Stimulants are oral solids dispensed mostly in retail and outpatient pharmacies, so the signs are the pharmacy's signs.

• Small, repeated count discrepancies. DEA's Pharmacist's Manual says the loss of a small quantity of controlled substances, repeated over a period of time, may indicate a significant problem that must be reported, and that a registrant in doubt should err on the side of caution and report (DEA, 2022, p. 62). The factors for deciding whether a loss is significant are in 21 CFR 1301.76(b).
• Stock that runs short of what was dispensed. ISMP lists an increase in the amount of drug needed on the unit or in the pharmacy, and frequent incorrect counts, as diversion signals (Grissinger, 2018).
• One person, one shift. A per-diem pharmacist working solo shifts diverted stimulants and benzodiazepines in a New Hampshire case in this site's registry; see sole-pharmacist shifts and diversion risk.
• Prescription fraud. Fake and altered prescriptions for stimulants are a pharmacy-counter problem, covered in DEA's warning on electronic prescription fraud.

The control that closes the gap: a reconciliation that compares the physical count with the acquisitions and dispositions since the last count, not a count alone. California requires that reconciliation for every Schedule II drug at least every three months (16 CCR 1715.65). Your state may not, but the method is the one that finds a stimulant loss.

Propofol and ketamine

Ketamine is Schedule III. Propofol is not federally scheduled. DEA proposed placing it in Schedule IV in October 2010 and recorded why: 96 percent of the abusers in FDA's adverse event reports were health care providers or trainees, 18 percent of academic anesthesiology programs surveyed reported diversion or abuse of propofol, and 28 percent of the reported abusers had died of overdose (75 FR, October 27, 2010). The proposal was never finalized; propofol is absent from DEA's list dated October 21, 2026 (DEA list). Alabama scheduled it under state law in Schedule IV, effective August 27, 2012 (Alabama Department of Public Health). Check your own state.

• No count at all. Where propofol is not scheduled it is usually open stock in the OR, endoscopy and ICU. The red flag is the absence of any record to compare: nobody can say how many vials were used last week. ASHP's answer is to designate non-scheduled drugs at high risk of diversion, with propofol as the example, as locally controlled items with the same handling as scheduled drugs (ASHP, 2022).
• Who dies. DEA noted that those who died worked at facilities with no pharmacy or security controls over access to propofol (75 FR, October 27, 2010). Impairment at work is the signal that arrives too late.
• Ketamine. As a Schedule III drug it is counted by estimate federally and its records may be mixed with others. In the OR it is handled with the opioids and shares their waste and witness risks.

The control that closes the gap: put propofol and ketamine on the same count, waste and witness procedure as the Schedule II injectables in the same areas, by policy. How a non-controlled discrepancy is handled differently from a controlled one is covered in CDS vs. non-CDS discrepancies.

Long-term care

A nursing home is usually not a DEA registrant. The drugs belong to residents, are dispensed by an outside pharmacy, and are administered by nurses from a cart. The federal rules that apply are CMS's conditions for Medicare and Medicaid facilities, surveyed under F-tags, and they are written around reconciliation rather than inventory.

The red flags CMS tells surveyors to look for are specific to this setting (CMS, Appendix PP, F755):

• a resident saying the medication is not working, listed by CMS as a sign of diversion for controlled medications generally;
• for liquids, a visible gap between the written balance and the bottle, a change in color or viscosity, and reports of spills;
• unusual access patterns in the tracking data for injectable scheduled drugs, which CMS says should be investigated, including whether residents need screening for bloodborne pathogens;
• used fentanyl patches disposed of in common areas, room trash cans or sharps containers, which CMS says do not prevent diversion;
• an emergency drug supply with no reconciliation procedure of its own.

The control that closes the gap: a written reconciliation interval that shortens when a discrepancy appears, and a discontinued-drug procedure with a dated record of each disposal. Discontinued and deceased residents' supplies are the stock that nobody is counting. What to do when a count does not match is covered in controlled substance discrepancies.

What applies to every class

Two federal rules do not depend on the drug. DEA's security standard lists the factors it weighs, among them “the adequacy of supervision over employees having access” and “the adequacy of the system for monitoring the receipt, manufacture, distribution, and disposition of controlled substances” (21 CFR 1301.71(b)). And an employee who knows of diversion by a fellow employee has an obligation to report it to a responsible security official of the employer, who must keep the report confidential (21 CFR 1301.91). Who you must tell once a red flag becomes a finding is set out in reporting employee diversion.

Sources

• 21 CFR 1301.71, 1301.76, 1301.91, 1304.04, 1304.11, 1304.22 and 1317.80, current text at the Legal Information Institute.
• DEA Diversion Control Division. Controlled Substances, Alphabetical Order, dated October 21, 2026; Pharmacist's Manual, 2022 edition.
• DEA. Schedules of Controlled Substances: Placement of Propofol Into Schedule IV; Proposed Rule. 75 FR, October 27, 2010.
• CMS. State Operations Manual, Appendix PP, F755 (rev. 225, August 8, 2024) and F761 (rev. 229, April 25, 2025).
• California Board of Pharmacy. 16 CCR 1715.65, order of adoption (April 7, 2022) and initial statement of reasons (April 14, 2021).
• Alabama Department of Public Health. State Committee of Public Health adds propofol to Alabama Controlled Substances List. July 27, 2012.
• Clark J, Fera T, Fortier C, et al. ASHP Guidelines on Preventing Diversion of Controlled Substances. Am J Health Syst Pharm. 2022;79(24):2279-2306.
• Berge KH, Dillon KR, Sikkink KM, Taylor TK, Lanier WL. Diversion of drugs within health care facilities, a multiple-victim crime. Mayo Clin Proc. 2012;87(7):674-682.
• Schaefer MK, Perz JF. Outbreaks of infections associated with drug diversion by US healthcare personnel. Mayo Clin Proc. 2014;89(7):878-887.
• Njuguna HN, Stinson D, Montgomery P, et al. Hepatitis C Virus Potentially Transmitted by Opioid Drug Diversion from a Nurse, Washington, August 2017 to March 2018. MMWR. 2019;68(16):374-376.
• Grissinger M. Partially Filled Vials and Syringes in Sharps Containers Are a Key Source of Drug Diversion. P T. 2018;43(12):714-717.

Read on October 26, 2026. Educational content, not legal advice; schedules and state rules change, so check the current DEA list and your state board before relying on a count interval.

What the public record shows

Counted from the DivertGuard case registry, which is compiled from board actions, court filings and press releases. It is a record of documented cases, not an estimate of how often diversion happens.

Further reading