When Jeremiah (Jay) Joson, PharmD, APh, BCPS, BCMTMS, was an inpatient pharmacy manager in 2013, his hospital was visited by the California Department of Public Health (CDPH), concerned about droperidol and ECG monitoring, or rather, lack thereof. It resulted in the removal of droperidol from the hospital formulary, despite the medical staff’s review and approval of its use. Fast forward 12 years, and droperidol is still a favorite punching bag for CDPH.

Despite all the buzzwords (“Evidence-based medicine!” “Guideline directed!”), CDPH still insists that following the Food and Drug Administration’s (FDA) package insert is the gold standard when it comes to medical practice. On December 4, 2001, the FDA issued a boxed warning for droperidol, noting an association with QT prolongation and torsade des pointes (TdP). The warning states, “For patients in whom the potential benefit of droperidol treatment is felt to outweigh the risks of potentially serious arrhythmias, ECG monitoring should be performed prior to treatment and continued for 2-3 hours after completing treatment to monitor for arrhythmias.”¹ Despite decades of evidence detailing the safety and efficacy of droperidol, its package insert includes just seven references, spanning a date range of 1989 to 1998, with one reference written entirely in German and another studying droperidol use in “chronically instrumented dogs.”¹ A study by van Zwieten in 2004 found that 49 percent of deaths attributed to droperidol required dosages greater than or equal to 50 mg, magnitudes greater than typical dosages used in the emergency department (ED).² However, as much of the current literature states, the association between droperidol and a prolonged QTc leading to TdP are severely overblown, except in the mind of a CDPH surveyor.

Ironically, many other medications and medication classes have a close association with QT prolongation but lack a boxed warning. A meta-analysis by Singh and colleagues involving 687 patients found that ondansetron was associated with a statistically significant prevalence of QTc prolongation in all age groups.³ On the contrary, a retrospective review by Cole and associates spanning four years found a droperidol induced TdP rate of 1 in 16,546, or 0.006 percent, less than that of ondansetron. Yet, ondansetron lacks a boxed warning for QT prolongation.⁴ A study by Nuttall spanning three years analyzed 35,536 administered doses of droperidol and found no patients developed TdP or death.⁵ Another study by Martel compared droperidol 5 mg, ziprasidone 10 mg, ziprasidone 20 mg, and lorazepam 2 mg for the treatment of agitation in the ED. Droperidol was found to be more effective at attaining sedation (64 percent) versus ziprasidone 10 mg (25 percent), ziprasidone 20 mg (35 percent), and lorazepam 2 mg (29 percent).⁶ Furthermore, droperidol had the lowest rate of respiratory depression (12 percent) versus all other agents studied (36 to 48 percent). No patients had ventricular arrhythmias, and QTc durations were similar in all groups. This year, the CDPH surveyor asked to see the evidence in our use of droperidol (typically dosages ≤ 5 mg without ECG monitoring in only the most combative patients). We presented the surveyor with the data, but our citation mentioned only the ECG requirements of the package insert while ignoring every article provided.

The CDPH surveyor made it a point to say that the use of droperidol should not be done out of “convenience.” On the contrary, droperidol is safe, not just for the patient but also our providers. A national poll in 2018 by the American College of Emergency Physicians (ACEP) reported that nearly half of respondents had been physically assaulted.⁷ In 2024, the number of physicians reporting that they, or a colleague, had been assaulted jumped to an astounding 91 percent.⁸ Workplace violence has become so prevalent that the U.S. Congress introduced both HR 2663/S. 1176⁹ and the SAVE act (HR 2584/S. 2768)¹⁰ to strengthen workplace violence prevention programs. Our ED colleagues, Drs. Pho, Seng, and Al-Saiegh can all attest to the increased level of violence seen over the past decade and the need for a medication that is both safe, effective, and responsive. Clinical guidelines by the ACEP for the treatment of agitation list droperidol as the preferred agent (Level B recommendation) for patients with severe agitation.¹¹ Similarly, Project BETA¹², an interdisciplinary group led by the American Association of Emergency Psychiatry (AAEP) to determine preferred pharmacotherapeutic agents for agitation, also lists droperidol. Lastly, a policy statement by the ACEP on the use of droperidol for agitation in the ED continues to recommend droperidol at initial doses of 5-10 mg IM/IV, regardless of initial monitoring capability or ECG availability.¹³

In the FDA’s June 2018 procedural document, Drug and Device Manufacturer Communications With Payors, Formulary Committees, and Similar Entities—Questions and Answers, the FDA notes that the term, “should,” which is utilized in the droperidol boxed warning for ECG monitoring before and after dose administration, is a suggestion or recommendation, “but not required.” ¹⁴ In a bulletin published by the FDA in 1982, they state that, “With respect to its role in medical practice, the package insert is informational only.”¹⁵ In fact, the Food, Drug, and Cosmetic Act does not limit the manner in which a physician may use an approved drug.¹⁵

21 years after droperidol’s boxed warning, CDPH continues to practice medicine, forcing providers to magically meet the FDA’s stringent requirements while simultaneously placing 12-lead ECGs on every hostile patient throwing bedpans. The realistic (or preferred?) outcome of this is the removal of droperidol from the hospital formulary which unfortunately happened at our institution.

Why does the boxed warning for droperidol still exist? Good question—we have not found an answer. Clearly, the FDA can (with enough motivation, we suppose) reverse course. It did so with varenicline on December 16, 2016 and canagliflozin on August 26, 2020.^16,17 Perhaps the FDA requires large clinical trial findings (as was cited by them as the reason for reversing their position on these two agents). Good luck with that; we doubt anyone is spending money on an ancient drug to perform a large clinical trial.

When will CDPH reign in its surveyors? When will the FDA unequivocally state that a package insert cannot be used by regulatory agencies to practice medicine? That to us has a higher chance of causing harm than droperidol induced TdP.

Mr. Joson is a clinical pharmacy and residency program director. 

Dr. Pho is a practicing emergency medicine physician and the medical director of a busy community emergency department in California’s Central Valley, which functions as a tertiary referral center within its network.

Mr. Al-Saiegh, a board-certified emergency medicine pharmacist specialist with over seven years practice experience with special interests in cardiac arrest resuscitation and high-performance resuscitation teams, first brought droperidol to his emergency department in 2020, pivotally advocating for its use as the “Swiss army knife” of the ED.

Dr. Seng has been a practicing Emergency Medicine physician for 12 years and works at several community and academic departments across Central California.

References

1. S. Food and Drug Administration. Droperidol prescribing information. Available at: [https://www.americanregent.com/media/1574/droperidol_prescribing-information.pdf](https://www.americanregent.com/media/1574/droperidol_prescribing-information.pdf). Accessed April 8, 20251.
2. van Zwieten K, Mullins ME, Jang T. Droperidol and the black box warning. Ann Emerg Med. 2004;43(1):139-40.
3. Singh K, Jain A, Panchal I, et al. Ondansetron-induced QT prolongation among various age groups: a systematic review and meta-analysis. Egypt Heart J. 2023;75(1):56.
4. Cole JB, Lee SC, Martel ML, et al. The incidence of QT prolongation and torsades des pointes in patients receiving droperidol in an urban emergency department. West J Emerg Med. 2020;21(4):728-736.
5. Nuttall GA, Malone AM, Michels CA, et al. Does low-dose droperidol increase the risk of polymorphic ventricular tachycardia or death in the surgical patient? Anesthesiology. 2013;118(2):382-6.
6. Martel ML, Driver BE, Miner JR, et al. Randomized double-blind trial of intramuscular droperidol, ziprasidone, and lorazepam for acute undifferentiated agitation in the emergency department. Acad Emerg Med. 2021;28(4):421-434.
7. American College of Emergency Physicians. Emergency department violence poll results. Available at: [https://www.emergencyphysicians.org/siteassets/files/pdfs/2018acep-emergency-department-violence-pollresults-2.pdf](https://www.emergencyphysicians.org/siteassets/files/pdfs/2018acep-emergency-department-violence-pollresults-2.pdf). Accessed April 8, 20257.
8. American College of Emergency Physicians. ACEP member poll: ED violence. Available at: [https://www.acep.org/siteassets/new-pdfs/advocacy/acepmemberpoll-edviolencejan2024.pdf](https://www.acep.org/siteassets/new-pdfs/advocacy/acepmemberpoll-edviolencejan2024.pdf). Accessed April 8, 20258.
9. S. Congress. H.R. 2663. Available at: [https://www.congress.gov/bill/118th-congress/house-bill/2663](https://www.congress.gov/bill/118th-congress/house-bill/2663). Accessed April 8, 20259.
10. S. Congress. H.R. 2584. Available at: [https://www.congress.gov/bill/118th-congress/house-bill/2584/text](https://www.congress.gov/bill/118th-congress/house-bill/2584/text). Accessed April 8, 202510.
11. American College of Emergency Physicians. Clinical policies: severe agitation. Available at: [https://www.acep.org/siteassets/new-pdfs/clinical-policies/severe-agitation-cp.pdf](https://www.acep.org/siteassets/new-pdfs/clinical-policies/severe-agitation-cp.pdf). Accessed April 8, 202511.
12. Roppolo LP, Morris DW, Khan F, et al. Improving the management of acutely agitated patients in the emergency department through implementation of Project BETA (Best Practices in the Evaluation and Treatment of Agitation). J Am Coll Emerg Physicians Open. 2020;1(5):898-907.
13. American College of Emergency Physicians. Use of droperidol in the emergency department. Available at: [https://www.acep.org/siteassets/new-pdfs/policy-statements/use-of-droperidol-in-the-emergency-department.pdf](https://www.acep.org/siteassets/new-pdfs/policy-statements/use-of-droperidol-in-the-emergency-department.pdf). Accessed April 8, 202513.
14. S. Food and Drug Administration. Drug and device manufacturer communications with payors, formulary committees, and similar entities. Available at: [https://www.fda.gov/regulatory-information/search-fda-guidance-documents/drug-and-device-manufacturer-communications-payors-formulary-committees-and-similar-entities](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/drug-and-device-manufacturer-communications-payors-formulary-committees-and-similar-entities). Accessed April 8, 202514.
15. S. Food and Drug Administration. FDA revises description of mental health side effects of varenicline. Available at: [https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-revises-description-mental-health-side-effects-stop-smoking](https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-revises-description-mental-health-side-effects-stop-smoking). Accessed April 8, 202515.
16. S. Food and Drug Administration. FDA removes boxed warning about risk of leg and foot amputations with diabetes medicine canagliflozin. Available at: [https://www.fda.gov/drugs/drug-safety-and-availability/fda-removes-boxed-warning-about-risk-leg-and-foot-amputations-diabetes-medicine-canagliflozin](https://www.fda.gov/drugs/drug-safety-and-availability/fda-removes-boxed-warning-about-risk-leg-and-foot-amputations-diabetes-medicine-canagliflozin). Accessed April 8, 202516.