CURRENT GUIDELINES FOR THE USE OF DROPERIDOL
Faculty:
L. Austin Fredrickson, MD, FACP
L. Austin Fredrickson is an Associate Professor of Internal Medicine at Northeast Ohio Medical University, where he serves as core faculty and teaches diagnostics, therapeutics, clinical skills, and health humanities. He is board-certified in general internal medicine and practices rural primary care.
Sandra Rogers, MD
Sandra Rogers, MD, is a primary care physician in Texas. She is board-certified in Family Medicine and Internal Medicine by the American Board of Family Medicine and the American Board of Internal Medicine.
Kristina (Tia) Neu, RN
Kristina (Tia) Neu is a licensed Registered Nurse and author currently developing in-service training for healthcare professionals. She is a National Board-Certified Health & Wellness and Lifestyle Medicine Coach. Her experience spans several areas of healthcare, including psychiatric nursing, medical nursing, motivational health coaching, chronic case management, dental hygiene, cardiac technology, and surgical technology.
Pamela Sardo, PharmD, BS
Pamela Sardo, PharmD, BS, is a freelance medical writer and licensed pharmacist. She is the founder and principal at Sardo Solutions in Texas. Pam received her BS from the University of Connecticut and her PharmD from the University of Rhode Island. Pam’s career spans many years in retail, clinics, hospitals, long-term care, Veterans Affairs, and managed health care responsibilities across a broad range of therapeutic classes and disease states.
Topic Overview
Droperidol is a butyrophenone, a typical antipsychotic and dopamine receptor antagonist that works in the chemoreceptor trigger zone. The labeled use of droperidol is for the treatment of nausea and vomiting in the surgical and diagnostic setting. However, it is often used for off-label purposes, including severe agitation. After decades of successful use in the surgical and emergency department settings, droperidol fell out of favor dramatically after the FDA issued a boxed warning due to the risk of QT prolongation. Over time, the available data suggest that droperidol is a safe and effective option for treating nausea and vomiting in the surgical and diagnostic settings.
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Credits: 2 contact hour(s) (0.2 CEU(s)) of continuing education credit.
Credit Types:
IPCE Credits - 2 Credits
AAPA Category 1 Credit™️ - 2 Credits
AMA PRA Category 1 Credit™️ - 2 Credits
Pharmacy - 2 Credits
Type of Activity: Knowledge
Media: Computer-Based Training (i.e., online courses)
Estimated time to complete activity: 2 contact hour(s) (0.2 CEU(s)), including Course Test and course evaluation.
Release Date: February 7, 2026 Expiration Date: February 7, 2029
Target Audience: This educational activity is for Physicians, Physician Assistants, Pharmacists, and Pharmacy Technicians
How to Earn Credit: From February 7, 2026, through February 7, 2029, participants must:
Read the “learning objectives” and “author and planning team disclosures;”
Study the section entitled “educational activity;” and
Complete the Course Test and Evaluation form. The Course Test will be graded automatically. Following successful completion of the Course Test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)
CME Credit: Credit for this course will be uploaded to CPE Monitor® for pharmacists. Physicians may receive AMA PRA Category 1 Credit™ and use these credits toward Maintenance of Certification (MOC) requirements. Physician Assistants may earn AAPA Category 1 CME credit, reportable through the PA Portfolio. All learners should verify their individual licensing board's specific requirements and eligibility criteria.
Learning Objectives: Upon completion of this educational activity, participants should be able to:
Identify the labelled uses of droperidol
Describe the professional position statement guiding droperidol use in surgical and emergency cases
Describe droperidol’s uses in combination with other drugs
Review the role of droperidol in multiple clinical settings
Disclosures
The following individuals were involved in developing this activity: L. Austin Fredrickson, MD, FACP; Sandra Rogers, MD; Kristina (Tia) Neu, RN; and Pamela Sardo, PharmD, BS. None of these individuals has a conflict of interest or financial relationship regarding the development of this activity. There are no financial relationships or commercial or financial support relevant to this activity to report or disclose by RxCe.com or any of the individuals involved in the development of this activity.
© RxCe.com LLC 2026: All rights reserved. No reproduction of all or part of any content herein is allowed without the prior, written permission of RxCe.com LLC.
Educational Activity
Current Guidelines for the Use of Droperidol
Introduction
Droperidol is a butyrophenone-class typical antipsychotic that has a labeled use in the United States for the reduction of nausea and vomiting that accompanies diagnostic and surgical procedures. The current guidance on its safe and effective use is discussed, along with its emerging use in emergency departments. Clinicians should also be aware of the potential adverse events associated with this drug.
Pharmacological Profile
Droperidol is a typical (first-generation) antipsychotic in the butyrophenone class.1,2 Droperidol is a dopamine receptor antagonist that works in the chemoreceptor trigger zone; it is also a peripheral alpha-adrenergic antagonist.1,2 It was approved for use in the United States in 1970, and it is now available only in generic form.3 It is available in the United States as a 2.5 mg/mL solution for injection in 2 mL single-dose vials.1
Typical antipsychotics are sometimes categorized as high-potency or low-potency or referred to by their chemical structure.2 The terms high-potency and low-potency were developed to compare the dose needed when using a typical antipsychotic to achieve the same therapeutic effect as a 100 mg dose of chlorpromazine. For example, haloperidol is considered high-potency because, in terms of effectiveness, a 1 mg dose is calculated as a dose equivalent to 100 mg of chlorpromazine.5
Droperidol is a high-potency, typical antipsychotic. Other examples of high-potency typical antipsychotics include fluphenazine, haloperidol, loxapine, perphenazine, pimozide, thiothixene, and trifluoperazine. Like other high-potency typical antipsychotics, droperidol has a high risk for extrapyramidal symptoms (EPS) but a low risk for anticholinergic and sedative effects.2 In contrast, low-potency typical antipsychotics, such as chlorpromazine and thioridazine, usually have a low risk for EPS but a high risk for anticholinergic and sedative effects.2
Droperidol acts on the vomiting center in the brain, which initiates and coordinates vomiting.6 The vomiting center communicates directly with peripheral pathways and receptors, the vestibular system, the cortex, and the chemoreceptor trigger zone. The chemoreceptor trigger zone is activated by dopamine, neurokinin-1, and serotonin.6 Droperidol, by its action as a dopamine receptor antagonist, interrupts the transmission of afferent signals to the vomiting center and prevents emesis.6 Droperidol, alone or in combination with other drugs, has been used successfully for decades to treat nausea and vomiting.7-9
Labeled Uses
Droperidol’s FDA-approved indication is to reduce the incidence of nausea and vomiting that accompanies diagnostic and surgical procedures, also known as post-operative nausea/vomiting (PONV).1,4 Without prophylaxis, postoperative vomiting may occur. Studies show PONV occurs in approximately 30% of all patients and up to 80% of high-risk patients. High-risk patients include females, non-smokers, patients who have had episodes of motion sickness or previous postoperative vomiting, and patients who are expected to need postoperative opioids.10,11
In addition to being a highly unpleasant experience, PONV can delay discharge from the healthcare facility and increase the risk for postoperative complications like aspiration, dehydration, esophageal rupture, increased intracranial pressure, pneumothorax, and wound dehiscence.7
Dosing and Administration
Administration
Droperidol is approved for administration via intramuscular (IM) injection or slow intravenous injection (slow IV push). Droperidol is sometimes given by intermittent IV infusion. However, because intermittent IV infusion is not an officially approved administration method, the package insert provides no information regarding dilution, compatibility, or stability.1
It can be mixed in normal saline (NS), 5% dextrose (D5W), or Lactated Ringer’s (LR).12 It should be administered slowly, and the patient should be closely monitored for side effects during the infusion.2
Pharmacokinetics
When administered intravenously or intramuscularly, droperidol has a rapid onset of action (3 to 10 minutes).1 Time to maximum effect is approximately 30 minutes, with a duration of effect of 2 to 4 hours (although sometimes lingering as long as 12 hours).12
Droperidol readily crosses the blood-brain barrier. Droperidol is metabolized in the liver, and the drug and its metabolites are excreted in the urine and feces.12
Dosage: Nausea and Vomiting
The dose should be individualized. The maximum initial dose for adults is 2.5 mg, administered IV or IM. Additional 1.25 mg doses may be used, but should be administered cautiously.1
For children aged 2 to 12 years, the maximum recommended initial dosage is 0.1 mg/kg, with additional doses administered cautiously.
For nausea and/or vomiting, a published study compared 0.625mg of IV droperidol to ondansetron 4mg IV, promethazine 12.5mg IV, and placebo for the prevention of PONV.13 Droperidol was found to be equivalent to both ondansetron and promethazine for the prevention of PONV.13
Special Populations
Geriatric
There are no specific dosing recommendations for droperidol use in geriatric patients.1,12 Adverse reactions of concern in geriatric patients include falls, orthostatic hypotension, and anticholinergic effects. Shared decision-making is very important because antipsychotics such as droperidol are potentially inappropriate for patients 65 years or older.1
Hepatic and Renal Impairment
Droperidol should be administered with caution to patients with liver and kidney dysfunction.12
Pregnancy and Breastfeeding
It is not recommended as a treatment for persistent nausea and vomiting during pregnancy.1,12 Animal studies have shown adverse fetal effects. There are no adequate, well-controlled studies of droperidol's teratogenic effects in humans, and the benefits of droperidol during pregnancy may outweigh the risks. It is not known if droperidol is excreted in breast milk.1,12
Look-Alike/Sound-Alike Concerns
Droperidol may be mistaken for dronabinol.1 Not only are the drug names similar, but their indications are also similar (since both medications can be used for nausea and/or vomiting). Physicians, pharmacists, and other providers should be aware of the potential for prescribing mix-ups. However, dispensing errors are unlikely with these medications, as dronabinol is available only in capsule form and at much higher doses than droperidol.
US Boxed Warning
According to the US Boxed Warning for droperidol, QT prolongation and torsades de pointes (TdP) have been reported after the use of droperidol, even at or below the recommended dosage. Fatalities have been reported, and this adverse effect has occurred in patients who did not have known risk factors for QT prolongation.1,2,4 Under the black box warning, droperidol should only be used if other treatments have not been effective or if other treatments have caused intolerable adverse effects.1,2,4
Following the FDA's issuance of a box warning for droperidol, its use decreased significantly.14 This decreased use was also driven by the perceived risks of QT prolongation, TdP, and sudden death reported from droperidol use. Other antiemetics, such as anticholinergics, glucocorticoids, phenothiazines, and serotonin receptor antagonists, are preferred for prophylaxis and/or treatment of postoperative nausea and vomiting.15,16
Cole, et al. (2020) stated: “We found the incidence of QTc prolongation and TdP in ED [emergency department] patients receiving droperidol to be extremely rare.” This publication suggested that the FDA boxed warning was overstated and that close ECG monitoring is useful only in high-risk patients.14 A subsequent study found that QTc intervals increased slightly 10 to 30 minutes after droperidol administration.17 These prolongations were brief (mostly below 500 msec) and did not lead to arrhythmias.17 The conclusion drawn from this study was that low-dose droperidol (≤ 2.5 mg) appears to be safe for non-agitated emergency department patients.17 Further research is needed to confirm how rare QTc prolongation and TdP are in emergency department patients receiving droperidol.18
After virtually disappearing due to restrictions and subsequently to product shortages and discontinuations,11 droperidol has reemerged following safety research.19,20 Additionally, the shortage of droperidol has subsided.21
An important 2015 position statement from the American Academy of Emergency Medicine found that the literature did not support mandating an EKG screening and monitoring for doses < 2.5 mg given either intramuscularly or intravenously.22,23 Combined with improved product availability, there is renewed interest in the use of droperidol.22,23
FDA-approved prescribing information still contains contraindications, warnings, and precautions. Droperidol should be used cautiously if the patient has risk factors for prolonged QT, which may include age > 65 years, alcohol use, bradycardia, cardiac hypertrophy, congestive heart failure (CHF), hypokalemia, hypomagnesemia, use of other drugs that can prolong the QT interval, and concurrent use of benzodiazepines, diuretics, IV opiates, and volatile anesthetics.1,2 According to the box warning, before the use of droperidol, a 12-lead ECG should be performed, and if the QT interval is > 440 msec (males) or > 450 msec (females), droperidol should not be given.1,4 Per prescribing information, the patient should be placed on continuous electrocardiogram (ECG) monitoring for 2-3 hours after the dose has been given, or as deemed clinically necessary by the prescribing clinician.1,2,4
RISK FACTORS FOR TORSADES DE POINTES21,24-27
Advanced age Baseline prolonged QT interval Bradycardia Cardiovascular disease, hepatic disease, and renal disease Electrolyte abnormalities, specifically hypocalcemia, hypokalemia, and hypomagnesemia Female gender High doses of a drug that prolongs the QT interval An overdose of a drug that can prolong the QT interval The use of drugs that inhibit the metabolism of a drug that causes a prolonged QT interval. The use of multiple drugs that cause a prolonged QT interval |
Drug-Drug Interactions
Droperidol interacts with an extremely large number of other medications (far too many to list). However, in general, droperidol drug interactions of the greatest concern are due to additive adverse pharmacological effects. In particular, any medication that adds to the anticholinergic, CNS-depressing, QT-prolonging, or serotonin-modulating effects of droperidol can lead to a clinically significant interaction.1,28 Utilizing an evidence-based drug-interaction checker can highlight concerning interactions.
Contraindications
Droperidol is contraindicated in patients with hypersensitivity to the drug or any of its components. Droperidol is contraindicated if the patient has known or suspected QT prolongation, including (but not limited to) individuals with congenital long QT syndrome.1,2,4
Adverse Effects
Reported possible side effects include the following:4
Mild to moderate hypotension
Mild to moderate tachycardia
Dysphoria
Postoperative drowsiness
Restlessness
Hyperactivity
Anxiety
Postoperative hallucinatory episodes
Serious adverse reactions include QT prolongation and TdP, severe hypotension, extrapyramidal side effects (such as dystonia, akathisia, oculogyric crisis), and neuroleptic malignant syndrome (NMS).
Pause and Ponder Patient Case: A 58-year-old female nonsmoker scheduled for surgery with a history of post-operative nausea. Her admission ECG reveals a QTc of 435 msec. Question: Is droperidol indicated for this case of PONV? |
Neuroleptic Malignant Syndrome (NMS)
The typical antipsychotics, including droperidol, have been implicated as a cause of NMS, a rare and potentially fatal adverse drug reaction.1,2,29-31 However, NMS is not limited to typical antipsychotic use.32 It is an adverse effect that is also seen with atypical antipsychotics, but they appear to have a lower incidence and clinical severity, as well as a lower frequency of lethal outcomes.32
Neuroleptic malignant syndrome can occur with normal use; however, studies indicate that there is an association between NMS and an alteration of antipsychotic treatment, especially in cases where the antipsychotic dose is increased, and when therapy with an antipsychotic is titrated rapidly or abruptly discontinued.32,33 Some case reports suggest that patients prescribed antipsychotics in combination with lithium are at greater risk of NMS than patients on monotherapy antipsychotic medications.34-37 However, some studies indicate there is insufficient evidence to reach a conclusive position on this point.36
The incidence and risk of NMS associated with droperidol are unknown, but there are reports of droperidol-induced NMS as a possible diagnosis.30,38 Neuroleptic malignant syndrome is rare, occurring in an estimated 0.01 to 0.02% of patients treated with antipsychotic medications.32 However, NMS causes death in approximately 10% of patients who develop the condition.33,38 This is a marked improvement from the 30% fatality rates reported two decades ago.33
Clinical tests cannot confirm neuroleptic malignant syndrome.29,39 Therefore, it is a diagnosis of exclusion, making its true incidence unknown.29,39 The diagnostic criteria for NMS require the presence of muscle rigidity and hyperthermia, and one or more of the following symptoms: autonomic instability (e.g., sweating, dysphagia, tremor, urinary incontinence, tachycardia, or blood pressure fluctuations), or altered consciousness (usually confusion), but may also include fluctuations in levels of consciousness, mutism, and coma.29,40 If medications such as droperidol are used during surgery, clinicians should monitor the patient for these symptoms during the postoperative period.29 Clinicians should maintain a high level of suspicion in diagnosing NMS when drugs are used that can lead to dopamine hypoactivity.37
Laboratory alterations linked to NMS are leukocytosis (elevated white blood cell count) and those related to muscle rigidity or rhabdomyolysis, such as elevations in serum aldolase, lactate dehydrogenase, transaminases, myoglobin, and creatine kinase, as well as myoglobinuria.29
The pathophysiology of NMS is not fully understood, but it is likely caused in part by dopamine receptor blockade that leads to dopamine hypoactivity.30,33,38 It can occur during the postoperative period as a result of the administration of major tranquilizers, including droperidol.30
Treatment of NMS is primarily supportive.29,38,41 If the patient has NMS, the offending drug should be immediately discontinued.38,41 Dopaminergic drugs, such as amantadine and bromocriptine, as well as the muscle relaxants, such as dantrolene, can be effective.38 Medications like lorazepam or diazepam (benzodiazepines) may also be used to treat NMS.30,41
Orthostatic Hypotension
Typical antipsychotics can cause orthostatic hypotension due to their activity as peripheral alpha-adrenergic receptor antagonists.1,42 This is a class effect, although the intensity of this effect varies throughout the class. Droperidol is a strong peripheral alpha-adrenergic antagonist with a notable propensity to cause orthostatic hypotension.1 Elderly patients are more likely to have orthostatic hypotension, probably due to decreased baroreceptor sensitivity.42
Extrapyramidal Symptoms
Drug-induced extrapyramidal symptoms are movement disorders that are thought to be primarily caused by dopamine receptor antagonism and an imbalance between dopaminergic and cholinergic activity in the nigrostriatal tract, an area of the brain that controls motor movements.1,2 Extrapyramidal symptoms are a well-known adverse effect of the typical antipsychotic, including droperidol.43
A variety of extrapyramidal symptoms (including but not limited to akathisia, dystonia, and oculogyric crisis) have been reported with droperidol, even when used at low doses.44,45
Off-Label Uses
Physicians may prescribe medications for uses that are not FDA-approved.19,46 It is essential to consult the prescribing information for comprehensive safety and efficacy information, and to research published literature and evidence before considering any off-label treatment. Caution is prudent when a medication is not FDA-approved for a patient's condition. Droperidol is used for various off-label indications, such as to sedate acutely agitated or violent patients, to treat acute migraine, and as an adjunct for general anesthesia induction and maintenance.23,46-48 Information regarding real-world clinical scenarios of off-label use is not an endorsement of these uses but is intended for educational purposes.
Acute Agitation
Droperidol is not approved as a treatment for acute agitation, but treating agitation is its most common off-label use.19 Clinical experience and research suggest that it is safe and effective for this purpose.19,49-53
A randomized clinical trial in 2017 found that midazolam and droperidol, droperidol alone, and olanzapine were all effective treatments for acutely agitated emergency department patients.49 Midazolam-droperidol in combination was slightly superior to the monotherapies for intravenous sedation of the acutely agitated emergency department patient. The clinical trial found no difference in adverse effect profiles between these treatments.49
A 2018 study reviewed the use of droperidol and midazolam for prehospital acute behavioral disturbance.50 The study reviewed the incidence of certain adverse effects, which included airway intervention, oxygen desaturation, respiratory depression, hypotension, excessive sedation, and dystonic reactions in patients receiving sedation.50 It also reviewed the time to sedation, the need for additional sedation, staff and patient injuries, and prehospital time. Droperidol achieved sedation faster (22 minutes vs 30 minutes for midazolam). There was a lower need for additional sedation and a lower incidence of adverse reactions compared to midazolam.50
The American Academy of Emergency Medicine issued a position statement on the use of droperidol in the emergency room, stating that “droperidol is an effective and safe medication in the treatment of nausea, headache, and agitation. Intramuscular doses of up to 10 mg of droperidol seem to be as safe and as effective as other medications used for sedation of the agitated patient.”23
Other Off-Label Uses
Other off-label uses have included the following:
Induction of sedation in agitated or violent patients (sometimes known as “chemical restraint”)51
Adjunct to general anesthesia induction or maintenance8
Treatment of anxiety before anesthesia19
Treatment of acute migraine48
Droperidol has been effective for nausea and vomiting associated with migraines, cannabinoid hyperemesis syndrome, and cyclic vomiting syndrome.20 A June 2025 study also links its use to a reduced length of stay for patients with cannabinoid hyperemesis syndrome.54
Dosage: Off-Label Uses
As is typical with off-label indications, dosage recommendations vary. Suggested dosages for sedating agitated or violent patients tend to be higher than the officially recommended nausea/vomiting dosage, often ranging from 2.5 mg up to 10 mg in a single dose, often in combination with a benzodiazepine.52,55 For other off-label uses, recommended dosages often mirror the approved labeling, with the caveat that dosages should be adjusted for patient-specific factors, such as age, weight, and concomitant medications.52,55
Droperidol’s Expanded Use in Emergency Settings
Droperidol continues to gain acceptance in emergency departments and Emergency Medical Services (EMS). It is now used for conditions such as severe agitation, nausea, or vomiting not related to surgery, and cases resistant to other treatments.56-59 For example, Maryland and San Francisco are among the jurisdictions that have added or updated EMS protocols in 2024 and 2025, respectively, to include droperidol for the treatment of nausea and agitation.60,61 Protocols specify dosages, administration routes (IV or IM), and required cardiac monitoring.60,61
Droperidol Combination Treatments
Droperidol has been combined with other drugs like dexamethasone, which is a corticosteroid.62 For severe agitation, droperidol 5 mg IM or IV may be administered with 5 mg of midazolam, maximum 10–20 mg/day.63 Droperidol has also been administered with fentanyl, but this drug combination was discontinued in the US.64
Summary
Droperidol is a butyrophenone typical antipsychotic with a variety of uses, notably for postoperative nausea and vomiting and for acute agitation. While fast-acting and reliable, the drug is associated with several potentially serious side effects, such as QT prolongation, torsades de pointes, and neuroleptic malignant syndrome. Despite a black box warning issued by the FDA in 2001 that resulted in restricted availability of the drug in many health systems, the drug seems to have regained popularity as a “tried and true” option in many settings, especially after the release of an important position statement from the American Academy of Emergency Medicine supporting its use.
Course Test
What is the indication for droperidol?
Treatment of schizophrenia
Reduction of nausea and vomiting during diagnostic and surgical procedures
Treatment of resistant bipolar disorder
Prevention of seizures after a complex surgical procedure
Droperidol is a ______________, typical antipsychotic.
high-potency
second generation
phenothiazine class
low-potency
Mothers who breastfeed should know that droperidol
is excreted in breast milk.
is contraindicated for breastfeeding mothers.
may or may not be excreted in breast milk.
has been associated with known adverse effects in nursing infants.
FDA-approved options for droperidol administration include
IM and slow IV push.
continuous IV infusion and SQ.
oral and continuous IV infusion.
IM and continuous IV infusion.
According to the American Academy of Emergency Medicine, droperidol
should never be used due to cardiac risk.
is effective and safe for treating nausea in the ER.
is only recommended for use in psychiatric hospitals.
is not recommended for pediatric patients.
What key monitoring step is recommended by professional guidelines before administering droperidol?
Blood glucose measurement
12-lead ECG to assess the QT interval
Liver function test
Skin allergy test
Droperidol has been combined with which corticosteroid for antiemetic purposes?
Hydrocortisone
Prednisone
Dexamethasone
Betamethasone
Droperidol is contraindicated if a patient
is concurrently receiving a benzodiazepine.
has congenital long QT syndrome.
is over 45 years old.
is pregnant.
Droperidol is gaining renewed interest in clinical settings for what reason?
Discovery of new adverse effects
Improved product availability and supportive position statements
Restricted use of antipsychotics
It is now discontinued worldwide, and alternatives are not available
Droperidol, by its action as a dopamine receptor antagonist, interrupts the transmission of ___________ signals to the vomiting center and prevents emesis.
efferent
tardive
involuntary
afferent
References
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Hernández-Rodríguez L, Bellolio F, Cabrera D, et al. Prospective real-time evaluation of the QTc interval variation after low-dose droperidol among emergency department patients. Am J Emerg Med. 2022;52:212-219. doi:10.1016/j.ajem.2021.12.039
Siegel RB, Motov SM, Marcolini EG. Droperidol Use in the Emergency Department: A Clinical Review. J Emerg Med. 2023;64(3):289-294. doi:10.1016/j.jemermed.2022.12.012
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