Droperidol (Inapsine) | Medication Reference

Bedside Snapshot

Primary Uses: Severe agitation, postoperative nausea/vomiting, cannabinoid hyperemesis, migraine-associated nausea
Agitation Dosing: 5–10 mg IV or IM once; may repeat 2.5–5 mg after 15–30 minutes with cardiac monitoring
Antiemetic Dosing: 0.625–1.25 mg IV or 1.25–2.5 mg IV/IM for postoperative nausea/vomiting; lower than agitation doses
Onset: 3–10 minutes IV, 10–20 minutes IM; full effect may take 20–30 minutes
Duration: 2–4 hours sedation; longer antiemetic effect
Black Box Warning: QT prolongation and torsades de pointes risk—dose-dependent; avoid in long QT, uncorrected electrolytes
Key Advantages: Faster onset than haloperidol, excellent for undifferentiated agitation and cannabinoid hyperemesis
Major Risks: QTc prolongation/torsades, hypotension, excessive sedation (especially with CNS depressants), EPS, rare NMS
Monitoring: Cardiac monitoring for doses ≥2.5 mg or high-risk patients; continuous vitals and respiratory status

Brand & Generic Names

Generic Name: Droperidol
Brand Names: Inapsine (U.S.); many facilities use generic droperidol injection

Medication Class

Butyrophenone Antipsychotic / Antiemetic

Pharmacology

Mechanism of Action:

Dopamine D2 receptor antagonism in the chemoreceptor trigger zone (CTZ) and vomiting center → potent antiemetic effect
D2 blockade in mesolimbic and mesocortical pathways → antipsychotic and sedative properties, useful for agitation and psychosis
α-adrenergic blockade and mild H1 antagonism → vasodilation, hypotension, and additional sedation
Blocks cardiac delayed rectifier potassium current (IKr/hERG) → dose-related QT prolongation, which can precipitate torsades de pointes in susceptible patients
Like other dopamine antagonists, can cause extrapyramidal symptoms (akathisia, dystonia, parkinsonism) and, rarely, neuroleptic malignant syndrome

Pharmacokinetics:

Onset: 3–10 minutes IV; 10–20 minutes IM; maximal clinical effect may not be evident until 20–30 minutes after administration
Duration: Sedative/antiagitation effects 2–4 hours, but residual antiemetic and CNS effects can persist longer
Distribution: Highly lipophilic, large volume of distribution; crosses the blood–brain barrier readily and is highly protein bound
Metabolism: Extensive hepatic metabolism via oxidative pathways (likely CYP-mediated) to inactive metabolites
Elimination: Primarily renal excretion of metabolites; terminal half-life ~2–3 hours, prolonged in hepatic impairment
Special populations: Elderly, debilitated, and patients with hepatic dysfunction may have prolonged and exaggerated responses—start at lower doses and titrate cautiously

Indications

Postoperative nausea and vomiting prophylaxis and treatment (labeled indication)
ED/ICU treatment of severe agitation or psychosis (often undifferentiated, including intoxication, stimulant use, or delirium) when parenteral sedation is required
Adjunct for migraine or headache syndromes in the ED, especially when nausea/vomiting are prominent and dopamine antagonists are used for abortive therapy
Treatment of cannabinoid hyperemesis syndrome and other nausea/vomiting syndromes in ED patients when standard antiemetics are insufficient
Rescue antiemetic in PACU/OR for refractory postoperative nausea/vomiting when other agents fail or cannot be used
Occasional use in procedural sedation/anesthesia as part of a neurolept–analgesic regimen (often combined historically with opioids like fentanyl)

Dosing & Administration

Available Forms:

Injection: 2.5 mg/mL in multi-dose or single-dose vials (commonly 2.5 mg/mL, 5 mg/2 mL, 10 mg/4 mL depending on product)
Intended for IV or IM administration only; no oral formulation in common use

Adult Dosing (ED/ICU/Perioperative – Always Follow Local Protocols):

Indication	Dose	Route	Notes
Postoperative Nausea/Vomiting Prophylaxis	0.625–1.25 mg	IV slowly	At induction or near end of anesthesia
Postoperative Nausea/Vomiting Treatment (ED/PACU)	0.625–1.25 mg	IV over 1–2 min	May repeat once if symptoms persist; typical total 1.25–2.5 mg
Severe Agitation/Psychosis (off-label ED)	5–10 mg initial	IV or IM	Onset 3–10 min IV, 10–20 min IM; may repeat 2.5–5 mg after 20–30 min with cardiac monitoring
Migraine/Cannabinoid Hyperemesis (ED)	0.625–2.5 mg	IV or IM	Commonly 1.25 mg IV or 2.5 mg IM; titrate to effect with QT monitoring
Elderly/High-risk QT Patients	0.625–1.25 mg (antiemetic) 2.5–5 mg (agitation)	IV or IM	Start low, titrate based on response and ECG

Combination Therapy: Often combined with benzodiazepine (e.g., midazolam) for severe agitation per ACEP guidelines.

Contraindications

Absolute Contraindications:

Known or suspected QT prolongation (e.g., baseline QTc >440 ms in males or >450 ms in females, or congenital long QT syndrome)
Known hypersensitivity to droperidol or other butyrophenones
History of torsades de pointes or other significant ventricular arrhythmias
Severe CNS depression or coma not due to a condition requiring droperidol use (e.g., post-ictal, head trauma) where further sedation is dangerous

Precautions:

Use extreme caution in patients with risk factors for QT prolongation: structural heart disease, bradycardia, electrolyte abnormalities (low K/Mg), concomitant QT-prolonging drugs (e.g., methadone, amiodarone, certain antiemetics and antipsychotics)
Elderly, debilitated, or volume-depleted patients: increased sensitivity to hypotension and CNS depression; start low and go slow
Hepatic impairment: decreased metabolism may prolong effects; consider dose reduction
Parkinson disease or Lewy body dementia: dopamine blockade may significantly worsen symptoms or cause severe EPS
Concomitant sedative-hypnotics (benzodiazepines, opioids, alcohol, other CNS depressants): additive sedation and respiratory depression—monitor closely and titrate carefully
Pregnancy: typically avoided for elective use, but may be used if benefits outweigh risks (e.g., refractory hyperemesis); consult OB when possible

Black Box Warning: QT prolongation and torsades de pointes risk requires attention to QTc and cardiac monitoring, particularly with higher cumulative doses or high-risk profiles.

Adverse Effects

Common:

Sedation, drowsiness, dizziness
Hypotension, especially with rapid IV push or in volume-depleted patients
Anxiety, restlessness, or mild akathisia
Headache, dry mouth
Injection site pain with IM administration

Serious (ED/ICU-relevant):

QT prolongation and torsades de pointes, potentially leading to ventricular fibrillation and sudden cardiac death
Severe hypotension or shock, particularly in patients with underlying hemodynamic instability or polypharmacy
Marked extrapyramidal symptoms (akathisia, dystonia, parkinsonism) requiring treatment with anticholinergics (e.g., benztropine, diphenhydramine)
Neuroleptic malignant syndrome (rare but life-threatening): hyperthermia, rigidity, autonomic instability, altered mental status, elevated CK
Respiratory depression and airway compromise when combined with other sedatives or in patients with underlying respiratory failure
Seizures (rare), especially in patients with seizure disorders or on pro-convulsant medications

Special Populations

Elderly Patients:

Increased sensitivity to sedation, hypotension, and EPS
Start with lower doses: 0.625–1.25 mg for antiemesis, 2.5–5 mg for agitation
Monitor cardiovascular and neurological status closely

Hepatic Impairment:

Reduced metabolism prolongs drug effects
Consider 25–50% dose reduction and extended monitoring

Renal Impairment:

No specific dose adjustment typically required for renal dysfunction alone
Monitor for prolonged effects if significant organ dysfunction present

Pregnancy & Lactation:

Pregnancy: Generally avoided for elective use; use only if benefit clearly outweighs risk (e.g., severe refractory hyperemesis gravidarum)
Lactation: Limited data; consider alternative agents when possible; if used, monitor infant for sedation

Cardiac Disease:

Baseline ECG recommended if available before administration
Use lowest effective dose with continuous cardiac monitoring
Correct electrolyte abnormalities (K, Mg) before dosing when feasible

Monitoring

Baseline Assessment:

Baseline and/or post-dose ECG in patients receiving droperidol, particularly those with cardiac disease, electrolyte abnormalities, or on other QT-prolonging medications
Review medication list for QT-prolonging agents (methadone, amiodarone, ondansetron, haloperidol, etc.)
Check electrolytes (K, Mg) when feasible before administration

During & After Administration:

Continuous cardiac monitoring for patients receiving ≥2.5 mg IV/IM, repeated doses, or any dose in high-risk populations (elderly, structural heart disease, significant polypharmacy)
Blood pressure and heart rate at regular intervals; more frequent checks or continuous monitoring in hemodynamically unstable patients
Level of consciousness, airway patency, and respiratory rate; consider continuous pulse oximetry and capnography when combined with other sedatives
Assessment for EPS (akathisia, dystonia, rigidity) after administration, particularly at higher or repeated doses
In agitation protocols: time to adequate sedation, need for rescue medication, and overall safety events (oversedation, desaturation, hypotension)

Clinical Pearls

Agitation Dosing: For undifferentiated ED agitation, 5–10 mg droperidol IV/IM often provides rapid, effective control with a single agent; consider combining with midazolam for severe agitation per current ACEP guidance.

Give It Time: Peak sedative effect may not be obvious until 20–30 minutes—avoid stacking multiple sedatives too quickly and overshooting.

Lower Doses for Antiemesis: For migraine or cannabinoid hyperemesis, lower doses (0.625–2.5 mg) are usually sufficient and carry less QT and EPS risk.

QT Prolongation: Always scan the med list for other QT-prolonging agents (e.g., methadone, amiodarone, ondansetron, haloperidol) and correct electrolytes before and after dosing when possible.

Elderly & Cardiac Patients: In older adults or those with cardiac disease, consider starting at 2.5–5 mg for agitation and monitor closely; you can always redose, but you can't undose.

EPS Treatment: If significant akathisia or dystonia occurs, treat promptly with diphenhydramine or benztropine and document the reaction; consider alternative agents next time.

Documentation: When you use droperidol for sedation, document: indication, dose, route, time, vital signs, QTc (if known), and response—this is crucial for medico-legal protection and handoff.

Safety with Appropriate Use: Despite the black box, modern data support the safety of ED-level dosing (≤10 mg) with appropriate patient selection and monitoring—don't be afraid of the drug, just be deliberate with it.

References

1. Akorn Pharmaceuticals. (2023). Inapsine (droperidol) prescribing information. Lake Forest, IL.
2. American College of Emergency Physicians. (2021). Clinical policy: Critical issues in the diagnosis and management of the adult psychiatric patient in the emergency department. Annals of Emergency Medicine, 78(6), e81-e117.
3. Perkins, J., Ho, J. D., Vilke, G. M., & DeMers, G. (2015). American Academy of Emergency Medicine position statement: Safety of droperidol use in the emergency department. The Journal of Emergency Medicine, 49(5), 791-793.
4. Cisewski, D. H., & Rosales, A. (2022). Droperidol in the emergency department: Evidence-based review of its use for acute agitation. American Journal of Emergency Medicine, 52, 170-175.
5. Edge, R., Lambie, A., & Liang, M. (2021). Droperidol for Agitation in Acute Care Settings: A Review of Clinical Effectiveness and Guidelines. CADTH Rapid Response Report. Canadian Agency for Drugs and Technologies in Health.