Droperidol

Multiple studies demonstrated safety of Droperidol and as of 2015 was cleared to return to market in U.S. (available as of 2019)
Developed in the 1960s and available in U.S. until 2012, when U.S. manufacturing ceased
1. Followed 2001 reports of QTc Prolongation
2. Mayo Clinic continued to use Droperidol between 2001 and 2020 without significant adverse events

Absolute contraindications
1. QTc Prolongation (>440 mSec in males, >450 msec in females)
Relative contraindications: Risk of QTc Prolongation
1. Congestive Heart Failure
2. Bradycardia (Heart Rate <50 beats per minute)
3. Concurrent Diuretic use
4. Cardiac hypertrophy
5. Hypokalemia
6. Hypomagnesemia
7. Other causes of Prolonged QT Interval due to Medication
  1. Class I Antiarrhythmics
  2. Class III Antiarrhythmics
  3. Monoamine Oxidase Inhibitors

Butyrophenone Neuroleptic (first generation Antipsychotic)
1. Very similar structure and function to Haloperidol
Potent Dopamine receptor Antagonist at D2
1. Antiemetic and Antipsychotic activity via dopamine Antagonist
Serotonin Antagonist activity
Antihistamine activity
Weak Alpha 1 Adrenergic ReceptorAntagonist
1. May result in peripheral vasodilation (Hypotension risk)

General Adult Dosing
1. IM: 5 to 10 mg IM (cummulative total dosing up to 20 mg per episode)
2. IV: 2.5 to 5 mg slow IV (with cummulative doses up to 10-20 mg per episode)
Antiemetic
1. Adults: 1.25 to 2.5 mg IM or IV slowly (may give up to 5 mg IV or IM)
2. Children: 0.1 mg/kg IM or IV slowly
Headache
1. Adults: 1.25 to 2.5 mg IM or slow IV (may give up to 5-10 mg IV/IM)
2. Typical emergency department dose: 2.5 mg slow IV
Agitation
1. Adults: 5 mg IM (range 2.5 to 10 mg IM) or slow IV
  1. May require adult doses of 10 mg IV/IM (up to 20 mg total per episode)
2. May combine with Midazolam 2 mg (up to 5 mg if needed)
  1. However, observe for significant CNS depression

No dosing adjustments required for renal or hepatic failure
Hepatic metabolism: CYP3A4
Rapid onset (esp. Droperidol IM compared with Haloperidol IM)
1. IV Onset: 3-10 minutes
2. IV Peak Effect: 30 minutes
3. IV Duration: 2-4 hours
4. IV Half Life: 2 hours

QT Prolongation
1. QT Prolongation >500 msecs occurs in 2.6% of patients
2. Avoid use with other agents causing Prolonged QT Interval due to Medication
3. May consider EKG before use (but not required)
4. Dose dependent effect (QTc Prolongation more likely at doses >2.5 mg)
5. FDA Black box warning due to observed QT Prolongation at therepeutic doses
  1. First reported in 2001, but rare in clinical use
  2. Report coincided with release of new, on patent Antiemetic (Ondansetron)
    1. Curiously, 12 years later Ondansetron was reported to have the potential for QTc Prolongation
6. Studies have since demonstrated its safety when used at moderate dose (<=2.5 mg)
Sedation
1. Usually resolves within 4 hours of dose
2. Alertness may be decreased for 12 hours after dose
Extrapyramidal Side Effects (Akasthisia in 2.9%, Dystonia)
1. Avoid rapid bolus! (author orders Droperidol added to a 1 Liter bag of saline)
2. May treat with Benztropine or Diphenhydramine
Neuroleptic Malignant Syndrome (rare case reports)
Orthostatic Hypotension

Unknown safety in Lactation
Pregnancy Category C
1. See Migraine Medications in Pregnancy
2. Teratogenic in animal studies and limited data in humans
3. Generally avoided in pregnancy by obstetricians
Monitoring
1. Baseline EKG
2. Continuous cardiac monitoring for 3 hours after dose

(2002) Mosby's Drug Consult, p. 001117
Lovecchio (2025) Crit Dec Emerg Med 39(9): 34
Hill (2000) Emerg Med Clin North Am 18(2):301-15 [PubMed]
Richman (2002) Am J Emerg Med 20(1):39-42 [PubMed]
Strayer (2020) EM:Rap 20(9): 7-9 [PubMed]