II. Background
- 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
- Followed 2001 reports of QTc Prolongation
- Mayo Clinic continued to use Droperidol between 2001 and 2020 without significant adverse events
III. Indications
- Antiemetic in refractory Vomiting
- Surgical or Diagnostic procedure
- Procedure related Nausea or Vomiting
- Conscious Sedation
- Migraine Headache
- Chemical Restraint (e.g. Sedation of the Violent Patient)
- Cannabinoid Hyperemesis
- First generation Antipsychotic (Neuroleptic)
IV. Contraindications
- Absolute contraindications
- QTc Prolongation (>440 mSec in males, >450 msec in females)
- Relative contraindications: Risk of QTc Prolongation
- Congestive Heart Failure
- Bradycardia (Heart Rate <50 beats per minute)
- Concurrent Diuretic use
- Cardiac hypertrophy
- Hypokalemia
- Hypomagnesemia
- Other causes of Prolonged QT Interval due to Medication
- Class I Antiarrhythmics
- Class III Antiarrhythmics
- Monoamine Oxidase Inhibitors
V. Mechanism
- Butyrophenone Neuroleptic (first generation Antipsychotic)
- Very similar structure and function to Haloperidol
- Potent Dopamine receptor Antagonist at D2
- Antiemetic and Antipsychotic activity via dopamine Antagonist
- Serotonin Antagonist activity
- Antihistamine activity
- Weak alpha receptor Antagonist
- May result in peripheral vascular dilitation
VI. Dosing
-
Antiemetic
- Adults: 1.25 to 2.5 mg IM or IV slowly (may give up to 5 mg IV or IM)
- Children: 0.1 mg/kg IM or IV slowly
-
Headache
- Adults: 1.25 to 5 mg IM or slow IV (typical emergency department dose 2.5 mg slow IV)
-
Agitation
- Adults: 5 mg IM (range 2.5 to 7.5 mg IM) or slow IV
- May combine with Midazolam 2 mg (up to 5 mg if needed)
- May require adult doses of 10 mg IV (up to 20 mg total per episode)
VII. Pharmacokinetics
- No dosing adjustments required for renal or hepatic failure
- Rapid onset (esp. Droperidol IM compared with Haloperidol IM)
- IV Onset: 3-10 minutes
- IV Peak Effect: 30 minutes
- IV Duration: 2-4 hours
- IV Half Life: 2 hours
VIII. Adverse Effects
-
QT Prolongation
- QT Prolongation >500 msecs occurs in 2.6% of patients
- Avoid use with other agents causing Prolonged QT Interval due to Medication
- May consider EKG before use (but not required)
- Dose dependent effect (QTc Prolongation more likely at doses >2.5 mg)
- FDA Black box warning due to observed QT Prolongation at therepeutic doses
- First reported in 2001, but rare in clinical use
- Report coincided with release of new, on patent Antiemetic (Ondansetron)
- Curiously, 12 years later Ondansetron was reported to have the potential for QTc Prolongation
- Studies have since demonstrated its safety when used at moderate dose (<=2.5 mg)
- Sedation
- Usually resolves within 4 hours of dose
- Alertness may be decreased for 12 hours after dose
- Neurologic effects (treat with Benztropine, Diphenhydramine)
- Extrapyramidal Side Effects
- Akasthisia (2.9% of cases)
- Dystonia
- Neuroleptic Malignant Syndrome
- Orthostatic Hypotension
IX. Safety
- Unknown safety in Lactation
- Pregnancy Category C
- See Migraine Medications in Pregnancy
- Teratogenic in animal studies and limited data in humans
- Generally avoided in pregnancy by obstetricians
- Monitoring
- Baseline EKG
- Continuous cardiac monitoring for 3 hours after dose
X. Drug Interactions
- Agents that prolong QT Interval (see above)
XI. Resources
XII. References
- (2002) Mosby's Drug Consult, p. 001117
- 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]