II. Background

  1. Multiple studies demonstrated safety of Droperidol and as of 2015 was cleared to return to market in U.S. (available as of 2019)
  2. 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

III. Indications: Not a first line drug due to QT Prolongation

IV. Contraindications

  1. Absolute contraindications
    1. QTc Prolongation (>440 mSec in males, >450 msec in females)
  2. 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

V. Mechanism

  1. Butyrophenone Neuroleptic (first generation Antipsychotic) similar to Haloperidol
  2. Potent Dopamine receptor Antagonist at D2
    1. Antiemetic and Antipsychotic activity via dopamine Antagonist
  3. Serotonin Antagonist activity
  4. Antihistamine activity
  5. Weak alpha receptor Antagonist
    1. May result in peripheral vascular dilitation

VI. Dosing

  1. 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
  2. Headache
    1. Adults: 1.25 to 5 mg IM or slow IV (typical emergency department dose 2.5 mg slow IV)
  3. Agitation
    1. Adults: 5 mg IM (range 2.5 to 7.5 mg IM) or slow IV
    2. May combine with Midazolam 2 mg (up to 5 mg if needed)
    3. May require adult doses of 10 mg IV (up to 20 mg total per episode)

VII. Pharmacokinetics

  1. No dosing adjustments required for renal or hepatic failure
  2. 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

VIII. Adverse Effects

  1. 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)
      1. Calver (2015) Ann Emerg Med 66(3): 230-8 +PMID:25890395 [PubMed]
      2. Gaw (2020) Am J Emerg Med 38(7): 1310-14 [PubMed]
      3. Jackson (2007) Am J Syst Pharm 64(11): 1174-86 [PubMed]
  2. Sedation
    1. Usually resolves within 4 hours of dose
    2. Alertness may be decreased for 12 hours after dose
  3. Neurologic effects (treat with Benztropine, Diphenhydramine)
    1. Extrapyramidal Side Effects
    2. Akasthisia (2.9% of cases)
    3. Dystonia
  4. Neuroleptic Malignant Syndrome
  5. Orthostatic Hypotension

IX. Safety

  1. Unknown safety in Lactation
  2. 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
  3. Monitoring
    1. Baseline EKG
    2. Continuous cardiac monitoring for 3 hours after dose

X. Drug Interactions

  1. Agents that prolong QT Interval (see above)
    1. See Prolonged QT Interval due to Medication

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