Droperidol (Monograph)
Brand name: Inapsine
Drug class: Dopamine Receptor Antagonists
Warning
- QT Interval Prolongation
-
QT interval prolongation and/or torsades de pointes (including fatalities) have occurred at doses at or below those recommended, in some cases when no known risk factors were present.
-
Because of potential for serious proarrhythmic effects and death, use only when response to other treatment is unacceptable (due to lack of efficacy or intolerable adverse effects).
-
Prior to administration, obtain 12-lead ECG to exclude the presence of prolonged QT interval (QTc interval >440 msec in males, >450 msec in females).
-
Do not administer droperidol if QT interval is prolonged.
-
If potential benefit outweighs risk of serious arrhythmia, monitor for arrhythmia with ECG prior to administration and for 2–3 hours after completion of therapy.
-
Contraindicated in patients with known or suspected QT prolongation, including congenital long QT syndrome.
-
Use with extreme caution in patients at risk for prolonged QT syndrome (e.g., CHF, bradycardia, diuretic use, cardiac hypertrophy, hypokalemia, hypomagnesemia, use of other drugs known to prolong QT interval). Other risk factors may include age >65 years, alcohol abuse, and concomitant use of benzodiazepines, volatile anesthetics, or IV opiates. (See Prolonged QT Syndrome under Cautions.)
-
Initiate droperidol at low dose and increase with caution as needed to achieve desired effect.
Introduction
Butyrophenone derivative; structurally similar to haloperidol; pharmacologically similar to haloperidol and phenothiazines.
Uses for Droperidol
Nausea and Vomiting Associated with Surgical and Diagnostic Procedures
Reduction of the incidence of nausea and vomiting associated with surgical and diagnostic procedures. Because of the risk of serious, sometimes fatal proarrhythmic effects, use only in patients who fail to respond adequately (because of insufficient efficacy or intolerable adverse effects) to other antiemetic therapy. (See Boxed Warning.)
Adjunct to Anesthesia and Neuroleptanalgesia
Has been used preoperatively† [off-label] and as an adjunct during induction and maintenance of general anesthesia† [off-label] and as an adjunct to regional anesthesia† [off-label]; also has been used in combination with an opiate analgesic (e.g., fentanyl) for neuroleptanalgesia† [off-label] as an anxiolytic and to potentially increase the opiate analgesic effect. No longer recommended for these uses because of the risk of serious adverse effects.
Nausea and Vomiting Associated with Cancer Chemotherapy
Has been used effectively alone or in combination antiemetic regimens to prevent and/or reduce cancer chemotherapy-induced nausea and vomiting† [off-label], principally that induced by cisplatin.
Delirium
Occasionally used in the management of delirium†; has been effective in the management of agitation (not necessarily delirium) and may be preferred to haloperidol in some delirious patients due to shorter half-life, more rapid onset of effect, and increased sedative effects.
Related/similar drugs
hydroxyzine, ondansetron, lorazepam, olanzapine, meclizine, Zofran, promethazine
Droperidol Dosage and Administration
General
-
Routinely monitor vital signs and ECG.
Administration
For solution and drug compatibility information, see Compatibility under Stability.
Administer IM or by slow IV injection.
Dosage
Individualize dosage according to the patient’s age, weight, physical status, and underlying pathologic condition. Also consider other drugs, type of anesthesia used, and surgical procedure.
Pediatric Patients
Nausea and Vomiting Associated with Surgical and Diagnostic Procedures
IV or IM
Children 2–12 years of age: Initially, up to 0.1 mg/kg (maximum of 2.5 mg), based on the patient’s age and clinical condition. Administer additional doses with caution and only if potential benefit outweighs potential risk.
Adults
Nausea and Vomiting Associated with Surgical and Diagnostic Procedures
IV or IM
Initially, up to 2.5 mg. Administer additional doses of 1.25 mg with caution to achieve the desired effect, if potential benefit outweighs the potential risk.
Delirium†
IM
Usually, 5 mg.
Prescribing Limits
Pediatric Patients
Nausea and Vomiting Associated with Surgical and Diagnostic Procedures
IV of IM
Children 2–12 years of age: Maximum initial dose of 0.1 mg/kg (up to 2.5 mg) based on age and clinical condition.
Adults
Nausea and Vomiting Associated with Surgical and Diagnostic Procedures
IV or IM
Maximum initial dose: 2.5 mg.
Special Populations
Geriatric, Debilitated, and High-Risk Patients
Reduce initial dose in geriatric, debilitated, or high-risk patients. Carefully adjust subsequent dosage (if needed) according to response and tolerance following the initial dose.
Cautions for Droperidol
Contraindications
-
Known or suspected QT interval prolongation (i.e., QTc interval >440 msec in males, >450 msec in females), including congenital long QT syndrome.
-
Known hypersensitivity to droperidol or any ingredient in the formulation.
Warnings/Precautions
Warnings
Prolonged QT Syndrome
QT interval prolongation and serious, sometimes fatal arrhythmias (torsades de pointes, ventricular arrhythmias, cardiac arrest) have occurred. (See Boxed Warning.)
ECG monitoring is recommended; do not use if QT interval prolongation is present.
Use with extreme caution in patients with risk factors for prolonged QT syndrome, including clinically important bradycardia (<50 bpm) or heart disease (e.g., CHF , cardiac hypertrophy); treatment with class I or III antiarrhythmic agents, MAO inhibitors, or other drugs known to prolong the QT interval; electrolyte imbalance (particularly hypomagnesemia or hypokalemia); or treatment with drugs (e.g., diuretics) that may cause electrolyte imbalance.
Promptly evaluate any signs or symptoms suggestive of irregular cardiac rhythm (e.g., palpitations, syncope).
Hypotension
Possibility of severe hypotension; parenteral fluids and other supportive measures should be readily available.
If hypotension occurs, consider possibility of hypovolemia and institute appropriate therapy with IV fluids.
Consider repositioning patient to improve venous return to the heart when operative conditions permit; however, during spinal and peridural anesthesia, placing the patient into a head-down position may result in a higher level of anesthesia than is desirable and may impair venous return to the heart. Because of the possibility of orthostatic hypotension, use care when moving and positioning patients during anesthesia.
If hypotension is not corrected with fluids or repositioning, consider use of pressor agents, but not epinephrine (may paradoxically decrease BP due to droperidol’s α-adrenergic blockade).
CNS Depression
CNS depressant effects; monitor vital signs routinely.
Concurrent Use With Opiate Agonists
When concurrent use of opiates and droperidol is required, administer opiates in reduced dosage. Be familiar with each drug, particularly widely differing durations of action.
Respiratory depression induced by opiates persists longer than analgesic effects. Before ordering opiate analgesics during anesthesia recovery, consider total dosage of administered opiates; if opiates are required during the recovery period, use initially in reduced dosages (as low as one-fourth to one-third of those usually recommended). Keep resuscitative equipment and an opiate antagonist readily available to manage apnea.
Neuroleptic Malignant Syndrome (NMS)
NMS (altered consciousness, muscular rigidity, autonomic instability) has occurred.
May be difficult to distinguish NMS from malignant hyperthermia perioperatively; consider prompt dantrolene treatment if increases in temperature, heart rate, and/or carbon dioxide production occur following administration of droperidol.
General Precautions
Anesthesia
Certain forms of conduction anesthesia (e.g., spinal anesthesia, peridural anesthesia) can alter respiration by blocking intercostal nerves and can cause peripheral vasodilation and hypotension; droperidol also has cardiovascular effects.
When droperidol is used to supplement these forms of anesthesia, be prepared to manage physiologic alterations involved.
Hemodynamic Assessments
Droperidol may decrease pulmonary arterial pressure and interfere with interpretation of hemodynamic measurements made during diagnostic or surgical procedures.
Monitoring
Monitor ECG and vital signs regularly.
Effects on EEG
When EEG is used for postoperative monitoring, consider that the EEG pattern returns to normal slowly following droperidol use.
Pheochromocytoma
Severe hypertension and tachycardia have occurred following droperidol administration in patients with diagnosed or suspected pheochromocytoma.
Specific Populations
Pregnancy
Category C.
Use in labor and delivery not recommended.
Lactation
Not known whether droperidol is distributed into milk. Use with caution.
Pediatric Use
Safety and efficacy not established in children <2 years of age.
Geriatric Use
Use with caution; reduce initial dose and carefully adjust subsequent dosage.
Hepatic Impairment
Use with caution.
Renal Impairment
Use with caution.
Common Adverse Effects
Hypotension, tachycardia, dysphoria, postoperative drowsiness, restlessness, hyperactivity, anxiety, extrapyramidal reactions (dystonia, akathisia, oculogyric crisis).
Drug Interactions
Drugs That Prolong QT Interval
Risk of prolonged QT interval and potentially serious or life-threatening arrhythmias. Avoid concomitant use of droperidol with drugs known to prolong the QT interval.
Specific Drugs
Drug |
Interaction |
Comments |
---|---|---|
Anesthetics, regional or conduction (e.g., spinal or peridural anesthesia) |
Possible altered respiration, peripheral vasodilation, and hypotension. (See Anesthesia under Cautions.) |
Use with caution |
Antiarrhythmics, class I or III |
Possible prolongation of the QT interval; potentially arrhythmogenic |
Avoid concomitant use of droperidol with drugs known to prolong the QT interval |
Antidepressants (e.g., tricyclics) |
Potentially arrhythmogenic; some antidepressants known to prolong the QT interval |
Avoid concomitant use of droperidol with drugs known to prolong the QT interval |
Antihistamines known to prolong the QT interval (terfenadine, astemizole [no longer commercially available in US]) |
Potentially arrhythmogenic |
Avoid concomitant use of droperidol with drugs known to prolong the QT interval |
Antimalarials |
Potentially arrhythmogenic; some antimalarials known to prolong the QT interval |
Avoid concomitant use of droperidol with drugs known to prolong the QT interval |
Calcium-channel blocking agents |
Potentially arrhythmogenic; some calcium-channel blockers known to prolong the QT interval |
Avoid concomitant use of droperidol with drugs known to prolong the QT interval |
CNS depressants (alcohol, barbiturates, benzodiazepines, general or volatile anesthetics, opiates and other analgesics, sedatives, tranquilizers) |
Possible additive or potentiated CNS depression |
Reduce initial droperidol dose in patients who have received other CNS depressants, or vice versa |
Cyclobenzaprine |
Torsades de pointes, with progression to ventricular fibrillation, reported with concomitant use of droperidol, cyclobenzaprine, and fluoxetine. (Possible mechanism: inhibition of cyclobenzaprine metabolism by fluoxetine; droperidol may have contributed to QT interval prolongation and development of torsades de pointes. ) |
|
Diuretics |
Potential for diuretic-induced hypokalemia or hypomagnesemia resulting in prolongation of the QT interval |
Use with caution |
Epinephrine |
Possible paradoxical decrease in BP due to droperidol’s α-adrenergic blockade |
Use pressor agents other than epinephrine to treat hypotension that is unresponsive to IV fluids or repositioning of the patient |
Fentanyl |
Increased BP reported (with or without preexisting hypertension) when droperidol administered with fentanyl or other parenteral analgesics (increased BP possibly resulted from unexplained changes in sympathetic activity after large doses or due to anesthetic/surgical stimulation during light anesthesia) |
|
Laxatives |
Potential for laxative-induced hypokalemia or hypomagnesemia resulting in prolongation of the QT interval |
Use with caution |
MAO inhibitors |
Risk factor for prolonged QT syndrome |
Use concomitantly with extreme caution or do not use |
Mineralocorticoids |
Supraphysiologic doses of steroid hormones with mineralocorticoid activity may induce hypokalemia or hypomagnesemia, prolonging the QT interval |
Use with caution |
Neuroleptic agents known to prolong the QT interval (e.g., phenothiazines) |
Potentially arrhythmogenic |
Avoid concomitant use of droperidol with drugs known to prolong the QT interval |
Droperidol Pharmacokinetics
Absorption
Onset
Onset occurs within 3–10 minutes following IM or IV administration, but peak effects may not be apparent until 30 minutes.
Duration
Following IM or IV administration, sedative and tranquilizing effects generally persist for 2–4 hours; alteration of consciousness may persist for up to 12 hours.
Distribution
Extent
Reportedly crosses the blood-brain barrier and is distributed into the CSF.
Reportedly crosses the placenta; not known whether droperidol is distributed into milk.
Elimination
Metabolism
Metabolized in the liver.
Elimination Route
Droperidol and its metabolites are excreted in urine (10% as unchanged drug) and feces.
Stability
Storage
Parenteral
Injection
15–25°C; protect from light.
Compatibility
Parenteral
Solution CompatibilityHID
Compatible |
---|
Dextrose 5% in water |
Ringer’s injection, lactated |
Sodium chloride 0.9% |
Drug CompatibilityHID
Compatible |
---|
Fentanyl citrate with ketamine HCl |
Compatible |
---|
Acyclovir sodium |
Amifostine |
Azithromycin |
Aztreonam |
Bivalirudin |
Bleomycin sulfate |
Cisatracurium besylate |
Cisplatin |
Cladribine |
Cyclophosphamide |
Dexmedetomidine HCl |
Docetaxel |
Doxorubicin HCl |
Doxorubicin HCl liposome injection |
Etoposide phosphate |
Famotidine |
Fenoldopam mesylate |
Filgrastim |
Fluconazole |
Fludarabine phosphate |
Gemcitabine HCl |
Granisetron HCl |
Hetastarch in lactated electrolyte injection (Hextend) |
Hydrocortisone sodium succinate |
Idarubicin HCl |
Linezolid |
Melphalan HCl |
Meperidine HCl |
Metoclopramide HCl |
Mitomycin |
Ondansetron HCl |
Oxaliplatin |
Paclitaxel |
Potassium chloride |
Propofol |
Remifentanil HCl |
Sargramostim |
Teniposide |
Thiotepa |
Vinblastine sulfate |
Vincristine sulfate |
Vinorelbine tartrate |
Incompatible |
Allopurinol sodium |
Amphotericin B cholesteryl sulfate complex |
Fluorouracil |
Foscarnet sodium |
Furosemide |
Leucovorin calcium |
Methotrexate sodium |
Nafcillin sodium |
Pemetrexed disodium |
Piperacillin sodium–tazobactam sodium |
Variable |
Heparin sodium |
Actions
-
Exhibits strong sedative and tranquilizing effects. Potentiates the actions of other CNS depressants but apparently has no analgesic activity.
-
Has antiemetic activity.
-
Acts principally at CNS subcortical levels; may cause extrapyramidal reactions.
-
Exhibits some α-adrenergic blocking activity; attenuates the cardiovascular response to sympathomimetic amines (e.g., reduces pressor effect of epinephrine).
-
Direct peripheral vasodilatory effects, alone or in conjunction with α-adrenergic blockade, may cause hypotension and decreased peripheral vascular resistance.
-
May decrease pulmonary arterial pressure (particularly if abnormally high).
-
May reduce the incidence of epinephrine-induced arrhythmias but does not appear to prevent other arrhythmias.
Advice to Patients
-
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses or alcohol use.
-
Importance of avoiding alcohol during therapy due to risk of additive effects.
-
Importance of women informing clinicians if they are or plan to become pregnant or to breast-feed.
-
Importance of informing patients of other important precautionary information. (See Cautions.)
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Parenteral |
Injection |
2.5 mg/mL* |
Droperidol Injection |
|
Inapsine |
Akorn |
AHFS DI Essentials™. © Copyright 2024, Selected Revisions May 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.
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