Boxed Warning
Arrhythmias:
Cases of QT prolongation and/or torsade de pointes have been reported in patients receiving droperidol at doses at or below recommended doses. Some cases have occurred in patients with no known risk factors for QT prolongation, and some cases have been fatal.
Due to its potential for serious proarrhythmic effects and death, reserve droperidol for use in the treatment of patients who fail to show an acceptable response to other adequate treatments, either because of insufficient effectiveness or the inability to achieve an effective dose due to intolerable adverse effects from those drugs.
Cases of QT prolongation and serious arrhythmias (eg, torsade de pointes) have been reported in patients treated with droperidol. Based on these reports, all patients should undergo a 12-lead ECG prior to administration of droperidol to determine if a prolonged QT interval (ie, QTc greater than 440 msec for males or 450 msec for females) is present. If there is a prolonged QT interval, do not administer droperidol. For patients in whom the potential benefit of droperidol treatment is felt to outweigh the risks of potentially serious arrhythmias, perform ECG monitoring prior to treatment and continue for 2 to 3 hours after completing treatment to monitor for arrhythmias.
Droperidol is contraindicated in patients with known or suspected QT prolongation, including patients with congenital long QT syndrome.
Administer droperidol with extreme caution to patients who may be at risk for development of prolonged QT syndrome (eg, congestive heart failure, bradycardia, use of a diuretic, cardiac hypertrophy, hypokalemia, hypomagnesemia, or administration of other drugs known to increase the QT interval). Other risk factors may include age greater than 65 years, alcohol abuse, and use of agents such as benzodiazepines, volatile anesthetics, and IV opiates. Initiate droperidol at a low dose and adjust upward, with caution, as needed to achieve the desired effect.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection:
Generic: 2.5 mg/mL (2 mL)
Pharmacology
Mechanism of Action
Droperidol is a butyrophenone antipsychotic; antiemetic effect is a result of blockade of dopamine stimulation of the chemoreceptor trigger zone. Other effects include alpha-adrenergic blockade, peripheral vascular dilation, and reduction of the pressor effect of epinephrine resulting in hypotension and decreased peripheral vascular resistance; may also reduce pulmonary artery pressure
Pharmacokinetics/Pharmacodynamics
Absorption
IM: Rapid (Cressman 1973)
Distribution
Crosses blood-brain barrier (McKeage 2006); Vd: Children: ~0.6 L/kg; Adults: ~1.5 L/kg McKeage 2006)
Metabolism
Hepatic, to p-fluorophenylacetic acid, benzimidazolone, p-hydroxypiperidine
Excretion
Urine (75%, <1% as unchanged drug); feces (22%, 11% as unchanged drug) (McKeage 2006)
Onset of Action
3 to 10 minutes; Peak effect: Within 30 minutes
Duration of Action
2 to 4 hours, may extend to 12 hours
Half-Life Elimination
Children ~ 1.7 hours; Adults: ~2 hours (McKeage 2006)
Protein Binding
85% to 90% (McKeage 2006)
Use: Labeled Indications
Postoperative nausea/vomiting (PONV): Prevention and/or treatment of nausea and vomiting from surgical and diagnostic procedures
Use: Off Label
Acute undifferentiated agitationbyes
Data from randomized, placebo- and active-control studies supports the use of droperidol as monotherapy or with concomitant benzodiazepines for decreasing time to sedation and reducing the risk of needing additional medications in the treatment of acute undifferentiated agitation, including agitation caused by trauma, acute psychiatric or medical disorders, or intoxication from alcohol or illicit substances Calver 2015, Chan 2013, Isbister 2010, Knott 2006, Martel 2005, Taylor 2016, Thomas 2016 Data from a meta-analysis supports the use of droperidol for decreasing time to tranquilization and reducing the risk of needing additional medications in the treatment of psychosis-induced aggression or agitation Khokhar 2016.
Based on the American Academy of Emergency Medicine (AAEP) position statement on the safety of droperidol use in the emergency department, droperidol is safe and effective for the management of agitation. Despite a recommendation by the Food and Drug Administration for strict ECG monitoring to detect QTc prolongation with droperidol use, the AAEP position statement does not recommend monitoring ECG for doses less than 2.5 mg Perkins 2015. Based on a clinical policy by the American College of Emergency Physicians (ACEP), antipsychotics like droperidol are effective and recommended for the management of acute agitation in patients with known psychiatric illness for which antipsychotics are indicated. Guidelines from the Society of Critical Care Medicine (SCCM) on the management of agitation in the intensive care unit do not mention the use of droperidol.
Contraindications
Hypersensitivity to droperidol or any component of the formulation; known or suspected QT prolongation, including congenital long QT syndrome (prolonged QTc is defined as >440 msec in males or >450 msec in females)
Canadian labeling: Additional contraindications (not in US labeling): Not for use in children ≤2 years of age
Dosage and Administration
Dosing: Adult
Note: Titrate carefully to desired effect
Acute undifferentiated agitation (off-label use):
IM: Initial: 5 to 10 mg, as monotherapy or in combination with a benzodiazepine; wait at least 10 to 30 minutes before providing additional medications for agitation if needed (Calver 2015; Isbister 2010; Martel 2005; Thomas 1992).
IV: Initial: 2.5 to 10 mg, as monotherapy or in combination with a benzodiazepine; may repeat droperidol dose every 5 minutes until sedation achieved; maximum dose 20 mg per episode; median required dose was 10 mg in one study (Chan 2013; Knott 2006; Taylor 2016; Thomas 1992).
Postoperative nausea/vomiting (PONV): IM, IV:
Manufacturer labeling: Maximum initial dose: 2.5 mg; additional doses of 1.25 mg may be administered with caution to achieve desired effect
Consensus guideline recommendations: 0.625 to 1.25 mg IV administered at the end of surgery (Gan 2007)
Dosing: Geriatric
Refer to adult dosing; use reduced initial dose.
Dosing: Pediatric
Dosage must be individualized, based on age, body weight, underlying medical conditions, physical status, concomitant medications, type of anesthesia, and surgical procedure.
Postoperative nausea and vomiting (PONV):
Prophylaxis if high risk for PONV: Note: Not the preferred agent: Children ≥2 years and Adolescents: IM, IV: 0.01 to 0.015 mg/kg/dose given near the end of surgery (Gan 2014); maximum dose: 1.25 mg/dose; administer additional doses after at least 6 hours with caution and only if potential benefit outweighs risks; Note: Previous reports suggested a higher dose of 0.075 mg/kg as effective; however, due to side effects associated with the higher doses, doses >0.05 mg/kg are considered excessive and no longer recommended (Gan 2007; Henzi 2000).
Treatment (not first line): Children 2 to 12 years; IM, IV: Maximum initial dose: 0.1 mg/kg/dose; administer additional doses with extreme caution and only if potential benefit outweighs risks
Reconstitution
IV infusion: Dilute in 50-100 mL NS or D5W.
Administration
IM, IV: Administer IM or IV; according to the manufacturer, IV push administration should be slow. For IV infusion, further dilute.
Storage
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light. Solutions diluted in NS or D5W are stable at room temperature for up to 7 days in PVC bags or glass bottles. Solutions diluted in LR are stable at room temperature for 24 hours in PVC bags and up to 7 days in glass bottles.
Drug Interactions
Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy
Acetylcholinesterase Inhibitors (Central): May enhance the neurotoxic (central) effect of Antipsychotic Agents. Severe extrapyramidal symptoms have occurred in some patients. Monitor therapy
Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Monitor therapy
Amisulpride: Antipsychotic Agents may enhance the adverse/toxic effect of Amisulpride. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Avoid combination
Amisulpride: May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Avoid combination
Amphetamines: Antipsychotic Agents may diminish the stimulatory effect of Amphetamines. Monitor therapy
Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Monitor therapy
Anti-Parkinson Agents (Dopamine Agonist): Antipsychotic Agents (First Generation [Typical]) may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Antipsychotic Agents (First Generation [Typical]). Management: Avoid concomitant therapy if possible and monitor for decreased effects of both agents when these combinations cannot be avoided. Atypical antipsychotics such as clozapine and quetiapine may be less likely to reduce the effects of anti-Parkinson agents. Consider therapy modification
Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification
Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Bromopride: Droperidol may enhance the adverse/toxic effect of Bromopride. Avoid combination
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Consider therapy modification
BuPROPion: May enhance the neuroexcitatory and/or seizure-potentiating effect of Agents With Seizure Threshold Lowering Potential. Monitor therapy
Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Ceritinib: May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy
ChlorproMAZINE: Droperidol may enhance the CNS depressant effect of ChlorproMAZINE. Droperidol may enhance the QTc-prolonging effect of ChlorproMAZINE. Management: Consider alternatives to this drug combination. If combined, dose reductions are recommended. Monitor for additive toxicities such as QTc interval prolongation, ventricular arrhythmias, and CNS depression. Consider therapy modification
Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Avoid combination
Clarithromycin: QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Clarithromycin. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy
CloZAPine: QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of CloZAPine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy
CNS Depressants: Droperidol may enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Exceptions: ChlorproMAZINE; CloZAPine; Flupentixol; Haloperidol; Methadone; OLANZapine; QUEtiapine; RisperiDONE; Thioridazine. Consider therapy modification
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Domperidone: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification
Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Avoid combination
Fexinidazole [INT]: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification
Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy
Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Monitor therapy
Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Avoid combination
Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Guanethidine: Antipsychotic Agents may diminish the therapeutic effect of Guanethidine. Monitor therapy
Haloperidol: QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy
HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification
Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification
Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification
Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification
Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Monitor therapy
Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Consider therapy modification
Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Avoid combination
Lithium: May enhance the neurotoxic effect of Antipsychotic Agents. Lithium may decrease the serum concentration of Antipsychotic Agents. Specifically noted with chlorpromazine. Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Mequitazine: Antipsychotic Agents may enhance the arrhythmogenic effect of Mequitazine. Management: Consider alternatives to one of these agents when possible. While this combination is not specifically contraindicated, mequitazine labeling describes this combination as discouraged. Consider therapy modification
Methadone: Droperidol may enhance the CNS depressant effect of Methadone. Droperidol may enhance the QTc-prolonging effect of Methadone. Management: Consider alternatives. If combined, dose reductions are recommended. Monitor for additive toxicities such as QTc interval prolongation, ventricular arrhythmias, and CNS depression. Patients with additional risk factors are at even higher risk. Consider therapy modification
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification
Methylphenidate: Antipsychotic Agents may enhance the adverse/toxic effect of Methylphenidate. Methylphenidate may enhance the adverse/toxic effect of Antipsychotic Agents. Monitor therapy
Metoclopramide: Droperidol may enhance the adverse/toxic effect of Metoclopramide. Avoid combination
MetyroSINE: May enhance the adverse/toxic effect of Droperidol. Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Monitor therapy
Ondansetron: May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination
Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination
Pentamidine (Systemic): May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification
Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Avoid combination
Piribedil: Antipsychotic Agents may diminish the therapeutic effect of Piribedil. Piribedil may diminish the therapeutic effect of Antipsychotic Agents. Management: Use of piribedil with antiemetic neuroleptics is contraindicated, and use with antipsychotic neuroleptics, except for clozapine, is not recommended. Avoid combination
Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Avoid combination
Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Avoid combination
Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Consider therapy modification
QT-prolonging Agents (Highest Risk): May enhance the QTc-prolonging effect of Droperidol. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Exceptions: ChlorproMAZINE; Methadone; Ziprasidone. Consider therapy modification
QT-prolonging Antidepressants (Moderate Risk): QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy
QT-prolonging Antipsychotics (Moderate Risk): May enhance the QTc-prolonging effect of Droperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Amisulpride; CloZAPine; Droperidol; Pimozide. Monitor therapy
QT-prolonging Class IC Antiarrhythmics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy
QT-prolonging Kinase Inhibitors (Moderate Risk): QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy
QT-prolonging Miscellaneous Agents (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Domperidone. Monitor therapy
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy
QT-prolonging Quinolone Antibiotics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy
Quinagolide: Antipsychotic Agents may diminish the therapeutic effect of Quinagolide. Monitor therapy
Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Monitor therapy
Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Avoid combination
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy
Saquinavir: QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Saquinavir. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy
Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Consider therapy modification
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy
Serotonergic Agents (High Risk): May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Monitor therapy
Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification
Sulpiride: Antipsychotic Agents may enhance the adverse/toxic effect of Sulpiride. Avoid combination
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification
Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification
Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination
Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Monitor therapy
Thiopental: Droperidol may enhance the therapeutic effect of Thiopental. Management: Consider thiopental dose reduction when used concomitantly with droperidol. Monitor patient response to treatment closely if using this combination. Consider therapy modification
Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Avoid combination
Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Voriconazole: May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy
Ziprasidone: Droperidol may enhance the QTc-prolonging effect of Ziprasidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Avoid combination
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification
Adverse Reactions
Frequency not defined.
Cardiovascular: Cardiac arrest, hypertension, hypotension (especially orthostatic), QTc prolongation (dose dependent), tachycardia, torsade de pointes, ventricular tachycardia
Central nervous system: Anxiety, chills, depression (postoperative, transient), dizziness, drowsiness (postoperative) increased, dysphoria, extrapyramidal symptoms (akathisia, dystonia, oculogyric crisis), hallucinations (postoperative), hyperactivity, neuroleptic malignant syndrome (NMS) (rare), restlessness
Respiratory: Bronchospasm, laryngospasm
Miscellaneous: Anaphylaxis, shivering
Warnings/Precautions
Concerns related to adverse effects:
- Arrhythmias: [US Boxed Warning]: Cases of QT prolongation and torsade de pointes, including some fatal cases, have been reported. Use extreme caution in patients with bradycardia (<50 bpm), cardiac disease, concurrent MAO inhibitor therapy, Class I and Class III antiarrhythmics or other drugs known to prolong QT interval, and electrolyte disturbances (hypokalemia or hypomagnesemia), including concomitant drugs which may alter electrolytes (diuretics).
- Anticholinergic effects: May cause anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention); use with caution in patients with decreased gastrointestinal motility, urinary retention, BPH, xerostomia, or visual problems. Relative to other neuroleptics, droperidol has a low potency of cholinergic blockade (Richelson 1999).
- CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).
- Esophageal dysmotility/aspiration: Antipsychotic use has been associated with esophageal dysmotility and aspiration; risk increases with age. Use with caution in patients at risk for aspiration pneumonia (eg, Alzheimer disease), particularly in patients >75 years (Herzig 2017; Maddalena 2004).
- Extrapyramidal symptoms: May cause extrapyramidal symptoms (EPS), including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia (risk of these reactions is generally much lower relative to typical/conventional antipsychotics; frequencies reported are similar to placebo). Risk of dystonia (and possibly other EPS) may be greater with increased doses, use of conventional antipsychotics, males, and younger patients. Factors associated with greater vulnerability to tardive dyskinesia include older in age, female gender combined with postmenopausal status, Parkinson disease, pseudoparkinsonism symptoms, affective disorders (particularly major depressive disorder), concurrent medical diseases such as diabetes, previous brain damage, alcoholism, poor treatment response, and use of high doses of antipsychotics (APA [Lehman 2004]; Soares-Weiser 2007). Consider therapy discontinuation with signs/symptoms of tardive dyskinesia.
- Hyperprolactinemia: May increase prolactin levels; clinical significance of hyperprolactinemia in patients with breast cancer or other prolactin-dependent tumors is unknown (Bargiota 2013; Froes Brandao 2016).
- Neuroleptic malignant syndrome (NMS): Use may be associated with neuroleptic malignant syndrome (NMS); monitor for mental status changes, fever, muscle rigidity and/or autonomic instability.
- Orthostatic hypotension: May cause orthostatic hypotension; use with caution in patients at risk of this effect or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, hypovolemia, or concurrent medication use which may predispose to hypotension/bradycardia).
- Temperature regulation: Impaired core body temperature regulation may occur; caution with strenuous exercise, heat exposure, dehydration, and concomitant medication possessing anticholinergic effects.
Disease-related concerns:
- Hepatic impairment: Use with caution in patients with severe hepatic impairment.
- Pheochromocytoma: Use with caution in patients with pheochromocytoma; severe hypertension and/or tachycardia may occur.
- Renal impairment: Use with caution in patients with renal impairment.
- Seizures: Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold (Chase 2002).
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information
Monitoring Parameters
To identify QT prolongation, a 12-lead ECG prior to use is recommended; continued ECG monitoring for 2-3 hours following administration is recommended. Vital signs; serum magnesium and potassium; mental status, abnormal involuntary movement scale (AIMS); observe for dystonias, extrapyramidal side effects, and temperature changes
Pregnancy
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse events were observed in some animal reproduction studies. Droperidol has been evaluated for the adjunctive management of hyperemesis gravidarum (Ferreira 2003; Nageotte 1996); however, use for the treatment of persistent symptoms of nausea and vomiting in pregnancy is not recommended (ACOG 189 2018).
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience anxiety, fatigue, or agitation. Have patient report immediately to prescriber abnormal movements, twitching, change in balance, difficulty swallowing, difficulty speaking, fast heartbeat, abnormal heartbeat, severe dizziness, passing out, sensing things that seem real but are not, chest pain, behavioral changes, or signs of neuroleptic malignant syndrome (fever, muscle cramps or stiffness, dizziness, severe headache, confusion, change in thinking, fast heartbeat, abnormal heartbeat, or sweating a lot) (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
