Inapsine

Generic Name: Droperidol
Class: Anxiolytics, Sedatives, and Hypnotics; Miscellaneous
VA Class: CN205
CAS Number: 548-73-2

Warning(s)

  • 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.114

  • 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).114

  • 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).114

  • Do not administer droperidol if QT interval is prolonged.114

  • 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.114

  • Contraindicated in patients with known or suspected QT prolongation, including congenital long QT syndrome.114

  • 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).114 Other risk factors may include age >65 years, alcohol abuse, and concomitant use of benzodiazepines, volatile anesthetics, or IV opiates.114 (See Prolonged QT Syndrome under Cautions.)

  • Initiate droperidol at low dose and increase with caution as needed to achieve desired effect.114

Introduction

Butyrophenone derivative; structurally similar to haloperidol; pharmacologically similar to haloperidol and phenothiazines.a

Uses for Inapsine

Nausea and Vomiting Associated with Surgical and Diagnostic Procedures

Reduction of the incidence of nausea and vomiting associated with surgical and diagnostic procedures.114 a 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.114 (See Boxed Warning.)

Adjunct to Anesthesia and Neuroleptanalgesia

Has been used preoperatively and as an adjunct during induction and maintenance of general anesthesia and as an adjunct to regional anesthesia; also has been used in combination with an opiate analgesic (e.g., fentanyl) for neuroleptanalgesia as an anxiolytic and to potentially increase the opiate analgesic effect.a No longer recommended for these uses because of the risk of serious adverse effects.112 113

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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, principally that induced by cisplatin.100 101 102 103 104 105 106 107

Delirium

Occasionally used in the management of delirium;108 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.108 109 110 111

Inapsine Dosage and Administration

General

  • Routinely monitor vital signs and ECG.114

Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer IM or by slow IV injection.114 a

Dosage

Individualize dosage according to the patient’s age, weight, physical status, and underlying pathologic condition.114 Also consider other drugs, type of anesthesia used, and surgical procedure.114

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.114 116 Administer additional doses with caution and only if potential benefit outweighs potential risk.114

Adults

Nausea and Vomiting Associated with Surgical and Diagnostic Procedures
IV or IM

Initially, up to 2.5 mg.114 Administer additional doses of 1.25 mg with caution to achieve the desired effect, if potential benefit outweighs the potential risk.114

Delirium
IM

Usually, 5 mg.108 110 111

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.114 116

Adults

Nausea and Vomiting Associated with Surgical and Diagnostic Procedures
IV or IM

Maximum initial dose: 2.5 mg.114

Special Populations

Geriatric, Debilitated, and High-Risk Patients

Reduce initial dose in geriatric, debilitated, or high-risk patients.114 Carefully adjust subsequent dosage (if needed) according to response and tolerance following the initial dose.114

Cautions for Inapsine

Contraindications

  • Known or suspected QT interval prolongation (i.e., QTc interval >440 msec in males, >450 msec in females), including congenital long QT syndrome.114

  • Known hypersensitivity to droperidol or any ingredient in the formulation.114

Warnings/Precautions

Warnings

Prolonged QT Syndrome

QT interval prolongation and serious, sometimes fatal arrhythmias (torsades de pointes, ventricular arrhythmias, cardiac arrest) have occurred.114 (See Boxed Warning.)

ECG monitoring is recommended; do not use if QT interval prolongation is present.114

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.114

Promptly evaluate any signs or symptoms suggestive of irregular cardiac rhythm (e.g., palpitations, syncope).114

Hypotension

Possibility of severe hypotension; parenteral fluids and other supportive measures should be readily available.114

If hypotension occurs, consider possibility of hypovolemia and institute appropriate therapy with IV fluids.114

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.114 Because of the possibility of orthostatic hypotension, use care when moving and positioning patients during anesthesia.114

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).114

CNS Depression

CNS depressant effects; monitor vital signs routinely.114

Concurrent Use With Opiate Agonists

When concurrent use of opiates and droperidol is required, administer opiates in reduced dosage.114 Be familiar with each drug, particularly widely differing durations of action.a

Respiratory depression induced by opiates persists longer than analgesic effects.a 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).a Keep resuscitative equipment and an opiate antagonist readily available to manage apnea.a

Neuroleptic Malignant Syndrome (NMS)

NMS (altered consciousness, muscular rigidity, autonomic instability) has occurred.114

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.114

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.114

When droperidol is used to supplement these forms of anesthesia, be prepared to manage physiologic alterations involved.114

Hemodynamic Assessments

Droperidol may decrease pulmonary arterial pressure and interfere with interpretation of hemodynamic measurements made during diagnostic or surgical procedures.112

Monitoring

Monitor ECG and vital signs regularly.114

Effects on EEG

When EEG is used for postoperative monitoring, consider that the EEG pattern returns to normal slowly following droperidol use.114

Pheochromocytoma

Severe hypertension and tachycardia have occurred following droperidol administration in patients with diagnosed or suspected pheochromocytoma.114

Specific Populations

Pregnancy

Category C.114

Use in labor and delivery not recommended.114

Lactation

Not known whether droperidol is distributed into milk.114 Use with caution.114

Pediatric Use

Safety and efficacy not established in children <2 years of age.114

Geriatric Use

Use with caution; reduce initial dose and carefully adjust subsequent dosage.a

Hepatic Impairment

Use with caution.114

Renal Impairment

Use with caution.114

Common Adverse Effects

Hypotension, tachycardia, dysphoria, postoperative drowsiness, restlessness, hyperactivity, anxiety, extrapyramidal reactions (dystonia, akathisia, oculogyric crisis).114 a

Interactions for Inapsine

Drugs That Prolong QT Interval

Risk of prolonged QT interval and potentially serious or life-threatening arrhythmias.114 Avoid concomitant use of droperidol with drugs known to prolong the QT interval.114

Specific Drugs

Drug

Interaction

Comments

Anesthetics, regional or conduction (e.g., spinal or peridural anesthesia)

Possible altered respiration, peripheral vasodilation, and hypotension.114 (See Anesthesia under Cautions.)

Use with caution114

Antiarrhythmics, class I or III

Possible prolongation of the QT interval; potentially arrhythmogenic114

Avoid concomitant use of droperidol with drugs known to prolong the QT interval114

Antidepressants (e.g., tricyclics)

Potentially arrhythmogenic; some antidepressants known to prolong the QT interval114

Avoid concomitant use of droperidol with drugs known to prolong the QT interval114

Antihistamines known to prolong the QT interval (terfenadine, astemizole [no longer commercially available in US])

Potentially arrhythmogenic114

Avoid concomitant use of droperidol with drugs known to prolong the QT interval114

Antimalarials

Potentially arrhythmogenic; some antimalarials known to prolong the QT interval114

Avoid concomitant use of droperidol with drugs known to prolong the QT interval114

Calcium-channel blocking agents

Potentially arrhythmogenic; some calcium-channel blockers known to prolong the QT interval114

Avoid concomitant use of droperidol with drugs known to prolong the QT interval114

CNS depressants (alcohol, barbiturates, benzodiazepines, general or volatile anesthetics, opiates and other analgesics, sedatives, tranquilizers)

Possible additive or potentiated CNS depression114 a

Reduce initial droperidol dose in patients who have received other CNS depressants, or vice versa114

Cyclobenzaprine

Torsades de pointes, with progression to ventricular fibrillation, reported with concomitant use of droperidol, cyclobenzaprine, and fluoxetine.115 (Possible mechanism: inhibition of cyclobenzaprine metabolism by fluoxetine; droperidol may have contributed to QT interval prolongation and development of torsades de pointes.115 )

Diuretics

Potential for diuretic-induced hypokalemia or hypomagnesemia resulting in prolongation of the QT interval114

Use with caution114

Epinephrine

Possible paradoxical decrease in BP due to droperidol’s α-adrenergic blockade114

Use pressor agents other than epinephrine to treat hypotension that is unresponsive to IV fluids or repositioning of the patient114

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)114

Laxatives

Potential for laxative-induced hypokalemia or hypomagnesemia resulting in prolongation of the QT interval114

Use with caution114

MAO inhibitors

Risk factor for prolonged QT syndrome114

Use concomitantly with extreme caution or do not use114

Mineralocorticoids

Supraphysiologic doses of steroid hormones with mineralocorticoid activity may induce hypokalemia or hypomagnesemia, prolonging the QT interval114

Use with caution114

Neuroleptic agents known to prolong the QT interval (e.g., phenothiazines)

Potentially arrhythmogenic114

Avoid concomitant use of droperidol with drugs known to prolong the QT interval114

Inapsine Pharmacokinetics

Absorption

Onset

Onset occurs within 3–10 minutes following IM or IV administration, but peak effects may not be apparent until 30 minutes.114

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.114

Distribution

Extent

Reportedly crosses the blood-brain barrier and is distributed into the CSF.a

Reportedly crosses the placenta; not known whether droperidol is distributed into milk.a

Elimination

Metabolism

Metabolized in the liver.a

Elimination Route

Droperidol and its metabolites are excreted in urine (10% as unchanged drug) and feces.a

Stability

Storage

Parenteral

Injection

15–25°C; protect from light.114

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution CompatibilityHID

Compatible

Dextrose 5% in water

Ringer’s injection, lactated

Sodium chloride 0.9%

Drug CompatibilityHID
Admixture Compatibility

Compatible

Fentanyl citrate with ketamine HCl

Y-Site CompatibilityHID

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.a Potentiates the actions of other CNS depressants but apparently has no analgesic activity.114 a

  • Has antiemetic activity.114 a

  • Acts principally at CNS subcortical levels;a may cause extrapyramidal reactions.114 a

  • Exhibits some α-adrenergic blocking activity; attenuates the cardiovascular response to sympathomimetic amines (e.g., reduces pressor effect of epinephrine).114 a

  • Direct peripheral vasodilatory effects, alone or in conjunction with α-adrenergic blockade, may cause hypotension and decreased peripheral vascular resistance.114 a

  • May decrease pulmonary arterial pressure (particularly if abnormally high).114 a

  • May reduce the incidence of epinephrine-induced arrhythmias but does not appear to prevent other arrhythmias.114 a

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.114

  • Importance of avoiding alcohol during therapy due to risk of additive effects.114

  • Importance of women informing clinicians if they are or plan to become pregnant or to breast-feed.114

  • Importance of informing patients of other important precautionary information.114 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Droperidol

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection

2.5 mg/mL*

Droperidol Injection

Inapsine

Akorn

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions June 20, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

100. Grossman B, Lessin LS, Cohen P. Droperidol prevents nausea and vomiting from cis-platinum. N Engl J Med. 1979; 301:47. [PubMed 449910]

101. Jacobs AJ, Deppe G, Cohen CJ. A comparison of the antiemetic effects of droperidol and prochlorperazine in chemotherapy with cis-platinum. Gynecol Oncol. 1980; 10:55-7. [PubMed 7190532]

102. Wilson J, Weltz M, Solimando D et al. Continuous infusion droperidol: anti-emetic therapy for cis-platinum (DDP) toxicity. Proc Am Soc Clin Oncol. 1981; 22:421.

103. Mason BA, Dambra J, Grossman B et al. Effective control of cisplatin-induced nausea using high-dose steroids and droperidol. Cancer Treat Rep. 1982; 66:243-5. [IDIS 145462] [PubMed 7198937]

104. Brown RE, Gregg RE, Hood JC. Droperidol treatment in streptozocin-induced nausea and vomiting. Drug Intell Clin Pharm. 1982; 16:775-6. [IDIS 157659] [PubMed 6216088]

105. Owens NJ, Schauer AR, Nightingale CH et al. Antiemetic efficacy of prochlorperazine, haloperidol, and droperidol in cisplatin-induced emesis. Clin Pharm. 1984; 3:167-70. [IDIS 182892] [PubMed 6373102]

106. Lewis GO, Bernath AM, Ellison NM et al. Double-blind crossover trial of droperidol, metoclopramide, and prochlorperazine as antiemetics in cisplatin therapy. Clin Pharm. 1984; 3:618-21. [IDIS 193407] [PubMed 6391784]

107. Cersosimo RJ, Bromer R, Hoffer S et al. The antiemetic activity of droperidol administered by intramuscular injection during cisplatin chemotherapy: a pilot study. Drug Intell Clin Pharm. 1985; 19:118-21. [IDIS 195459] [PubMed 4038643]

108. Trzepacz P, Breitbart W, Levenson J et al for the American Psychiatric Association Working Group on Delirium. Practice guideline for the treatment of patients with delirium. Am J Psychiatry. 1999; 156(Supp 5):1-20.

109. Van Leeuwen A, Molders J, Sterkmans P et al. Droperidol in acutely agitated patients. J Nerv Ment Dis. 1977; 164:280-3. [PubMed 321727]

110. Resnick M, Burton B. Droperidol vs haloperidol in the initial management of acutely agitated patients. J Clin Psychiatry. 1984; 45:298-9. [IDIS 188732] [PubMed 6376480]

111. Thomas H, Schwartz E, Petrilli R et al. Droperidol versus haloperidol for chemical restraint of agutated and combative patients. Ann Emerg Med. 1992; 21:407-13. [PubMed 1554179]

112. Ahmed S. Dear healthcare professional letter regarding QT prolongation and torsades de pointes. Emeryville, CA: Akorn Inc.; 2001 Dec 4.

113. FDA strengthens warnings for droperidol. FDA Talk Paper. Rockville, MD: Food and Drug Administration; 2001 Dec 5.

114. Taylor Pharmaceuticals. Inapsine (droperidol) injection for intravenous or intramuscular use prescribing information. Decatur, IL; 2001 Nov.

115. Michalets EL, Smith LK, Van Tassel ED. Torsade de pointes resulting from the addition of droperidol to an existing cytochrome P450 drug interaction. Ann Pharmacother. 1998; 32:761-5. [IDIS 408347] [PubMed 9681092]

116. Gunn VL, Nechyba C, eds. The Harriett Lane handbook: a manual for pediatric house officers. 16th ed. Philadelphia, PA: Mosby; 2002:672-3.

a. AHFS drug information 2004. McEvoy GK, ed. Droperidol. Bethesda, MD: American Society of Health-System Pharmacists; 2004:2412-14

HID. Trissel LA. Handbook on injectable drugs. 17th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2013:428-32.

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