Droperidol, a butyrophenone derivative that is structurally similar to haloperidol, has pharmacologic actions similar to those of haloperidol and phenothiazines.
Droperidol is used to reduce the incidence of nausea and vomiting during surgical and diagnostic procedures. However, because of the risk of serious, sometimes fatal proarrhythmic effects, the manufacturer states that use of droperidol should be reserved only for those patients who have failed to respond adequately to other drugs in the treatment of perioperative nausea and vomiting, either because of insufficient efficacy or intolerable adverse effects.114 (See Cautions: Precautions and Contraindications.)
The drug also has been used preoperatively† and as an adjunct during induction and maintenance of general anesthesia† and as an adjunct to regional anesthesia†. Droperidol also has been used in combination with an opiate analgesic, such as fentanyl, for neuroleptanalgesia† as an anxiolytic and to potentially increase the analgesic effect of the opiate. However, because of the risk of serious adverse effects, the manufacturer no longer recommends these uses.112, 113
Droperidol 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
Antipsychotic agents, principally haloperidol but occasionally droperidol, are used in the management of delirium†.108 (See Uses: Delirium, in Haloperidol 28:16.08.32.) Because droperidol has been shown to be effective in the management of agitation, although not necessarily delirium, in hospitalized patients, the drug may be preferred in some delirious patients due to its shorter half-life, more rapid onset of effect, and increased sedative effects compared with haloperidol.108, 109, 110, 111
Droperidol is administered IM or by slow IV injection.
Dosage of droperidol should be individualized according to the patient's age, weight, physical status, and underlying pathologic condition. Other factors to be considered when determining the dosage of droperidol include other drugs and type of anesthesia used as well as the surgical procedure involved. The initial dose of droperidol should be appropriately reduced in geriatric, debilitated, or high-risk patients and in those who have received other CNS depressants, including analgesics or anesthetics. (See Cautions: Precautions and Contraindications.) Subsequent dosage if needed in such patients should be carefully adjusted according to the patient's response and tolerance following the initial dose.
The maximum recommended initial adult IM or IV dose of droperidol is 2.5 mg.114 Additional doses of 1.25 mg may be administered with caution to achieve the desired effect, if the potential benefit outweighs the potential risk.114
The maximum recommended initial IM or IV dose of droperidol in children 2-12 years of age is 0.1 mg/kg (up to 2.5 mg), based on the patient's age and clinical condition.114, 116 Additional doses should be administered with caution, and only if the potential benefit outweighs the potential risk.114
For use in the management of delirium, the usual adult droperidol dose is 5 mg IM.108, 110, 111
Adverse effects of droperidol are qualitatively similar to those of haloperidol.
Droperidol may cause potentially fatal prolongation of the QT interval, torsades de pointes, cardiac arrest, and ventricular tachycardia.114 These adverse effects have been reported in patients receiving dosages of droperidol that were above, within, or below recommended dosages and also have occurred in patients without known risk factors for QT prolongation. 112, 113, 114 Dose-related increases in QT interval within 10 minutes of droperidol administration were observed in one clinical study in patients without known cardiac disease.114, 112 At least one case of torsades de pointes that recurred upon rechallenge has been reported.114 Patients developing symptoms suggestive of irregular cardiac rhythms (e.g., palpitations, syncope) after administration of droperidol should be promptly evaluated.114
The most frequent somatic adverse effects associated with droperidol are transient, mild to moderate hypotension and occasionally tachycardia, which may occur immediately following administration of the drug; hypotension may also occur during the immediate postoperative period. If hypotension is severe or persists for an extended period of time, the possibility of hypovolemia should be considered and appropriate therapy with parenteral fluids should be instituted. Severe hypotension that cannot be corrected by fluid replacement or other supportive measures may be alleviated by administration of norepinephrine or phenylephrine; epinephrine should not be used since droperidol can cause a reversal of epinephrine's pressor effects, resulting in a paradoxical lowering of blood pressure.
Elevated blood pressure has occurred in patients with or without preexisting hypertension, following administration of droperidol combined with fentanyl or other parenteral analgesics; it has been suggested that this effect may result from unexplained alterations in sympathetic activity following administration of large doses, or from anesthetic or surgical stimulation during light anesthesia.
Severe hypertension and tachycardia have occurred in patients with diagnosed or suspected pheochromocytoma after administration of droperidol.114
Extrapyramidal reactions may occur in patients receiving droperidol and most often consist of dystonic reactions, akathisia, and oculogyric crises. Other manifestations include extended neck, flexed arms, fine tremor of limbs, and upward rotation of eyes. Common adverse behavioral effects including dysphoria, restlessness, hyperactivity, and anxiety may also occur as a result of either inadequate dosage of droperidol or part of the symptom complex of akathisia. Most patients respond rapidly to treatment with an anticholinergic antiparkinsonian agent.
Postoperative drowsiness occurs frequently with droperidol. Other less frequent adverse nervous system effects of droperidol include dizziness, chills, and/or shivering. Hallucinations (possibly emergence delirium), which are sometimes associated with transient periods of mental depression, and nightmares have occurred postoperatively when droperidol was administered prior to surgery.
Rarely, neuroleptic malignant syndrome, which may be characterized by altered consciousness, muscle rigidity, and autonomic instability, has occurred in patients receiving droperidol.114 For additional information on neuroleptic malignant syndrome (NMS), see Extrapyramidal Reactions in Cautions: Nervous System Effects in the Phenothiazines General Statement 28:16.08.24.
When droperidol is used with an opiate analgesic such as fentanyl, respiratory depression, apnea, and muscle rigidity, particularly involving the muscles of respiration, may occur, and if left untreated, can progress to respiratory arrest.
Laryngospasm, bronchospasm, and anaphylaxis have occurred in some patients receiving droperidol. Facial sweating has reportedly occurred.
Precautions and Contraindications
Droperidol shares the toxic potentials of phenothiazines, and the usual precautions of phenothiazine therapy should be observed. (See Cautions in the Phenothiazines General Statement 28:16.08.24.)
Because cases of QT-interval prolongation and severe cardiac arrhythmias, including torsades de pointes, have been reported, the manufacturer states that a 12-lead ECG should be obtained from all patients prior to administration of droperidol, and the drug should not be administered in male or female patients with a QTc interval exceeding 440 or 450 msec, respectively.114 The manufacturer also states that droperidol should be used only in patients who have failed to respond adequately to other drugs, either because of insufficient efficacy or intolerable adverse effects. 112, 113, 114 If the anticipated benefits appear to outweigh the risks of droperidol, ECG monitoring should be performed prior to administering the drug and continued for 2-3 hours after completing therapy to monitor for arrhythmias.114 In addition, droperidol should be initiated at a low dosage and titrated upward, with caution, to achieve the desired effect. (See Dosage and Administration: Dosage)114
Droperidol should be used with extreme caution in patients who may be at risk for development of prolonged QT syndrome (e.g., congestive heart failure, bradycardia, use of a diuretic, cardiac hypertrophy, hypokalemia, hypomagnesemia, use of drugs known to prolong the QT interval).114 Other risk factors for prolongation of the QT interval include age (i.e., older than 65 years of age), alcohol abuse, and the concomitant use of benzodiazepines, volatile anesthetics, or IV opiates.114
Because of the possibility of severe hypotension in patients receiving droperidol, parenteral fluids and other supportive measures should be readily available. As with other CNS depressants, patients should be carefully monitored following administration of droperidol; vital signs should be monitored routinely.
When droperidol is administered with an opiate analgesic such as fentanyl, the cautions applicable to each ingredient should be considered, and the clinician should be familiar with the special properties of each drug, particularly the widely differing durations of action; the respiratory depressant effect (i.e., alterations in respiratory rate and alveolar ventilation) of fentanyl and other opiate analgesics persists longer than the analgesic effect. When opiate analgesics are administered concurrently with droperidol, the total dosage of all opiate analgesics administered should be considered by the clinician before ordering opiate analgesics during recovery from anesthesia. If opiates are required during recovery from anesthesia, they should be used initially in reduced dosages (as low as one-fourth to one-third of the usual recommended dosages). In addition, when such combinations are used, resuscitative equipment and an opiate antagonist should be readily available to manage apnea.
Because certain forms of conduction anesthesia (e.g., spinal anesthesia, peridural anesthesia) can cause peripheral vasodilation, and because droperidol also has cardiovascular effects (see Pharmacology), the anesthetist should be familiar with, and be prepared to manage, the physiologic alterations involved when droperidol is used to supplement these forms of anesthesia. If hypotension occurs, the possibility of hypovolemia should be considered and appropriate therapy with parenteral fluids should be instituted. Repositioning the patient to improve venous return to the heart also should be considered 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, care should be used when moving and positioning patients during anesthesia.
Since droperidol may decrease pulmonary arterial pressure, the drug may interfere with interpretation of hemodynamic measurements used during diagnostic or surgical procedures.
Droperidol should be used with caution in patients with impaired hepatic and renal function.
Since the EEG pattern returns to normal slowly following administration of droperidol, this should be considered when the EEG is used for postoperative monitoring.
Since droperidol is frequently used with fentanyl, it should be noted that fentanyl may produce bradycardia. Although fentanyl-induced bradycardia may be treated with atropine, fentanyl should be used with caution in patients with preexisting cardiac bradyarrhythmias.
Because it may be difficult to distinguish neuroleptic malignant syndrome (NMS) from malignant hyperthermia in the perioperative period, patients who experience increases in temperature, heart rate, and/or carbon dioxide production after receiving droperidol should be treated with dantrolene.114
Droperidol is contraindicated in patients with known hypersensitivity to the drug. Droperidol also is contraindicated in patients with known or suspected QT prolongation (i.e., QTc interval exceeding 440 msec in men and 450 msec in women), including patients with congenital long QT syndrome.112
Safety and efficacy of droperidol in children younger than 2 years of age have not been established.
Safe use of droperidol during pregnancy has not been established and the drug should be used during pregnancy only when the potential benefits justify the possible risks to the fetus. There are insufficient data to determine the safety to the infant of droperidol use in obstetric procedures.
It is not known if droperidol is distributed into milk.
Drugs that Prolong QT Interval
Drugs that have the potential to prolong the QT interval (e.g., class I or III antiarrhythmics, certain antihistamines, antimalarials, calcium-channel blockers, certain neuroleptics, antidepressants) should not be used concomitantly with droperidol.114 Droperidol should be used with caution in patients receiving drugs (e.g., diuretics, laxatives, supraphysiologic doses of steroid hormones with mineralocorticoid potential) that may induce hypokalemia or hypomagnesemia, which may prolong the QT interval.114
Concomitant use of droperidol in a patient also receiving cyclobenzaprine and fluoxetine resulted in the development of torsades de pointes which progressed into ventricular fibrillation.115 Although the exact mechanism of this interaction has not been established, some clinicians suggest that the metabolism of cyclobenzaprine by the cytochrome P-450 (CYP) enzyme system was inhibited by fluoxetine; subsequent administration of droperidol may have contributed to the increase in QT interval prolongation and development of torsades de pointes.115
Droperidol may be additive with, or may potentiate, the action of other CNS depressants such as opiates or other analgesics, barbiturates or other sedatives, anesthetics, or alcohol. When droperidol is used concomitantly with other CNS depressants, the dosage of each drug should be reduced.
Overdosage of droperidol produces effects that are extensions of its pharmacologic actions and may include QT prolongation and severe cardiac arrhythmias (e.g., torsades de pointes).
Treatment of droperidol overdosage generally involves symptomatic and supportive care. Appropriate supportive therapy should be instituted if hypoventilation, apnea, or hypotension occurs. The patient should be carefully observed for 24 hours following overdosage, and body warmth and adequate fluid intake should be maintained. An anticholinergic agent should be administered if clinically important extrapyramidal reactions occur.114
Droperidol has pharmacologic actions similar to those of haloperidol and phenothiazines.
Within the CNS, droperidol acts principally at subcortical levels and exhibits a strong sedative effect. The drug also inhibits sympathetic postganglionic α-adrenergic receptor binding sites; however, therapeutic dosages of droperidol do not appear to completely block these receptors. Droperidol has antiemetic activity, but does not appear to exhibit analgesic activity.
Like phenothiazines, droperidol may cause extrapyramidal reactions. (See Cautions: Nervous System Effects.)
In animals, droperidol produces catalepsy, reverses behavioral effects mediated by amphetamine and apomorphine, and causes a reduction in the sensitivity to epinephrine and norepinephrine.
Because of its inhibitory effects on α-adrenergic receptor binding sites, droperidol attenuates the cardiovascular response to sympathomimetic amines. Droperidol also produces direct peripheral vasodilation, which alone or in conjunction with its α-adrenergic blocking activity may cause hypotension and decreased peripheral vascular resistance. Droperidol may decrease pulmonary arterial pressure (particularly in patients with preexisting elevations in pulmonary arterial pressure) and reduce the incidence of epinephrine-induced arrhythmias; however, droperidol's activity against other arrhythmias has not been observed.
Following IM or IV administration, the onset of pharmacologic action of droperidol occurs within 3-10 minutes, but peak pharmacologic effects may not be apparent until 30 minutes. The sedative and tranquilizing effects of droperidol generally persist for 2-4 hours following IM or IV administration of a single dose; alteration of consciousness may persist for up to 12 hours.
Distribution of droperidol into human body tissues and fluids has not been fully characterized. Droperidol reportedly crosses the blood-brain barrier and is distributed into the CSF. The drug reportedly crosses the placenta, but data are limited. It is not known if droperidol is distributed into milk.
Although the exact metabolic fate of droperidol is not clearly established, the drug is metabolized in the liver. The butyrophenone moiety of droperidol is metabolized to p -fluorophenylacetic acid, which is then conjugated with glycine. The nitrogenous moiety of droperidol appears to be metabolized to benzimidazolone and p -hydroxypiperidine.
Droperidol and its metabolites are excreted in urine and feces. Approximately 10% of the drug is excreted unchanged in urine.
Droperidol is a butyrophenone derivative that is structurally similar to haloperidol. Droperidol occurs as a white to light tan, amorphous or microcrystalline powder and has solubilities of approximately 0.1 mg/mL in water and 7.14 mg/mL in alcohol at 25°C. Droperidol injection is a sterile solution of the drug in water for injection. The commercially available injection is adjusted to a pH of 3-3.8 with lactic acid.
Commercially available droperidol injection should be protected from light and stored at room temperature (15-25°C). Droperidol injection is physically and/or chemically incompatible with some drugs (e.g., parenteral barbiturates), but the compatibility depends on several factors (e.g., concentrations of the drugs, specific diluents used, resulting pH, temperature). Specialized references should be consulted for specific compatibility information.
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.
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.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection | 2.5 mg/mL* | Droperidol Injection | |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
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