Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: Kyowa Kirin Ltd, Galabank Business Park, Galashiels, TD1 1QH, United Kingdom, Tel. +44 (0)1896 664000
Pharmacotherapeutic group: Butyrophenone derivatives
ATC code: N05AD08
Droperidol is a butyrophenone neuroleptic. Its pharmacologic profile is characterised mainly by dopamine-blocking and weak α1-adrenolytic effects. Droperidol is devoid of anticholinergic and antihistaminic activity.
Droperidol’s inhibitory action on dopaminergic receptors in the chemotrigger zone in the area postrema, gives it a potent antiemetic effect, especially useful for the prevention and treatment of postoperative nausea and vomiting and/or nausea and vomiting induced by opioid analgesics.
At a dose of 0.15 mg/kg, droperidol induces a fall in mean blood pressure (MBP), due to a decrease in cardiac output in a first phase, and then subsequently due to a decrease in pre-load. These changes occur independently of any alteration in myocardial contractility or vascular resistance. Droperidol does not affect myocardial contractility or heart rate, therefore has no negative inotropic effect. Its weak α1-adrenergic blockade can cause a modest hypotension and decreased peripheral vascular resistance and may decrease pulmonary arterial pressure (particularly if it is abnormally high). It may also reduce the incidence of epinephrine-induced arrhythmia, but it does not prevent other forms of cardiac arrhythmia.
Droperidol has a specific antiarrhythmic effect at a dose of 0.2 mg/kg by an effect on myocardial contractility (prolongation of the refractory period) and a decrease in blood pressure.
Two studies (one placebo-controlled and one comparative active treatment-controlled) performed in the general anaesthesia setting and designed to better identify the QTc changes associated with postoperative nausea and vomiting treatment by small dose of droperidol (0.625 and 1.25 mg intravenous, and 0.75 mg intravenous, respectively) identified a QT interval prolongation at 3-6 min after administration of 0.625 and 1.25 mg droperidol (respectively 15 ± 40 and 22 ± 41 ms), but these changes did not differ significantly from that seen with saline (12 ± 35 ms). There were no statistically significant differences amongst the droperidol and saline groups in the number of patients with greater than 10% prolongation in QTc versus baseline. There was no evidence of droperidol-induced QTc prolongation after surgery.
No ectopic heartbeats were reported from the electrocardiographic records or 12-lead recordings during the perioperative period. The comparative active-treatment study with 0.75 mg intravenous droperidol identified a significant QTc interval prolongation (maximal of 17 ± 9 ms at the second minute after droperidol injection when compared with pre-treatment QTc measurement), with the QTc interval significantly lower after the 90th minute.
The action of a single intravenous dose commences 2-3 minutes following administration. The tranquillising and sedative effects tend to persist for 2 to 4 hours, although alertness may be affected for up to 12 hours.
Following intravenous administration, plasma concentrations fall rapidly during the first 15 minutes; this is metabolism independent, redistribution of the drug. Plasma protein binding amounts to 85-90%. The distribution volume is approximately 1.5 l/kg.
Droperidol is extensively metabolised in the liver, and undergoes oxidation, dealkylation, demethylation and hydroxylation by cytochrome P450 isoenzymes 1A2 and 3A4, and to a lesser extent by 2C19. The metabolites are devoid of neuroleptic activity.
Elimination occurs mainly through metabolism; 75% is excreted via the kidneys. Only 1% of the active substance is excreted unchanged with urine, and 11% with faeces. Plasma clearance is 0.8 (0.4-1.8) l/min. The elimination half-life (t½ß) is 134 ± 13 min.
In a study of 12 children (age 3.5 to 12 years), the values for distribution volume and clearance reported were lower than those found in the adult population (0.58 ± 0.29 l/kg and 4.66 ± 2.28 ml/kg*min respectively) and decrease in parallel. The elimination half-life (101.5 ± 26.4 min) was similar to that found in adults.
Non-clinical data reveal no special hazard for humans based on conventional studies of repeated dose toxicity, genotoxic or carcinogenic potential, and reproductive toxicity.
Electrophysiological in vitro and in vivo studies indicate an overall risk of droperidol to prolong the QT interval in humans.
In humans, the free peak plasma concentration is approximately 4-fold higher to 25-fold lower than the droperidol concentrations affecting the endpoints examined in the different in vitro and in vivo test systems used to assess the impact of this drug on cardiac repolarisation. Plasma levels fall by about one order of magnitude over the first twenty minutes after administration.
This product is unlikely to represent a risk to the environment following its prescribed use in patients.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
