Dexmedetomidine
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [2]
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Overview
Dexmedetomidine is a general anesthetic that is FDA approved for the {{{indicationType}}} of premedication for anesthetic procedure, nonintubated patients, sedation, intubated/mechanically ventilated ICU patients. Common adverse reactions include cardiovascular: hypertension (12% to 13% ), tachycardia (2% to 5% ), gastrointestinal: nausea (3% to 11% ), xerostomia (3% to 4% )..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Cough, Fentanyl- or sufentanil-induced: 0.1 mcg/kg, 0.25 mcg/kg, or 0.5 mcg/kg IV over 5 minutes immediately prior to sufentanil [1] and 0.5 or 1 mcg/kg IV over 10 minutes immediately prior to fentanyl [2] were used in clinical trials Cough, Fentanyl- or sufentanil-induced: (combination with midazolam) 0.6 mcg/kg IV over 10 minutes plus midazolam 0.06 mg/kg IV over 5 seconds, administered 2 minutes prior to fentanyl, was used in a clinical trial [3] Premedication for anesthetic procedure, Nonintubated patients: initial, loading infusion of 1 mcg/kg IV over 10 minutes; for less invasive procedures (ie, ophthalmic surgery), initial loading infusion of 0.5 mcg/kg IV over 10 minutes may be sufficient [4] Premedication for anesthetic procedure, Nonintubated patients: maintenance, 0.6 mcg/kg/hr IV infusion titrated to desired clinical effect with doses ranging from 0.2 to 1 mcg/kg/hr [4] Premedication for anesthetic procedure, Nonintubated patients: (awake, fiberoptic intubation) initial loading infusion of 1 mcg/kg IV over 10 minutes, followed by maintenance infusion of 0.7 mcg/kg/hr until endotracheal tube is secured [4] Premedication for anesthetic procedure, Nonintubated patients: 1 mcg/kg INTRANASALLY, diluted in NS to a total volume of 0.8 mL and administered bilaterally (0.4 mL each nostril), provided effective sedation in a small randomized study [5] Sedation, Intubated/mechanically ventilated ICU patients: initial, loading infusion of 1 mcg/kg IV over 10 minutes; no loading dose required when converting from alternate sedative therapy [4] Sedation, Intubated/mechanically ventilated ICU patients: maintenance, 0.2 to 0.7 mcg/kg/hr continuous IV infusion titrated to desired clinical effect for a MAX of 24 hours [4]
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
Anesthetics adverse reaction - ShiveringView additional information.
Cough, Fentanyl- or sufentanil-inducedView additional information.
General anesthesia; AdjunctView additional information.
Sedation, During awake craniotomyView additional information.
Non–Guideline-Supported Use
There is limited information about Off-Label Non–Guideline-Supported Use of Dexmedetomidine in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
safety and efficacy not established in pediatric patients [4] Premedication for anesthetic procedure, Nonintubated patients: 2 mcg/kg IV bolus over 10 minutes, then 1 mcg/kg/hour IV until completion of nuclear medicine imaging was used in a clinical study (mean age, 5.7 years) [6] Premedication for anesthetic procedure, Nonintubated patients: 0.5 to 1 mcg/kg IV every 3 to 5 minutes (mean total dose, 2.1 mcg/kg; mean infusion rate, 1.5 mcg/kg/hr) provided sedation during EEG testing in a retrospective review (mean age, 5.6 years) [7] Premedication for anesthetic procedure, Nonintubated patients: initial, 1 to 4.5 mcg/kg IM (mean dose, 2.6 mcg/kg) provided sedation during EEG testing in a retrospective review; a second, lower dose (mean dose, 2 mcg/kg) was given if adequate sedation was not achieved 10 minutes after first dose (mean age, 3.5 years) [8] Premedication for anesthetic procedure, Nonintubated patients: 1 to 2 mcg/kg INTRANASALLY, administered bilaterally, provided effective sedation prior to anesthesia induction in 2 randomized studies (ages, 1 to 8 years)
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information about Off-Label Guideline-Supported Use of Dexmedetomidine in pediatric patients.
Non–Guideline-Supported Use
There is limited information about Off-Label Non–Guideline-Supported Use of Dexmedetomidine in pediatric patients.
Contraindications
None
Warnings
Drug Administration
Precedex should be administered only by persons skilled in the management of patients in the intensive care or operating room setting. Due to the known pharmacological effects of Precedex, patients should be continuously monitored while receiving Precedex.
5.2 Hypotension, Bradycardia, and Sinus Arrest
Clinically significant episodes of bradycardia and sinus arrest have been reported with Precedex administration in young, healthy adult volunteers with high vagal tone or with different routes of administration including rapid intravenous or bolus administration.
Reports of hypotension and bradycardia have been associated with Precedex infusion. If medical intervention is required, treatment may include decreasing or stopping the infusion of Precedex, increasing the rate of intravenous fluid administration, elevation of the lower extremities, and use of pressor agents. Because Precedex has the potential to augment bradycardia induced by vagal stimuli, clinicians should be prepared to intervene. The intravenous administration of anticholinergic agents (e.g., glycopyrrolate, atropine) should be considered to modify vagal tone. In clinical trials, glycopyrrolate or atropine were effective in the treatment of most episodes of Precedex-induced bradycardia. However, in some patients with significant cardiovascular dysfunction, more advanced resuscitative measures were required.
Caution should be exercised when administering Precedex to patients with advanced heart block and/or severe ventricular dysfunction. Because Precedex decreases sympathetic nervous system activity, hypotension and/or bradycardia may be expected to be more pronounced in patients with hypovolemia, diabetes mellitus, or chronic hypertension and in elderly patients.
In clinical trials where other vasodilators or negative chronotropic agents were co-administered with Precedex an additive pharmacodynamic effect was not observed. Nonetheless, caution should be used when such agents are administered concomitantly with Precedex.
5.3 Transient Hypertension
Transient hypertension has been observed primarily during the loading dose in association with the initial peripheral vasoconstrictive effects of Precedex. Treatment of the transient hypertension has generally not been necessary, although reduction of the loading infusion rate may be desirable.
5.4 Arousability
Some patients receiving Precedex have been observed to be arousable and alert when stimulated. This alone should not be considered as evidence of lack of efficacy in the absence of other clinical signs and symptoms.
5.5 Withdrawal
Intensive Care Unit Sedation
With administration up to 7 days, regardless of dose, 12 (5%) Precedex adult subjects experienced at least 1 event related to withdrawal within the first 24 hours after discontinuing study drug and 7 (3%) Precedex adult subjects experienced at least 1 event 24 to 48 hours after end of study drug. The most common events were nausea, vomiting, and agitation.
In adult subjects, tachycardia and hypertension requiring intervention in the 48 hours following study drug discontinuation occurred at frequencies of <5%. If tachycardia and/or hypertension occurs after discontinuation of Precedex supportive therapy is indicated.
Procedural Sedation
In adult subjects, withdrawal symptoms were not seen after discontinuation of short term infusions of Precedex (<6 hours).
5.6 Tolerance and Tachyphylaxis
Use of dexmedetomidine beyond 24 hours has been associated with tolerance and tachyphylaxis and a dose-related increase in adverse reactions [see Adverse Reactions (6.1)].
5.7 Hepatic Impairment
Since Precedex clearance decreases with severity of hepatic impairment, dose reduction should be considered in patients with impaired hepatic function [see Dosage and Administration (2.2)].
Adverse Reactions
Clinical Trials Experience
Clinical Studies Experience
Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice.
Use of Precedex has been associated with the following serious adverse reactions:
Hypotension, bradycardia and sinus arrest [see Warnings and Precautions (5.2)] Transient hypertension [see Warnings and Precautions (5.3)]
Most common treatment-emergent adverse reactions, occurring in greater than 2% of patients in both Intensive Care Unit and procedural sedation studies include hypotension, bradycardia and dry mouth.
Intensive Care Unit Sedation
Adverse reaction information is derived from the continuous infusion trials of Precedex for sedation in the Intensive Care Unit setting in which 1007 adult patients received Precedex. The mean total dose was 7.4 mcg/kg (range: 0.8 to 84.1), mean dose per hour was 0.5 mcg/kg/hr (range: 0.1 to 6.0) and the mean duration of infusion of 15.9 hours (range: 0.2 to 157.2). The population was between 17 to 88 years of age, 43% ≥65 years of age, 77% male and 93% Caucasian. Treatment-emergent adverse reactions occurring at an incidence of >2% are provided in Table 2. The most frequent adverse reactions were hypotension, bradycardia and dry mouth [see Warnings and Precautions (5.2)].
Adverse reaction information was also derived from the placebo-controlled, continuous infusion trials of Precedex for sedation in the surgical intensive care unit setting in which 387 adult patients received Precedex for less than 24 hours. The most frequently observed treatment-emergent adverse events included hypotension, hypertension, nausea, bradycardia, fever, vomiting, hypoxia, tachycardia and anemia (see Table 3).
In a controlled clinical trial, Precedex was compared to midazolam for ICU sedation exceeding 24 hours duration in adult patients. Key treatment emergent adverse events occurring in dexmedetomidine or midazolam treated patients in the randomized active comparator continuous infusion long-term intensive care unit sedation study are provided in Table 4. The number (%) of subjects who had a dose-related increase in treatment-emergent adverse events by maintenance adjusted dose rate range in the Precedex group is provided in Table 5.
The following adverse events occurred between 2 and 5% for Precedex and Midazolam, respectively: renal failure acute (2.5%, 0.8%), acute respiratory distress syndrome (2.5%, 0.8%), and respiratory failure (4.5%, 3.3%).
Procedural Sedation
Adverse reaction information is derived from the two trials for procedural sedation in which 318 adult patients received Precedex. The mean total dose was 1.6 mcg/kg (range: 0.5 to 6.7), mean dose per hour was 1.3 mcg/kg/hr (range: 0.3 to 6.1) and the mean duration of infusion of 1.5 hours (range: 0.1 to 6.2). The population was between 18 to 93 years of age, 30% ≥65 years of age, 52% male and 61% Caucasian.
Treatment-emergent adverse reactions occurring at an incidence of >2% are provided in Table 6. The most frequent adverse reactions were hypotension, bradycardia, and dry mouth [see Warnings and Precautions (5.2)]. Pre-specified criteria for the vital signs to be reported as adverse reactions are footnoted below the table. The decrease in respiratory rate and hypoxia was similar between Precedex and comparator groups in both studies.
Postmarketing Experience
The following adverse reactions have been identified during post approval use of Precedex. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Hypotension and bradycardia were the most common adverse reactions associated with the use of Precedex during post approval use of the drug.
Drug Interactions
Anesthetics, Sedatives, Hypnotics, Opioids
Co-administration of Precedex with anesthetics, sedatives, hypnotics, and opioids is likely to lead to an enhancement of effects. Specific studies have confirmed these effects with sevoflurane, isoflurane, propofol, alfentanil, and midazolam. No pharmacokinetic interactions between Precedex and isoflurane, propofol, alfentanil and midazolam have been demonstrated. However, due to possible pharmacodynamic interactions, when co-administered with Precedex, a reduction in dosage of Precedex or the concomitant anesthetic, sedative, hypnotic or opioid may be required.
7.2 Neuromuscular Blockers
In one study of 10 healthy adult volunteers, administration of Precedex for 45 minutes at a plasma concentration of one ng/mL resulted in no clinically meaningful increases in the magnitude of neuromuscular blockade associated with rocuronium administration.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA): C There are no adequate and well-controlled studies of Precedex use in pregnant women. In an in vitro human placenta study, placental transfer of dexmedetomidine occurred. In a study in the pregnant rat, placental transfer of dexmedetomidine was observed when radiolabeled dexmedetomidine was administered subcutaneously. Thus, fetal exposure should be expected in humans, and Precedex should be used during pregnancy only if the potential benefits justify the potential risk to the fetus.
Teratogenic effects were not observed in rats following subcutaneous administration of dexmedetomidine during the period of fetal organogenesis (from gestation day 5 to 16) with doses up to 200 mcg/kg (representing a dose approximately equal to the maximum recommended human intravenous dose based on body surface area) or in rabbits following intravenous administration of dexmedetomidine during the period of fetal organogenesis (from gestation day 6 to 18) with doses up to 96 mcg/kg (representing approximately half the human exposure at the maximum recommended dose based on plasma area under the time-curve comparison). However, fetal toxicity, as evidenced by increased post-implantation losses and reduced live pups, was observed in rats at a subcutaneous dose of 200 mcg/kg. The no-effect dose in rats was 20 mcg/kg (representing a dose less than the maximum recommended human intravenous dose based on a body surface area comparison). In another reproductive toxicity study when dexmedetomidine was administered subcutaneously to pregnant rats at 8 and 32 mcg/kg (representing a dose less than the maximum recommended human intravenous dose based on a body surface area comparison) from gestation day 16 through weaning, lower offspring weights were observed. Additionally, when offspring of the 32 mcg/kg group were allowed to mate, elevated fetal and embryocidal toxicity and delayed motor development was observed in second generation offspring.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Dexmedetomidine in women who are pregnant.
Labor and Delivery
The safety of Precedex during labor and delivery has not been studied.
Nursing Mothers
It is not known whether Precedex is excreted in human milk. Radio-labeled dexmedetomidine administered subcutaneously to lactating female rats was excreted in milk. Because many drugs are excreted in human milk, caution should be exercised when Precedex is administered to a nursing woman.
Pediatric Use
Safety and efficacy have not been established for Procedural or ICU Sedation in pediatric patients. One assessor-blinded trial in pediatric patients and two open label studies in neonates were conducted to assess efficacy for ICU sedation. These studies did not meet their primary efficacy endpoints and the safety data submitted were insufficient to fully characterize the safety profile of Precedex for this patient population. The use of Precedex for procedural sedation in pediatric patients has not been evaluated.
Geriatic Use
Intensive Care Unit Sedation
A total of 729 patients in the clinical studies were 65 years of age and over. A total of 200 patients were 75 years of age and over. In patients greater than 65 years of age, a higher incidence of bradycardia and hypotension was observed following administration of Precedex [see Warnings and Precautions (5.2)]. Therefore a dose reduction may be considered in patients over 65 years of age [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].
Procedural Sedation
A total of 131 patients in the clinical studies were 65 years of age and over. A total of 47 patients were 75 years of age and over. Hypotension occurred in a higher incidence in Precedex-treated patients 65 years or older (72%) and 75 years or older (74%) as compared to patients <65 years (47%). A reduced loading dose of 0.5 mcg/kg given over 10 minutes is recommended and a reduction in the maintenance infusion should be considered for patients greater than 65 years of age.
8.6 Hepatic Impairment
Since Precedex clearance decreases with increasing severity of hepatic impairment, dose reduction should be considered in patients with impaired hepatic function [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].
Gender
There is no FDA guidance on the use of Dexmedetomidine with respect to specific gender populations.
Race
There is no FDA guidance on the use of Dexmedetomidine with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Dexmedetomidine in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Dexmedetomidine in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Dexmedetomidine in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Dexmedetomidine in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Dexmedetomidine Administration in the drug label.
Monitoring
There is limited information regarding Dexmedetomidine Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Dexmedetomidine and IV administrations.
Overdosage
There is limited information regarding Dexmedetomidine overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Dexmedetomidine Pharmacology in the drug label.
Mechanism of Action
There is limited information regarding Dexmedetomidine Mechanism of Action in the drug label.
Structure
There is limited information regarding Dexmedetomidine Structure in the drug label.
Pharmacodynamics
There is limited information regarding Dexmedetomidine Pharmacodynamics in the drug label.
Pharmacokinetics
There is limited information regarding Dexmedetomidine Pharmacokinetics in the drug label.
Nonclinical Toxicology
There is limited information regarding Dexmedetomidine Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Dexmedetomidine Clinical Studies in the drug label.
How Supplied
There is limited information regarding Dexmedetomidine How Supplied in the drug label.
Storage
There is limited information regarding Dexmedetomidine Storage in the drug label.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
There is limited information regarding Dexmedetomidine Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Dexmedetomidine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Dexmedetomidine Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Dexmedetomidine Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.