Dexmedetomidine

Class: Anxiolytics, Sedatives, and Hypnotics; Miscellaneous
- α2-Adrenergic Agonists
VA Class: CN309
Chemical Name: (S)-4-[1-(2,3-Dimethylphenyl)ethyl]-1H-imidazole monohydrochloride
Molecular Formula: C₁₃H₁₆N₂•HCl
CAS Number: 145108-58-3
Brands: Precedex

Medically reviewed by Drugs.com. Last updated on Jan 13, 2020.

• Overview
• Side Effects
• Dosage
• Professional
• Interactions
• More

Introduction

Relatively selective α₂-adrenergic agonist with sedative properties.^{1 2 3 4 5 6 7 8 13}

Uses for Dexmedetomidine

Sedation in Critical Care Settings

Sedation of initially intubated and mechanically ventilated patients in an intensive care setting (i.e., ICU).^{1 800 801}

May be used to provide mild to moderate levels of sedation, but not considered suitable for deep sedation.^{21 23 800 820}

FDA-labeled for use only for short-term (<24 hours) sedation;¹ however, has been used for prolonged sedation† in the intensive care setting.^{23 801 817 818 819 820} (See Tolerance and Tachyphylaxis under Cautions.)

Produces sedation, anxiolysis, and analgesia without causing significant respiratory depression.^{24 801 817 818}

Appears to be as effective as propofol and benzodiazepines (e.g., midazolam, lorazepam) for sedation in critically ill mechanically ventilated adults; however, because of some modest clinical benefits (e.g., reduced duration of mechanical ventilation, shorter time to extubation, reduced risk of delirium), nonbenzodiazepine sedatives (dexmedetomidine or propofol) are generally preferred to benzodiazepines.^{800 801 817 818 819 820}

When selecting an appropriate sedative agent, consider patient's individual sedation goals in addition to specific drug-related (e.g., pharmacology, pharmacokinetics, adverse effects, availability, costs) and patient-related (e.g., comorbid conditions such as anxiety, seizures, or alcohol or benzodiazepine withdrawal) factors.^{23 24 800 801}

Patients receiving dexmedetomidine are more arousable than those receiving other sedatives, which may be particularly useful for daily awakening trials.^{21 23 820}

Because dexmedetomidine does not have a substantial respiratory depressant effect, infusions of the drug can be continued following extubation, if needed.^{1 801}

Procedural Sedation

Sedation of nonintubated patients prior to and/or during surgical or other procedures.^{1 16 30 31 823}

Comparative efficacy with other sedative agents not established.⁸¹⁷ May be preferred in certain patients (e.g., those in whom respiratory compromise with benzodiazepines is a concern); however, consider risks versus benefits.⁸¹⁷

Dexmedetomidine Dosage and Administration

General

• Administer only by individuals experienced in the management of patients in an intensive care or surgical setting.¹

• Individualize dosage and titrate to desired level of sedation.¹

• Monitor patient continuously.^{1 15}

Administration

IV Administration

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

Administer by IV infusion.¹

May adsorb to some types of natural rubber; use administration components made with synthetic or coated natural rubber gaskets.¹

Commercially available as an injection concentrate that must be diluted prior to IV infusion or as a premixed ready-to-use solution (dexmedetomidine hydrochloride in 0.9% sodium chloride injection).¹

Dilution

Must dilute the injection concentrate in 0.9% sodium chloride injection prior to administration.¹ To prepare the 4-mcg/mL concentration used for loading and maintenance infusions, one method of dilution is to add 2 mL of the concentrate (100 mcg/mL) to 48 mL of 0.9% sodium chloride injection.¹

Rate of Administration

Administer by slow IV infusion via a controlled-infusion device.¹

Rapid IV infusion associated with loss of α₂-adrenergic selectivity¹ and adverse cardiovascular effects.^{1 2 3 15} (See Actions and also see Cardiovascular Effects under Cautions.)

Dosage

Available as dexmedetomidine hydrochloride; dosage is expressed in terms of dexmedetomidine.¹

Adults

Sedation in Critical Care Settings

IV

Initiation of sedation: 1 mcg/kg as a loading infusion over 10 minutes.¹ Because of risk of adverse hemodynamic effects, many clinicians do not recommend a loading dose; if a loading dose is used, caution is advised, particularly in patients with bradycardia, heart block, or hemodynamic instability.^{21 22 25 801 817} Manufacturer states loading dose may not be required in patients converting from an alternative sedative agent.¹

Maintenance of sedation: Continuous IV infusion at a rate of 0.2–0.7 mcg/kg per hour recommended.¹ Adjust infusion rate to desired level of sedation;¹ in most cases, a light rather than deep level of sedation is recommended in critically ill, mechanically ventilated patients.⁸⁰¹ Assess depth and quality of sedation using a validated and reliable assessment tool.^{800 801} Adjust dosage slowly to reduce risk of hypotension and other adverse effects.^{24 817}

Evidence from clinical studies supports use of infusion rates up to 1.5 mcg/kg per hour.^{23 24 801 817 818 819 820}

Manufacturer states that continuous IV infusion of dexmedetomidine should not exceed 24 hours.^{1 817} However, the drug has been used for prolonged (>24 hours) sedation in the ICU.^{817 818 819 820}

Procedural Sedation

IV

Initiation of sedation: 1 mcg/kg as a loading infusion over 10 minutes.¹ A loading infusion of 0.5 mcg/kg over 10 minutes may be suitable for less invasive procedures (e.g., ophthalmic surgery).¹ For awake fiberoptic intubation, a loading infusion of 1 mcg/kg over 10 minutes is recommended.¹

Maintenance of sedation: Initiate maintenance infusion at a rate of 0.6 mcg/kg per hour; adjust rate within range of 0.2–1 mcg/kg per hour to achieve desired level of sedation.¹ For awake fiberoptic intubation in adults, a maintenance infusion of 0.7 mcg/kg per hour is recommended until endotracheal tube is secured.¹

Special Populations

Hepatic Impairment

Consider dosage reduction.¹

Renal Impairment

Manufacturer makes no special dosage recommendations.¹

Geriatric Patients

For initiation and maintenance of ICU sedation in geriatric patients >65 years of age, consider dosage reduction.¹

For procedural sedation in geriatric patients >65 years of age, reduce loading dose to 0.5 mcg/kg over 10 minutes; consider dosage reduction for maintenance of procedural sedation.¹

Cautions for Dexmedetomidine

Contraindications

• None.¹

Warnings/Precautions

Administration Precautions

To minimize risk of adverse effects, follow recommendations for administration and monitoring of dexmedetomidine therapy.¹ (See General under Dosage and Administration.)

Cardiovascular Effects

Bradycardia and sinus arrest reported in young, healthy adults with high vagal tone; also associated with other methods of administration, including rapid IV administration.¹

Hypotension and/or bradycardia reported frequently; although intervention rarely required, some cases resulted in fatality.^{1 8 9 21 23 818 820} May be more pronounced in geriatric patients or those with hypovolemia, diabetes mellitus, or chronic hypertension.¹ If treatment is required, consider slowing or stopping dexmedetomidine infusion, increasing IV fluids, elevating lower extremities, and/or use of vasopressors; consider IV anticholinergic agents (e.g., atropine sulfate, glycopyrrolate) to modify vagal tone.¹ More advanced resuscitative measures may be necessary in patients with significant cardiovascular dysfunction.¹

Transient hypertension reported with loading dose; treatment generally not required, although reduction in the loading dose infusion rate may be desirable.¹

Supraventricular and ventricular tachycardia, atrial fibrillation, extrasystoles, and cardiac arrest reported during postmarketing experience.^{1 15}

Use with caution in patients with (or at risk of) advanced heart block and/or severe ventricular dysfunction, and in patients receiving concomitant drugs that slow cardiac conduction.^{1 817}

Withdrawal Effects

Abrupt withdrawal of dexmedetomidine may result in clonidine-like withdrawal symptoms.¹ Withdrawal-related events (e.g., nausea, vomiting, agitation, tachycardia, hypertension) reported following discontinuance of therapy in some patients after prolonged (up to 7 days) infusion for ICU sedation.¹ Withdrawal symptoms not reported with short-term (<6 hours) infusions for procedural sedation.¹

If tachycardia and/or hypertension occurs after discontinuance of dexmedetomidine, institute supportive therapy.¹

Arousability

Some patients observed to be arousable and alert when stimulated; should not be considered as evidence of lack of efficacy in the absence of other signs and symptoms.¹

Tolerance and Tachyphylaxis

Use of dexmedetomidine for durations >24 hours associated with tolerance, tachyphylaxis, and dose-related increase in adverse effects.¹

Specific Populations

Pregnancy

Category C.¹

No adequate and well-controlled studies in pregnant women.¹ No evidence of teratogenicity in animal studies; however, fetal toxicity (e.g., postimplantation loss, reduced pup viability, reduced pup weight) observed.¹

Use during pregnancy only when potential benefits justify potential risks to fetus.¹

Lactation

Distributed into milk in rats; not known whether distributed into human milk.¹ Caution if used in nursing women.¹

Pediatric Use

Manufacturer states safety and efficacy not established in pediatric patients <18 years of age.¹ However, the drug has been used in pediatric patients undergoing sedation in the ICU or other settings to facilitate mechanical ventilation or other procedures (e.g., radiologic imaging).^{25 26 27} Additional study is needed to evaluate the drug's safety in this population.^{21 25 26}

Geriatric Use

Hypotension and/or bradycardia may be more pronounced.¹ Consider dosage reduction.¹ (See Geriatric Patients under Dosage and Administration.)

Renal Impairment

Pharmacokinetics in patients with severe renal impairment (Cl_cr <30 mL/minute) and healthy individuals are similar.¹

Hepatic Impairment

Clearance may be reduced.¹ Consider dosage reduction.¹ (See Hepatic Impairment under Dosage and Administration.)

Common Adverse Effects

Short-term (<24 hours) infusions for ICU sedation: Hypotension, hypertension, nausea, bradycardia, fever, vomiting, hypovolemia, atelectasis, atrial fibrillation, hypoxia, tachycardia, hemorrhage, anemia, dry mouth.¹

Long-term (>24 hours) infusions for ICU sedation: Hypotension, bradycardia, hypertension, tachycardia, hypokalemia, agitation, hyperglycemia, constipation, hypoglycemia, respiratory failure.¹

Procedural sedation: Hypotension, respiratory depression, bradycardia, hypertension, tachycardia, nausea, dry mouth.¹

Interactions for Dexmedetomidine

Metabolized by CYP isoenzymes, principally CYP2A6.¹ However, no evidence of clinically important CYP-mediated drug interactions in vitro.¹

Drugs with Negative Chronotropic Effects

Potential pharmacodynamic interaction (additive pharmacodynamic effects).¹ Use with caution.¹

Protein-bound Drugs

Pharmacokinetic interaction unlikely.¹

Specific Drugs

Dexmedetomidine Pharmacokinetics

Distribution

Extent

Rapidly distributed.¹ Rapidly crosses blood-brain barrier.²⁵

Crosses the placenta and is distributed into milk in rats.¹

Plasma Protein Binding

Approximately 94%.¹

Elimination

Metabolism

Undergoes almost complete biotransformation by direct glucuronidation, aliphatic hydroxylation by CYP2A6, and N-methylation.^{1 15}

Elimination Route

Excreted in urine (95%) and feces (4%).¹

Half-life

Terminal elimination half-life is approximately 2 hours.^{2 3 6}

Special Populations

Clearance decreases with increasing severity of hepatic impairment.¹ In patients with mild, moderate, or severe hepatic impairment, mean clearance values were 74, 64, or 53%, respectively, of those in healthy individuals.¹

Pharmacokinetics in patients with severe renal impairment (Cl_cr <30 mL/minute) not substantially altered.¹

Stability

Storage

Parenteral

Injection Concentrate

25°C (may be exposed to 15–30°C).¹

Premixed Injection in 0.9% Sodium Chloride Injection

25°C (may be exposed to 15–30°C).¹

Compatibility

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

Should not be infused through the same IV line with blood or plasma.¹

Parenteral

Solution Compatibility

Drug Compatibility

Actions

• Dose-related sedative, anxiolytic, analgesic, and anesthetic-sparing effects;^{2 3 5 6 8 13} does not appear to reduce dosage requirements of skeletal muscle relaxants.^{3 12}

• Helps maintain intraoperative hemodynamic stability by blunting sympathetic response to surgery.^{2 3 5 6 8 13}

• Does not cause respiratory depression in healthy individuals when given by IV infusion in recommended dosages.¹

• Compared with clonidine, dexmedetomidine has a shorter half-life^{2 3 5} (about 2 versus 8–12 hours)^{2 3 6} and greater α₂-selectivity, with potential for reduced incidence of undesirable α₁-adrenergic effects (e.g., hypotension, bradycardia).³

• Exhibits α₂-selectivity when given by slow IV infusion in low to moderate doses (10–300 mcg/kg); selectivity diminishes at ¹² high doses (e.g., 1000 mcg/kg) or with rapid IV administration.¹

Advice to Patients

• When dexmedetomidine hydrochloride is used for short-term IV sedation, dosage must be individualized and titrated to the desired clinical effect.¹ BP, heart rate, and oxygen concentrations are continuously monitored during the infusion and as clinically appropriate after discontinuance.¹

• Risk of withdrawal reactions and other adverse effects.¹ When dexmedetomidine is infused for >6 hours, patients should report any nervousness, agitation, and/or headaches that may occur for up to 48 hours following dexmedetomidine administration to their clinician.¹ In addition, patients should report symptoms that may occur within 48 hours following administration (e.g., weakness, confusion, excessive sweating, weight loss, abdominal pain, salt cravings, diarrhea, constipation, dizziness, lightheadedness) to their clinician.¹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant diseases.¹

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

• Importance of informing patients of other important precautionary information. (See Cautions.)¹

Preparations

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.

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

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

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