Dexmedetomidine Hydrochloride

Pronunciation: (dex-ME-de-TOE-mi-deen HYE-droe-KLOR-ide)
Class: Sedative and hypnotic, nonbarbiturate

Trade Names

Precedex
- Injection, solution, concentrate 100 mcg/mL

Pharmacology

Relatively selective alpha-2 adrenergic agonist with sedative properties.

Pharmacokinetics

Absorption

Pharmacokinetics are linear in the dose range of 0.2 to 0.7 mcg/kg/h.

Distribution

Steady-state Vd is approximately 118 L. Following IV administration, distribution half-life is approximately 6 min. Average plasma protein binding is 94%.

Metabolism

Undergoes almost complete biotransformation via direct glucuronidation as well as CYP2A6.

Elimination

Terminal elimination half-life is approximately 2 h. Cl is approximately 39 L/h. Excreted in the urine (95%) and feces (4%). No unchanged drug is detected in the urine.

Special Populations

Renal Function Impairment

Pharmacokinetics not different in patients with severe renal impairment (CrCl less than 30 mL/min) compared with healthy individuals.

Hepatic Function Impairment

Cl and plasma protein binding are decreased in patients with hepatic impairment. Dosage adjustment may be necessary in patients with hepatic impairment.

Elderly

Pharmacokinetics are not altered by age.

Children

Pharmacokinetics have not been studied in children.

Gender

No difference in pharmacokinetics based on gender.

Indications and Usage

Sedation of initially intubated and mechanically ventilated patients during treatment in an intensive care setting; sedation of nonintubated patients prior to and/or during surgical and other procedures.

Unlabeled Uses

Adjunct to regional anesthesia; bridge to intensive care unit (ICU) sedation and analgesia; in selected patients with CHF; supplement to regional block in patients undergoing carotid endarterectomy or during awake craniotomy; to control agitation while receiving noninvasive ventilatory support, such as mask continuous or bilevel positive airway pressure; to minimize withdrawal phenomena in critically ill patients who have received long-term benzodiazepines and opioids during their hospitalization; to reduce nausea and vomiting in children with cyclic vomiting syndrome; treatment of shivering.

Contraindications

None well documented.

Dosage and Administration

Initiation of Procedural Sedation
Adults Loading dose

IV 1 mcg/kg over 10 min, including awake fiberoptic intubation patients. For less invasive procedures (eg, ophthalmic surgery), a loading dose of 0.5 mcg/kg over 10 min may be suitable.

Maintenance dose

IV Start with 0.6 mcg/kg/h and titrate to achieve desired clinical effect with doses ranging from 0.2 to 1 mcg/kg/h. For awake fiberoptic intubation, a maintenance infusion of 0.7 mcg/kg/h is recommended until the endotracheal tube is secured.

ICU Sedation
Adults Loading dose

IV Up to 1 mcg/kg over 10 min. For patients being converted from alternate sedative therapy, a loading dose may not be required.

Maintenance dose

IV 0.2 to 0.7 mcg/kg/h. Adjust rate of infusion to achieve desired level of sedation.

Elderly Initiation of procedural sedation

IV Use a loading dose of 0.5 mcg/kg over 10 min. Consider a dose reduction for the maintenance dose.

ICU sedation

IV Consider a dose reduction.

Hepatic function impairment

IV Consider a dose reduction.

General Advice

• Administer by continuous IV infusion not exceeding 24 h.
• Administer using a controlled infusion devise.
• Preparation of solution is the same for loading and maintenance doses. Dilute with sodium chloride 0.9% to achieve required concentration (4 mcg/mL) prior to administration.
• Withdraw 2 mL of dexmedetomidine and add to 48 mL of sodium chloride 0.9% injection to achieve a total volume of 50 mL. Shake gently to mix.
• Do not administer through the same IV catheter with blood or plasma.
• Incompatible with amphotericin B and diazepam.
• Use administration components made with synthetic or coated natural rubber gaskets.

Storage/Stability

Store between 59° and 86°F.

Drug Interactions

Anesthetics, hypnotics, opioids, sedatives

Additive effects are anticipated. When coadministered with dexmedetomidine, a reduction in dosage of dexmedetomidine or the concomitant anesthetic, sedative, hypnotic, or opioid may be required.

Adverse Reactions

Cardiovascular

Hypotension (56%); bradycardia (42%); hypotension requiring intervention, systolic hypertension (28%); tachycardia (25%); hypertension requiring intervention (19%); hypertension (16%); diastolic hypertension (12%); tachycardia requiring intervention (10%); bradycardia requiring intervention (5%); atrial fibrillation (4%); arrhythmia, AV block, BP fluctuations, cardiac arrest, extrasystoles, heart block, heart disorder, MI, supraventricular tachycardia, T-wave inversion, ventricular arrhythmia, ventricular tachycardia (postmarketing).

CNS

Agitation (8%); anxiety (5%); confusion, convulsion, delirium, dizziness, hallucination, headache, illusion, neuralgia, neuritis, speech disorder (postmarketing).

Dermatologic

Increased sweating (postmarketing).

EENT

Abnormal vision, photopsia (postmarketing).

GI

Nausea (11%); constipation (6%); dry mouth (4%); abdominal pain, diarrhea (postmarketing).

Genitourinary

Acute renal failure, oliguria (2%); decreased urine output (1%); increased BUN (postmarketing).

Hematologic

Anemia (3%).

Hepatic

Abnormal hepatic function, hyperbilirubinemia, increased ALT, increased AST, increased GGT (postmarketing).

Metabolic-Nutritional

Hypokalemia (9%); hyperglycemia (7%); hypoglycemia, peripheral edema (5%); hypovolemia (3%); thirst (2%); hypocalcemia, hypomagnesemia (1%); acidosis, hyperkalemia, increased alkaline phosphatase (postmarketing).

Respiratory

Respiratory depression (37%); respiratory failure (6%); acute respiratory distress syndrome (3%); pleural effusion (2%); wheezing (1%); apnea, bronchospasm, dyspnea, hypercapnia, hypoventilation, hypoxia, pulmonary congestion, respiratory acidosis (postmarketing).

Miscellaneous

Pyrexia (7%); generalized edema (2%); hemorrhage, hyperpyrexia, light anesthesia, pain, rigors (postmarketing).

Precautions

Monitor Continuously monitor patients because of known pharmacologic effects.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy have not been established.

Elderly

Increased incidence of bradycardia and hypotension in elderly patients. Consider a dosage reduction.

Hepatic Function

Consider dosage reduction in patients with impaired hepatic function.

Alertness

Some patients may be arousable and alert when stimulated. Do not consider this alone to be evidence of lack of efficacy.

Bradycardia, hypotension, sinus arrest

Have been reported in patients with high vagal tone or with different routes of administration, including rapid IV or bolus administration. Bradycardia and/or hypotension may be more pronounced in elderly patients or in patients with chronic hypertension, diabetes mellitus, or hypovolemia. Administer with caution to patients with advanced heart block and/or severe ventricular dysfunction.

Tolerance/Tachyphylaxis

Has been associated with use beyond 24 h.

Transient hypertension

May occur in association with peripheral vasoconstriction, primarily during the loading dose.

Withdrawal symptoms

Withdrawal symptoms, including agitation, hypertension, nausea, tachycardia, and vomiting, may occur up to 48 h after discontinuation of dexmedetomidine.

Overdosage

Symptoms

Bradycardia, cardiac arrest, first-degree AV block, hypotension, second-degree heart block.

Patient Information

• Instruct patients who receive an infusion for more than 6 h to report agitation, headache, and nervousness to health care provider. These symptoms may occur for up to 48 h after infusion.
• Instruct patients to report the following symptoms to health care provider, which may occur within 48 h of administration: abdominal pain, confusion, constipation, diarrhea, dizziness or light-headedness, excessive sweating, salt cravings, weakness, or weight loss.

Copyright © 2009 Wolters Kluwer Health.