dexmedetomidine (Rx)

>10%

Hypotension (25-28%)

Hypertension (12-16%)

Nausea (9-11%)

1-10%

Bradycardia (5-7%)

Pyrexia (4-5%)

Atrial fibrillation (4%)

Dry mouth (3-4%)

Vomiting (3-4%)

Hypoxia (2-4%)

Hypovolemia (3%)

Atelectasis (3%)

Tachycardia (2-3%)

Postprocedural hemorrhage (2-3%)

Anemia (2-3%)

Agitation (2%)

Hyperthermia (2%)

Pain (2%)

Hyperglycemia (2%)

Chills or rigors (2%)

Hyperglycemia (2%)

Oliguria (2%)

Thirst (2%)

Acidosis (1-2%)

Pleural effusion (1-2%)

Pulmonary edema (1%)

Hypocalcemia (1%)

Urine output decreased (1%)

Sinus tachycardia (1%)

<1%

Ventricular tachycardia

Wheezing

Peripheral edema

Postmarketing Reports

Blood and lymphatic system disorders: Anemia

Cardiac disorders: Arrhythmia, atrial fibrillation, atrioventricular block, bradycardia, cardiac arrest, cardiac disorder, extrasystoles, myocardial infarction, supraventricular tachycardia, tachycardia, ventricular arrhythmia, ventricular tachycardia

Eye disorders: Photopsia, visual impairment

Gastrointestinal disorders: Abdominal pain, diarrhea, nausea, vomiting

General: Chills, hyperpyrexia, pain, pyrexia, thirst

Investigations: AST/ALT increased, blood alkaline phosphatase increased, blood urea increased, EKG T wave inversion, GGT increased, QT prolonged

Metabolism and nutrition disorders: Acidosis, hyperkalemia, hypoglycemia, hypovolemia, hypernatremia

Nervous system disorders: Convulsion, dizziness, headache, neuralgia, neuritis, speech disorder

Psychiatric disorders: Agitation, confusional state, delirium, hallucination, illusion

Renal and urinary disorders: Oliguria, polyuria

Respiratory, thoracic, and mediastinal disorders: Apnea, bronchospasm, dyspnea, hypercapnia, hypoventilation, hypoxia, pulmonary congestion, respiratory acidosis

Skin and subcutaneous tissue disorders: Hyperhidrosis, pruritus, rash, urticaria

Surgical and medical procedures: Light anesthesia

Vascular disorders: Blood pressure fluctuation, hemorrhage, hypertension, hypotension

Contraindications

None

Cautions

Continuously monitor patients while on therapy; therapy should be administered only by persons skilled in the management of patients in the intensive care or operating room setting

Bradycardia and sinus arrest have occurred in young healthy volunteers with high vagal tone or with different routes of administration, including rapid IV bolus administration

Caution with advanced heart block and/or severe ventricular dysfunction; because dexmedetomidine 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 older patients

Transient hypertension reported primarily during loading dose; consider reduction in loading infusion rate

Patients can become aroused/alert with stimulation; this alone should not be considered as lack of efficacy

Prolonged exposure to dexmedetomidine beyond 24 hours may be associated with tolerance and tachyphylaxis and a dose-related increase in adverse events (eg, ARDS, respiratory failure, agitation)

Use with caution in hepatic impairment; consider dose reduction

Hypotension and bradycardia may necessitate medical intervention; may be more pronounced in patients with hypovolemia, diabetes mellitus, or chronic hypertension, and in the elderly; use with caution in patients with advanced heart block or severe ventricular dysfunction

Withdrawal symptoms after discontinuation reported when administered for longer than 6 hr; most common events reported include nausea, vomiting, and agitation

Tachycardia and hypertension reported, requiring intervention 48 hr following study drug discontinuation; if tachycardia and/or hypertension occurs after discontinuation, supportive therapy is indicated

Drug interaction overview

• Caution if coadministered with other vasodilators or negative chronotropic agents owing to additive pharmacodynamic effects
• Coadministration with anesthetics, sedatives, hypnotics, and opioids is likely to lead to an enhancement of pharmacodynamic effects

Pregnancy

There are no adequate and well-controlled studies of use in pregnant women

In an in vitro human placenta study, placental transfer of dexmedetomidine occurred

Animal studies

• In pregnant rats, dexmedetomidine placental transfer observed when radiolabeled dexmedetomidine was administered SC
• Thus, fetal exposure should be expected in humans; use during pregnancy only if potential benefits justify potential fetal risk

Lactation

Unknown if excreted in human milk

Radio-labeled dexmedetomidine administered SC to lactating female rats was excreted in milk

Because many drugs are excreted in human milk, caution should be exercised when administered to breastfeeding women

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Centrally acting alpha2-adrenoceptor agonist that has sedative and anesthetic properties possibly by activating G-proteins in the brainstem, which results in the inhibition of norepinephrine release

Pharmacokinetics

Half-life, elimination: 6 min; 2 hr (terminal)

Peak plasma: 0.3-1.5 ng/mL

Protein bound: 94%

Vd: 118 L

Metabolism: Liver, including glucuronidation and CYP2A6

Metabolites: 3-hydroxy, 3-carboxy, 3-hydroxy N-methyl, 3-carboxy N-methyl, and N-methyl O-glucuronide dexmedetomidine

Total body clearance: 39 L/hr

Excretion: Urine (95%); feces (4%)

IV Incompatibilities

Y-site: amphotericin B, diazepam

IV Compatibilities

Solution: D5W, LR, 0.9% NaCl, mannitol 20%, MgSO4 100 mg/mL, KCl 0.3%

Y-site (partial list): amiodarone, cefepime, cefoperazone, ceftriaxone, chlorpromazine, ciprofloxacin, clindamycin, digoxin, diphenhydramine, dobutamine, dopamine, epinephrine, fluconazole, furosemide, heparin, hydroxyzine, labetalol, lidocaine, linezolid, lorazepam, meperidine, metoclopramide, MgSO4, metronidazole, KCl, nitroglycerin, prochlorperazine, promethazine, NaHCO3, Na-nitroprusside, TMP-SMX, vancomycin, verapamil

Not specified: atracurium, atropine, etomidate, fentanyl, glycopyrrolate, midazolam, mivacurium, morphine, pancuronium, phenylephrine, succinylcholine, thiopental, vecuronium

IV Preparation

200 mcg/2 mL (100 mcg/mL) vial

• Must be diluted with 0.9% NaCl to achieve required concentration (4 mcg/mL) before
• Preparation of solutions is the same, whether for the loading dose or maintenance infusion
• Withdraw 2 mL of 100 mcg/mL dexmedetomidine and add to 48 mL of 0.9% NaCl to a total of 50 mL
• Shake gently to mix well

IV Administration

Use controlled infusion device; use components made with synthetic or coated natural rubber gaskets

Infuse loading dose over 10 min

Maintenance dose: Administer by IV continuous infusion at recommended rate; individualized infusion rte and adjust rate to desired clinical response

Storage

Controlled room temperature of 25ºC (77ºF); excursions allowed from 15-30ºC (59-86ºF)