Not necessary to discontinue the drug prior to extubation provided that duration of infusion is ≤24 hours.
Administration
IV Administration
For solution and drug compatibility information, see Compatibility under Stability.
Administer by IV infusion.
May adsorb to some types of natural rubber; use administration components made with synthetic or coated natural rubber gaskets.
Vials are for single use only.
Dilution
Must be diluted in 0.9% sodium chloride injection prior to administration. For preparation of the 4-mcg/mL concentration used for loading and maintenance infusions, add 2 mL of the concentrate (100 mcg/mL) to 48 mL of 0.9% sodium chloride injection.
Rate of Administration
Administer by slow IV infusion via a controlled-infusion device (pump).
Rapid IV infusion associated with loss of α2-adrenergic selectivity and adverse cardiovascular effects. (See Actions and also see Cardiac Arrhythmias under Cautions.)
Dosage
Available as dexmedetomidine hydrochloride; dosage is expressed in terms of dexmedetomidine.
Adults
Sedation in Critical-care Settings
IV
Initially, 1 mcg/kg as a loading infusion over 10 minutes, followed by maintenance infusion of 0.2–0.7 mcg/kg per hour for ≤24 hours.
Special Populations
Hepatic Impairment
Consider dosage reduction.
Renal Impairment
Consider dosage reduction; metabolites may accumulate with long-term infusion.
Bradycardia and sinus arrest reported in young, healthy adults with high vagal tone; also associated with other methods of administration, including rapid IV administration.
General Precautions
Cardiovascular Precautions
Possible hypotension and bradycardia; may be more pronounced in geriatric patients or those with hypovolemia, diabetes mellitus, or chronic hypertension. If treatment is required, consider slowing or stopping dexmedetomidine infusion, increasing IV fluids, elevating lower extremities, and/or vasopressors; consider IV anticholinergic agents (e.g., atropine sulfate, glycopyrrolate) to modify vagal tone.
Transient hypertension reported with loading dose; treatment generally not required.
Use with caution in patients with advanced heart block and/or severe ventricular dysfunction.
Withdrawal Reactions
Potential for withdrawal manifestations (e.g., nervousness, agitation, headaches, rapid rise in blood pressure, elevated plasma catecholamine concentrations) if administered chronically and stopped abruptly. Should not be administered for >24 hours.
Nervous System Effects
Some patients observed to be arousable and alert when stimulated; should not be considered as lack of efficacy in the absence of other signs and symptoms.
Adrenal Insufficiency
Cortisol response to corticotropin stimulation decreased by approximately 40% in dogs after sub-Q infusion of dexmedetomidine for one week; however, no changes noted after single-dose administration.
Negligible displacement of warfarin from protein binding sites in vitro
Pharmacokinetics
Distribution
Extent
Rapidly distributed.
Crosses the placenta and is distributed into milk when administered sub-Q to rats.
Plasma Protein Binding
Approximately 94%.
Elimination
Metabolism
Undergoes almost complete biotransformation by direct glucuronidation, aliphatic hydroxylation by CYP2A6, and N-methylation.
Elimination Route
Excreted in urine (95%) and feces (4%).
Half-life
Terminal elimination half-life is approximately 2 hours.
Special Populations
In patients with mild, moderate, or severe hepatic impairment, mean clearance values were 74, 64, or 53%, respectively, of those in healthy subjects.
Pharmacokinetics of dexmedetomidine metabolites in patients with renal impairment not determined to date; potential for accumulation with long-term infusion.
Stability
Storage
Parenteral
Injection Concentrate
25°C (may be exposed to temperatures ranging from 15–30°C).
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.
Dose-related sedative, anxiolytic, analgesic, and anesthetic-sparing effects; does not appear to reduce dosage requirements of skeletal muscle relaxants.
Helps maintain intraoperative hemodynamic stability by blunting sympathetic response to surgery.
Does not cause respiratory depression in healthy individuals when given by IV infusion in recommended dosages.
Compared with clonidine, dexmedetomidine has a shorter half-life (about 2 versus 8–12 hours) and greater α2-selectivity, with potential for reduced incidence of undesirable α1-adrenergic effects (e.g., hypotension, bradycardia).
Exhibits α2-selectivity when given by slow IV infusion in low to moderate doses (10–300 mcg/kg); selectivity diminishes at high doses (e.g., 1000 mcg/kg) or with rapid IV administration.
Advice to Patients
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant diseases.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Remember, keep this and all other medicines out of the reach of children,
never share your medicines with others, and use this medication only for the indication prescribed.
