Dexmedetomidine Hydrochloride

Class: Anxiolytics, Sedatives, and Hypnotics; Miscellaneous
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

Introduction

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

Uses for Dexmedetomidine Hydrochloride

Sedation in Critical-care Settings

Sedation of initially intubated and mechanically ventilated patients in an intensive-care setting.1

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Dexmedetomidine Hydrochloride Dosage and Administration

General

  • Should be administered only by individuals experienced in the management of patients in an intensive-care setting.1

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

  • Monitor patient continuously.1 15

  • Should not be infused for periods >24 hours.1

  • Not necessary to discontinue the drug prior to extubation provided that duration of infusion is ≤24 hours.1

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

Vials are for single use only.1

Dilution

Must be diluted in 0.9% sodium chloride injection prior to administration.1 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.1

Rate of Administration

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

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

Dosage

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

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.1

Special Populations

Hepatic Impairment

Consider dosage reduction.1

Renal Impairment

Consider dosage reduction; metabolites may accumulate with long-term infusion.1

Geriatric Patients

Consider dosage reduction.1

Cautions for Dexmedetomidine Hydrochloride

Contraindications

  • Known hypersensitivity to dexmedetomidine hydrochloride.1

Warnings/Precautions

Warnings

Cardiac Arrhythmias

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

General Precautions

Cardiovascular Precautions

Possible hypotension and bradycardia;1 8 9 may be more pronounced in geriatric patients or those with hypovolemia, diabetes mellitus, or chronic hypertension.16 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.16

Transient hypertension reported with loading dose; treatment generally not required.1

Supraventricular and ventricular tachycardia, atrial fibrillation, extrasystoles, and cardiac arrest reported rarely.1 15

Use with caution in patients with advanced heart block and/or severe ventricular dysfunction.1

Withdrawal Reactions

Potential for withdrawal manifestations (e.g., nervousness,1 agitation,1 headaches,1 rapid rise in blood pressure,1 elevated plasma catecholamine concentrations1 ) if administered chronically and stopped abruptly.1 Should not be administered for >24 hours.1

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.1

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.16

Specific Populations

Pregnancy

Category C.1 Use during labor and delivery, including cesarean section deliveries, is not recommended.1

Lactation

Distributed into milk in rats.1 Caution if used in nursing women.1

Pediatric Use

Safety and efficacy not established in children <18 years of age.1

Geriatric Use

Use with caution in patients >65 years of age.1

Hypotension and/or bradycardia may be more pronounced.1

Monitor renal function.1

Renal Impairment

Use with caution.1 (See Renal Impairment under Dosage and Administration.)

Hepatic Impairment

Use with caution.1 (See Dosage and Administration.)

Common Adverse Effects

Hypotension,1 8 hypertension,1 nausea,1 bradycardia,1 8 fever,1 16 vomiting,1 16 hypoxia,1 tachycardia,16 anemia.1

Interactions for Dexmedetomidine Hydrochloride

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

Agents with Negative Chronotropic Effects

Potential pharmacodynamic interaction (additive pharmacodynamic effects).16 Use with caution.16

Protein-bound Drugs

Pharmacokinetic interaction unlikely.1

Specific Drugs

Drug

Interaction

Comments

Anesthetics

Additive pharmacologic effects1 8

May require reduction in anesthetic dosage1 8

Digoxin

Negligible change in dexmedetomidine protein binding in vitro; negligible displacement of digoxin from protein binding sites in vitro1

Fentanyl

Negligible change in dexmedetomidine protein binding in vitro1

Ibuprofen

Negligible displacement of ibuprofen from protein binding sites in vitro1

Ketorolac

Negligible change in dexmedetomidine protein binding in vitro1

Lidocaine

Negligible change in dexmedetomidine protein binding in vitro1

Neuromuscular blocking agents

Increased plasma rocuronium concentrations1 12

No clinically important effect on neuromuscular blockade1 12

Opiate agonists

Additive pharmacologic effects1 8

May require reduction in opiate agonist dosage1 8

Phenytoin

Negligible displacement of phenytoin from protein binding sites in vitro1

Propranolol

Negligible displacement of propranolol from protein binding sites in vitro1

Sedatives/hypnotics

Additive pharmacologic effects1 8

May require reduction in sedative/hypnotic dosage1 8

Theophylline

Negligible change in dexmedetomidine protein binding in vitro; negligible displacement of theophylline from protein binding sites in vitro1

Vasodilators

Additive pharmacologic effects16

Use with caution16

Warfarin

Negligible displacement of warfarin from protein binding sites in vitro1

Dexmedetomidine Hydrochloride Pharmacokinetics

Distribution

Extent

Rapidly distributed.16

Crosses the placenta and is distributed into milk when administered sub-Q to rats.1

Plasma Protein Binding

Approximately 94%.16

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%).16

Half-life

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

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.16

Pharmacokinetics of dexmedetomidine metabolites in patients with renal impairment not determined to date; potential for accumulation with long-term infusion.16

Stability

Storage

Parenteral

Injection Concentrate

25°C (may be exposed to temperatures ranging from 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

Compatible1

Dextrose 5%

Lactated Ringer’s

Mannitol 20%

Sodium chloride 0.9%

Drug Compatibility
Y-Site Injection Compatibility

Compatible1 HID

Alfentanil HCl

Amikacin sulfate

Aminophylline

Amiodarone HCl

Ampicillin sodium

Ampicillin sodium-sulbactam sodium

Atracurium besylate

Atropine sulfate

Azithromycin

Azetreonam

Bretylium tosylate

Bumetanide

Butorphanol tartrate

Calcium gluconate

Cefazolin sodium

Cefepime HCl

Cefotaxime sodium

Cefoxitin sodium

Ceftizoxime sodium

Ceftriaxone sodium

Cefuroxime sodium

Chlorpromazine HCl

Cimetidine HCl

Ciprofloxacin

Clindamycin phosphate

Co-trimoxazole

Dexamethasone sodium phosphate

Digoxin

Diltiazem HCl

Diphenhydramine HCl

Dobutamine HCl

Dolasetron mesylate

Dopamine HCl

Doxycycline hyclate

Droperidol

Enalaprilat

Ephedrine sulfate

Epinephrine HCl

Erythromycin lactobionate

Esmolol HCl

Etomidate

Famotidine

Fentanyl citrate

Fenoldopam mesylate

Fluconazole

Furosemide

Gentamicin sulfate

Glycopyrrolate

Granisetron HCl

Haloperidol lactate

Heparin sodium

Hydromorphone HCl

Hydroxyzine HCl

Inamrinone lactate

Isoproterenol HCl

Ketorolac tromethamine

Labetalol HCl

Levofloxacin

Lidocaine HCl

Linezolid

Lorazepam

Magnesium sulfate

Meperidine HCl

Methylprednisolone sodium succinate

Metoclopramide HCl

Metronidazole

Midazolam HCl

Milrinone lactate

Mivacurium chloride

Morphine sulfate

Nalbuphine HCl

Nitroglycerin

Norepinephrine bitartrate

Ofloxacin

Ondansetron HCl

Pancuronium bromide

Phenylephrine HCl

Piperacillin sodium-tazobactam sodium

Potassium chloride

Procainamide HCl

Prochlorperazine edisylate

Promethazine HCl

Propofol

Ranitidine HCl

Remifentanil HCl

Rocuronium bromide

Sodium bicarbonate

Sodium nitroprusside

Succinylcholine chloride

Sufentanil citrate

Theophylline

Thiopental sodium

Ticarcillin disodium-clavulanate potassium

Tobramycin sulfate

Vancomycin

Vecuronium bromide

Verapamil

Incompatible

Amphotericin B

Diazepam

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-life2 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

  • 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.

Dexmedetomidine Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection concentrate, for IV infusion

100 mcg (of dexmedetomidine) per mL

Precedex (preservative-free)

Abbott

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions August 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Abbott Laboratories. Precedex (dexmedetomidine) injection prescribing information. North Chicago, IL; 2000 Feb.

2. Khan ZP, Ferguson CN, Jones RM. Alpha-2 and imidazoline receptor agonists. Anaesthesia. 1999; 54:146-65. [IDIS 424011] [PubMed 10215710]

3. Kamibayashi T, Harasawa K, Maze M. Alpha-2 adrenergic agonists. Can J Anaesth. 1997; 44:R13-R18. [IDIS 388191] [PubMed 9196836]

4. Peden CJ, Prys-Roberts C. Dexmedetomidine—a powerful new adjunct to anaesthesia? Br J Anaesth. 1992; 68:123-5. Editorial.

5. Shipton EA. Alpha-adrenergic agonists in anaesthesia and analgesia. S Afr Med J. 1991; 79:578-80. [IDIS 285945] [PubMed 1674173]

6. Jalonen J, Hynynen M, Kuitunen A et al. Dexmedetomidine as an anesthetic adjunct in coronary artery bypass grafting. Anesthesiology. 1997; 86:331-45. [IDIS 382076] [PubMed 9054252]

7. Aho M, Lehtinen A-M, Erkola O et al. The effect of intravenously administered dexmedetomidine on perioperative hemodynamics and isoflurane requirements in patients undergoing abdominal hysterectomy. Anesthesiology. 1991; 74:997-1002. [IDIS 284603] [PubMed 1675042]

8. Aho MS, Erkola OA, Scheinin H et al. Effect of intravenously administered dexmedetomidine on pain after laparoscopic tubal ligation. Anesth Analg. 1991; 73:112-8. [IDIS 285764] [PubMed 1854025]

9. Lawrence CJ, De Lange S. Effects of a single pre-operative dexmedetomidine dose on isoflurane requirements and peri-operative haemodynamic stability. Anaesthesia. 1997; 52:736-44. [IDIS 390419] [PubMed 9291757]

10. Talke P, Li J, Jain U et al. Effects of perioperative dexmedetomidine infusion in patients undergoing vascular surgery. Anesthesiology. 1995; 82:620-33. [IDIS 344466] [PubMed 7879930]

11. Jaakola M-L, Ali-Melkkila T, Kanto J et al. Dexmedetomidine reduces intraocular pressure, intubation responses and anaesthetic requirements in patients undergoing ophthalmic surgery. Br J Anaesth. 1992; 68:570-5. [IDIS 297845] [PubMed 1351736]

12. Talke PO, Caldwell JE, Richardson CA et al. The effects of dexmedetomidine on neuromuscular blockade in human volunteers. Anesth Analg. 1999; 88:633-9. [IDIS 425244] [PubMed 10072019]

13. Khan ZP, Munday IT, Jones RM et al. Effects of dexmedetomidine on isoflurane requirements in healthy volunteers. 1. Pharmacodynamic and pharmacokinetic interactions. Br J Anaesth. 1999; 83:372-80. [IDIS 434895] [PubMed 10655905]

14. Aho M, Erkola O, Kallio A et al. Dexmedetomidine infusion for maintenance of anesthesia in patients undergoing abdominal hysterectomy. Anesth Analg. 1992; 75:940-6. [IDIS 306164] [PubMed 1359809]

15. Abbott, Abbott Park, IL: Personal communication.

16. Abbott Laboratories. Precedex (dexmedetomidine) injection prescribing information. North Chicago, IL; 2001 Feb.

HID. Trissel LA. Handbook on injectable drugs. 14th ed; Bethesda, MD: American Society of Health-System Pharmacists; 2007:489-95.

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