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
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
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 |
ActionsActions
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.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | For injection concentrate, for IV infusion | 100 mcg (of dexmedetomidine) per mL | Precedex (preservative-free) | Abbott |
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions August 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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