Dexmedetomidine Hcl Drug Information
Generic name: DEXMEDETOMIDINE HCL
Uses of Dexmedetomidine Hcl
Procedural Sedation
Dexmedetomidine hydrochloride injection is indicated for sedation of non-intubated patients prior to and/or during surgical and other procedures.
Dosage & Administration of Dexmedetomidine Hcl
Dosing Guidelines
Dexmedetomidine hydrochloride injection dosing should be individualized and titrated to desired clinical response. Dexmedetomidine hydrochloride injection is not indicated for infusions lasting longer than 24 hours. Dexmedetomidine hydrochloride injection should be administered using a controlled infusion device.
- Dosage Information Table 1: Dosage Information INDICATION DOSAGE AND ADMINISTRATION Initiation of Procedural Sedation For adult patients: a loading infusion of one mcg/kg over 10 minutes.
- For patients over 65 years of age: a loading infusion of 0.5 mcg/kg over 10 minutes.
- For adult patients with impaired hepatic function: a dose reduction should be considered.
- Maintenance of Procedural Sedation For adult patients: the maintenance infusion is generally initiated at 0.6 mcg/kg/ hour and titrated to achieve desired clinical effect with doses ranging from 0.2 to 1 mcg/kg/ hour.
- For patients over 65 years of age: a dose reduction should be considered.
Dosage Adjustment Due to possible pharmacodynamic interactions, a reduction in dosage of dexmedetomidine hydrochloride injection or other concomitant anesthetics, sedatives, hypnotics or opioids may be required when co-administered. Dosage reductions may need to be considered for adult patients with hepatic impairment, and geriatric patients.
Preparation of Solution
Strict aseptic technique must always be maintained during handling of dexmedetomidine hydrochloride injection. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Preparation of solutions is the same, whether for the loading dose or maintenance infusion.
Shake gently to mix well.
Administration with Other Fluids
Dexmedetomidine hydrochloride injection infusion should not be co-administered through the same intravenous catheter with blood or plasma because physical compatibility has not been established. Dexmedetomidine hydrochloride injection has been shown to be incompatible when administered with the following drugs: amphotericin B, diazepam. Dexmedetomidine hydrochloride injection has been shown to be compatible when administered with the following intravenous fluids: 0.9% sodium chloride in water 5% dextrose in water 20% mannitol Lactated Ringer’s solution 100 mg/mL magnesium sulfate solution 0.3% potassium chloride solution
Compatibility with Natural Rubber
Compatibility studies have demonstrated the potential for absorption of dexmedetomidine hydrochloride injection to some types of natural rubber. Although dexmedetomidine hydrochloride injection is dosed to effect, it is advisable to use administration components made with synthetic or coated natural rubber gaskets.
| INDICATION | DOSAGE AND ADMINISTRATION |
| Initiation of Procedural Sedation | For adult patients: a loading infusion of one mcg/kg over 10 minutes. For less invasive procedures such as ophthalmic surgery, a loading infusion of 0.5 mcg/kg given over 10 minutes may be suitable. For awake fiberoptic intubation in adult patients: a loading infusion of one mcg/kg over 10 minutes. For patients over 65 years of age: a loading infusion of 0.5 mcg/kg over 10 minutes [ see Use in Specific Populations (8.5) ]. For adult patients with impaired hepatic function: a dose reduction should be considered [ see Use in Specific Populations (8.6), Clinical Pharmacology (12.3 ) ]. |
| Maintenance of Procedural Sedation | For adult patients: the maintenance infusion is generally initiated at 0.6 mcg/kg/ hour and titrated to achieve desired clinical effect with doses ranging from 0.2 to 1 mcg/kg/ hour. The rate of the maintenance infusion should be adjusted to achieve the targeted level of sedation. For awake fiberoptic intubation in adult patients: a maintenance infusion of 0.7 mcg/kg/ hour is recommended until the endotracheal tube is secured. For patients over 65 years of age: a dose reduction should be considered [ see Use in Specific Populations (8.5) ]. For adult patients with impaired hepatic function: a dose reduction should be considered [ see Use in Specific Populations (8.6 ), Clinical Pharmacology (12.3) ]. |
Side Effects of Dexmedetomidine Hcl
Clinical Studies Experience
Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice. Use of dexmedetomidine hydrochloride has been associated with the following serious adverse reactions: Hypotension, bradycardia and sinus arrest Transient hypertension Most common treatment-emergent adverse reactions, occurring in greater than 2% of patients in procedural sedation studies include hypotension, bradycardia and dry mouth. Procedural Sedation Adverse reaction information is derived from the two trials for procedural sedation in which 318 adult patients received dexmedetomidine hydrochloride.
Treatment-emergent adverse reactions occurring at an incidence of >2% are provided in Table 2. The most frequent adverse reactions were hypotension, bradycardia, and dry mouth. Pre-specified criteria for the vital signs to be reported as adverse reactions are footnoted below the table.
The decrease in respiratory rate and hypoxia was similar between dexmedetomidine hydrochloride and comparator groups in both studies. Table 2. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Hypotension and bradycardia were the most common adverse reactions associated with the use of dexmedetomidine hydrochloride during post approval use of the drug. Table 3: Adverse Reactions Experienced During Post-approval Use of Dexmedetomidine hydrochloride
| Adverse Event | Dexmedetomidine hydrochloride N = 318 (%) | Placebo N = 113 (%) |
|---|---|---|
| Hypotension 1 | 54% | 30% |
| Respiratory depression 2 | 37% | 32% |
| Bradycardia 3 | 14% | 4% |
| Hypertension 4 | 13% | 24% |
| Tachycardia 5 | 5% | 17% |
| Nausea | 3% | 2% |
| Dry mouth | 3% | 1% |
| Hypoxia 6 | 2% | 3% |
| Bradypnea | 2% | 4% |
| System Organ Class | Preferred Term |
|---|---|
| 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 Disorders and Administration Site Conditions | Chills, hyperpyrexia, pain, pyrexia, thirst |
| Hepatobiliary Disorders | Hepatic function abnormal, hyperbilirubinemia |
| Investigations | Alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased, blood urea increased, electrocardiogram T wave inversion, gammaglutamyltransferase increased, electrocardiogram 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 |
| Surgical and Medical Procedures | Light anesthesia |
| Vascular Disorders | Blood pressure fluctuation, hemorrhage, hypertension, hypotension |
Warnings & Cautions for Dexmedetomidine Hcl
Drug Administration
Dexmedetomidine hydrochloride should be administered only by persons skilled in the management of patients in the operating room setting. Due to the known pharmacological effects of dexmedetomidine hydrochloride, patients should be continuously monitored while receiving dexmedetomidine hydrochloride.
Hypotension, Bradycardia, and Sinus Arrest
Clinically significant episodes of bradycardia and sinus arrest have been reported with dexmedetomidine hydrochloride administration in young, healthy adult volunteers with high vagal tone or with different routes of administration including rapid intravenous or bolus administration. Reports of hypotension and bradycardia have been associated with dexmedetomidine hydrochloride infusion. Some of these cases have resulted in fatalities.
If medical intervention is required, treatment may include decreasing or stopping the infusion of dexmedetomidine hydrochloride, increasing the rate of intravenous fluid administration, elevation of the lower extremities, and use of pressor agents. Because dexmedetomidine hydrochloride has the potential to augment bradycardia induced by vagal stimuli, clinicians should be prepared to intervene. The intravenous administration of anticholinergic agents (e.g., glycopyrrolate, atropine) should be considered to modify vagal tone.
In clinical trials, glycopyrrolate or atropine were effective in the treatment of most episodes of dexmedetomidine hydrochloride-induced bradycardia. However, in some patients with significant cardiovascular dysfunction, more advanced resuscitative measures were required. Caution should be exercised when administering dexmedetomidine hydrochloride to patients with advanced heart block and/or severe ventricular dysfunction.
Because dexmedetomidine hydrochloride 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 elderly patients. In clinical trials where other vasodilators or negative chronotropic agents were co-administered with dexmedetomidine hydrochloride an additive pharmacodynamic effect was not observed. Nonetheless, caution should be used when such agents are administered concomitantly with dexmedetomidine hydrochloride.
Transient Hypertension
Transient hypertension has been observed primarily during the loading dose in association with the initial peripheral vasoconstrictive effects of dexmedetomidine hydrochloride. Treatment of the transient hypertension has generally not been necessary, although reduction of the loading infusion rate may be desirable.
Arousability
Some patients receiving dexmedetomidine hydrochloride have been observed to be arousable and alert when stimulated. This alone should not be considered as evidence of lack of efficacy in the absence of other clinical signs and symptoms.
Withdrawal Procedural Sedation
In adult subjects, withdrawal symptoms were not seen after discontinuation of short term infusions of dexmedetomidine hydrochloride (<6 hours).
Tolerance and Tachyphylaxis Use of dexmedetomidine beyond 24 hours has been associated with tolerance and tachyphylaxis and a dose-related increase in adverse reactions.
Hepatic Impairment
Since dexmedetomidine hydrochloride clearance decreases with severity of hepatic impairment, dose reduction should be considered in patients with impaired hepatic function.
Drug Interactions with Dexmedetomidine Hcl
Anesthetics, Sedatives, Hypnotics, Opioids Co-administration of dexmedetomidine hydrochloride with anesthetics, sedatives, hypnotics, and opioids is likely to lead to an enhancement of effects. Specific studies have confirmed these effects with sevoflurane, isoflurane, propofol, alfentanil, and midazolam. No pharmacokinetic interactions between dexmedetomidine hydrochloride and isoflurane, propofol, alfentanil and midazolam have been demonstrated.
However, due to possible pharmacodynamic interactions, when co-administered with dexmedetomidine hydrochloride, a reduction in dosage of dexmedetomidine hydrochloride or the concomitant anesthetic, sedative, hypnotic or opioid may be required.
Neuromuscular Blockers
In one study of 10 healthy adult volunteers, administration of dexmedetomidine hydrochloride for 45 minutes at a plasma concentration of 1 ng/mL resulted in no clinically meaningful increases in the magnitude of neuromuscular blockade associated with rocuronium administration.
Pregnancy Safety for Dexmedetomidine Hcl
- Pregnancy Teratogenic Effects: Pregnancy Category C: There are no adequate and well-controlled studies of dexmedetomidine hydrochloride use in pregnant women. In an in vitro human placenta study, placental transfer of dexmedetomidine occurred. In a study in the pregnant rat, placental transfer of dexmedetomidine was observed when radiolabeled dexmedetomidine was administered subcutaneously. Thus, fetal exposure should be expected in humans, and dexmedetomidine hydrochloride should be used during pregnancy only if the potential benefits justify the potential risk to the fetus. Teratogenic effects were not observed in rats following subcutaneous administration of dexmedetomidine during the period of fetal organogenesis (from gestation day 5 to 16) with doses up to 200 mcg/kg (representing a dose approximately equal to the maximum recommended human intravenous dose based on body surface area) or in rabbits following intravenous administration of dexmedetomidine during the period of fetal organogenesis (from gestation day 6 to 18) with doses up to 96 mcg/kg (representing approximately half the human exposure at the maximum recommended dose based on plasma area under the time-curve comparison). However, fetal toxicity, as evidenced by increased post-implantation losses and reduced live pups, was observed in rats at a subcutaneous dose of 200 mcg/kg. The no-effect dose in rats was 20 mcg/kg (representing a dose less than the maximum recommended human intravenous dose based on a body surface area comparison). In another reproductive toxicity study when dexmedetomidine was administered subcutaneously to pregnant rats at 8 and 32 mcg/kg (representing a dose less than the maximum recommended human intravenous dose based on a body surface area comparison) from gestation day 16 through weaning, lower offspring weights were observed. Additionally, when offspring of the 32 mcg/kg group were allowed to mate, elevated fetal and embryocidal toxicity and delayed motor development was observed in second generation offspring.
Pediatric Use of Dexmedetomidine Hcl
Pediatric Use Safety and efficacy have not been established for Procedural Sedation in pediatric patients. The use of dexmedetomidine for procedural sedation in pediatric patients has not been evaluated.
Overdosage Information for Dexmedetomidine Hcl
The tolerability of dexmedetomidine hydrochloride was studied in one study in which healthy adult subjects were administered doses at and above the recommended dose of 0.2 to 0.7 mcg/kg/hr. The maximum blood concentration achieved in this study was approximately 13 times the upper boundary of the therapeutic range. The most notable effects observed in two subjects who achieved the highest doses were first degree atrioventricular block and second degree heart block.
No hemodynamic compromise was noted with the atrioventricular block and the heart block resolved spontaneously within one minute. One patient who received a loading bolus dose of undiluted dexmedetomidine hydrochloride (19.4 mcg/kg), had cardiac arrest from which he was successfully resuscitated.
Clinical Studies of Dexmedetomidine Hcl
Procedural Sedation
The safety and efficacy of dexmedetomidine hydrochloride for sedation of non-intubated patients prior to and/or during surgical and other procedures was evaluated in two randomized, double-blind, placebo-controlled multicenter clinical trials. Study 1 evaluated the sedative properties of dexmedetomidine hydrochloride in patients having a variety of elective surgeries/procedures performed under monitored anesthesia care. Study 2 evaluated dexmedetomidine hydrochloride in patients undergoing awake fiberoptic intubation prior to a surgical or diagnostic procedure.
In Study 1, the sedative properties of dexmedetomidine hydrochloride were evaluated by comparing the percent of patients not requiring rescue midazolam to achieve a specified level of sedation using the standardized Observer’s Assessment of Alertness/Sedation Scale (Table 5). Table 5 Observer’s Assessment of Alertness/Sedation Patients were randomized to receive a loading infusion of either dexmedetomidine hydrochloride 1 mcg/kg, dexmedetomidine hydrochloride 0.5 mcg/kg, or placebo (normal saline) given over 10 minutes and followed by a maintenance infusion started at 0.6 mcg/kg/hr. The maintenance infusion of study drug could be titrated from 0.2 mcg/kg/hr to 1 mcg/kg/hr to achieve the targeted sedation score (Observer’s Assessment of Alertness/Sedation Scale ≤4).
Patients were allowed to receive rescue midazolam as needed to achieve and/or maintain an Observer’s Assessment of Alertness/Sedation Scale < 4. After achieving the desired level of sedation, a local or regional anesthetic block was performed. Demographic characteristics were similar between the dexmedetomidine hydrochloride and comparator groups.
Efficacy results showed that dexmedetomidine hydrochloride was more effective than the comparator group when used to sedate non-intubated patients requiring monitored anesthesia care during surgical and other procedures. (see Table 7) In Study 2, the sedative properties of dexmedetomidine hydrochloride were evaluated by comparing the percent of patients requiring rescue midazolam to achieve or maintain a specified level of sedation using the Ramsay Sedation Scale score > 2 (see Table 6). Table 6: Ramsay Level of Sedation Scale Patients were randomized to receive a loading infusion of dexmedetomidine hydrochloride 1 mcg/kg or placebo (normal saline) given over 10 minutes and followed by a fixed maintenance infusion of 0.7 mcg/kg/hr. After achieving the desired level of sedation, topicalization of the airway occurred.
Patients were allowed to receive rescue midazolam as needed to achieve and/or maintain a Ramsay Sedation Scale > 2. For efficacy results see Table 7. Table 7.
Key Efficacy Results of Procedural Sedation Studies − 2.9 − a Based on ITT population defined as all randomized and treated patients. b Normal approximation to the binomial with continuity correction.
| Assessment Categories | ||||
| Responsiveness | Speech | Facial Expression | Eyes | Composite Score |
| Responds readily to name spoken in normal tone | Normal | Normal | Clear, no ptosis | 5 (alert) |
| Lethargic response to name spoken in normal tone | Mild slowing or thickening | Mild relaxation | Glazed or mild ptosis (less than half the eye) | 4 |
| Responds only after name is called loudly and/or repeatedly | Slurring or prominent slowing | Marked relaxation (slack jaw) | Glazed and marked ptosis (half the eye or more) | 3 |
| Responds only after mild prodding or shaking | Few recognizable words | -- | -- | 2 |
| Does not respond to mild prodding or shaking | -- | -- | -- | 1 (deep sleep) |
| Clinical Score | Level of Sedation Achieved |
|---|---|
| 6 | Asleep, no response |
| 5 | Asleep, sluggish response to light glabellar tap or loud auditory stimulus |
| 4 | Asleep, but with brisk response to light glabellar tap or loud auditory stimulus |
| 3 | Patient responds to commands |
| 2 | Patient cooperative, oriented, and tranquil |
| 1 | Patient anxious, agitated, or restless |
| Study | Loading Infusion Treatment Arm | Number of Patients Enrolled a | % Not Requiring Midazolam Rescue | Confidence b Interval on the Difference vs. Placebo | Mean (SD) Total Dose (mg) of Rescue Midazolam Required | Confidence b Intervals of the Mean Rescue Dose |
|---|---|---|---|---|---|---|
| Study 1 | Dexmedetomidine 0.5 mcg/kg | 134 | 40 | 37 (27,48) | 1.4 (1.7) | -2.7 (-3.4, -2) |
| Dexmedetomidine 1 mcg/kg | 129 | 54 | 51 (40,62) | 0.9 (1.5) | -3.1 (-3.8, -2.5) | |
| placebo | 63 | 3 | − | 4.1 (3) | − | |
| Study 2 | Dexmedetomidine 1 mcg/kg | 55 | 53 | 39 (20,57) | 1.1 (1.5) | -1.8 (-2.7, -0.9) |
| placebo | 50 | 14 | − | 2.9 (3) | − |
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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