Dexmedetomidine (Page 2 of 8)

2.5 Administration with Other Fluids

Dexmedetomidine injection infusion should not be co-administered through the same intravenous catheter with blood or plasma because physical compatibility has not been established.

Dexmedetomidine injection has been shown to be incompatible when administered with the following drugs: amphotericin B, diazepam.

Dexmedetomidine 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

2.6 Compatibility with Natural Rubber

Compatibility studies have demonstrated the potential for absorption of dexmedetomidine injection to some types of natural rubber. Although dexmedetomidine injection is dosed to effect, it is advisable to use administration components made with synthetic or coated natural rubber gaskets.

3 DOSAGE FORMS AND STRENGTHS

Dexmedetomidine Injection USP, 200 mcg/2 mL (100 mcg/mL) is a clear and colorless solution in a single-dose vial, to be used after dilution.

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 Drug Administration

Dexmedetomidine injection should be administered only by persons skilled in the management of patients in the intensive care or operating room setting. Due to the known pharmacological effects of dexmedetomidine injection, patients should be continuously monitored while receiving dexmedetomidine injection.

5.2 Hypotension, Bradycardia, and Sinus Arrest

Clinically significant episodes of bradycardia and sinus arrest have been reported with dexmedetomidine injection 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 injection infusion. Some of these cases have resulted in fatalities. If medical intervention is required, treatment may include decreasing or stopping the infusion of dexmedetomidine injection, increasing the rate of intravenous fluid administration, elevation of the lower extremities, and use of pressor agents. Because dexmedetomidine injection 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 injection-induced bradycardia. However, in some patients with significant cardiovascular dysfunction, more advanced resuscitative measures were required.

Caution should be exercised when administering dexmedetomidine injection to patients with advanced heart block and/or severe ventricular dysfunction. Because dexmedetomidine injection 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 injection an additive pharmacodynamic effect was not observed. Nonetheless, caution should be used when such agents are administered concomitantly with dexmedetomidine injection.

5.3 Transient Hypertension

Transient hypertension has been observed primarily during the loading dose in association with the initial peripheral vasoconstrictive effects of dexmedetomidine injection. Treatment of the transient hypertension has generally not been necessary, although reduction of the loading infusion rate may be desirable.

5.4 Arousability

Some patients receiving dexmedetomidine injection 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.

5.5 Withdrawal

Intensive Care Unit Sedation

With administration up to 7 days, regardless of dose, 12 (5%) dexmedetomidine injection adult subjects experienced at least 1 event related to withdrawal within the first 24 hours after discontinuing study drug and 7 (3%) dexmedetomidine injection adult subjects experienced at least 1 event 24 to 48 hours after end of study drug. The most common events were nausea, vomiting, and agitation [see Adverse Reactions (6.1)].

In adult subjects, tachycardia and hypertension requiring intervention in the 48 hours following study drug discontinuation occurred at frequencies of < 5%.

Procedural Sedation

In adult subjects, withdrawal symptoms were not seen after discontinuation of short-term infusions of dexmedetomidine injection (< 6 hours).

In pediatric patients, mild transient withdrawal symptoms of emergence delirium or agitation were seen after discontinuation of short-term infusions of dexmedetomidine injection (< 2 hours).

Pediatric use information is approved for Hospira Inc.’s PRECEDEX™ (dexmedetomidine hydrochloride) injection and PRECEDEX™ (dexmedetomidine hydrochloride) in sodium chloride injection. However, due to Hospira Inc.’s marketing exclusivity rights, this drug product is not labeled with that information.

5.6 Tolerance and Tachyphylaxis

Use of dexmedetomidine beyond 24 hours has been associated with tolerance and tachyphylaxis and a dose-related increase in adverse reactions [see Adverse Reactions (6.1)].

5.7 Hyperthermia or Pyrexia

Dexmedetomidine injection may induce hyperthermia or pyrexia, which may be resistant to traditional cooling methods, such as administration of cooled intravenous fluids and antipyretic medications. Discontinue dexmedetomidine injection if drug-related hyperthermia or pyrexia is suspected and monitor patients until body temperature normalizes.

5.8 Hepatic Impairment

Since dexmedetomidine clearance decreases with severity of hepatic impairment, dose reduction should be considered in patients with impaired hepatic function [see Dosage and Administration (2.2, 2.3)].

6 ADVERSE REACTIONS

The following clinically significant adverse reactions are described elsewhere in the labeling:

Hypotension, bradycardia and sinus arrest [see Warnings and Precautions (5.2)]
Transient hypertension [see Warnings and Precautions (5.3)]

6.1 Clinical Trials 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 the clinical trials of another drug and may not reflect the rates observed in practice.

Most common treatment-emergent adverse reactions, occurring in greater than 2% of adult patients in both Intensive Care Unit and procedural sedation studies include hypotension, bradycardia and dry mouth.

Intensive Care Unit Sedation

Adverse reaction information is derived from the continuous infusion trials of dexmedetomidine injection for sedation in the Intensive Care Unit setting in which 1,007 adult patients received dexmedetomidine injection. The mean total dose was 7.4 mcg/kg (range: 0.8 to 84.1), mean dose per hour was 0.5 mcg/kg/hr (range: 0.1 to 6.0) and the mean duration of infusion of 15.9 hours (range: 0.2 to 157.2). The population was between 17 to 88 years of age, 43% ≥ 65 years of age, 77% male and 93% Caucasian. Treatment-emergent adverse reactions occurring at an incidence of > 2% are provided in Table 3. The most frequent adverse reactions were hypotension, bradycardia and dry mouth [see Warnings and Precautions (5.2)].

Table 3: Adverse Reactions with an Incidence > 2%-Adult Intensive Care Unit Sedation Population < 24 hours *
*
26 subjects in the all dexmedetomidine injection group and 10 subjects in the randomized dexmedetomidine injection group had exposure for greater than 24 hours.

Adverse Event

All Dexmedetomidine Injection(N = 1007)(%)

Randomized

Dexmedetomidine Injection

(N = 798)

(%)

Placebo

(N = 400)

(%)

Propofol

(N = 188)

(%)

Hypotension

25%

24%

12%

13%

Hypertension

12%

13%

19%

4%

Nausea

9%

9%

9%

11%

Bradycardia

5%

5%

3%

0

Atrial Fibrillation

4%

5%

3%

7%

Pyrexia

4%

4%

4%

4%

Dry Mouth

4%

3%

1%

1%

Vomiting

3%

3%

5%

3%

Hypovolemia

3%

3%

2%

5%

Atelectasis

3%

3%

3%

6%

Pleural Effusion

2%

2%

1%

6%

Agitation

2%

2%

3%

1%

Tachycardia

2%

2%

4%

1%

Anemia

2%

2%

2%

2%

Hyperthermia

2%

2%

3%

0

Chills

2%

2%

3%

2%

Hyperglycemia

2%

2%

2%

3%

Hypoxia

2%

2%

2%

3%

Post-procedural Hemorrhage

2%

2%

3%

4%

Pulmonary Edema

1%

1%

1%

3%

Hypocalcemia

1%

1%

0

2%

Acidosis

1%

1%

1%

2%

Urine Output Decreased

1%

1%

0

2%

Sinus Tachycardia

1%

1%

1%

2%

Ventricular Tachycardia

< 1%

1%

1%

5%

Wheezing

< 1%

1%

0

2%

Edema Peripheral

< 1%

0

1%

2%

Adverse reaction information was also derived from the placebo-controlled, continuous infusion trials of dexmedetomidine injection for sedation in the surgical intensive care unit setting in which 387 adult patients received dexmedetomidine injection for less than 24 hours. The most frequently observed treatment-emergent adverse events included hypotension, hypertension, nausea, bradycardia, fever, vomiting, hypoxia, tachycardia and anemia (see Table 4).

Table 4: Treatment-Emergent Adverse Events Occurring in > 1% of All Dexmedetomidine-Treated Adult Patients in the Randomized Placebo-Controlled Continuous Infusion < 24 Hours ICU Sedation Studies

Adverse Event

Randomized Dexmedetomidine

(N = 387)

Placebo

(N = 379)

Hypotension

28%

13%

Hypertension

16%

18%

Nausea

11%

9%

Bradycardia

7%

3%

Fever

5%

4%

Vomiting

4%

6%

Atrial Fibrillation

4%

3%

Hypoxia

4%

4%

Tachycardia

3%

5%

Hemorrhage

3%

4%

Anemia

3%

2%

Dry Mouth

3%

1%

Rigors

2%

3%

Agitation

2%

3%

Hyperpyrexia

2%

3%

Pain

2%

2%

Hyperglycemia

2%

2%

Acidosis

2%

2%

Pleural Effusion

2%

1%

Oliguria

2%

< 1%

Thirst

2%

< 1%

In a controlled clinical trial, dexmedetomidine injection was compared to midazolam for ICU sedation exceeding 24 hours duration in adult patients. Key treatment emergent adverse events occurring in dexmedetomidine or midazolam treated adult patients in the randomized active comparator continuous infusion long-term intensive care unit sedation study are provided in Table 5. The number (%) of adult subjects who had a dose-related increase in treatment-emergent adverse events by maintenance adjusted dose rate range in the dexmedetomidine injection group is provided in Table 6.

Table 5: Key Treatment-Emergent Adverse Events Occurring in Dexmedetomidine- or Midazolam-Treated Adult Patients in the Randomized Active Comparator Continuous Infusion Long-Term Intensive Care Unit Sedation Study
*
Hypotension was defined in absolute terms as Systolic blood pressure of < 80 mmHg or Diastolic blood pressure of < 50 mmHg or in relative terms as ≤ 30% lower than pre-study drug infusion value.
Bradycardia was defined in absolute terms as < 40 bpm or in relative terms as ≤ 30% lower than pre-study drug infusion value.
Hypertension was defined in absolute terms as Systolic blood pressure > 180 mmHg or Diastolic blood pressure of > 100 mmHg or in relative terms as ≥ 30% higher than pre-study drug infusion value.
§
Tachycardia was defined in absolute terms as > 120 bpm or in relative terms as ≥ 30% greater than pre-study drug infusion value.
Includes any type of hypertension.

Adverse Event

Dexmedetomidine

(N = 244)

Midazolam

(N = 122)

Hypotension *

56%

56%

Hypotension Requiring Intervention

28%

27%

Bradycardia

42%

19%

Bradycardia Requiring Intervention

5%

1%

Systolic Hypertension

28%

42%

Tachycardia §

25%

44%

Tachycardia Requiring Intervention

10%

10%

Diastolic Hypertension

12%

15%

Hypertension

11%

15%

Hypertension Requiring Intervention

19%

30%

Hypokalemia

9%

13%

Pyrexia

7%

2%

Agitation

7%

6%

Hyperglycemia

7%

2%

Constipation

6%

6%

Hypoglycemia

5%

6%

Respiratory Failure

5%

3%

Renal Failure Acute

2%

1%

Acute Respiratory Distress Syndrome

2%

1%

Generalized Edema

2%

6%

Hypomagnesemia

1%

7%

The following adverse events occurred between 2 and 5% for dexmedetomidine injection and Midazolam, respectively: renal failure acute (2.5%, 0.8%), acute respiratory distress syndrome (2.5%, 0.8%), and respiratory failure (4.5%, 3.3%).

Table 6: Number (%) of Adult Subjects Who Had a Dose-Related Increase in Treatment Emergent Adverse Events by Maintenance Adjusted Dose Rate Range in the Dexmedetomidine Injection Group
*
Average maintenance dose over the entire study drug administration.

Dexmedetomidine Injection (mcg/kg/hr)

Adverse Event

≤ 0.7 *

(N = 95)

> 0.7 to ≤ 1.1 *

(N = 78)

> 1.1 *

(N = 71)

Constipation

6%

5%

14%

Agitation

5%

8%

14%

Anxiety

5%

5%

9%

Edema Peripheral

3%

5%

7%

Atrial Fibrillation

2%

4%

9%

Respiratory Failure

2%

6%

10%

Acute Respiratory Distress Syndrome

1%

3%

9%

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2024. All Rights Reserved.