Dexmedetomidine

DEXMEDETOMIDINE- dexmedetomidine hydrochloride injection, solution, concentrate
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1 INDICATIONS AND USAGE

1.2 Procedural Sedation

Dexmedetomidine Injection is indicated for sedation of non-intubated patients prior to and/or during surgical and other procedures.

2 DOSAGE AND ADMINISTRATION

2.1 Dosing Guidelines

• Dexmedetomidine injection dosing should be individualized and titrated to desired clinical response.
• Dexmedetomidine injection is not indicated for infusions lasting longer than 24 hours.
• Dexmedetomidine injection should be administered using a controlled infusion device.

2.2 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 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)] .

2.3 Dosage Adjustment

Due to possible pharmacodynamic interactions, a reduction in dosage of dexmedetomidine injection or other concomitant anesthetics, sedatives, hypnotics or opioids may be required when co-administered [see Drug Interactions ( 7.1)] .

Dosage reductions may need to be considered for adult patients with hepatic impairment, and geriatric patients [see Warnings and Precautions ( 5.7), Use in Specific Populations ( 8.6), Clinical Pharmacology ( 12.3)] .

2.4 Preparation of Solution

Strict aseptic technique must always be maintained during handling of dexmedetomidine injection.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Dexmedetomidine injection, 200 mcg per 2 mL (100 mcg per mL)

Dexmedetomidine injection must be diluted with 0.9% sodium chloride injection to achieve required concentration (4 mcg per mL) prior to administration. Preparation of solutions is the same, whether for the loading dose or maintenance infusion.

To prepare the infusion, withdraw 2 mL of dexmedetomidine injection, and add to 48 mL of 0.9% sodium chloride injection to a total of 50 mL. Shake gently to mix well.

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

Dexmedetomidine Injection, USP, 200 mcg per 2 mL dexmedetomidine (100 mcg per mL) in a glass vial. To be used after dilution.

4 CONTRAINDICATIONS

None

5 WARNINGS AND PRECAUTIONS

5.1 Drug Administration

Dexmedetomidine 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, patients should be continuously monitored while receiving dexmedetomidine.

5.2 Hypotension, Bradycardia, and Sinus Arrest

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

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