1.1 Intensive Care Unit Sedation

Precedex® is indicated for sedation of initially intubated and mechanically ventilated patients during treatment in an intensive care setting. Precedex should be administered by continuous infusion not to exceed 24 hours.

Precedex has been continuously infused in mechanically ventilated patients prior to extubation, during extubation, and post-extubation. It is not necessary to discontinue Precedex prior to extubation.

1.2 Procedural Sedation

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

2.1 Dosing Guidelines

• Precedex dosing should be individualized and titrated to desired clinical response.

• Precedex is not indicated for infusions lasting longer than 24 hours.

• Precedex should be administered using a controlled infusion device.

2.2 Dosage Information

2.3 Dosage Adjustment

Due to possible pharmacodynamic interactions, a reduction in dosage of Precedex 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 patients with hepatic impairment, and geriatric patients [see Warnings and Precautions (5.6), Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

2.4 Preparation of Solution

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

Strict aseptic technique must always be maintained during handling of Precedex.

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

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

2.5 Administration with Other Fluids

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

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

Precedex 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 Precedex to some types of natural rubber. Although Precedex is dosed to effect, it is advisable to use administration components made with synthetic or coated natural rubber gaskets.

5.1 Drug Administration

Precedex 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 Precedex, patients should be continuously monitored while receiving Precedex.

5.2 Hypotension, Bradycardia, and Sinus Arrest

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

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

5.3 Transient Hypertension

Transient hypertension has been observed primarily during the loading dose in association with the initial peripheral vasoconstrictive effects of Precedex. 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 Precedex 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%) Precedex subjects experienced at least 1 event related to withdrawal within the first 24 hours after discontinuing study drug and 7 (3%) Precedex subjects experienced at least 1 event 24 to 48 hours after end of study drug. The most common events were nausea, vomiting, and agitation.

Tachycardia and hypertension requiring intervention in the 48 hours following study drug discontinuation occurred at frequencies of <5%. If tachycardia and/or hypertension occurs after discontinuation of Precedex supportive therapy is indicated.

Procedural Sedation

Withdrawal symptoms were not seen after discontinuation of short term infusions of Precedex (<6 hours).

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 Hepatic Impairment

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

6.1 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 Precedex has been associated with the following serious adverse reactions:

• Hypotension, bradycardia and sinus arrest [see Warnings and Precautions (5.2)]

• Transient hypertension [see Warnings and Precautions (5.3)]

Most common treatment-emergent adverse reactions, occurring in greater than 2% of 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 Precedex for sedation in the Intensive Care Unit setting in which 1007 patients received Precedex. 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 2. The most frequent adverse reactions were hypotension, bradycardia and dry mouth [see Warnings and Precautions (5.2)].

Tags： 责任编辑：admin
【大 中 小】【打印】 【繁体】【投稿】【收藏】 【推荐】【举报】【评论】 【关闭】 【返回顶部】
分享到:
上一篇：Precedex	下一篇：Isentress