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Precedex (Dexmedetomidine Hydrochloride) - Warnings and Precautions

 
 



WARNINGS AND PRECAUTIONS

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.

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 situations where other vasodilators or negative chronotropic agents are administered, co-administration of Precedex could have an additive pharmacodynamic effect and should be administered with caution.

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.

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.

Withdrawal

Intensive Care Unit Sedation

If Precedex were to be administered for more than 24 hours and stopped abruptly, withdrawal symptoms similar to those reported for another alpha-2-adrenergic agent, clonidine, may result. These symptoms include nervousness, agitation, and headaches, accompanied or followed by a rapid rise in blood pressure and elevated catecholamine concentrations in the plasma.

Procedural Sedation

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

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) ].

USE IN SPECIFIC POPULATIONS

Pregnancy

Pregnancy Category C: Teratogenic effects were not observed following administration of Precedex at subcutaneous doses up to 200 mcg/kg in rats from day 5 to day 16 of gestation and intravenous doses up to 96 mcg/kg in rabbits from day 6 to day 18 of gestation. The dose in rats is approximately 2 times the maximum recommended human intravenous dose on a mcg/m2 basis. The exposure in rabbits is approximately equal to that in humans at the maximum recommended intravenous dose based on plasma area-under-the-curve values. However, fetal toxicity, as evidenced by increased post-implantation losses and reduced live pups, was observed in rats at subcutaneous dose of 200 mcg/kg. The no-effect dose was 20 mcg/kg (less than the maximum recommended human intravenous dose on a mcg/m2 basis). In another reproductive study when Precedex was administered subcutaneously to pregnant rats from gestation day 16 through nursing, it caused lower pup weights at 8 and 32 mcg/kg as well as fetal and embryocidal toxicity of second generation offspring at a dose of 32 mcg/kg (less than the maximum recommended human intravenous dose on a mcg/m2 basis). Precedex also produced delayed motor development in pups at a dose of 32 mcg/kg (less than the maximum recommended human intravenous dose on a mcg/m2 basis). No such effects were observed at a dose of 2 mcg/kg (less than the maximum recommended intravenous dose on a mcg/m2 basis).

Placental transfer of Precedex was observed when radiolabeled Precedex was administered subcutaneously to pregnant rats.

There are no adequate and well-controlled studies in pregnant women. Precedex should be used during pregnancy only if the potential benefits justify the potential risk to the fetus.

Labor and Delivery

The safety of Precedex during labor and delivery has not been studied. Therefore, Precedex is not recommended during labor and delivery including cesarean section deliveries.

Nursing Mothers

It is not known whether Precedex is excreted in human milk. Radio-labeled Precedex administered subcutaneously to lactating female rats was excreted in milk. Because many drugs are excreted in human milk, caution should be exercised when Precedex is administered to a nursing woman.

Pediatric Use

There have been no clinical studies to establish the safety and efficacy of Precedex in pediatric patients below 18 years of age. Therefore, Precedex should not be used in this population.

Geriatric Use

Precedex is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection in elderly patients, and it may be useful to monitor renal function.

Intensive Care Unit Sedation

A total of 729 patients in the clinical studies were 65 years of age and over. A total of 200 patients were 75 years of age and over. In patients greater than 65 years of age, a higher incidence of bradycardia and hypotension was observed following administration of Precedex [ see Warnings and Precautions (5.2) ]. Therefore a dose reduction may be considered in patients over 65 years of age [ see Dosage and Administration (2.2) and Clinical Pharmacology (12.3) ].

Procedural Sedation

A total of 131 patients in the clinical studies were 65 years of age and over. A total of 47 patients were 75 years of age and over. Hypotension occurred in a higher incidence in Precedex-treated patients 65 years or older (72%) and 75 years or older (74%) as compared to patients <65 years (47%). A reduced loading dose of 0.5 mcg/kg given over 10 minutes is recommended and a reduction in the maintenance infusion should be considered for patients greater than 65 years of age.

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) and Clinical Pharmacology (12.3) ].

Renal Impairment

[ see Use in Specific Populations (8.5) and Clinical Pharmacology (12.3) ].

Page last updated: 2008-11-21

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