Dexdor Special Precautions

Drug Administration: Dexdor 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 Dexdor, patients should be continuously monitored while receiving Dexdor.
Hypotension, Bradycardia, and Sinus Arrest: Clinically significant episodes of bradycardia and sinus arrest have been reported with Dexdor 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 Dexdor infusion. Some of these cases have resulted in fatalities. If medical intervention is required, treatment may include decreasing or stopping the infusion of Dexdor, increasing the rate of intravenous fluid administration, elevation of the lower extremities, and use of pressor agents. Because Dexdor 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 Dexdor-induced bradycardia. However, in some patients with significant cardiovascular dysfunction, more advanced resuscitative measures were required.
Caution should be exercised when administering Dexdor to patients with advanced heart block and/or severe ventricular dysfunction. Because Dexdor 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 Dexdor an additive pharmacodynamic effect was not observed. Nonetheless, caution should be used when such agents are administered concomitantly with Dexdor.
Transient Hypertension: Transient hypertension has been observed primarily during the loading dose in association with the initial peripheral vasoconstrictive effects of Dexdor. Treatment of the transient hypertension has generally not been necessary, although reduction of the loading infusion rate may be desirable.
Arousability: Some patients receiving Dexdor 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: Alpha-2 agonists have rarely been associated with withdrawal reactions when stopped abruptly after prolonged use. This possibility should be considered if the patient develops agitation and hypertension shortly after stopping dexmedetomidine.
With administration up to 14 days, regardless of dose, 2-7% of Dexdor adult subjects experienced signs of sympathetic activation indicating withdrawal syndrome within the first 48 hours after discontinuing study drug. The most common events were nausea, vomiting, agitation, anxiety and sweating.
In adult subjects, 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 Dexdor supportive therapy is indicated.
Procedural Sedation: In adult subjects, withdrawal symptoms were not seen after discontinuation of short term infusions of Dexdor (<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 [see Clinical Studies Experience under Adverse Reactions].
Hepatic Impairment: Since Dexdor clearance decreases with increasing severity of hepatic impairment, dose reduction should be considered in patients with impaired hepatic function [see Dosage Information under Dosage & Administration].
DRUG ABUSE AND DEPENDENCE: Controlled Substance: Dexdor (dexmedetomidine hydrochloride) is not a controlled substance.
Dependence: The dependence potential of Dexdor has not been studied in humans. However, since studies in rodents and primates have demonstrated that Dexdor exhibits pharmacologic actions similar to those of clonidine, it is possible that Dexdor may produce a clonidine-like withdrawal syndrome upon abrupt discontinuation [see Withdrawal Intensive Care Unit Sedation as previously mentioned].
Use in Children: Safety and efficacy have not been established for Procedural or ICU Sedation in pediatric patients. One assessor-blinded trial in pediatric patients and two open label studies in neonates were conducted to assess efficacy for ICU sedation. These studies did not meet their primary efficacy endpoints and the safety data submitted were insufficient to fully characterize the safety profile of Dexdor for this patient population. The use of Dexdor for procedural sedation in pediatric patients has not been evaluated.
Use in the Elderly: Intensive Care Unit Sedation: In patients greater than 65 years of age, a higher incidence of bradycardia and hypotension was observed following administration of Dexdor [see Hypotension, Bradycardia, and Sinus Arrest as previously mentioned]. Therefore, a dose reduction may be considered in patients over 65 years of age [see Dosage Information under Dosage & Administration and PHARMACOLOGY: Pharmacokinetics under Actions].
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 Dexdor-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.