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 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 PRECEDEX infusion. Some of these cases have resulted in fatalities. 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

5.6 Diabetes Insipidus

Cases of diabetes insipidus (DI) have been reported with use of dexmedetomidine in the setting of sedation. Signs of DI in this setting include polyuria (output >125 mL/hr), diluted urine (osmolality <300 mOsm/kg), and hypernatremia (serum sodium >145 mmol/L). If unrecognized, this condition can lead to hemodynamic instability including unstable blood pressure and increased risk of other cardiovascular sequelae.

In reported cases, signs of DI have spontaneously resolved following discontinuation of dexmedetomidine, with resolution often occurring after 24 hours. Monitor urine output and laboratory data for signs of DI during and after dexmedetomidine administration. If DI is suspected, adjust fluid management, provide supportive care, and consider discontinuing dexmedetomidine. If such care is insufficient, or in a setting where dexmedetomidine is used for an extended treatment period, consider expert consultation to assist with patient management.

5.7 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)].

5.8 Hyperthermia or Pyrexia

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

5.9 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, 2.3)].