Hypotension, bradycardia and sinus arrest [see Warnings and Precautions (5.2)]
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 the clinical trials of another drug and may not reflect the rates observed in practice.
Most common treatment-emergent adverse reactions, occurring in greater than 2% of adult 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 1,007 adult 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 3. The most frequent adverse reactions were hypotension, bradycardia and dry mouth [see Warnings and Precautions (5.2)].
Adverse reaction information was also derived from the placebo-controlled, continuous infusion trials of PRECEDEX for sedation in the surgical intensive care unit setting in which 387 adult patients received PRECEDEX for less than 24 hours. The most frequently observed treatment-emergent adverse events included hypotension, hypertension, nausea, bradycardia, fever, vomiting, hypoxia, tachycardia and anemia (see Table 4).
In a controlled clinical trial, PRECEDEX was compared to midazolam for ICU sedation exceeding 24 hours duration in adult patients. Key treatment emergent adverse events occurring in dexmedetomidine or midazolam treated adult patients in the randomized active comparator continuous infusion long-term intensive care unit sedation study are provided in Table 5. The number (%) of adult subjects who had a dose-related increase in treatment-emergent adverse events by maintenance adjusted dose rate range in the PRECEDEX group is provided in Table 6.
The following adverse events occurred between 2 and 5% for PRECEDEX and Midazolam, respectively: renal failure acute (2.5%, 0.8%), acute respiratory distress syndrome (2.5%, 0.8%), and respiratory failure (4.5%, 3.3%).
Adult Procedural Sedation
Adverse reaction information is derived from the two trials for adult procedural sedation [see Clinical Studies (14.2)] in which 318 adult patients received PRECEDEX. The mean total dose was 1.6 mcg/kg (range: 0.5 to 6.7), mean dose per hour was 1.3 mcg/kg/hr (range: 0.3 to 6.1) and the mean duration of infusion of 1.5 hours (range: 0.1 to 6.2). The population was between 18 to 93 years of age, ASA I-IV, 30% ≥65 years of age, 52% male and 61% Caucasian.
Treatment-emergent adverse reactions occurring in adults at an incidence of >2% are provided in Table 7. The most frequent adverse reactions were hypotension, bradycardia, and dry mouth [see Warnings and Precautions (5.2)]. Pre-specified criteria for the vital signs to be reported as adverse reactions are footnoted below the table. The decrease in respiratory rate and hypoxia was similar between PRECEDEX and comparator groups in both studies.
Pediatric Sedation for Magnetic Resonance Imaging
Adverse reaction information is derived from a trial for sedation of pediatric procedural during a non‑invasive procedure [see Clinical Studies (14.2)] in which 122 pediatric patients aged 1 month to less than 17 years undergoing magnetic resonance imaging (MRI) scans received PRECEDEX. In pediatric patients 1 month to less than 2 years old, the median total dose for the PRECEDEX low, middle, and high dose treatment groups was 8.30, 18.90, and 22.75 mcg, respectively. The median duration of treatment ranged from 52.5 to 69 minutes across treatment groups. In pediatric patients 2 to less than 17 years old, the median total dose for the PRECEDEX low, middle, and high dose treatment groups was 21.30, 43.90, and 80.25 mcg, respectively. The median duration of treatment ranged from 56.5 to 66 minutes across treatment groups.
All-causality treatment-emergent adverse reactions occurring in the combined age group of pediatric patients during the procedure at an incidence of >5% are provided in Table 8. The most frequent treatment-emergent adverse events were bradypnea, bradycardia, hypertension, and hypotension [see Warnings and Precautions (5.2, 5.3)]. In the combined age group and in each age group, increased incidence in bradycardia and hypertension was observed with increasing PRECEDEX dose. Mild transient withdrawal symptoms of emergence delirium or agitation occurred in 3 of 122 patients after discontinuation of PRECEDEX infusion [see Warnings and Precautions (5.5)]. All reported treatment‑emergent adverse reactions were mild to moderate in severity and the majority resolved without medical intervention. No subject in the study required airway intervention, including a jaw thrust or insertion of a nasal or oral airway. A similar profile was observed in the pediatric patients 1 month to less than 2 years old and in pediatric patients 2 to less than 17 years old. Pre‑specified criteria for the vital signs to be reported as adverse events are footnoted below the table.